Oxford Handbook of Acute Medicine 4th (2019) PDF
Oxford Handbook of Acute Medicine 4th (2019) PDF
Oxford Handbook of Acute Medicine 4th (2019) PDF
Oxford Handbook of
Acute Medicine
ii
Oxford Handbook of
Acute
Medicine
FOURTH EDITION
Punit S. Ramrakha
Consultant Cardiologist
Buckinghamshire Hospitals NHS Trust
and Hammersmith Hospital
London, UK
Kevin P. Moore
Professor of Hepatology
Royal Free and University College London
Medical School
University College London, UK
Amir H. Sam
Consultant Physician and Endocrinologist
Hammersmith Hospital,
and Reader in Endocrinology
Imperial College London, UK
1
iv
1
Great Clarendon Street, Oxford, OX2 6DP,
United Kingdom
Oxford University Press is a department of the University of Oxford.
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Oxford University Press in the UK and in certain other countries
© Punit S. Ramrakha and Kevin P. Moore 1997, 2004, 2010, 2019
The moral rights of the authors have been asserted
First edition published 1997
Second edition published 2004
Third edition published 2010
Fourth edition published 2019
Impression: 1
All rights reserved. No part of this publication may be reproduced, stored in
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Published in the United States of America by Oxford University Press
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Library of Congress Control Number: 2018941855
ISBN 978–0–19–879742–5
Printed and bound in China by
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Oxford University Press makes no representation, express or implied, that the
drug dosages in this book are correct. Readers must therefore always check
the product information and clinical procedures with the most up-to-date
published product information and data sheets provided by the manufacturers
and the most recent codes of conduct and safety regulations. The authors and
the publishers do not accept responsibility or legal liability for any errors in the
text or for the misuse or misapplication of material in this work. Except where
otherwise stated, drug dosages and recommendations are for the non-pregnant
adult who is not breast-feeding
Links to third party websites are provided by Oxford in good faith and
for information only. Oxford disclaims any responsibility for the materials
contained in any third party website referenced in this work.
The first edition of the Oxford Handbook of Acute Medicine was published
in 1997. Since then, acute medicine has evolved as a fully established spe-
cialty within the UK, and over 95% of hospitals now have an acute med-
ical unit. Importantly, acute medicine is developing in Europe and Australia
as part of providing high-quality care for patients presenting as a medical
emergency to hospital. Such patients now constitute the largest group of
patients occupying inpatient hospital beds. It is imperative therefore that
all staff are trained in the management of acute medical emergencies and,
importantly, have easy access to information to support the management of
this acutely unwell subgroup of patients. This textbook is clearly structured
and is supported by useful diagrams and algorithms, and hence the informa-
tion is readily accessible. The practical procedure section is comprehensive.
While many practising clinicians will not be required to undertake all these
procedures, they will be involved in discussion on these issues with patients
and relatives, and this text will be an invaluable guide.
The handbook series from Oxford University Press already provides
useful information to many clinicians working in clinical practice. Irrespective
of age or seniority, for clinicians directly involved in the early diagnosis and
management of patients who present acutely, this book will provide a con-
cise aid. The clear and up-to-date content of this text reflects the experi-
ence of the authors, and I am personally delighted to provide a foreword
to a book which will undoubtedly help support the growing number of
trainees working in the field of acute medicine.
Derek Bell
Professor of Acute Medicine
Imperial College London
vi
vi
Preface
vii
Acknowledgements
We would like to thank all of the contributors who provided initial drafts
of chapters which have evolved over time, as well as friends and col-
leagues who gave up their time to read a chapter and verify its accuracy.
We would also like to thank OUP for their encouragement during the re-
writing of this book. PSR is indebted to Sanjana, Aarav, and Dhruv for their
support and motivation. KPM is indebted to Janet, Alice, and Thomas for
their continued patience when the portable computer accompanied family
holidays. Finally, we would like to acknowledge the environment at the
Hammersmith Hospital where we trained and learned that acute medicine
is both interesting and fun.
vii
ix
Contents
Specialist reviewers x
Symbols and abbreviations xii
1 Cardiac emergencies 1
2 Respiratory emergencies 171
3 Gastroenterological emergencies 227
4 Renal emergencies 289
5 Shock 327
6 Neurological emergencies 347
7 Infectious diseases 469
8 Emergencies in HIV-positive patients 505
9 Diabetes and endocrine emergencies 545
10 Haematological emergencies 607
11 Rheumatological emergencies 659
12 Dermatological emergencies 691
13 Psychiatric emergencies 711
14 Drug overdoses 739
15 Practical procedures 783
16 Differential diagnoses of common presentations 863
17 Acute medicine and the older patient 891
Appendix 907
Index 915
x
Specialist reviewers
xii
E cross reference
i increased
d decreased
l leading to
7 approximately
M website
α alpha
β beta
δ delta
♀ female
♂ male
> greater than
< less than
≥ equal to or greater than
≤ equal to or less than
± plus or minus
°C degree Celsius
®
registered trademark
™
trademark
© copyright
A&E accident and emergency
AA Alcoholics Anonymous
AAA abdominal aortic aneurysm
AAV ANCA-associated vasculitis
Ab antibody
ABG arterial blood gas
ABPI ankle–brachial pressure index
ACEI angiotensin-converting enzyme inhibitor
ACE-III Addenbrooke’s Cognitive Examination-III
AChR acetylcholine receptor
ACS acute coronary syndrome
ACT artemisinin-based combination therapy; activated clotting time
ACTH adrenocorticotrophic hormone
AD adrenaline
ADH antidiuretic hormone
AF atrial fibrillation
AFB acid-fast bacilli
Ag antigen
AGEP acute generalized exanthematous pustulosis
AIDS acquired immunodeficiency syndrome
AKI acute kidney injury
ALI acute lung injury
ALL acute lymphoblastic leukaemia
ALP alkaline phosphatase
ALS advanced life support
ALT alanine transaminase
AMA anti-mitochondrial antibody
AMHP approved mental health professional
AML acute myeloid leukaemia
AMU acute medical unit
ANA anti-nuclear antibody
ANCA anti-neutrophil cytoplasmic antibody
AP anteroposterior
APL acute promyelocytic leukaemia
APSAC anisoylated plasminogen streptokinase activator complex
(anistreplase)
APTT activated partial thromboplastin time
AR aortic regurgitation
ARB angiotensin receptor blocker
ARDS adult respiratory distress syndrome
ARF acute renal failure
ASA acetyl salicylic acid
ASD atrial septal defect
ASPECTS Alberta Stroke Programme Early CT score
AST aspartate transaminase
ATN acute tubular necrosis
ATP adenosine triphosphate
AV atrioventricular
AVF arteriovenous fistula
AVNRT atrioventricular-nodal re-entry tachycardia
AVPU Alert, Voice, Pain, Unresponsive
AVR aortic valve replacement
AVRT accessory pathway tachycardia
AXR abdominal X-ray
BAL bronchoalveolar lavage
BBV bloodborne virus
bd twice a day
BIH benign intracranial hypertension
xvi
IgG immunoglobulin G
IgM immunoglobulin M
IGF insulin growth factor
IHD ischaemic heart disease
IIH idiopathic intracranial hypertension
IJV internal jugular vein
IL interleukin
IM intramuscular
in inch
INR international normalized ratio
IPPV intermittent positive pressure ventilation
IRIS immune reconstitution inflammatory syndrome
ITP idiopathic thrombocytopenic purpura
ITU intensive therapy unit
IU international unit
IV intravenous
IVC inferior vena cava
IVDU intravenous drug user
IVI intravenous infusion
IVIG intravenous immunoglobulin
IVU intravenous urogram
J joule
JVP jugular venous pressure
K+ potassium
KCl potassium chloride
KDIGO Kidney Disease Improving Global Outcomes
kg kilogram
kPa kilopascal
KS Kaposi’s sarcoma
KUB kidneys, ureters, and bladder
L litre
LA left atrium
LAD left anterior descending coronary artery
LBBB left bundle branch block
LDH lactate dehydrogenase
LDL low-density lipoprotein
LFT liver function test
LGV lymphogranuloma venereum
LH luteinizing hormone
LHRH luteinizing hormone-releasing hormone
LIJ left internal jugular
x
mL millilitre
mm millimetre
mmHg millimetre of mercury
mmol millimole
MMSE Mini Mental State Examination
MoCA Montreal cognitive assessment
MOF multi-organ failure
mOsm milliosmole
MPGN membranoproliferative glomerulonephritis
MR magnetic resonance; mitral regurgitation
MRA magnetic resonance angiography
MRCP magnetic resonance cholangio-pancreatography
MRI magnetic resonance imaging
MRSA meticillin-resistant Staphylococcus aureus
ms millisecond
MS multiple sclerosis
MSM men who have sex with men
MSSA meticillin-sensitive Staphylococcus aureus
MSU midstream urine
mU milliunit
MUGA multigated acquisition (scan)
mV millivolt
MV mitral valve
MVP mitral valve prolapse
MVR mitral valve replacement
MVT monomorphic ventricular tachycardia
Na+ sodium
NA noradrenaline
NABQI N-acetyl-p-benzoquinoneimine
nAnB non-A/non-B (hepatitis)
NaTHNaC National Travel Health Network and Centre
NBM nil by mouth
NBTV non-bacterial thrombotic vegetation
NCS nerve conduction studies
ng nanogram
NG nasogastric
NHL non-Hodgkin’s lymphoma
NHS National Health Service
NICE National Institute for Health and Care Excellence
NIHSS National Institutes of Health Stroke Scale
NIPPV nasal intermittent positive pressure ventilation
xxi
Fig. 8.2 The typical appearance of cytomegalovirus retinitis in a patient with AIDS,
characterized by retinal necrosis with an irregular granular border, patchy retinal
haemorrhage, and retinal infl ammatory sheathing of the retinal vessels. Reproduced
from Easty D, et al. Oxford Textbook of Ophthalmology, 1999, with permission from
Oxford University Press.
Fig. 12.1 Morbilliform eruption caused by administration of ampicillin to a patient with
infectious mononucleosis. Reproduced from MacKie R. Clinical Dermatology, 2003,
with permission from Oxford University Press.
Fig. 12.2 Erythema multiforme on the leg, note the presence of target lesions.
Reproduced from MacKie R. Clinical Dermatology, 2003, with permission from Oxford
University Press.
Fig. 12.3 Blisters of bullous pemphigoid. Large, tense, raised lesions are seen on an
erythematous eczematized base. Reproduced from MacKie R. Clinical Dermatology, 2003,
with permission from Oxford University Press.
Chapter 1 1
Cardiac emergencies
Ventricular tachycardia: drugs 70
Narrow complex tachyarrhythmias (SVT) 72
Dosages of selected antiarrhythmics for SVT 75
Atrial fibrillation: assessment 76
Atrial fibrillation: management 78
Atrial fibrillation: rate control 81
Atrial flutter 82
Multifocal atrial tachycardia 83
Accessory pathway tachycardia (AV re-entrant tachycardia) 84
Atrioventricular nodal re-entry tachycardia 85
Bradyarrhythmias: general approach 86
Sinus bradycardia or junctional rhythm 88
Intraventricular conduction disturbances 89
Types of atrioventricular conduction block 90
Pulmonary oedema: assessment 92
Pulmonary oedema: causes 94
Pulmonary oedema: management 1 95
Pulmonary oedema: management 2 96
Pulmonary oedema: management 3 98
Pulmonary oedema: specific conditions 100
Infective endocarditis (IE) 102
IE: diagnosis 104
IE: investigations 105
IE: antibiotics 106
IE: monitoring treatment 108
Culture-negative endocarditis 110
Right-sided endocarditis 112
Prosthetic valve endocarditis 113
Surgery for IE 114
Endocarditis prophylaxis 116
Acute aortic regurgitation 118
Acute mitral regurgitation 120
Deep vein thrombosis (DVT): assessment 122
DVT: management 124
Pulmonary embolism (PE): assessment 126
PE: investigations 1 128
PE: investigations 2 130
PE: management 1 132
PE: management 2 134
Fat embolism 136
Hypertensive emergencies 138
Hypertensive emergencies: management 140
Hypertensive emergencies: drug treatment 142
Hypertensive emergency with retinopathy
(accelerated and malignant hypertension) 144
Hypertensive encephalopathy 146
Aortic dissection: assessment 148
CARDIAC EMERGENCIES 3
Check
Shake and shout
responsiveness
If breathing:
Check breathing Look, listen, and feel
recovery position
Assess
Signs of a circulation
10s only
Fig. 1.1 Adult basic life support. Send or go for help as soon as possible, according
to guidelines. For further information, see the Resuscitation Council (UK) website
M http://www.resus.org.uk
6
Fig. 1.3 Universal treatment algorithm (for further details, see the Resuscitation
Council (UK) website M http://www.resus.org.uk).
10
No ST elevation ST elevation
Fig. 1.4 Nomenclature of ACS. Patients with ACS may present with or without
ST-elevation on the ECG. The majority of patients with ST-elevation (large arrows)
ultimately develop Q-wave MI (QwMI), whereas a minority (small arrow) develop a
non-Q-wave MI (NQ-MI). Patients without ST-elevation experience either UA or an
NSTEMI, depending on the absence or presence of cardiac enzymes (e.g. troponin)
detected in the blood.
Reprinted from Progress in Cardiovascular Diseases, 46(5), Kamineni R, et al. ‘Acute coronary syn-
dromes: initial evaluation and risk stratification’, 379–92, Copyright 2004, with permission from
Elsevier.
12
STEMI: diagnosis 1
This is based on a combination of history, ECG, and biochemical markers
of cardiac injury. In practice, history and ECG changes are normally diag-
nostic, resulting in immediate reperfusion/medical treatment. Biochemical
markers of cardiac injury usually become available later and help reconfirm
the diagnosis, as well as provide prognostic information (magnitude of rise).
ECG changes
(Also see Box 1.3.)
• ST-segment elevation occurs within minutes and may last for up to
2 weeks. ST-elevation of ≥2mm in adjacent chest leads and ≥1mm in
adjacent limb leads is necessary to fulfil thrombolysis criteria. Persisting
ST-elevation after 1 month suggests formation of LV aneurysm.
Infarction site can be localized from ECG changes, as indicated in
Table 1.1.
• Pathological Q waves indicate significant abnormal electrical conduction
but are not synonymous with irreversible myocardial damage. In the
context of a ‘transmural infarction’, they may take hours or days to
develop and usually remain indefinitely. In the standard leads, the
Q wave should be ≥25% of the R wave and 0.04s in duration, with
negative T waves. In the precordial leads, Q waves in V4 should be
>0.4mV (four small squares) and in V6 >0.2mV (two small squares), in
the absence of LBBB (QRS width <0.1s or three small squares).
• ST-segment depression (ischaemia at distance) in a 2nd territory (in
patients with ST-segment elevation) is secondary to ischaemia in a
territory other than the area of infarction (often indicative of multi-
vessel disease) or reciprocal electrical phenomena. Overall it implies a
poorer prognosis.
• PR-segment elevation/depression and alterations in the contour of the P
wave are generally indicative of atrial infarction. Most patients will also
have abnormal atrial rhythms such as atrial fibrillation (AF)/flutter and
wandering atrial pacemaker and atrioventricular (AV) nodal rhythms.
• T-wave inversion may be immediate or delayed and generally persists
after the ST-elevation has resolved.
• Non-diagnostic changes, but the ones that may be ischaemic, include new
LBBB or right bundle branch block (RBBB), tachyarrhythmias, transient
tall peaked T waves or T-wave inversion, axis shift (extreme left or
right), or AV block.
STEMI: diagnosis 1 15
STEMI: diagnosis 2
Biochemical markers of cardiac injury
Serial measurements evaluating a temporal rise and fall should be obtained
to allow a more accurate diagnosis. CK and creatine kinase-muscle/brain
(CK-MB) from a skeletal muscle source tend to remain elevated for a
greater time period, in comparison to a cardiac source.
CK
• Levels twice the upper limit of normal are taken as being abnormal.
• Serum levels rise within 4–8h post-STEMI and fall to normal within
3–4 days. The peak level occurs at about 24h but may be earlier (12h)
and higher in patients who have had reperfusion (thrombolysis or PCI);
enzymes from the damaged muscle are ‘washed out’ of the infarcted
area with restored circulation.
• False positive rates of 715% occur in patients with alcohol intoxication,
muscle disease or trauma, vigorous exercise, convulsions, IM injections,
hypothyroidism, pulmonary embolism (PE), and thoracic outlet
syndrome.
CK-MB isoenzyme is more specific for myocardial disease. Levels may be
elevated despite a normal total CK. However, CK-MB is also present in
small quantities in other tissues (skeletal muscle, tongue, diaphragm, uterus,
and prostate), and trauma or surgery may lead to false positive results. If
there is doubt about myocardial injury with CK-MB levels obtained, a car-
diac troponin must be measured.
Cardiac troponins (TnT, TnI)
• Both TnI and TnT are highly sensitive and specific markers of cardiac
injury.
• Serum levels start to rise by 3h post-MI, and elevation may persist up to
7–14 days. This is advantageous for diagnosis of late MI.
• In most STEMI cases, the diagnosis can be made using a combination of
the clinical picture and serial CK/CK-MB levels. In the event of normal
CK-MB levels and suspected non-cardiac sources of CK, troponins can
be used.
• Troponins can also be elevated in non-ischaemic myocyte damage such
as myocarditis, cardiomyopathy, and pericarditis.
Other markers
There are multiple other markers, but with increasing clinical availability
of troponins, measurements are not recommended. These include aspar-
tate transaminase (AST) (rise 18–36h post-MI) and lactate dehydrogenase
(LDH) (rise 24–36h post-MI).
The time course of the various markers is seen in Fig. 1.5.
For key points on non-ACS causes of raised troponin, see Box 1.4.
STEMI: diagnosis 2 17
Myoglobin
and CK isoforms
50 Troponin
(large MI)
Multiples of the AMI cutoff limit
20
10
5
CKMB
2
Troponin
1 (small MI)
STEMI: general measures
(See Box 1.6.)
Immediate stabilizing measures
These are as outlined in E Acute coronary syndrome, pp. 10–11.
Control of cardiac pain
• Diamorphine 2.5–10mg IV is the drug of choice and may be repeated
to ensure adequate pain relief, unless evidence of emerging toxicity
(hypotension, respiratory depression). Nausea and vomiting should be
treated with metoclopramide (10mg IV) or a phenothiazine.
• O2 to be administered at 2–5L/min if O2 saturation <90%. Hypoxaemia
is frequently seen post-MI due to ventilation–perfusion abnormalities
secondary to LVF. In patients with refractory pulmonary oedema,
continuous positive airways pressure (CPAP) or via formal ET intubation
may be necessary. Beware of carbon dioxide (CO2) retention in patients
with COPD.
• Nitrates may lessen pain and can be given, providing that the patient is
not hypotensive (SL or IV). They need to be used cautiously in inferior
STEMI, especially with RV infarction, as venodilation may impair RV
filling and precipitate hypotension. Nitrate therapy has no effect on
mortality (ISIS-4).
Correction of electrolytes
Both low potassium and magnesium may be arrhythmogenic and must be
supplemented, especially in the context of arrhythmias.
Strategies to limit infarct size
β-
blockade, angiotensin-
converting enzyme inhibitor (ACEI), and
reperfusion.
Beta-blockade
• Early β-blockade in limiting infarct size, reducing mortality, and
early malignant arrhythmias. All patients (including primary PCI and
thrombolysis patients) should have early β-blockade, but those with the
following features will benefit most:
• Hyperdynamic state (sinus tachycardia, iBP)
• Ongoing or recurrent pain/reinfarction
• Tachyarrhythmias such as AF.
• Absolute contraindications: HR <60bpm, systolic BP (SBP) <100mmHg,
moderate to severe heart failure, AV conduction defect, severe airways
disease.
• Relative contraindications: asthma, current use of calcium channel
blocker and/or β-blocker, severe peripheral vascular disease with
critical limb ischaemia, large inferior MI involving the RV.
• Use a short-acting agent IV initially (metoprolol 1–2mg at a time,
repeated at 1-to 2-min intervals to a maximum dose of 15–20mg)
under continuous ECG and BP monitoring. Aim for a pulse rate of
60bpm and SBP of 100–110mmHg. If haemodynamic stability continues
15–30min after last IV dose, start metoprolol 50mg three times daily
(tds). Esmolol is an ultra-short-acting IV β-blocker, which may be tried if
there is concern whether the patient will tolerate β-blockers.
STEMI: general measures 19
ACEIs
After receiving aspirin, β-blockade (if appropriate), and reperfusion, all pa-
tients with STEMI/LBBB infarction should receive an ACEI within the first
24h of presentation.
• Patients with high-risk/large infarcts, particularly with an anterior STEMI,
a previous MI, heart failure, or impaired LV function on imaging (Echo)
or those who are elderly will benefit most.
• The effect of ACEIs appears to be a class effect—use the drug with
which you are familiar [e.g. ramipril 1.25mg once daily (od)].
20
STEMI: reperfusion by primary
percutaneous coronary intervention
Time is of the essence for reperfusion, and each institution should have its
recommended protocol. It is imperative that there are no delays in both the
decision-making and implementation processes for reperfusion. If primary
PCI is chosen, one telephone call should ensure a rapid response.
Primary PCI
• Primary PCI is the current gold standard reperfusion strategy for
treatment of STEMI.
• Primary PCI requires significant coordination between the emergency
services, community hospitals, and invasive centres. It must only be
performed if:
• A primary PCI programme is available and
• The patient presents to an invasive centre and can undergo
catheterization without delay.
Indications for primary PCI
• All patients with chest pain and ST-segment elevation or new LBBB fulfil
primary PCI criteria (compare with indications for thrombolysis).
• This will include a group of patients where ST-segment elevation may
not fulfil the thrombolysis criteria.
• In general, patients in whom thrombolysis is contraindicated should
be managed by primary PCI. Cases where there is a significant risk of
bleeding must be managed individually.
Outcome in primary PCI
• Data from >10 large randomized trials demonstrate a superior outcome
in patients with STEMI who are treated with primary PCI, in comparison
to thrombolysis.
• There is a significant short-term, as well as long-term, reduction in
mortality and major adverse cardiac events (MACE) (death, non-fatal
reinfarction, and non-fatal stroke) in STEMI patients treated with
primary PCI. Furthermore, primary PCI patients have overall better LV
function, a higher vessel patency rate, and less recurrent myocardial
ischaemia.
• Multiple studies (including PRAGUE-2 and DANAMI-2) have also
demonstrated that interhospital transportation for primary PCI
(community hospital to invasive centre) is safe and primary PCI continues
to remain superior to thrombolysis despite the time delays involved.
Complications
• These include bleeding from arterial puncture site, stroke, recurrent
infarction, need for emergency coronary artery bypass graft (CABG),
and death, which are similar to high-risk PCI cases (1%).
• The best results are obtained from high-volume centres with experience
of primary PCI.
• Each primary PCI centre will have its own policy for management of
cases, including the use of low-molecular weight heparin (LMWH)/
unfractionated heparin (UFH) and antiplatelet agents (e.g. IIb/IIIa). It is
generally accepted that, in the acute phase, only the ‘culprit’ lesion(s)/
vessel(s) will be treated. The pattern of disease in the remainder of
the vessels will determine whether total revascularization should be
performed as an inpatient or elective case at some stage in the future.
• STEMI patients treated with primary PCI can be discharged safely within
72h of admission without the need for further risk stratification.
• Primary PCI is more cost-effective in the long term, with significant
savings from fewer days in hospital, a lower need for readmission, and
less heart failure.
• Post-discharge care, secondary prevention, and rehabilitation remain
identical to other MI cases.
Rescue PCI
As an adjunct to thrombolysis, PCI should be reserved for patients who
remain symptomatic post-thrombolysis (failure to reperfuse) or develop
cardiogenic shock (E Cardiogenic shock, pp. 44–5). We recommend all
patients who do not settle post-thrombolysis [ongoing symptoms and on-
going ST elevation with/without symptoms (<50% resolution of ST eleva-
tion at 90min post-lysis)] should be discussed with the local cardiac centre
for urgent catheterization and revascularization.
For key points on STEMI, see Boxes 1.5 and 1.6.
STEMI: reperfusion therapy
(thrombolysis) 1
Reperfusion occurs in 50– 70% of patients who receive thrombolysis
within 4h of onset of pain (compared with 720% of controls). As with
primary PCI, thrombolysis also results in reduction in mortality, LV dys-
function, heart failure, cardiogenic shock, and arrhythmias. However, the
magnitude of the benefits obtained is smaller. Furthermore, patients must
undergo cardiac catheterization to delineate their coronary anatomy before
revascularization (achieved at the same time with primary PCI). Time is,
once again, of paramount importance and thrombolysis should be adminis-
tered as soon as possible (see Box 1.5).
Indications for thrombolysis
• Typical cardiac pain within previous 12h and ST elevation in two
contiguous ECG leads (>1mm in limb leads or >2mm in V1–V6).
• Cardiac pain with new/presumed new LBBB on ECG.
• If ECG is equivocal on arrival, repeat at 15-to 30-min intervals to
monitor progression.
• Thrombolysis should not be given if the ECG is normal or if there is
isolated ST depression (must exclude true posterior infarct).
• Remember patients with diabetes may present with dyspnoea or
collapse without chest pain. Look for new ST elevation on the ECG.
• True posterior infarction presents with ST depression in anterior
chest leads (V1–V3), often with ST changes in inferior leads as well. If
suspected, administer thrombolysis.
Timing of thrombolysis
• Greatest benefit is achieved with early thrombolysis (especially if given
within 4h of onset of first pain).
• Patients presenting between 12 and 24h from onset of pain should be
thrombolysed if there are any persisting symptoms and/or ST-segment
elevation on the ECGs.
• Patients presenting within 12–24h from the onset of pain whose clinical
picture and ECGs appear to have settled should be managed initially as
an NSTEMI, followed by early catheterization.
Choice of thrombolytic agent
• This is partly determined by the local thrombolysis strategy.
• Allergic reactions and episodes of hypotension are greater with
streptokinase (SK).
• Bolus agents are easier and quicker to administer, with a decrease in
drug errors, in comparison to first-generation infusions.
• Recombinant tissue plasminogen activator (rtPA) has a greater
reperfusion capacity and a marginally higher 30-day survival benefit than
SK, but an i risk of haemorrhage.
• More recent recombinant plasminogen activator (rPA) derivatives have
a higher 90-min TIMI-III flow rate, but similar 30-day mortality benefit
to rtPA.
STEMI: thrombolysis 2
Complications of thrombolysis
• Bleeding is seen in up to 10% of patients. Most are minor at sites
of vascular puncture. Local pressure is sufficient, but occasionally
transfusion may be required. In extreme cases, SK may be reversed by
tranexamic acid (10mg/kg slow IV infusion).
• Hypotension during the infusion is common with SK. Lay the patient
supine, and slow/stop the infusion until the BP rises. Treatment with
cautious (100–500mL) fluid challenges may be required, especially in
inferior/RV infarction. Hypotension is not an allergic reaction and does
not warrant treatment as such.
• Allergic reactions are common with SK and include low-grade fever,
rash, nausea, headaches, and flushing. Give hydrocortisone 100mg IV,
with chlorphenamine 10mg IV.
• Intracranial haemorrhage is seen in 70.3% of patients treated with SK
and 70.6% of those with rtPA.
• Reperfusion arrhythmias (most commonly a short, self-limiting run
of idioventricular rhythm) may occur as the metabolites are washed
out of the ischaemia tissue (E Ventricular tachyarrhythmia post-
MI, p. 40; E Bradyarrhythmias and indications for pacing, p. 41;
E Bradyarrhythmias post-MI, p. 41).
• Systemic embolization may occur from lysis of thrombus within the left
atrium (LA), left ventricle (LV), or aortic aneurysm.
Absolute contraindications to thrombolysis
• Active internal bleeding.
• Suspected aortic dissection.
• Recent head trauma and/or intracranial neoplasm.
• Previous haemorrhagic stroke at any time.
• Previous ischaemic stroke within the past 1 year.
• Previous allergic reaction to a fibrinolytic agent.
• Trauma and/or surgery within the past 2 weeks at risk of bleeding.
Relative contraindications to thrombolysis
• Trauma and/or surgery >2 weeks previously.
• Severe uncontrolled hypertension (BP >180/110) with/without
treatment.
• Non-haemorrhagic stroke over 1 year ago.
• Known bleeding diathesis or current use of anticoagulation within
therapeutic range [international normalized ratio (INR) 2 or over].
• Significant liver or renal dysfunction.
• Prolonged (>10min) of CPR.
• Prior exposure to SK (especially previous 6–9 months).
• Pregnancy or postpartum.
• LP (lumbar puncture) within previous 1 month.
• Menstrual bleeding or lactation.
• History of chronic severe hypertension.
• Non-compressible vascular punctures (e.g. subclavian central venous lines).
• Proliferative diabetic retinopathy (risk of intraocular bleed).
STEMI: thrombolysis 2 25
26
Surgery for acute STEMI
Emergency surgical revascularization (CABG) cannot be widely applied to
patients who suffer an MI outside of the hospital. CABG in uncomplicated
STEMI patients after 6h from presentation is contraindicated secondary to
significant haemorrhage into areas of infarction. Unstable patients have a
very high perioperative mortality.
CABG in the context of an acute STEMI is of value in the following
situations:
• Persistent or recurrent chest pain despite thrombolysis/primary PCI.
• High-risk coronary anatomy on catheterization [left main stem (LMS),
left anterior descending artery (LAD) ostial disease].
• Complicated STEMI [acute mitral regurgitation (MR), ventricular septal
defect (VSD)].
• Patients who have undergone successful thrombolysis, but with surgical
coronary anatomy on catheterization.
• Patients known to have surgical coronary anatomy on catheterization
performed prior to admission with STEMI.
STEMI: additional measures 27
STEMI: additional measures
Low-molecular weight and unfractionated heparin
LMWH
• There are trial data for the use of LMWH and thrombolysis [e.g.
enoxaparin 30mg IV bolus, then 1mg/kg subcutaneously (SC) every 12h].
• LMWH can be used at a prophylactic dose to prevent thromboembolic
events in patients slow to mobilize, as an alternative to UFH.
UFH
• There is no indication for ‘routine’ IV heparin following SK.
• IV heparin [4000U/max. IV bolus, followed by 1000U/h max. adjusted
for an activated partial thromboplastin time (APTT) ratio of 1.5–2.0
times control] should be used routinely, following rtPA and its
derivatives, for 24–48h.
Clopidogrel (and other antiplatelets, e.g. prasugrel, ticagrelor)
• The addition of clopidogrel to aspirin and fibrinolytics has been shown
to reduce the incidence of death or MACE by 20% at 30 days.
• If coronary stents are deployed, the patient should remain on dual anti-
platelet therapy (DAPT) ideally for 12 months, as for patients with NSTEMI.
Glycoprotein IIb/IIIa inhibitors
• There does not appear to be any benefit of glycoprotein (GP) IIb/IIIa in
combination with full-or reduced-dose thrombolytics in STEMI.
• GP IIb/IIIa inhibitors are recommended routinely in the context of
STEMI patients treated with primary PCI. Best data are with abciximab.
• They can also be used in the context of rescue PCI, subsequent to failed
thrombolysis, although there is a greater risk of bleeding. Each case
must be judged on its merits.
Magnesium
• Earlier trials giving Mg2+ before or with thrombolytics showed some benefit
in mortality. ISIS-4 showed no benefit from the routine use of IV Mg2+ post-
MI. However, Mg2+ was given late (6h) after thrombolysis, by which time its
protective effect on reperfusion injury may have been lost. Trials are ongoing.
• Current accepted role for Mg2+ is confined to Mg2+-deplete patients and
patients with reperfusion, supraventricular, and ventricular arrhythmias.
• Dose: 8mmol in 20mL of 5% glucose over 20min, followed by 65mmol
in 100mL of 5% glucose over 24h (contraindications: serum creatinine
>300 micromol/L, third-degree AV block).
Calcium antagonists
• Best avoided, especially in the presence of LV impairment.
• Diltiazem and verapamil started after day 4–5 in post-MI patients with
normal LV function have a small beneficial effect.
• Amlodipine is safe to be used in patients with poor LV post-MI.
• Nifedipine has been shown to increase mortality and should be avoided.
Digoxin
• Has little role in the management of an acute STEMI and heart failure
complicating an acute MI.
• Can be used safely in the management of arrhythmias and heart rate (HR).
28
STEMI
Complications No complications
• Heart failure
• Shock
• Post MI rest or low-
threshold angina Assess LV function
• Non-sustained or
sustained VT ≥
24h post MI
EF ≤45% EF ≥45%
Functional test
• Sub-maximal exercise
ECG test
• Dobutamine stress
echocardiography
• Other
Inpatient
angiography
followed by Positive Negative
electrophysiological for for
study ischaemia ischaemia
Outpatient
angiography
STEMI: complications
Complications
• Continuing chest pain.
• Fever.
• New systolic murmur: VSD, acute MR, or pericarditis.
• Arrhythmia: VT, AV block ectopics, and bradycardia.
• Pump failure: hypotension, cardiac failure, and cardiogenic shock.
Complications are encountered more commonly in patients post-STEMI
but can also be found in NSTEMI patients (E Non-ST-elevation myocardial
infarction/unstable angina, pp. 46–7). In NSTEMI patients, complications
are more common where multiple cardiac events have occurred.
Further chest pain
• Chest pain post-MI is not necessarily angina. A careful history is needed
to characterize the pain. If there is doubt about the aetiology of the
pain in the absence of ECG changes, stress/thallium imaging may aid
diagnosis.
• A bruised sensation and musculoskeletal pain are common in the first
24–48h, especially in patients who have received CPR or repeated
direct current (DC) shock. Use topical agents for skin burns.
• Recurrent infarction is an umbrella term including both extension of
infarction in the original territory and repeated infarct in a 2nd territory.
• Usually associated with recurrent ST elevation.
• If cardiac enzymes are not yet back to normal, a significant change is a
2-fold rise above the previous nadir.
• Patients should ideally undergo immediate PCI. Thrombolysis
is an alternative, but a less attractive, approach. Standard
thrombolysis criteria must be met (E STEMI: reperfusion therapy
(thrombolysis) 1, pp. 22–3). Bleeding is a risk (NB SK should not be
used on a 2nd occasion).
• Post-infarction angina (angina developing within 10 days of MI) should be
treated with standard medical therapy. All patients with angina prior to
discharge should undergo cardiac catheterization and revascularization
as an inpatient.
• Pericarditis presents as sharp, pleuritic, and positional chest pain, usually
1–3 days post-infarct. It is more common with STEMI. A pericardial
friction rub may be audible. ECG changes are rarely seen. Treat with
high-dose aspirin [600mg four times daily (qds) PO], covering with a
proton pump inhibitor (PPI) (e.g. lansoprazole 30mg od PO). Other
NSAIDs have been associated with a higher incidence of LV rupture and
i coronary vascular resistance and are probably best avoided.
• Pericardial effusion is more common with anterior MI, especially if
complicated by cardiac failure. Tamponade is rare and the result of
ventricular rupture and/or haemorrhagic effusions. Detection is with a
combination of clinical features and Echo. Most small effusions resolve
gradually over a few months, with no active intervention.
STEMI: complications 33
Cocaine-induced MI
• The incidence of cocaine-induced MI, LV dysfunction, and arrhythmias
are on the increase (see Box 1.8).
• It has been estimated that 14–25% of young patients presenting to
urban emergency departments with non-traumatic chest pain may have
detectable levels of cocaine and its metabolites in their circulation. Of
this group, 6% have enzymatic evidence of MI (figures are from the
United States).
• Most patients are young, non-white, ♂ cigarette smokers, without
other risk factors for IHD.
Diagnosis
• Can be difficult and must be suspected in any young individual with chest
discomfort at low risk of developing OHD.
• Chest pain occurs most commonly within 12h of cocaine use. Effects
can return up to 24–36h later, secondary to long-lasting active
metabolites.
• ECG is abnormal, with multiple non-specific repolarization changes in
up to 80% of cases, and 740% may have diagnostic changes of STEMI
qualifying for reperfusion therapy (E STEMI: diagnosis 1, p. 14).
• Biochemical markers of cardiac injury can be misleading, as most patients
will have elevated CK levels secondary to rhabdomyolysis. TnT and TnI
are vital to confirm myocardial injury.
Management
General measures
• These are the same as for anyone presenting with MI. High-flow O2
5–10L, unless there is a contraindication; analgesia; aspirin 75mg od.
• GTN: to be given at high doses as IV infusion (>10mg/h final
levels) and dose titrated to symptoms and haemodynamic response
(E STEMI: general measures, pp. 18–19).
• Benzodiazepines: are critical to reduce anxiety and tachycardia.
Second-line agents
• Verapamil is given in high doses and has the dual function of reducing
cardiac workload, hence restoring O2 supply and demand, as well
as reversing coronary vasoconstriction. Should be given cautiously
as 1-to 2-mg IV bolus at a time (up to 10mg total), with continuous
haemodynamic monitoring. This should be followed by a high-dose oral
preparation to cover the 24-h period for at least 72h after the last dose
of cocaine (80–120mg PO tds).
• Phentolamine is an α-adrenergic antagonist and readily reverses cocaine-
induced vasoconstriction (2–5mg IV and repeated if necessary). It can
be used in conjunction with verapamil.
• Labetalol has both α- and β-adrenergic activity and can be used after
verapamil and phentolamine if the patient remains hypertensive. It is
effective in lowering cocaine-induced hypertension but has no effect on
coronary vasoconstriction.
Cocaine-induced MI 39
Bradyarrhythmias post-MI 41
Bradyarrhythmias post-MI
First-degree AV block
• Common and no treatment required.
• Significant PR prolongation (>0.20s) is a contraindication to β-blockade.
Second-degree AV block
• This indicates a large infarction affecting the conducting systems, and
mortality is generally i in this group of patients.
• Mobitz type I is self-limiting, with no symptoms. Generally, requires no
specific treatment. If symptomatic or progression to complete heart
block (CHB), will need temporary pacing.
• Mobitz type II, 2:1, 3:1 should be treated with temporary pacing,
regardless of whether it progresses to CHB.
Third-degree AV block
• In the context of an inferior MI, can be transient and does not require
temporary pacing, unless there is haemodynamic instability or an escape
rhythm of <40bpm.
• Temporary pacing is required with anterior MI and unstable inferior MI.
42
Cardiogenic shock
• Affects between 5 and 20% of patients, and up to 15% of MI patients
can present with cardiogenic shock.
• Management involves a complex interaction between many medical,
surgical, and intensive care teams. with multiple invasive and non-
invasive measures. Despite significant advances, prognosis remains poor.
Therefore, the absolute wishes of the patient with regard to such an
invasive strategy should be respected from the outset.
Diagnosis
A combination of clinical and physiological measures:
• Clinical: marked, persistent (>30min) hypotension with SBP
<80–90mmHg.
• Physiological: low cardiac index (<1.8L/mm/m2), with elevated LV filling
pressure (PCWP >18mmHg).
Management
• Complex and must be quick.
• Correct reversible factors, including:
• Arrhythmias and aim to restore sinus rhythm.
• Acid–base balance, electrolyte abnormalities.
• Ventilation abnormalities: intubate if necessary.
• Rapid haemodynamic, echocardiographic, and angiographic evaluation:
• Haemodynamic: to ensure adequate monitoring and access, including
central venous lines, Swan–Ganz, arterial line insertion, urinary
catheter.
• Echocardiographic: to assess ventricular systolic function and exclude
mechanical lesions, which may need to be dealt with by emergency
cardiac surgery, including MR (NB Tall v waves on PCWP trace), VSD,
and ventricular aneurysm/pseudoaneurysm.
• Angiographic: with a view to PCI or CABG if appropriate.
• Aim to improve haemodynamic status, achieving SBP ≥90mmHg, guided
by physical signs and LV filling pressures. As a general guide:
• PCWP <15mmHg: cautious IV fluids (colloids) in 100–200mL aliquots.
• PCWP >15mmHg: inotropic support with diuretics (if pulmonary
oedema).
• Inotropes should be avoided, if at all possible, in acutely ischaemic
patients. The aim should be to rapidly restore/maximize coronary flow
and offload the LV. Early revascularization is vital and has been shown to
decrease mortality. IABP will partially help achieve improved coronary
perfusion, reduce LVEDP, and improve BP, although has not been shown
to improve survival in randomized trials.
• If haemodynamic status does not improve post-revascularization and
IABP insertion, inotropes should be used. Choice of agent can be
difficult and should partly be guided by local protocols and expertise.
Generally accepted choices depend on the clinical picture and include:
• If patient is hypotensive (with pulmonary oedema): start with
dopamine (up to 5 micrograms/kg/min), and if ineffective, substitute
with adrenaline and/or noradrenaline (NA).
Cardiogenic shock 45
Non-cardiac Chronic
NSTE-ACS STEMI
diagnosis stable angina
Inpatient
Low risk High risk
angiography
Outpatient
angiography
NSTE-ACS: diagnosis
Diagnosis in NSTE-ACS is an evolving process and may not be clear on
presentation. A combination of history, serial changes in ECG, and serial
changes in biochemical markers of myocardial injury determines the diag-
nosis. Once a patient has been designated a diagnosis of ACS with prob-
able/possible NSTE-ACS ,they will require the following.
Serial ECGs
Changes can be transient and/or fixed, especially if a diagnosis of NSTEMI
is made. See Table 1.1 for localization of infarcts from ECG changes.
• ST-segment depression of ≥0.05mV is highly specific of myocardial
ischaemia (unless isolated in V1–V3 suggesting a posterior STEMI).
• T-wave inversion is sensitive, but non-specific, for acute ischaemia,
unless very deep (≥0.3mV).
• Rarely Q waves may evolve or there may be transient/new LBBB.
Serial biochemical markers of cardiac injury
These are used to differentiate between NSTEMI and UA, as well as to de-
termine prognosis. We recommend levels at 6, 12, 24, and 48h after the last
episode of pain. A positive biochemical marker (CK, CK-MB, or troponin)
in the context of one or more of the aforementioned ECG changes is diag-
nostic of NSTEMI. If serial markers over a 24-to 72-h period from the last
episode of chest pain remain negative, UA is diagnosed.
• Cardiac TnT and TnI: are both highly cardiac-specific and sensitive,
can detect ‘microinfarction’ in the presence of normal CK-MB,
are not affected by skeletal muscle injury, and convey prognostic
information (worse prognosis if positive). Troponins can be raised in
non-atherosclerotic myocardial damage (cardiomyopathy, myocarditis,
pericarditis) and should therefore be interpreted in the context of the
clinical picture. Both TnT and TnI rise within 3h of infarction. TnT may
persist up to 10–14 days, and TnI up to 7–10 days. Results must be
interpreted with caution in patients with chronic renal failure (CRF). See
Fig. 1.5.
• CK levels do not always reach the diagnostic twice the upper limit of
normal and generally have little value in diagnosis of NSTEMI.
• CK-MB has low sensitivity and specificity; CK-MB isoforms improve
sensitivity (CK-MB2 >1U/L or CK-MB2:CK-MB1 ratio >1.5), but
isoform assays are not widely available clinically.
• Myoglobin is non-cardiac-specific, but levels can be detected as early
as 2h after onset of symptoms. A negative test is useful in ruling out
myocardial necrosis.
Continuous ECG monitoring
Can detect episodes of silent ischaemia and arrhythmia. Both have been
shown to be more prolonged in NSTEMI than in UA.
NSTE-ACS: diagnosis 49
50
NSTE-ACS: risk stratification
NSTE-ACS are a heterogeneous group of conditions with variable out-
comes. An assessment of risk for adverse outcome is vital to ensure forma-
tion of an adequate management plan.
Risk stratification should begin on initial evaluation and continue
throughout the hospital stay. At each stage, patients with a high chance of a
poor outcome should be identified and managed appropriately.
We recommend at least two formal risk stratification processes.
Early risk stratification
(See Table 1.2.) This should take place on presentation and forms part of
the initial assessment used to make a diagnosis. It involves a combination of
clinical features, ECG changes, and biochemical markers of cardiac injury,
as demonstrated in Table 1.2. Patients are divided into high risk and inter-
mediate/low risk.
• High-risk patients should be admitted to the CCU, follow an early
invasive strategy, and be managed with a combination of:
• Acetyl salicylic acid (ASA), clopidogrel/ticagrelor, LMWH, IIb/IIIa
inhibitor.
• Anti-ischaemic therapy (first-line β-blocker, GTN).
• Early invasive strategy (inpatient catheterization and PCI within 48h of
admission).
• Intermediate/low-risk patients should be admitted to a monitored bed
on a step-down unit and undergo a 2nd inpatient risk stratification
once their symptoms have settled, to determine the timing of invasive
investigations. Initial management should include:
• ASA, clopidogrel/ticagrelor, LMWH.
• Anti-ischaemic therapy (first-line β-blocker, GTN).
• Undergoing late risk stratification in 48–72h from admission.
Late risk stratification
(See E STEMI: reperfusion therapy (thrombolysis) 1, pp. 22–3.) This in-
volves a number of non-invasive tests to determine the optimal timing for
invasive investigations in intermediate/low-risk patients. Suggested guide-
lines are summarized under E NSTE-ACS: late risk stratification, p. 52.
It is generally performed if there have been no further episodes of pain/
ischaemia at 24–48h after admission.
• Intermediate/low-risk patients who develop recurrent pain and/or
ischaemic ECG changes at any point during their admission, heart failure,
or haemodynamic instability in the absence of a non-cardiac cause
should be managed as high-risk patients (early invasive strategy
± IIb/IIIa inhibitor).
• Fig. 1.8 is a summary of a recommended integrated care pathway
combining diagnosis, risk stratification, and treatment.
• There are other risk stratification assessment scores, including
Braunwald and TIMI. As recommended earlier, high-risk patients from
these assessments should also follow an early invasive strategy, and
intermediate/low-risk patients a more conservative strategy.
50:1–157, copyright 2007 with permission from Wolters Kluwer Health, Inc. M http://circ.ahajournals.org/content/116/7/e148.
51
52
NSTE-ACS: medical management 1 53
NSTE-ACS: medical management 1
Anti-ischaemic therapy
All patients should be treated with a combination of the listed agents to
ensure adequate symptom control and a favourable haemodynamic status
(SBP 8 100–110mmHg, PR 860). All patients should be treated with ad-
equate analgesia, IV nitrates, β-blockers, and statins (if no contraindica-
tions). Other agents can also be added, depending on the clinical picture.
• Analgesia: diamorphine 2.5–5mg IV (with metoclopramide 10mg
IV). Acts as anxiolytic. Reduces pain and SBP through venodilatation
and reduction in sympathetic arteriolar constriction. Can result in
hypotension (responsive to volume therapy) and respiratory depression
(reversal with naloxone 400 micrograms–2mg IV).
• Nitrates: GTN infusion (50mg in 50mL of normal saline at 1–10mL/h),
titrated to pain and keeping SBP >100mmHg. Tolerance to continuous
infusion develops within 24h, and the lowest efficacious dose should
be used. Common side effects are headache and hypotension, both
of which are reversible on withdrawal of medication. Absolute
contraindication is use of sildenafil in the previous 24h. This can result in
exaggerated and prolonged hypotension.
• β-blockers: should be started on presentation, unless contraindicated.
Initially use a short-acting agent (e.g. metoprolol 12.5–100mg PO tds),
which, if tolerated, may be converted to a longer-acting agent (e.g.
atenolol 25–1000mg od). Rapid β-blockade may be achieved using
short-acting IV agents such as metoprolol (E Beta-blockers, p. 751).
Aim for HR of 750–60bpm. Mild LVF is not an absolute contraindication
to β-blocker therapy. Pulmonary congestion may be due to ischaemic
LV systolic dysfunction and/or reduced compliance. If there is overt
heart failure, β-blockade is contraindicated and a calcium antagonist
(amlodipine 5–10mg od) can be used. By reducing HR and BP,
β-blockers reduce myocardial O2 demand, and thus angina. When either
used alone or in combination with nitrates and/or calcium antagonists,
β-blockers are effective in reducing the frequency and duration of both
symptomatic and silent ischaemic episodes.
• Calcium antagonists: diltiazem 60–360mg PO, verapamil 40–120mg
PO tds. Their use aims to reduce HR and BP and is a useful adjunct to
treatment with analgesia/nitrates/β-blockers. Amlodipine/felodipine
5–10mg PO od can be used with pulmonary oedema and in poor LV
function. Calcium antagonists alone do not appear to reduce mortality or
risk of MI in patients with UA. However, when combined with nitrates
and/or β-blockers, they are effective in reducing symptomatic and silent
ischaemic episodes, non-fatal MI, and the need for revascularization.
• Statins (HMG-CoA reductase inhibitors): high-dose statins (atorvastatin
80mg od) have been shown to reduce mortality and recurrent MI in the
acute setting. The role of statins in primary and secondary prevention of
future cardiovascular events is well documented.
• ACEIs: unlike patients with STEMI in whom early introduction of an
ACEI has significant prognostic benefits, specific trials in the NSTE-ACS
setting are lacking. However, there is good evidence that both patients
with low and high risk of cardiovascular disease will benefit from long-
term ACE inhibition (HOPE and EUROPA trials).
54
NSTE-ACS: medical management 2
Antiplatelet therapy
All patients should be given aspirin and clopidogrel/ ticagrelor (unless
contraindicated). IIb/IIIa antagonists for high-risk patients only.
• Aspirin (300mg PO): should be administered immediately in
the emergency department and continued indefinitely (unless
contraindicated). It has been shown to consistently reduce mortality
and recurrent ischaemic events in many trials. In patients with aspirin
hypersensitivity or major gastrointestinal (GI) intolerance, clopidogrel
75mg od should be used.
• Thienopyridines: clopidogrel (300mg) or ticagrelor (180mg) should be
given on admission to all patients with proven NSTE-ACS, regardless
of risk, and be continued [75mg od clopidogrel, 90mg twice daily (bd)
ticagrelor] for at least 12 months. The PLATO trial showed a decrease
in recurrent MI and stroke with ticagrelor, compared to clopidogrel;
however, there was a greater incidence of fatal intracranial bleeding.
Clopidogrel/ticagrelor should be withheld in patients requiring CABG
for 5–7 days to reduce haemorrhagic complications.
• GP IIb/IIIa antagonists: there are multiple short-and long-acting
commercially available molecules. These agents may be used in
conjunction with aspirin, clopidogrel/ticagrelor, and LMWH (or UFH).
Eptifibatide and tirofiban should be used in high-risk patients with
ongoing ischaemia and elevated troponin, in whom an early invasive
management strategy is not planned/available (<24h). In patients with
an early invasive strategy, all IIb/IIIa antagonists can be used. Infusion
is generally continued for 12h post-PCI. Taken as a group, these agents
protect NSTE-ACS patients from death and non-fatal MI during the
acute phase of their presentation and 24h post-intervention. See Box
1.9 for doses and administration regimen.
Antithrombotic therapy
All patients should be given an LMWH.
• LMWHs: have been shown to be as good as, or superior to, UFH in
short-term reduction of death, MI, and revascularization in patients
with NSTE-ACS. They should be used in conjunction with aspirin and
clopidogrel in all patients on presentation and be continued for 2–5 days
after the last episode of pain and ischaemic ECG changes. Other
advantages over UFH include SC administration, lack of monitoring, and
reduced resistance and thrombocytopenia. Box 1.9 lists the doses of
various agents in use for treating NSTE-ACS.
• UFH: multiple trials have demonstrated a reduction in the risk of
death and MI in patients with UA/NSTEMI. UFH should be started on
presentation, as an alternative to LMWH, in conjunction with aspirin
and clopidogrel. Infusion should be continued for 2–5 days subsequent
to the last episode of pain and/or ischaemic ECG changes. An initial
bolus of 60–70U/kg (maximum 5000U) should be followed by an
infusion of 12–15U/kg/h (8 1000U/h). The infusion rate should be
altered to achieve an APTT value of 1.5–2.0 times control. Coagulation
should be checked initially every 6h, followed by once every 24h after
two consistent values have been obtained.
NSTE-ACS: medical management 2 55
Thrombolysis
There is no evidence to suggest that combining thrombolytic agents with
aspirin, LMWH, and conventional anti-ischaemic therapy is of benefit. In the
TIMI IIIB trial, the rtPA group had a worse outcome at 6 weeks and the risk
of bleeding was also greater in the thrombolysis group.
For management key points for NSTEMI, see Box 1.10.
Arrhythmias: general approach
Both tachyarrhythmias and bradyarrhythmias may present with significant
symptoms and haemodynamic compromise. The approach to patients with
arrhythmias depends upon:
• The effects of the rhythm on the patient.
• The diagnosis from the ECG and the rhythm.
• Any underlying cardiac abnormality or identifiable precipitant (see
Box 1.11).
Effects of the rhythm on the patient
Patients with signs of severe haemodynamic compromise
• Impending cardiac arrest.
• Severe pulmonary oedema.
• Shock: SBP <90mmHg.
• Depressed consciousness.
If the patient is in cardiac arrest, then follow the ALS protocol. If the
patient is conscious, but severely compromised, then seek urgent
anaesthetic support and urgent synchronized DC cardioversion to manage
tachyarrhythmias. For bradyarrhythmias, inotropic support (e.g. isopren-
aline), external pacing, or temporary transvenous pacing should be con-
sidered (E Bradyarrhythmias: general approach, pp. 86–7).
Patients with mild to moderate compromise
• Mild pulmonary oedema.
• Low cardiac output, with cool peripheries and oliguria.
• Angina at rest.
Try to record a 12-lead ECG, if possible, and a long rhythm strip before
giving any pharmacological agents and/or defibrillation. This will be invalu-
able for long-term management. If they deteriorate, treat as for severe
haemodynamic compromise.
Diagnosing the arrhythmia
The main distinctions to make are:
• Tachy-(>120/min) versus brady-(<60/min) arrhythmia.
• Narrow (≤120ms or three small squares) versus broad QRS complex.
• Regular versus irregular rhythm.
Arrhythmias: general approach 59
• Magnesium • β-blockade
• DC shock
Monomorphic ventricular
tachycardia (MVT)
Management
(See Box 1.13.)
1. Assess airway, breathing, and circulation immediately.
2. If patient is haemodynamically unstable
• If develops VT while monitored, consider precordial thump—this can
induce a mechanical premature ventricular complex, interrupting the
VT circuit and terminating the arrhythmia. It must not delay external
defibrillation.
• Immediate unsynchronized external defibrillation (200J, 200J, 360J).
Patient is often unconscious and if so, no sedation is required.
3. If patient is haemodynamically stable
• Patient should initially be treated with IV pharmacological agents. If this
is unsuccessful, they can be electrically cardioverted under sedation/
anaesthesia.
• Chemical cardioversion is empiric, and the choice of agent depends on
local policy and expertise. We recommend IV amiodarone, sotalol, or
procainamide as first-line agents. Amiodarone is the agent of choice in
the context of poor LV function. Second-line agents include lidocaine
and β-blockers (the latter is particularly valuable in the setting of MI/
acute ischaemia).
• Give IV magnesium (8mmol bolus over 2–5min, followed by 60mmol
in 50mL of glucose over 24h) for all patients, especially if there is a risk
of hypomagnesaemia (e.g. diuretics, excessive ethanol intake). With
recurrent VT, a bolus dose can be repeated safely. Save a serum sample
for analysis later.
4. Correct reversible factors
• Ischaemia must be treated, especially in the context of post-
infarction VT. This can initially be achieved with β-blockers. Patients
should undergo revascularization at the earliest opportunity
(E STEMI: reperfusion by primary percutaneous coronary intervention,
pp. 20–1).
• Electrolyte abnormalities must be corrected (aim K+ ≥4.0–4.5, Mg2+ ≥1.0).
• Acidosis: if severe (pH ≤7.1), give bicarbonate (8.4% sodium
bicarbonate 50mL via a central line over 20min).
5. If there is recurrent or persistent VT
• Synchronized DC shock under sedation or anaesthesia, with an
anaesthetist present in case of sudden deterioration.
• Overdrive pacing using a temporary transvenous wire may be used to
terminate VT. The combination of prolonged temporary pacing and
antiarrhythmics for recurrent VT is particularly effective in situations
where the VT is provoked by bradycardia. If possible, rhythm strips of
onset of runs of VT must be analysed, looking for bradycardia, heart
block, or sick sinus syndrome. Dual-chamber temporary pacing may
improve cardiac output by restoring AV synchrony.
Investigations
• ECG: acute MI, prolonged QT interval.
• CXR: cardiomegaly, pulmonary oedema.
• U&Es: hypokalaemia, renal impairment.
• Mg2+, Ca2+: ? deficiency.
• Cardiac enzymes: small rises common after DC shock.
• ABG: ? hypoxia, acidosis.
• Echo: for LV function and to exclude structural abnormality
(e.g. aneurysm).
Once the acute episode is over, consider referral to a cardiologist for:
• Holter monitoring.
• Exercise testing.
• Coronary angiography.
• VT stimulation (provocation) testing.
68
Management
Congenital long QT
• PVT in congenital QT prolongation is adrenergically driven, and
treatment must include long-term β-blockade (e.g. propranolol).
• Other adjunctive treatment includes pacemaker implantation and left
stellate ganglionectomy.
• Patients should be considered for ICD therapy. On occasions, decisions
may be difficult because of the young age of patients.
Acquired long QT
• The primary principle is to correct QT prolongation.
• Offending agent(s) must be identified and discontinued immediately.
• PVT in acquired QT prolongation is often secondary to prolonged
pauses, which must be avoided.
• All patients should receive IV Mg2+ (8mmol as a bolus over 2–5min,
followed by a 60mmol infusion over 24h).
• Overdrive temporary pacing (either ventricular or atrial) terminates the
arrhythmia. Continued pacing prevents recurrence of PVT.
• Isoprenaline may be used, while preparations are being made for pacing.
This accelerates the atrial rate and captures the ventricles. Aim for a
rate of 110–120bpm.
References
1. M http://www.brugada.org
70
Ventricular tachycardia: drugs
(See Table 1.5.)
Ventricular tachycardia: drugs 71
72
Atrial tachycardia
(ectopic focus
± re-entry)
Atrioventricular
Sinus re-entrant
node tachycardia
(AVRT)
AV nodal
re-entry AV node
tachycardia
(AVNRT)
Atrial fibrillation: assessment
Presentation
• AF may present with palpitations, chest pain, breathlessness, collapse,
or hypotension. Less commonly, it may present with an embolic event
(stroke, peripheral embolus) or be asymptomatic. It occurs in 10–15%
of patients post-MI.
• Look for signs of an underlying cause (see Box 1.15).
• Try to establish the duration of the AF—this will determine subsequent
management (see later sections).
Investigations
These should be directed at looking for a precipitant and underlying heart
disease. All patients should have:
• ECG:
• Broad QRS if aberrant conduction.
• ST-T-wave changes may be due to rapid rate, digoxin, or underlying
cardiac disease.
• CXR: cardiomegaly, pulmonary oedema, intrathoracic precipitant, valve
calcification (mitral stenosis).
• U&Es: hypokalaemia, renal impairment.
• Cardiac enzymes: ? MI. Small rise after DC shock.
• Thyroid function: thyrotoxicosis may present as AF only.
• Drug levels: especially if taking digoxin.
• Mg2+, Ca2+.
• ABG: if hypoxic, shocked, or ? acidotic.
• Transthoracic (TTE)/transoesophageal echocardiography (TOE): for
LV function and valve lesions and to exclude intracardiac thrombus or
particularly thrombus in the LA appendage prior to cardioversion to
sinus rhythm.
• Other investigations depend on suspected precipitant.
Immediate management
Stabilize the patient
• General measures (E Tachyarrhythmias heart rate >120bpm,
pp. 60–1) are as for any patient with an arrhythmia. Obtain venous
access. Send bloods (E Tachyarrhythmias heart rate >120bpm,
pp. 60–1) and, if possible, check K+ immediately on an ITU machine.
• Correct any electrolyte abnormality.
• If severe acidosis (pH ≤7.1), give 8.4% sodium bicarbonate 50mL slowly
IV over 20min.
• CSM or IV adenosine may help confirm the diagnosis, revealing chaotic
atrial activity. This is particularly helpful in patients with a rate of
150 bpm where atrial flutter should always be considered. CSM or
adenosine will slow the ventricular rate and reveal flutter waves.
• Does the ECG in AF show intermittent or constant delta waves? This
suggests WPW, and digoxin and verapamil are contraindicated.
Atrial fibrillation: assessment 77
Further management
• Cardiovert to sinus rhythm, if appropriate.
• Control the ventricular response rate.
• Try to prevent further episodes of AF.
Atrial fibrillation: management
(See Box 1.16.)
Rate control versus cardioversion
• Important principles required to make a decision are:
• Are there advantages in immediate cardioversion (e.g. ongoing
ischaemia with fast ventricular rhythm, pulmonary oedema,
d consciousness, haemodynamic instability)?
• If the patient is cardioverted, will they remain in sinus rhythm (e.g.
underlying sepsis/thyroid disease, large LA, poor LV, MV disease)?
• What are the risks of thromboembolic complications and is
anticoagulation required (helpful to calculate the CHADS2 and
CHA2D2-Vasc scores)?
• Cardioversion can be achieved chemically or with external defibrillation.
Haemodynamically unstable patients
• All hypotensive patients should undergo external defibrillation using a
synchronized shock of initially150J biphasic DC (E DC cardioversion 1,
pp. 818–19).
• Do not attempt to defibrillate hypotensive patients with known chronic
AF or a known underlying cause driving a fast ventricular response.
Chances of success are very low (e.g. mitral stenosis, severe LV
dysfunction, hyperthyroidism, sepsis).
• Relative contraindications to defibrillation need to be weighed against
the patient’s clinical condition. If possible, aim to optimize the clinical
picture before cardioversion:
• Hypokalaemia may be quickly corrected by giving 20mmol over 1h in
100mL of normal saline via a central line.
• If digoxin toxicity is a possibility, ensure K+ is 4.5–5mmol/L and give
magnesium sulfate 8mmol in 50mL of normal saline over 15min,
before attempting defibrillation at low energies initially (e.g. 20–50J).
• AF of >48h duration carries a significant risk of thromboembolic
complications, unless the patient is on long-term anticoagulation and
INR has been therapeutic. Consider performing TOE first.
• The procedure is detailed under E DC cardioversion 1, pp. 818–19.
• If DC shock fails initially:
• Give IV amiodarone 300mg over 60min via a central line (followed by
IV infusion of 900–1200mg over 24h).
• Correct hypokalaemia (aim for K+ 4.5–5.0mmol/L).
• Attempt further DC shock.
Haemodynamically stable patients
• The initial aim should be rapid pharmacological rate control, followed by
a decision regarding restoration of sinus rhythm if appropriate.
• When making a decision regarding restoration of sinus rhythm, current
evidence must be taken into account:
• Management of AF with a rhythm control strategy alone has no
survival benefit over a rate control strategy, as long as moderate-and
high-risk patients are anticoagulated.
Atrial fibrillation: management 79
• Consider anticoagulation.
Atrial flutter
• This is rarely seen in the absence of underlying CAD, valve disease,
myocardial disease, pericarditis, PE, or thyrotoxicosis.
• The atrial rate is 280–320/min, and atrial activity is seen as flutter waves
in inferior leads and V1 on the ECG.
• The AV node conduction is slower (most commonly 2:1 block,
sometimes 3:1 or 4:1), and this determines the ventricular rate.
• Vagotonic manoeuvres and adenosine increase the AV block and reveal
the flutter waves but only very rarely terminate the arrhythmia.
Management
• Atrial flutter should be treated in exactly the same way as AF.
• DC cardioversion is the therapy of choice, as flutter can be resistant to
pharmacological therapy.
• Lower energies are needed (50–100J).
• If flutter has been present >48h, perform TOE and then cardiovert,
with LMWH/UFH cover (as for AF).
• Medical management:
• Pharmacological agents recommended are similar to AF. Rate control
and reversion rates can be low.
• Digoxin, verapamil, and β-blockers can all be used to slow ventricular
response. IV preparations can be used for more rapid action. The
overall response can be poor. IV verapamil (2.5–5mg over 1–2min,
repeated every 5min to a maximum dose of 20mg) will slow the
response rate and occasionally restore sinus rhythm in 15–20% of
patients.
• Ibutilide and dofetilide have been reported to have reversion rates
of 50% and 70%, respectively. Alternative agents are amiodarone,
flecainide, quinidine, and procainamide.
NB Class Ia drugs can enhance AV conduction and must always be
•
Bradyarrhythmias: general approach
• Ask specifically about previous cardiac disease, palpitations, blackouts,
dizziness, chest pain, symptoms of heart failure, and recent drugs.
• Examine carefully, noting the BP, JVP waveform (? cannon waves), heart
sounds and murmurs, and signs of heart failure.
Investigations
• 12-lead ECG and rhythm strip:
• Look specifically for the relationship between P waves and QRS
complex.
• A long rhythm strip is sometimes necessary to detect CHB if atrial
and ventricular rates are similar.
• Blood tests:
FBC, biochemistry, glucose (urgently).
•
maximum of 3mg.
• Give isoprenaline 0.2mg IV (Min-I-Jet® ) if there is a delay in pacing and
the patient remains unstable. Set up an infusion (1mg in 100mL bag of
normal saline, starting at 1mL/min, titrating to HR).
• Set up an external pacing system (see Box 1.17), if available, and
arrange for transfer to a screening room for transvenous pacing. If
fluoroscopy is not available, ‘blind’ transvenous pacing using a balloon-
tipped pacing wire may be attempted.
• Bradycardia in shock is a poor prognostic sign. Look for a source of
blood loss, and begin aggressive resuscitation with fluids and inotropes.
Bradyarrhythmias: general approach 87
Types of atrioventricular
conduction block
First-degree heart block
• Prolongation of the PR interval (>0.22s, >5 small squares).
Second-degree heart block
• Mobitz type 1 (Wenckebach): progressive increase in PR interval, with
intermittent complete AV block (P wave not conducted).
• Mobitz type 2: the PR interval is constant, but there is intermittent failure
to conduct the P wave. Often occurs in the presence of broad QRS
complex.
• 2:1, 3:1, etc.: as in Mobitz type 2, the PR interval is constant, but every
second (in 2:1) or third (in 3:1) P wave is not conducted on a regular basis.
Third-degree (complete) heart block
Complete AV dissociation. If the P and QRS rates are similar, a long
rhythm strip or exercise (to speed up the atrial rate) will help demonstrate
dissociation.
Causes
• Associated with acute infarction or ischaemia.
• Drugs (β-blockers, digitalis, calcium channel blockers).
• Conduction system fibrosis (Lev and Len’gre syndromes).
• i vagal tone.
• Trauma or following cardiac surgery.
• Hypothyroidism (rarely thyrotoxicosis).
• Hypothermia.
• Hyperkalaemia.
• Hypoxia.
• Valvular disease (aortic stenosis, incompetence, endocarditis).
• Myocarditis (diphtheria, rheumatic fever, viral, Chagas’ disease).
• Associated with neuromuscular disease, i.e. myotonic dystrophy.
• Collagen vascular disease [systemic lupus erythematosus (SLE),
rheumatoid arthritis (RA), scleroderma].
• Cardiomyopathies (haemochromatosis, amyloidosis).
• Granulomatous disease (sarcoid).
• Congenital heart block.
• Congenital heart disease [atrial septal defect (ASD), Ebstein’s, patent
ductus arteriosus (PDA)].
Management
• Principles are listed under E Bradyarrhythmias: general approach,
pp. 86–7.
• In summary, all symptomatic patients must have pacing (temporary or
permanent). The higher the level of block (irrespective of symptoms),
the greater the progression to CHB and/or chances of asystole.
• See E Indications for temporary pacing, pp. 806–7 for situations when
temporary pacing is indicated. Some cardiologists may prefer to implant
a permanent system straightaway.
Pulmonary oedema: assessment
Presentation
• Acute breathlessness, cough, frothy bloodstained (pink) sputum.
• Collapse, cardiac arrest, or shock.
• Associated features may reflect underlying cause:
• Chest pain or palpitations: ? IHD/MI, arrhythmia.
• Preceding history of dyspnoea on exertion: ? IHD, poor LV.
• Oliguria, haematuria: ? acute renal failure (ARF) (E Acute kidney
injury 1, pp. 290–2).
• Seizures, signs of intracranial bleed.
Causes
A diagnosis of pulmonary oedema or ‘heart failure’ is not adequate. An
underlying cause must be sought in order to direct treatment appropriately.
These may be divided into:
• i pulmonary capillary pressure (hydrostatic).
• i pulmonary capillary permeability.
• i intravascular oncotic pressure.
Often a combination of factors are involved (e.g. pneumonia, hypoxia, car-
diac ischaemia) (see Box 1.19).
The main differential diagnosis is acute (infective) exacerbation of COPD
(previous history, quiet breath sounds, wheeze, fewer crackles). It may be
difficult to differentiate the two clinically, and indeed sometimes they could
coexist.
Principles of management
1. Stabilize the patient—relieve distress and begin definitive treatment.
2. Look for an underlying cause.
3. Address haemodynamic and respiratory issues.
4. Optimize and introduce long-term therapy.
Initial rapid assessment
• If the patient is very unwell (e.g. unable to speak, hypoxic, SBP
<100mmHg), introduce stabilizing measures and begin treatment
immediately before detailed examination and investigations (see
Box 1.18).
• If the patient is stable and/or if there is doubt as to the diagnosis, give
O2 and diuretic, but await the outcome of clinical examination and CXR
before deciding on definitive treatment.
Urgent investigations for all patients
• ECG: sinus tachycardia most common. ? any cardiac arrhythmia (AF,
SVT, VT). ? evidence of acute ST change (STEMI, NSTEMI, UA). ?
evidence of underlying heart disease [left ventricular hypertrophy
(LVH), p mitrale].
• CXR: to confirm the diagnosis, look for interstitial shadowing, enlarged
hila, prominent upper lobe vessels, pleural effusion, and Kerley B lines.
Cardiomegaly may or may not be present. Also exclude pneumothorax,
PE (oligaemic lung fields), and consolidation.
Pulmonary oedema: assessment 93
Pulmonary oedema: causes
Look for an underlying cause for pulmonary oedema (see Box 1.19).
Pulmonary oedema: management 1 95
Pulmonary oedema: management 1
Stabilize the patient
• Patients with acute pulmonary oedema should initially be continuously
monitored and managed where full resuscitation facilities are available.
• Sit the patient up in bed.
• Give 60–100% O2 by face mask (unless contraindicated—COPD).
• If the patient is severely distressed, summon the ‘on-call’ anaesthetist
and inform ITU. If dyspnoea cannot be significantly improved by
acute measures (see following text), the patient may require CPAP or
mechanical ventilation.
• Treat any haemodynamically unstable arrhythmia—urgent synchronized
DC shock may be required.
• Give:
• Diamorphine 2.5–5mg IV (caution abnormal ABGs).
• Metoclopramide 10mg IV.
• Furosemide 40–120mg slow IV injection.
• Secure venous access, and send blood for urgent U&Es, FBC, and
cardiac enzymes (including troponin).
• Unless thrombolysis is indicated, take ABG.
• If SBP is ≥90mmHg and the patient does not have aortic stenosis:
• Give SL GTN spray (two puffs).
• Start IV GTN infusion 1–10mg/h; increase the infusion rate every
15–20min, titrating against BP (aiming to keep SBP 7100mmHg).
• If SBP is <90mmHg, treat the patient as cardiogenic shock
(E Cardiogenic shock, pp. 44–5).
• Insert a urinary catheter to monitor urine output, if appropriate.
• Repeat ABG and K+ if the clinical condition deteriorates/fails to improve,
or after 2h if there is improvement and the original sample was abnormal
(serial K+ monitoring could also be performed from venous blood).
• Monitor pulse, BP, RR, O2 saturation with a pulse oximeter (if an
accurate reading can be obtained), and urine output.
Further management
Subsequent management of the patient is aimed at ensuring adequate ven-
tilation/gas exchange, ensuring haemodynamic stability, and correcting any
reversible precipitants of acute pulmonary oedema.
• Assess the patient’s respiratory function:
• Does the patient require respiratory support?(E Respiratory
failure: assessment, pp. 198–9)
• Assess the patient’s haemodynamic status:
• Is the patient in shock? (E Non-VF/VT (asystole and PEA), pp. 8–9)
• Look for an underlying cause (E Pulmonary oedema: causes, p. 94)
• Conditions that require specific treatment:
• Acute AR and MR (E Acute mitral regurgitation, pp. 120–1).
• Diastolic LV dysfunction (E Hypotension and shock post-MI, p. 42).
• Fluid overload (E Pulmonary oedema: specific conditions, p. 100).
• Renal failure (E Acute kidney injury 2, pp. 294–5).
• Severe anaemia.
• Hypoproteinaemia (E Pulmonary oedema: specific conditions, p. 100).
• Sepsis (E Sepsis syndrome and septic shock, pp. 336–7).
96
Pulmonary oedema: management 2
If the patient remains unstable and/or deteriorates, take the following steps.
Assess the patient’s respiratory function
• Wheeze may be caused by interstitial pulmonary oedema. If there is
a history of asthma, give nebulized salbutamol (2.5–5mg), nebulized
ipratropium bromide (500 micrograms), and hydrocortisone (200mg)
IV. Consider commencing an aminophylline infusion. This will relieve
bronchospasm, as well as ‘offload’ by systemic vasodilatation (E Acute
severe asthma: immediate therapy, p. 186). However, it may worsen
tachycardia, and it can be arrhythmogenic and lower potassium levels
(K+) (supplement to ensure K+ levels are 4–5mmol/L).
• Indications for further respiratory support include:
• Patient exhaustion or continuing severe breathlessness.
• Persistent PaO2 <8kPa.
• Rising PaCO2.
• Persistent or worsening acidosis (pH <7.2).
• CPAP: this may be tried for cooperative patients, who can protect
their airway, have adequate respiratory muscle strength, and are not
hypotensive. The positive pressure reduces venous return to the heart
and may compromise BP.
• ET intubation and mechanical ventilation may be required, and some
positive end-expiratory pressure (PEEP) should be used (E Positive
end-expiratory pressure, p. 831).
• Discuss the patient with the on-call anaesthetist or ITU team EARLY.
Assess the patient’s haemodynamic status
It is important to distinguish between cardiogenic and non-cardiogenic pul-
monary oedema, as further treatment is different between the two groups.
This may be difficult clinically. A PA (Swan–Ganz) catheter can be con-
sidered in experienced centres if the patient’s condition will allow.
• Non-cardiogenic pulmonary oedema occurs when the hydrostatic
pressure within the capillary system overcomes the plasma oncotic
pressure. In patients with hypoalbuminaemia, this will occur at PCWP
<15mmHg. The critical PCWP may be estimated by serum albumin
(g/L) × 0.57. Thus, a patient with a serum albumin of 15g/L will develop
hydrostatic pulmonary oedema at an LA pressure of 8mmHg; a serum
albumin of 30g/L will require an LA pressure of >17mmHg, etc.
• Cardiogenic pulmonary oedema is often associated with significant
systemic hypotension or low output states. Contributing factors include
conditions where there is ‘mechanical’ impairment to forward flow [e.g.
valvular heart disease (especially if acute), VSD] or severe myocardial
disease (large MI, myocarditis, cardiomyopathy).
• The gradient between PA diastolic pressure and PCWP (PAD–PCWP)
is generally <5mmHg in cardiogenic, and >5mmHg in non-cardiogenic,
pulmonary oedema (e.g. ARDS).
• The pulse and BP are most commonly elevated due to circulating
catecholamines and overactivity of the renin–angiotensin system.
Examination reveals sweating, cool and ‘shut-down’ peripheries, and
high pulse volume (assess the carotid or femoral pulses).
Pulmonary oedema: management 2 97
Management
(See Box 1.20.)
The general approach involves combination of diuretics, vasodilators, and
inotropes. Patients may be divided into two groups:
• Patients in shock (with SBP <100mmHg) (E Pulmonary
oedema: management 3, pp. 98–9).
• Haemodynamically stable patients with SBP >100mmHg (E Pulmonary
oedema: management 3, pp. 98–9).
Pulmonary oedema: management 3
Patients with SBP <100mmHg
• The patient is in incipient (or overt) shock. The most common aetiology
is cardiogenic shock, but remember non-cardiogenic causes (e.g. ARDS,
septic shock; E Shock, pp. 328–9).
• Optimal monitoring and access: central line ± PA catheter (Swan–Ganz),
urinary catheter, arterial line (monitoring BP and ABGs). Internal jugular
lines are preferable, as the risk of pneumothorax is lower.
• Ensure the patient is not underfilled, using PCWP as a guide (<10mmHg)
(mistaken diagnosis, e.g. septic shock from bilateral pneumonia).
• Is there a mechanical cause that may require emergency surgery?
• Arrange an urgent Echo to rule out:
—VSD and acute MR in all patients with recent MI with/without new murmur
(E STEMI: complications, pp. 32–3).
—Prosthetic heart valve dysfunction (e.g. dehiscence, infection) or pre-
existing native aortic or mitral disease that may require surgery.
• Discuss the patient early on with a cardiologist/cardiac surgeon.
The choice of inotropic agent depends on the clinical condition of the pa-
tient and, to some extent, the underlying diagnosis.
• Treatment of septic shock is discussed elsewhere (E Sepsis syndrome
and septic shock, pp. 336–7).
• SBP 80–100mmHg and cool peripheries: start dobutamine infusion at
5 micrograms/kg/min, increasing by 2.5 micrograms/kg/min every
10–15min to a maximum of 20 micrograms/kg/min until BP
>100mmHg. This may be combined with dopamine (2.5–5 micrograms/
kg/min). However, tachycardia and/or hypotension secondary to
peripheral vasodilatation may limit its effectiveness. PDIs (enoximone or
milrinone) should be considered where dobutamine fails.
• SBP <80mmHg: give a slow IV bolus of adrenaline (2–5mL of 1 in 1000
solution Min-I-Jet® ), and repeat if necessary.
• Dopamine at doses of >2.5 micrograms/kg/min has a pressor action,
in addition to direct and indirect inotropic effects, and may be used
at higher doses (10–20 micrograms/kg/min) if the BP remains low.
However, it tends to raise the pulmonary capillary filling pressure
further and should be combined with vasodilators (e.g. nitroprusside
or hydralazine) once the BP is restored (E Hypertensive emergencies:
drug treatment, pp. 142–3). Beware of arrhythmias at these doses.
• Adrenaline infusion may be preferred to high-dose dopamine as
an alternative inotrope. Once the BP is restored (>100mmHg),
vasodilators, such as nitroprusside/hydralazine or GTN infusion,
should be added to counteract the pressor effects. Adrenaline can be
combined with dobutamine and/or a PDI, especially in the context of
a poor ventricle.
• Intra-aortic balloon counterpulsation should also be used with/without
inotropes in the context of a potentially reversible cause for pulmonary
oedema and shock (e.g. ongoing myocardial ischaemia, VSD, acute MR)
(E Ventricular septal defect post-myocardial infarction (MI), pp. 34–5).
• Further doses of diuretic may be given.
Pulmonary oedema: management 3 99
Infective endocarditis (IE)
Clinical presentation of IE is highly variable and dependent on a combin-
ation of intracardiac pathology, evolution of the infection, and possible
extracardiac involvement. Presentation can be insidious, as in streptococcal
infections, with striking constitutional symptoms, such as with Staphylococcus
aureus.
Presenting features can include the following:
• Symptoms and signs of the infection: these include malaise, anorexia,
weight loss, fever, rigors, and night sweats. Long-standing infection
produces anaemia, clubbing, and splenomegaly.
• Cardiac manifestations of the infection: congestive cardiac failure (CCF),
palpitations, tachycardia, new murmur, pericarditis, or AV block.
• Symptoms and signs due to immune complex deposition:
• Skin: petechiae (most common), splinter haemorrhages, Osler’s
nodes [small tender nodules (pulp infarcts) on hands and feet, which
persist for hours to days], Janeway lesions (non-tender, erythematous,
and/or haemorrhagic areas on the palms and soles).
• Eye: Roth spots (oval retinal haemorrhages with a pale centre, located
near the optic disc), conjunctival splinter haemorrhages, retinal flame
haemorrhages.
• Renal: microscopic haematuria, glomerulonephritis, and renal
impairment.
• Cerebral: toxic encephalopathy.
• Musculoskeletal: arthralgia or arthritis.
Complications of the infection
• Local effects:
• Valve destruction results in a new or changing murmur. This may
result in progressive heart failure and pulmonary oedema.
• A new harsh pan-systolic murmur and acute deterioration may be due
to perforation of the interventricular septum or rupture of the sinus
of Valsalva aneurysm into the RV.
• High-degree AV block (2–4% of IE) occurs with intracardiac extension
of the infection into the interventricular septum (e.g. from aortic valve
endocarditis).
• Intracardiac abscess may be seen with any valve infection (25–50% of
aortic endocarditis, 1–5% of mitral, but rarely with tricuspid) and is
most common in prosthetic valve endocarditis (PVE).
• Embolic events:
• Septic emboli are seen in 20–45% of patients and may involve any
circulation (brain, limbs, coronary, kidney, or spleen); PEs with
tricuspid endocarditis.
Forty to 45% of patients who have had an embolic event will have
•
another.
• The risk depends on the organism (most common with Gram
negative infections, S. aureus, or Candida) (see Box 1.22) and the
presence and size of vegetations (emboli in 30% of patients with no
vegetation on Echo, 40% with vegetations of <5mm, and 65% with
vegetations of >5mm).
Ask specifically for a history of dental work, infections, surgery, IV drug use,
or instrumentation, which may have led to bacteraemia. Examine for any
potential sources of infection, especially teeth or skin lesions. Risk factors
for endocarditis are shown in Box 1.21.
IE: diagnosis
Clinical features can be non-specific, and diagnosis difficult. A high index of
suspicion must be maintained if patients present with unexplained fever,
a predisposing cardiac lesion, bacteraemia, and an embolic phenomenon.
The Duke classification has been devised to help with the diagnosis:
• Definite endocarditis: two major criteria, or one major and three minor
criteria, or five minor criteria.
• Possible endocarditis: findings which fall short of definite endocarditis but
are not rejected.
• Rejected diagnosis: firm alternative diagnosis, or sustained resolution of
clinical features with <4 days of antibiotic therapy.
Major criteria
Positive blood culture
• Typical microorganism for IE from two separate blood cultures.
• Persistently positive blood culture.
Evidence of endocardial involvement
• Positive echocardiogram:
• Oscillating intracardiac mass (vegetation).
• Abscess.
• New partial dehiscence of prosthetic valve.
• New valve regurgitation.
Minor criteria
• Predisposing condition or drug use.
• Fever >38°C.
• Vascular phenomena: arterial emboli, septic pulmonary infarcts, mycotic
aneurysm, intracranial and conjunctival haemorrhage, Janeway lesions.
• Immunologic phenomena: glomerulonephritis, Osler’s nodes, Roth
spots, rheumatoid factor.
• Microbiological evidence: positive blood cultures, but not meeting major
criteria, or serological evidence of organism consistent with IE.
• Echo: positive for IE, but not meeting major criteria.
For common organisms in IE, see Box 1.22.
IE: investigations 105
IE: investigations
• Blood cultures Take 3–4 sets of cultures from different sites at least an
hour apart, and inoculate a minimum of 10mL/bottle
for the optimal pick-up rate. Both aerobic and anaer-
obic bottles must be used. Lab should be advised that
IE is a possibility, especially if unusual organisms are
suspected. In stable patients on antibiotic therapy, doses
must be delayed to allow culture on successive days.
Ask for prolonged (fungal) cultures in IV drug users.
• FBC May show normochromic, normocytic anaemia (ex-
clude haematinic deficiency), fragmented red blood
cells (RBCs), and low haptoglobins, with mechan-
ical valves, neutrophil leucocytosis, and perhaps
thrombocytopenia.
• U&Es May be deranged (this should be monitored
throughout treatment).
• LFTs May be deranged, especially with an increase in alkaline
phosphatase (ALP) and gamma-glutamyl transferase
(GGT). Raised LDH if there is RBC fragmentation.
• ESR/CRP Acute phase reaction.
• Urinalysis Microscopic haematuria ± proteinuria.
• Immunology Polyclonal elevation in serum immunoglobulins (Igs),
complement levels.
• ECG May have changes associated with any underlying
cause. There may be AV block or conduction defects
(especially aortic root abscess) and rarely (embolic)
acute MI.
• CXR May be normal. Look for pulmonary oedema or mul-
tiple infected or infarcted areas from septic emboli
(tricuspid endocarditis) and to exclude chest cause for
sepsis.
• Echo TTE may confirm the presence of valve lesions and/or
demonstrate vegetations if >2mm in size. TOE is more
sensitive for aortic root and mitral leaflet involvement.
A normal Echo does not exclude the diagnosis.
• MRI Useful in investigation of paravalvular extension, aortic
root aneurysm, and fistulae.
• Dentition All patients should have an orthopentamograph
(OPG)—a panoramic dental X-ray, and a dental opinion.
• Swabs Any potential sites of infection (skin lesions).
• V/Q scan In cases where right-sided endocarditis is suspected,
this may show multiple mismatched defects.
• Save serum for Aspergillus precipitins, Candida antibodies (rise in titre),
Q fever (Coxiella burnetti), complement fixation test,
Chlamydia complement fixation test, Brucella agglutinins,
Legionella antibodies, Bartonella spp.
061
IE: antibiotics
‘Blind’ treatment for endocarditis
IE is usually a clinical diagnosis and must be considered in any patient with a
typical history, fever, and a murmur with no other explanation. Often anti-
biotics need to be started before the culture results are available. Be guided
by the clinical setting (see Table 1.9); see Box 1.23 for suggested doses.
IE: antibiotics 107
Duration of treatment
• This is controversial, with a trend towards shorter courses.
Microbiology and infectious disease (ID) opinion is important, especially
in resistant and/or uncommon organisms. Box 1.24 shows one
suggested protocol.
• The duration of treatment varies, depending on the severity of infection
and the infecting organism. IV therapy is usually for at least 2 weeks, and
total antibiotic therapy is for 4–6 weeks.
• If the patient is well following this period, antibiotic treatment may be
stopped. Provided no surgery is indicated (E Surgery for IE, pp. 114–15),
the patient may be discharged and followed up in outpatient clinic.
• Patients should be advised of the need for endocarditis prophylaxis in
the future (see Table 1.10).
• Patients with valvular damage following infection should be followed
long term, and patients with VSDs should be considered for closure.
IE: monitoring treatment
Patients need careful clinical monitoring both during and for several months
after the infection. Reappearance of features suggestive of IE must be in-
vestigated thoroughly to rule out recurrent infection or resistance to the
treatment regimen.
Clinical features
• Signs of continued infection, persistent pyrexia, and persistence of
systemic symptoms.
• Persistent fever may be due to drug resistance, concomitant infection
(central line, urine, chest, septic emboli to lungs or abdomen), or allergy
(? eosinophilia, ? leucopenia, ? proteinuria: common with penicillin but
may be due to any antibiotic; consider changing or stopping antibiotics
for 2–3 days).
• Changes in any cardiac murmurs or signs of cardiac failure.
• Development of any new embolic phenomena.
• Inspect venous access sites daily. Change peripheral cannulae every
3–4 days.
Echo
• Regular (weekly) TTEs may identify clinically silent, but progressive,
valve destruction and development of intracardiac abscesses or
vegetations.
• The tips of long-standing central lines may develop sterile fibrinous
‘fronds’, which may be visible on TOE—change the line and send the tip
for culture.
• ‘Vegetations’ need not be due to infection (see Box 1.25).
ECG
Looking specifically for AV block or conduction abnormalities suggesting
intracardiac extension of the infection. A daily ECG must be performed.
Microbiology
• Repeated blood cultures (especially if there is continued fever).
• Regular aminoglycoside and vancomycin levels (ensuring the absence
of toxic levels and the presence of therapeutic levels). Gentamicin
ototoxicity may develop with prolonged use, even in the absence of
toxic levels.
• Back titration to ensure that minimum inhibitory and bactericidal
concentrations are being achieved.
Laboratory indices
• Regular (daily) urinalysis.
• Regular U&Es and LFTs.
• Regular CRP (ESR every 2 weeks).
• FBC: rising Hb and falling WCC suggests successful treatment; watch for
β-lactam-associated neutropenia.
• Serum magnesium (if on gentamicin).
References
2. Michel PL, Acar J (1995). Native cardiac disease predisposing to infective endocarditis. Eur Heart J
16(suppl B):2–6.
10
Culture-negative endocarditis
• The most common reason for persistently negative blood cultures is
prior antibiotic therapy, and this affects up to 15% of patients with a
diagnosis of IE (see Box 1.26).
• If the clinical response to the antibiotics is good, these should be
continued.
• For persisting fever:
• Withhold antibiotics if not already started.
• Consider other investigations for a ‘pyrexia of unknown origin’ (PUO)
(E Pyrexia of unknown origin, p. 534).
• If clinical suspicion of IE is high, it warrants further investigation.
• Repeated physical examination for any new signs.
• Regular Echo and TOE. ‘Vegetations’ need not be due to infection
(see Box 1.25).
• Repeated blood cultures, especially when the temperature is raised.
Discuss with microbiology about prolonged culturing times (4+
weeks) and special culturing and subculturing techniques. Most
HACEK-group organisms can be detected (see Box 1.26).
• Consider unusual causes of endocarditis.
• Q-fever (Coxiella burnetii): complement fixation tests identify antibodies
to phase 1 and 2 antigens. Phase 2 antigens are raised in acute
illness, and phase 1 antigens in chronic illnesses such as endocarditis.
Polymerase chain reaction (PCR) can be performed on operative
specimens. Treat with indefinite (life-long) oral doxycycline ± co-
trimoxazole, rifampicin, or quinolone.
• Chlamydia psittaci: commonly, there is a history of exposure to birds and
there may be an associated atypical pneumonia. Diagnosis is confirmed
using complement fixation tests to detect raised antibody titres.
• Brucellosis: blood cultures may be positive, although organisms may take
up to 8 weeks to grow. Serology usually confirms the diagnosis.
• Fungi: Candida is the most common species and may be cultured.
Detection of antibodies may be helpful, although levels may be raised
in normals. Detection of a rising titre is of more use. Other fungal
infections (e.g. histoplasmosis, aspergillosis) are rare but may be
diagnosed with culture or serology, although these are commonly
negative. Antigen assays may be positive, or the organism may be
isolated from biopsy material. Fungal IE is more common in patients
with prosthetic valves and IV drug users. Bulky vegetations are common.
Treatment is with amphotericin ± flucytosine. Prosthetic valves must be
removed. Mortality is >50%.
Right-sided endocarditis
• May present as multiple infected PEs (abscesses).
• Always consider this diagnosis in IV drug users (or patients with venous
access).
• Endocarditis on endocardial permanent pacemaker leads is a rare, but
recognized, cause.
• Patients most commonly have staphylococcal infection and are unwell,
requiring immediate treatment and often early surgery.
• Lesions may be sterilized with IV antibiotics.
• Surgery may be required for:
• Resistant organisms (S. aureus, Pseudomonas, Candida, and infection
with multiple organisms).
• Increasing vegetation size in spite of therapy.
• Infections on pacemaker leads (surgical removal of lead and repair or
excision of tricuspid valve).
• Recurrent mycotic emboli.
Surgery for IE
Discuss early with the regional cardiothoracic centre—immediate interven-
tion may be appropriate.
• Surgical intervention may be necessary either during active infection
or later because of the degree of valve destruction. Optimal timing
depends on a number of factors:
• Haemodynamic tolerance of lesion.
• Outcome of the infection.
• Presence of complications.
• Choice of antimicrobial therapy should be modified, depending on
microbiological results from intraoperative specimens. Samples should
be sent for culture, staining, immunological testing, and PCR, depending
on the suspected organism.
• Duration of antimicrobial treatment is dependent on the clinical picture:
• Culture-negative operative specimens: 2–3 weeks for valve infection
and 3–4 weeks for abscess.
• Culture-positive operative specimens: 3–4 weeks for valve infection
and 4–6 weeks for abscess.
• Timing is dictated by the clinical picture. Indications for urgent surgery
are listed in Box 1.27. In patients with neurological injury, surgery should
be delayed to avoid intracranial haemorrhage if cardiac function permits
(embolic infarct: delay 10–14 days; haemorrhage: 21–28 days and when
ruptured mycotic aneurysms have been repaired).
• Box 1.27 summarizes the absolute and relative indications for surgery.
Haemodynamic tolerance of lesion
• If the patient is haemodynamically stable, surgery may be delayed until
after the antibiotic course is completed. Final management depends
on the valve affected, the degree of destruction, and its effect on
ventricular function. Severe AR and MR usually require surgery; tricuspid
regurgitation, if well tolerated, is managed medically.
• Decompensation (severe CCF or low cardiac output syndrome with
functional renal failure) may respond to surgery, but mortality is high.
• ‘Metastable’ patients who have been successfully treated after an
episode of acute decompensation should be considered for early
operation after 2–3 weeks of antibiotic therapy.
Outcome of infection
• Persistence or relapse of infection (clinical and laboratory indices),
despite appropriate antibiotics at an adequate dose, may be due to
either a resistant organism or an abscess (paravalvular, extracardiac).
Consider valve replacement if no extracardiac focus is found.
• The organism may influence the decision—consider early surgery for
fungal endocarditis or PVE with Escherichia coli or S. aureus.
Surgery for IE 115
Presence of complications
Urgent surgery indications comprise:
• High-degree AV block.
• Perforation of interventricular septum.
• Rupture of the sinus of Valsalva aneurysm into the RV.
• Intracardiac abscess.
• Recurrent septic emboli.
• PVE, especially associated with an unstable prosthesis.
Endocarditis prophylaxis
NB This is one regimen (after Leport et al.).3 Refer to your local policy.
See Boxes 1.28 and 1.29.
Box 1.21 shows cardiac conditions at risk of IE. High and moderate risk
requires prophylaxis; ‘low’ risk does not.
The regimen may be modified, depending on the ‘degree of risk’ (both
patient-and procedure-related), as shown in Table 1.10.
References
3. Leport C, Horstkotte D, Burckhardt D (1995). Antibiotic prophylaxis from an international group
of experts towards a European consensus. Group of Experts of the International Society for
Chemotherapy. Eur Heart J 16(Suppl B):126–31.
DVT: management
• If there is a high clinical suspicion of DVT, start empiric anticoagulation
with LMWH. (Stop this if subsequent investigations are negative.)
• Below-knee DVT: treat with compression stockings and SC prophylactic
doses of LMWH until mobile, to deter proximal propagation of the
thrombus.
• Above-knee DVT: thrombi within the thigh veins warrant full
anticoagulation with LMWH/UFH and subsequently oral anticoagulant.
• See management algorithm in Fig. 1.10.
Anticoagulation
Heparin
• LMWHs have now superseded UFH for both DVT and PE.
• Treat with LMWH before starting oral anticoagulation.
• LMWH are administered primarily as a once-daily SC injection, and the
dosage is determined by patient weight.
Warfarin
• Always start LMWH before starting warfarin and continue until the
INR is within therapeutic range. Protein C (a vitamin K-dependent
anticoagulant) has a shorter half-life than the other coagulation factors
and levels fall sooner, resulting in a transient procoagulant tendency.
• Continue warfarin (INR 2–2.5) for 3 months (this varies, depending on
the cause of DVT, from 6 weeks to life).
• If recurrent DVT, or patient is at high risk of recurrence, consider life-
long anticoagulation.
Novel anticoagulants
Direct acting oral anticoagulants (dabigatran, apixaban, rivaroxaban and
edoxaban) are licensed for treatment of DVT or PE and do not require
routine testing.
• Dabigatran and edoxaban should be started after 5 days of treatment
with LMWH. The oral anticoagulant and LMWH should not be given
together (see BNF for details).
• Apixaban and rivaroxaban do not require LMWH treatment before
use, but require an initial period of treatment with a higher dose of the
oral anticoagulant followed by a lower maintenance dose (see BNF for
details).
Thrombolysis
• This should be considered for recurrent, extensive proximal venous
thrombosis (e.g. femoral or iliac veins), as it is more effective than
anticoagulation alone in promoting clot dissolution and produces
a better clinical outcome. Given the lack of evidence base for this
approach, an experienced clinician should be involved in this decision.
• Catheter-directed thrombolytic therapy (rtPA or SK) is superior to
systemic thrombolysis.
• One approach is SK 250 000U over 30min, then 100 000U every hour
for 24–72h (see data sheet). For contraindications to thrombolysis, see
E STEMI: thrombolysis 2, pp. 24.
DVT: management 125
Further management
• Women taking the combined oral contraceptive pill (OCP) should be
advised to stop this.
• If there are contraindications to anticoagulation, consider the insertion
of a caval filter to prevent PE; however, such filters are best removed
after 2 weeks to prevent long-term peripheral oedema from venous
stasis.
• All patients should be treated with thigh-high compression stockings to
try to reduce symptomatic venous distension when mobilizing.
Suspected DVT
Normal Abnormal
Arrange USS
D-dimer D-dimer
Normal
Clot on USS
USS
Discharge to GP
with letter
Provide with shaped Refer to
elasticated tubular outpatient
stockinette and DVT team
A&E RC at least 1
week on Tues or Thurs
Practice points
• A normal D-dimer excludes a PE with 795% accuracy, but a positive
D-dimer can be secondary to other disorders.
281
PE: investigations 1
General investigations
• ABG: a normal ABG does not exclude a PE. dPaO2 is invariable with
larger PEs. Other changes include mild respiratory alkalosis and dPaCO2
(due to tachypnoea) and metabolic acidosis (secondary to shock).
• ECG: commonly shows sinus tachycardia and non-specific ST-and T-
wave changes in the anterior chest leads. The classical changes of acute
cor pulmonale, such as S1Q3T3, right axis deviation, or RBBB, are only
seen with massive PE. Less common findings include atrial flutter or AF.
• CXR: may be normal, and a near-normal chest film in the context
of severe respiratory compromise is highly suggestive of a PE. Less
commonly may show focal pulmonary oligaemia (Westermark’s sign), a
raised hemidiaphragm, a small pleural effusion, wedge-shaped shadows
based on the pleura, sub-segmental atelectasis, or dilated proximal PAs.
• Blood tests: there is no specific test. FBC may show neutrophil
leucocytosis; mildly elevated CK, troponin, and bilirubin may be seen.
• Echo/TOE: insensitive for diagnosis but can exclude other causes of
hypotension and raised right-sided pressures (e.g. tamponade, RV
infarction; E Right ventricular infarction, p. 28). In PE, it might show RV
dilatation and global hypokinesia, with sparing of the apex (McConnell’s
sign), and PA dilatation. Doppler may show tricuspid/pulmonary
regurgitation, allowing estimation of RV systolic pressure.Sometimes, in
bigger PE, the thrombus in the PA may be visible.
For underlying causes, see Box 1.32.
Specific investigations
D-dimer
• A highly sensitive, but non-specific, test in acute PE.
• Useful in ruling out PE in patients with low or intermediate probability.
• Results can be affected by advancing age, pregnancy, trauma, surgery,
malignancy, and inflammatory states.
Ventilation/perfusion lung scanning
A perfusion lung scan (with IV technetium-99-labelled albumin) should be
performed in all suspected cases of PE. A ventilation scan (inhaled xenon-
133) in conjunction increases the specificity by assessing whether the
defects in the ventilation and perfusion scans ‘match’ or ‘mismatch’. Pre-
existing lung disease makes interpretation difficult.
• A normal perfusion scan rules out significant-sized PE and is reported as
low probability for PE.
• Abnormal scans are reported as medium or high probability:
A high probability scan is strongly associated with PE, but there is a
•
PE: investigations 1 129
PE: investigations 2
CTPA
• This is the recommended initial lung imaging modality in patients with
non-massive PE.
• Allows direct visualization of emboli, as well as other potential
parenchymal disease, which may provide an alternative explanation for
symptoms.
• Sensitivity and specificity are high (>90%) for lobar PAs, but not so high
for segmental and sub-segmental PAs.
• A patient with a positive CTPA does not require further investigation
for PE.
• A patient with a negative CTPA in the context of a high/intermediate
probability of a PE should undergo further investigation.
Evaluation of leg veins with USS
• Not very reliable. Almost half of patients with PE do not have evidence
of a DVT and therefore, a negative result cannot rule out a PE.
• Useful second-line investigation as an adjunct to CTPA and V/Q scan.
• Outcome studies have demonstrated that it would be safe not to
anticoagulate patients with a negative CTPA and lower limb USS who
have an intermediate/low probability of a PE.
Pulmonary angiography
• Is the ‘gold standard’ investigation.
• It is indicated in patients in whom a diagnosis of embolism cannot be
established by non-invasive means. Look for sharp cut-off of vessels or
obvious filling defects.
• An invasive investigation, and can be associated with 0.5% mortality.
• If there is an obvious filling defect, the catheter, or a guidewire passed
through the catheter, may be used to disobliterate the thrombus.
• After angiography, the catheter may be used to give thrombolysis
directly into the affected PA (E PE: management 1, p. 132).
• The contrast can cause systemic vasodilatation and haemodynamic
collapse in hypotensive patients.
Magnetic resonance pulmonary angiography
• Results are comparable to pulmonary angiography in preliminary
studies.
• It can simultaneously assess ventricular function.
Fig. 1.11 summarizes one proposed pathway for investigation of potential
PE patients.
PE: investigations 2 131
Suspected PE
Monitored area
O2, IV fluids, analgesia
ABG, ECG, CXR, bloods
Discharge
Results do not
Results confirm
confirm clinical
clinical suspicion
suspicion
PE: management 1
1. Stabilize the patient
• Unless an alternative diagnosis is made, the patient should be treated as
for a PE until this can be excluded.
• Monitor cardiac rhythm, pulse, BP, and respiratory rate (RR) every
15min with continuous pulse oximetry and a cardiac monitor. Ensure full
resuscitation facilities are available.
• Obtain venous access and start IV fluids (crystalloid or colloid).
• Give maximal inspired O2 via face mask to correct hypoxia. Mechanical
ventilation may be necessary if the patient is tiring (beware of
cardiovascular collapse when sedation is given for ET intubation).
• Give LMWH or UFH to all patients with high or intermediate risk of PE
until diagnosis is confirmed. A meta-analysis of multiple trials has shown
LMWH to be superior to UFH, with a reduction in mortality and
bleeding complications. For doses, consult the local formulary.
• If there is evidence of haemodynamic instability (systemic hypotension,
features of right heart failure) or cardiac arrest, patients may benefit
from thrombolysis with rtPA or SK—beware as doses used are different
from treatment of STEMI (see Box 1.33).
2. Analgesia
• Patients may respond to oral NSAIDs (remember gastric protection, as
these patients are also anticoagulated).
• Opiate analgesia to be used with caution. The vasodilatation caused by
these drugs may precipitate or worsen hypotension. Give small doses
(1–2mg diamorphine IV) slowly. Hypotension should respond to IV
colloid.
• Avoid IM injections (anticoagulation and possible thrombolysis).
3. Investigations with a view to a definite diagnosis
See E PE: investigations 1, p. 128 and E PE: investigations 2, p. 130.
4. Anticoagulate
• Patients with a positive diagnosis must undergo anticoagulation with
warfarin (or one of the newer licensed novel oral anticoagulants—this
will depend on local protocols). There should be a period of overlap
with LMWH/UFH until INR values are therapeutic. Target INR is 2–3
for most cases (see Box 1.34).
• Standard duration of anticoagulation is:
• 4–6 weeks for temporary risk factor.
• 3 months for first idiopathic cases.
• At least 6 months for other cases.
• With recurrent events and underlying predisposition to
thromboembolic events (e.g. antiphospholipid antibody syndrome),
life-long anticoagulation may be needed (as well as higher target
INR >3).
PE: management 1 133
PE: management 2
Cardiac arrest
(Also see E Universal treatment algorithm, pp. 8–9.)
• Massive PE may present as cardiac arrest with EMD. Exclude the other
causes of EMD (E Universal treatment algorithm, pp. 8–9).
• Chest compressions may help break up the thrombus and allow it to
progress more distally, thereby restoring some cardiac output.
• If clinical suspicion of PE is high and there is no absolute contraindication
to thrombolysis, give rtPA [similar in dose to STEMI, with a maximum of
50mg (see Box 1.33), followed by heparin].
• If cardiac output returns, consider pulmonary angiography or inserting a
PA catheter to try to mechanically disrupt the embolus.
Hypotension
The acute increase in pulmonary vascular resistance (PVR) results in RV
dilatation and pressure overload, which mechanically impairs LV filling and
function. Patients require a higher than normal right-sided filling pressure
but may be worsened by fluid overload.
• Insert an internal jugular sheath prior to anticoagulation. This can be
used for access later, if necessary.
• If hypotensive, give colloid (e.g. 500mL of Haemaccel® stat).
• If hypotension persists, invasive monitoring and/or inotropic support is
required. The JVP is a poor indicator of left-sided filling pressures in such
cases. Adrenaline is the inotrope of choice.
• Femoro-femoral cardiopulmonary bypass or extracorporeal
membrane oxygenation in a specialized centre may be used to support
the circulation until thrombolysis or surgical embolectomy can be
performed.
• Pulmonary angiography in a hypotensive patient is hazardous, as the
contrast may cause systemic vasodilatation and cardiovascular collapse.
Pulmonary embolectomy
• In patients who have contraindications to thrombolysis and are in shock
requiring inotropic support, there may be a role for embolectomy if
appropriate skills are on site.
• This can be performed percutaneously in the catheterization laboratory
using a number of devices or surgically on cardiopulmonary bypass.
• Percutaneous procedures may be combined with peripheral or central
thrombolysis.
• Seek specialist advice early. Best results are obtained before onset of
cardiogenic shock.
• Radiological confirmation of extent and site of embolism is preferable
before thoracotomy.
• Mortality is 725–30%.
PE: management 2 135
Fat embolism
Commonly seen in patients with major trauma. There is embolization of
fat and microaggregates of platelets, RBCs, and fibrin in systemic and pul-
monary circulation. Pulmonary damage may result directly from the emboli
(infarction) or by chemical pneumonitis and ARDS (E Adult respiratory
distress syndrome 1, p. 204).
Clinical features
• There may be a history of fractures, followed (24–48h later) by chest
pain, breathlessness, cough, haemoptysis, confusion, and rash.
• Examination reveals fever (38–39°C), widespread petechial rash
(25–50%), cyanosis, and tachypnoea. There may be scattered
crepitations in the chest, although examination may be normal. Changes
in mental state may be the first sign with confusion, drowsiness, seizures,
and coma. Examine the eyes for conjunctival and retinal haemorrhages;
occasionally, fat globules may be seen in the retinal vessels. Severe fat
embolism may present as shock.
Investigations
• ABG: hypoxia and respiratory alkalosis (with low PaCO2), as for
thromboembolic PE.
• FBC: thrombocytopenia, acute intravascular haemolysis.
• Coagulation: disseminated intravascular coagulation (DIC).
• U&Es and glucose: renal failure, hypoglycaemia.
• Ca2+: may be low.
• Urine: microscopy for fat and dipstick for Hb.
• ECG: usually non-specific (sinus tachycardia; occasionally signs of right
heart strain).
• CXR: usually lags behind the clinical course. There may be patchy
bilateral air space opacification. Effusions are rare.
• CT head: consider if there is a possibility of head injury with expanding
subdural or epidural bleed.
Differential diagnosis
Pulmonary thromboembolism, other causes of ARDS (E Adult respiratory
distress syndrome 1, p. 204), septic shock, hypovolaemia, cardiac or pul-
monary contusion, head injury, aspiration pneumonia, transfusion reaction.
Management
• Treat respiratory failure (E Respiratory failure: management,
pp. 202–3). Give O2 (maximal via face mask; CPAP and mechanical
ventilation if necessary).
• Ensure adequate circulating volume and cardiac output. Central venous
pressure (CVP) is not a good guide to left-sided filling pressures, and a
PA catheter (Swan–Ganz) should be used to guide fluid replacement.
Try to keep PCWP 12–15mmHg, and give diuretics if necessary. Use
inotropes to support circulation, as required (E Adult respiratory
distress syndrome 3, pp. 208–9).
Hypertensive emergencies
Hypertensive crisis
Hypertensive crisis is defined as a severe elevation in BP [SBP >200mmHg,
diastolic BP (DBP) >120mmHg]. Rate of change in BP is important.
A rapid rise is poorly tolerated and leads to end-organ damage, whereas
a gradual rise in a patient with existing poor BP control is tolerated better.
Hypertensive crisis is classified as:
• Hypertensive emergency where a high BP is complicated by acute target
organ dysfunction (see Box 1.35) and includes:
• Hypertensive emergency with retinopathy where there is marked
elevation in BP (classically DBP >140mmHg), with retinal
haemorrhages and exudates (previously called accelerated
hypertension), and
• Hypertensive emergency with papilloedema, with a similarly high BP and
papilloedema (previously called malignant hypertension).
• Hypertensive urgency where there is a similar rise in BP, but without
target organ damage.
Conditions which may present with hypertensive
emergency
• Essential hypertension.
• Renovascular hypertension: atheroma, fibromuscular dysplasia, acute
renal occlusion.
• Renal parenchymal disease: acute glomerulonephritis, vasculitis,
scleroderma.
• Endocrine disorders: phaeochromocytoma, Cushing’s syndrome,
primary hyperaldosteronism, thyrotoxicosis, hyperparathyroidism,
acromegaly, adrenal carcinoma.
• Eclampsia and pre-eclampsia.
• Vasculitis.
• Drugs: cocaine, amphetamines, monoamine oxidase inhibitor (MAOI)
interactions, ciclosporin, β-blocker, and clonidine withdrawal.
• Autonomic hyperactivity in the presence of spinal cord injury.
• Coarctation of the aorta.
Presentation
• Occasionally, minimal non-specific symptoms such as mild headache and
nosebleed.
• A small group of patients present with symptoms resulting from BP-
induced microvascular damage:
• Neurological symptoms: severe headache, nausea, vomiting,
visual loss, focal neurological deficits, fits, confusion, intracerebral
haemorrhage, coma.
• Chest pain (hypertensive heart disease, MI, or aortic dissection)
and CCF.
• Symptoms of renal failure: renal impairment may be chronic
(secondary to long-standing hypertension) or acute (from necrotizing
vasculitis of malignant hypertension).
Hypertensive emergencies: management
Priorities in management
• Confirm the diagnosis and assess the severity.
• Identify those patients needing specific emergency treatment.
• Plan long-term treatment.
Diagnosis and severity
• Ask about previous BP recordings, previous and current treatment,
sympathomimetics, antidepressants, non-prescription drugs, and
recreational drugs.
• Check the BP yourself, in both arms, after a period of rest and, if
possible, on standing. Monitor the patient’s BP regularly while they are
in accident and emergency (A&E).
• Examine carefully for clinical evidence of cardiac enlargement or heart
failure, peripheral pulses, renal masses, or focal neurological deficit.
Always examine the fundi—dilate if necessary.
Investigations
All patients should have:
• FBC: MAHA with malignant hypertension.
• U&Es: renal impairment and/or dK+ (diffuse intrarenal ischaemia and
secondary hyperaldosteronism).
• Coagulation screen: DIC with malignant hypertension.
• CXR: cardiac enlargement:
• Aortic contour (? dissection).
• Pulmonary oedema.
• Urinalysis: protein and red cells ± casts.
• ECG: voltage criteria for LVH (see Box 1.36).
Other investigations, depending on the clinical picture and possible aeti-
ology, include:
• 24-h urine collection:
• Creatinine clearance.
• Free catecholamines, metanephrines, or vanillyl mandelic acid (VMA).
• Echo: LVH, aortic dissection.
• Renal USS and Doppler: size of kidneys and renal artery stenosis.
• Magnetic resonance (MR) renal angiogram: renal artery stenosis.
• CT/MR brain: intracranial bleed.
• Drug screen: cocaine, amphetamine, others.
Indications for admission
• DBP persistently ≥120mmHg.
• Retinal haemorrhages, exudates, or papilloedema.
• Renal impairment.
Treatment principles
• Rapid reduction in BP must be avoided and can be very dangerous. This
can result in cerebral and cardiac hypoperfusion (an abrupt change of
>25% in BP will exceed cerebral BP autoregulation).
• Initial BP reduction of 25% to be achieved over 1–4h, with a less rapid
reduction over 24h to a DBP of 100mmHg.
• The only two situations where BP must be lowered rapidly are in the
context of aortic dissection and MI.
Treatment
(Also see E Hypertensive emergencies: drug treatment, p. 142.)
• The majority of patients who are alert and otherwise well may be
treated with oral therapy to lower BP gradually.
• For stable patients, first-line treatment should be with a low-dose
calcium antagonist (e.g. amlodipine 5mg). Alternatively, a β-blocker,
ACEI, or diuretic may be used.
• Urgent invasive monitoring (arterial line) prior to drug therapy is
indicated for patients with:
• Evidence of hypertensive encephalopathy.
• Complications of hypertension (e.g. aortic dissection, acute
pulmonary oedema, or renal failure).
• Treatment of an underlying condition (e.g. glomerulonephritis,
phaeochromocytoma, CREST crisis).
• Patients with persistent DBP ≥140mmHg.
• Eclampsia.
• Sublingual nifedipine must be avoided.
Conditions requiring specific treatment are listed in Box 1.37.
Long-term management
• Investigate, as appropriate, for an underlying cause.
• Select a treatment regimen that is tolerated and effective. Tell the
patient why long-term therapy is important.
• Try to reduce all cardiovascular risk factors by advising the patient to
stop smoking, giving appropriate dietary advice (cholesterol), and aiming
for optimal diabetic control.
• Monitor long-term control and look for end-organ damage (regular
fundoscopy, ECG, U&Es). Even poor control is better than no control.
Hypertensive emergencies: drug
treatment
(See Tables 1.12 and 1.13.)
NB It is dangerous to reduce the BP quickly. Aim to reduce the DBP to 100–110mmHg within
2–4h. Unless there are good reasons to commence IV therapy, always use oral medicines.
Hypertensive emergency
with retinopathy (accelerated and
malignant hypertension)
This is part of a continuum of disorders characterized by hypertension
(DBP often >120mmHg) and acute microvascular damage (seen best in the
retina, but present in all organs). It may be difficult to decide whether the
damage in some vascular beds is the cause or effect of hypertension. An
example is in the context of acute glomerulonephritis.
• Accelerated hypertension (grade 3 retinopathy; see Box 1.38) may
progress to malignant hypertension, with widespread necrotizing
vasculitis of the arterioles (and papilloedema).
• Presentation is commonly with headache or visual loss and varying
degrees of confusion. More severe cases present with renal failure,
heart failure, microangiopathic haemolytic anaemia (MAHA), and DIC.
Management
• Transfer the patient to medical HDU/ITU.
• Insert an arterial line, and consider a central venous line if there is
evidence of necrotizing vasculitis and DIC. Catheterize the bladder.
• Monitor the neurological state, ECG, and fluid balance.
• Aim to lower the DBP to 100mmHg or by 15–20mmHg, whichever is
higher, over the first 24h.
• Those with early features may be treated successfully with oral therapy
(β-blockers, calcium channel blockers).
• Patients with late symptoms or who deteriorate should be given
parenteral therapy, aiming for more rapid lowering of BP.
• If there is evidence of pulmonary oedema or encephalopathy, give
furosemide 40–80mg IV.
• If there is no LVF, give a bolus of labetalol, followed by an infusion. For
patients with LVF, nitroprusside or hydralazine is preferable.
• Consult the renal team for patients with ARF or evidence of acute
glomerulonephritis (>2+ proteinuria, red cell casts). ARF is managed
as described under E Acute kidney injury: management, pp. 298–9.
Dopamine should be avoided, as it may worsen hypertension.
• Consider giving an ACEI. High circulating renin levels may not allow
control of hypertension, which, in turn, causes progressive renal failure.
ACEIs will block this vicious circle. There may be marked first-dose
hypotension, so start cautiously.
• Haemolysis and DIC should recover with control of BP.
Hypertensive encephalopathy
• Caused by cerebral oedema secondary to loss of cerebral
autoregulatory function.
• Usually gradual onset and may occur in previously normotensive
patients at BPs as low as 150/100mmHg. It is rare in patients with
chronic hypertension and pressures are also much higher.
Symptoms
• Headache, nausea and vomiting, confusion, grade III and IV hypertensive
retinopathy.
• Late features consist of focal neurological signs, fits, and coma.
Diagnosis
• A diagnosis of exclusion and other differential diagnoses must be ruled
out (e.g. stroke, encephalitis, tumours, bleeding, vasculitis).
• History is helpful, particularly of previous seizures, SAH usually being
sudden in onset, and strokes being associated with focal neurological
deficit.
• Always exclude hypoglycaemia.
• Starting BP-lowering treatment for hypertension associated with a
stroke can cause extension of the stroke.
• An urgent MRI or CT brain must be obtained to rule out some of the
differential diagnoses.
Management
• The primary principle of BP control is to reduce DBP by 25% or reduce
DBP to 100mmHg, whichever is higher, over a period of 1–2h.
• Transfer the patient to ITU for invasive monitoring (E Hypertensive
emergency with retinopathy (accelerated and malignant hypertension),
pp. 144–5).
• Monitor the neurological state, ECG, and fluid balance.
• Correct electrolyte abnormalities (K+, Mg2+, Ca2+).
• Give furosemide 40–80mg IV.
• Nitroprusside is the first-line agent, as it allows easy control of BP
changes, despite its tendency to increase cerebral blood flow.
• Labetalol and calcium channel blockers are second-line agents and
should be added in, if necessary.
• It is vital to avoid agents with potential sedative action such as
β-blockers, clonidine, and methyldopa.
• In selected patients who are stable and present at the very early stages,
oral therapy with a combination of β-blockers and calcium blockers may
be sufficient.
Aortic dissection: assessment
Aortic dissection is a surgical/medical emergency and, untreated, has a
1-year mortality of >90%. Dissection begins with formation of a tear in
the intima, and the force of the blood cleaves the media longitudinally to
various lengths. Predisposing factors are summarized in Box 1.39.
Classification
There are three classifications, as illustrated in Fig. 1.12 (DeBakey, Stanford,
and descriptive). Dissections involving the ascending and/or aortic arch
are surgical emergencies, and those exclusive to the descending aorta are
treated medically.
Stanford
classification Type A Type B
Presentation
• Chest pain: classically abrupt onset of very severe, most commonly
anterior, chest pain radiating to the interscapular region. Usually
tearing in nature and, unlike the pain of MI, most severe at its onset.
Pain felt maximally in the anterior chest is associated with ascending
aortic dissection, whereas interscapular pain suggests dissection of
the descending aorta. Patients often use adjectives such as ‘tearing’,
‘ripping’, ‘sharp’, and ‘stabbing’ to describe the pain.
• Sudden death or shock: usually due to aortic rupture or cardiac tamponade.
• CCF: due to acute aortic incompetence and/or MI from dissection
extending into the coronary arteries (usually RCA).
• Patients may also present with symptoms and signs of occlusion of one
of the branches of the aorta. Examples include:
• Stroke or acute limb ischaemia: due to compression or dissection.
• Paraplegia with deficits: spinal artery occlusion.
• MI infarction: usually the RCA.
• Renal failure and renovascular hypertension.
• Abdominal pain: coeliac axis or mesenteric artery occlusion.
• Aortic dissection may be painless.
• Ask specifically about history of hypertension, previous heart murmurs or
aortic valve disease, and previous CXRs that may be useful for comparison.
Examination
• This may be normal.
• Most patients are hypertensive on presentation. Hypotension is
more common in dissections of the ascending aorta (20–25%) and
Practice points
Unilateral tongue weakness after a car crash with whiplash injury suggests
carotid artery dissection.
501
Aortic dissection: investigations
General
• ECG: may be normal or non-specific (LVH, ST/T abnormalities). Look
specifically for evidence of acute MI (inferior MI is seen if the dissection
compromises the RCA ostium).
• CXR: may appear normal but, with hindsight, is almost always abnormal.
Look for widened upper mediastinum, haziness or enlargement of the
aortic knuckle, irregular aortic contour, separation (>5mm) of intimal
calcium from outer aortic contour, displacement of trachea to the right,
enlarged cardiac silhouette (pericardial effusion), and pleural effusion
(usually on the left). Compare with previous films, if available.
• Bloods: baseline FBC, U&Es, cardiac enzymes, as well as cross-match.
A novel monoclonal antibody assay to smooth muscle myosin heavy
chains can accurately differentiate an acute dissection from an MI.
Diagnostic
• Echocardiography: TTE may be useful in diagnosing aortic root dilatation,
AR, and pericardial effusion/tamponade. TOE is the investigation of
choice, as it allows better evaluation of both the ascending aorta and
descending aorta, may identify the origin of the intimal tear, allows
evaluation of the origins of the coronary arteries in relation to the
dissection flap, and provides information on aortic insufficiency. It is not
good at imaging the distal ascending aorta and proximal arch.
• MR angiography: is the gold standard for diagnosing aortic dissection.
It has all the positive features of TOE and, in particular, also provides
accurate information on all segments of the ascending/arch/descending
aorta, entry/exit sites, and branch vessels. Images can be displayed in
multiple views, as well as reconstructed in three dimensions. However,
there are a number of disadvantages, including: (1) availability of service
out of hours and cost; (2) presence of metallic valves or pacemakers
may preclude the patient from having an MRI; and (3) monitoring of
unstable patients in the scanner can be difficult and unsafe.
• Spiral (helical) CT with contrast: allows three-dimensional display of all
segments of the aorta and adjacent structures. True and false lumens
are identified by differential contrast flow and enter and exit sites of the
intimal flap, as well as pleural and pericardial fluids. However, it cannot
demonstrate disruption of the aortic valve, which may be associated
with ascending aortic dissection.
• Angiography: using the femoral or axillary approach, may demonstrate
altered flow in the two lumens, aortic valve incompetence, involvement
of the branches, and the site of the intimal tear. It is invasive and
associated with a higher risk of complications in an already high-risk
patient. It has largely been superseded by CT/MRI and TOE.
Aortic dissection: management 1
Stabilize the patient
• If the diagnosis is suspected, transfer the patient to an area where full
resuscitation facilities are readily available.
• Secure venous access with large-bore cannulae (e.g. green/grey
Venflon®).
• Take blood for FBC, U&Es, and cross-match (10U).
• When the diagnosis is confirmed or in cases with cardiovascular
complications, transfer to ITU; insert an arterial line (radial unless the
subclavian artery is compromised when a femoral line is preferred), a
central venous line, and a urinary catheter.
• Immediate measures should be taken to correct BP (E Aortic
dissection: management 2, pp. 154–5).
• Adequate analgesia (diamorphine 2.5–10mg IV and metoclopramide
10mg IV).
Plan the definitive treatment
(See Box 1.41.)
This depends on the type of dissection (see Fig. 1.13) and its effects on
the patient. General principles are:
• Patients with involvement of the ascending aorta should have
emergency surgical repair and BP control.
• Patients with dissection limited to the descending aorta are managed
initially medically with aggressive BP control.
However, this may change in the near future with emerging encouraging
data from deployment of endovascular stent grafts.
Indications and principles for surgery
• Involvement of the ascending aorta.
• External rupture (haemopericardium, haemothorax, effusions).
• Arterial compromise (limb ischaemia, renal failure, stroke).
• Contraindications to medical therapy (AR, LVF).
• Progression (continued pain, expansion of haematoma on further
imaging, loss of pulses, pericardial rub, or aortic insufficiency).
The aim of surgical therapy is to replace the ascending aorta, thereby
preventing retrograde dissection and cardiac tamponade (main cause of
death). The aortic valve may need reconstruction and resuspension, unless
it is structurally abnormal (bicuspid or Marfan’s) where it is replaced.
Indications and principles for medical management
Medical therapy is the treatment of choice for:
• Uncomplicated type B dissection.
• Stable isolated arch dissection.
• Chronic (>2 weeks’ duration) stable type B dissection.
In all but those patients who are hypotensive, initial management is aimed
at reducing systemic BP and myocardial contractility. The goal is to stop
the spread of the intramural haematoma and to prevent rupture. The best
guide is control of pain. Strict bed rest in a quiet room is essential.
Aortic dissection: management 2
Control blood pressure
Reduce SBP to 100–120mmHg.
• Start on IV β-blocker (if no contraindications), aiming to reduce the HR
to 60–70bpm (see Table 1.14).
• Once this is achieved, if BP remains high, add a vasodilator such as
sodium nitroprusside (see Table 1.14). Vasodilators in the absence of
β-blockade may increase myocardial contractility and the rate of rise
in pressure (dP/dt). Theoretically, this may promote extension of the
dissection.
• Further antihypertensive therapy may be necessary, and other
conventional agents such as calcium channel blockers, β-blockers, and
ACEIs can be used.
• In patients with AR and CCF, myocardial depressants should not be
given. Aim to control BP with vasodilators only.
Hypotension
May be due to haemorrhage or cardiac tamponade.
• Resuscitate with rapid IV volume (ideally colloid or blood, but crystalloid
may be used also). A PA wedge catheter (Swan–Ganz) should be used
to monitor the wedge pressure and guide fluid replacement.
• If there are signs of AR or tamponade, arrange for an urgent Echo and
discuss with the surgeons.
Emerging indications and principles for interventional
therapy
There are increasing reports and short case series demonstrating favourable
outcome (prognostic as well as symptomatic) data on using endovascular
stent grafts in the management of primarily type B and also, to a lesser ex-
tent, type A aortic dissections.
On the basis of current evidence, endovascular stent grafts should be
considered to seal the entry to the false lumen and to enlarge the com-
pressed true lumen in the following situations:
• Unstable type B dissection.
• Malperfusion syndrome (proximal aortic stent graft and/or distal
fenestration/stenting of branch arteries).
• Routine management of type B dissection (under evaluation).
Cardiac tamponade
If the patient is relatively stable, pericardiocentesis may precipitate haemo-
dynamic collapse and should be avoided. The patient should be transferred
to the operating theatre for direct repair as urgently as possible. In the con-
text of tamponade and EMD or marked hypotension, pericardiocentesis is
warranted.
Long-term treatment
Must involve strict BP control.
Prognosis
• Mortality for untreated aortic dissection is roughly 20–30% at 24h and
65–75% at 2 weeks.
• For dissections confined to the descending aorta, short-term survival
is better (up to 80%), but 730–50% will have progression of dissection,
despite aggressive medical therapy, and will require surgery.
• Operative mortality is in the order of 10–25% and depends on the
condition of the patient preoperatively. Post-operative 5-year actuarial
survival of up to 75% may be expected.
Acute pericarditis: assessment
Presentation
• Typically presents as central chest pain, often pleuritic, relieved by sitting
forward and can be associated with breathlessness.
• Other symptoms (e.g. fever, cough, arthralgia, rash, faintness/dizziness
secondary to pain/iHR) may reflect the underlying disease (see
Box 1.42).
• A pericardial friction rub is pathognomonic. This may be positional
and transient and may be confused with the murmur of tricuspid
regurgitation or MR.
• Venous pressure rises if an effusion develops. Look for signs of cardiac
tamponade (E Cardiac tamponade: presentation, pp. 162–3).
Investigations
ECG
• May be normal in up to 10%.
• ‘Saddle-shaped’ ST-segment elevation (concave upwards), with variable
T inversion (usually late stages) and PR-segment depression (opposite
to P-wave polarity). Minimal lead involvement to be considered,
typically including I, II, aVL, aVF, and V3–V6.
• ST segment is always depressed in aVR, frequently depressed or
isoelectric in V1, and sometimes in depressed in V2.
• May be difficult to distinguish from acute MI. Features suggesting
pericarditis are:
• Concave ST elevation (versus convex).
• All leads involved (versus a territory, e.g. inferior).
• Failure of usual ST evolution and no Q waves.
• No AV block, bundle branch block, or QT prolongation.
• Early repolarization (a normal variant) may be mistaken for pericarditis. In
the former, ST elevation occurs in precordial and rarely in V6 or limb leads
and is unlikely to show ST depression in V1 or PR-segment depression.
• Usually not helpful in diagnosing pericarditis post-MI.
• The voltage drops as an effusion develops, and in tamponade, there is
electrical alternans, best seen in QRS complexes.
Echo
• May demonstrate a pericardial collection.
• Useful to monitor LV function in case of deterioration due to associated
myopericarditis.
• We recommend every patient has an Echo prior to discharge to assess
LV function.
Other investigations depend on the suspected aetiology
All patients should have:
• FBC and biochemical profile.
• ESR and CRP (levels rise proportionate to intensity of disease).
• Serial cardiac enzymes (CK, CK-MB, troponin). Elevations indicate sub-
pericardial myocarditis.
• CXR (heart size, pulmonary oedema, infection).
Where appropriate
• Viral titres (acute + 2 weeks later) and obtain virology opinion.
• Blood cultures.
• Autoantibody screen (rheumatoid factor, ANA, anti-DNA, complement
levels).
• TFTs.
• Fungal precipitins (if immunosuppressed), Mantoux test.
• Sputum culture and cytology.
• Diagnostic pericardial tap (culture, cytology).
Acute pericarditis: management
General measures
• Admit? Depends on clinical picture. We recommend admission of
most patients for observation for complications, especially effusions,
tamponade, and myocarditis. Patients should be discharged when
pain-free.
• Bed rest.
• Analgesia: NSAIDs are the mainstay. Ibuprofen is well tolerated and
increases coronary flow (200–800mg qds). Aspirin is an alternative
(600mg qds PO). Indometacin should be avoided in adults, as it reduces
coronary flow and has marked side effects. Use PPI (lansoprazole 30mg
od) to minimize GI side effects. Opioid analgesia may be required.
Colchicine used as monotherapy or in addition to NSAIDs may help
settle pain acutely and prevent recurrence.
• Steroids: these may be used if the pain does not settle within 48h [e.g.
prednisolone enteric-coated (EC) 40–60mg PO od for up to 2 weeks,
tapering down when pain settles]. Use in conjunction with NSAID,
and taper steroids first before stopping NSAID. It is also of value if
pericarditis secondary to autoimmune disorders.
• Colchicine: evidence suggests that, either used as monotherapy or in
conjunction with NSAIDs, it may help to settle pain acutely and prevent
relapses (1mg/day in divided doses). Stop if the patient develops
diarrhoea and nausea (1mg stat, 500 micrograms q6h for 48h).
• Pericardiocentesis: this should be considered for significant effusion or if
there are signs of tamponade (E Cardiac tamponade: presentation,
pp. 162–3).
• Antibiotics: these should be given only if bacterial infection is suspected.
• Oral anticoagulants: should be discontinued (risk of haemopericardium).
Patient should be given IV UFH, which is easier to reverse (IV
protamine) if complications arise.
Bacterial pericarditis
• The most common pathogens are Pneumococcus, staphylococci,
streptococci, Gram-negative rods, and Neisseria spp.
• Risk factors include pre-existing pericardial effusion (e.g. uraemic
pericarditis) and immunosuppression [iatrogenic, lymphoma, leukaemia,
human immunodeficiency virus (HIV)].
• The infection may have spread from mediastinitis, IE, pneumonia, or a
sub-diaphragmatic abscess.
• Suspect in patients with high fever, night sweats, dyspnoea, and raised
JVP (chest pain may be mild or absent); there may be other intrathoracic
infection (e.g. pneumonia).
• If suspected, take blood cultures and start IV flucloxacillin (2g qds)
and IV gentamicin or IV cefotaxime (2g tds). Adjust treatment when
sensitivities known.
• Significant-sized pericardial collections should be drained to dryness,
if possible. Send fluid for Gram and Ziehl–Neelsen (ZN) stain, fungal
smear, and culture. Surgical drainage may be required for recurrent
effusions.
• Patients with TB pericarditis are very prone to developing cardiac
constriction. Steroids have not been shown to prevent this, but they
do prevent progression once constrictive symptoms develop. Surgical
pericardectomy may be required. Take advice from cardiologists and
ID team.
Viral pericarditis
• Pathogens include Coxsackie A + B, echovirus, adenovirus, mumps,
Ebstein–Barr virus (EBV), varicella-zoster virus (VZV), cytomegalovirus
(CMV), hepatitis B, and HIV.
• Usually a self-limiting illness (1–3 weeks) and can be seasonal. Common
in young individuals with no associated cardiac history.
• Twenty to 30% develop recurrent pericarditis.
• Complications include recurrent pericarditis (20–30%), myocarditis,
dilated cardiomyopathy, pericardial effusion and tamponade, and late
pericardial constriction.
• Treatment is supportive (E Acute pericarditis: management, p. 158).
Uraemic pericarditis
This is an indication for urgent dialysis (see Box 4.3).
Dressler’s syndrome, post-cardiotomy syndrome
• Complicates 71% of acute MI and 10–15% of patients following cardiac
surgery presenting 2–4 weeks later (up to 3 months later).
• Consists of recurrent pericarditis, fever, anaemia, high ESR, neutrophil
leucocytosis, pleural effusions, and transient pulmonary infiltrates
on CXR.
• Treat with bed rest, and NSAIDs (aspirin 600mg PO qds) and steroids
for persisting symptoms (E Acute pericarditis: management, p. 158).
• Pericarditis following acute MI (E STEMI: complications, pp. 32–3).
Neoplastic pericarditis
• The 1-year survival of patients with malignant effusive pericarditis is
≤25%. Approach to treatment depends on the underlying malignancy
and symptoms.
• Asymptomatic pericardial effusions do not require drainage. Treat the
underlying malignancy (± mediastinal radiotherapy). Recurrent effusions
may need formation of a surgical pericardial window.
• Drainage is indicated for cardiac tamponade.
Myopericarditis
• Although it can occur with all cases of pericarditis, it is more common in
the context of acquired immune deficiency syndrome (AIDS), vasculitis/
connective tissue disorders, rheumatic fever, and TB infection.
• Clinical suspicion should be higher in the context of pericarditis
accompanied by significant arrhythmia (especially ventricular) and
features of LV dysfunction and sinus tachycardia out of proportion to
the clinical picture (fever, pain, persistence over >5–6 days).
• Biochemical markers of myocardial injury are often positive (especially
TnT or TnI).
• In the absence of heart failure, treatment is as for uncomplicated
pericarditis. Steroids should be avoided, unless indicated as part of
treatment for the underlying cause. Heart failure should be treated
conventionally. Interferon can be used to treat enteroviral infections,
and globulins for CMV.
• Pericardial effusions must be drained with care, as the effusion may
be ‘splinting’ a dilated/myocarditic heart. Drainage can lead to rapid
dilatation and cardiovascular collapse.
• Prognosis is generally good and most recover, unless there is severe LV
impairment.
621
Cardiac tamponade: presentation
Cardiac tamponade occurs when a pericardial effusion causes haemo-
dynamically significant cardiac compression. The presentation depends on
the speed with which fluid accumulates within the pericardium. Acute tam-
ponade may occur with 100–200mL in a relatively restricted pericardial sac.
Chronic pericardial collections may contain up to 1000mL of fluid without
clinical tamponade.
Causes
Acute tamponade ‘Subacute’ tamponade
• Cardiac trauma. • Malignant disease.
• Iatrogenic: • Idiopathic pericarditis:
• Post-cardiac surgery. • Uraemia.
• Post-cardiac catheterization. • Infections:
• Post-pacing/EPS. • Bacterial.
• Aortic dissection. • TB.
• Spontaneous bleed: • Radiation.
• Anticoagulation. • Hypothyroidism.
• Uraemia. • Post-pericardotomy.
• Thrombocytopenia. • SLE.
• Cardiac rupture post-MI.
Presentation
• Patients commonly present either with cardiac arrest (commonly EMD)
or with hypotension, confusion, stupor, and shock.
• Patients who develop cardiac tamponade slowly are usually acutely
unwell, but not in extremis. Their main symptoms include:
• Breathlessness, leading to air hunger at rest.
• There may be a preceding history of chest discomfort.
• Symptoms resulting from compression of adjacent structures by a
large effusion (i.e. dysphagia, cough, hoarseness, or hiccough).
• There may be symptoms due to the underlying cause (see Box 1.43).
• Insidious development may present with complications of tamponade,
including renal failure, liver and/or mesenteric ischaemia, and
abdominal plethora.
Important physical signs
Most physical findings are non-specific. They include:
• Tachycardia (except in hypothyroidism and uraemia).
• Hypotension (± shock) with postural hypotension.
• Raised JVP (often >10cm) with a prominent systolic x descent and
an absent diastolic y descent (see Fig. 1.13). If the JVP is visible and
either remains static or rises with inspiration, it indicates concomitant
pericardial constriction (Kussmaul’s sign).
• Auscultation may reveal diminished heart sounds. Pericardial rub may be
present and suggests a small pericardial collection.
• Look for pulsus paradoxus (a decrease in the palpable pulse and SBP of
>10mmHg on inspiration). This may be so marked that the pulse and
Korotkoff sounds may be completely lost during inspiration. This can be
30
25
20
(mmHg)
15
10
5
0
Inspiration Inspiration
Cardiac tamponade: management
Tamponade should be suspected in patients with hypotension, elevated
venous pressure, falling BP, iHR and iRR (with clear chest), and pulsus
paradoxus, especially if predisposing factors are present.
Investigations
• CXR: the heart size may be normal (e.g. in acute haemopericardium
following cardiac trauma). With slower accumulation of pericardial
fluid (>250mL), the cardiac silhouette will enlarge with a globular
appearance. The size of the effusion is unrelated to its haemodynamic
significance. Look for signs of pulmonary oedema.
• ECG: usually shows sinus tachycardia, with low-voltage complexes and
variable ST-segment changes. With large effusions, ‘electrical alternans’
may be present with beat-to-beat variation in the QRS morphology
resulting from movement of the heart within the pericardial effusion.
• Echocardiography: confirms the presence of a pericardial effusion. The
diagnosis of tamponade is a clinical one. Echo signs highly suggestive of
tamponade include:
• Chamber collapse during diastole (RA, RV, RVOT).
• Marked variation in transvalvular flow.
• Dilated IVC, with little or no diameter change on respiration.
• If available, examine the CVP trace for the characteristic exaggerated x
descent and absent y descent.
Management
Following confirmation of the diagnosis:
• While preparing for drainage of the pericardial fluid, the patient’s
circulation may temporarily be supported by loading with IV colloid
(500–1000mL stat) and starting inotropes (i.e. adrenaline).
• In patients with an adequate BP, cautious systemic vasodilatation with
hydralazine or nitroprusside, in conjunction with volume loading, may
increase forward cardiac output. This is not to be recommended
routinely, as it may cause acute deterioration.
• The effusion should be urgently drained (E Pericardial aspiration 1,
pp. 814–15 for pericardiocentesis), guided by Echo or fluoroscopy. In
the event of circulatory collapse, drainage must happen immediately without
imaging.
• Surgical drainage is indicated if the effusion is secondary to trauma.
• Avoid intubation and positive pressure ventilation, as this reduces
cardiac output.
• In patients with cardiac arrest, chest compression has little or no value,
as there is no room for additional filling.
• Uraemic patients will also need dialysis.
• The cause of the effusion should be established (see Box 1.43).
Pericardial fluid should be sent for cytology, microbiology (including TB),
and, if appropriate, Hb, glucose, and amylase.
Further management is of the underlying cause.
Special cases
Recurrent pericardial effusion
In some cases, pericardial effusion recurs. This requires either a change in
treatment of the underlying cause or a formal surgical drainage procedure
such as a surgical pericardial window or pericardiectomy.
Low-pressure tamponade
Seen in the setting of dehydration. The JVP is not raised, RA pressure is
normal, and tamponade occurs even with small volumes of pericardial fluid.
• The patient may respond well to IV fluids.
• If there is a significant pericardial collection, this should be drained.
61
Chapter 2 171
Respiratory emergencies
Acute pneumonia: assessment
Presentation
• Classically cough (productive or non-productive), fever, breathlessness,
chest pain, abnormal CXR. There may be prodromal symptoms of
coryza, headache, and muscle aches.
• The aetiological agent cannot be predicted from the clinical features (see
Box 2.1).
• Immunocompromised patients may present with agitation, fever,
tachypnoea, and droutine oximetry readings. CXR abnormalities may
be subtle.
• Patients with right-sided endocarditis (e.g. IV drug users) may present
with haemoptysis, fever, and patchy consolidation ± cavitation.
Severity assessment
• Severity assessment is the key to deciding the site of care (i.e. home,
medical ward, or critical care ward) and guiding general management
and antibiotic treatment.
• The ‘CURB-65’ score may be used as a severity assessment tool (see
Boxes 2.2 and 2.3):
• CURB-65 score ≥3: high risk of mortality; should be admitted and
managed as having severe pneumonia.
• CURB-65 score of 2: irisk of mortality, need short-stay inpatient
treatment or hospital-supervised outpatient treatment.
• CURB-65 score of 0–1: low risk of mortality, may be suitable for home
treatment.
Management
General resuscitation and investigations
• Check ‘ABC’ (airway, breathing, and circulation). Arrange for urgent CXR.
• Secure venous access: if there are signs of dehydration, start IV
crystalloids; examine regularly for signs of fluid overload.
• Send bloods: FBC, U&Es, LFTs, CRP.
• Check ABG: correct hypoxia (PaO2 ≤10kPa) with O2, at least 35%. If
hypoxia fails to correct, despite maximum inspired O2, or there is
hypercapnia (PaCO2 ≥6kPa), the patient is likely to require ventilation.
Patients in type 2 respiratory will require controlled O2 therapy. Involve
ITU early to plan the patient’s care.
• Culture blood and sputum.
• Pain relief: paracetamol or an NSAID usually suffice. Morphine may be
required; respiratory depression is unlikely to be a problem if PaCO2 is
low or normal and it may be reversed with naloxone.
Indications for intensive care
• Patients with >2 components of CURB (Confusion, raised Urea, raised
Respiratory rate, low BP; see Box 2.2) who do not respond rapidly.
• Persisting hypoxia with PaO2 <8kPa despite maximal O2 administration.
• Progressive hypercapnia (PaCO2 ≥6kPa), progressive exhaustion.
• Severe acidosis (pH <7.26).
• Shock, depressed consciousness.
• Involve ITU early—this may help avoid ventilation as an emergency.
Further reading
British Thoracic Society, Community Acquired Pneumonia in Adults Guideline Group. Guidelines
for the management of community acquired pneumonia in adults: update 2009. M https://www.
brit-thoracic.org.uk/document-library/clinical-information/pneumonia/adult-pneumonia/
bts-guidelines-for-the-management-of-community-acquired-pneumonia-in-adults-2009-update/
741
Acute pneumonia: investigations
Investigations
All patients should have:
• ABGs (on air and O2).
• FBC, U&Es, LFTS, ESR, CRP.
• ECG.
• CXR (see Fig. 2.1).
• Blood cultures.
• Sputum culture, Gram stain, ZN stain (if suspicious of TB), cytology.
• Pleural fluid aspiration (if present) for microscopy, culture, and
sensitivity (MC&S), protein, and pH.
• Pneumococcal antigen: urine, sputum, or blood.
• Serology (acute and convalescent).
• Cold agglutinins (Mycoplasma days 7–14).
• Urine for Legionella antigen, sputum for Legionella culture, and direct
immunofluorescence.
Where appropriate, consider:
• Bronchoscopy [± bronchoalveolar lavage (BAL)] (if
immunocompromised, or if fails to respond to first-line antibiotics and
no organism identified).
• Echo (? right heart endocarditis; E Infective endocarditis (IE),
pp. 102–3).
• CTPA (to exclude infected pulmonary infarct).
• Transbronchial or open lung biopsy.
• Aspiration of pleural fluid for MC&S.
• Viral titres.
Acute pneumonia: management
Treatment
• For management key points, see Box 2.4.
• ‘Blind’ treatment should be started as soon as appropriate cultures
have been sent (see Table 2.1). Modify therapy in light of subsequent
investigations or positive cultures.
• Start on IV therapy (for at least 48h in patients with high CURB scores);
adjust according to clinical condition and response (see Table 2.1).
• All patients should receive appropriate O2 therapy (aim SpO2 94–98%;
88–92% if known COPD/risk of hypercapnic respiratory failure).
• In patients with COPD or asthma, consider treatment with salbutamol
(2.5–5mg nebulized q4–6h) to relieve bronchospasm. This may also
‘loosen secretions’ and improve mucociliary action.
• Continue IV fluids, as necessary, to keep the patient well hydrated.
• Prophylaxis for venous thromboembolism (VTE) with LMWH should be
considered for all patients who are not fully mobile.
• Monitor response to therapy with:
• FBC, CRP.
• Pulse oximetry or ABGs.
• CXR at days 3–5 (sooner if deteriorating).
• Total duration of therapy usually 5–7 days (in low-risk patients), up to
10 days (in high-risk patients).
• Follow-up CXR 4–6 weeks after discharge mandatory to exclude an
underlying endobronchial lesion.
• Patients should not be discharged if they have >1 of the following
features of instability: temperature >37.8°C; pulse rate >100 bpm; RR
>24/min; SBP <90mmHg; O2 saturation <90%; abnormal mental status;
and inability to maintain oral intake.
Choice of antibiotics
In severely ill patients, the history may point to a likely pathogen:
• COPD: S. pneumoniae, H. influenzae, M. catarrhalis.
• Alcoholism: S. pneumoniae, S. aureus, H. influenzae, Klebsiella, TB,
anaerobes, Gram –ve bacteria.
• Recent ‘flu’: S. aureus, S. pneumoniae, H. influenzae.
• Risk of aspiration: anaerobes, Gram –ve bacteria.
• Contact with birds: Chlamydia psittaci.
• Haemoptysis: streptococci, S. aureus, lung abscess, necrotizing Gram –
ve bacteria, invasive aspergillosis.
• Diarrhoea, abdominal pain: Legionella.
• Pharyngitis/otitis media: Mycoplasma, anaemia/cold agglutinins.
• Risk factors for HIV: S. pneumoniae, H. influenzae, CMV, Pneumocystis
jiroveci (carinii) pneumonia (PCP), Cryptococcus.
• Hospital-acquired: Gram –ve bacteria, S. aureus.
• Neutropenia: Pseudomonas aeruginosa, Gram –ve bacteria, Aspergillus.
• Drug addicts: S. aureus, Candida.
• Nursing home patients: higher risk of aspiration—anaerobes, Gram –ve
bacteria.
Acute pneumonia: complications
Community-acquired pneumonia that fails to respond
• Review the diagnosis (? PE, pulmonary oedema, pulmonary vasculitis,
alveolar haemorrhage, cavitation, organizing pneumonia, eosinophilic
pneumonia, bronchiectasis).
• Repeat CXR, and arrange for CT chest to look for cavitation or
empyema. Refer to the respiratory team. Repeat culture of relevant
specimens (e.g. sputum, blood). Consider possible resistant organism or
underlying disease, e.g. bronchial carcinoma.
• Consider bronchoscopy to exclude TB, PCP, or an obstructing lesion.
• Review antibiotic dosages, and intensify (e.g. inadequate oral
clarithromycin for Mycoplasma pneumonia).
Parapneumonic pleural effusion or empyema
• Parapneumonic pleural effusions develop in up to 50% of patients with
bacterial pneumonia admitted to hospital.
• Image-guided diagnostic tap should be performed on all parapneumonic
effusions to exclude an empyema. Send pleural fluid for MC&S, urgent
Gram stain, and pH analysis.
• Empyema (visibly cloudy fluid, pus, or organisms on Gram stain) or a
complicated parapneumonic effusion (visibly clear fluid with pH <7.2)
should be removed with pleural space drainage under US guidance.
Discuss with respiratory physicians.
• US may help look at the level of the effusion and demonstrate loculation
with an empyema.
• If an empyema fails to resolve with pleural space drainage, arrange
chest CT and discuss with cardiothoracic surgeons (E Indications for
specialist referral, p. 221).
Cavitation or abscess
Any severe pneumonia may cavitate, but particularly S. aureus, Klebsiella
spp., TB, aspiration pneumonia, bronchial obstruction (foreign body, tu-
mour), or PEs (thrombus or septic emboli, e.g. from DVT with superadded
infection or tricuspid endocarditis; E Right-sided endocarditis, p. 112).
Treatment
• Seek advice from the respiratory team. Most respond to appropriate
antibiotics but may require a more prolonged course. Surgical drainage
or CT-guided percutaneous aspiration may be necessary.
• ‘Blind’ treatment: cefuroxime 1.5g tds IV (or cefotaxime 2g tds IV)
+ flucloxacillin 1–2g qds IV + gentamicin loading dose (100–120mg
IV), then 6–7mg/kg od (according to renal function and levels) ±
metronidazole 500mg IV tds.
• Long-term antibiotics (4–6 weeks) likely to be required.
Other complications
• Respiratory failure (E Respiratory failure: assessment, pp. 198–9).
• Rhabdomyolysis (E Rhabdomyolysis, pp. 306–7).
• DIC (especially Legionella) (E Disseminated intravascular coagulation,
p. 633).
801
Mycoplasma pneumonia
• Disease of young adults. Low-grade fever, dry cough, headache,
and myalgia. Erythema multiforme may be seen in 725%; 75% have
meningoencephalitis.
• Epidemics occur every 4 years in the UK.
• WCC is often normal; ESR is high; specific immunoglobulin M (IgM)
is seen early, then levels decline. 750% develop cold agglutinins (also
seen in measles, EBV) which may cause haemolysis. CXR may show
reticulonodular shadowing (lower lobe > upper lobe), which may take
over 6 weeks to resolve (unlike bacterial pneumonia).
• Treatment is with erythromycin 500mg qds PO/IV, clarithromycin 500mg
bd PO/IV, or tetracycline 500mg qds PO/IV.
Legionella pneumonia
• Illness of middle-aged men; more severe in smokers. Incubation 2–10
days, followed by high fever, rigors, headache, myalgia, dry cough,
progressive respiratory distress, and confusion. Abdominal pain,
diarrhoea, nausea and vomiting, and palpable hepatomegaly are seen in
730%. Complications include pericarditis (± effusion), encephalopathy
[cerebrospinal fluid (CSF) is usually normal], and rarely renal failure.
• Moderate leucocytosis (≤20 × 109/L, neutrophilia, lymphopenia),
hyponatraemia, deranged LFTs, proteinuria, haematuria, and
myoglobinuria. Diagnosis: rise in specific IgM and immunoglobulin G
(IgG) titres (urine, blood, sputum).
• Worth sending urine for urinary Legionella antigen.
• CXR may show anything from diffuse patchy infiltrates to lobar or
segmental changes and usually deteriorates in spite of treatment. Pleural
effusions are seen in 750%.
• Treatment is with clarithromycin 500mg bd PO/IV. Continue therapy
for 14–21 days. Add rifampicin (600mg bd PO/IV) if symptoms do not
settle within 72h.
• Pontiac fever is a self-limiting (2–5 days), acute, non-pneumonic
Legionella infection with high fever, rigors, myalgia, headache, and
tracheobronchitis.
Viral pneumonia
Clinical features resemble Mycoplasma pneumonia (E Mycoplasma pneu-
monia, p. 180). Diagnosis is by a 4-fold increase in specific antibody titres.
CMV
Most common viral infection in AIDS and following solid organ or bone
marrow transplantation (BMT), presenting as fever, dry cough, and pro-
gressive respiratory distress with hypoxia and bilateral crackles. CXR shows
diffuse infiltrates; a miliary pattern is associated with rapid progression and
poor outcome, whereas an interstitial pattern has a better prognosis (see
Fig. 2.1). Treat with ganciclovir 5mg/kg IV q12h for 2–3 weeks.
Coxsackie and echovirus
Titres often rise in ‘epidemic pleurodynia’ (Bornholm’s disease), a self-
limiting illness with chest pain, exacerbated by coughing and deep breathing,
myalgia, and muscle tenderness. Treatment: analgesia (paracetamol,
NSAIDs).
Varicella pneumonia
More common in smokers and immunosuppressed patients. All patients
with varicella pneumonitis should be treated with aciclovir 10mg/kg IV
8-hourly.
Chlamydia pneumonia
• C. pneumoniae presents in older adults with headaches and longer
duration of symptoms before hospital admission. Extra-pulmonary
manifestations may include meningoencephalitis, Guillain–Barré
syndrome (GBS), arthritis, and myocarditis.
• Treatment: erythromycin 500mg qds PO/IV, clarithromycin 500mg bd
PO/IV, or tetracycline 500mg qds PO/IV.
821
Psittacosis
• C. psittaci produces fever, cough, myalgia, and, in severe cases, delirium
(psittacosis). Complications include pericarditis, myocarditis, and
hepatosplenomegaly. Diagnosis is by serology.
• Acquired from birds and animals (so may be a clue in the history), but
human-to-human spread may occur.
• Treat with tetracycline 500mg PO qds for 2–3 weeks.
In summary, the likely aetiological agent causing CAP cannot be accur-
ately predicted from the clinical features. However, some patient groups/
signs and symptoms tend to be more commonly associated with certain
pathogens:
• S. pneumoniae: increasing age, comorbidity, high fever, pleuritic
chest pain.
• Bacteraemic S. pneumoniae: ♀, excess alcohol, diabetes mellitus (DM),
COPD, dry cough.
• Legionella: younger patient, smoker, absence of comorbidity, diarrhoea,
neurological symptoms, multisystem involvement.
• Mycoplasma: younger patient, prior antibiotics, less multisystem
involvement.
• C. pneumoniae: longer duration of symptoms prehospital admission and
headache.
• Coxiella burnetti: ♂, dry cough, high fever.
Miscellaneous conditions
Hypersensitivity pneumonitis (extrinsic allergic alveolitis)
May mimic viral pneumonia and present as breathlessness, dry cough, my-
algia, and fever, with neutrophilia (eosinophils usually normal acutely) and
patchy radiographic changes. There is usually a history of exposure to the
allergen, and serum precipitins are detectable. BAL shows predominance of
mast cells and lymphocytes. Treatment is with steroids.
Pulmonary eosinophilia
This is a heterogenous group of disorders characterized by eosinophilic
pulmonary infiltrates, producing respiratory symptoms, CXR shadowing,
and blood and sputum eosinophilia. The cause may be unknown, as in
cryptogenic eosinophilic pneumonia, or it may be due to drugs (e.g.
nitrofurantoin, phenytoin, and ampicillin), helminth infections (e.g. Ascaris
lumbricoides, hookworms, Strongyloides stercoralis), tropical pulmonary eo-
sinophilia (lymphatic filarial infection), or small-vessel systemic vasculitis
(Churg–Strauss).
Allergic bronchopulmonary aspergillosis
This is a hypersensitivity reaction of airways colonized by Aspergillus spp.
producing pulmonary eosinophilia. It typically occurs in asthmatics with
repeated episodes of bronchial obstruction, inflammation, and mucus im-
paction, resulting in bronchiectasis and upper lobe fibrosis. Such patients
are usually Aspergillus skin-prick test [immunoglobulin E (IgE)] and serum
precipitins (IgG) positive. Treatment depends on the underlying condition.
Cryptogenic organizing pneumonia
May present with fever, malaise, cough, breathlessness, and pulmonary
shadows on CXR. Characteristically, infiltrates in different lobes over dif-
ferent time courses, or pneumonia unresponsive to antibiotics. Excessive
proliferation of granulation tissue within small airways and alveoli, crypto-
genic organizing pneumonia (COP) is the idiopathic form of bronchiolitis
obliterans organizing pneumonia (BOOP). Organizing pneumonia can also
be associated with collagen vascular diseases (RA, lupus, dermatomyositis),
chronic infection (Legionella, CMV, Mycoplasma), and drugs (amiodarone,
bleomycin). Treatment is with steroids.
Alveolar haemorrhage
Intrapulmonary haemorrhage may present with cough, fever, and breath-
lessness. Haemoptysis may be absent in 30%. The CXR may show diffuse
alveolar opacities. BAL shows predominantly RBCs. Causes include sys-
temic vasculitis (e.g. Wegener’s granulomatosis, microscopic polyangiitis),
collagen vascular diseases (e.g. SLE), Goodpasture’s syndrome, ARDS, and
idiopathic pulmonary haemosiderosis. Treatment depends on the cause.
Bronchoalveolar cell carcinoma
May mimic an acute pneumonia radiologically, although the typical symp-
toms of pneumonia are usually not present, unless there is superadded in-
fection. Diagnosis is made by lung biopsy.
841
Acute asthma: assessment
Presentation
• The classical triad is wheeze ± chest tightness, breathlessness, and cough.
Symptoms are often worse at night and first thing in the morning. Acute
attacks may build up over minutes, hours, or days, and the patients may
deteriorate very rapidly and present as respiratory or cardiorespiratory
arrest.
• Factors increasing the risk of severe life-threatening asthma
include: previous ventilation, hospital admission for asthma in the last
year, heavy rescue medication use, >3 classes of asthma medication,
repeated attendances at A&E for asthma care, and brittle asthma.
Precipitants
• No clear precipitating cause can be identified in over 30% of patients.
• Exposure to known allergen or irritant (e.g. pollens, animals, dusts,
cigarette smoke).
• Upper respiratory tract infection (URTI) (commonly viral).
• Lower respiratory tract infection (LRTI)—viral or bacterial.
• Neglect or poor compliance with regular inhaled or oral steroids.
• Emotional stress.
• Cold air or exercise-induced asthma.
Markers of severity
• For assessment of the severity of asthma, see Box 2.5.
• The severity of an attack may be easily underestimated. Assess:
• The degree of airflow obstruction.
• The effect of iwork of breathing on the patient.
• The extent of V/Q mismatch.
• For any evidence of ventilatory failure.
[Patients with marked ‘morning dips’ in the peak expiratory flow (PEF) are
at risk of sudden severe attacks.]
Investigations
• ABG: patients with SpO2 <92% on air or with other features of severe
asthma require ABG measurement. Hypoxaemia on room air is almost
invariable. In attempting to maintain alveolar ventilation initially, there
is hypocapnia and respiratory alkalosis. iPaCO2 suggests incipient
respiratory failure due to exhaustion; contact ITU immediately. Poorly
controlled asthma over several days may be recognized by a mild ‘non-
anion gap’ acidosis (serum bicarbonate 20–24mmol/L). Lactic acidosis is
seen with severe asthma.
• Pulse oximetry: continuous oximetry is essential; aim for 94–98%.
• CXR: to exclude pneumothorax and diagnose any parenchymal infection.
• ECG: usually normal; in severe asthmatics, signs of right heart strain may
be present.
• FBC, U&Es, CRP: assess for signs of infection and eosinophilia; K+ may be
lowered by high doses of β-agonists.
Acute exacerbation
of COPD: management
(See Box 2.11.)
Treat hypoxia and respiratory failure
• The distinction between ‘pink puffers’ (breathless to maintain PaO2
and so keep PaCO2 down) and ‘blue bloaters’ (lose breathless drive to
maintain PaO2 and so PaCO2 rises) is unhelpful, as most patients have
features of both.
• Commence O2 therapy: uncontrolled O2 therapy may worsen CO2
retention in some patients. While awaiting ABGs, give controlled
24–28% O2 via a Venturi mask. Nasal cannulae give unreliable inspired
O2 concentration and may be dangerous. Once ABG results available,
adjust FiO2 accordingly.
• ABGs:
• If the patient is not retaining CO2 (PaCO2 <6kPa) and is hypoxic (PaO2
<10kPa), then give O2 28–40%. Repeat ABGs 30min later (sooner
if conscious level deteriorates) to ensure correction of hypoxia and
exclude rising PaCO2. Aim to maintain O2 saturations 88–92%.
• If CO2 retention is present, then use 24–28% O2 and consider
ventilatory support. Non-invasive ventilation (NIV) is the first-line
treatment of choice for COPD exacerbations with type 2 respiratory
failure in patients who fail to respond to initial therapy. It allows the
administration of higher O2 concentrations without an uncontrolled
rise in PaCO2. NIV reduces the need for intubation, decreases
mortality and hospital stay, and should be considered in all patients
with COPD exacerbations with PaCO2 ≥6.0kPa and pH ≤7.35 who
have failed to respond to initial bronchodilator therapy.
• Mechanical ventilation: this should be considered in patients unlikely or
unable to tolerate NIV (E Mechanical ventilation, p. 828).
• Respiratory stimulants: these have generally been superseded by NIV.
However, where NIV is not available or has not been successful and
mechanical ventilation is not considered appropriate, a trial of doxapram
may be worthwhile. It is not beneficial in type 2 respiratory failure due
to poor respiratory effort.
Treat bronchospasm and obstruction
• Nebulized β-agonists (salbutamol 2.5mg or terbutaline 10mg q4h and
PRN) via O2 or air if CO2 retention. (If the patient is very hypoxic, give
2L/min O2 via nasal cannulae while nebulizer in progress.)
• Patients with COPD may have relatively fixed bronchospasm, but where
the patient is very unwell, then consider IV aminophylline and/or IV
β-agonists, as for severe asthma (see Box 2.5).
• Include nebulized ipratropium bromide 500 micrograms 6-hourly. This
tends to be more effective in patients with COPD than in those with
asthma.
• Give steroids: 30mg prednisolone PO for 7–10 days; there is no
advantage in prolonging therapy.
• Urgent physiotherapy may help clear bronchial secretions.
Pneumothorax
Unless very small, consider aspiration ± drain (E Pneumothorax: assess-
ment, pp. 210–11).
Pulmonary oedema
See E Pulmonary oedema: assessment, pp. 92–3.
Pulmonary embolism
See E Pulmonary embolism (PE): assessment, p. 126.
981
Respiratory failure: assessment
Respiratory failure is present when gas exchange becomes significantly im-
paired. Clinically, it is not possible to predict the PaO2 or PaCO2, and so this
diagnosis relies on ABG analysis. There are two types:
• Type 1: hypoxia PaO2 ≤8kPa on air or O2 with normal or low PaCO2 (i.e.
mainly V/Q mismatch).
• Type 2: hypoxia PaO2 ≤8kPa on air or O2 with raised PaCO2 (>6kPa) (i.e.
predominantly alveolar hypoventilation).
In practice, both types may coexist.
Presentation
(See Box 2.12.)
• Shortness of breath is the most common presentation. Ask about the
speed of onset (sudden onset may suggest pneumothorax, PE, or
cardiac failure).
• Respiratory failure may present without dyspnoea, particularly
exacerbations of COPD with hypoventilation and non-respiratory
causes such as GBS (E Guillain–Barré syndrome, pp. 452–3) or
drug overdose. Neuromuscular respiratory failure is discussed under
E Neuromuscular respiratory failure: assessment, pp. 440–1.
• Confusion may be the sole presentation in the elderly.
The history may point to the cause of respiratory failure:
• History of asthma/chronic bronchitis and smoking.
• History of other chronic lung disease (e.g. fibrosing alveolitis,
sarcoidosis).
• Sputum production and fevers (pneumonia).
• Swollen legs due to the development of cor pulmonale or hypoxic/
hypercapnic renal fluid retention in patients with chronic lung disease.
• Haemoptysis (pneumonia, PE).
• Cardiac history, including palpitations and/or chest pain.
• Drug and/or overdose history.
• Neurological symptoms, including painful legs and paraesthesiae (GBS).
• Allergies.
Try to assess the functional capacity when well, e.g. distance walked on flat,
stairs climbed without stopping, frequency of attacks, previous admissions,?
ever ventilated, concurrent illnesses (heart disease, renal impairment, liver
impairment), etc.
Physical examination
• Listen to the breathing: stridor (upper airway obstruction), wheeze
(localized or generalized airflow limitation secondary to asthma, COPD,
pulmonary oedema), coarse crackles (due to consolidation of fluid),
fine crackles (due to fibrotic change), bronchial breathing (indicates
consolidation or collapse but may also occur with fibrosis or above a
pleural effusion).
• Look for cyanosis, signs of pneumothorax (hyperresonance, reduced
breath sounds), or pleural effusion (stony dull, reduced breath sounds).
Respiratory failure: investigations
Urgent investigations
• ABG: on air immediately, or if very unwell while on O2 (note FiO2).
• CXR (see Fig. 2.1).
• ECG: look for signs of PE (tachycardia, RBBB, anterior T-wave changes,
RAD, rarely S1Q3T3; E Pulmonary embolism (PE): assessment, p. 126),
tachyarrhythmias, or myocardial ischaemia.
• Blood tests: FBC (anaemia, leucocytosis), U&Es, glucose.
• Inspect sputum: yellow, green, mucoid, streaky, or frank blood.
• FEV1 and FVC: if suspected muscle weakness (e.g. GBS).
• Septic screen: sputum culture, blood cultures if febrile or if CXR suggests
infection.
Where indicated, consider
• Aspirin and paracetamol levels.
• Plasma and urine for toxicology.
• Urinalysis for glucose and ketones.
• Examine the CXR systematically for any abnormality.
CXR assessment
• Consolidation/alveolar shadowing: may be lobar or patchy. Presence of
an air bronchogram suggests pneumonia.
• Pulmonary oedema due to LVF (cardiogenic): typically perihilar (‘bats-
wing’), upper lobe venous congestion, Kerley B lines in peripheral lung
fields, ± pleural effusions, ± cardiomegaly.
• Non-cardiogenic pulmonary oedema (ARDS/ALI): typically peripheral
alveolar shadowing ± air bronchogram, no upper lobe venous
congestion, Kerley B lines, pleural effusions, or cardiomegaly.
• Pleural effusions.
• Masses suggesting bronchogenic carcinoma.
• PE: wedge-shaped peripheral opacities, small pleural effusions, localized
areas of oligaemia, enlarged PA.
• Pneumothorax (distinguish from large bullae).
• Trauma/rib fractures.
• Interstitial lung disease: small lung fields, interstitial reticulonodular
shadowing peripherally and basally.
Respiratory failure: management
See E Neuromuscular respiratory failure: assessment, pp. 440–1 for
neuromuscular respiratory failure.
The severity of respiratory failure depends upon response to O2. Failure
of hypoxia to correct on 40–60% O2 or progressive hypercapnia implies
that non-invasive or mechanical ventilation may be necessary, depending on
the clinical condition and underlying cause.
Poor prognostic signs on presentation include
• Inability to speak due to dyspnoea.
• RR (>40/min).
• PEF ≤33% of predicted in acute asthma.
• Tachycardia (HR ≥100bpm) or bradycardia (HR ≤60bpm).
• Exhaustion or coma (ventilatory support is required urgently).
• Stridor (this indicates upper airway obstruction; E Acute upper airway
obstruction, pp. 224–5).
• Pulse oximetry saturation of <90%.
• Shock (tachycardia + hypotension). May indicate tension pneumothorax
(E Tension pneumothorax, p. 216), severe LVF (E Pulmonary
oedema: assessment, pp. 92–3), severe pneumonia (pE Acute
pneumonia: management, pp. 176–7), or large PE (E Pulmonary
embolism (PE): assessment, p. 126).
Hypercapnia is the end-result of many causes of respiratory failure (including
asthma and pneumonia), not just COPD, and indicates a tiring patient. Even
if relatively elderly, the patient may respond well to ventilation, with a satis-
factory final outcome, depending on the disease and premorbid condition.
General resuscitation (ABC)
• Ensure the airway is patent and the mouth is clear.
• If stridor is present, request anaesthetic and/or ear, nose, and throat
(ENT) assistance urgently (E Acute upper airway obstruction,
pp. 224–5).
• Sit the patient up (unless hypotensive), and administer O2 at 60% unless
there is a history of COPD (use 24–28% O2).
• Ensure that respiratory effort is adequate and effective (measure RR
and assess the depth of respiration); use pulse oximetry to monitor
the PaO2.
• If the patient is exhausted, with a failing respiratory drive, call for
anaesthetic assistance and consider urgent transfer to ITU (see
Box 2.13).
• In comatose patients with poor respiratory effort, consider drug
overdose with opiates (pinpoint pupils) or benzodiazepines. Give
naloxone 200–400 micrograms (2–4 micrograms/kg) IV bolus,
followed by an infusion, depending on response, and/or IV flumazenil
(200 micrograms over 15s, then 100 micrograms at 60s intervals if
required—max. total dose 1mg (2mg if on ITU).
• Methods of respiratory support are discussed under E Principles of
respiratory support, pp. 826–7.
• Secure IV access.
• Measure BP and HR; look for signs of cardiac failure (raised JVP,
inspiratory crackles, oedema) or signs of PE (raised JVP, tachycardia,
hypotension, normal breath sounds ± pleural rub).
See Box 2.14 for management key points.
• Emerging therapy:
• Statins, insulin, ACEI, and macrolides all have anti-inflammatory and
immunomodulatory ± antithrombotic actions. Conflicting evidence
exists with regard to the mortality benefit associated with any
individual treatment or indeed combinations of drugs in ALI/ARDS.
Macrolides show particular promise in pneumonia-induced ALI, as
they have the added benefit of antimicrobial activity.
• Cell-based therapy, particularly use of mesenchymal stem/stromal
cells, is an attractive option being extensively investigated.
• Sepsis: evidence suggests that some patients with refractory septic
shock (ongoing/increasing vasopressor requirements) may have
‘relative’ or ‘functional’ adrenal insufficiency and may benefit from
‘supraphysiological’ steroid replacement (200–300mg/day of
hydrocortisone). Identification of patients likely to benefit is unclear at
present, but adrenocorticotrophic hormone (ACTH) stimulation test
may help discriminate.
See Box 2.17 for causes of sudden deterioration in ARDS.
Outcome
• Outcome for ALI/ARDS has improved in recent years, with overall
mortality rates of 740%.
• Patients with ALI/ARDS and sepsis, liver disease, non-pulmonary organ
dysfunction, or advanced age have higher mortality rates.
• In survivors, although formal lung function tests are abnormal,
respiratory compromise at 1–2 years is unusual.
• There is increasing evidence that survivors suffer considerable
neuromuscular and psychological disability. This may reflect the period
of prolonged critical illness, rather than be specific for ALI/ARDS.
Further reading
Diaz JV, Brower R, Calfee CS, Matthay MA. Therapeutic strategies for severe acute lung injury. Crit
Care Med. 2010;38:1644–50.
Sweeney RM, Griffiths M, McAuley D. Treatment of acute lung injury: current and emerging pharma-
cological therapies. Semin Respir Crit Care Med. 2013;34:487–98.
021
Pneumothorax: assessment
Presentation
Most individuals presenting to hospital with a spontaneous pneumothorax
have no recognized underlying lung disease. The most common presenting
symptoms are:
• Breathlessness: usually abrupt in onset (young, fit patients may have
very little, but patients with COPD or asthma may present with
sudden deterioration). The presence of breathlessness influences the
management strategy.
• Chest pain: dull, central, heavy; or there may be a pleuritic element.
• In an inpatient, consider the diagnosis in anyone who is:
• Breathless after an invasive thoracic procedure (e.g. subclavian vein
cannulation).
• Increasingly hypoxic or has rising inflation pressures on mechanical
ventilation.
Causes
• Primary/spontaneous: healthy subjects, no known underlying lung disease.
More common in tall, young men who smoke, aged 20–40 years.
Probably due to rupture of apical subpleural blebs/bullae.
• Secondary/spontaneous (SSP): pleural rupture due to underlying lung
disease: emphysema, fibrosing alveolitis, cystic fibrosis, sarcoidosis.
Symptoms tend to be greater in SSP, even if the pneumothorax is
relatively small in size.
• Infection: cavitating pneumonia, e.g. staphylococcal, lung abscess, TB, PCP.
• Trauma: particularly chest trauma in road traffic accident (RTA).
• Iatrogenic: after pleural biopsy or aspiration, transbronchial biopsy,
percutaneous lung biopsy, subclavian vein cannulation, and mechanical
ventilation with high airway pressures.
Investigations: the chest radiograph
• The classical clinical signs may not always be present.
• Standard erect CXR in inspiration is recommended for initial diagnosis.
• In a supine patient, a pneumothorax may not be easy to see. Look for
hyperlucency of one lung field or a line parallel to the chest wall (caused
by retraction of the right middle lobe). An erect CXR may show
blunting of the costophrenic angle on the affected side.
• If a patient has COPD and marked bullous disease, take care that the
suspected pneumothorax is not a large, thin-walled bulla. CT scanning is
recommended for uncertain or complex cases.
Pneumothorax: assessment 211
Pneumothorax: management
See Figs. 2.2 and 2.3. See Box 2.18 for management key points.
Who to discharge from A&E
Patients with primary spontaneous pneumothorax (PSP) or SSP and breath-
lessness associated with any size of pneumothorax should undergo active
intervention, as well as supportive treatment (including O2).
• Small PSP, rim of air <2cm on CXR, no significant dyspnoea, and no
underlying chronic lung disease.
• Large PSP following successful aspiration (<2cm rim of air on repeat
CXR), no significant dyspnoea or underlying lung disease.
• All patients with an SSP should be referred early to a chest physician.
• Follow-up in chest clinic in 10–14 days with a repeat CXR.
• Advise the patient to return to A&E if breathless or increasing
chest pain.
• Air travel should be avoided until full resolution.
Who to admit for observation
• All patients with pneumothorax secondary to trauma or with an
underlying lung disease, even if aspiration has been successful—
discharge after 24h if follow-up CXR shows no recurrence.
• Patients in whom aspiration has failed to re-expand the lung fully.
• Give O2 (>35% unless there is clinical evidence of COPD, in which case
start with 24–28% and check ABGs). This accelerates the reabsorption
of the pneumothorax up to 4-fold. Most of the pneumothorax is
nitrogen (N2) (air), and supplemental O2 decreases the partial pressure
of N2 in blood, increasing the gradient for its reabsorption.
Attempt chest aspiration in patients with
• Primary pneumothorax: all large primary pneumothoraces, whether
symptomatic or not.
• Secondary pneumothorax: all small secondary pneumothoraces, only
if asymptomatic and <50 years. Admit for observation, and if there is
minimal or no pneumothorax on CXR after 24h, discharge with follow-
up in chest clinic in 10–14 days with CXR.
• Needle aspiration should not be repeated, unless there were technical
difficulties.
Proceed to intercostal chest tube drainage in patients with
• Primary pneumothorax: failed aspiration.
• Secondary pneumothorax: small pneumothorax if symptomatic or
>50 years; failed aspiration after one attempt.
• Miscellaneous: associated hydro-or haemopneumothorax, all
mechanically ventilated patients with a pneumothorax, all patients with a
pneumothorax requiring interhospital transfer.
Pneumothorax: management 213
Practice points
• There are NO indications in the standard management for a
pneumothorax for clamping chest drains. If patients are to be moved,
keep the drain bottle below chest height, but DO NOT CLAMP.
• NEVER clamp a chest drain, unless you know what you are doing.
Acute pneumothorax: management
See Figs. 2.2 and 2.3.
Primary pneumothorax
No
Size >2cm and/or breathlessness
Yes
Yes
Attempt aspiration. Successful?
No
No
Tension pneumothorax
• Usually seen in patients receiving mechanical ventilation or post-CPR.
• Patient is usually distressed and tachypnoeic, with cyanosis, profuse
sweating, and marked tachycardia and hypotension.
• This requires immediate attention.
Management
• Do not leave the patient unattended. Give maximal inspired O2 to
reverse hypoxia.
• Insert an 18G (green) cannula (or the largest available), perpendicular
to the chest wall, into the second intercostal space in the mid-clavicular
line on the side of the pneumothorax on clinical examination (reduced
breath sounds and trachea deviated away). Relief should be almost
immediate. Leave the cannula in place until the air ceases to rush out.
• Insert a chest drain as soon as possible.
• If no air rushes out when the cannula is inserted, the patient does not
have a tension pneumothorax and the cannula should be removed.
Haemoptysis: assessment 217
Haemoptysis: assessment
Presentation
• Haemoptysis is coughing up of blood from the lungs or tracheobronchial
tree (see Box 2.19).
• Massive haemoptysis is defined as ≥400mL over 3h or ≥600mL over
24h. The common causes of massive haemoptysis are bronchiectasis,
bronchial carcinoma, infection (e.g. TB, lung abscess, or aspergilloma),
or trauma.
• Often the cause is obvious from the history. Patients with large bleeds
may be able to locate the site of bleeding by a ‘gurgling’ within the chest.
Ask specifically for smoking and drug history.
• Examine for an underlying cause (see Box 2.19) and to assess the
haemodynamic and respiratory effects of the bleed.
• Consider that the blood may be coming from somewhere other than
the lungs: upper respiratory tract, GI tract, nasopharynx.
Poor prognostic factors
These include:
• Increasing age.
• Pre-existing lung or cardiac disease.
• Respiratory compromise (rate, cyanosis).
• Hypoxia (PaO2 ≤10kPa on air).
• Ongoing haemoptysis of large amounts of fresh blood.
• Shock (postural or supine hypotension—rare).
Haemoptysis: management
Initial management
See Box 2.20 for management key points.
Stabilize the patient
• Massive haemoptysis should usually be managed at a hospital with
cardiothoracic surgical backup, and urgent transfer should be considered
if this is not available.
• Give high inspired O2.
• Place the patient in the recovery position, with the bleeding lung down
(if it is known which side the bleeding is from) to try to keep the
unaffected lung free of blood.
• If aspiration of blood is threatened, get anaesthetic help urgently;
anaesthetize, intubate, and ventilate. A double-lumen ETT may be used
to isolate the lungs, but the narrow lumen may make subsequent flexible
bronchoscopy difficult.
• Insert a large-bore peripheral cannula, followed by a central line if
indicated; the internal jugular route is preferred to minimize the risk of
pneumothorax.
• Support the circulation; haemoptyses are rarely severe enough to
warrant transfusion. But cross-match 2–4U if bleeding ongoing. Monitor
the urine output, pulse, BP, and, if appropriate, CVP.
Investigations
All patients should have the following:
• Blood for FBC, U&Es, coagulation studies, and cross-match.
• ABGs.
• ECG.
• CXR.
• Sputum (microscopy and culture, cytology).
• Flexible bronchoscopy.
Diagnose the source of bleeding
• CXR: this should be examined systematically for a mass lesion ± hilar
nodes, bronchiectasis (tramline shadows), and old or new cavities which
may suggest aspergillomas. Look for causes of minor haemoptysis, if this
is the current problem.
• Fibreoptic or rigid bronchoscopy: this should be performed urgently
in all cases of massive haemoptysis. This is unlikely to localize the
exact source but may help localize the lung or lobe affected, to guide
surgeons or radiologists. Bleeding may be arrested by endoscopically
administered adrenaline (1mL of 1:10 000) or, in massive haemoptysis, a
balloon catheter may be inflated for 24–48h within a segmental or sub-
segmental bronchus.
• Selective pulmonary angiography: can identify the bleeding source in
90% of patients and, when combined with embolization, is effective
in controlling bleeding in up to 90%. Multiple procedures may be
necessary.
• High-resolution CT chest: may help identify parenchymal lesions and
peripheral endobronchial lesions.
Haemoptysis: management 219
Pleural effusions
Presentation
• Dyspnoea.
• Chest discomfort or sensation of heaviness.
• Symptoms of malignancy: loss of appetite, weight, and energy.
• Symptoms of infection: fever, cough, sputum, night sweats.
Severity depends on
• Speed of onset (e.g. traumatic or post-procedural).
• Haemodynamic compromise (hypotension, tachycardia).
• Hypoxia or respiratory failure.
• Presence of underlying disease (e.g. heart failure, COPD).
Causes
Transudate (protein <30g/L) Exudate (protein >30g/L)
• Raised venous pressure: • Infection:
• Cardiac failure. • Pneumonia.
• Constrictive pericarditis. • Empyema (bacterial or TB).
• Fluid overload. • Subphrenic abscess.
• Hypoproteinaemia: • Malignancy:
• Nephrotic syndrome. • Primary bronchial.
• Cirrhosis with ascites. • Mesothelioma.
• Protein-losing enteropathy. • Secondary (and lymphoma).
• Miscellaneous: • Lymphangitis carcinomatosa.
• Hypothyroidism. • Miscellaneous:
• Meigs’ syndrome. • Haemothorax (trauma,
• Yellow nail syndrome. iatrogenic).
• Chylothorax (thoracic duct
trauma).
• Autoimmune (RA, SLE,
Dressler’s).
• Pancreatitis.
Management
See Box 2.22 for management key points.
• If acute, then stabilize the patient and insert a chest drain.
• If effusion is chronic, then reach a diagnosis and treat accordingly.
• Image guidance: a recent CXR should be available prior to performing
aspiration/drainage. Thoracic US guidance is strongly recommended for
all procedures for pleural fluid. Prior marking of the spot for subsequent
remote intervention is not recommended, except for large pleural
effusions.
Acute massive effusion
• Give O2.
• IV access: via a wide-bore cannula or an internal jugular central line
(being careful not to cause further lung injury).
• Take blood: for FBC, clotting, and urgent cross-match (6U).
• Correct coagulopathies.
Practice points
If there is dmovement of one side of the chest, that is the side of path-
ology (e.g. fluid, infection, pneumothorax).
Empyema 223
Empyema
This is a serious complication of bacterial chest infection (E Acute pneu-
monia: complications, p. 179). All effusions associated with sepsis or pneu-
monia should be tapped and pH assessed if non-purulent and pleural
infection suspected.
• To avoid long-term scarring and loculated infection, the empyema
requires urgent drainage by US guidance and usually the positioning of
an intercostal drain.
• Frequently, drainage fails as the empyema organizes with dense
adhesions producing loculations. This can be assessed by US. Surgical
drainage may be required.
• Empyema should always be discussed with a respiratory physician or
cardiothoracic surgeon.
• There is no indication for routine use of intrapleural fibrinolytics.
• All patients with pleural infection are high risk for the development
of VTE and should receive adequate thromboprophylaxis unless
contraindicated.
See Box 2.23 for Light’s criteria for pleural fluid analysis.
Practice points
The sun should never set on an empyema! Patients with purulent/turbid
pleural fluid (or positive Gram stain) should receive prompt pleural space
chest tube drainage under image guidance (small-bore 10–14F will be ad-
equate in most cases, with regular flushing to avoid blockage).
Further reading
British Thoracic Society, Pleural Disease Guideline Group (2010). BTS pleural disease guideline 2010.
M https://www.brit-thoracic.org.uk/document-library/clinical-information/pleural-disease/
pleural-disease-guidelines-2010/pleural-disease-guideline
24
Management
• If severe, liaise immediately with ITU and ENT or general surgeons
(potential for urgent tracheostomy).
• Priorities are:
• Stabilize the patient: ensure adequate airway.
• Identify the cause of obstruction.
• Specific treatment measures.
Stabilize the patient
• Take ABGs, and give high percentage O2 (≥60%).
• If a clear cause of obstruction (foreign body, post-operative thyroid
surgery) (see Box 2.24), then take appropriate measures to gain patient
airway.
• If the patient is becoming increasingly exhausted or there is acute failure
of ventilation, then summon colleagues and be prepared to intubate or
perform a tracheostomy.
Foreign body
With total upper airway obstruction, perform the Heimlich manoeuvre
(stand behind the patient, grip the wrists across the patient’s upper ab-
domen, and tug sharply to raise the intrathoracic pressure and expel the
foreign body). Otherwise perform a CXR, and liaise with the respiratory/
ENT/cardiothoracic teams for retrieval under direct vision.
Epiglottitis
Usually H. influenzae type b, also S. pneumoniae. Treat with third-generation
cephalosporin, e.g. cefotaxime 2g tds (adults). Children more likely to re-
quire intubation, but if any concerns over airway, then the patient (adult or
child) should be monitored on ITU after anaesthetic assessment.
Diphtheria
Uncommon in the UK; occasionally seen in patients returning from abroad.
Toxin-mediated problems include myocarditis and neuritis. Treat with diph-
theria antitoxin + antibiotic eradication of organism (consult microbiology).
Tumour obstruction
Unlikely to cause life-threatening obstruction without warning symptoms
over at least a few days. If significant stridor is present, then administer
200mg of hydrocortisone, and thereafter prednisolone 40mg od PO. If la-
ryngeal origin, liaise with ENT regarding tracheostomy. Lung cancer in the
trachea, or extrinsic cancer eroding into the trachea, will require urgent
radiotherapy (or occasionally laser or cryotherapy via a bronchoscope).
26
Chapter 3 227
Gastroenterological
emergencies
Assessment of severity
It is essential to categorize patients at the time of admission into high or low
risk of death [recent NICE guidelines advise using Blatchford scores (see
Table 3.2) on admission].2 Patients with a Blatchford score of >0 should be
considered for endoscopy; if score = 0, can consider early discharge.
Most deaths occur in the elderly with comorbid disease.
In general, high-risk factors include the following:
• Age >60 years (30% risk of death if >90 years).
• Shock (SBP <100mmHg in patients <60 years or <120mmHg in patients
>60 years). Measure postural change in BP in patients who are not
shocked, and change in HR.
• Inappropriate bradycardia or HR >120bpm.
• Chronic liver disease.
• Other chronic disease (e.g. cardiac, respiratory, renal).
• Bleeding diathesis.
• dconscious level.
Management
Liaise with specialists early (on-call endoscopy team and surgeons). An ex-
perienced anaesthetist should be informed. Most patients will have stopped
bleeding by the time they are seen; however, all upper GI bleeds should be
taken seriously, as they may re-bleed in hospital, and mortality following a
re-bleed is high.
Priorities are:
• To stabilize the patient: protect the airway and restore the circulating
volume.
• To identify the source of the bleed.
• Definitive treatment of the cause of bleeding.
Table 3.2 Blatchford score*
The Blatchford score admission risk marker Score value
Blood urea (mmol/L)
≥6.5 to <8.0 2
≥8.0 to <10.0 3
≥10.0 to <25 4
≥25 6
Hb (g/L) for men
≥120 to <130 1
≥100 to <120 3
<100 6
Hb (g/L) for women
≥100 to <120 1
<100 6
SBP (mmHg)
100–109 1
90–99 2
<90 3
Other markers
Pulse ≥100bpm 1
Presentation with melaena 1
Presentation with syncope 2
Hepatic disease 2
Cardiac failure 2
*
Reprinted from The Lancet, 356, Blatchford O et al., ‘A risk score to predict need for treatment
for uppergastrointestinal haemorrhage’, 1318–21, Copyright 2000, with permission from Elsevier.
References
2. National Institute for Health and Care Excellence (2012). Acute upper gastrointestinal bleeding in
over 16s: management. Clinical guideline [CG141]. M https://www.nice.org.uk/Guidance/cg141
23
References
3. National Institute for Health and Care Excellence (2012). Acute upper gastrointestinal bleeding in
over 16s: management. Clinical guideline [CG141]. M https://www.nice.org.uk/Guidance/cg141
234
Erosive gastritis/oesophagitis
These generally present as relatively minor bleeds but may be significant.
Represent 715% of upper GI bleeds and are associated with prior use of
aspirin or other NSAIDs in previously fit patients, or ‘stress’ in the critically
ill patient (e.g. patients on ITU).
• Management: at endoscopy, there is commonly a generalized ooze
of blood from the inflamed mucosa. Initial management is as before
(see Box 3.1).
• Give PPI or sucralfate 1–2g qds PO or via an NG tube.
• PPIs are better than H2-antagonists in healing oesophagitis and
oesophageal ulcers.
• Correct any clotting disorder.
• If the lesions are too diffuse and bleeding continues, partial gastric
resection may be necessary.
• Prognosis: <5% of patients with haemorrhagic gastritis require surgery.
Overall mortality is <10%.
236
Variceal haemorrhage: medical
management
Oesophageal and gastric varices develop with portal hypertension of
whatever cause. Bleeding from varices is typically vigorous and difficult to
control, and often occurs in the setting of abnormal clotting, thrombocyto-
penia, and sepsis.
Diagnosis
History and physical examination may raise the suspicion of a variceal
source of bleeding, but 730% of cirrhotics have a non-variceal source of
bleeding. The most reliable method is upper GI endoscopy, which should be
performed as soon as is feasible. Bleeding may occur from either gastric or
oesophageal varices, or rarely portal hypertensive gastropathy.
Medical management
(See Box 3.3.)
• Initial resuscitation is as described under E Acute upper GI bleeding 2,
pp. 230–1.
• Transfuse with blood, FFP, and platelets, as necessary, according
to haematological parameters, to try to stop the bleeding. Give
vitamin K 10mg IV once only to exclude vitamin K deficiency. Avoid
overtransfusion (may increase the risk of rebleeding).
• Antibiotics: take blood, urine, and ascitic fluid for culture and microscopy.
Start broad-spectrum antibiotics. Several studies have shown that
variceal bleeding is associated with sepsis and that antibiotics also
reduce re-bleeding rates. Commence a third-generation cephalosporin
or ciprofloxacin and amoxicillin. Treat for 5 days.
• Terlipressin: (2mg initially, and then 1–2mg every 4–6h, for up to
72h) is effective in controlling variceal bleeding by causing splanchnic
vasoconstriction (relative reduction in mortality of 734%). Avoid high
doses (2mg), if possible. Serious side effects occur in 4% and include
cardiac ischaemia, peripheral vasoconstriction (which may produce
significant hypertension), and skin and splanchnic ischaemia. Octreotide
is a synthetic analogue of somatostatin. A Cochrane review found
that octreotide had no effect on mortality and had a minimal effect on
transfusion requirements.4 It is not recommended.
• Band ligation of varices: is most commonly used and is safer than
injection sclerotherapy. It should be repeated at 2-weekly intervals until
the varices have been obliterated.
• Endoscopic injection: of sclerosant into the varices or para-variceal
can control the bleeding acutely. Side effects (serious in 7%) include
retrosternal pain and fever immediately post-injection, mucosal
ulceration, late oesophageal strictures, and PE. Gastric varices should be
injected with cyanoacrylate glue.
• Balloon tamponade: a Sengstaken–Blakemore tube may be inserted
(E Insertion of Sengstaken–Blakemore tube, p. 844), with inflation of
the gastric balloon ONLY. This should not be left in place for >12h, as
ischaemic ulceration may occur. Apply 1kg traction to compress the
gastro-oesophageal junction and reduce blood flow to the varices.
References
4. Ioannou GN, Doust J, Rockey DC. Terlipressin for acute esophageal variceal hemorrhage.
Cochrane Database Syst Rev 2003;1:CD002147. M http://www.cochrane.org/reviews/en/
ab002147.html
238
Variceal haemorrhage: further
management
Radiological management
TIPS is available in specialized units. Using a jugular or femoral approach, the
hepatic veins are cannulated and an expandable stent is placed between the
hepatic veins (low pressure) and the portal venous system (high pressure).
The portal pressure should be decompressed to below 12mmHg.
Surgical management
This has been largely superseded by TIPS.
• Emergency porto-caval shunting is effective in controlling the bleed
(>95%) but has a high operative mortality (>50%) and does not
influence long-term survival. Few surgeons can do this now.
• Oesophageal transection is never used now but remains an option.
Danis stent
Some centres have started using self-expanding, removable metal stents to
compress bleeding oesophageal varices. The stent is normally inserted with
the help of an endoscope (but can be inserted without). It is removed after
2 weeks. Further procedures, such as TIPS or surgery, may be carried out
to reduce the risk of further bleeds.
Prognosis
• Overall mortality is 30%. This is highest in those with severe liver
disease (Child–Pugh grade C; see Table 3.3).
• Success rates for cessation of acute bleeding varices are:
• Injection sclerotherapy or banding: 770–85%.
• Balloon tamponade: 780%.
• Terlipressin: 770%.
Long-term management
• Band ligation every 2 weeks until variceal obliteration more rapidly
(39 days versus 72 days).
• Injection sclerotherapy is rarely used now.
• Propranolol (up to 80mg tds; aim for a 30–40% reduction in resting HR,
but confirm reduction of portal pressure by measurement of wedged
hepatic venous pressure gradient) reduces the rate of re-bleeding from
varices and portal hypertensive gastropathy. It has not been shown to
decrease mortality.
• TIPS or shunt procedures provide a more definite cure, and bleeding
tends to recur only when the shunt blocks, but there is an i incidence
of chronic hepatic encephalopathy. It is very effective.
Mallory–Weiss tear
This is a tear in the mucosa at the gastro-oesophageal junction following
severe retching and is particularly common following large bouts of alcohol.
The vomit is normal initially and becomes bright red.
Management
• Most stop bleeding spontaneously.
• Tamponade with a Sengstaken–Blakemore tube may be used.
• Surgical oversewing of bleeding point or selective arteriography and
embolization of the feeding artery may be necessary.
Mallory–Weiss tear 241
24
Acute gastroenteritis: assessment
Food poisoning is an acute attack of abdominal pain, diarrhoea ± vomiting
1–40h after ingesting contaminated foodstuffs and lasting 1–7 days. With
the exception of an acute attack of inflammatory bowel disease (IBD) and
mesenteric ischaemia (E Inflammatory bowel disease 1, p. 254), the ma-
jority of acute-onset diarrhoea has an infective aetiology.
Differential diagnosis of acute diarrhoea
Common
• Gastroenteritis (bacterial, viral, • Food intolerance/allergy
protozoal). (e.g. lactase deficiency).
• Clostridium difficile diarrhoea • Drugs (see Box 3.7).
(pseudomembranous colitis).
• IBD.
Less common
• Coeliac disease. • Pancreatic insufficiency.
• Tumour (benign or malignant). • Bile salt enteropathy.
• Carcinoid syndrome. • Hyperthyroidism.
• Bacterial overgrowth. • Autonomic neuropathy.
• Irritable bowel syndrome. • Ischaemic bowel.
Presenting features
Ask specifically about:
• Recent eating habits, especially restaurants and food prepared by
caterers. Anyone else (family/friends) with similar symptoms?
• Time interval between eating any suspicious substance and onset of
symptoms. Early onset of vomiting or diarrhoea (6–12h) suggests
ingestion of preformed toxin (e.g. Staphylococcus exotoxin). Enterotoxin-
producing organisms may take 1–3 days to produce symptoms.
• Recent travel (enterotoxigenic Escherichia coli, Salmonella, Giardia, or
amoeba)? Recent medication? Any antibiotics (C. difficile)?
• Past medical history, e.g. gastric surgery or immunosuppression (drugs
or HIV).
• Oro-anal intercourse increases the risk of amoebiasis, giardiasis, and
shigellosis. Insertive anal intercourse increases the risk of rectal syphilis,
rectal gonorrhoea, Chlamydia trachomatis, and herpes simplex virus
(HSV) infection of the rectum and perianal area (diarrhoea in HIV-
infected patients is discussed under E Gastrointestinal presentations in
HIV-positive patients: assessment, p. 528).
• The gross appearance of the diarrhoea may help: frankly bloody
stool—Campylobacter or Shigella; watery, ‘rice-water stool’—
classically secretory diarrhoea due to cholera, enterotoxigenic E. coli,
or neuroendocrine tumours. Typhoid classically associated with
constipation when typically presents with fever, though early phase
(often prodromal) may have greenish ‘pea-soup’ diarrhoea.
• Abdominal pain may be present: usually cramp-like or tenesmus.
• Fever: common with severe bacterial diarrhoea and acute exacerbations
of CD or ulcerative colitis (UC).
Investigations
• FBC iWBC; ihaematocrit (dehydration).
• U&Es iurea (dehydration); dK+.
• Blood cultures Systemic infection may occur.
• Stool cultures Fresh samples, mandatory for wet mount micros-
copy for ova, cysts, and parasites, culture, and
antibiotic sensitivities. White blood cells (WBCs)
in stool implies intestinal inflammation (mucosal
invasion, toxin, IBD, ischaemic colitis).
• C. difficile toxin Specifically request this for all patients who have
recently taken antibiotics or who develop diar-
rhoea in hospital.
• Sigmoidoscopy and Useful for persistent bloody diarrhoea
rectal biopsy (>4–5 days) without diagnosis or improvement.
Management
It is important to maintain hydration in patients with diarrhoea and to avoid
loperamide, unless infective causes have been excluded. Box 3.4 contains
general guidelines only.
Bacterial gastroenteritis
Salmonella spp.
May produce acute gastroenteritis (e.g. S. enteritidis, 770–80% of cases),
enteric fever (S. typhi and S. typhimurium; E Enteric fever (typhoid),
pp. 490–1), or asymptomatic carriage. Acute gastroenteritis often occurs
in epidemics and is derived from poultry, eggs, or egg products, and occa-
sionally pets (terrapins).
• Symptoms: 8–48h after ingestion, with headache, vomiting (worse than
either Shigella or Campylobacter), fever, and diarrhoea lasting 2–4 days
(rarely bloody, with mucus). Reactive arthritis may occur (in HLA-B27
+ve). Enteric fever (E Enteric fever (typhoid), pp. 490–1).
• Management: usually self-limiting after 2–5 days, and treatment is
supportive for most cases. Some antibiotics can prolong carriage of the
illness and make clinical relapse more likely.
Clostridium perfringens (type A)
Fifteen to 25% of cases of bacterial food poisoning. Spores are heat-resistant
and may germinate during reheating or slow cooking of meats. Enterotoxin
is released when sporulation occurs in the intestine. Incubation 8–22h.
• Symptoms: diarrhoea, abdominal pain, nausea (rare to get vomiting). No
fever. Lasts 12–24h.
• Management: supportive.
Campylobacter
Campylobacter infections are common (5–10% of patients with acute diar-
rhoea). The incubation period is 3–7 days; symptoms last for 1–2 weeks.
Presentation often follows eating contaminated poultry.
• Symptoms: flu-like illness, followed by headache, myalgia, abdominal pain
(continuous, then colicky), diarrhoea, and rectal bleeding occasionally.
Rarely complicated by reactive arthritis (1–2%), GBS, or Reiter’s
syndrome.
• Management: usually self-limiting, <5 days. Treatment comprises either
erythromycin or tetracycline. Anti-diarrhoeals are contraindicated.
Staphylococcus aureus
(2–5% of cases) Can multiply at room temperature in foods rich in carbo-
hydrates and salt (dairy products, cold meats, mayonnaise). A heat-stable
exotoxin produces nausea, vomiting, and diarrhoea 1–6h after ingestion.
Fever is uncommon. Treatment is supportive.
Bacillus cereus
Associated with slow-cooking foods and reheated rice (fast-food take-
aways). It produces a toxin that causes vomiting within 1–5h, and diarrhoea
8–16h later. Treatment is supportive.
Vibrio parahaemolyticus
Produces epigastric pain (cf. those above), diarrhoea, vomiting, and fever
12–18h after ingestion of raw seafood (shellfish). May last up to 5 days.
Vibrio cholerae is uncommon in western nations. It produces profuse secre-
tory diarrhoea. The disease is usually self-limiting (5–7 days), but tetracyc-
lines may be used.
Yersinia enterocolitica
Incubation period is 4–10 days after contact with infected animals, water,
or ice cream.
• Symptoms: diarrhoea (80%), abdominal pain (80%), fever (40%), bloody
stool (10%), mesenteric adenitis, lymphadenopathy, reactive arthritis.
Diagnosed by serology, rather than culture.
• Management: supportive.
Shiga toxin-producing E. coli (e.g. O157:H7)
Infection is usually from contaminated meat/burgers. The incubation period
is 75 days. Stools become bloody over 24–48h, secondary to diffuse colitis.
Most patients resolve over 5–7 days without treatment. However, some pa-
tients, especially children, may go to develop haemolytic uraemic syndrome
(HUS), with tiredness, microangiopathic anaemia, thrombocytopenia, renal
failure, and encephalopathy. Most recover with supportive care. Antibiotics
are contraindicated, as some antibiotics increase shiga toxin release and ex-
acerbate or cause the development of HUS.
246
Viral gastroenteritis
In addition to diarrhoea, URTI-like symptoms, abdominal cramps, head-
ache, and fever may occur. High frequency of vomiting. The causative
agent is usually not found, but many viruses are implicated (e.g. echovirus,
Norwalk virus, rotavirus, and adenoviruses). Self-limiting illness (3–5 days).
Management
Oral fluids and restricting solid foods and dairy product intake usually
suffice. If <65 years old, and volume-deplete or moderate to severe diar-
rhoea, consider 1–2 days of loperamide. If excessive vomiting, treat with
antiemetics (e.g. prochlorperazine).
Clostridium difficile
Patients with C. difficile infection can be asymptomatic (carrier) or pre-
sent with diarrhoea and toxic megacolon at the extreme. Caused by two
necrolytic toxins (A and B) produced by C. difficile. It is the most common
cause of hospital-acquired diarrhoea. Infection typically follows antibiotic
therapy. Diarrhoea may occur during or up to 4 weeks following cessation
of treatment.
Symptoms
Diarrhoea is usually profuse and watery, and may be bloody in 75% of pa-
tients. It is commonly associated with abdominal cramps and tenderness,
fever (>38.5°C when severe), and an elevated WCC (>30 × 109/L).
Diagnosis
Diagnosis is based on the detection of C. difficile toxin or toxin gene in stool.
Culture of the organism itself is unhelpful; 75% of healthy adults carry the
organism. Sigmoidoscopy is not diagnostic but may show mucosal inflam-
mation, together with multiple yellow plaques (pseudomembranous col-
itis), which is highly suggestive and should prompt laboratory investigation.
Laboratory testing consists of checking for the antigen and toxin. If the
antigen is negative, diarrhoea is highly unlikely to be due to C. difficile infec-
tion. For other combinations, see Management section below.
Management
• General considerations: rehydrate and correct electrolyte abnormalities.
Complications include toxic megacolon and colonic perforation. Faecal
transplantation from healthy individuals has shown promising results in
clinical trials (80% cure rate on first transplant, with further 80% cure
rate if the first transplant is unsuccessful).
• Antigen positive and toxin positive: isolate and barrier-nurse. Mild
disease responds to oral metronidazole (400mg tds). Oral vancomycin
250mg qds for 7–14 days is an alternative. Severe disease requires
oral vancomycin as first line, and addition of IV metronidazole if not
improving. Fidaxomicin may be considered in patients who cannot
tolerate vancomycin, although more data are needed.
• Antigen positive, toxin negative: isolate if symptomatic; review (and
stop, if possible) antibiotics; stop PPIs and laxatives, if possible. If
high risk (age >65, on antibiotics/PPI, antibiotics within last 30 days,
recurrent hospital admissions), consider oral metronidazole and/or
vancomycin.
248
Giardiasis
Giardia lamblia is transmitted by the faeco-oral route. Risk factors include
recent travel, immunosuppression, homosexuality, and achlorhydria.
Symptoms
More chronic diarrhoeal illness with epigastric discomfort due to duodenal
infestation. Malaise, bloating, flatulence, and occasionally malabsorption
occur. Diagnosis is by stool microscopy for cysts or trophozoites or by duo-
denal aspiration. If negative, consider blind therapeutic trial.
Management
Metronidazole is the treatment of choice—2g daily for 3 days or 400mg tds
PO for 5 days. Alternatives include tinidazole (2g, single dose) or mepacrine
hydrochloride 100mg tds for 5–7 days. Lactose intolerance post-infection
may persist for up to 6 weeks.
Travellers’ diarrhoea
Travel through developing countries is commonly associated with self-
limiting acute diarrhoeal illness transmitted through food and water. The
most frequent pathogen is enterotoxigenic E. coli (40% of cases) (see
Box 3.5). The illness lasts 3–5 days, with nausea, watery diarrhoea, and
abdominal cramps. Oral rehydration is usually sufficient. Antimotility
agents (e.g. loperamide) may be used with caution. Antibiotic treatment
(ciprofloxacin 500mg bd) may help patients with more protracted illness.
Alternatives include doxycycline or co- trimoxazole (for travellers from
South East Asia, azithromycin may be a better choice of empiric therapy
due to high quinolone resistance). Diarrhoea that persists for >7 days re-
quires further investigation, including stool microscopy and culture, ser-
ology, sigmoidoscopy, and biopsy (see Box 3.6). A 3-to 5-day course of a
broad-spectrum antibiotic, such as ciprofloxacin, may terminate the illness.
For common drugs that may cause acute diarrhoea, see Box 3.7.
Bloody diarrhoea
Causes
• Acute infectious colitis:
• Bacillary dysentery (Shigella spp.).
• Salmonellosis (E Enteric fever (typhoid), pp. 490–1).
• Campylobacter (E Bacterial gastroenteritis, pp. 244–5).
• Amoebic dysentery.
• Haemorrhagic colitis (shiga-like toxin-producing E. coli).
• Pseudomembranous colitis (E Clostridium difficile, p. 247).
• Ischaemic colitis.
• Lymphogranuloma venereum (LGV).
• IBD (UC or CD).
Presenting features
• Ask about the duration of symptoms and recent eating habits. Others
affected? Recent travel (enterotoxigenic E. coli, Salmonella, or amoeba)?
Any antibiotics (C. difficile)?
• The gross appearance of the stool may help. IBD may result in rectal
bleeding (fresh red blood) in patients with disease largely confined to
the rectum and sigmoid colon. Diffuse disease tends to be associated
with diarrhoea. Infectious colitis results in frankly bloody stool
(Campylobacter or Shigella).
• Abdominal pain may be present: usually cramp-like or tenesmus.
• Vomiting is uncommon in acute IBD.
• Systemic features, such as general malaise and lethargy, dehydration
with electrolyte imbalance, or fever, are seen with severe bacterial
diarrhoeas and acute exacerbations of CD or UC. Skin, joints, and eyes
may be involved either in IBD or following an acute infection.
• Previous altered bowel habit, weight loss, smoking history, vascular
disease (mesenteric infarction), and mesenteric angina may be relevant.
Examination
Look for:
• Fever, signs of dehydration (tachycardia, postural hypotension), and
abdominal distension. Abdominal tenderness or rebound over affected
colon (IBD) may indicate colonic dilatation or perforation. An abdominal
mass may indicate a tumour or an inflammatory mass.
• Mouth ulcers and perianal disease are common in active IBD.
• Erythema nodosum and pyoderma gangrenosum occur in IBD; Yersinia
may produce erythema nodosum. Rose spots indicate typhoid fever.
• Joint involvement (often an asymmetrical, non-deforming synovitis,
involving large joints of the lower limbs) may occur in active IBD, but
also in infectious colitis (e.g. Campylobacter, Yersinia).
• Uveitis is associated with both IBD and acute infectious colitis.
Investigations
The priority is to exclude any infectious cause for the bloody diarrhoea and
to monitor for complications.
• Blood tests: FBC, U&Es, LFTs, CRP, ESR, coagulation studies.
• Microbiology: stool MC&S, blood cultures, C. difficile toxin, ova, cysts,
and parasites.
• Sigmoidoscopy biopsy: may help to distinguish between acute infectious
colitis and IBD (i risk of perforation during colonoscopy). Appearance
of pseudomembranes (a yellow layer of exudate resembling a
membrane) indicates possible C. difficile.
• Imaging: plain abdominal X-ray (AXR) may help monitor colonic
dilatation. Contrast studies are contraindicated acutely.
Practice points
• Always test for C. difficile in patients with new-onset bloody
diarrhoea.
• In unexplained extreme leucocytosis (e.g. WCC >35 000), consider
C. difficile.
25
Bacterial dysentery
This is due to infection with Shigella (S. dysenteriae, S. flexneri, S. boydii,
S. sonnei), Salmonella, Campylobacter, or some Shigella-like E. coli (0157:H7).
Transmitted by the faeco-oral route, and clusters of cases are often found.
Symptoms
• It causes mild diarrhoea to a severe systemic illness between 1–7 days
following exposure.
• Fever (usually resolves in 3–4 days).
• Abdominal cramps with tenesmus.
• Watery diarrhoea ± nausea and vomiting (resolves by day 7). Bloody
diarrhoea occurs later (after 24–72h) due to invasion of the mucosa.
• Diagnosed by stool culture. E. coli infections may be complicated
by HUS.
Management
• Patients may require IV fluid replacement.
• Antibiotics should be reserved for the most severe cases. Ciprofloxacin
(500mg PO bd for 7–10 days) is usually effective, but in resistant cases,
co-trimoxazole or ciprofloxacin may be used.
• Antimotility agents, such as loperamide and codeine, are
contraindicated, as they prolong carriage and worsen symptoms.
Amoebic dysentery
E. histolytica can produce intermittent diarrhoea or a more severe illness
that resembles IBD. There is an i risk in homosexuals and in those with re-
cent travel to third-world countries. It is transmitted by the faeco-oral route.
Diagnosis is through serology or antigen testing, together with identifica-
tion of the parasite in stool or extraintestinal sites (such as liver abscess pus).
Symptoms
• Diarrhoea or loose stool (± blood), abdominal discomfort, mild fever.
In severe cases, liver abscess.
• Fulminant attacks present abruptly with high fever, cramping abdominal
pain, and profuse bloody diarrhoea.
• Marked abdominal tenderness and tenesmus are present.
• Diagnosis is made by identifying amoebic cysts on stool microscopy.
• May be complicated by the development of amoebic liver abscess.
Treatment
• Aimed at replacement of fluid, electrolytes, and blood loss, and
eradication of the organism.
• In acute invasive intestinal amoebiasis, oral metronidazole (800mg
tds for 5–10 days) is the treatment of choice. Tinidazole (2g daily for
2–3 days) is also effective. This should be followed with oral diloxanide
furoate (500mg tds for 10 days) to destroy gut cysts.
• Metronidazole (or tinidazole) and diloxanide furoate are also effective
for liver abscesses, and US-guided aspiration may help improve
penetration of the drugs and shorten the illness.
• Diloxanide furoate is the treatment of choice for asymptomatic patients
with E. histolytica cysts in the stool, as metronidazole and tinidazole are
relatively ineffective.
254
Indications for surgery
• In UC, failure of symptoms to resolve after 5 days of medical therapy is
an indication for pan-proctocolectomy. A staged procedure (colectomy
first) is recommended in this situation.
• Colonic perforation, uncontrollable bleeding, and fulminating disease
require urgent proctocolectomy; 730% of all patients with UC will
require a colectomy at some stage.
• Toxic dilatation prior to treatment is not an indication for surgery
(failure of the colonic diameter to decrease after 24h). The
development of dilatation during treatment is an indication for surgery.
• Surgery in CD is not ‘curative’ and is only indicated for perforation,
obstruction, abscess formation, and fistulae (enterocutaneous or
enterovesical). There is a high recurrence rate after surgery.
Jaundice: assessment
Jaundice requires urgent investigation and diagnosis. It may herald the onset
of severe hepatitis and acute liver (± renal) failure (E Acute liver failure: as-
sessment and investigations, pp. 276–7). It may indicate obstructive jaundice
which can be complicated by cholangitis and septicaemia (E Biliary ob-
struction, pp. 272–3).
History
• Non-specific symptoms include anorexia, pruritus, malaise, lethargy,
drowsiness, confusion, or coma. Dark urine and pale stools may be
features of either obstructive jaundice or hepatitis.
• Colicky right upper quadrant (RUQ) pain, previous biliary colic, or
known gallstones suggests biliary colic (E Biliary obstruction,
pp. 272–3). Fever, rigors, abdominal pain, and fluctuating jaundice should
raise the suspicion of cholangitis. Painless jaundice and weight loss
suggest pancreatic malignancy.
• Take a detailed drug history, including over-the-counter (OTC),
herbal, homeopathic, or proprietary preparations. Ask about use of
paracetamol and alcohol.
• Risk factors for infectious hepatitis: blood transfusion, IV drugs, tattoos,
being homosexual, travel, ethnic origin, ingestion of shellfish.
Examination
• Note the degree of jaundice, and look for stigmata of chronic liver
disease (spider naevi or telangiectasia, palmar erythema, Dupuytren’s
contractures, etc.). Lymphadenopathy may reflect malignancy. Hepatic
encephalopathy results in falling conscious level and liver flap.
• Note the BP and the diastolic carefully—it falls with liver failure.
Oliguria or shock may occur with acute liver failure (E Acute liver
failure: assessment and investigations, pp. 276–7). Examine for pleural
effusions (may occur with ascites).
• Examine the abdomen for ascites, hepatomegaly, splenomegaly (portal
hypertension or intravascular haemolysis), or masses.
Causes of jaundice
• Viral hepatitis.
• Alcoholic hepatitis ± cirrhosis.
• Drug-induced hepatitis (including paracetamol).
• End-stage cirrhosis (alcoholic, chronic viral hepatitis, haemochromatosis,
Wilson’s disease, cryptogenic cirrhosis, etc.).
• Haemolytic anaemia.
• Gilbert’s syndrome (mild jaundice).
• Biliary obstruction (stones or turnover).
• Intrahepatic cholestasis, post-hepatitic [primary biliary cirrhosis (PBC),
PSC, sepsis, drugs].
• Autoimmune hepatitis.
• Ischaemic hepatitis.
• Sepsis.
• Leptospirosis.
• Malaria.
Jaundice: assessment 261
Viral hepatitis
Hepatitis A, hepatitis B, or delta co-infection of hepatitis B virus (HBV) car-
riers can lead to acute hepatitis with jaundice. Acute hepatitis C can pre-
sent with jaundice, but this is less usual. EBV infection frequently causes
abnormal LFTs, including mild or moderate jaundice, and is often associated
with splenomegaly and lymphadenopathy during the acute phase. Patients
should be asked about IV drug use, recent tattoos, sexual contacts, and any
family or contact history of jaundice or hepatitis. Consider CMV hepatitis
in immunocompromised patients. Hepatitis E is usually self-limiting (can be-
come chronic in immunocompromised patients).
• Prodromal ‘flu-like’ illness and very high transaminase (up to 74000U/L),
with a small increase in ALP activity.
• If there is no coagulopathy, encephalopathy, or renal failure, send the
patient home, and await virology results. Arrange repeat LFTs and
clotting at 2-to 3-day intervals, and see the results (but not necessarily
the patient). See the patient again within a week. Instruct the patient and
carers to return if increasingly unwell or drowsy.
Hepatitis A
Patients with acute hepatitis A (anti-HAV IgM positive) require no specific
treatment, but all household and school contacts should be immunized with
HAV vaccine ± normal human Ig5 (see Box 3.12 for details). Patients with
acute hepatitis A may rarely develop acute liver failure, although the prog-
nosis is relatively good (>80% survival) with conservative management.
Acute hepatitis A may be associated with high fever (40°C).
Hepatitis B
HBsAg appears in serum 1–10 weeks after an acute exposure to hepatitis
B and prior to the onset of symptoms or increased alanine transaminase
(ALT). As HBsAg disappears from serum, HBsAb appears, and there may be
a window period when both are negative. Detection of anti-HBc IgM is usu-
ally regarded as an indication of acute HBV infection; however, anti-HBc IgM
may remain detectable up to 2 years after the acute infection, and anti-HBc
may increase to detectable levels during exacerbations of chronic hepatitis B.
In the majority of patients who recover, HBsAg becomes undetectable
after 4–6 months. Persistence of HBsAg for >6 months suggests chronic in-
fection. The rate of progression from acute to chronic hepatitis B is <1–5%
for adult-acquired infection. Patients with acute HBV do not require acute
antiviral treatment. However, many clinicians treat patients with severe
hepatitis (e.g. INR >1.5) or protracted symptoms or marked jaundice for
>4 weeks after presentation, as well as those who are immunocomprom-
ised or have pre-existing liver disease, since this may reduce the likelihood
of re-infection post-liver transplantation.
For HBsAg-positive patients, family and close contacts should be tested
for HBsAg, HBsAb, and anti-HBc IgM. Prophylactic-specific hepatitis B im-
munoglobulin (‘HBIG’ 500U IM) is protective if given within 10 days of
exposure to HBV; however, only use for persons with clear exposure to
HBsAg-contaminated material (needle-stick or sexual contacts who are
HBsAb-negative). Follow up for at least 6 months. See Table 3.4 for a sum-
mary of the investigation results in different HBV states.
Hepatitis C
HCV RNA is usually detectable in serum by PCR within 8 weeks following
exposure, but may be earlier. Transmission is predominantly through blood
exposure. Sexual or perinatal transmission are rare (<5% risk). Acute
hepatitis C accounts for <5% of cases of acute viral hepatitis in the United
Kingdom (UK). Most cases are asymptomatic; <25% develop an increase
in serum bilirubin, and serum ALT is usually <1000U/L. The presence of
HCV RNA in serum is the first evidence of HCV infection and is detectable
within 2 months following exposure. Anti-HCV enzyme-linked immuno-
sorbent assay (ELISA) tests become positive between 2 and 6 months after
exposure.
The primary goal of HCV therapy is to cure the infection with the new
direct acting antivirals (DAAs). Cure is defined as achieving a sustained viro-
logical response (SVR) defined as undetectable HCV RNA. The aims are
to: (1) prevent the complications of HCV-related liver and extrahepatic
diseases; (2) improve quality of life and remove stigma; and (3) prevent
onward transmission of HCV.
All patients with HCV, regardless of previous therapy, should be con-
sidered for treatment. Overall, cure rates of 95% or above, approaching
100%, can be achieved with the new HCV DAAs.
References
5. Public Health England (2017). Public health control and management of hepatitis A: 2017 guide-
lines. M https://www.gov.uk/government/publications/hepatitis-a-infection-prevention-and-
control-guidance.
Alcoholic hepatitis
• Acute hepatitis may be asymptomatic or present with nausea, vomiting,
and anorexia, rarely RUQ pain. Fever may reflect severe liver damage,
but infection needs to be excluded. Most patients who present with
alcoholic hepatitis have cirrhosis at presentation.
• The term alcoholic hepatitis is a misnomer, as the transaminases rarely
exceed 200U/L and are always <400U/L. AST is always higher than
ALT (this is in contrast to most other liver diseases).
• Investigations are summarized in Table 3.5.
Practice points
• AST level is normally > ALT level, and both are usually <200U/L in
alcoholic hepatitis. Never diagnose alcoholic hepatitis if AST or ALT
exceed 400U/L.
• Muscle injury or excessive exercise can increase both AST and ALT.
• Very high AST or ALT levels (i.e. >1000U/L) should suggest
paracetamol (acetaminophen) overdose, ischaemia, viral hepatitis, or
autoimmune hepatitis. In paracetamol overdose, AST or ALT can be
>10 000 U/L.
Management
• Admit most patients to hospital, unless mild (bilirubin <50 micromol/L,
normal PT) or patient in abstinent environment.
• Give thiamine (100–200mg/day), folic acid, and multivitamins.
• Prescribe detox regime (e.g. reducing dose of chlordiazepoxide).
Review the patient, as the dose ± frequency may need to be increased.
• Monitor and correct K+, Mg2+, PO43–, and glucose.
• Start a high-calorie, high-protein (1.5g/kg of body weight) diet. Low-
protein diets are contraindicated.
• If clinically suspected, start broad-spectrum antibiotics (e.g. cefotaxime
± fluconazole (50–100mg IV daily) as prophylaxis against fungal
infections.
• Patients with a Glasgow Alcoholic Hepatitis score (GAHs) (see
Table 3.6) of ≥9 or discriminant function score (see Box 3.13) of
≥32 are classed as having severe alcoholic hepatitis and should be
treated with prednisolone 40mg/day for 4 weeks. The only practical
contraindication is untreated sepsis. If there is doubt, then give broad-
spectrum antibiotics for 24–48h prior to steroids. An alternative to
treatment with steroids is pentoxyfylline (400mg tds PO)—a large
multicentre trial STOPAH will shortly publish the results comparing
steroid versus pentoxyfylline therapy in this group.
• Delirium tremens or severe agitation may be managed with low-dose
diazepam or oral clomethiazole PO (E Acute alcohol withdrawal,
pp. 436–7; E Acute alcohol withdrawal, p. 718–19). Treat seizures
in the standard way (E Status epilepticus (tonic–clonic), p. 408–9;
E Acute alcohol withdrawal, p. 436–7).
Drug-induced hepatitis
Patients with drug-induced jaundice should be monitored three times per
week or admitted for observation, as many are serious and may not re-
solve. Stop the suspected drug immediately, and observe. Look for rash and
eosinophilia, and exclude other causes (see Box 3.14). This is important,
as drug reaction with eosinophilia and systemic symptoms (DRESS) is a
rare, potentially life-threatening drug-induced hypersensitivity reaction that
includes skin eruption, haematologic abnormalities (eosinophilia, atypical
lymphocytosis), lymphadenopathy, and internal organ involvement (liver,
kidney, lung). (For paracetamol overdose, see E Acute liver failure: as-
sessment and investigations, pp. 276–7.) Drugs causing jaundice are listed in
Box 3.14. Drugs causing a rise in transaminases, but rarely causing jaundice,
are not listed. All drug-induced causes of jaundice should be reported to
the Medicines and Healthcare Products Regulatory Agency, as drug-induced
jaundice is associated with poor prognosis (yellow pages at the back of
the BNF).
Autoimmune hepatitis
This is characterized by elevated transaminases, up to a few thousand, usu-
ally <2000U/L, positive anti-smooth muscle (SM) antibodies, ± anti-liver
kidney-1 (LK-1) antibodies, positive ANA, and raised IgG (polyclonal). Total
globulins (total protein–albumin) should be <35g/L in health. i globulin
(>45g/L) should always raise suspicion of autoimmune hepatitis. Confirm
with liver biopsy. Treatment: steroids (prednisolone 30– 40mg od) ±
azathioprine (1mg/kg) as a steroid-sparing agent once excluded viral hepa-
titis (i.e. HBsAg negative). If there is failure to respond in a young patient
(<30 years), consider Wilson’s disease.
Acholuric jaundice
This is characterized by absence of bilirubin in the urine. May be caused
by haemolytic anaemia (previous history, excess urinary urobilinogen,
splenomegaly, reticulocytosis, etc.) or a congenital disorder of conjugation
(Gilbert’s syndrome, 2% of the population). Fasting (<400cal) for 48–72h
will increase serum unconjugated bilirubin in patients with Gilbert’s syn-
drome (bilirubin rarely >80 micromol/L).
Sepsis
Any severe infections may cause jaundice (including pneumonia). Most se-
vere with intra-abdominal sepsis. LFTs may be cholestatic or characterized
by a predominant rise in bilirubin levels only. Exclude other causes, and treat
infection with antibiotics ± surgical drainage.
Ischaemic hepatitis
Presentation
Occurs with significant hypotension or hepatic arterial occlusion.
Predisposing factors include CCF ± hypoxia. In its mildest form, it manifests
as mildly deranged LFTs (hepatitic picture, i PT) in a patient with CCF,
and in its most severe form, it may present as acute liver failure. Look for
hypoxia, hypotension (may have normalized by the time of assessment—
look at anaesthetic charts), signs of arteriopathy (abdominal bruits from
hepatic arterial occlusion), signs of RVF on the ECG (AF is a rare cause).
May cause confusion ± encephalopathy. Exclude other causes of hepatitis
(E Jaundice: assessment, pp. 260–1).
Management
Most will respond to correction of the underlying aetiology. Correct hypo-
tension (E Shock: assessment, pp. 330–1), and give O2 to correct hyp-
oxia. If the hepatic artery or coeliac axis is occluded, prognosis is poor and
depends on the extent of hepatic necrosis. Usually age and the extent of
disease preclude salvage surgery. Discuss with a specialist centre. If signs
of severe (acute) liver failure are present, see E Acute liver failure: man-
agement, pp. 278–9 for guidance. Most patients are not fit enough for liver
transplantation.
270
Obstructive jaundice
See E Biliary obstruction, pp. 272–3.
Gallstone disease
Gallstone disease affects 10–20% of the population. The stones may be pre-
dominantly cholesterol (>80%), pigment stones (<25% of cholesterol; mul-
tiple, irregular, friable), or mixed (faceted, calcium-containing). The majority
are asymptomatic and diagnosed incidentally. Some risk factors include ♀
sex, age (over 40), pregnancy, obesity, and rapid weight loss.
Complications of gallstones
• Biliary colic.
• Obstructive jaundice.
• Cholecystitis ± empyema and gangrene of gall bladder.
• Cholangitis septicaemia or liver abscesses.
• Acute pancreatitis (E Acute pancreatitis: assessment, pp. 284–5).
• Perforation and peritonitis.
• Gall bladder fistula, gallstone ileus.
Biliary colic
Presentation
Abdominal pain (RUQ) radiating to the epigastrium, back, or shoulders, as-
sociated with nausea and vomiting. Attacks commonly follow a heavy meal
and pass spontaneously. Differential diagnosis includes acute MI, leaking
aortic aneurysm, peptic ulcer, intestinal obstruction or ischaemia, pancrea-
titis, renal colic, and pneumonia.
Investigations
USS to detect the stone and gall bladder distension. Urine microscopy,
CXR, and ECG will help exclude other conditions.
Management
• Pain relief: can usually be achieved with NSAIDs (first line) ± opioids.
• Laparoscopic cholecystectomy in the longer term. If the patient is not
a surgical candidate, medical dissolution of gallstones can be attempted
with ursodeoxycholic acid (UDCA) (10–14mg/kg daily, at bedtime).
Acute cholecystitis
Presentation
Sudden-onset severe RUQ pain and symptoms, similar to biliary colic, with
fever and persisting symptoms. Persistent vomiting suggests a bile duct
stone. Physical signs include fever, tachycardia, sweating, RUQ tenderness,
and peritonism, especially in inspiration (Murphy’s sign), ± palpable gall
bladder (rare). Jaundice (733%) suggests obstruction of the common bile
duct (CBD). Acalculous cholecystitis is seen in the elderly or patients with
coexisting disease or trauma, in the ITU, and in those on TPN. Mortality
may be high.
Investigations
• Blood tests i WCC is usual. LFTs may show i bilirubin, and
cholestatic LFTs; ± i amylase.
• USS Should demonstrate gallstones or biliary sludge ±
thickening of gall bladder wall ± peri-cholecystic fluid.
• AXR Gallstones visible in 710% of patients. Local peritonitis
may produce a ‘sentinel loop’.
• Hepatobiliary Using 99Tc-label is usually diagnostic.
iminodiacetic
acid (HIDA) scan
Management
• NBM and IV fluids; insert an NG tube if there is severe vomiting.
• Antibiotics should cover enteric organisms and Enterococcus (e.g.
cefuroxime 750mg IV tds + metronidazole 500mg IV tds).
• Early inpatient laparoscopic cholecystectomy is the treatment of choice.
• Complications include perforation, gallstone ileus, or fistula.
27
Biliary obstruction
Biliary obstruction or apparent biliary obstruction will be associated with
either a dilated or a non-dilated biliary system, and the patient may be ei-
ther septic or aseptic. Biliary dilatation in patients with mechanical biliary
obstruction may not always be apparent on USS. See Box 3.15 for causes
of biliary obstruction.
Presentation
• Jaundice ± fluctuation.
• RUQ pain ± tenderness (may be painless).
• Fever (indicates infection or cholecystitis).
• Itching.
• Dark urine ± pale stools (not very useful in practice).
• Septic shock.
Investigations
• Blood i WCC indicates sepsis. U&Es may indicate renal failure
tests or pre-renal uraemia. LFTs show i bilirubin, ii ALP, and
ii GGT; i amylase with concomitant pancreatitis; transient
i ALT, AST with passage of a stone and persistent in chol-
angitis (usually i ≤400U/L; higher suggests hepatitis). Blood
cultures and CRP mandatory.
• USS This is mandatory and should be performed within 12h, if
possible, to demonstrate the presence of dilated ducts ±
gallstones. Post-cholecystectomy slight dilatation (70.8cm) of
CBD is normal.
• AXR Aerobilia may indicate a gas-forming organism or recent
instrumentation. There may be localized ileus.
• ERCP Shows stones in CBD and allows examination of GIT and
ampulla to exclude other pathology. Give broad-spectrum
antibiotics if intervention is planned.
• MRCP Magnetic resonance cholangiopancreatography is a very ac-
curate non-invasive investigation.
• CT Useful, especially if malignancy suspected. Perform full-
staging CT if malignancy present.
Obstructive jaundice
ALP >4 × normal
γ-GT >10 × normal
AST/ALT <400U/L
USS liver
?? Bile duct dilatation
Ascites
Presentation
The patient may present with symptoms due to the fluid (abdominal dis-
tension, weight gain, abdominal pain), the underlying cause (jaundice,
haematemesis, fever or night sweats, frothy urine due to proteinuria), or
complications of ascites (dyspnoea, anorexia, reflux oesophagitis, herniae,
pleural effusions, scrotal or leg oedema, peritonitis). Ask specifically about
alcohol, risk factors for chronic liver disease, GI bleeding (portal hyper-
tension), previous pancreatitis, risk factors for TB, cardiac history, exercise
tolerance, and menstrual history (? ovarian malignancy) (see Box 3.16).
Differential diagnosis
• Ovarian cyst.
• Obesity (simple or metabolic).
• Pregnancy.
• Abdominal mass.
Investigations
• Blood tests U&Es, glucose, FBC, PT, LFTs, blood cultures, amylase.
• Ascitic tap An ascitic tap should be carried out in all patients, unless
a diagnosis of malignant ascites is certain. Inoculate blood
culture bottles, and send the fluid in a sterile pot for micros-
copy and WBC (E Ascitic tap (paracentesis), p. 841).
• Imaging Plain AXR shows a ground-glass pattern, with loss of the
psoas shadow. USS can detect as little as 30mL. Note
the size and texture of the liver and spleen; check the
patency of hepatic veins (ask for Doppler US). CT scan
may be required.
• Urine Urine Na+ (cirrhotic ascites), 24-h protein.
Management
Patients with symptomatic ascites may need admission. Treat the
underlying cause.
• Cirrhotic ascites: salt-restrict to 80–120mmol/day (corresponding to
4.6–6.9g salt/day). This includes avoiding normal saline infusion, if possible.
• Paracentesis: if tense or moderate ascites, drain all ascites as quickly as
possible (maximum 25L in 5h), and simultaneously give 8g of albumin
per litre of ascites removed as 20% albumin (not required for malignant
or exudative ascites). Do not paracentese if the patient has spontaneous
bacterial peritonitis (SBP), as this can precipitate HRS.
• Diuresis: be cautious if starting diuretics in renal failure, hyponatraemia
or abnormal serum K+ concentration. Start spironolactone at
100mg/day, increasing to 400mg/day (100mg per week). Add
furosemide 40mg/day if response is poor. Stop all diuretics if severe
hyponatremia (<120mmol/L), progressive renal failure, worsening
hepatic encephalopathy, or incapacitating muscle cramps. Do not
commence diuretics in patients who are hypovolaemic.
• If there is renal impairment (creatinine >140 micromol/L), consider
giving an extra colloid and crystalloid volume challenge (e.g. 500mL of
Gelofusine® over 1h, followed by 1L of normal saline over 4h).
Ascites 275
Practice points
• Salt-restrict to 4.6–6.9g/day—equivalent to a no added-salt diet, with
avoidance of pre-prepared meals.
• Do not perform large-volume paracentesis until SBP is treated—can
remove small volumes to aid breathing if ascites is very tense.
• No need to give albumin if draining malignant (exudative) ascites in
non-cirrhotic patients.
• Stop all diuretics in severe hyponatraemia (Na+ <120mmol/L).
• Stop furosemide in severe hypokalaemia (K+ <3.0mmol/L).
• Stop aldosterone antagonists in severe hyperkalaemia (K+ >6.0mmol/L).
• Maximum weight loss with diuresis should be 0.5kg/day in patients
without oedema, and 1kg/day in patients with oedema.
• Diuretics should be discontinued permanently in patients with
diuretic-induced complications.
• ACEIs are contraindicated in patients with cirrhosis due to the effect
on renal function.
276
Investigations
• Blood tests (daily): U&Es, glucose (and 2-hourly blood glucose testing),
FBC, PT, LFTs (albumin is usually normal on admission, unless ‘acute-on-
chronic’), PO43–, ABGs. Blood group and cross-match on admission.
• Blood tests (for diagnosis): viral serology (HAV IgM, HBsAg, HBc Ab
IgM, delta in HBsAg +ve, EBV, CMV, HSV), drug screen (especially
paracetamol—but may be normal by the time of presentation), plasma
caeruloplasmin (if <50 years ± 24-h urine copper).
• Bacteriology: blood cultures, urine, sputum ± ascites (if present) MC&S
daily (including fungal cultures). Throat and vaginal swabs.
• USS (liver): to assess hepatic veins, portal vein patency, size (if possible),
spleen size, and nodes (lymphoma).
• ECG/CXR: repeat CXR daily (infection/ARDS).
• Electroencephalogram (EEG): may be helpful in the assessment of hepatic
encephalopathy, though not widely used.
• Liver biopsy: rarely necessary but will exclude underlying malignant
infiltration or cirrhosis where the diagnosis is in doubt. The transjugular
approach is preferred, as it carries a lower risk of haemorrhage
(E Percutaneous liver biopsy, p. 845).
Hepatic encephalopathy
Hepatic encephalopathy is a neuropsychiatric disturbance of cognitive func-
tion in a patient with acute-on-chronic liver disease (E ‘Acute-on-chronic’
liver failure, p. 280).
Clinically, there is usually an altered conscious level, asterixis (liver flap),
abnormal EEG, impaired psychometric tests, and an elevated serum am-
monia concentration (useful in monitoring treatment, and not in diagnosis
of hepatic encephalopathy). Patients may present with Parkinsonian fea-
tures. However, in patients with chronic liver disease, it may be subclin-
ical, with subtle changes in awareness or attention span. It is graded (see
Box 3.18). Consider CT head, as intracranial bleed may present with a re-
duced conscious level.
Treatment
The aim of treatment is to improve morbidity.
• Exclude other causes of confusion (E Confusional states and
delirium: assessment, p. 432).
• Identify and correct the precipitating causes (see Box 3.22).
• Give lactulose—this semi-synthetic disaccharide is poorly absorbed. It
is digested in the large bowel and undergoes fermentation. This alters
faecal pH and nitrogen utilization by bowel flora. Lactulose enemas can
be given if the patient cannot take lactulose orally or via an NG tube.
• Lactitol has a similar action to lactulose but has fewer side effects.
Titrate the dose to achieve 2–3 bowel motions per day.
• Phosphate enemas help to purge the large bowel. Most useful in the
context of an acute food load (e.g. GI bleeding).
• Dietary restriction is controversial and may be harmful in malnourished
patients. Ensure adequate calorie intake.
Liver abscesses
Presentation
• Commonly present with fever and night sweats, nausea, vomiting,
weight loss, or RUQ or intercostal pain.
• The underlying cause (e.g. appendicitis) may be silent or barely noticed.
Ask about recent abdominal pain, altered bowel habit, diarrhoea, biliary
colic, blood PR, or IBD.
• Ask about travel history, occupation (farming is a risk factor for
Echinococcus), or contact with infected persons (TB).
• Intrauterine devices are a risk factor for actinomycosis, which can
present with liver abscesses.
• Examine for jaundice, hepatomegaly, pleural effusions (commonly
right-sided), intercostal tenderness (characteristic of amoebic
abscesses), abdominal masses (tumour or inflammatory mass), and
lymphadenopathy. Perform a rectal and vaginal examination for pelvic
tumour.
• Severe infection may be associated with septic shock (E Sepsis
syndrome and septic shock, pp. 336–7).
Causes
• Pyogenic organisms (appendicitis, diverticulitis, carcinoma, biliary).
• Amoebic abscess (E. histolytica).
• Hydatid cyst (Echinococcus granulosus).
• TB (very rare).
Investigations
• U&Es: renal impairment with sepsis.
• LFTs: non-specific, tend to be cholestatic; may be normal with amoebic
abscess, d albumin.
• i CRP, i ESR.
• PT: may be prolonged with multiple abscesses.
• FBC: leucocytosis, eosinophilia, non-specific anaemia.
• Microbiology: blood and urine cultures, as well as culture and Gram-
stain any materials obtained from USS or CT scan (if there is suspicion
of hydatid disease, aspiration is contraindicated). Amoebic and
hydatid serology must be sent. Stool may contain amoebic cysts or
vegetative forms.
• Radiology:
CXR (looking for effusion or pulmonary TB).
•
• USS of the liver, biliary tree, and abdomen (iliac fossae, in particular)
and CT scan with contrast, looking for masses. Both pyogenic
and amoebic abscesses tend to be thick-walled; hydatid cysts are
thin-walled, and there may be daughter cysts. Solid tumours are
echodense but may have necrotic hypodense centres
• Positron emission tomography (PET) scan will show up pyogenic foci
in the liver and elsewhere (e.g. terminal ileitis); amoebic abscesses do
not take up the label.
Management
• Pyogenic abscess: aspirate any large abscesses under US or CT guidance.
Surgical or ERCP drainage are also potential options, depending on the
position of the cyst(s). It is pointless to try and drain multiple abscesses.
If there is a continuing intra-abdominal source, it is virtually impossible
to eradicate liver abscesses without removing or dealing with that
source (e.g. appendix). Broad-spectrum antibiotics (e.g. cefotaxime and
metronidazole).
• Amoebic abscess (E Amoebic dysentery, p. 253): percutaneous
aspiration—if cyst is at risk of rupture or if there is clinical deterioration
or lack of response to treatment. Treat with metronidazole (or
tinidazole), followed by diloxanide furoate. Secondary bacterial infection
occurs in up to 20%.
• Hydatid disease: laparoscopic (or open) surgical de-roofing of the cyst
is the treatment of choice. Albendazole may help reduce the risk of
recurrence post-surgery or be used in inoperable cases. Percutaneous
treatment via puncture, aspiration, injection, and re-aspiration (PAIR)
is an acceptable alternative approach. Percutaneous aspiration alone is
ineffective and should be avoided.
• TB abscess: anti-tuberculous therapy.
Practice points
• Pyogenic and amoebic abscesses cannot be distinguished on the basis
of radiologic appearances alone.
• Ensure the source of the liver abscess is treated (e.g. appendix, biliary
sepsis).
284
Acute pancreatitis: assessment
Acute pancreatitis is increasingly managed by physicians, particularly if it
presents in an unusual way (e.g. chest pain).
Presentation
• Abdominal pain: epigastric or generalized, of rapid onset, but may
occur anywhere (including chest); dull, constant, and boring. Radiation
to the back or between the scapulae, often relieved by leaning forward
(differential diagnosis is leaking aortic aneurysm).
• Nausea, vomiting, and dehydration ± jaundice.
• Peritonitis with epigastric tenderness, localized rebound tenderness,
or generalized abdominal rigidity. An abdominal mass may indicate a
pancreatic pseudocyst or an abscess. Bowel sounds usually absent.
• Tachycardia and hypotension; shock/collapse and respiratory failure in
severe cases (especially in the elderly).
• Very rarely, signs of bleeding in the pancreatic bed, Grey–Turner’s
sign (ecchymosis in the flanks) or Cullen’s sign (periumbilical bruising),
tender red skin nodules (due to subcutaneous fat necrosis).
• Hypocalcaemic tetany.
Investigations
• Amylase Elevated, but not specific (see Box 3.23), especially if
only up to 4× upper limit of normal. A persistently
raised amylase (several days to weeks) may indicate the
development of a pseudocyst.
• FBC Raised haematocrit and leucocytosis.
• U&Es Urea may be raised with hypovolaemia.
• Glucose May be raised.
• LFTs AST and bilirubin often elevated, especially in gallstone
pancreatitis. Disproportionately elevated GGT may indi-
cate an alcohol aetiology.
• Ca2+ Hypocalcaemia (unless precipitant was i Ca2+).
• CRP Elevated: used to monitor progression of the attack.
• ABGs Mandatory; hypoxia ± metabolic acidosis.
• AXR Generalized ileus or sentinel loops (dilated gas-filled loops
in the region of the pancreas). Look for evidence of pan-
creatic calcification (chronic pancreatitis) or biliary stone.
• CXR May show pleural effusion, elevated diaphragm, or pul-
monary infiltrates.
• USS May confirm diagnosis of gallstones ± biliary obstruc-
tion, pseudocysts, and abscesses.
• CT abdomen Dynamic contrast-enhanced, is reliable at detection of
pancreatic necrosis and grading severity, after 3–4 days.
Assessment of severity
• Severity of disease has no correlation with the elevation of serum
amylase. Several prognostic indices have been published, but it takes
48h to fully appreciate disease severity (see Box 3.24).
• Mortality from acute pancreatitis is 710% and rises to 40% in those
developing a pancreatic abscess. Mortality is highest in those with a first
episode of pancreatitis. Around 15% of patients presenting with acute
pancreatitis have recurrent disease.
• No scoring system is perfect, and some take 48h to complete (e.g.
Ranson, Glasgow).
Practice points
Severe acute abdominal pain is nearly always due to a surgical cause.
286
Acute pancreatitis: management
The principles of management are:
• Liaise with surgeons.
• Supportive measures: the majority will subside in 3–10 days.
• Careful observation for the development of complications.
• Identify the cause (see Box 3.25).
For key points in management, see Box 3.26.
Supportive treatment
• Establish IV access. If there is shock, markers of moderate to severe
pancreatitis, hypoxia not readily correcting with O2, or other coexisting
disease or in cases of elderly patients, insert a CVP line to help control
fluid balance.
• Patients are usually severely volume-depleted—give prompt fluid
replacement with crystalloids. Monitor urine output, and insert a urinary
catheter if required.
• O2 should be given if there is hypoxia on air (use continuous pulse
oximetry in severe cases and 6-hourly for the first 48h for the rest, to
monitor for respiratory failure).
• NBM initially. However, recent guidelines advocate a low-residue,
low-fat, soft diet when the patient appears to be improving.6 The same
guidelines advocate NG tube, over NJ (nasojejunal), feeding, mainly due
to NJ placement being invasive and expensive.
• Monitor blood glucose regularly, and treat with insulin if high.
• Pain relief: NSAIDs ± opioids; pethidine causes the least spasm of the
sphincter of Oddi.
• Antibiotic prophylaxis with cefuroxime decreases secondary infections.
• Octreotide (somatostatin analogue): this suppresses pancreatic enzyme
secretion but is of unproven benefit.
• Peritoneal lavage: there is no proven benefit.
• H2-antagonists have not been shown to affect mortality.
Complications
(Seen in 720% of cases.)
Local Systemic
• Abscess. • Electrolyte imbalance.
• Pseudocyst ± infection. • d Ca2+, d Mg2+.
• Biliary obstruction. • ARF.
• Ascites, pleural effusion. • Shock.
• Fistula. • Respiratory failure.
• Splenic, portal, or mesenteric. • Sepsis vein obstruction.
Septic complications
Sepsis is the most common cause of death. This should be suspected when
there is persistent fever, leucocytosis, pain/tenderness, or an overall clinical
deterioration. These signs are an indication for multiple blood cultures and
an abdominal CT. Pancreatic pseudocysts are more common in alcoholic
pancreatitis (15% versus 3% in gallstone pancreatitis), but infection is more
common in gallstone pancreatitis.
Biliary pancreatitis
Patients with acute pancreatitis and concurrent cholangitis need to undergo
urgent ERCP within 24h.6 ERCP within 72h of presentation reduces com-
plications and mortality in patients with severe gallstone pancreatitis. The
benefit has not been demonstrated in mild cases. In the absence of cholan-
gitis and/or jaundice, MRCP or endoscopic ultrasound scan (EUS) should
be performed before ERCP if gallstones are suspected.
Indications for surgery
Infected pancreatic necrosis or pancreatic abscess. Radiologically guided
percutaneous drainage is now preferred to surgery for pancreatic pseudo-
cysts. Patients with mild pancreatitis, who have gallstones in their gall
bladder, should be considered for cholecystectomy prior to discharge.6
References
6. Tenner S, Baillie J, DeWitt J, Swaroop Vege S. American College of Gastroenterology
Guideline: management of acute pancreatitis. Am J Gastroenterol 2013;108:1400–15. M http://
gi.org/wp-content/uploads/2013/09/ACG_Guideline_AcutePancreatitis_September_2013.pdf.
Chapter 4 289
Renal emergencies
Presentation
• May be asymptomatic.
• Elevated serum creatinine during biochemical screening.
• Detection of oliguria by nursing staff.
• Malaise, confusion, seizures, or coma.
• Nausea, anorexia, or vomiting.
• Oliguria or abnormal urine colour.
I aVR V1 V4
II aVL V2 V5
III aVF V3 V6
Anuria
Anuria implies that there is no urine output.
Causes
• Obstructed urinary tract—bilateral ureteric or bladder outflow.
• Renal infarction—thromboembolic, renal artery injury (dissection,
thrombosis).
• Rapidly progressive glomerulonephritis.
• Shock.
• Other causes of AKI may rarely cause anuria. ATN usually causes
oliguria.
Assessment
Assess as for AKI. However, also:
• Ask specifically about symptoms of prostatism or haematuria (tumour)
and backache (stones, aneurysm).
• Recent renal angiography or angioplasty (cholesterol embolization, renal
infarction).
• Constitutional symptoms suggestive of glomerulonephritis.
• Has the patient previously lost a kidney?
• Does the patient have a renal transplant?
• Examine for palpable bladder, enlarged prostate, or other pelvic masses.
Insert a urinary catheter to exclude retention. A bladder scan will also
demonstrate urinary retention.
Management
(See E Acute kidney injury: management, pp. 298–9.)
If patient is anuric:
• General measures such as careful assessment of fluid balance and
appropriate fluid resuscitation. Antibiotics if an obstructed, infected
system is suspected. If fluid-overloaded/refractory hyperkalaemia, will
require RRT.
• If the bladder is empty, an urgent USS is needed to confirm renal
perfusion and exclude urinary tract obstruction (or obstruction of a
solitary functioning system). Antegrade imaging can determine the level
of obstruction, but consult with the urologists and radiologists.
• Absence of hydronephrosis does not exclude obstruction.
• USS with Doppler of renal vessels. Arrange a CT scan ± contrast if USS
normal and dissection is suspected. A non-contrast CT will demonstrate
an obstructing stone.
• If no evidence of obstruction (one cannot exclude acute obstruction
on USS), an isotope renogram will provide further information on
renal perfusion. Nuclear medicine imaging can also determine if non-
obstructive hydronephrosis is present.
• Involve the urologists for further management of obstruction.
Interstitial nephritis
This is caused by inflammatory cell infiltration of the renal interstitium, usu-
ally induced by drugs (NSAIDs, penicillin, cephalosporins, sulfonamides,
allopurinol, rifampicin, mesalazine, interferon, PPIs), autoimmune con-
ditions (sarcoid, SLE, IgG4- related disease), and some infections (e.g.
Legionella, Leptospirosis, viral). Other causes include DM, sickle-cell disease,
reflux nephropathy, and renal transplant rejection. Drugs are the most
common cause, and it is not a dose-dependent effect.
Presentation
Non-oliguric AKI. Fever, rash, eosinophilia (triad not commonly occurring),
and urinary eosinophils. Precipitating cause usually precedes renal im-
pairment by a few days to 2 weeks (very variable). Usually low-grade
proteinuria.
Diagnosis
Renal biopsy.
Treatment
Stop the offending drug. Use of steroids in this setting remains controver-
sial, with no RCTs performed and published studies demonstrating variable
benefits. However, many continue to give steroids. Mycophenolate mofetil
has also been given to patients in whom glucocorticoid therapy may have
failed.
306
Rhabdomyolysis
This is the development of AKI due to extensive muscle damage and re-
sulting muscle cell death and the release of myoglobin; 77% of all cases of
AKI. For causes, see Box 4.5.
Presentation
• Most cases occur following muscle trauma (e.g. crush syndrome) or
severe physical exertion (e.g. marathon running or military training).
• Prolonged immobility (e.g. after drug OD and coma) may result in
pressure necrosis of the muscles.
• Malignant hyperthermia or malignant neuroleptic syndrome.
• Drugs (e.g. statins) and infections.
• Symptoms include swollen tender muscles, dirty red-brown urine (like
Coca-Cola® mixed with urine), and/or oliguria.
• Myoglobin is present in muscle as ferrous (Fe2+) myoglobin, and
myoglobin is deposited in the kidney as ferric (Fe3+) myoglobin. Further
oxidation of myoglobin by hydroperoxides generates a potent oxidizing
species ferryl (Fe4+) myoglobin that causes renal injury. Obstruction
of the tubules also occurs. Alkalinization works by stabilizing ferryl
myoglobin and making it less reactive.
Investigations
• U&Es: typically marked increase in serum K+, i creatinine:urea ratio.
• Ca2+: low Ca2+ occurs in a significant proportion of patients, with
deposition of Ca2+ into bone. Later on, hypercalcaemia can result.
• PO43–: high as PO43– released during muscle cell death.
• Urate: usually i with tissue necrosis, also d excretion.
• LFTs: AST very high—from skeletal muscle.
• CK: very high (up to 1 × 106 U/L).
• LDH: elevated.
• ABG: metabolic acidosis, hypoxic if there is associated acute lung injury
(trauma) or infection.
• Urine: the urine looks red-brown. Urinalysis is positive for blood
(myoglobin tests positive), but no RBC seen on microscopy. Urinary
myoglobin is diagnostic.
• Miscellaneous: FBC, glucose, blood cultures, ESR, CRP, serum for
toxicology ± virology, plasma myoglobin, ECG. Serum looks clear (cf.
haemolysis), as myoglobin does not bind haptoglobins and is filtered by
the glomerulus and then excreted.
Management
Patients are often febrile, volume-depleted, and unwell. Myalgia may be pre-
sent. The priorities are:
• Hyperkalaemia needs urgent treatment (E Acute kidney
injury: management, pp. 298–9).
• Volume replacement: to prevent the risk of AKI due to rhabdomyolsis,
aggressive fluid management is required, often with several litres of
fluid in the first few hours. To prevent fluid overload, especially in those
oliguric patients, regular assessment of fluid balance is required, with
documentation of urine output.
Rhabdomyolysis 307
Hepatorenal syndrome
This is defined as the onset of renal failure or AKI in patients with severe
liver disease in the absence of renal pathology. It may occur in either cir-
rhosis or acute liver failure. It may be characterized by a low urine Na+
(<10mmol/L), but this is not a criterion in the diagnosis. It may be acute
(type 1) occurring within 2 weeks, or insidious in development in patients
with refractory ascites (type 2). Renal vasoconstriction occurs in order to
maintain renal perfusion and GFR.
Presentation
• An increase in serum creatinine is most commonly found as an incidental
finding during biochemical screening of patients with ascites (cirrhosis)
or jaundice (especially common in alcoholic hepatitis). Significant
haematuria and proteinuria are not features.
• Causes of renal failure in cirrhosis that should be excluded before a
diagnosis of HRS is made include hypovolaemia, shock, intrinsic renal
disease, and concomitant use of nephrotoxic drugs.
• The most common precipitant of HRS in patients with advanced liver
disease is sepsis; 30% of patients with SBP develop HRS. GI bleeding is
an additional precipitant.
There are many causes of renal failure and liver disease which are not syn-
onymous with HRS, and should be actively excluded. These include:
• Hypovolaemia: caused by bleeding, overdiuresis, or post-paracentesis
circulatory dysfunction.
• Sepsis.
• Nephrotoxic drugs given to patients with liver disease (e.g. gentamicin).
• Chronic viral hepatitis (HBV or HCV) with glomerulonephritis.
• IgA nephropathy.
• Leptospirosis (marked hyperbilirubinaemia, liver enzymes near normal).
• Paracetamol OD.
• Rhabdomyolysis may mimic liver disease and HRS by causing DIC (high
PT) and high AST (muscle injury).
Investigations
See E Acute kidney injury: investigations, pp. 296–7.
Management
• Exclude other causes of renal failure in liver disease (see
E ‘Presentation’ above).
• ± insert a urinary catheter, and monitor urine output.
• Volume challenge; stop diuretics; 20% IV albumin.
• Ideally CVP should be monitored to help in the management of fluid
balance, and particularly to prevent volume overload.
• Broad-spectrum antibiotics: based on current evidence, terlipressin
should be considered to be the first-line therapeutic agent for patients
presenting with type 1 HRS. Contraindicated in patients with IHD
and peripheral vascular disease. Most studies have used terlipressin
(initially 0.5–1mg every 4h), together with albumin therapy (1g/kg day 1,
Management
(See Box 4.7.)
• Stabilize the patient: resuscitate severely ill patients with IV fluids ±
inotropes, guided by CVP and BP (see Box 4.7).
• Give IV antibiotics. The choice of antibiotics may depend on previous
culture results, as well as local guidelines. Discuss with microbiology for
advice. Continue antibiotics for 7–14 days.
• Organize drainage of infected and obstructed urinary system.
• Fluid balance: maintain high fluid intake (e.g. 3L/24h). Monitor fluid
balance and urine output carefully for the first 48–72h.
• Analgesia: try opiates. Avoid NSAIDs in AKI.
• Pyonephrosis, renal or perinephric abscess: requires urgent advice—
contact the urologists. Save a sample for MC&S.
• When patient recovered, investigate for any underlying cause: flexible
cystoscopy, investigation of bladder emptying, and imaging such as CT
kidneys, ureters, and bladder (KUB). Dimercaptosuccinic acid (DMSA)
renal scan will demonstrate scarring.
Obstruction
Lumbar fascia
Skin
Calculus (lumbar triangle)
Perinephric abscess
Prognosis
760% of all stones will pass (depending on the location and size of the
stone) (half of these within 48h). 730% will require surgical removal, and
10% will recur. The risk of idiopathic stone recurrence is altered slightly by
diet but is d by a high fluid intake (>1.5L/day leads to a 6-fold decrease).
It is important to control hypercalciuria if present (low-calcium diet, thia-
zide diuretics), treating hypercalcaemia if present (E Hypercalcaemia,
pp. 572–4), urinary alkalinization (hyperuricaemia, renal tubular acidosis,
cystinuria), urinary acidification to pH <5.5, allopurinol (urate stones), or
penicillamine (cystine stones). Patients with staghorn calculus are recom-
mended to undergo a surgical procedure to remove the stone.
Haematuria
History
Haematuria is either visible and symptomatic or microscopic and
asymptomatic.
• Severity of haematuria: pink urine, frank blood, or clots?
• Timing of haematuria: bleeding occurring at start or end of micturition
suggests bladder neck, prostate, or urethral source. Blood mixed with
the stream suggests a source higher in the urinary tract.
• History of trauma: even seemingly minor trauma can cause bleeding
from congenital lesions of the urinary tract.
• Unilateral loin pain: consider calculi, tumour, cystic disease, or
hydronephrosis. Painless haematuria suggests neoplasm.
• Disturbance of micturition: frequency, urgency, dysuria, hesitancy, poor
stream, and dribbling suggest cystitis. Bleeding and pain at the end of the
stream is typical of a bladder stone.
• Constitutional symptoms: sore throats, arthralgia, malaise, and rash may
indicate glomerulonephritis. AF is associated with renal emboli. Fever,
dysuria, or abdominal pain may indicate infection. Bruising or other
bleeding may indicate a bleeding diathesis.
For causes of haematuria, see Box 4.9.
Physical examination
• General examination: hypertension (chronic or acute renal disease),
irregular pulse or heart murmurs (source of emboli), anaemia, bruising
or purpura, oedema, or pleural effusions.
• Urinary tract examination: loin or abdominal tenderness, renal mass,
pelvic mass, prostate enlargement, testes. Urine microscopy.
Investigations
• Urinalysis Positive result seen with myoglobinuria
(E Rhabdomyolysis, pp. 306–7) and haemoglobinuria.
Proteinuria suggests renal pathology.
• Microscopy RBC casts or dysmorphic red cells suggest a glomerular origin.
WBC casts suggest pyelonephritis. Other findings include crys-
tals (stone disease), ova (schistosomiasis), and malignant cells.
• FBC Thrombocytopenia and anaemia (haemolysis, leucocytosis)
may indicate infection.
• U&Es For renal function.
• Clotting For coagulopathy.
• G&S If post-traumatic or severe.
• Immunology If glomerulonephritis is suspected. Refer to the renal team.
screen
• US May diagnose polycystic disease, ureteric obstruction by
stone or tumour, or gross renal abnormalities.
• CT scan May demonstrate stones, hydronephrosis, renal injury or
tumour, cystic disease, or urothelial tumour.
• Cystoscopy To exclude other causes of bleeding from the lower urinary
tract. Should be performed in patients with macroscopic
haematuria or undiagnosed microscopic haematuria.
Haematuria 315
Management
• Admit patients with:
• Post-traumatic haematuria (refer to urology).
• Severe unexplained haematuria (including bleeding diathesis),
especially if there is clot retention. Insert a large (22G) triple-lumen
urinary catheter for continuous bladder irrigation with monosol (not
glucose) to wash out clots.
• Haematuria, proteinuria, and renal impairment suggest
glomerulonephritis. Arrange for an urgent renal referral and biopsy.
• Severe infection, e.g. pyelonephritis. Commence antibiotics after
taking cultures.
• Pain relief (pethidine 25–50mg IV, with an antiemetic). Propantheline
bromide 15mg tds PO relieves painful bladder spasm of haemorrhagic
cystitis and clot retention (may cause urinary retention).
• Correct any bleeding diathesis (FFP or vitamin K for warfarin).
Renovascular disease
Renal artery stenosis may be atherosclerotic (common in the elderly and
diabetics), with excessive activation of the renin–angiotensin–aldosterone
axis and resultant hypertension, or fibromuscular dysplasia (10%) (young
patients). Fibromuscular dysplasia occurs in young patients, usually ♀, and
may involve other vascular beds such as peripheral, coronary, or cerebral.
Renal artery stenosis should be considered in all patients with:
• Flash pulmonary oedema (sudden, unexpected onset).
• Peripheral vascular disease, aortic dissection, and type 2 diabetes.
• Unequal kidneys on USS.
• Acute deterioration in renal function following the initiation of ACEI.
• Hypertension/coronary or carotid artery disease.
• Complete anuria in renovascular disease in a solitary kidney with an
occluded artery.
• Patients with hypokalaemia.
Investigations
• USS: to look at renal size and asymmetry, and Doppler flow through the
renal arteries.
• Isotope renogram.
• Magnetic resonance angiography (MRA) CT angiography: risk of
contrast nephropathy.
• Be guided by your local radiologists.
• Digital subtraction angiography is sometimes used.
Management
• Avoid NSAIDs.
• Lipid-lowering therapy with statins.
• Recent trend by nephrologists to carefully introduce angiotensin
blockade to treat hypertension, with gradual introduction and
withdrawal if there is a significant decline in GFR.
• Diuretics due to salt and water retention.
• Refer to a dedicated team of interventional radiologists/vascular/
nephrology if there is >70% stenosis with intractable hypertension (>5
drugs) and flash pulmonary oedema with declining renal function. The
ASTRAL trial suggests that patients do not benefit from stents with
respect to improving BP control. The CORAL trial did not demonstrate
benefit in stenting in the prevention of cardiovascular or renal events.
However, a small subset of high-risk patients may benefit.
• Fibromuscular dysplasia can be successfully managed with angioplasty in
symptomatic patients.
• Stenting may permit the use of angiotensin blockade in previously
intolerant patients.
• Mortality rate is i in patients with atherosclerotic renovascular disease,
with most dying from their associated IHD.
Cholesterol embolism
Most commonly seen in arteriopaths after manipulation of vasculature (e.g.
angiography) and is followed by AKI. Usually silent. There is partial occlu-
sion of small-and medium-sized arteries, resulting in ischaemic atrophy.
More florid presentation includes: widespread purpura (livedo reticularis),
dusky and cyanotic peripheries with intact pedal pulses, GI bleeding/is-
chaemia, myalgia, and AKI. It can be spontaneous or follow therapy with
heparin or warfarin.
Diagnosis
Eosinophilia, renal impairment, hypocomplementaemia, ESR, ANCA nega-
tive. Urinary sediment is usually benign; mild proteinuria may be seen. Renal
biopsy shows cholesterol clefts.
Management
The renal impairment is usually irreversible or only partially reversible [in
contrast to ATN and contrast-induced nephropathy (CIN)]. Anticoagulation
is contraindicated. Treatment is supportive.
831
Contrast-induced nephropathy
This is an acute impairment of renal function, which follows exposure
(within 3 days) to radiocontrast materials. Defined as an increase in cre-
atinine of 44.2micromol or a 25% increase in creatinine from baseline value.
Incidence in an unselected population is 2–7% but increases to 25% if renal
function is already impaired. Pre-expand the plasma volume with normal sa-
line or sodium bicarbonate. In patients at risk of CIN, an alternative to con-
trast in vascular angiography studies is carbon dioxide. Higher risk of CIN
following coronary angiography compared to enhanced CT scans, as well
as higher risk following intra-arterial administration compared to venous
administration.
Risk factors
• Chronic kidney disease (eGFR <60mL/min/1.73m2).
• Renovascular disease.
• Proteinuria (increases risk 3-fold).
• DM (risk depends on renal function (chronic kidney disease and DM risk
of 25%).
• CCF.
• Recent MI.
• Multiple myeloma.
• Dehydration/hypovolaemia.
• Sepsis.
• Concomitant nephrotoxins (e.g. gentamicin, NSAIDs, amphotericin,
high-dose loop diuretics).
• Age (>75 years).
Management
There is no specific treatment. Prevention is the best policy.
• Monitor renal function 48–72h following contrast.
• Ensure good hydration pre-procedure (give patients who are at risk IV
fluids pre-procedure).
• Avoid high-osmolar contrast media.
• Use minimal amounts of constrast.
• Stop nephrotoxic drugs (especially NSAIDs) peri-procedure. Avoid
diuretics.
• Stop metformin 48h before contrast (if GFR <60mL/min/1.73m2).
• Continue IV fluid following procedure for 12h.
• Acetylcysteine is no longer thought to be effective. Conflicting results in
different trials and meta-analysis.
• i risk of adverse outcomes following an episode of CIN AKI.
• No current evidence for RRT following contrast in patients with chronic
kidney disease to prevent contrast nephropathy.
Urine appearance
Typical urine is pale yellow to amber in colour. Other colours do not neces-
sarily imply pathology:
• Red: haematuria, haemoglobinuria, beetroot, rifampicin, senna,
porphyrinuria.
• Brown: haematuria, haemoglobinuria, myoglobinuria, jaundice,
chloroquine, carotene.
• Black: haematuria, haemoglobinuria, myoglobinuria, alkaptonuria (black
on standing).
• Green: triamterene, propofol.
• Darkening on standing: porphyrinuria [fluorescence in ultraviolet (UV)
light], metronidazole, imipenem, or cilastatin.
320
Renal–pulmonary syndromes
Consists of rapidly progressive glomerulonephritis with alveolar haemor-
rhage. There are several underlying causes of renal–pulmonary syndrome,
with a variety of presentations. Patients may deteriorate rapidly with respira-
tory/renal failure and require ITU. Early diagnosis is key to allow prompt
treatment and recovery of renal function. The most common causes are
AAV and anti-GBM disease. Rarer causes include SLE, cryoglobulinaemic
vasculitis, IgA vasculitis, and scleroderma.
Presentation
• May present acutely over a few days.
• Haemoptysis, shortness of breath, hypoxia, and cough may be present.
• Oliguria or anuria AKI.
• Extrarenal features may be present: fever, rash, arthralgia, depending on
the underlying diagnosis.
• GPA may be characterized by upper airway and ENT
involvement: epistaxis, nasal symptoms.
• EGPA: asthma, nasal polyps may be present.
Investigations
• FBC: anaemia, i platelets in AAV and anti-GBM disease, eosinophilia
in EGPA.
• U+E: AKI.
• LFTs: i ALP.
• CRP: elevated.
• Urine dipstick: blood and protein with glomerulonephritis.
• Immunology tests: ANCA, anti-GBM, complement, cryoglobulinaemia
(consider hepatitis), rheumatoid factor, ANA, dsDNA.
• Virology: hepatitis, HIV.
• CXR: sensitive, but not specific, for pulmonary haemorrhage. Some
patients may not demonstrate alveolar shadowing.
• High-resolution CT (HRCT): may demonstrate ground-glass changes.
• PFTs: measurement of elevated transfer factor.
Diagnosis
• Renal biopsy to diagnose glomerulonephritis.
Treatment
• May require ITU for respiratory support/renal support.
• Immunosuppression consisting of steroids (initially 60mg/day, followed
by gradual tapering over 6–9 months) and cyclophosphamide (usually
IV over 3–6 months). Azathioprine maintenance therapy used in
AAV after completion of cyclophosphamide [measure thiopurine
methyltransferase (TPMT) levels]. Mycophenolate can also be used.
• Rituximab-based regimes are also used during induction and
maintenance treatment.
Nephrotic syndrome
In adults, causes:
• minimal change disease (MCD) (15%).
• focal segmental glomerulosclerosis (FSGS) (35%).
• membranous nephropathy (35%).
• membranoproliferative glomerulonephritis (MPGN) (5%).
• other (10%).
Nephrotic syndrome consists of significant proteinuria (3g/24h), with low
albumin, high cholesterol, and oedema. Patients are prothrombotic and may
present with DVT/PE or renal vein thrombosis.
General measures
• Assess as per AKI: request full immunology screen, virology; investigate
for paraprotein.
• Drug history important: NSAIDs, lithium, pamidronate, heroin.
• USS: workup for renal biopsy.
• Patients may have significant oedema and require admission for IV
diuresis with furosemide. This can be given as a 24-h infusion
(250–500mg over 24h).
• Severe oedema; consider adding in metolazone 2.5mg—initially
alternate days.
• Fluid-restrict and daily weights.
• Lying and standing BPs.
• Monitor input and urine output and HR, with care to avoid overdiuresis
and contraction of intravascular compartment resulting in further AKI.
• Prophylactic heparin due to prothrombotic tendency (unless a
contraindication: stop 24h before a renal biopsy).
• Statin.
• If hypertensive, ACEI or ARB will have an additional anti-proteinuria
effect.
• Rapid decline in renal function; consider renal vein thrombosis.
• Prepare for renal biopsy.
Minimal change disease
• Microscopic haematuria present in 10–30%. Chronic kidney disease/
end-stage renal failure not typically seen. AKI may be seen in 20–25% of
patients, typically in older patients.
• Usually idiopathic.
• Drug history important: NSAID, lithium use.
FSGS
Genetic testing can be performed in patients presenting early on in life
and in childhood. May be primary/idiopathic, or secondary—mutations
(actinin), associated with virus infections (HIV, parvovirus B19), medica-
tions (pamidronate, lithium), hyperfiltration (obesity, diabetes), malignancy
(lymphoma). Previous glomerulonephritis resulting in scarring.
Membranous nephropathy
Sixty to 80% of patients present with nephrotic syndrome, with microscopic
haematuria in 50%. Over 70% of patients with primary membranous neph-
ropathy are positive for anti-phospholipase A2-receptor antibody. Many
secondary causes to consider include: hepatitis B, malignancy, and SLE.
Spontaneous remission occurs in up to 30%.
MPGN
Classification based on renal biopsy findings (presence or absence of Ig
and/or complement staining). Investigate for paraproteinaemias, auto-
immune disease, and infections. Treatment is aimed at the underlying cause.
Treatment
Depends on the underlying cause.
• MCD: prednisolone 1mg/kg until complete remission, then slow tapper.
Over 50% of adults will relapse, requiring repeated steroids. With
frequent relapses or steroid dependency, a calcineurin inhibitor (CNI),
e.g. tacrolimus, may be added. Cyclophosphamide for 8 weeks has also
been used. Rituximab may also decrease relapse rate.
• FSGS: prednisolone high dose or CNI. Some patients may not respond
to treatment and progress to end-stage renal failure. FSGS may reoccur
in renal transplant.
• Membranous nephropathy: observe for 6 months, due to a proportion
of patients entering spontaneous remission. Those with nephrotic-range
proteinuria/or nephrotic syndrome with life-threatening features at
presentation would be treated. Treatment consists of steroids and an
alkylating agent or CNI therapy. Rituximab has also been used.
324
Hepatorenal syndrome
Nadim MK, Kellum JA, Davenport A, et al.; The ADQI Workgroup.
Hepatorenal syndrome: the 8th international consensus conference of the
Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2012;16:R23.
Prevention of contrast-induced AKI
KDIGO. KDIGO clinical practice guideline for glomerulonephritis. Kidney
Int 2012;2:139–259.
The Renal Association, British Cardiovascular Intervention Society, Royal
College of Radiologists. Prevention of contrast induced acute kidney injury
(CI-AKI) in adult patients. M https://renal.org/wp-content/uploads/2017/
06/Prevention_of_Contrast_Induced_Acute_Kidney_Injury_CI-AKI_In_
Adult_Patients-1.pdf
Chapter 5 327
Shock
Shock 328
Shock: assessment 330
Shock: management 332
Sepsis syndrome and septic shock 336
Septic shock: management 338
Sepsis syndrome/septic shock: antibiotics 340
Toxic shock syndrome 341
Anaphylaxis 342
Lactic acidosis 344
328
Shock
Shock is defined as inadequate perfusion of vital organs. Concurrent hypo-
tension need not necessarily be present. Unwell patients with a lactate
>2mmol/L may have inadequate perfusion. The drop in BP is a late finding,
particularly in young, fit people, so resuscitation should ideally commence
before this point is reached.
Priorities
• If the BP is unrecordable, call the cardiac arrest team. Begin basic life
support with chest compressions; attach a defibrillator, and establish
venous access.
• If the BP (MAP <60mmHg) is low or falling, call for urgent support and/or
specialist help, e.g. intensive care unit.
• The cause of hypotension is often apparent. If it is not, then one can
usually make a rapid clinical assessment of likely causes:
• Hypovolaemia.
• Cardiac failure.
• Systemic vasodilatation, e.g. sepsis, anaphylaxis, neurogenic.
• Obstruction (e.g. PE, tension pneumothorax, tamponade).
• Combined causes.
Differential diagnosis of shock
Cardiac pump failure
• MI (E ST elevation myocardial infarction (STEMI), pp. 12–13).
• Dissection of the thoracic aorta (E Aortic dissection: assessment,
pp. 148–9).
• Cardiac arrhythmias (E Arrhythmias: general approach, p. 58).
• Acute valvular failure or acute VSD (E Ventricular septal defect post-
myocardial infarction (MI), pp. 34–5).
• Drug overdose (cardiac depressants; E Overdoses: general approach,
pp. 740–1).
• Myocarditis.
Hypovolaemia
• Haemorrhage (GIT) (E Acute upper gastrointestinal bleeding 1,
pp. 228–9), aortic dissection or leaking AAA, trauma (fractures, liver or
spleen injury, haemothorax, occult).
• Fluid losses (diarrhoea, vomiting, polyuria, or burns).
• ‘Third space’ fluid losses (acute pancreatitis; E Acute
pancreatitis: assessment, pp. 284–5).
• Adrenal failure (E Addisonian crisis: assessment, pp. 578–80).
Systemic vasodilatation
• Sepsis.
• Liver failure (E Acute liver failure: assessment and investigations,
pp. 276–7).
• Drug overdose (calcium antagonists or other vasodilators, drugs causing
multi-organ failure, e.g. paracetamol, paraquat).
• Adrenal failure (may be both hypovolaemic and vasodilated).
• Neurogenic shock (bradycardia and hypotension, autonomic failure).
Shock 329
Systemic vasodilatation: anaphylaxis
• Recent drug therapy.
• Food allergy (e.g. peanut).
• Insect stings.
Obstruction
• Cardiac tamponade (E Cardiac tamponade: presentation, pp. 162–3).
• PE (E Pulmonary embolism (PE): assessment, p. 126).
• Tension pneumothorax (E Tension pneumothorax, p. 216).
30
Shock: assessment
If the BP is unrecordable, then call the cardiac arrest team. Begin basic life
support (Airway, Breathing, Circulation, Disability/neurology, Exposure/
environment), with emphasis on good-quality CPR, and establish venous
access. If the cause of hypotension is not obvious, perform a rapid clinical
examination, looking specifically for the following:
• Check the airway is unobstructed. Give high-flow (60–100%) O2 by face
mask. If airway is unprotected or breathing inadequate, ETT. A laryngeal
mask airway (LMA) can be used to help oxygenation but does not
protect the airway like ETT. Check both lungs are ventilated (? tension
pneumothorax).
• Note the respiratory rate (i in acidosis, pneumothorax, embolus, and
cardiac failure, but often i regardless of cause).
• Check cardiac rhythm, and treat if abnormal (E Tachyarrhythmias heart
rate >120bpm, pp. 60–1; E Treatment options in tachyarrhythmias,
p. 62; E Broad complex tachycardia: diagnosis, p. 64; E Monomorphic
ventricular tachycardia (MVT), pp. 66–7; E Polymorphic ventricular
tachycardia, pp. 68–9; E Ventricular tachycardia: drugs, p. 70;
E Narrow complex tachyarrhythmias (SVT), pp. 72–3; E Dosages of
selected antiarrhythmics for SVT, p. 75; E Atrial fibrillation: assessment,
pp. 76–7; E Atrial fibrillation: management, pp. 78–9; E Atrial
fibrillation: rate control, p. 81; E Atrial flutter, p. 82; E Multifocal atrial
tachycardia, p. 83; E Accessory pathway tachycardia (AV re-entrant
tachycardia), p. 84; E Atrioventricular nodal re-entry tachycardia, p. 85;
E Bradyarrhythmias: general approach, pp. 86–7; E Sinus bradycardia
or junctional rhythm, p. 88; E Intraventricular conduction disturbances,
p. 89; E Types of atrioventricular conduction block, p. 90).
• Is the JVP elevated (see Box 5.1)?
• Is the BP the same in both arms (thoracic aortic dissection)?
• Are there any unusual cardiac murmurs? (Acute valvular lesion, flow
murmurs, including an S3, are often heard in vasodilated patients.)
• Is the patient cold and clammy? This suggests cardiac failure or
hypovolaemia. NB Patients with septic shock may also be peripherally
shut down. Check for fever (temperature may be subnormal, especially
in the elderly and children).
• Is the patient warm and systemically vasodilated (capillary refill time).
Palpate for bounding pulses.
• Is the patient clinically dehydrated or hypovolaemic (skin turgor, mucous
membranes, postural fall in BP)?
• Any evidence of haematemesis (blood around the mouth) or melaena
[per rectum (PR) examination]?
• Is there any evidence of anaphylaxis, including urticaria, wheeze, or soft
tissue swelling (e.g. eyelids or lips)?
• Examine the abdomen. Is there fullness or a pulsatile mass in the
abdomen (ruptured aneurysm)? Is there evidence of an acute abdomen
[aneurysm (mottled legs), pancreatitis, perforated viscus]?
• Is conscious level impaired [AVPU (Alert, Voice, Pain, Unresponsive),
Glasgow Coma Scale (GCS)]?
• Is there evidence of trauma or fractures?
Shock: assessment 331
Investigations
ECG
• NSTEMI, STEMI, Q waves, arrhythmias, PE (tachycardia, right heart
strain, S1, Q3, T3), pericarditis (global ST elevation with PR depression).
CXR
• Pneumothorax, PE (oligaemia), dissection (wide mediastinum),
tamponade (globular cardiomegaly), pleural effusion (blunted
costophrenic angles).
Blood tests
• FBC (haemorrhage, d platelets in liver disease and sepsis), U&Es (renal
impairment, adrenal failure), glucose, coagulation screen (liver disease,
DIC), LFTs, troponin, CK, group and screen/cross-match.
ABGs
• Acidaemia, renal, lactate, ketoacidosis.
Septic screen
• Culture of blood, urine, sputum, and viral swabs.
Miscellaneous
• Echo (suspected tamponade, dissection, valve dysfunction), FAST scan,
LP, USS, CT abdomen and head.
Shock: management
General measures
• Check the airway patency; give O2 (60–100%) by face mask to optimize
O2 saturation. If conscious level is impaired (GCS <8), or airway is
compromised, or oxygenation is inadequate, consider airway adjuncts
(nasopharyngeal, Guedel) and subsequent intubation (or supraglottic
device, such as LMA, if ETT is not possible).
• Lie the patient flat; elevate the legs to improve venous return and
demonstrate hypovolaemia.
• Insert two large-bore IV cannulae, and commence infusion of a
crystalloid (Ringer’s lactate/Hartmann’s solution, Plasma-Lyte; 0.9%
saline if hyperkalaemia or hypercalcaemia suspected). In most cases
of shock, including cardiac causes, it is usually beneficial and safe
to give a crystalloid (250mL boluses over 5–10min), while a more
detailed assessment is being carried out. If the fluid challenge brings
improvement, give a further fluid challenge while assessing the situation.
If large volumes of crystalloid are needed, it is best to avoid exclusive
use of 0.9% saline, which may cause hyperchloraemia and metabolic
acidosis. Aim for 30mL/kg of crystalloid if septic shock.
• Send blood for U&Es, Mg2+, bone profile, glucose, CRP, FBC,
coagulation screen, X-match, blood cultures, and blood gas (venous
and/or arterial).
• Insert an arterial line for more accurate assessment of the BP and
arterial sampling. Catheterize the bladder to monitor the urine output.
Metaraminol and ephedrine can be given through a peripheral line to
temporarily improve the BP.
• Titrate fluid replacement according to appropriate available dynamic
parameters: stroke volume (variation <10%), central venous SpO2
(>75mmHg), venous–arterial CO2 gap (≤0.5mmHg), HR, BP, peripheral
tissue perfusion, and urine output (>0.5mL/kg/h). Overenthusiastic
fluid administration in patients with cardiac pump failure will precipitate
pulmonary oedema.
• Persistent hypotension, despite adequate filling, is an indication for
inotropic support, assuming that tension pneumothorax and PE have
been excluded. Insert a central venous line for inotrope infusions. The
choice of first-line agent varies to some extent, depending upon the
underlying diagnosis, but NA is a reasonable choice supported by RCTs.
• Treat the underlying condition, and enlist specialist help early.
• Ensure someone takes time to talk to the relatives to explain the patient
is seriously ill and may die. Discuss the resuscitation status.
See Box 5.2.
Cardiogenic shock (cardiac pump failure)
• Manage cardiac ischaemia, arrhythmias, and electrolyte disturbances.
• Possible concurrent hypovolaemia? Consider cautious IV fluid challenges,
rather than infusions. Optimize filling, guided by physical signs and
response in filling pressures and stroke volume to fluid challenges
(100–250mL of crystalloid).
Shock: management 333
• If BP allows (aim for SBP >100mmHg), start a nitrate infusion (e.g. GTN
1–10mg/h).
• If very hypotensive, start an IV inotrope infusion. NA should be
commenced. The addition of levosimendan or dobutamine should be
considered, as per local protocols.
• Milronone and/or sildenafil may help in the presence of severe
pulmonary hypertension, but expert assistance is advised.
• Low-dose diamorphine (e.g. 2.5mg) is beneficial, as it vasodilates,
reduces anxiety, and lowers the metabolic rate.
• Consider non-invasive (CPAP) or invasive ventilation in patients with
severe heart failure, as this decreases the work of breathing and benefits
both LV afterload and preload.
• If there is a potentially reversible cause for cardiogenic shock, consider
intra-aortic balloon counterpulsation with heparin anticoagulation as
an option, but this does not improve survival in RCTs (E Intra-aortic
balloon counterpulsation 1, p. 822).
• TTE would be helpful in assessing cardiac function and response to fluid
and vasopressors.
Hypovolaemic shock
• Fluid replacement with crystalloids; colloids do not offer a survival
advantage but achieve a more rapid haemodynamic response.
• Give blood to maintain Hb 70–90g/L; 90–100g/L in ACS or sepsis.
• Na+ and K+ abnormalities should be treated. Metabolic acidosis often
responds to fluid replacement alone.
• If the patient remains hypotensive in spite of fluids, consider other
causes of shock (sepsis, tamponade, tension pneumothorax, etc.).
Reperfusion injury may occasionally manifest itself as a hypotensive
and vasodilated circulation. If fluid-replete, commence inotropes–NA,
perhaps with the addition of levosimendan or dobutamine if a low
cardiac output state is suspected.
• If oliguria persists in an overloaded, resuscitated patient, furosemide
(0.5–1.0mg/kg IV bolus, followed by an infusion of 1–10mg/h IV) may
be given to try and maintain a urine output, as this may make fluid
management easier. There is no evidence that furosemide improves
outcome.
Practice points
Survival advantage is not gained with saline, compared to albumin,1 gel-
atin,2 or starch,3 for fluid resuscitation for sepsis.
References
1. Patel A, Laffan MA, Waheed U, Brett SJ.Randomised trials of human albumin for adults with
sepsis: systematic review and meta-analysis with trial sequential analysis of all-cause mortality. BMJ
2014;349:g4561.
2. Patel A, Brett SJ. Gelatin solutions for critically unwell septic adults. Br J Hosp Med (Lond)
2013;74:657.
3. Patel A, Waheed U, Brett SJ. Randomised trials of 6 % tetrastarch (hydroxyethyl starch 130/0.4
or 0.42) for severe sepsis reporting mortality: systematic review and meta-analysis. Intensive Care
Med 2013;39:811–22.
Shock: management 335
36
examine patients but to look at charts. Always examine the patient at least
twice a day and determine whether the clinical parameters match those on
the ICU chart.
Ask yourself twice a day
• Is gas exchange satisfactory? Watch for developing ARDS (E Adult
respiratory distress syndrome 1, p. 204) or ventilator-associated
pneumonia. Examine the chest daily for deterioration that may be masked
on ABG by adjustments of mechanical ventilation and do a CXR if needed.
• Is the circulation adequate? Note the BP (and MAP), filling pressures, and
cardiac output. Examine the peripheries (are they cool and shut down, or
warm?). Is the urine output satisfactory? Is there a swing on the arterial
trace, suggestive of hypovolaemia? Is there a developing metabolic
acidosis, or rising lactate, which may indicate tissue hypoperfusion?
• Fluid requirements. (What is the fluid balance? Is the patient clinically
dry, euvolaemic, or oedematous?)
• Is the patient receiving adequate nutrition (TPN or enteral)? Give
enteral nutrition, if possible; even 10mL/h will benefit the gut mucosa.
Give with TPN if the gut function is not adequate, but ensure regular
aspiration of any unabsorbed feed.
• What do the tests show [U&Es, LFTs, Ca2+, PO43–, Mg2+, CRP, cultures
(blood, urine, sputum, lines and tips, etc.)]?
• Are there signs of sepsis? Is there a new focus of infection?
Prognosis
The incidence of bacteraemia is 7/1000 admissions to hospital. Of these,
20% develop septic shock and 750% of these die (see Table 5.1; also see
Box 5.3).
Septic shock: management
Patients with established shock require adequate haemodynamic moni-
toring and high-dependency facilities.
Check the airway is clear. Give high-flow O2—if there is refractory hyp-
oxia, intubate and ventilate. Insert a large-bore peripheral venous cannula to
begin fluid resuscitation. Insert a central line and an arterial line.
Key recommendations from the updated Surviving Sepsis Campaign
guidelines (2012)4 for management of severe sepsis and septic shock are
summarized here:
• Early goal-directed resuscitation: during the first 6h after recognition
(in patients with hypotension or serum lactate >4mmol/L) is current
practice but not supported by multiple RCTs.
• Resuscitation goals include:
• MAP ≥65mmHg.
• Central venous O2 saturation ≥70%.
• Urine output ≥0.5mL/kg/h.
• Source identification:
• Within first 6h of presentation.
• Blood cultures before antibiotic therapy.
• Culture all sites as clinically indicated.
• Imaging studies performed promptly to confirm potential source of
infection.
• Broad-spectrum antibiotics:
• Within 1h of diagnosis of severe sepsis/septic shock (give first dose
of antibiotics yourself ).
• Daily reassessment of antimicrobial therapy with microbiology and
clinical data.
• Antibiotic therapy guided by clinical response; normally 7–10 days, but
longer if response is slow or if there are undrainable foci of infection
or immunologic deficiencies.
• Source control: abscess drainage, tissue debridement, or removal of
IV access devices if potentially infected as soon as possible, following
successful initial resuscitation (exception: infected pancreatic necrosis
where surgical intervention is best delayed).
• IV fluids:
• Crystalloid fluid challenge (e.g. 1L of crystalloids over 30min) to
restore circulating volume; aim for 30mL/kg.
• Rate of fluid administration should be reduced if cardiac filling
pressures increase without concurrent haemodynamic improvement.
• Vasopressors:
• NA or dobutamine (administered centrally) are first line.
• Vasopressin infusion (or long-acting terlipressin bolus) may be
added to NA.
• Inotropic therapy: consider dobutamine when cardiac output remains
low, despite fluid resuscitation and vasopressor therapy.
• Steroids: hydrocortisone (50mg 6-hourly), after adequate fluid
resuscitation, may be considered in refractory shock but does not
improve survival.
• Blood products:
• Target Hb of 70–90g/dL. Aim for a higher target in the presence
of tissue hypoperfusion, CAD, intracerebral pathology, or acute
haemorrhage.
• Do not use FFP to correct laboratory clotting abnormalities, unless
there is bleeding or planned invasive procedures.
• Administer platelets when platelet counts are <20 × 109/L and there
is significant bleeding risk.
• Liaise closely with haematology, especially if DIC is suspected.
• Ventilation:
• A strategy of low tidal volume, driving pressure, and inspiratory
plateau pressure to prevent ARDS.
• Positive end-expiratory pressure (PEEP).
• Head of bed elevation in mechanically ventilated patients, unless
contraindicated.
• Glucose control: use IV insulin to control hyperglycaemia, targeting a
blood glucose <10mmol/L after initial stabilization.
• Renal replacement: continuous haemofiltration is the preferred method.
• DVT prophylaxis: low-dose UFH (renal impairment) or LMWH, unless
contraindicated, with dynamic compression (e.g. Flowtron®) of the legs,
unless contraindicated.
• Stress ulcer prophylaxis: H2 blockers or PPIs.
• Consideration of limitation of support (where appropriate): discuss
advance care planning with patients and families. Describe likely
outcomes and set realistic expectations.
References
4. Dellinger RP, Levy MM, Rhodes A, et al. (2012). Surviving Sepsis Campaign: international guide-
lines for management of severe sepsis and septic shock. Intensive Care Med 39:165–228.
340
Anaphylaxis
Anaphylaxis is a severe, life-threatening generalized or systemic hypersen-
sitivity reaction, characterized by rapidly developing life-threatening airway
and/ or breathing and/ or circulation problems, usually associated with
skin and mucosal changes. The UK incidence of anaphylactic reactions is
increasing.
Atopic individuals are particularly at risk, but it may occur in the absence
of a past history. Urticarial disease may also present with anaphylaxis.
Precipitants include:
• Insect bites (especially wasp and bee stings).
• Foods and food additives (e.g. peanuts, fish, eggs).
• Drugs and IV infusions (blood products and IV immunoglobulin,
vaccines, antibiotics, aspirin and other NSAIDs, iron injections, heparin,
monoclonal antibodies, e.g. rituximab).
Presentation
Cutaneous features include skin redness, pruritus, urticaria, conjunctival
injection, angio-oedema, and rhinitis. More severe manifestations include
laryngeal obstruction (choking sensation, cough, stridor), bronchospasm,
tachycardia, hypotension, and shock.
Management
(See Fig. 5.1.)
• Remove the suspected precipitant if still being received.
• Maintain the airway: if respiratory obstruction is imminent, intubate and
ventilate. Consider emergency cricothyroidotomy (E Percutaneous
cricothyrotomy, p. 832) with a 14G needle and jet insufflation with 100%
O2 if intubation not possible.
• Give 100% O2: if there is refractory hypoxaemia, intubate and ventilate.
• Lie the patient flat with head-down tilt if hypotensive/legs raised.
• Give IM adrenaline 0.5–1mg (0.5–1mL of 1 in 1000 adrenaline injection),
and repeat every 10min according to BP and pulse.
• If IV access is present, use small IV doses of adrenaline (0.1–0.2mg), then
review response. SC adrenaline should not be given in anaphylactic shock
due to variable absorption.
• Establish venous access, and start IV crystalloid fluids (e.g. 500mL
over 30min). Persistent hypotension requires a continuous adrenaline
infusion, titrated to BP response.
• Give IV hydrocortisone 200mg and chlorphenamine 10mg.
• Continue H1 antagonist (e.g. chlorphenamine 4mg every 4–6h) for at
least 24–48h longer if urticaria and pruritus persist.
• If bronchospasm does not subside, treat as severe asthma (including
salbutamol, nebulized or intratracheal adrenaline, aminophylline).
• Once stable, consider investigations such as timed trypase levels, IgE
level, complement.
Angioneurotic oedema (C1 esterase inhibitor deficiency)
See E C1 esterase inhibitor deficiency (angioneurotic oedema), p. 689.
Anaphylaxis 343
Anaphylaxis?
IM adrenaline
0.5mL of 1 in 1000 (0.5mg)
and repeat IM adrenaline after 5min if no better
Lactic acidosis
Lactic acidosis is a metabolic acidosis due to excess production, or reduced
metabolism, of lactic acid. It may be divided into two types: type A (tissue
hypoperfusion) and type B (non-hypoxic).
Presentation
Patients are usually critically ill. Clinical features include:
• Shock (often BP <80/40mmHg).
• Kussmaul respiration.
• Tachypnoea.
• Deteriorating conscious level.
• Multi-organ failure, including hepatic, cardiac, and renal failure.
• Clinical signs of poor tissue perfusion (cold, cyanotic peripheries).
Investigations
• ABGs (pH <7.34, severe if pH <7.2).
• Serum electrolytes, including bicarbonate and chloride to calculate the
anion gap, if lactate unavailable. Raised anion gap >16mmol/L [anion
gap = (Na+ + K+) –(bicarbonate + chloride)].
• FBC (anaemia, neutrophilia).
• Blood glucose.
• Blood lactate level >4mmol/L (mainly done on ABG analysers).
• Screen for sepsis (blood cultures, CRP, MSU, etc.).
• Spot urine (50mL) for drug screen if cause unknown.
• CXR looking for consolidation or signs of ARDS.
Assessment of severity
Severity is assessed by blood lactate concentration and the degree of
acidaemia. This may be confounded by the presence of AKI. In the early
stages, the arterial pH may be normal or even raised, as elevated lactate
levels in the CNS cause hyperventilation, with compensatory respiratory al-
kalosis. The best predictor of survival is the arterial pH. Patients presenting
with a lactate of >5mmol/L and a pH <7.35 have a mortality of >50%.
Management
The principle of management is diagnosis and treatment of the cause (see
Box 5.4). All patients should be managed in a high -dependency area.
• Sepsis: start broad-spectrum antibiotics (e.g. cefotaxime +
metronidazole).
• Diabetic lactic acidosis: insulin and fluids, as needed (E Diabetic
ketoacidosis: assessment, pp. 546–7).
• Shock: consider invasive haemodynamic monitoring
(E Shock: management, pp. 332–3).
• Renal failure: treat by continuous haemo(dia)filtration. These patients are
usually too unstable to tolerate haemodialysis.
• Methanol: infuse ethanol or fomepizole (competitive metabolism;
E Toxic alcohols, pp. 780–1).
• Acidaemia: the role of bicarbonate is controversial, as it may lower
CSF pH. There is no benefit of bicarbonate over equimolar saline in
controlled trials.
Chapter 6 347
Neurological emergencies
Coma: assessment
Presentation
Coma is a ‘state of unarousable unresponsiveness’.
• No evidence of arousal: there is no spontaneous eye opening,
comprehensible speech, or voluntary limb movement.
• Unresponsive to external stimuli and surrounding environment, although
abnormal postures may be adopted, eyes may open, or grunts may be
elicited in response to pain.
• Involuntary movements, e.g. seizures or myoclonic jerks, may occur.
• GCS (E Glasgow Coma Scale (GCS), p. 458) is a useful way of
assessing and monitoring level of consciousness.
• Signs of brain shift (E Examination of brainstem function 3, pp. 464–5)
may accompany a decreasing level of consciousness.
Causes
For practical purposes, it is best to divide these into:
• Metabolic.
• Toxic.
• Infective.
• Structural lesions.
With or without:
• Focal brainstem signs.
• Lateralizing cerebral signs.
• Meningeal irritation.
In general, toxic and metabolic causes usually do not produce focal signs
(except rarely with hypoglycaemia or liver or renal failure), whereas infec-
tions and structural lesions do. Meningism offers a very useful clue about the
cause of coma (see E Coma with meningism, p. 349).
Coma without focal/lateralizing neurological signs
• Anoxia/hypoperfusion.
• Metabolic, e.g. hypo-/hyperglycaemia, acidosis/alkalosis, hypo-or
hypernatraemia, hypercalcaemia, hepatic or renal failure.
• Intoxications, e.g. alcohol, opiates, benzodiazepines, tricyclics,
neuroleptics, lithium, barbiturates, carbon monoxide.
• Endocrine: hypothyroidism.
• Hypo-or hyperthermia.
• Epilepsy.
• Hypertensive encephalopathy.
Coma with focal/lateralizing neurological signs (due to brainstem or
bihemispheric cerebral dysfunction)
• Vascular: cerebral haemorrhage or infarction (e.g. large-territory infarct
or basilar artery thrombosis).
• Supra-or infratentorial space-occupying lesion (SOL): tumour,
haematoma, abscess. In order to produce coma, these either have
to be within the brainstem or compress it by producing a brain shift
(E Examination of brainstem function 3, pp. 464–5).
Coma: assessment 349
Coma with meningism
• Meningitis, encephalitis.
• SAH.
Assessment of severity
• GCS (E Glasgow Coma Scale (GCS), p. 458).
• Signs of brain shift (E Examination of brainstem function 3, pp. 464–5)
and/or brainstem compromise.
• Precipitating lesion or injury.
• Length of time in comatose state.
• Comorbidities.
350
Coma: immediate management
Priorities
1. Stabilize the patient (airway, breathing, circulation). Give O2.
2. Consider giving thiamine, glucose, naloxone, or flumazenil.
3. Examine the patient. Is there meningism? Establish the GCS score. Is
there evidence of brainstem failure? Are there focal or lateralizing signs?
4. Plan for further investigations.
5. Observe for signs of deterioration, and attempt to reverse them.
For treatments to be considered in coma, see Box 6.1.
Stabilize the patient
• Open the airway by laying the patient on their side. Note the pattern of
breathing (E Examination of brainstem function 2, p. 462). If there is
apnoea or laboured or disturbed breathing, intubation and ventilation
should be considered. Measure ABGs.
• Support the circulation. Correct hypotension with fluids and/or
inotropes. If prolonged therapy is required, both require careful and
frequent monitoring of CVP and/or pulmonary artery wedge pressure
(PAWP). Search for any occult source of bleeding, e.g. intra-abdominal.
• Treat seizures with usual drugs (E Status epilepticus (tonic–clonic) 1,
pp. 408–9), but beware of over-sedation and hypotension.
• Take blood for glucose, U&Es, Ca2+, liver enzymes, albumin, clotting
screen, FBC, and toxicology (including urgent paracetamol and salicylate
levels). Urine should be saved for toxicology screen.
Give thiamine, glucose, naloxone, or flumazenil
• Check blood glucose. There is a good argument for giving 50mL of
50% glucose immediately for presumed hypoglycaemia because this will
usually not cause any harm.
• The only concern is that glucose may precipitate Wernicke’s
encephalopathy (WE) in malnourished individuals. Some clinicians
therefore favour giving a bolus of thiamine 100–200mg IV beforehand.
• Naloxone should only be given if opiate intoxication is likely (small
pupils) and the patient is in a coma or has a markedly reduced RR. In
adults, naloxone 0.8–2.0mg IV should be given at intervals of 2–3min to
a maximum of 10mg.
• Flumazenil should only be administered if benzodiazepine intoxication
is likely; it is contraindicated in epileptics who have received prolonged
benzodiazepine therapy. In adults, flumazenil 200 micrograms should
be given over 15s; further 100-microgram boluses may be given at 1-
min intervals (usual dose is 300–600 micrograms, maximum total dose
outside intensive care setting is 1mg).
• Both naloxone and flumazenil may be given as IVIs if drowsiness recurs,
but intensive care monitoring is advisable.
Coma: clues from examination
History
If available, this will often be the most useful source of assessment. Even
if the history is not extensive, a witness is vital to establish whether coma
commenced suddenly (suggestive of a vascular event) or whether there
was a gradual decline in level of consciousness over hours or days and for
relevant premorbid history (e.g. previous generalized seizures, use of drugs,
etc.). Individuals known to suffer from specific diseases may be wearing
a MedicAlert bracelet or carrying their regular medication. An enormous
amount may be learnt from a rapid, but thorough, examination.
General examination
This should establish the following:1,2
• Core temperature: fever usually indicates an infection but sometimes
results from diencephalic lesions. Hypothermia is often forgotten as a
cause for coma; the possibility of myxoedema should be considered.
Ideally, prognosis should be based on normothermic state.
• HR and rhythm: may indicate a dysrhythmia as the reason for poor
cerebral perfusion.
• BP: prolonged hypotension of any cause will lead to anoxia and
ischaemia. Apart from a cardiac cause, occult bleeding, a cause of sepsis,
and drug intoxication need to be considered.
• Respiratory pattern: shallow, slow breathing should alert the examiner to
the possibility of drug intoxication, e.g. opiates. Deep, rapid Kussmaul
breathing suggests acidosis. Brainstem compromise can cause distinctive
patterns of breathing (see Fig. 6.4).
• Breath: alcohol, ketones, hepatic or uraemic fetor?
• Skin: there may be signs of trauma to the head. Bruising over the scalp
or mastoids and blood in the nostrils or external auditory meatus raise
the possibility of a basal skull fracture. A rash suggests the possibility of
meningitis. Look for signs of chronic liver disease or sallow discoloration
of uraemia. IV drug abuse suggested by needle tracks.
• Heart: occasionally bacterial endocarditis or vasculitides associated with
heart murmurs present with coma.
• Abdomen: look for enlargement of organs which may give clues to the
cause of coma. It is important not to miss an acute intra-abdominal
event such as perforation of a viscus or a leaking aortic aneurysm.
• Fundi: papilloedema indicates raised ICP, but its absence does not
exclude that possibility. Subhyaloid haemorrhages are pathognomonic
of SAH but are rare. Changes of diabetic or hypertensive retinopathy
suggest the possibility of encephalopathy secondary to these conditions.
Is there meningism?
Neck stiffness should be assessed only if it is certain that there has been no
trauma to the cervical spine. Stiffness suggests meningeal irritation, either
because of inflammation or infiltrative processes affecting the meninges or
because of the presence of blood. Meningism raises the possibility of men-
ingitis, meningoencephalitis, or SAH. Start antibiotics immediately if menin-
gitis is suspected.
Assess the GCS
This may reveal brainstem dysfunction or lateralizing signs. When testing
the motor response, decorticate or decerebrate posturing may become
evident (E Examination of brainstem function 1, pp. 460–1). If there is a
change in these signs, it may indicate a brain shift (E Examination of brain-
stem function 3, pp. 464–5).
Look for evidence of brainstem dysfunction
See E Examination of brainstem function 1, pp. 460–1 for details.
• Test and observe:
• Pupillary response.
• Corneal reflex.
• Resting position of the eyes.
• Spontaneous eye movements.
• Oculocephalic response/doll’s head manoeuvre (if no C-spine injury).
• Oculovestibular response/caloric stimulation.
• Swallowing.
• If intubated: cough and gag to suction.
• Respiratory pattern.
• If intubated: ventilator dependency.
• There will be evidence of brainstem failure either because there is
structural damage (intrinsic lesion or extrinsic compression due to
brain shift; see E Examination of brainstem function 3, pp. 464–5)
or because of metabolic coma such as drug intoxication with diffuse,
usually reversible, dysfunction.
• If there is focal brainstem dysfunction, the cause is most likely structural
or intrinsic brainstem disease.
• If there is rostro-caudal progression of brainstem signs, consider
a herniation syndrome (E Examination of brainstem function 3,
pp. 464–5).
• If there appears to be diffuse brainstem dysfunction, it may not be easy
to distinguish between structural and metabolic aetiologies. The most
important clue is that in metabolic coma, irrespective of their size, the
pupils continue to react, except in very few exceptional cases (atropine,
hyoscine, or glutethimide intoxication will depress brainstem function
and produce pupillary abnormalities).
Are there lateralizing signs?
Testing of brainstem reflexes, assessing the GCS score, and general exam-
ination may reveal facial asymmetry and differences in muscle tone, clonus,
reflexes, and plantar responses between the two sides. All these features
point towards the possibility of a structural lesion, although occasionally
metabolic coma is associated with focal neurological signs.
References
1. Posner JB, Saper CB, Schiff ND, Plum F (2007). Plum and Posner’s Diagnosis of Stupor and Coma
(Contemporary Neurology Series), 4th edn. Oxford University Press, New York, NY.
2. Bates D. The management of medical coma. J Neurol Neurosurg Psychiat. 1993;56:589–98.
354
Coma: management
Plan for further investigations
The history, physical examination, and/or laboratory studies may help
make the diagnosis. Often, however, a diagnosis cannot be reached so rap-
idly. The practical approach is to divide patients according to the following
scheme.
Brainstem function intact
Urgent CT head scan. This will reveal one of the following:
• Operable lesions (e.g. subdural, subarachnoid, or intracerebral
haemorrhage): refer to neurosurgery as appropriate.
• Inoperable lesions: treatment is supportive.
• Normal CT: an LP should be performed. Measure the opening
pressure. CSF analysis may suggest an infective process (e.g. meningitis,
encephalitis) (E Acute bacterial meningitis: assessment, p. 371). If the
CSF is normal, the most likely diagnosis is a metabolic coma.
Brainstem function not intact
• Consider whether there are signs of brain shift (E Examination of
brainstem function 3, pp. 464–5).
• If a herniation syndrome appears to be progressing rapidly, mannitol
should be given, hyperventilation commenced, and a neurosurgeon
contacted urgently (E Raised intracranial pressure, pp. 388–90).
• If the tempo of events is not so rapid, mannitol may be given and an
urgent CT scan arranged.
• Even if the brainstem signs appear to be non-progressive, a CT scan
should be arranged to exclude the possibility of an operable posterior
fossa mass or haemorrhage (e.g. cerebellar haemorrhage).
• If the CT is normal, an LP should be performed to exclude infection.
If this too is normal, the diagnostic possibilities are intrinsic brainstem
disease not detected by CT, metabolic coma, paraneoplasia, and
parainfectious or possibly infection, e.g. encephalitis, without leucocytic
response.
• MRI is more sensitive in detecting intrinsic brainstem pathology, but
fluid attenuation inversion recovery (FLAIR) sequences are limited in
sensitivity in this part of the brain. Additionally, standard 5-mm slices
may be too thick for some discrete pathologies.
• LP should be repeated the next day if there is no improvement in the
patient’s condition. Treatment is supportive.
Monitoring progress
• Regular observations of vital signs and neurological state (and GCS
score).
• An important cause of deterioration in structural brain lesions is brain
shift leading to herniation syndromes (E Examination of brainstem
function 3, pp. 464–5). The emergency treatment of raised ICP is
discussed under E Raised ICP: further management, p. 392.
• Other reasons for deterioration are electrolyte or metabolic changes,
hypovolaemia, or fluid overload. Monitor regularly.
Coma: management 355
Prognosis
In coma due to head injury, prognosis is clearly related to the GCS score.
Patients scoring 8 or less have a poor prognosis. In non-traumatic coma,
the GCS score alone is not a very good predictor. Patients with drug in-
toxications may have low scores on admission but, in general, have good
outcomes. Prognosis in non-traumatic coma is gauged by simple features
of the examination. (e.g. if after 24h, pupillary responses, corneal reflexes,
and oculovestibular response remain absent, survival is extremely un-
likely).3 Early myoclonus (within 24h) after hypoxic–ischamic brain injury
is a poor prognostic marker. Prognosis requires assessment at least 3 days
subsequent to rewarming (if therapeutically cooled or patient presented in
hypothermic coma).
References
3. Levy DE, Bates D, Caronna JJ, et al. Prognosis in nontraumatic coma. Arch Int Med.
1981;94: 293–301.
356
Limb weakness: assessment
History
The history should establish if there has been:
• Sudden onset or gradual progression.
• Weakness or incoordination.
• Upper limb or facial weakness.
• Asymmetrical or symmetrical weakness.
• Associated sensory symptoms, e.g. paraesthesiae or numbness.
• Difficulty with swallowing, speech, micturition, or defecation.
• Back or neck pain.
• Lhermitte’s phenomenon (flexion of the neck causing sensory
symptoms radiating down the limbs) suggests cervical cord
inflammation, radiation-induced myelopathy, or vitamin B12-deficient
subacute degeneration of the cord.
• Systemic symptoms, e.g. malaise, fever, diarrhoea and vomiting,
arthralgia.
• Recent trauma.
• Previous medical history, e.g. hypertension, IHD, stroke, DM,
connective tissue diseases, immunosuppression.
• Drug history, e.g. phenytoin, isoniazid, vincristine, metronidazole.
• Social history, e.g. smoker (cord infarct), vegan (vitamin B12 deficiency),
travel history (infectious, e.g. TB, parasitic), sexual history (e.g. HIV).
Examination
• What is the pattern of weakness? Some common patterns, together with
associated features, are illustrated under E Limb weakness: localizing
the lesion, p. 358. This should help to localize the level of the lesion in
the nervous system.
• Is the weakness upper (UMN) or lower motor neuron (LMN)/combination?
• If UMN, is it pyramidal? That is, extensor more than flexor weakness
in the upper limbs, and flexor greater than extensor weakness in the
lower limbs.
• Is there fatiguable weakness with repetitive effort? As in myasthenia.
• Are there any involuntary movements? Tremor [e.g. multiple sclerosis (MS)],
myoclonic jerks, or fits (e.g. venous sinus thrombosis) may be noted.
• What is the gait like? This is important to test, if at all possible. It
may demonstrate, for example, a hemiplegic gait, ataxia (cerebellar
or sensory), a waddling (myopathic) gait, steppage (LMN) gait, or
festinating movements of the parkinsonian patient.
• Is there any sensory loss? Where? Is there a ‘sensory level’? Sensory changes
are often the most difficult to elicit. Do not forget to test all modalities
or to test the back of the legs up to the anal sphincter.
• What modalities of sensation are lost? Dorsal column loss produces
a ‘discriminatory’ loss with impaired two-point discrimination, joint
position and vibration loss, and sensory ataxia. Spinothalamic loss
usually produces a lack of awareness of pain and temperature.
The history and examination should help to localize the lesion and, together
with the patient’s age, give an indication of the likely pathological process
involved.4
Investigations
The initial investigation of choice depends upon the likely diagnosis.
Investigations to consider are given in Box 6.2.
Diagnoses not to miss
• Spinal cord compression (E Spinal cord compression: assessment,
p. 448).
• GBS (E Guillain–Barré syndrome, pp. 452–3).
• Subdural haematoma (E Subdural haematoma, pp. 400–1).
• Stroke (E Stroke: overview, pp. 412–13).
Diagnoses to consider
• Demyelination (MS, neuromyelitis, post-infectious, etc.).
• Malignancy (malignant meningitis, intracranial mass).
• Syringomyelia.
• Motor neuron disease.
• Vitamin deficiency (subacute combined degeneration—vitamin B12).
• Peripheral neuropathy (toxic, DM, autoimmune, amyloid, etc.).
• TB, syphilis.
Practice points
A patient who can cycle easily, but only walk yards, usually has lumbar
stenosis or parkinsonism.
References
4. Adapted from Lindsay KW, Bone I, Fuller G (2010). General approach to history and examin-
ation: In: Lindsay KW, Bone I, Callender R. Neurology and Neurosurgery Illustrated, 5th edn, pp. 1–2.
Churchill Livingstone, London.
358
Acute dizziness: assessment
History
Determine whether:
• There is true vertigo, i.e. a sensation that either the patient or their
environment is rotating. Distinguish this from ‘light-headedness’ more
likely related to pre-syncope.
• Symptoms started acutely are progressively worsening or are transient
(see ‘vertebrobasilar TIAs’ under E Transient ischaemic attacks,
pp. 430–1). Vestibular neuritis typically begins over a period of a few
hours, peaks in the first day, and then improves within days. Infarction
causes a vestibular syndrome that typically has an abrupt onset. TIAs
often last for <30min. Abrupt onset of vertigo for seconds after a
change in head position is characteristic of benign paroxysmal positional
vertigo.5
• Symptoms worse with certain postures: vertigo is worse with certain
head positions in benign positional vertigo and some cases of central
nystagmus (see Box 6.3). Postural hypotension is frequently caused by
drugs and can be caused by acute blood loss; uncommonly, it is due to
autonomic failure.
• There is associated tinnitus (as in Ménière’s disease).
• Hearing loss is present in Ménière’s disease, cerebellopontine angle
lesions, e.g. acoustic neuroma (Vth, VIIth, and VIIIth nerves + ataxia).
• Ear discharge may occur with middle ear disease.
• Associated focal neurological symptoms, e.g. unilateral weakness,
clumsiness, paraesthesiae, or numbness.
• Headache: sudden onset in intracerebral haemorrhage; progressive with
features of i ICP in mass lesions (e.g. acoustic neuroma). History of
migraine (suggesting migrainous vertigo).
• Any recent head injury?
• Systemic symptoms, e.g. weakness and lethargy in anaemia.
• Previous medical/psychiatric history, e.g. hypertension, IHD, DM, risk
factors for stroke or TIAs (E Transient ischaemic attacks, pp. 430–1),
episodes of neurological disturbance, panic attacks, and anxiety.
• Drug history is pertinent to both true vertigo (e.g. phenytoin, gentamicin,
furosemide) and dizziness (e.g. antihypertensives, antidepressants, drugs
for Parkinson’s disease, hypoglycaemics).
Examination
• Ear: is there a discharge? Is the tympanic membrane normal?
• Neurological examination: should discover whether there are any focal
signs due to brainstem or cerebellar disease (E Examination of
brainstem function 1, pp. 460–1). Non-contiguous brainstem pathology
may be due to patchy demyelination. Do not forget to assess the
corneal reflex, the absence of which is one of the earliest signs of
an ipsilateral acoustic neuroma. Observe the gait, if possible; it may
be ataxic. Examine extraocular eye movements. Is there intranuclear
ophthalmoplegia (vascular/demyelinating brainstem disease)? Examine
carefully for nystagmus (see Box 6.3). Hallpike manoeuvre involves
positioning the patient’s head over one side of the bed and watching
for nystagmus. Benign positional vertigo: nystagmus develops after a brief
delay, but it fatigues and, with repetition, adapts. Central nystagmus: no
initial delay, fatiguability, or adaptation. Head impulse test involves the
examiner holding the patient’s head while the patient fixates on the
examiner’s nose; rapid, small left and right rotations of the head should
not displace the patient’s gaze from the examiner’s nose; if it does, with
a corrective ‘catch-up’ saccade, peripheral vestibular disturbance is
likely on the side towards which the head was turned. Fundoscopy may
reveal papilloedema (suggestive of an intracranial SOL) or optic atrophy
(which occurs with previous demyelination in MS).
• General examination: measure BP lying and then after 3 and 5min of
standing (including pulse). Postural hypotension is a common cause of
dizziness.
References
5. Hotson JR, Baloh RW. Acute vestibular syndrome. N Engl J Med. 1998;339:680–5.
362
Acute dizziness: management
Investigations
These depend upon the likely diagnosis.
• Cerebellopontine angle lesions, such as acoustic neuroma, may be
imaged by CT with contrast, but in general, posterior fossa and brainstem
disease is better appraised by MRI scanning.
• Pure tone audiometry is a sensitive way of detecting sensorineural loss.
• Measure blood sugar and FBC, if indicated.
For management, see Tables 6.2 and 6.3.
Investigations
See E Stroke: other investigations, p. 418.
NB An ESR and CRP should be performed in any patient aged >50 years
who presents with monocular blindness and unilateral headache. It is rarely
normal in temporal arteritis. If the ESR is elevated and the presentation is
compatible with temporal arteritis, high-dose corticosteroid therapy should
be considered (initially 60mg/day PO) because the other eye is also at risk
of anterior ischaemic optic neuropathy.
36
Binocular sustained loss
• Field loss, e.g. quadrantanopia (stroke, tumour, inflammation),
hemianopia, bitemporal (pituitary lesions): initially CT scan.
• Hypotension (e.g. cardiac failure).
• Basilar artery thrombosis : dysrhythmias or vertebrobasilar insufficiency
may produce transient episodes of binocular visual loss. CT scan.
• Posterior reversible encephalopathy syndrome (PRES) with headaches,
confusion, seizures, and visual loss: triggered by hypertension, renal
failure, eclampsia, and immunosuppressants. Improves over days or
weeks. MRI brain required.
• Toxic optic neuropathies (e.g. tobacco, alcohol, methanol).
• Genetic (e.g. Leber’s hereditary optic neuropathy).
Fig. 6.1 Central retinal vein occlusion with assorted closure of the arterial
circulation above the macula (E Approach to acute/subacute visual loss, pp. 366–7).
Reproduced from Easty D, et al. Oxford Textbook of Ophthalmology, 1999, with permission from
Oxford University Press.
368
towards fornices
Blanch on pressure
Mobile over sclera
Subconjunctival Bright red sclera with Normal Normal Normal Normal Normal
haemorrhage white rim around
limbus
may not be possible as with the corneal clouding of acute glaucoma.
*
Reproduced with permission from Judge RD et al. (1989). Clinical Diagnosis, 5th edn.
• Are there any anterior chamber abnormalities? In acute anterior uveitis,
• Is there a rash or vesicles on the face, nose, or eyelid? Herpes zoster can
Painful red eye: assessment
See E Lumbar puncture 2, p. 858 for reference intervals for CSF analysis.
Meningitis with lymphocytic CSF
Presentation
• Viral meningitis may be indistinguishable on clinical grounds from acute
early bacterial meningitis, but it is usually self-limiting.
• TB meningitis is usually preceded by a history of malaise and systemic
illness for days to weeks before meningeal features develop. However,
it may present very acutely. TB meningitis may be associated with basal
arachnoiditis, vasculitis, and infarction, leading to focal neurological signs,
e.g. cranial nerve palsies, obstructive hydrocephalus with papilloedema.
• Cryptococcal or syphilitic meningitis in the immunocompromised
present with features indistinguishable from TB meningitis.
• Malignant meningitis (including metastases and lymphoma) may present
with constitutional features. CSF cytology in large volumes and often
repeated samples are needed for diagnosis.
Causes
Viral Non-viral
• Coxsackie. • TB.
• Echo. • Cryptococcus.
• Mumps. • Leptospirosis.
• Herpes simplex type 1. • Lyme disease.
• Varicella-zoster. • Syphilis.
• HIV. • Brucellosis.
• Lymphocytic • Parameningeal infection
choriomeningitis virus. with a CSF reaction.
CSF findings
The CSF usually demonstrates lymphocytosis. but the CSF in viral meningitis
may initially demonstrate predominantly neutrophils. It is important not to
dismiss the possibility of TB meningitis if CSF glucose is normal; the tuber-
culin test may also be negative initially. Mycobacterium tuberculosis is seen in
the initial CSF of 740% of patients with TB meningitis. Send CSF for viral
and TB PCR (the latter is specific, but not sensitive enough to rule out if not
present when clinically likely).
Treatment regimens
• Viral meningitis: usually supportive treatment only. Treat with aciclovir
only if encephalitic features (e.g. confusion, seizures).
• TB meningitis: for 2 months—rifampicin (450mg/day if weight <50kg
or 600mg/day if weight >50kg; many clinicians give up to 2–3 times
the dose), ethambutol (15mg/kg/day), pyrazinamide (1.5g/day if
weight <50kg; 2g/day if weight >50kg), and isoniazid 300mg/day
(double if severely unwell). Then continue rifampicin and isoniazid
alone for further 7–10 months. Give treatment IV if any concern about
absorption PO/NG. Give pyridoxine 10mg daily as prophylaxis against
isoniazid neuropathy. Adjunctive prednisolone from start (2.5mg/
kg/day IV, then PO) for 4 weeks (then 4-week taper), regardless of
severity. Consult your local respiratory/ID specialists for advice. Test
HIV status.
Head injury: presentation
For symptoms following a head injury, see Box 6.7.
• Varies from transient ‘stunning’ for a few seconds to coma.
• A fraction of patients who attend A&E need to be admitted for
observation (indications for admission are given in Box 6.12).
In the alert patient, determine the following.
• Circumstances surrounding injury. Was it caused by endogenous factors,
e.g. loss of consciousness while driving? Or exogenous factors, e.g.
another driver? Was there extracranial trauma?
• Period of loss of consciousness. This relates to the severity of diffuse
brain damage.
• Period of post-traumatic amnesia. The period of permanent memory
loss after injury also reflects the degree of damage. (NB The period of
retrograde amnesia or memory loss for events prior to injury does not
correlate with the severity of brain damage.)
• Headache/vomiting. Common after a head injury, but if they persist, raised
ICP should be considered (E Raised intracranial pressure, pp. 388–90).
• GCS score.
• Skull fracture present?
• Neurological signs. Are there any focal neurological signs?
• Extracranial injury. Is there evidence of occult blood loss?
The drowsy or unconscious patient needs the following:
• Urgent assistance from senior A&E staff and anaesthetists.
• Protection of airway: the patient who has deteriorating level of
consciousness or is in coma should be intubated because hypocarbia
and adequate oxygenation are effective means of reducing ICP rapidly. If
the patient is neurologically stable and protecting their airway, intubation
may not be necessary. Assume there is a cervical spine injury until an X-
ray (of all seven cervical vertebrae) demonstrates otherwise.
• Hyperventilation: the pattern of breathing should be noted
(E Examination of brainstem function 2, p. 462). Hyperventilation of
intubated patients with the aim of lowering PaCO2 is controversial—
consult an intensivist.
• Support of circulation: hypotension should be treated initially with
colloid. If persistent or severe, exclude a cardiac cause (ECG) and occult
haemorrhage (e.g. intra-abdominal).
• Treatment of seizures: diazepam 5–10mg IV/PR, which may be repeated
to a maximum of 20mg. If seizures continue, consider IV phenytoin
(E Status epilepticus (tonic–clonic) 1, pp. 408–9).
• Rapid survey of the chest, abdomen, and limbs: looking for a flail segment
or haemo-/pneumothorax, possible intra-abdominal bleeding (if there
are any doubts, peritoneal lavage may be required), limb lacerations, and
long bone fractures.
• Brief history: should be obtained from the ambulance crew or relatives.
The patient may have lost consciousness just before the injury, e.g.
due to SAH, seizure, or hypoglycaemia. The tempo of neurological
deterioration should be established.
• Guidelines for performing skull X-rays and CT head scans: see E Head
injury: assessment, p. 382.
Practice points
• Younger patients after head injury typically present with extradural
haemorrhage, while subdural haemorrhage is more common in the
elderly.
382
Head injury: assessment
Examination
Rapid neurological assessment should take only a few minutes
• The level of consciousness must be noted with the GCS score
(E Glasgow Coma Scale (GCS), p. 458).
• Note the size, shape, and reactions of the pupils to bright light.
• Resting eye position and spontaneous eye movements should be
observed. If the latter are not full and the patient is unresponsive, test
oculocephalic and/or oculovestibular responses (E Oculocephalic and
oculovestibular responses, pp. 466–7).
• The doll’s head manoeuvre should not be attempted if cervical spine
injury has not been excluded.
• Test the corneal reflex [cranial nerves V (sensory) and VII (motor)].
• Motor function should be assessed (E Glasgow Coma Scale (GCS),
p. 458); any asymmetry should be noted.
• Look for features suggesting brain shift and herniation (E Examination
of brainstem function 3, pp. 464–5).
Head and spine assessment
• The skull should be examined for a fracture. Extensive periorbital
haematomas, bruising behind the ear (Battle’s sign), bleeding from the
ear, and CSF rhinorrhoea/otorrhoea suggest a basal skull fracture. Look
for facial (maxillary and mandibular) fractures.
• Only 1% of patients will have a skull fracture. This greatly increases
the chances of an intracranial haematoma (from 1:1000 to 1:30 in
alert patients; from 1:100 to 1:4 in confused/comatose patients). NB
Potentially fatal injuries are not always associated with skull fracture.
• Consider the possibility of spinal cord trauma. ‘Log-roll’ the patient,
and examine the back for tenderness over the spinous processes,
paraspinal swelling, or a gap between the spinous processes. The
limbs may have been found to be flaccid and unresponsive to pain
during the neurological assessment. There may be painless retention
of urine.
For indications for skull X-ray, see Box 6.8.
Do not use plain X-rays of the skull to diagnose significant brain injury
without prior discussion with a neuroscience unit. However, they are useful
as part of the skeletal survey in children presenting with suspected non-
accidental injury.
For definite indications for CT scan, see Box 6.9.
For things to look for on C-spine films, see Box 6.10.
References
11. National Institute for Health and Care Excellence (2014). Head injury: assessment and early man-
agement. Clinical guideline [CG176]. M https://www.nice.org.uk/guidance/cg176
384
Stabilize the patient
• Open the airway by laying the patient on their side. Give O2. Measure
ABGs. Intubation and mechanical ventilation may be necessary because
of respiratory compromise. It may also be necessary to reduce ICP
by hyperventilating the patient (E Measures to reduce ICP, p. 390) to
keep PaCO2 between 3.3 and 4.0kPa (25–30mmHg).
• Correct hypotension. Volume expansion with colloids or infusions of
inotropes needs to be conducted with careful and frequent monitoring
of CVP and/or PAWP. In general, patients with raised ICP should be
fluid-restricted to 1.5–2.0L/day. So if volume expansion is required, it
should be kept to the minimum required to restore BP.
• Treat seizures (E Status epilepticus (tonic–clonic) 1, pp. 408–9).
• Examine rapidly for signs of head injury (E Head injury: presentation,
p. 380). If the patient is hypotensive, examine carefully for any
occult site of bleeding. If there is a rash, consider the possibility of
meningococcal meningitis; take blood cultures and give antibiotics
(E Acute bacterial meningitis: immediate management, pp. 372–3).
• Take blood for glucose (this may be raised in DKA or hyperosmolar
non-ketotic states; it may be very low in liver failure), U&Es [biochemical
assessment of dehydration and renal function, K+ for susceptibility
to dysrhythmia, hyponatraemia from inappropriate antidiuretic
hormone (ADH), or hypernatraemia from aggressive diuretic-induced
dehydration], LFTs, albumin, clotting studies and ammonium (to assess
liver function), FBC, and blood culture.
390
Measures to reduce ICP
The value of ICP monitoring is a controversial subject. Irrespective of
whether or not your patient’s ICP is monitored, the following interventions
should be considered.
• Elevate the head of the bed to 30° (once cervical spine injury has been
excluded) to promote venous drainage.
• Hyperventilation, so that PaCO2 is kept between 3.7 and 3.9kPa, will
promote cerebral vasoconstriction and lower cerebral blood volume—
this requires intubation and paralysis. It will also lower the BP and may
compromise cerebral circulation. In patients with liver failure, this is no
longer recommended. Discuss with your local ITU.
• Mannitol: 0.5–1g/kg over 10–15min (250mL of 20% solution for an
average adult) reduces ICP within 20min, and its effects should last for
2–6h. If required, further boluses of smaller doses of mannitol
(0.25–0.5g/kg) may be given every few hours. U&Es and serum
osmolality should be monitored, as profound diuresis may result. Serum
osmolality should not be allowed to rise over 320mOsm/kg.
• Corticosteroids are of benefit in reducing oedema around SOLs
(E Intracranial space-occupying lesion, pp. 394–5) but are not helpful
in the treatment of stroke or head injury. Dexamethasone is given as
a loading dose of 10mg IV. It may be followed by 4–6mg q6h PO/via
NG tube.
• Fluid restriction to 1.5–2.0L/day. U&Es must be checked frequently.
• Cooling to 35°C reduces cerebral ischaemia.
• Avoid/treat hyperglycaemia because it exacerbates ischaemia.
References
13. Posner JB, Saper CB, Schiff ND, Plum F (2007). Plum and Posner’s Diagnosis of Stupor and Coma
(Contemporary Neurology Series), 4th edn. Oxford University Press, New York, NY.
Intracranial space-occupying lesion
Presentation
• Symptoms of raised ICP: headache, nausea, and vomiting (E Raised
intracranial pressure, pp. 388–90).
• Papilloedema: is present in the minority of cases.
• Focal neurological symptoms and signs: these depend upon the location
of the lesion, its extent and that of surrounding cerebral oedema,
and compression of long tract fibres or cranial nerves. Some lesions,
particularly those in the frontal lobe, are relatively ‘silent’ and may
produce no signs or simply a change in personality.
• Seizures.
• Impaired level of consciousness: ranging from confusion to coma.
• Signs of brain shift (E Examination of brainstem function 3, pp. 464–5)
may be present.
• Fever: suggests an infection. There may be a recent history of earache/
discharge, toothache, foreign travel, or immunocompromise.
• Acute onset of symptoms: suggests the possibility of a vascular event,
either an infarct or bleeding into another type of lesion, e.g. tumour.
For common causes of intracranial SOLs, see Box 6.15.
Management
(See Box 6.16.) Depends upon the diagnosis. In a comatose individual with
known inoperable brain metastases, it is usually not appropriate to inter-
vene. On the other hand, if a patient presents for the first time with signs
suggestive of an SOL, the diagnosis needs to be established.
• Assess severity:
• If comatose, protect the airway and manage as described under
E Coma: immediate management, p. 350.
• If there are signs of brain shift which suggest impending transtentorial
herniation (E Examination of brainstem function 3, pp. 464–5), give
dexamethasone [10mg IV (loading dose), followed by 4–6mg PO or
NG q6h] and/or mannitol 0.5–1g/kg over 10–15min (100–250mL of
20% solution for an average adult), and hyperventilate to keep PaCO2
between 3.7 and 3.9kPa. This may be followed by smaller doses of
mannitol every few hours (E Measures to reduce ICP, p. 390).
If the patient is alert and stable, it is best to await CT scan and, in the
•
Practice points
Hemisensory loss involving the trunk is likely to be due to a deep lesion
involving the thalamus or deep white matter. Complete hemisensory loss may
be seen in functional disorders and can be distinguished by placing a tuning
fork on each side of the forehead and the sternum (1cm apart). Patients with
functional disease might report that vibration is absent on the affected side
(but present 1cm away on the unaffected side), which is anatomically unlikely.
Further reading
Hawkes C. Smart handles and red flags in neurological diagnosis. Hosp Med. 2002;63:732–42.
396
Extradural haemorrhage
Presentation
There are no specific diagnostic features. Consider the diagnosis in any
head-injured patient who fails to improve or continues to deteriorate.
• Head injury: is almost invariable.
• Skull fracture: present in over 90% of adult cases.
• Headache and vomiting: may occur.
• Impaired level of consciousness: there may be an initial lucid interval
following a head injury, but extradural haematomas may be present
in patients who have been in a coma continuously after the injury.
Uncommonly, if the cause is a dural venous sinus tear (rather than shearing
of a meningeal artery), the lucid interval may extend for several days.
• Seizures.
• Contralateral hemiparesis and extensor plantar: may be elicited.
• Signs of brain shift (E Examination of brainstem function 3, pp. 464–5).
Causes
Common Rare
• Head injury tearing of • Head injury dural sinus tear.
meningeal artery (commonly • Intracranial infection (sinuses,
middle meningeal). middle ear, orbit).
• Anticoagulants/blood
dyscrasia.
Assessment of severity
Bilateral extensor plantars or spasticity, extensor response to painful stimuli,
and coma are severe effects of an extradural haemorrhage.
Management
Depends upon the tempo of presentation. Priorities are:
• Stabilize the patient: protect the airway; give O2, and support breathing
and circulation. Assume C-spine injury till excluded.
• Treat seizures (E Status epilepticus (tonic–clonic) 1, pp. 408–9).
• Urgent CT scan:
• Haematomas with >5mm midline shift on CT and/or >25mL
calculated volume require urgent evacuation.
• If the extradural haemorrhage is considered too small to warrant
surgery on a CT scan performed within 6h of injury, the scan should
be repeated after a few hours, irrespective of whether there has been
a deterioration in the patient’s condition.
• Closely monitor the neurological state (including GCS score):
• If the patient slips into coma and signs of tentorial herniation
(E Examination of brainstem function 3, pp. 464–5) are progressing
rapidly, give 1g/kg of 20% mannitol as a bolus and inform on-call
surgeons.
• If there is evidence of brain shift, discuss with neurosurgeons—ICP
should be reduced with mannitol (0.5–1.0g/kg of 20% mannitol) and
hyperventilation.
• All patients must be discussed with neurosurgeons: neurological impairment
is potentially reversible if the extradural haematoma is treated early.
Intracerebral haemorrhage
Presentation
• Headache, nausea, and vomiting of sudden onset is common.
• Focal neurological deficit: the nature of this depends upon the location
of the haemorrhage. Putaminal haemorrhages (30% of cases) or
lobar bleeds (30% of cases) may lead to contralateral hemiparesis and
sensory loss, visual field disturbance, dysphasia (left hemisphere), or
spatial neglect (more severe with right hemisphere lesions). In other
words, they may present like a middle cerebral artery (MCA) infarct
(E Cerebral infarction syndromes, p. 424), but often there is a greater
alteration in the level of consciousness. Thalamic haemorrhages (10%
cases) may result in eye signs (forced downgaze, upgaze paralysis, or
skew deviation), as well as contralateral sensory loss and hemiparesis.
Cerebellar haemorrhage is dealt with under E Cerebellar stroke,
pp. 426–7 and pontine bleeds under E Brainstem stroke, p. 428.
• Seizures may occur.
• Global neurological deficit with a decreasing level of consciousness
progressing to coma. There may be signs of brain shift (E Examination
of brainstem function 3, pp. 464–5).
• Hypertension.
Common predisposing factors
• Hypertension (40–50%): more commonly deep brain bleeds.
• Cerebral amyloid angiopathy: more superficial lobar bleeds.
• Anticoagulants.
• Metastatic neoplasm: bleeds may occur within the lesion.
• Drug abuse (alcohol, cocaine, pseudoephedrine, amphetamines).
Assessment of severity
A low GCS score (<9), a large-volume haematoma, and the presence of
ventricular blood on the initial CT are factors that are predictive of a high
mortality rate.
Management
Priorities are (see Box 6.17):
1 Stabilize the patient: protect the airway; give O2 if required; support
the circulation if necessary or appropriate; commence general
measures for treating a comatose patient (E Coma: immediate
management, p. 350) if necessary. If there is evidence of raised ICP, it
should be reduced.
2 Correct bleeding tendency or effects of anticoagulants.
3 Make a definitive diagnosis with an urgent CT scan. Liaise with the
regional neurosurgery unit early, as surgical intervention may be of
benefit. Whether aggressive intervention is appropriate should be
decided early.
4 If appropriate, intensive care/high dependency ward nursing
observations are required for the drowsy or comatose patient if they
are not transferred to a neurosurgical centre immediately.
Further reading
Keep RF, Hua Y, Xi G. Intracerebral haemorrhage: mechanisms of injury and therapeutic targets.
Lancet Neurol 2012;11:720–31.
40
Subdural haematoma
Presentation
• This may present in one of two ways: acute or chronic. Both are usually
the result of tearing of bridging veins (between the cortical surface and
venous sinuses).
• Acute haemorrhage into the subdural space follows head injury and
can be impossible to distinguish on clinical grounds from extradural
haemorrhage (E Extradural haemorrhage, p. 396).
• A chronic haematoma is also preceded in most cases by head injury, but
this is often so trivial that patients are unable to recollect it.
• Both types of patient may present with:
• Skull fracture (more common in acute cases).
• Headache.
• Impaired and fluctuating level of consciousness, ranging from mild
confusion through cognitive decline (e.g. impaired memory) to coma.
The diagnosis should be considered in any individual, particularly the
elderly, who presents with intellectual deterioration or ‘dementia’ of
relatively recent onset.
• Focal neurological signs (hemiparesis, dysphasia, hemianopia, etc.).
• Seizures occur in a minority of patients.
• Signs of brain shift (E Status epilepticus (tonic–clonic) 1, pp. 408–9)
or papilloedema.
Common predisposing factors
• Head injury: in young or old.
• Old age: cortical atrophy stretches bridging veins.
• Long-standing alcohol abuse.
• Anticoagulant use.
Assessment of severity
The following are severe effects of a subdural haemorrhage:
• Bilateral extensor plantars or spasticity.
• Extensor response to painful stimuli.
• Coma.
Management
Depends upon the tempo of presentation.
• In suspected chronic cases, a CT scan is required less urgently, unless
there has been an acute deterioration on a background of a steady
neurological decline. Chronic haematomas become isodense with the
brain and are therefore sometimes difficult to distinguish; MRI may be
better.
• In acute cases, priorities are (see Box 6.18):
• Protection of the airway, give O2, and support the breathing and
circulation as necessary.
• Liaison with the neurosurgical team early.
• Close monitoring of the neurological state (GCS score).
Subarachnoid haemorrhage: assessment
Presentation
• Headache: classically sudden and severe (‘thunderclap’), radiating
behind the occiput, with associated neck stiffness. Often, the time from
onset to peak of headache is only a few seconds, but less dramatic
presentations are common. Consider the diagnosis in any unusually
severe headache, especially if the patient does not have a previous
history of headaches and is >40 years. Many aneurysmal bleeds occur
at/after sexual intercourse, but most coital headaches are not SAHs;
10% of patients with subarachnoid bleeds are bending or lifting heavy
objects at the onset of symptoms.
• Nausea, vomiting, dizziness: may be transient or protracted.
• Impaired level of consciousness: there may be an initial transient loss of
consciousness, followed by variable impairment. Patients may present
in coma.
• Early focal neurological signs: may occur, especially if there has been a
concomitant intracerebral haemorrhage. Third nerve palsy raises the
possibility of a posterior communicating artery aneurysm.
• Seizures: are uncommon, but SAH in a person known to have fits
suggests an underlying AV malformation.
• Sentinel bleed: between 20% and 50% of patients with documented SAH
report a distinct, unusually severe headache in the days or weeks before
the index bleed.16 These are often misdiagnosed as simple headaches or
migraine, so a high degree of suspicion is required.
• Patients may present with secondary head injury following collapse.
Blood seen on CT scanning may be attributed to trauma.
Causes
Common Rare
• Aneurysm (70%). • Clotting disorder/anticoagulants.
• AV malformation (5%). • Tumour.
• No known cause in up to 20%. • Vasculitis.
• Associated with polycystic kidney
disease (berry aneurysm).
Practice points
• First and worst headache in someone not prone to headaches should
suggest SAH.
• Thunderclap headache may be due to a ruptured intracranial
aneurysm.17
• Recurrent thunderclap headaches may herald reversible
vasocontriction syndrome (need CT or MRA).
• Patients who wake, often at the same time, with severe unilateral
orbital pain lasting less than a couple of hours will usually have cluster
headache. Mostly middle-aged ♂.17
References
16. Edlow JA, Caplan LR. Avoiding pitfalls in the diagnosis of subarachnoid hemorrhage. N Engl J Med
2000;342:29–35.
17. Hawkes C. Smart handles and red flags in neurological diagnosis. Hosp Med 2002;63:732–42.
40
Subarachnoid haemorrhage: immediate
management
Confirm the diagnosis
• Urgent HRCT scanning is required. This will clinch the diagnosis in
95% of patients scanned within 24h. Furthermore, it gives valuable
information regarding a possible location of the aneurysm and may
even demonstrate AV malformation. It may also display concomitant
intracerebral and/or intraventricular bleeds.
• LP is not usually required, unless the CT scan is normal but the history
is highly suggestive. It is important to examine the CSF for blood under
these circumstances; the presenting event may be a ‘warning leak’.
Blood in the CSF may result from a traumatic tap. If this is the case,
there may be diminishing numbers of red cells in each successive tube of
CSF (although this is not always reliable). If the blood has been present
for >6h, the supernatant should be xanthochromic after centrifugation.
• Once the diagnosis is confirmed, discuss with regional neurosurgeons.
• Transfer grade 1 and 2 patients as soon as possible. Surgery will prevent
re-bleeding, and although the optimal time for operation is debated
(2 days versus 7–10 days post-bleed), outcome is probably improved by
early transfer.
• Surgery on poor-prognosis patients is unrewarding; they are usually
managed conservatively. However, suitability for surgery should be
reassessed if their condition improves.
Stabilize the patient
(See Box 6.19.)
• Protect the airway by laying the drowsy patient in the recovery position.
Give O2.
• Consider measures to reduce ICP if signs suggest it is raised (E Raised
intracranial pressure, pp. 388–90), but avoid dehydration and
hypotension.
• Treat seizures with usual drugs (E Status epilepticus (tonic–clonic) 1,
pp. 408–9), but beware of over-sedation and hypotension.
• Correct hypotension, if necessary, with colloid or inotropes.
• To avoid hypertension, the patient should be nursed in a quiet room;
sedatives may be required, and stool softeners should be given to avoid
straining. Once the diagnosis is established, nimodipine is usually given
to reduce vasospasm; it helps also to reduce BP.
• ECG monitoring and treat dysrhythmias if they compromise BP or threaten
thromboembolism. Rarely, SAH is associated with (neurogenic)
pulmonary oedema.
• Take blood for clotting screen (if bleeding diathesis suspected) and
U&Es (biochemical assessment of dehydration, K+ for susceptibility
to dysrhythmia, hyponatraemia from inappropriate ADH or from
aggressive diuretic-induced dehydration).
Further reading
Burrows AM, Korumilli R, Lanzino G. How we do it: acute management of subarachnoid hemor-
rhage. Neurol Res 2013;35:111–16.
406
Subarachnoid haemorrhage: further
management
Specific therapies
• Nimodipine is a calcium channel blocker which works preferentially
on cerebral vessels to reduce vasospasm (and consequent cerebral
ischaemia).18 It has been shown to reduce morbidity and mortality
following SAH. Give 60mg PO (or in the comatose patient) every 4h;
IV therapy is costly and requires central venous access.
• Antifibrinolytics were introduced to prevent lysis of clot and re-bleeding.
They have been associated with thrombotic complications and are not
advised at present.
• Appropriate analgesia (codeine phosphate 30–60mg every 4–6h) and
antiemetics should be given for awake patients.19
Observe for deterioration; attempt to reverse it
Neurological observations should be performed regularly. If there is a deteri-
oration, e.g. lowering of the level of consciousness, a CT scan should be
performed. There are several possible mechanisms for deterioration:
• Cerebral ischaemia is usually insidious and multifocal. It may give rise to
focal and/or global neurological deterioration. Volume expansion with
colloid or induced hypertension with inotropes have been attempted,
but these procedures have not been properly studied.
• Re-bleeding may be immediately fatal or lead to apnoea. It is reported
that assisted ventilation for 1h may be all that is necessary for
spontaneous breathing to return to the majority of apnoeic individuals.20
Patients who re-bleed are at high risk of further bleeding and should be
considered for emergency aneurysm clipping.
• Acute hydrocephalus may be treated with ventricular drainage. This can
lead to dramatic improvement in the patient’s condition.
Refer for definitive treatment
Unless the patient has a poor prognosis (see Hunt & Hess Scale in
E Subarachnoid haemorrhage: assessment, p. 402), they should be cared
for at a neurosurgical centre. The complications listed here should be man-
aged by clinicians experienced in treating them.
References
18. Pickard JD, Murray GD, Illingworth R, et al. (1989). Effect of oral nimodipine on cerebral in-
farction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial. BMJ
1989;298:636–42.
19. Kirkpatrick PJ. Subarachnoid haemorrhage and intracranial aneurysms: what neurologists need to
know. J Neurol Neurosurg Psychiat 2002;73(Suppl 1):i28–33.
20. van Gijn J. Subarachnoid haemorrhage. Lancet 1992;339:653–5.
References
23. Smith D, Chadwick D. The management of epilepsy. J Neurol Neurosurg Psychiat 2001;70(Suppl
2):ii15–21.
241
Stroke: overview
Presentation
• Sudden-onset focal deficit of cerebral function is the most common
presentation.
• Alternative presentations can include apparent confusion (e.g. due
to dysphasia or visuospatial impairment), seizures, declining levels of
consciousness or global loss of brain function, and coma.
• If symptoms last for >24h (or lead to death) and there is no apparent
cause other than a vascular event, the diagnosis is most likely to be a
stroke. If the symptoms last <24h and, after adequate investigation, are
presumed to be due to thrombosis or embolism, the diagnosis is a TIA.
TIAs tend, however, to last from minutes to 1–2h.
Causes
• Thrombosis or embolism causing cerebral infarction (80% cases).
• Primary intracerebral haemorrhage (15% cases).
• SAH (5% cases).
• Cerebral venous thrombosis (1%).
Risk factors
See Box 6.22.
Differential diagnosis
Many conditions may masquerade as a stroke:
• Cerebral tumour (primary or • Functional (psychogenic).
secondary). • Subdural haematoma.
• Brain abscess. • Todd’s paresis (post-seizure).
• Demyelination. • Hypoglycaemic attack.
• Focal migraine. • Encephalitis.
An alternative diagnosis to stroke is more likely in:
• Patients <45 years. • Absence of risk factors.
• Presence of seizures. • Fluctuating levels of consciousness.
• Presence of papilloedema. • Pyrexia (at presentation).
• Prolonged and/or discontinuous evolution of symptoms.
In general, a stroke commences suddenly and the deficit is at its peak and
established within 24h. If the evolution of symptoms is longer or progresses
in a stuttering way over days or weeks, an SOL must be suspected. If there
is a variable depression of consciousness, the diagnosis of a subdural
haematoma should be entertained, and pyrexia at presentation should alert
one to the possibility of a cerebral abscess.
Seizures occur in 5–10% of strokes at their onset, although they are
frequent sequelae. Papilloedema would be extremely unusual in arterial
strokes but may occur in cerebral venous sinus thrombosis. Consider this
diagnosis, particularly in patients who may have become dehydrated and
young women (particularly during the puerperium) with headache and seiz-
ures ± focal signs.
Stroke: overview 413
Practice points
Hemisensory loss involving the trunk is likely to be due to a deep lesion
involving the thalamus or deep white matter. Complete hemisensory loss
may be seen in functional disorders and can be distinguished by placing a
tuning fork on each side of the forehead and the sternum (1cm apart).
Patients with functional disease might report that vibration is absent on
the affected side (but present 1cm away on the unaffected side), which is
anatomically unlikely.
41
Stroke: haemorrhage or infarct?
Intracerebral haemorrhage can have an apoplectic onset with a combin-
ation of headache, neck stiffness, vomiting, and loss of consciousness of
acute onset. Conscious level can be depressed for >24h; there may be bilat-
eral extensor plantar responses, and the BP is more likely to be raised 24h
after admission. But although features such as these have been integrated
into scoring systems, it is not possible with certainty to differentiate an
ischaemic from a haemorrhagic stroke on clinical grounds alone. A CT scan
is required.
When to scan?
All patients suspected of having a stroke should be scanned as soon as
possible, at least within 24h of onset. If onset within a few hours, imaging
should occur immediately. CT is the investigation of choice in the majority
of cases because it is better at detecting haemorrhage in the early stages,
compared with standard MRI sequences, allowing triage for thrombo-
lytic treatment, and is more readily available as an imaging modality. After
the first 24h, and in cases where the stroke is suspected to involve the
brainstem or cerebellum, MRI is superior. Where the CT scan is normal,
diffusion-weighted MRI may reveal areas of cerebral ischaemia or infarction.
Urgent CT should be performed in the presence of
• Depressed level of consciousness.
• History of anticoagulant treatment or known coagulopathy.
• No available history.
• Features suggesting an alternative diagnosis requiring immediate action,
in particular:
• SAH (severe headache, depressed level of consciousness, neck
stiffness).
• Subdural haemorrhage (headache, history of minor trauma,
progressive or fluctuating signs and symptoms).
• SOL (depressed level of consciousness, progressive signs,
papilloedema).
• Cerebral infection (headache, fever, neck stiffness, cranial nerve
palsies).
• Indications for thrombolysis (see Box 6.23) or early anticoagulation.
Brain imaging should always be undertaken before anticoagulant treatment
is started.
Stroke: thrombolysis/thrombectomy
(See Boxes 6.23 and 6.24.)
Stroke: thrombolysis/thrombectomy 417
Box 6.23 (Contd.)
• Eligibility criteria for treatment in the 3–4.5h after an acute stroke are
similar to those for treatment at earlier time periods, with any one of
the following additional exclusion criteria:
• Patients older than 80 years.
• All patients taking oral anticoagulants are excluded, regardless of
the INR.
• Patients with baseline National Institutes of Health Stroke Scale
(NIHSS) score >25.
• Patients with a history of stroke and DM.
Source: data from Report of the Quality Standards Subcommitee of the American Academy of
Neurology (1996). ‘Practice advisory: thrombolytic therapy for acute ischemic stroke –summary
statement.’ Neurology 47: 835–9; and Adams HP, et al. (2003). ‘Guidelines for the early man-
agement of patients with ischemic stroke: A scientific statement from the Stroke Council of the
American Stroke Association.’ Stroke 34: 1056–83.
contraindication).
• Within 6h of stroke (but perfusion mismatch imaging may allow a
delayed approach).
• Preceding thrombolysis can occur.
841
Stroke: other investigations
Apart from a CT scan, there are some basic tests that most patients sus-
pected of having a stroke should have:
• FBC: to detect polycythaemia, thrombocythaemia, or
thrombocytopenia.
• ESR and CRP: to screen for vasculitis, endocarditis, hyperviscosity.
• Electrolytes and Ca2+: a neurological defect may be non-vascular and
caused by hyponatraemia, hypercalcaemia, or renal failure.
• Glucose: to exclude hypoglycaemia and non-ketotic hyperglycaemia
(which can mimic stroke) and DM (a risk factor).
• Cholesterol.
• PT/INR: if the patient is taking warfarin.
• ECG: to determine cardiac rhythm and exclude acute MI.
• Carotid Doppler ultrasound: to exclude high-grade (>70%) stenosis or
dissection. This should be performed in patients who would be suitable
for carotid endarterectomy or angioplasty. A bruit need not be present!
• Cardiac echocardiography: may demonstrate the presence of valvular
disease or intracardiac clot, or may detect some rare causes of stroke
such as atrial myxoma or PFO. The yield of a clinically meaningful
abnormality on standard TTE is low in unselected ischaemic stroke.
Young patients, or those without common risk factors for stroke (see
Box 6.22), should be investigated further. Possible tests include:
• Serum protein, electrophoresis, viscosity: in hyperviscosity syndromes, the
ESR is usually raised, but not always.
• Autoantibody screen: particularly for SLE).
• Haemostatic profile: in haemorrhagic stroke not apparently secondary
to hypertension, measurement of PT, APTT, bleeding time, and
fibrin degradation products may be indicated. In cerebral infarcts,
blood should be taken for proteins S and C, antithrombin III, and
anticardiolipin antibodies. APTT may be prolonged in anticardiolipin
syndrome. Consider testing for sickle-cell in black patients. The factor V
Leiden mutation may be an important risk factor for the development
of venous thrombosis.
• Toxicology screen: on admission sample if drug abuse (e.g. cocaine,
pseudoephedrine, or amphetamines) suspected.
• Urine tests: may detect homocystinuria (without other
clinical manifestations) or porphyria. If BP is labile, consider
phaeochromocytoma and measure urinary catecholamines.
• CSF analysis: may be necessary if the diagnosis of stroke is not well
established, e.g. normal CT scan and no risk factors.
• Cerebral angiography: is also reserved for cases where the diagnosis
is not well established and in those in whom cerebral vasculitis or
malformation is suspected.
• MRI: is more sensitive at detecting small infarcts, cerebral venous
thrombosis, and lesions in the posterior fossa. In expert hands, contrast-
enhanced MRA may be comparable to conventional angiography.
Stroke: management
(See Box 6.25.)
Stroke: management 421
Box 6.25 (Contd.)
• Anticoagulants should not be started until brain imaging has excluded
a haemorrhage and not until 14 days have passed from the onset of an
ischaemic stroke.
• Treatment with a statin (e.g. 40mg simvastatin) if total cholesterol
>3.5mmol/L, unless contraindicated.
• Any patient with a carotid artery territory stroke and carotid artery
stenosis of 70–99%, without severe disability, should be considered
for carotid endarterectomy.
*
Indications for decompressive craniectomy: clinical deficits suggestive of
an MCA territory infarction with a score on the NIHSS of >15; decrease
in the level of consciousness to a score of ≥1 on item 1a of the NIHSS;
signs on CT of an infarct of at least 50% of the MCA territory, or an in-
farct volume >143cm2, as shown on MRI with diffusion-weighted imaging.
There are recent trial data to suggest benefit in those over 60 years, as
well as those under 60 years.
42
Stroke: complications
Cerebral complications
Further neurological deterioration may be caused by the following:
• Transtentorial herniation (E Examination of brainstem function 3,
pp. 464–5) is the most common cause of death within the first week and
carries a mortality of 80%. It is due to raised ICP (E Raised intracranial
pressure, pp. 388–90) secondary to cerebral oedema and, in ischaemic
stroke, is most common after large MCA infarcts. Corticosteroids do
not improve outcome; mannitol and hyperventilation may be useful
temporary measures (E Raised intracranial pressure, pp. 388–90);
surgical decompression may be indicated in large haemorrhages,
particularly cerebellar ones.
• Haemorrhagic transformation occurs in 30% of ischaemic strokes (and up
to 70% of cardioembolic strokes), usually 12h to 4 days after the event.
Neurological deterioration is usually due to a mass effect.
• Acute hydrocephalus due to compression of the aqueduct of Sylvius by
oedema or blood may occur. Ventricular shunting may be of value.
• Seizures complicate 10% of infarcts and are most common in
large, haemorrhagic, and cortical strokes. They usually respond to
monotherapy (e.g. phenytoin).
• SIADH occurs in 10–15% of strokes. It may initiate or worsen cerebral
oedema and is treated by fluid restriction.
• Depression occurs in 50% and may require therapy if it persists.24
Systemic complications
• Aspiration is common. Dysphagia occurs in at least half of all cases of
stroke; the incidence is higher in those with brainstem involvement or
pre-existing cerebrovascular disease. It is often undetected at bedside
and usually leads to aspiration. Testing the gag reflex is not a sufficient
assessment; swallowing must be observed, and if there is any suspicion,
video-fluoroscopy may be used. Patients should generally be fed upright.25
• Infection is a common cause of death following a stroke. Pneumonia
(including aspiration) and UTIs are the usual problems.
• Fever usually occurs as a result of infection or DVT. Occasionally, it is a
direct result of cerebral damage.
• VTE: the incidence of DVT following a stroke is comparable to that following
hip or knee arthroplasty. PE accounts for up to 25% of early deaths
following a stroke. Use of prophylactic anticoagulants reduces the incidence
of VTE, but it is associated with an i risk of haemorrhagic transformation
which may outweigh any benefit. Many physicians use prophylactic LMWH,
although the Royal College of Physicians (RCP) guidelines recommend
compression stockings only. In the absence of intracranial haemorrhage,
subclinical or overt proximal DVT should be treated with standard therapy.
Below-knee DVT should be managed with compression stockings and serial
USS monitoring for evidence of proximal extension.
• Pressure sores occur easily, unless patients are regularly turned.
References
24. Oppenheimer S, Hachinski V. Complications of acute stroke. Lancet 1992;339:721–4.
25. Perry L, Love CP. Screening for dysphagia and aspiration in acute stroke: a systematic review.
Dysphagia 2001 Winter;16:7–18.
Stroke: secondary prevention
• Attempt to modify ‘risk factors’ (see Box 6.22): target BP should be below
140/85mmHg (lower in diabetics). There is little to choose between
the different classes of drugs—all reduce the risk of further events.
Consider statins, especially in those with coexisting IHD.26
• Antiplatelet drugs: aspirin reduces the recurrence of stroke and death
from other causes. In the absence of absolute contraindications, aspirin
(300mg initially for 2 weeks and clopidogrel 75mg od thereafter)
should be given immediately after the onset of stroke symptoms once
haemorrhage has been ruled out. Patients should be treated chronically
with clopidogrel 75mg daily.
• Anticoagulants: to prevent recurrence of ischaemic stroke, warfarin is
superior to aspirin in valvular, non-valvular, and paroxysmal AF, but
it is associated with i risk of major bleeding. The balance of benefit
may depend on the patient group but generally favours warfarin,
particularly in valvular AF. Aim for an INR of 2–3, provided there are
no contraindications and regular checks of INR are practicable. Current
practice is to delay warfarinization for 2 weeks after the event, and to
repeat the scan where the infarct is very large or where there is clinical
suspicion of haemorrhagic transformation. There is no place for either
UFH or LMWH. In such cases, it is best to discuss the management with
a senior colleague. IV heparinization should be commenced immediately
in patients with proven cerebral venous thrombosis (regardless of the
presence of haemorrhagic change on CT), and many neurologists would
also do the same for carotid/vertebral dissection.
• Carotid endarterectomy: should be considered in all patients with >70%
of ipsilesional stenosis. The operation has an appreciable morbidity
(including further stroke) and mortality but appears to improve overall
prognosis in selected patients. In centres with experience of the
procedure, carotid angioplasty may be an alternative, particularly in
patients who are considered poor surgical candidates.
• PFO: some advocate closure using an endovascular device, but there
is only anecdotal evidence of its effectiveness. Current prospective
evidence suggests that stroke patients with PFOs treated with aspirin
or warfarin only do not have an i risk of recurrent stroke or death,
compared with controls.27
• HRT and the OCP: combined HRT increases the risk of ischaemic stroke
and should be stopped. The combined, but not the progestogen-only,
OCP also appears to be associated with an i risk of stroke. Switch to a
progestogen-only formulation or alternative forms of contraception.
References
26. Marshall RS, Mohr JP. Current management of ischaemic stroke. J Neurol Neurosurg Psychiat
1993;56:6–16.
27. Homma S, Sacco RL, Di Tullio MR, et al.; PFO in Cryptogenic Stroke Study (PICSS) Investigators.
Effect of medical treatment in stroke patients with patent foramen ovale: patent foramen ovale
in Cryptogenic Stroke Study. Circulation 2002;105:2625–31.
42
Brainstem stroke
Presentation
Sudden onset of:
• Headache, nausea, vomiting, vertigo.
• Weakness: bilateral or unilateral.
• Sensory symptoms (e.g. paraesthesiae): may be confined to the face and,
if unilateral, may be contralateral to weakness.
• Ophthalmoplegia, gaze deviation, or dysconjugate eye movements: in
unilateral pontine lesions, conjugate gaze deviation is directed away from
the lesion and towards the side of the hemiparesis if there is one. The
reverse applies for frontal cortical strokes.
• Horner’s syndrome.
• Ptosis: caused by a midbrain infarct in the absence of an accompanying
third nerve palsy or Horner’s syndrome is bilateral due to the levator
subnucleus of the IIIrd nerve being in the midline.
• Nystagmus.
• Hearing loss: caused by damage to the VIIth nerve nucleus or fascicle.
• Dysarthria or dysphagia.
• Ataxia: which may be uni-or bilateral due to dysfunction of cerebellar
connections.
• Impaired level of consciousness: ranges from transient loss of
consciousness to coma.
• Altered pattern of respiration.
Signs associated with brainstem dysfunction are explained under
E Examination of brainstem function 1, pp. 460–1, E Examination of
brainstem function 2, p. 462, and E Examination of brainstem function 3,
pp. 464–5. They result because of damage either to the nuclei (including
cranial nerve nuclei) within the brainstem, to the cranial nerves, or to the
long tracts which traverse and/or decussate within the brainstem. ‘Crossed
signs’ may occur in brainstem strokes, e.g. part of the lateral medullary/
Wallenberg’s syndrome consists of loss of pain and temperature sensation
from the contralateral trunk and limbs (crossed spinothalamic) and ipsi-
lateral loss of the same sensory modalities from the face (uncrossed tri-
geminal tract). There are a large number of other eponymous syndromes
associated with damage to particular zones within the brainstem. Learning
these is not particularly rewarding; better to concentrate on the principles
of brainstem anatomy.26
Causes
Thrombosis, embolism, haemorrhage, or vertebral artery dissection (espe-
cially following neck manipulation).
Assessment of severity
• Reduced level of consciousness and coma carry worse prognosis.
• Extent of brainstem dysfunction may be appreciated from systematic
examination of brainstem function (E Examination of brainstem
function 1, pp. 460–1; E Examination of brainstem function 2, p. 462;
E Examination of brainstem function 3, pp. 464–5).
• Basilar occlusion carries a very poor prognosis (80% mortality).
Brainstem stroke 427
Management
Consult a neurologist. The imaging modality of choice is MRI; this should
be performed urgently to rule out other diagnoses. Some centres may con-
sider intra-arterial thrombolysis in patients with basilar occlusion if the pa-
tient is referred swiftly. Urgent intervention is required for:
• Metabolic coma with brainstem depression, e.g. opiates (E Opioids,
p. 770).
• Transtentorial herniation causing progressive brainstem compression
(E Examination of brainstem function 3, pp. 464–5).
• Posterior fossa mass with tonsillar herniation causing brainstem
compression.
• Cerebellar haemorrhage with/without brainstem compression
(E Examination of brainstem function 3, pp. 464–5).
References
26. Rowland L (1991). Clinical syndrome of the spinal cord and brainstem. In: Kandel ER, Schwartz
JH, Jessell TM, eds. Principles of Neural Science, 3rd edn. Appleton & Lange, Norwalk, CT; pp.
711–30.
428
Cerebellar stroke
Presentation
The triad of headache, nausea/vomiting, and ataxia is the classical syn-
drome. But it occurs in <50% of cases and, of course, is common in a
number of other conditions. Patients present with symptoms and signs
which are often attributed to brainstem or labyrinthine causes.27,28 Always
consider the possibility of a cerebellar stroke as a serious alternative diag-
nosis because surgical decompression can be lifesaving if there is a mass
effect within the posterior fossa. If the diagnosis is a possibility, ask for an
urgent CT scan, or better still, an MRI.
• Headache, nausea/vomiting: sudden or progressive over hours to days.
Location of headache varies widely.
• Dizziness or true vertigo: occurs in 30% of cases.
• Visual disturbance: diplopia, blurred vision, or oscillopsia.
• Gait/limb ataxia: most alert patients report or demonstrate this.
• Nystagmus or gaze palsy.
• Speech disturbance: dysarthria or dysphonia in 50% of alert patients.
• Loss of consciousness: may be transient, but many present in coma.
• Hypertension.
Predisposing factors
• Hypertension (>50%).
• Greater proportion of embolic cause of stroke in cerebellar infarction.
• Anticoagulants: there is a disproportionately higher risk of cerebellar
haemorrhage (cf. intracerebral haemorrhage) in patients taking warfarin.
• Metastatic neoplasm.
Assessment of severity
Patients who present in coma, or subsequently develop it, will die unless
they receive surgical treatment. There is debate about the prognosis of
those who remain alert.
Management
Make a definitive diagnosis with an urgent CT scan. (Is there a haemor-
rhage/infarct? Is there distortion of the fourth ventricle and aqueduct with
dilatation of the lateral ventricles?) Liaise with the regional neurosurgery
unit early.
Priorities
1 Stabilize the patient and protect the airway (E Coma: assessment,
pp. 348–9).
2 Correct the bleeding tendency or effects of anticoagulants.
3 Intensive care/high dependency ward nursing observations if the
patient is not transferred to a neurosurgical centre immediately.
4 Definitive surgical decompression, if necessary and possible.
References
27. Dunne JW, Chakera T, Kermode S. Cerebellar haemorrhage—diagnosis and treatment: a study
of 75 consecutive cases. Q J Med 1987;64:739–54.
28. [No authors listed]. Cerebellar stroke. Lancet 1988;1:1031–2.
Cerebellar stroke 429
430
Management
The objective is to prevent recurrence or a complete stroke. The risk
of stroke must be assessed, using a validated scoring system such as the
ABCD2*. For management of TIAs, see Box 6.26.
The ABCD2* is a prognostic score to identify people at high risk of stroke
after a TIA. It is calculated based on:
• A: age (≥60 years, 1 point).
• B: BP at presentation (≥140/90mmHg, 1 point).
• C: clinical features (unilateral weakness, 2 points; or speech disturbance
without weakness, 1 point).
• D: duration of symptoms (≥60min, 2 points; or 10–59min, 1 point).
The calculation of ABCD2 also includes the presence of DM (1 point). Total
scores range from 0 (low risk) to 7 (high risk).
Further reading
Johnstone JC, Rothwell PM, Nguyen-Huynh MN, et al. Validation and refinement of scores to predict
very early stroke risk after transient ischaemic attack. Lancet 2007;369:283–92.
432
Wernicke–Korsakoff syndrome
• WE comprises the triad of ophthalmoplegia (nystagmus, VIth nerve
palsy), ataxia (cerebellar type), and confusional state. In Korsakoff ’s
syndrome, confusion predominates, often with overt psychosis, amnesia
(antegrade and retrograde), and confabulation. Withdrawal symptoms
may also occur.
• Diagnosis: reduced red cell transketolase activity (not usually available).
• Treat with IV thiamine (Pabrinex®), two pairs of ampoules tds for
2 days; if no response, discontinue; if there is an improvement, continue
one pair of ampoules IM/IV daily for 5 days or as long as improvement
continues. Ongoing oral thiamine treatment should follow parenteral
thiamine.
Seizures
• Withdrawal seizures are typically self-limiting; if needed, use IV
diazepam (Diazemuls®) 10mg over 5min (E Status epilepticus (tonic–
clonic) 1, pp. 408–9).
• The most important issue here is to prevent the occurrence of seizures
in the first place. This is mainly achieved by treating the patient with
an appropriate alcohol withdrawal regime, usually chlordiazepoxide or
diazepam (see Box 6.29 and Table 6.7). Consider adding lorazepam to
prevent further seizures.
• Review the reducing withdrawal regime if the seizure occurred while
already on a regime, as it may be suboptimal or reducing too quickly.
• A carbamazepine regime may be used for treatment of alcohol
withdrawal; however, evidence shows this is not superior to
benzodiazepines in seizure prevention, and combining both conferred
no added benefit.
• Phenytoin is no longer recommended to treat alcohol withdrawal seizures.
Follow-up
Arrange a referral to an alcohol dependence clinic.
438
Table 6.7 Titrated fixed-dose chlordiazepoxide protocol for treatment of alcohol withdrawal
Typical recent daily consumption 15–25 units 30–49 units 50–60 units
Severity of alcohol dependence MODERATE SADQ score 15–25 SEVERE SADQ score 30–40 VERY SEVERE SADQ score 40–60
Starting doses of chlordiazepoxide 15–25mg qds 30–40mg qds 50mg qds
Chapter 6
Neuromuscular respiratory
failure: assessment
Presentation
A number of disorders of the peripheral nerve, neuromuscular junction,
or muscle may present with hypercapnic (type 2) respiratory failure or
impending failure. There are many differences between these conditions,
but consider the diagnosis in the presence of the following features:
• Limb weakness: progressing over hours or days with diminished/no
reflexes but no UMN signs.
• Neck flexion/extension weakness: typical for many causes. Often mirrors
bulbar dysfunction.
• Muscular tenderness or pain: may be a feature (e.g. back pain in GBS, limb
pain in radiculitis/plexopathy or vasculitic neuropathy, muscle pain in
inflammatory myopathy).
• Facial weakness.
• Ptosis (myasthenia, botulism, Lambert–Eaton, myopathy).
• Bulbar dysfunction: is a particularly ominous sign because it may lead to
improper clearance of secretions and aspiration.
• Paradoxical abdominal movement: if the diaphragm is paralysed, it moves
passively into the thorax, with a fall in intrapleural pressure produced
by expansion of the ribcage in inspiration. As a result, the anterior
abdominal wall also moves in (rather than out) during inspiration.
• Dyspnoea or distress in supine position: if the diaphragm is paralysed,
movement of abdominal contents towards the thorax is more
prominent when the patient lies flat because gravity no longer acts
to counteract this passive movement. As a result, the volume of air
inspired is reduced. This is a rare, but important, cause of orthopnoea.
• Sensory symptoms: may be present with or without glove-and-stocking
sensory loss.
• Autonomic instability: may be a prominent feature of GBS and may lead
to cardiac arrest.
• Pneumonia: in known neuromuscular disease.
• Respiratory arrest: a common pitfall is to consider the degree of
respiratory distress unimpressive. Peripheral weakness, in combination
with an expressionless ‘myopathic’ facies, may lead to a false sense of
well-being when the patient may, in fact, be confronting an impending
respiratory arrest.
Assessment of severity
• Measurement of forced vital capacity (FVC) is mandatory (measured
with Wright respirometer available from an anaesthetic nurse or
ICU). Note that O2 saturations, peak flow rate, and forced expiratory
volume in 1s (FEV1) do not correlate with the degree of neuromuscular
impairment.
• FVC <30mL/kg causes impaired clearance of secretions.
• FVC <15mL/kg suggests ventilatory failure and is an indication for
immediate intubation and ventilation, regardless of other parameters
of respiratory function.
• ABGs: hypercapnia occurs relatively late.
• CXR: to determine the extent of consolidation if there is concomitant
aspiration or infective pneumonia. Subtle linear atelectasis is often seen
as a direct result of reduced lung volume.
42
Neuromuscular respiratory
failure: investigations and management
For investigations of neuromuscular respiratory failure, see Box 6.30.
Management
• Assess severity and measure FVC frequently.
• Consider intubation and ventilatory support if in adults FVC <1L or
15mL/kg (or there is a progressive decline). Do not use suxamethonium
as a muscle relaxant. It may cause a sudden rise in K+ in patients with
denervated muscles.
• Liaise with the neurologist early. Consider transfer to a regional
neurology unit if the patient is well and FVC >25mL/kg and stable. If
the patient is unwell and FVC <15mL/kg or falling precipitously from a
higher level, intubate electively and then consider transfer. All patients
should be accompanied by an anaesthetist.
• For investigations, see Table 6.8. Most of these conditions will not come
into the differential, but it is advised that blood be taken for virology
screen and autoimmune profile, and 20mL be saved for retrospective
analysis if required.
• ECG monitoring and frequent observation of BP and pulse are required
if GBS is suspected, because there is a high incidence of autonomic
instability.
• Consider specific therapies (see Table 6.8) and:
• GBS (E Guillain–Barré syndrome, pp. 452–3).
• Myasthenia gravis (E Myasthenic crises, pp. 444–6).
• Botulism (E Botulism, pp. 454–5).
• Heavy metal intoxication (E Drug overdoses and antidotes, pp. 742).
• Organophosphate exposure (E Drug overdoses and antidotes,
p. 742).
• Porphyria.
• Rhabdomyolysis (E Rhabdomyolysis, pp. 306–7).
• SC heparin prophylaxis for DVT.
• Enteral nutrition should be considered early.
Myasthenic crises
Presentation
• Generalized weakness: usually worse proximally, and classically painless
and fatiguable. There may be ptosis and diplopia. Reflexes and sensation
are normal. Patients with pure ocular myasthenia for >2 years rarely
generalize.
• Dyspnoea: the patient may not, at first glance, appear very distressed.
An expressionless myopathic facies, together with weak muscles of
respiration, may give a false sense of well-being.
• Bulbar dysfunction: is potentially dangerous, as it may lead to impaired
clearance of secretions and aspiration pneumonia.
• Exhaustion and ventilatory failure: leading to coma.
• History of penicillamine use: may cause a syndrome identical to
idiopathic myasthenia gravis.29
Common predisposing factors
Infection, surgery, and drugs (see Box 6.31). NB Corticosteroids used
to treat myasthenia can initially lead to an acute crisis (so start low and
go slow).
Assessment of severity
• Vital capacity is the most useful indicator. ABGs are not sensitive enough
and demonstrate hypercarbia late.
• Bulbar dysfunction.
Cholinergic crisis
It may not be possible on clinical evaluation to distinguish between
worsening myasthenia and excessive anticholinesterase treatment (which
leads to weakness by producing depolarization block). Consider with-
drawing anticholinesterases only after consulting a neurologist. Note that
cholinergic crisis is very rare, compared to myasthenic crisis.
Management
• Stabilize the patient: protect the airway; intubate and ventilate if
necessary. Ensure there are no electrolyte disturbances (d K+, d Ca2+,
i Mg2+) or drugs prescribed which exacerbate weakness.
• Consider Tensilon® (edrophonium) test (E Tensilon® (edrophonium)
test, p. 445). Anticholinesterase treatment may be helpful if cholinergic
crisis is excluded. If there is no effect with Tensilon®, reconsider the
diagnosis. Withhold all anticholinesterase medications for 72h. The
Tensilon® test may be repeated at intervals.
• Immunosuppression should be supervised by a
neurologist: prednisolone 60–80mg/day produces improvement after
10–12 days but should be introduced with care (start low and go slow)
because there may be initial worsening of weakness. High-dose steroids
are given until remission occurs. Azathioprine (2.5mg/kg) has also been
used for maintenance therapy but takes months to have an effect.
• Plasmapheresis is used to remove circulating antibody. It usually involves
exchange of 50mL/kg/day over several days. Most centres use IVIG
therapy, instead of plasmapheresis.
Myasthenic crises 445
Ice test
1 The test consists of the application of ice to the eyes for 2–3min,
ensuring that the ice is covered (e.g. in a bag) to prevent ice burns.
Avoid prolonged exposure (cold burns and false negatives).
2 If positive, the patient’s ptosis improves.
3 The results of the test can be deemed positive with an improvement
of the patient’s diplopia or a raise of 2mm of the palpebral fissure
following the removal of the ice pack.30
References
29. Thomas CE, Mayer AS, Gungor Y, et al. Myasthenia gravis: clinical feature, mortality, complica-
tions, and risk factors for prolonged intuition. Neurology 1997;48:1253–60.
30. Sethi KD, Rivner MH, Swift TR. Ice pack test for myasthenia gravis. Neurology 1987;37:1383–5.
Myasthenic crises 447
48
Guillain–Barré syndrome
Presentation
• Progressive weakness of more than one limb: in an individual who may
recently have experienced a mild respiratory or GI febrile illness.
Weakness is as commonly proximal as distal. It is usually symmetrical
but may be asymmetrical.
• Diminished tendon reflexes/areflexia: is typical.
• Sensory symptoms: paraesthesiae often precedes weakness. Sensory loss
is not usually profound, although there may be a glove-and-stocking
distribution impairment of two-point discrimination, joint position, and
vibration sense. If there is a sensory level, spinal cord compression
(E Spinal cord compression: management, p. 450) should be the
diagnosis, until proven otherwise.
• Limb or back pain: is a major symptom in 30%. Back pain can precede
symptoms of weakness.
• Cranial nerve dysfunction: occurs in 50%. Bulbar function and muscles of
mastication are affected in 30%; ocular muscles in 10% of patients.
• Ventilatory failure: see E Neuromuscular respiratory failure: assessment,
pp. 440–1.
• Autonomic dysfunction: is common—sweating, tachycardia, sudden
swings of BP, dysrhythmias, and cardiac arrest. Bladder or bowel
dysfunction occurs, but if it is present from the outset or if it is
persistent, reconsider the diagnosis.
• Miller–Fisher variant: ophthalmoplegia (giving rise to diplopia), ataxia, and
areflexia, without significant weakness or sensory signs. Associated with
anti-GQ1b antibodies in the serum.
Causes
GBS probably represents an immune-mediated attack on peripheral nerves.
Infections which may precede it include CMV, Campylobacter jejuni, EBV,
hepatitis B, Mycoplasma, and HSV.
Assessment of severity
Poor prognostic features on presentation include:
• Rapid onset.
• Requirement for ventilation (bulbar compromise, reducing vital capacity,
respiratory failure).
• Age >40 years.
• Reduced amplitude of compound muscle action potential (<10% of
control) and extensive spontaneous fibrillation in distal muscles suggesting
denervation (NB electrophysiological studies may be normal in early GBS).
• Presence of autonomic dysfunction.
• Axonal variant (often with preceding C. jejuni infection).
A grading system has been devised to follow a patient’s progress:
• Grade 1: able to run.
• Grade 2: able to walk 5m but not to run.
• Grade 3: able to walk 5m with assistance.
• Grade 4: chair-/bed-bound.
• Grade 5: ventilated.
Practice points
Acute onset of bilateral facial palsy is usually due to GBS. Long-standing
bilateral facial weakness is usually due to sarcoid, HIV, facial-onset sen-
sorimotor neuropathy, or Lyme disease.31
Management
It is important to appreciate that GBS is a diagnosis of exclusion, with an
extensive differential. The pace at which alternative diagnoses need to be
excluded depends upon the history and findings.
Management of a patient with GBS is that of any patient with neuromus-
cular paralysis, although there are a few important specific measures:
• Monitor FVC twice daily.
• Autonomic instability is a common feature, so ECG monitoring and
frequent assessment of BP and pulse are advisable, particularly in any
patient with bulbar or respiratory involvement (NB tracheal suction may
lead to bradycardia or asystole).
• CSF analysis may be required. CSF protein may be normal initially
but characteristically rises markedly and peaks in 4–6 weeks. If CSF
lymphocytes are prominent in number, consider HIV seroconversion.
• Steroids are of no benefit in GBS and can worsen matters.
• Plasma exchange is proven to be better than supportive treatment
alone. IVIG (0.4g/kg for 5 days) is as effective as plasma exchange and is
currently the standard treatment. Therapy should not be commenced
without prior discussion with a neurologist.
• DVT prophylaxis.
For key points in the management of GBS, see Box 6.34.
Prognosis
Around 65% are able to resume manual work; 8% die in the acute stage
(usually from autonomic dysfunction or PE), and the remainder are left with
residual disability. The prognosis is worse in those with more severe disease.
References
31. Winer JB. An update in Guillain-Barré syndrome. Autoimmune Dis 2014;2014:793024.
45
Botulism
Presentation
Botulism is caused by exotoxins of Clostridium botulinum. There are three
syndromes: food-borne, SC drug users wound, and infantile. The latter two
causes are rare and will not be discussed here. The most common form of
botulism is food-borne, with outbreaks usually attributed to canned food.
Patients present with symptoms usually within 18h of ingestion of the toxin
(see Box 6.35):
• Sore throat, fatigue, dizziness, blurred vision.
• Nausea, vomiting, constipation.
• Rapidly progressive weakness, often beginning in the extraocular
and/or pharyngeal muscles and descending symmetrically in severe
cases to give upper and lower limb paralysis and respiratory failure
(E Neuromuscular respiratory failure: assessment, pp. 440–1;
E Neuromuscular respiratory failure: investigations and management,
p. 442).
• Paraesthesiae may occur, but there are no sensory signs.
• Parasympathetic dysfunction causes a dry mouth, ileus, and dilated non-
reactive pupils in an alert patient. This pupillary response may help to
distinguish botulism from other neuromuscular disorders; however, in
most cases, the pupils remain reactive.
Wound botulism is similar, except GI upset does not occur.
Assessment of severity
Limb weakness and ventilatory failure are indicators of severe dis-
ease. Patients with these features have a worse prognosis, as do patients
>20 years and those who have ingested type A toxin.
Management
• Assess severity; measure FVC frequently, and attempt to exclude
other important causes of neuromuscular failure (E Neuromuscular
respiratory failure: assessment, pp. 440–1). In particular, a Tensilon®
test should be performed to exclude myasthenia gravis (E Tensilon®
(edrophonium) test, p. 445); nerve conduction should be normal, but it
is important to exclude GBS (E Guillain–Barré syndrome, pp. 452–3);
EMG is frequently abnormal in botulism (decrement of compound
muscle action potential at slow rates of repetitive stimulation of 3s–1 and
facilitation of motor response at rapid rates of 50s–1). Serum and stool
should be assayed for toxin and C. botulinum.
• General management is described elsewhere (E Neuromuscular
respiratory failure: assessment, pp. 440–1; E Neuromuscular
respiratory failure: investigations and management, p. 442).
• Specific treatment: if botulism is suspected, 10 000U of trivalent (A,
B, E) antitoxin should be administered IV immediately and at 4-hourly
intervals. 720% of patients have minor allergic reactions to this and
require corticosteroid and antihistamines, as for anaphylaxis (for
supplies outside normal working hours, contact Department of Health
Duty Officer (UK), tel: 020 7210 3000).
Botulism 455
Tetanus
Presentation
Tetanus is caused by the effects of exotoxins produced by Clostridium tetani.
It occurs after C. tetani spores have gained access to tissues. The wound
may be very trivial, and in 20% of cases, there is no history or evidence
of injury. Incubation of spores may take weeks, but most patients present
within 15 days with:
• Pain and stiffness of the jaw.
• Rigidity and difficulty in opening the mouth: trismus or ‘lockjaw’.
• Generalized rigidity of facial muscles, leading to the classical risus
sardonicus or clenched teeth expression.
• Rigidity of body musculature, leading to neck retraction and spinal
extension.
• Reflex spasms are painful spasms elicited by stimuli such as pressure
or noise. These usually occur 1–3 days after the initial symptoms and
are potentially very dangerous, as they may endanger respiration and
precipitate cardiorespiratory collapse.
• Convulsive seizures.
• Autonomic dysfunction with both sympathetic (sweating, hypertension,
tachycardia, dysrhythmias, hyperpyrexia) and parasympathetic
(bradycardia, asystole) involvement.
Causes
Exotoxin blocks inhibitory pathways within the CNS.
Assessment of severity
Rapidly progressing features and the onset of spasms signify worse disease
and prognosis.
Management
• Assess severity: in severe spasms/respiratory failure, ventilation will be
required. Otherwise patients should be nursed in a quiet, dark room (to
reduce reflex spasms) under close observation. Sedation with diazepam
may be necessary, but beware of respiratory depression.
• General management: as discussed under E Neuromuscular respiratory
failure: assessment, pp. 440–1.
• Specific treatment: human hyperimmune globulin 3000–10 000U IV
or IM should be given to neutralize the circulating toxin. This will not
ameliorate existing symptoms but will prevent further binding of the
toxin to CNS. Penicillin IV (1.2g qds), or alternatively tetracycline 500mg
qds, should be prescribed to treat C. tetani.
• Wound care and debridement as appropriate: swabs should be sent for
culture but often do not grow the organism.
• Prophylaxis in patients who have previously been immunized: for any
wound, give a booster dose of tetanus toxoid if the patient has not
received a booster in the last 10 years. If the wound appears dirty and
infected, or the patient has never been immunized/cannot recall/unable
to give a history, give human antitoxin (250U IM), in addition to the
toxoid.
Tetanus 457
458
Table 6.9 GCS*
Eye opening
Spontaneously 4
To speech 3
To painful stimulus 2
No response 1
Best verbal response
Orientated 5
Disorientated 4
Inappropriate words 3
Incomprehensible sounds 2
No response 1
Best motor response
Obeys verbal commands 6
Localizes painful stimuli 5
Withdrawal to pain 4
Flexion to pain 3
Extension to pain 2
No response 1
*
Adapted from The Lancet, 304(7872), Graham Teasdale and Bryan Jennett, ‘Assessment of
coma and impaired consciousness: a practical scale’, pp. 81–4, Copyright (1974), with permission
from Elsevier.
One minute
Brain death
This is irreversible loss of the capacity for consciousness combined with
irreversible loss of the capacity to breathe. Without the brainstem, both
these functions are lost. But patients with severe, irreversible brain damage
who have no brainstem function may survive for weeks or months, pro-
vided they have a normal circulation and are mechanically ventilated.
Criteria for brain death have therefore been developed. It has been shown
that patients who fulfil these, even if they are ventilated, will eventually de-
velop cardiovascular collapse.
Preconditions
• There must be no doubt that the patient has irremediable structural
brain damage which has been diagnosed with certainty. Usually, this is a
head injury or an intracranial haemorrhage, but it may be anoxia post-
cardiac arrest when it is not always possible immediately to be certain
that brain damage is irremediable.
• The patient must be in apnoeic coma (unresponsive to noxious stimuli
and on a mechanical ventilator), with no spontaneous respiratory effort.
• There must be no possibility of drug intoxication and no paralysing or
anaesthetic drugs should have been administered recently. Hypothermia
must be excluded as a cause of coma and the core temperature (rectal
or external auditory meatus) should be >35°C.
• There must be no significant metabolic, endocrine, or electrolyte
disturbance, either causing or contributing to coma.
Tests for confirming brain death
All brainstem reflexes must be absent
• Pupils fixed and unresponsive to bright light (they need not be dilated).
Paralytic eye drops, ocular injury, and lesions of the IInd/IIIrd cranial
nerves may pose problems in this assessment.
• Absent corneal reflexes.
• Absent VORs on irrigation of each ear, in turn, with 20mL of ice-cold water.
• No motor response within the cranial nerve distribution (eye, face,
head) elicited by stimulation of any somatic area (nail bed, supraorbital,
and Achilles tendon pressure on each side). Purely spinal reflexes, e.g.
deep tendon reflexes, may be retained.
• No reflex response to touching the pharynx (gag reflex) nor to a suction
catheter passed into the trachea (cough reflex).
Apnoea
• No respiratory movements when the ventilator is disconnected and
PaCO2 reaches 6.65kPa. (In order to avoid anoxia during this procedure,
the patient should be ventilated with 100% O2 for 10min beforehand;
during disconnection, 6L/min 100% O2 should be delivered via a tracheal
catheter. If just prior to disconnection, PaCO2 is <3.5kPa, give 5% CO2 in
O2 via the ventilator until this level is reached, usually within 5min.)
The tests must be performed by two experienced clinicians, and all the above
should be repeated after an interval which depends upon the clinical context.
NB Consider the patient a potential organ donor. Discuss with relatives,
and contact the transplant coordinator for your area. Alternatively, contact
the duty officer for the UK Transplant Support Service (tel: 01179 757575).
Chapter 7 469
Infectious diseases
Fig. 7.1 Erythema nodosum. The lesions can be very faint but are indurated and
painful on palpation. Reproduced from MacKie R. Clinical Dermatology, 2003, with
permission from Oxford University Press.
47
Malaria: assessment
There are 72000 cases of malaria in the UK each year, with 1% mortality.
The 2016 UK national guidelines can be accessed at: M https://www.
journalofinfection.com/article/S0163-4453(16)00047-5/pdf
Organism
• P. falciparum is the causative agent of the most severe and potentially
fatal form of malaria.
• P. vivax and P. ovale may cause chronic, recurrent disease, and there is
emerging evidence that P. vivax can cause more severe presentations
than previously thought. P. malariae rarely causes life-threatening disease
and can be managed as an outpatient.
• Different species can be distinguished by their morphology on a blood
film, but this needs expert interpretation. Malaria antigen blood dipstick
testing can differentiate reliably between P. falciparum and P. vivax. Mixed
infections can occur. If in doubt, therapy should be directed against
P. falciparum.
Symptoms
• Incubation period from 6 days minimum up to 3 months (usually within
1 month) for P. falciparum, up to 2 years for P. vivax and P. ovale, and up
to 20 years for P. malariae.
• High fever, chills, and rigors, followed by sweating. Alternate-day fever is
described, but many patients do not exhibit this.
• Headache is a very common symptom. If associated with impairment
in consciousness, behavioural change, or seizure activity, consider
hypoglycaemia. Cerebral malaria is defined as unrousable coma (GCS
score ≤9). Retinal haemorrhages, drowsiness, and other neurological
signs may indicate lesser cerebral involvement, which may progress.
• Generalized flu-like symptoms, malaise, and myalgia.
• Abdominal symptoms: anorexia, pain, vomiting, and diarrhoea
(especially in children).
Examination
• No specific features.
• Pyrexia in most, but not all, cases, often up to 40°C during paroxysms.
• Splenomegaly.
• Anaemia and jaundice.
• Indications of severity (see Box 7.2).
Malaria: assessment 475
Malaria: investigations
All patients should have FBC, U&Es, creatinine, LFTs, and blood glucose. In
ill patients, blood gases, blood cultures, lactate, and clotting studies should
be performed. Urine dipstick/MC&S, stool culture, CXR, and LP may be
appropriate.
• FBC: anaemia, non-immune haemolysis, leucopenia, and
thrombocytopenia suggest P. falciparum.
• Blood films: repeated blood samples over several hours should be
examined by an experienced individual if the patient is unwell and
malaria was not found on the initial blood film. At least three films
should be examined (separated by at least 12h). A malaria antigen blood
dipstick test for P. falciparum should also be performed (for P. falciparum,
this is as sensitive as a blood film read by an experienced microscopist
but is less sensitive for P. vivax and P. ovale). If in doubt, seek advice
from an expert urgently and send the films to a reference laboratory for
a definitive opinion. Thin films make speciation easier and are used to
calculate the percentage parasitaemia.
• Parasitaemia: severe—>2% parasitaemia or schizonts on film.
• G6PD status: some treatment options cause haemolysis in G6PD
deficiency.
• Glucose: hypoglycaemia may occur with P. falciparum or IV quinine
therapy, especially during pregnancy.
• U&Es, LFTs: ARF and haemoglobinuria may occur in severe P. falciparum.
Elevated unconjugated bilirubin, AST, and LDH reflect haemolysis.
• Blood cultures: even if malaria is confirmed. Other infections, such as
Gram –ve septicaemia, may also be present (termed ‘algid’ malaria).
• Head CT scan and LP: may be required in suspected cerebral malaria to
exclude other pathologies.
• ABG: metabolic acidosis (pH <7.3) indicates severe malaria.
Malaria: management 477
Malaria: management
General measures
(See Box 7.3.)
• Malaria should be managed in consultation with an ID specialist.
• All cases of P. falciparum malaria should be admitted to hospital.
• Lower fever with tepid sponging and paracetamol.
• If severe malaria or cerebral malaria, admit to HDU/ITU.
• Fits can be controlled with diazepam.
• In severe cases, catheterize the bladder to monitor urine output, and
insert a CVP line to help manage fluid balance, as ARDS can easily be
precipitated in these patients. Renal support may be required.
• 2-hourly blood glucose estimations. Regular temperature, pulse, and
respiratory rate (TPR), BP, and urine output.
• Pre-treatment ECG required when IV quinine is being used (causes QT
prolongation), but do not delay giving therapy.
• In severe cases, repeat blood films at least twice daily until parasitaemia
is clearly falling, and then perform daily. Daily U&Es, FBC, and LFTs.
• Thrombocytopenia is usual and rarely needs support, unless platelet
count <20 × 109/L or bleeding.
• Discuss any severe or complicated malaria with an ID unit early.
P. falciparum acquired on the Thai borders and in neighbouring countries
may be drug-resistant and need treatment with less commonly available
antimalarials.
478
Malaria: antimalarial therapy
For advice in the UK, phone the Imported Fever Service on 0844 7788990
(treatment); or for travel prophylaxis, phone the National Travel Health
Network and Centre (NaTHNaC) on 0845 6026712. See Box 7.3 for key
points in the management of malaria.
P. falciparum
Uncomplicated, non-severe P. falciparum in adults
• Artemether-lumefantrine: if weight >35kg, four tablets stat, then four
tablets at 8, 24, 36, 48, and 60h.
• Atovaquone/proguanil (Malarone®) is licensed for the treatment of
non-severe P. falciparum. For adults, four tablets od for 3 days.
• Quinine 600mg tds PO, reduced to bd if the patient develops severe
cinchonism (nausea, tinnitus, deafness). For 5–7 days until afebrile and
blood film negative plus either doxycycline 100mg bd PO or (particularly
if pregnant or <12 years old) clindamycin 450mg tds PO for 7 days.
• Parenteral treatment of malaria should be given if there is >2%
parasitaemia, the patient is pregnant, or in patients unable to swallow
tablets.
Complicated or severe P. falciparum in adults
• Discuss with an ID physician and ITU at the earliest opportunity.
• Artesunate regimen: 2.4mg/kg given as an IV injection stat, repeated
at 12h, 24h, and then daily thereafter. After completion of a minimum
of 24h therapy (maximum 5 days), a full course of an oral artemisinin-
based combination therapy (ACT) should be taken when the patient can
tolerate oral medication.
• Where artesunate cannot be obtained rapidly, use quinine
dihydrochloride IV 20mg/kg in 5% glucose or glucose-saline over 4h
(maximum dose 1.4g). After 8h, the patient should be treated with
quinine at 10mg/kg infused over 4h (maximum dose 0.7g), repeated
every 8h for 48h. Watch carefully for toxicity (QT prolongation and
hypoglycaemia). Consider change to an oral regime at 48h with quinine
600mg tds to complete 5–7 days of treatment.
• Quinine treatment should be accompanied by a second drug
(doxycycline 100mg bd or clindamycin 450mg tds) for 7 days.
• Chloroquine resistance is widespread. It is not used to treat P. falciparum
malaria.
Intensive care management of severe or complicated malaria
• Careful management of fluid balance to optimize O2 delivery and reduce
acidosis.
• Monitoring of CVP to prevent pulmonary oedema and ARDS.
• Regular blood glucose monitoring to detect and prevent hypoglycaemia.
• Consider broad-spectrum antibiotics if evidence of shock or
concomitant bacterial infection.
• Haemofiltration for renal failure or control of acidosis or fluid/
electrolyte imbalance.
• Consider medication to control seizures.
480
Table 7.2 Rashes: features of the common childhood exanthems
Infection Morphology Distribution Incubation Infectivity Associated features Complications
Varicella Clear vesicles on Lesions occur 10–21 days 4 days before Pyrexia 1–2 days, flu- Bacterial infection
(chickenpox) erythematous in crops, start rash to 5 days like prodrome Varicella pneumonia
Chapter 7
(See Table 7.2.)
base (5–12mm), on trunk, after last Encephalitis
evolving into and spread lesion scabs
pustules that peripherally. Reactivates as herpes zoster
burst and crust Mucosal lesions
common
Measles Maculopapular, Starts on head 10–14 days A few days Co ryza, Otitis media, bacterial
morbilliform and neck, before until conjunctivitis, cough, pneumonia, measles
spreading up to 18 days lymphadenopathy, pneumonia, encephalitis
peripherally after rash Koplik’s spots in late (1:1000), deafness, subacute
onset prodrome sclerosing panencephalitis
(SSPE)
Infectious diseases
Meningococcal infection: assessment
Meningococcal meningitis and septicaemia are severe systemic infections
caused by Neisseria meningitidis. 710% of the population carry N. meningitidis
in their nose or throat, but few develop invasive disease. Outbreaks are
most common in teenagers, young adults, and crowded environments.
Meningism is absent in 30% of cases. It is a notifiable disease, necessitating
an urgent phone call to Public Health, including out of hours.
Rashes
Purpuric lesions are the hallmark of meningococcal septicaemia, but several
different patterns may be seen either separately or together. Furthermore,
rash is a late sign, and the absence of a rash should not detract from a pos-
sible diagnosis of meningococcal infection.
• Petechial: initially 1–2mm discrete lesions, frequently on the trunk, lower
body, and conjunctivae. Enlarge with disease progression and correlate
with thrombocytopenia and DIC, which are poor prognostic signs.
• Ecchymoses: the petechial lesions coalesce and enlarge to form
widespread purpura and ecchymoses, particularly on the peripheries.
• Purpura fulminans: in extreme cases, entire limbs or sections of the body
become purpuric and necrotic due to DIC and vascular occlusion.
• Maculopapular: non-purpuric and easily mistaken for a viral rash,
occurring early in some patients. May look like flea bites.
Presentation
• Predominantly septicaemia: symptoms and signs of septicaemia, shock,
and respiratory distress. May progress from first signs to death within
a couple of hours. Purpuric rash almost always develops but may be
absent at presentation. Patient often not meningitic. Give antibiotics
immediately after blood cultures. Call ICU immediately. Do not perform
LP or CT scan.
• Predominantly meningitis: no shock, no respiratory distress. Neurological
signs predominate, and a rash may or may not be present.
• Bacteraemia without meningitis or sepsis: non-specific flu-like symptoms ±
rash. Positive blood cultures. Rash less often present. May develop focal
spread such as septic arthritis and pericarditis.
• Chronic meningococcaemia: low-grade fever, purpuric rash, and arthritis,
often confused with gonococcaemia. Sepsis and meningitis do not
develop, and the illness may last for weeks unless recognized.
• Recurrent meningococcaemia: suspect immunocompromise, particularly
complement deficiency.
Antibiotics
IV 2g cefotaxime or ceftriaxone (E Meningococcal infection: management,
p. 488).
Investigations
• Blood cultures: immediately. Also take EDTA blood sample for PCR and
throat swab. FBC, U&Es, glucose, LFTs, clotting.
• Brain CT scan: recent guidelines from the British Infection Association
recommend that an LP can be performed without a head CT scan
in patients with simple meningitis, i.e. not obviously septicaemic, no
focal neurological signs, and no decrease in conscious level. A CT
scan should be performed prior to LP in all cases of meningitis with
depressed consciousness (GCS score <12 or fluctuating coma score,
focal neurology, papilloedema, fits, bradycardia, and hypertension).
Give antibiotics before CT scan. Do not delay treatment. Do not delay
resuscitation or transfer of a sick patient to ICU to perform an LP, but if
feasible and safe, consider once appropriate care instigated.
• LP: do not perform in patients with predominantly septicaemia (may be
dangerous if DIC). Do not delay antibiotics beyond 30min (see Box 7.4).
Differential diagnosis of purpuric rash and fever
• Gonococcaemia.
• Bacterial septicaemia with DIC.
• Haematologic malignancy with sepsis.
• Henoch–Schönlein purpura.
• In travellers consider:
• Rocky mountain spotted fever (USA).
• VHFs (E Viral haemorrhagic fevers, p. 492).
Meningococcal infection: management
Antibiotic therapy
(See Box 7.5.)
• Treatment must be started immediately if a diagnosis of predominantly
meningococcal septicaemia is suspected. If the diagnosis is predominantly
meningitis, perform an LP if no contraindications, but do not delay for
>30min before antibiotics are given.
• If called by a GP, then instruct the GP to administer benzylpenicillin
1.2g IM/IV or a third-generation cephalosporin before arranging urgent
transfer to hospital.
Treatment
• Cefotaxime 2g qds or ceftriaxone 2g bd.
• If the patient has had definite anaphylaxis or near anaphylaxis to
penicillin, then urgent discussion with microbiology or ID experts
is indicated. Chloramphenicol 25mg/kg qds (max. 1g qds) may be
considered, but advice should be sought.
• If there is a possibility that the patient has pneumococcal meningitis and
is severely obtunded, start dexamethasone 0.15mg/kg (to max. 10mg)
IV qds for 4 days, with or just before the first dose of antibiotics—this
has been shown to reduce morbidity substantially.
Prophylaxis
• Notify the case immediately to the local Consultant in Communicable
Disease Control (CCDC).
• The CCDC will advise on antibiotic prophylaxis.
• Close contacts only, i.e. household, kissing contacts, close family,
institutional contacts (if from a nursing home), etc. in previous
7–10 days.
• Staff members only if involved in resuscitation or ET intubation and
suctioning without a mask on.
• Drug choice: ciprofloxacin 500mg as a single dose is now the
prophylactic agent of choice for all age groups; alternatives include
rifampicin 600mg bd for 2 days or ceftriaxone 250mg IM stat.
Supportive therapy
• Intensive care monitoring is essential in any shocked patient or if
significant impairment of consciousness.
• If shocked, urgent fluid replacement, aided by invasive monitoring, is
essential. Supportive care for septic shock is discussed under E Sepsis
syndrome and septic shock, pp. 336–7.
• Treatment of DIC is supportive.
Prognosis
• Meningitis without shock: mortality 710%, neurological sequelae
uncommon. Coma is a poor prognostic sign.
• Fulminant meningococcaemia: mortality related to organ failure between
20% and 80%.
Further information is available in the form of a NICE guideline at
M https://www.nice.org.uk/guidance/cg102
Management
• Supportive care: if toxaemic, admit to ITU. Urinary catheter and CVP line
to manage fluid balance. May need renal support.
• Antibiotics: multiple drug resistance has become a problem, and
ampicillin can no longer be used for empirical treatment. Third-
generation cephalosporins (e.g. ceftriaxone 2g IV od) are now the
empiric treatment of choice until sensitivities are known; if sensitive,
quinolones, e.g. ciprofloxacin, 750mg bd PO for 14 days or 400mg bd IV
may be appropriate. Azithromycin is a potential oral alternative if the
isolate is quinolone-resistant.
• Surgery: is essential for bowel perforation (add metronidazole).
• Infection control: notify the case to Public Health. Spread is faecal/oral,
and individuals should not prepare food until follow-up stool cultures
(off antibiotics) are negative.
• Consider vaccination.
Viral haemorrhagic fevers
VHFs are a group of illnesses caused by several different families of viruses
(see Table 7.3). The incubation period is 3–21 days. The range of clinical
disease caused by these viruses is marked, but many cause severe life-
threatening disease, e.g. Ebola and Marburg viruses. VHFs are endemic in
some areas of Africa, South America, and Asia and should be considered in
febrile travellers returning from endemic areas.
Many patients with suspected VHFs will turn out to have malaria, but
when suspected, their management should always be discussed with an ID
specialist.
• Dengue fever is commonly imported into the UK (estimated at 100–150
cases/year) and presents with fever, headache, and rash. Cases of the
other haemorrhagic fevers are imported only once every few years.
• Recognition is important not least because Lassa, Ebola, Marburg,
and CCHF have been transmitted to health-care workers of patients
(including laboratory staff ). Discuss suspected cases urgently with
specialist high-security ID centres regarding investigations and possible
transfer.
• Suspected cases include patients with onset of their fever within 21 days
of leaving an endemic area, particularly if a malaria film is negative.
• Limit local blood tests to an absolute minimum if a VHF is suspected
(but always perform malaria testing).
Rickettsial infections
• These present with fever, headache, and rash and should be included in
the differential diagnosis of febrile travellers. Recognition is important
because rickettsial illnesses have significant mortality if left untreated.
Isolation is not necessary. Incubation is about 5–14 days.
• Rickettsia conorii and Rickettsia africae are probably the two most
common of the group to be imported into the UK, usually from Africa,
but rickettsiae are widely distributed across the world (see Table 7.4).
• Molecular and direct serological diagnostic techniques are not widely
available, so treatment has to be given on clinical suspicion. Serology
is not positive until the second week of the illness at the earliest and
may take 3–4 weeks to become positive (and may be modified by
treatment).
• First-line treatment is with doxycycline 100mg bd PO for up to
7 days (other tetracyclines, chloramphenicol, or quinolones have also
been used).
Human bites 495
Q fever
Coxiella burnetii is a disease of rural areas (reservoirs in sheep and cattle)
and transmitted by inhalation of infectious particles in dust, contact with
infected carcasses (e.g. in abattoirs), and tickbites. There have been recent
outbreaks in the Netherlands, Australia, and the Mediterranean and Middle
East regions.
• Presentation: non-specific symptoms, fever, myalgia, malaise, sweats; dry
cough and features of atypical pneumonia; hepatitis; pyrexia of unknown
origin (PUO) and splenomegaly.
• Investigations: patchy CXR shadowing (lower lobes), hepatic
granulomata. Complement fixation tests identify antibodies to phase 1
antigens (chronic infection, e.g. endocarditis; E Infective endocarditis
(IE), pp. 102–3) and phase 2 antigens (acute infection). Treat with oral
doxycycline (to try to prevent chronic infection), co-trimoxazole,
rifampicin, or a quinolone.
Human bites
• Superficial abrasions: clean the wound. Re-dress the area daily.
• Give tetanus prophylaxis, as needed. Check hepatitis B status, and
immunize if necessary (E Viral hepatitis, pp. 262–4). HIV counselling
and urgent post-exposure prophylaxis (PEP) if indicated (E Post-
exposure prophylaxis, p. 542–3). HCV has also been transmitted by
human bite, so appropriate follow-up needed (there is no HCV PEP).
• Have a low threshold for admission to hospital and IV antibiotic
therapy: the human mouth contains a number of aerobic and anaerobic
organisms that may produce aggressive necrotizing infection, particularly
if the ‘closed’ spaces of the hand or feet are involved.
• Antibiotic therapy: all wounds that penetrate the dermis require
antibiotics. Aerobic and anaerobic cultures should be taken prior to
treatment with antibiotics. A suggested regimen is co-amoxiclav
500/125mg tds PO or IV. Consult your local microbiologists.
• Facial bites: cosmetically significant bites should be referred to a plastic
surgeon. Puncture wounds should be cleaned thoroughly and treated
with prophylactic antibiotics (as described earlier).
• Hand bites: should be referred to the orthopaedic or plastic surgery
team; exploration is recommended. Clean the wound thoroughly. Give
the first dose of antibiotics IV and subsequent doses PO, unless there
are signs of GI upset.
496
Non-human mammalian bites
• General management is as for human bites (E Human bites, p. 495).
Clean the wound, swab for aerobic and anaerobic cultures, tetanus
prophylaxis as needed, and prophylactic antibiotics (E Human bites,
p. 495).
• Rabies is transmitted by infected saliva inoculated through the skin or by
inhalation of aerosolized virus (from infected bats). Presenting features
are a viral prodrome, followed by paraesthesiae and fasciculations.
Agitation, confusion, muscle spasms, localized paralysis, and brainstem
dysfunction follow. There is no effective treatment once symptoms
appear; prevention is essential. Rabies prophylaxis (vaccine plus rabies-
specific Ig) should be considered in all cases if the bite occurred outside
the UK, or if the bite was from a bat within the UK or from an animal in
a quarantine facility. Discuss with local virology or ID experts. For up-
to-date advice, see M https://www.gov.uk/government/publications/
human-rabies-public-health-management-of-a-suspected-case
• Rabies vaccine should be given prophylactically (in the deltoid) to
those at risk of bites from infected animals (vets, animal handlers,
field workers, UK bat handlers), as well as frequent travellers to
endemic areas.
• Some Old World monkeys, particularly rhesus and cynomolgus
macaques are infected with simian herpes B virus (causes a similar illness
in monkeys as HSV does in humans). It can be transmitted by bite and
saliva and has caused fatal disseminated infection in humans. If the bite is
from a macaque from a colony not deemed clear of the virus, consider
starting valaciclovir 1g tds for 14 days, pending further investigation.
Cellulitis
• Cellulitis is a relatively common presentation to acute medical services
where patients present with a red, hot, swollen, and painful area of
skin/soft tissue. This most frequently affects a limb, predominantly a leg.
Cellulitis is almost always unilateral. Chronic swelling of both legs due to
venous insufficiency or cardiac failure is often quite red in appearance.
Presentations where both legs are red must be carefully assessed for
alternative diagnoses, including dermatitis, vascular phenomena/venous
stasis, and haemosiderin deposition.
• Cellulitis is most frequently caused by S. aureus or group A Streptococcus
(or group B, C, or G Streptococcus or other organisms less frequently).
• Often there is no clear lesion or ulcer to swab for microbiology,
although all patients managed for cellulitis should have an MRSA screen,
as confirmed colonization with MRSA would instigate a change in
antimicrobial therapy.
• Where IV antimicrobials are indicated, local antimicrobial policies should
be observed. Flucloxacillin 2g qds (barring allergy, renal impairment, or
drug interactions) is frequently the preferred option. Many patients can
be managed with just oral antimicrobials, and a total course length of
10–14 days may be warranted. Clindamycin may be helpful where there
is evidence of exotoxin production by the causative organism (blistering,
desquamation), although studies on how this alters outcomes are
pending.
Necrotizing fasciitis
• Necrotizing fasciitis is a rare infection of the subcutaneous tissues that
tracks along fascial planes. It is usually caused by group A streptococci
but may also be polymicrobial. Urgent surgical debridement is the
mainstay of treatment. Samples should be sent for urgent Gram stain, as
well as culture and sensitivity testing.
• Patients are usually extremely unwell. Consider this diagnosis in all
patients with skin/soft tissue infection who appear disproportionately
septic or where there is disproportionate pain.
• Erythematous, exquisitely tender area, sometimes with underlying
crepitus. X-ray may show gas in subcutaneous tissues.
• Mainstay of treatment is urgent debridement of all necrotic tissue by
senior surgeon. Further imaging prior to theatre merely delays the
procedure without providing further therapeutic information.
• Clindamycin is an important component of any antimicrobial therapy,
which inhibits bacterial exotoxin production. Advice should be sought
from local microbiology/ID experts, but one suggested treatment
regime is ciprofloxacin 400mg bd IV, clindamycin 600mg–1.2g qds IV,
benzylpenicillin 1.2–2.4g 4-hourly. For nectrotizing fasciitis infections
in IVDUs, complex regimes may be needed—take advice from
microbiology or ID specialists.
• Patients usually require daily debridement in theatre, followed by
reconstructive surgery.
498
Bioterrorism 499
Bioterrorism
• Possible agents of bioterrorism include anthrax (B. anthracis), botulism
(Clostridium botulinum), brucellosis (Brucella melitensis associated with
goats and Brucella abortus from other livestock), glanders/melioidosis
(Burkholderia mallei, Burkholderia pseudomallei), plague (Yersinia pestis), Q
fever (C. burnetti), smallpox, tularaemia (Francisella tularensis), and VHFs.
• There is increasing awareness of the possibility of a deliberate release
of biological and chemical agents. Historically, plague, Salmonella spp.,
and anthrax have all been used, as have nerve gases and biological
toxins. More recent large-scale releases have been Sarin gas (a nerve
gas) on the Tokyo underground in 1995 and anthrax spores (as a white
powder in the mail) in the USA in 2001.
• Releases are likely to be either airborne or food and water
contamination.
• Clues that a deliberate release may have occurred would be the
unexpected appearance of an infection outside its normal range (e.g.
anthrax in a city), an infection appearing in a patient unlikely to contract
the disease, or a sudden cluster of patients with the same pattern of
symptoms. ‘White powder’ incidents also continue to cause concern.
• Any suspicion of a deliberate release should be communicated urgently
to the consultant microbiologist and Public Health practitioner (CCDC)
on-call.
(See Table 7.5.)
50
500
Table 7.5 Characteristics of some bioterrorism agents
Agent Clinical Person-to-person transmission risk Treatment Prophylaxis
Smallpox Initially macules, then deep Yes Supportive Vaccination (post-
Chapter 7
Tuberculosis
Mycobacterium tuberculosis is a widely disseminated bacteria, estimated
to have colonized up to a third of the world’s population. The risk of
developing clinical disease is 5% in the first 5 years after exposure, and an
additional 5% over subsequent lifetime. In the UK, the incidence of TB is
increasing, and changing patterns in presentation can make acute clinical
assessment complex.
Presentation
• Confirm any risk factors for TB, including: immigration from an area of
high incidence, homelessness, alcohol misuse, DM, immunosuppression
(including from HIV, or iatrogenic).
• Pulmonary: worldwide 90% of cases, in the UK only 50%; typically
indolent presentation; productive cough, fever, sweats, weight loss.
While these symptoms should prompt a search for TB, lymphoma and
some other conditions can also present like this.
• Extra-pulmonary: pleural TB can present similarly to pulmonary
disease; nodal disease often just with fever, sweats, and weight loss;
GI and genitourinary disease can also present with indolent non-
specific symptoms, or with abdominal or flank pain; skeletal TB most
frequently affects the spine but may also present with monoarthritis
(most frequently the knee, but other joints may be affected); CNS TB
can present with headaches, confusion, or reduced GCS scores. Less
commonly, erythema nodosum, pericardial disease, or scrofuloderma
may be apparent.
• In the immunocompromised or elderly, classic symptoms may be absent.
Investigations
• Radiology: CXR changes in pulmonary disease typically include apical
consolidation, often with paratracheal adenopathy. In extra-pulmonary
disease, CT can be suggestive, but there are few pathognomic signs.
• Microbiology: in pulmonary disease, sputum (×3) for ZN/auramine stain
can give an indication of disease within 24h, but sensitivity is typically
730–40%; culture usually becomes positive at 10–14 days but can take
up to 6 weeks. In those not expectorating, BAL or an enterostring may
be used, and in children, gastric aspirates are useful. In extra-pulmonary
disease, obtaining tissue for culture is key. In CNS disease, the CSF
typically demonstrates 10–1000 WCC/microlitre, a low glucose, and a
high protein, but it is rarely ZN-positive. Culture may take up to 6 weeks
and antimicrobial susceptibility testing typically takes a further 2 weeks.
• Nucleic acid tests: PCR for TB is advocated for respiratory samples and
has a higher sensitivity than ZN staining. It can also be used to discern
rifampicin resistance and is recommended by NICE when risk factors for
multidrug-resistant (MDR)-TB are present. PCR on samples other than
sputum has a lower sensitivity.
• Interferon-gamma release assay: the enzyme-linked immunospot
(ELISpot) or QuantiFERON® tests indicate previous exposure to
M. tuberculosis (i.e. are tests for latent disease) but do not give an
indication of active disease and can actually give a false negative result in
some instances of active disease and in some immune-deficient states.
Tuberculosis 503
Management
• Refer: involve ID/respiratory teams early when TB is in the differential;
alert the microbiology laboratory as to clinical suspicion, so samples can
be appropriately processed.
• Drug treatment: focuses on combination therapy. This should only be
initiated by, or on the advice of, a clinician experienced in treating TB.
In acute medicine, the only urgent indication to start TB therapy is CNS
disease. The standard regime is quadruple therapy for 2 months (see
Box 7.7), then dual therapy for a further 4 months in pulmonary disease,
extending to complete 9–12 months in total for some extra-pulmonary
disease.
• Drug resistance: currently isoniazid mono-resistance is 710% in the UK,
with MDR at 71–2% and very few cases of extended drug resistance.
• Steroids: only definitively indicated in CNS and pericardial disease.
Public Health
• Isolation: a side room with respiratory precautions for suspected
pulmonary disease. Negative pressure ventilation is indicated for
drug-resistant cases.
• Notification: TB is notifiable, and the local Health Protection Team
should be made aware by the treating physician upon making or
suspecting the diagnosis.
• Limiting transmission: compulsory treatment for patients with pulmonary
TB who decline therapy is not possible; for patients at risk of non-
compliance, involving a TB expert early is crucial.
Chapter 8 505
Emergencies in
HIV-positive patients
HIV testing
In most situations, HIV testing is carried out with informed consent by
genitourinary medicine (GUM)/sexually transmitted infection (STI) clinics, in
primary care, or as part of routine antenatal care. However, the presentation
of individuals with potentially HIV-related complications or at potential risk
of previous HIV exposure to the emergency clinician provides an opportunity
to diagnose the infection. While most choose to have an HIV test within the
confidential setting of a specific HIV-testing service, any health-care provider
should possess the essential skills for appropriate discussion of HIV testing.
HIV testing should no longer be exceptional but should be considered with in-
formed consent in all patients with clinical indicator diseases or presentations.
Pretest discussion
In-depth discussion is only necessary where there is a high probability of a
positive result, otherwise a simple yes/no question may be appropriate. If
the patient declines or has further questions, then it is important to dispel
any misconceptions and detail the benefits of testing (specifically that early
diagnosis has a better prognosis through access to treatment and that the dis-
ease, while currently incurable, has a good life expectancy, etc.). If the chance
of a positive result is high, more detail about testing should be given prior
to testing. The following issues should be included in a ‘pretest’ discussion:
• Rationale for testing (see Box 8.2).
• Benefits of knowing the status.
• When and by whom the result will be given.
• ‘Window period’ of infection (i.e. may take up to 8 weeks from
exposure for an HIV antibody test to become positive).
• Confidentiality: testing for HIV, and any result whether positive or
negative, does not require disclosure to a GP. A positive result does not
necessarily need to be disclosed to third parties without consent but will
have implications for insurance/mortgages.
Post-test discussion
The following principles should be followed in a ‘post-test’ discussion:
• Giving a positive result should follow the principles of breaking
bad news.
• If a result is positive, early referral to an HIV clinician is essential.
• If a result is negative, the window period should be reinforced
(particularly in situations where seroconversion is suspected;
E Primary HIV infection, p. 510).
• If a result is negative, the opportunity for future risk reduction should be
considered.
HIV testing without consent
It is rarely necessary to test for HIV infection without consent. However,
this is justified in the following settings:
• Testing of organ transplantation donors.
• Testing of the unconscious/confused patient where HIV infection is
suspected and the management of the patient will be materially changed
by knowledge of their HIV status.
CD4 count
500 Toxoplasmosis
Cryptosporidia
400 Cryptococcus Atypical mycobacteria
Kaposi’s sarcoma Cytomegalovirus
300 Aspergillus
Lymphoma
200
100
0
Time after infection
PRESENTATION WITH HIV COMPLICATIONS AND INFECTIONS
Fig. 8.1 CD4 count is used as a guide to a patient’s susceptibility to complications of HIV infection.
513
451
• Bacterial: MC&S.
• Mycobacterial: ZN microscopy, culture, and consider PCR.
• Viral: PCR for CMV, HSV, VZV, JC virus (PML), EBV (lymphoma).
• Other: Indian ink microscopy and CrAg (near 100% sensitivity and
specificity for neurological cryptococcal disease), fungal culture,
and STS.
• Bottle 2 and both fluoride tubes to biochemistry for protein and
paired glucose measurement.
• Bottle 3 to cytology (rarely diagnostic) or immunology, if indicated.
• Raised CSF cell count and protein (up to 1g/L) can be an incidental
finding in asymptomatic HIV infection; conversely, there may be little
inflammatory response, e.g. in cryptococcal meningitis.
520
520
Table 8.2 Treatment for acute neurological conditions in HIV-infected patients
Condition Possible presentations Diagnostic tests Treatment
HIV Encephalitis or aseptic Diagnosis of exclusion HAART
meningitis Brain biopsy diagnostic, but not
Chapter 8
(See Table 8.2.)
Dementia/psychiatric performed for this reason
presentation
Seizures
Toxoplasmosis SOL 90% anti-Toxoplasma antibody positive Sulfadiazine 1–2g IV/PO qds + pyrimethamine 100mg
Seizures but does not discriminate active from PO od on first day, then 75mg PO od + folinic acid
Confusion inactive disease 15mg PO od for 4–6 weeks
Encephalitic illness CT: ring-enhancing lesions Clindamycin 1.2g PO/IV qds + pyrimethamine 100mg
Brain biopsy gold standard, perform if no PO od on first day, then 75mg PO od + folinic acid
response to empirical therapy 15mg PO od
Atovaquone 750mg PO tds for 21 days
(consider use of dexamethasone to reduce cerebral
oedema)
Cryptococcosis Headachec± meningism CSF: pleiocytosis with low glucose but Amphotericin 0.25mg–1mg/kg IV od for up to
SOL (cryptococcoma) may be normal in 20–30%. India ink stain, 6 weeks ± flucytosine 100mg/kg PO/IV qds for
Seizures culture, and CrAg 2 weeks (liposomal formulations may be used if
Serum CrAg positive in 95% concerns regarding nephrotoxicity)
Acute neurological conditions in
HIV-infected patients: treatment
Confusion
Fluconazole 400mg bd, daily/regular LPs to reduce
ICP ≤20cmH2O is essential
Mycobacterium Headache ± meningism CSF: pleiocytosis with low glucose in Obtain specialist microbiological advice; initiate therapy
most cases; ZN stain positive in only with at least four agents (preferably including those with
Emergencies in HIV-positive patients
10–20%. CSF culture takes 4–6 weeks CNS penetration, i.e. isoniazid + pyrazinamide), and
consider steroids if fits or worsening neurological signs
Table 8.3 Clinical, laboratory, and CXR findings that may distinguish PCP
from bacterial pneumonia
Findings PCP Bacterial
CD4 cell count <200 cells/mm3 Any
Symptoms Non-productive cough Productive cough
Purulent sputum
Symptom A few weeks 3–5 days
duration
Signs Occasionally bilateral fine Focal lung signs
crackles (usually minimal signs)
Laboratory WBC variable WBC frequently
tests elevated
Chest radiograph findings
Distribution Diffuse > focal Focal >diffuse
Location Bilateral, perihilar initially Unilateral,
segmental/lobar
Pattern Diffuse, interstitial infiltrates Often lobar or
focal consolidation
Cysts 10–15% 5–10% (Klebsiella,
staphylococcal)
Pleural effusions Very rare 25–30%
Practice points
• Beware ‘normal’ CXR: respiratory history is the most important.
• If CD4 count <200 cells/mm3 and the history is compatible, consider
PCP as the most likely respiratory infection, and start empirical
therapy.
• Diagnostic investigations should be done as soon as possible.
• TB is still common among people living with HIV in the UK.
524
Treatment of aspergillosis, other fungi, nocardiosis, and CMV pneumonitis should be undertaken
by clinicians experienced in the use of antimicrobials for these pathogens, given their increased
toxicity and drug–drug interactions.
528
Gastrointestinal presentations in
HIV-positive patients: assessment
Opportunistic infections, malignancies, and antiretroviral drug toxicity can
all frequently manifest as symptoms/signs in the GIT.
Key symptoms and signs
• General: assess hydration, weight, and nutritional status.
• Diarrhoea: can be caused by multiple pathogens (both common and
opportunistic) (see Table 8.5), drug therapy, or advanced HIV per se.
The presence of associated symptoms (fever, abdominal pain, blood
PR) should be established. An awareness of the CD4 count will assist in
directing management.
• Weight loss: can be caused by advanced HIV infection, may be the result
of chronic diarrhoea/malabsorption, may be the presenting symptom
of an underlying malignancy or opportunistic infection, or may represent
toxicity to antiretroviral therapy (particularly subcutaneous fat loss).
• Abdominal pain: can be a feature of GI infections (see Table 8.5), biliary
tree disease, or pancreatitis—which may be drug-induced, notably by
nucleoside analogues, particularly didanosine. Lactic acidosis and hepatic
steatosis are rare complications of antiretroviral therapy that may
present as vague abdominal pain.
• Loin pain/nephrolithiasis: is a well-recognized side effect of indinavir
therapy. Stones are unlikely to be seen on plain X-rays and usually
respond to conservative management with fluid input, without the need
to discontinue the offending agent. With severe episodes (haematuria
and confirmed calculi on renal tract investigation), change therapy as
there is a risk of further episodes and progressive renal damage.
• Jaundice: may be the result of viral hepatitis (acute or chronic), biliary
tract disease, drug-induced hepatitis, or hepatic involvement by other
opportunistic infections or tumours. Also associated with atazanavir
where, for this specific drug, the development of unconjugated
hyperbilirubinaemia may occur in susceptible individuals who have
minor abnormalities of the bile acid transporter genes (e.g. MDR). It is a
benign side effect but can cause significant jaundice in some patients.
• Dysphagia: is most commonly caused by candidal infection (oral Candida
is usually present), and less commonly by ulceration secondary to HSV,
VZV, CMV, or idiopathic (aphthous).
• Oral lesions: oral Candida (usually in a pseudomembranous form, appearing
as white plaques, but may be erythematous or hyperplastic) and oral hairy
leukoplakia (white plaques on the side of the tongue) are common signs
in individuals with HIV infection and may be the first presenting features of
advancing infection. KS may present as red/purple macules on the palate
or gingival margin. Oral chancres of primary syphilis may occasionally be
seen, in MSM more frequently than in heterosexual patients.
Practice points
There is an epidemic of acute hepatitis C and syphilis in sexually active
men who have sex with men in the UK. Always test for these organisms
if there are concerns or symptoms.
Gastrointestinal presentations in
HIV-positive patients: investigations
General investigations
• FBC, U&Es, LFTs, CRP: check for evidence of anaemia, dehydration, and
hepatic dysfunction.
• Blood cultures: bacterial GI infections are more likely to be accompanied
by systemic infection in the immunocompromised host. Mycobacterial
blood cultures (particularly considering atypical mycobacteria in
individuals with CD4 counts <100 cells/mm3).
• Amylase: check for pancreatitis in individuals with abdominal pain.
• Uncuffed serum lactate: consider the possibility of lactic acidosis in
the unwell patient receiving antiretroviral therapy with non-specific
abdominal symptoms. Send to a lab rapidly for an accurate result.
• Hepatitis serology: consider acute hepatitis A/B/E (or hepatitis D super-
infection if already HBV-positive) in the jaundiced patient and chronic
hepatitis B/C in patients with evidence of chronic liver disease. New
onset of abnormal LFTs may be due to hepatitis C.
• Syphilis serology.
• Rectal/genital STI swabs: send swabs for Chlamydia/LGV/gonorrhoea if
there are rectal/lower GI symptoms.
Specific investigations
• Stool specimens: should be examined/cultured for bacteria and ova, cysts,
and parasites. At least three stool specimens should be sent. Clostridium
difficile toxin should be requested in individuals who have taken or
are taking antibiotics. In an individual with severe immunosuppression
(CD4 count <100 cells/mm3) and negative conventional stool analysis,
examination for microsporidial species should be performed.
• AXR: look for evidence of toxic dilatation in the patient presenting
with diarrhoea/abdominal pain. The major causes are CMV (with CD4
count <100 cells/mm3) and bacterial infections (Salmonella, Shigella,
Campylobacter) at higher CD4 counts.
• USS: look for evidence of hepatic/biliary abnormality in patients with
jaundice/abnormal LFTs, evidence of ascites in patients with abdominal
distension, and abdominal masses/lymphadenopathy in individuals with
opportunistic infections/tumours.
• CT scanning: look for evidence of masses/lymphadenopathy in
individuals with abdominal pain, which may represent involvement by
underlying opportunistic infections or tumours.
• Upper GI endoscopy: look for oesophageal lesions in patients with
dysphagia and gastric lesions in patients with abdominal pain. Perform
duodenal biopsies in individuals with chronic diarrhoea where no
pathogen has been isolated.
• Sigmoidoscopy/colonoscopy: look for evidence of involvement by
opportunistic pathogens/tumours in patients with chronic diarrhoea or
abdominal pain. Rectal/colonic biopsies should be performed in patients
with chronic diarrhoea where no pathogen has been isolated.
• ERCP/MRCP: should be considered in individuals with evidence of
obstructive jaundice where no cause has been found, or in individuals with
chronic abdominal pain looking for any evidence of ascending cholangitis.
530
Gastrointestinal presentations in
HIV-positive patients: management
• General principles of rehydration, analgesia, and nutritional support
should apply.
• If the CD4 count is >200 cells/mm3, patients are usually treated in a
similar way to HIV-seronegative individuals.
• Specific therapy should be directed towards the suspected/proven
underlying cause (see Table 8.6). Consider empiric treatment with
antibacterial agents for acute diarrhoea where a bacterial cause is likely.
This should be treated according to sensitivities and local protocol,
unless the patient is compromised. In the unwell patient with diarrhoea,
consider additional anti-CMV therapy (usually ganciclovir) if the CD4
count is <100 cells/mm3.
• Antiretroviral therapy should not be discontinued or modified without
discussion with an experienced HIV clinician.
532
Table 8.6 GI pathogens in HIV-positive patients
Pathogen Clinical presentation Diagnosis Treatment
Candida Oral: usually white plaques. Usually Usually based upon clinical appearance Oral: usually with fluconazole (50mg × 5 days)
CD4 count <350 Can be confirmed by biopsy/culture or 400mg stat
Chapter 8
with CD4 count <100 analysis or on biopsy/electron microscopy Effective HIV treatment results in clinical
improvement
Isospora Watery diarrhoea in individuals AFB smear of stool Co-trimoxazole usually effective
with CD4 count <100
Entamoeba Diarrhoea ± blood and abdominal Ova, cysts, and parasites of stool Metronidazole 800mg tds or tinidazole, then
histolytica pain. Any CD4 count diloxanide
Giardia Watery diarrhoea. Any CD4 count Ova, cysts, and parasites of stool Metronidazole 400mg tds for 10 days or
tinidazole 2g PO on days 1 and 5
CMV Oesophageal: dysphagia with Demonstration of organisms by Specific CMV therapy (usually ganciclovir 5mg/
ulceration immunocytochemistry of biopsy specimens kg bd for 3–4 weeks).
Gastric/upper GI: abdominal pain Effective anti-HIV therapy should reduce risk of
Colonic: diarrhoea ± abdominal recurrence/other end-organ disease
pain. Toxic dilatation may occur.
CD4 <100
Herpes simplex Oesophageal ulceration, or Demonstration of organisms on biopsy/culture Aciclovir 200–800mg 5×/day or 5mg/kg IV for
proctitis/colitis 2–3 weeks
Herpes zoster Oesopha-geal ul-ceration Demonstra-tion of or-ganisms on bi-op-sy/ Aciclovir 400–800mg 5×/day or 5–10mg/kg IV
cultu-re for 2–3 weeks
Mycobacterium Chronic, watery diarrhoea ± Blood cultures (specific mycobac-terial culture: Three agents (usually rifabutin, ethambutol, and
avium complex ab-dominal pain. Usually systemic may take several weeks) or demon-stration of clarithromycin or azithromycin)
symptoms (fever, weight loss, organisms on biopsy Effective anti-HIV therapy is associated with
pancyto-penia). CD4 count <50 clinical response
Clostridium Watery diarrhoea. History of Stool toxin assay Stop culprit antibiotic(s) if possible
difficile antibiotics Any CD4 count Metronidazole 400mg tds PO–10 days
Vancomycin 125mg qds × 10 days
GASTROINTESTINAL PRESENTATIONS IN HIV: MANAGEMENT
533
534
Pyrexia of unknown origin
Assessment
• Look for signs/symptoms of focal infection.
• Check for neutropenia.
• Consider TB.
• Consider line sepsis if indwelling IV cannulae.
• Consider drug-related fever (detailed drug history, including
antiretroviral agents).
• Consider underlying lymphoma.
• Detailed travel history is essential.
Investigations
• Usual investigation of fever.
• CrAg.
• Mycobacterial blood cultures (MAI if CD4 count <100 cells/mm3).
• Consider:
• CT scan head.
• CT scan chest and abdomen.
• Lymph node biopsy (if significant lymphadenopathy).
• Bone marrow examination.
• Fludeoxyglucose positron emission tomography (FDG-PET) CT body.
Treatment
• Unless clinically unwell, most clinicians would recommend withholding
empiric antimicrobial therapy.
• Specific antimicrobial (or other) therapy should be directed against the
suspected underlying pathogen/process.
Dermatological presentations
• Seroconversion can present with a viral exanthematous rash.
• Consider drug-related causes (including antiretroviral agents), but do
not discontinue antiretroviral agents (unless essential) without discussion
with an HIV clinician.
• In particular, patients recently having commenced nevirapine therapy
may be at risk of Stevens–Johnson syndrome or toxic epidermal
necrolysis, and patients having recently commenced abacavir may be at
risk of a hypersensitivity syndrome (E Antiretroviral toxicity,
pp. 538–9). Milder rashes are common after initiation of any
antiretroviral and usually self-limiting, and usually HAART can be
continued with an antihistamine for symptom control.
• Most dermatological complaints can behave atypically and more
severely in individuals with HIV infection:
• Shingles (varicella-zoster) may present with multi-dermatomal lesions
and/or neurological involvement.
• Herpes simplex may present with more severe lesions, more frequent
recurrences, or prolonged outbreaks. There may also be neurological
involvement, requiring higher doses of aciclovir than used in
immunocompetent patients.
• Seborrhoeic dermatitis may present more aggressively in the HIV-
positive patient and may be recalcitrant to conventional therapy.
• Early syphilis should be considered in any HIV-positive patient with
dermatological lesions.
Haematological presentations
Cytopenias may be the result of HIV infection per se, antiretroviral (or
other drug) toxicity, or bone marrow involvement by opportunistic infec-
tions or tumours.
• Mild to moderate thrombocytopenia is a common finding in the HIV-
infected patient; a severe idiopathic thrombocytopenic purpura (ITP)
picture is well recognized. Usually responds to antiretroviral therapy, but
steroids/Ig may be required in severe cases.
• Anaemia is a recognized side effect of antiretroviral therapy—notably
zidovudine (AZT) therapy.
• Neutropenia is a recognized side effect of zidovudine (AZT) and
ganciclovir therapy, and occurs more frequently in the HIV-infected
patient receiving chemotherapy for malignancy. Standard management
of neutropenia should apply.
538
Antiretroviral toxicity
• Newer agents tend to be less toxic than older agents (such
as zidovudine, didanosine, and stavudine), which are now less
commonly used.
• Many clinicians are unfamiliar with the agents used to treat HIV
infection. They are associated with multiple toxicities, some of which
may present to the emergency clinician. Always consider discussing the
case with a clinician experienced in the use and toxicity of these drugs.
• The key principles of management are to recognize the possibility
of iatrogenic illness and to exert caution in management. In order to
minimize the risk of development of resistance and to preserve future
treatment options, antiretroviral agents should be discontinued only in
discussion with an HIV clinician. If necessary, the toxic agent is switched
and the withdrawal of one or two of a combination of agents (thus
leaving an individual on suboptimal therapy) should be avoided.
• In individuals receiving antiretroviral therapy who present systemically
unwell, the possibility of lactic acidosis should always be considered (see
E Mitochondrial toxicity, pp. 538–9).
Rash and hypersensitivity
• Abacavir hypersensitivity reaction (4%) can present as a fever or
maculopapular rash (usually in the first 2 months of treatment), often
associated with one or more other symptoms or signs (fever, sore
throat, GI or respiratory symptoms, laboratory abnormalities). If strongly
suspected, abacavir should be discontinued and the patient never
rechallenged (risk of fatal hypersensitivity reaction). This decision should
be taken by an experienced HIV clinician. Most clinicians now use the HLA-
B5701 test to predict the likelihood of abacavir hypersensitivity (90% risk).
• Non-nucleoside reverse transcriptase inhibitors (efavirenz and
nevirapine): maculopapular rash (710%), peaking at 2 weeks, often
associated with abnormal LFTs. Sometimes can be ‘pushed through’
with antihistamines (cetirizine) but needs close monitoring (associated
severe or life-threatening hepatotoxicity not uncommon). Stevens–
Johnson syndrome and toxic epidermal necrolysis are well recognized,
but uncommon, side effects of nevirapine. Stevens–Johnson syndrome
is more common in patients who start treatment with high CD4 counts.
Nevirapine should not be used in patients with a high CD4 count, as it
increases the risk of Stevens–Johnson syndrome.
Mitochondrial toxicity
Usually attributed to the unwanted inhibition of mitochondrial DNA poly-
merase gamma by nucleoside reverse transcriptase inhibitors (particularly
stavudine and didanosine). Over months, this can lead to mitochondrial
dysfunction which can manifest as:
• Lactic acidosis/hepatic steatosis resulting from general mitochondrial
dysfunction. If suspected (general malaise, abdominal pain, metabolic
acidosis, abnormal LFTs), an uncuffed blood sample should be sent
for immediate lactate measurement, and if high (>5mmol/L) with
associated acidosis, the offending drug(s) stopped. This condition can be
rapidly fatal, and admission to ICU is occasionally required.
Practice points
Always discuss treatment initiation/change with an experienced HIV clin-
ician. Do not stop antiretroviral therapy without discussion with an ex-
perienced HIV clinician.
540
Post-exposure prophylaxis
Evidence that PEP may be effective can be drawn from both animal and
vertical transmission studies. The most compelling data are from a case-
controlled study of health-care workers where the administration of zi-
dovudine (AZT) monotherapy was shown to be associated with 780%
reduction in HIV transmission.
Most hospitals/emergency departments will have established protocols
for the management of PEP (see Box 8.4). However, the following general
principles apply:
• The risk of HIV transmission is the product of the risk of the ‘donor’
being HIV-positive and the risk of HIV infection from the exposure.
• To estimate the risk of the donor being HIV-positive, an understanding
of the epidemiology of the ‘risk group’ of the individual is helpful.
• For example, the risk of a sexually active homosexual man in the UK
being HIV-positive is estimated at 712.5% in London and 5.9% across
the UK as a whole.
• The risk of an IVDU being HIV-positive is <1.1%.
• The risk of a heterosexual being HIV-positive requires knowledge of
the HIV prevalence in the country in which they have been sexually
active (as high as 20–50% in some sub-Saharan African countries). In
the black African population in the UK, prevalence has been estimated
at 4.1% among men and 7.1% among women.
Inoculation injuries
The risk of HIV transmission from exposures has been estimated at:
• Needle-stick injury: 1 in 333.
• Splash injury (to eyes or diseased skin): <1 in 1000.
• Human bite: <1 in 10 000 (PEP not recommended).
• Injury from discarded sharps in the community: risk usually low, as HIV
becomes non-viable after a few hours and the use of the sharps prior to
being discarded is usually unknown.
NB Do not forget that optimal management of sharps injuries includes
immediate wound management (bleeding and simple washing) and consid-
eration of exposure to hepatitis B (assess vaccination status and consider
accelerated vaccination or Ig) and hepatitis C.
Sexual exposure
The risk of HIV transmission through sexual exposure from a known HIV-
positive individual not on HAART is estimated at:
• Unprotected receptive vaginal sex (♂ to ♀): 1 in 1000.
• Unprotected insertive vaginal sex (♀ to ♂): 1 in 1219.
• Unprotected anal sex (risk to insertive partner): 1 in 666.
• Unprotected anal sex (risk to receptive partner): 1 in 90.
• Oral sex with ejaculation (both receptive and insertive): <1 in 10 000.
Chapter 9 545
Diabetic ketoacidosis: assessment
DKA predominantly occurs in patients with type 1 diabetes mellitus
(T1DM) and insulin-dependent type 2 diabetes mellitus (T2DM). It is also
being increasingly recognized in the initial presentation of an atypical form
of T2DM in non-white patients known as ketosis-prone T2DM where there
is a severe, transient defect in insulin secretion.
Clinical features
These include:
• Polyuria and polydipsia; patients become dehydrated over a few days.
• Weight loss, weakness.
• Hyperventilation or breathlessness; the acidosis causes Kussmaul’s
respiration (a deep sighing respiration).
• Abdominal pain: DKA may present as an ‘acute abdomen’.
• Vomiting: exacerbates dehydration.
• Confusion, coma occurs in 10%.
• On examination, pay attention to the haemodynamic stability, state of
hydration, ventilation rate, level of consciousness, and septic foci.
Investigations
• Blood glucose Assess capillary and venous blood glucose. This need
not be very high (≥11mmol/L) (see ‘Note’ below).
• Venous gas Assess the degree of acidosis (see ‘Note’ below).
• U&E, Mg2+ Assess serum K+ and renal function.
Corrected Na+ = Na+ + 1.6 × [(plasma glucose
− 55)/5.5]
Serum osmolality = 2 × (Na+) + urea + glucose
• Urinalysis Ketones strongly positive (≥2+) (see ‘Note’ below).
• Urinary HCG Exclude pregnancy in ♀ of childbearing potential.
• FBC WBC may be elevated (neutrophilia): a leukaemoid
reaction can occur in absence of infection.
• Septic screen Urine and blood cultures.
• Plasma ketones Ketones elevated (≥3mmol/L) (see ‘Note’ below).
• CXR Look specifically for any infection.
• Amylase May be high, with abdominal pain and vomiting, in
absence of pancreatitis. Acute pancreatitis may occur
in 7–10% of patients with DKA (often in association
with hypertriglyceridaemia).
Note
• Diagnosis of DKA requires all three of:
• Blood glucose ≥11mmol/L.
• Ketonaemia ≥3mmol/L (≥2+ on urinalysis).
• Metabolic acidosis with venous or arterial pH ≤7.30 and/or serum
bicarbonate ≤15mmol/L.
• Consider hyperosmolar hyperglycaemic syndrome (HHS)
(E Hyperosmolar hyperglycaemic syndrome, pp. 552–3) and other
causes of hyperglycaemia/acidosis, e.g. aspirin OD and lactic acidosis.
DKA: management
General measures
• Initiate rehydration and fixed-dose IV insulin therapy without delay.
• Site two IV cannulae: one in each arm (one for 0.9% saline and one for
insulin ± glucose). Start fluid replacement (see E Fluid replacement,
p. 548).
• Consider a central line in patients with poor prognostic features.
• NBM for at least 6h (gastroparesis is common).
• NG tube: if there is impaired conscious level, to prevent vomiting and
aspiration.
• Urinary catheter if oliguria is present or serum creatinine is high.
• Broad-spectrum antibiotics if infection suspected.
• Prophylactic-dose LMWH should be given unless contraindicated.
• Some patients may require monitoring on an ECG for T-wave changes
during treatment.
• Monitor blood glucose, capillary ketones, and urine output hourly.
• Venous blood gas (pH, bicarbonate K+) at 0, 4, 6, 12, and 18h and
before stopping the fixed-rate insulin regimen.
• U&Es at 0, 6, 12, and 24h (Mg2+ levels should be monitored daily).
Fluid replacement
Use normal (0.9%) saline to replace the fluid deficit. The average fluid loss
in DKA is 100mL/kg. (More cautious fluid replacement is needed for pa-
tients with cardiac and renal disease, elderly patients, young patients aged
18–25 years, and pregnant patients.)
• 1L of 0.9% saline over 1h*.
• 1L of 0.9% saline over 2h × 2*.
• 1L of 0.9% saline over 4h × 2*.
• 1L of 0.9% saline over 6h.* .
• If SBP <90mmHg, give 500mL of 0.9% saline IV over 15–20min. Repeat
further if SBP <100mmHg. If poor response, consider septic shock or
cardiac failure. Central venous monitoring needed to guide further fluid
management.
• When blood glucose reaches ≤14mmol/L, IV 10% glucose is given at
125mL/h concurrently with 0.9% saline (through an IV cannula in the
other arm). Consider reducing 0.9% saline infusion if risk of overload.
• Use of bicarbonate is not recommended routinely.
Potassium replacement
Total body K+ is depleted, and plasma K+ level falls rapidly as K+ shifts into
cells under the action of insulin. Do not give potassium chloride (KCl) in the
first litre or if serum K+ is >5.5mmol/L. All subsequent fluid for the next
24h should contain KCl, unless the urine output is <30mL/h or serum K+
remains in excess of 5.5mmol/L (see Table 9.1).
Insulin replacement
The only indication for delaying insulin is a serum K+ level of <3.3mmol/L,
as insulin will worsen hypokalaemia by driving K+ into cells. Patients with an
*
Plus K+ replacement; see E Potassium replacement, p. 548
DKA: management 549
DKA: management key points
(See Box 9.2.)
Further reading
Joint British Diabetes Societies Inpatient Care Group (2013). The management of diabetic ketoacid-
osis in adults, 2nd edn. M https://www.diabetes.org.uk/resources-s3/2017-09/Management-of-
DKA-241013.pdf
52
Management: general measures
The goals are to normalize plasma osmolality and blood glucose, to replace
fluid and electrolyte losses, and to prevent complications.
• Manage in well-staffed acute medical unit (AMU) or HDU/ITU if
concerning features.
• Rehydration is the mainstay of treatment. Cautious in the elderly.
• May need CVP monitoring to guide rehydration.
• NBM for at least 6h, and insert an NG tube in patients with impaired
conscious level to prevent vomiting and aspiration.
• Urinary catheter if there is oliguria or high serum creatinine.
• Prophylactic-dose LMWH should be given unless contraindicated. Full-
dose anticoagulation if ACS/VTE suspected.
• Treatment of sepsis or precipitating factors.
• High risk of feet ulceration. Examine the feet daily, and use heel
protection if reduced consciousness or uncooperative.
• Monitor blood glucose, U&Es, plasma osmolality, and urine output
hourly for the first 6h and 2-hourly thereafter if response satisfactory.
• Continuous pulse oximetry, and consider cardiac monitoring in high-risk
patients.
Fluid replacement
The average fluid lost is 8–10L. This should be replaced cautiously over 48h,
especially as most patients are elderly. Remember that 0.9% normal saline
is hypotonic, relative to the patient’s serum, and is therefore the fluid of
choice, even with hypernatraemia.
• Aim for positive balance of 3–6L by 12h. Longer if comorbidities.
• If in doubt, replace fluid cautiously. Over-correction can lead to fluid
overload, cerebral oedema, and central pontine myelinolysis.
• 1L of normal saline over the first 60min, then:
• 1L of normal saline with K+ (see Table 9.1) every 2h × 2, then:
• 1L of normal saline with K+ (see Table 9.1) every 6h until rehydrated
(748h).
• Monitor plasma osmolality. Best indicator of rate of change of
hyperosmolar state to treatment.
• As hyperglycaemia is treated, an initial rise in Na+ is expected. This is
not an indication for hypotonic fluid. A rise in Na+ is only a concern if
plasma osmolality is not decreasing.
NB ‘Corrected’ serum Na+ = measured serum Na+ + [the increment above
normal in blood glucose (in mmol/L)/2.3].
• Use 0.45% normal saline only if plasma osmolality not decreasing
despite positive balance.
• Aim for rate of fall in plasma Na+ of <10mmol/L in 24h.
54
HHS 2
Blood glucose and insulin
Aim for a fall in blood glucose of <5mmol/h. Reducing the serum glucose
level acutely to below 14mmol/L may promote the development of cere-
bral oedema. Patients with HHS tend to be more sensitive to the effects
of insulin.
• Do not start insulin, unless significant ketonaemia is present. Use low-
dose IV insulin (0.05U/kg/h) only if ketonaemia (urine >2+ or plasma
>1) or if blood glucose not falling with rehydration alone.
• Increase insulin by 1U/h if there is no fall in glucose.
• If blood glucose <14mmol/L, commence 5% or 10% glucose infusion at
125mL/h concurrently with normal saline; stop IV insulin, and continue
to monitor blood glucose.
• If the patient is eating and drinking regularly, stop IV insulin; continue
rehydration, and consider starting SC insulin with target glucose of
10–15mmol/L. If previously on oral agents, restart on advice from the
specialist diabetes team.
Poor prognostic features in HHS
Consider HDU/ITU management:
• Serum oxygen saturations <92%.
• SBP <90.
• Pulse >100 or <60bpm.
• GCS score <12.
• Oliguria.
• Hypothermia.
• K+ <3.5mmol/L or >6mmol/L.
• Lactate >6.
• pH <7.0.
• Anion gap >16.
• Plasma osmolality >350.
• Plasma Na+ >160.
• CVA or ACS.
• Significant comorbidities, e.g. cardiac or renal failure.
HHS: management key points
(See Box 9.3.)
Further reading
Joint British Diabetes Societies Inpatient Care Group (2012). The management of hyperosmolar hyper-
glycaemic state (HHS) in adults with diabetes. M http://www.diabetologists-abcd.org.uk/JBDS/
JBDS_IP_HHS_Adults.pdf
56
Hypoglycaemia: assessment
• All unconscious patients should be assumed to be hypoglycaemic until
proven otherwise. Always check a blood glucose using a bedside blood
glucose meter immediately, and confirm with a lab glucose.
• Almost 8% of adult inpatients experience hypoglycaemia. The most
common cause of coma in a patient with DM is hypoglycaemia due to
insulin or sulfonylureas.
• Patients who are not known to have DM should have laboratory blood
glucose, and insulin and C-peptide determination (for insulinoma or
factitious drug administration) before glucose treatment.
Presentation
Sympathetic overactivity Neuroglycopenia (glucose <2.6mmol/L)
(glucose <3.6mmol/L) • Confusion.
• Tachycardia. • Slurred speech.
• Palpitations. • Focal neurological defect
• Sweating. (stroke-like syndromes).
• Anxiety. • Coma.
• Pallor.
• Tremor.
• Cold extremities.
• Patients with well-controlled DM have more frequent episodes of
hypoglycaemia and can become desensitized to sympathetic activation.
These patients may develop neuroglycopenia before sympathetic
activation and complain of ‘loss of warning’ (hypoglycaemic
unawareness).
• β-blockers blunt the symptoms of sympathetic activation, and patients
taking these drugs lose the early warning of hypoglycaemia.
• Patients with poorly controlled DM develop sympathetic signs early
and avoid these by running a high blood glucose. They may complain of
having a ‘hypo’ when their blood sugar is normal or high. They do not
require glucose treatment. Re-education and gradual improvement of
glucose control may be needed.
• Patients who have type 1 or pancreatic diabetes for a longer duration
may have more frequent and severe episodes of hypoglycaemia.
Investigations
• Blood glucose (bedside glucose meter must be confirmed by lab glucose
for a new admission or hypoglycaemic coma).
• For patients not known to have DM, take blood (clotted, heparin, and
fluoride oxalate tubes) prior to giving glucose, for insulin and C-peptide
levels (send blood to the lab on ice for immediate centrifugation).
• Other investigations depend on the presentation (new admission
vs inpatients) and cause (dictated by history and medications) (see
Box 9.4).
Hypoglycaemia: assessment 557
Note
• A lab glucose of <2.2mmol/L is defined as a severe attack.
• Coma usually occurs with blood glucose <1.5mmol/L.
• Low C-peptide and high insulin levels indicate exogenous insulin; high C-
peptide and insulin levels indicate endogenous insulin, e.g. surreptitious
drug (sulfonylurea) ingestion or insulinoma.
Causes of hypoglycaemia
In the majority of inpatients with DM, hypoglycaemia occurs due to:
• i insulin and sulfonylureas:
• Prescription errors such as wrong insulin, dose, or time.
• Inappropriate use of drugs or insulins.
• Sliding scale.
• d insulin or medication requirements:
• Acute illness, e.g. sepsis, renal or liver failure.
• Drugs, e.g. reduction in steroids.
• Reduced oral intake or change in dietary pattern.
Other causes are summarized in Box 9.4 and should be considered in any
new presentation or recurrent causes of hypoglycaemia.
Hypoglycaemia: management
Acute measures
(See Box 9.5.)
• Remember to take blood prior to glucose administration (glucose,
insulin, C-peptide) (E Hypoglycaemia: assessment, pp. 556–7).
• If there is a history of chronic alcohol intake or malnourishment, give IV
thiamine 1–2mg/kg to avoid precipitating WE.
• Mild (patient conscious, orientated, and able to swallow):
• If the patient is conscious and cooperative, give 15–20g of quick-
acting carbohydrate (see Box 9.5). Test glucose after 10–15min; if
<4mmol/L, repeat treatment up to three times.*
• Moderate (patient conscious, but confused/disorientated or aggressive,
and able to swallow):
• If cooperative and safe to swallow, treat as for mild hypoglycaemia;
otherwise give either 1.5–2 tubes of Glucogel® squeezed into
the mouth between the teeth and gums or treat as for severe
hypoglycaemia. Test glucose after 10–15min; if <4mmol/L, repeat
treatment up to three times.*
• Severe (patient unconscious, fitting, or aggressive):
• 80mL of 20% glucose IV over 10min (or 160mL of 10% glucose IV
over 10min); 50% glucose IV is not advised.
• If IV access is difficult, give 1mg of glucagon IM. Glucagon is not
effective if recurrent hypos, liver disease, starved, or NBM and
can only be used once. Test glucose after 10–15min. It should be
>4mmol/L.*
*
If repeated three times, consider IV 10% glucose at 100mL/h or 1mg glucagon IM (if no IV access
and not given already). Once blood glucose >4mmol/L, give 20g of long-acting carbohydrate (two
biscuits or a slice of bread) or the next meal if due. If IM glucagon given, give 40g of long-acting
carbohydrate to replenish glycogen stores. If NBM, give 10% glucose infusion at 10mL/h and review
glucose hourly.
Hypoglycaemia: further management
Further management
• Review glucose regularly in all patients. Give hypoglycaemia education,
and refer to the diabetes specialist nurse (DSN) if diabetic.
• Patients should regain consciousness or become coherent within
10min, although complete cognitive/neurological recovery may lag by
30–45min. Do not give further boluses of IV glucose without repeating
the blood glucose. If the patient does not wake up after 710min, repeat
the blood glucose and consider another cause of coma (e.g. head injury
while hypoglycaemic; E Head injury: presentation, p. 380).
• Prolonged severe hypoglycaemia (>4h) may result in permanent
cerebral dysfunction.
• Patients on sulfonylureas may become hypoglycaemic following a CVA
or other illness preventing adequate food intake.
• Recurrent hypoglycaemia may herald the onset of diabetic nephropathy,
as this decreases insulin requirements—insulin is partly degraded by the
kidney and sulfonylureas are really excreted.
• Review the patient’s current medication, and inspect all tablets from home.
• Admit if risk of recurrent hypoglycaemia, e.g. with OD of long-acting
insulin or sulfonylurea. Observe with hourly blood glucose and 10% IV
glucose at 125mL/h.
• Consider psychiatric review if self-inflicted.
• Two episodes of hypoglycaemia requiring emergency (third-party)
assistance requires Driver and Vehicle Licensing Authority (DVLA)
notification [one episode if category C (heavy goods vehicle, HGV) licence].
For key points in the management of hypoglycaemia, see Box 9.6.
Further reading
Joint British Diabetes Societies for Inpatient Care (2018). The hospital management of hypoglycaemia
in adults with diabetes mellitus, 3rd edn. M https://diabetes-resources-production.s3.eu-west-1.
amazonaws.com/resources-s3/2018-05/JBDS_HypoGuidelineRevised2.pdf%2008.05.18.pdf
560
Further reading
National Institute for Health and Care Excellence (2016). Diabetic foot problems: prevention and man-
agement. NICE guideline [NG19]. M https://www.nice.org.uk/guidance/NG19
562
Hyponatraemia: assessment
Presentation
• Mild hyponatraemia (Na+ 130–135mmol/L) is common, especially in
patients taking thiazide diuretics and is usually asymptomatic. Moderate
hyponatraemia (Na+ 120–129mmol/L) is usually asymptomatic, unless it
has developed rapidly.
• Severe hyponatraemia (Na+ <120mmol/L) may be associated with
disturbed mental state, restlessness, headache, confusion, irritability, and
nausea and vomiting. Severe symptoms, such as seizures, GCS scores
<8 or coma, and cardiorespiratory compromise, prevail as Na+ acutely
(<24h) drops below 115mmol/L.
History
History should focus on drugs, fluid losses (diarrhoea, frequency, sweating),
alcohol misuse, symptoms of cortisol deficiency, and symptoms or history
of thyroid, cardiac, lung, liver, or renal disease.
Examination
Examination should focus on careful assessment of volume status and, in par-
ticular, should assess whether the patient is hypovolaemic, normovolaemic,
or overloaded/oedematous. Patients should therefore have an assessment
of their lying and standing BP, HR, JVP or CVP, skin turgor, and the presence
of oedema or ascites.
Patients who are hyponatraemic and hypovolaemic are salt-depleted.
Investigations
• In addition to U&Es, other tests should be aimed at excluding other
causes of hyponatraemia (E Hyponatraemia: causes, pp. 372–3).
Common initial tests include:
• Measurement of serum osmolarity and its comparison to the
calculated osmolarity [2 × (Na+ + K+) + urea + glucose]. An increase
in osmolar gap is seen with substances such as ethylene glycol, severe
hyperglycaemia, mannitol, etc.
• Spot urine Na+ estimation, combined with clinical assessment of fluid
status, may help determine the underlying cause:
• Volume depletion from an extrarenal cause
(E Hyponatraemia: causes, pp. 372–3) is normally associated with a
low urinary Na+ (<10mmol/L).
• Volume depletion with a high urinary Na+ (>20mmol/L) suggests
inappropriate renal salt-wasting (e.g. intrinsic renal disease,
hypothyroidism, adrenal insufficiency, diuretics).
• Fluid overload with a low urinary Na+ (<10mmol/L) is seen in
conditions such as CCF, cirrhosis, or nephrotic syndrome where there
is Na+ retention in response to poor renal perfusion.
Euvolaemia with high urinary Na+ is seen with SIADH and rarely with
•
severe myxoedema.
Hyponatraemia: assessment 563
General principles
• Assessment of the patient’s volume status (neck veins, orthostatic
hypotension, cardiac signs of fluid overload, ascites, skin turgor) will
help in both diagnosis and subsequent treatment.
• Mild asymptomatic hyponatraemia will usually respond to treatment of
the underlying cause, and no specific therapy is necessary.
Correction of hyponatraemia should be gradual to avoid volume overload
and/or central pontine myelinolysis. Aim to restore serum Na+ to
7125mmol/L actively, and allow to rise gradually after that by treating
the underlying cause.
• Chronic hyponatraemia (>48h) can be corrected gradually. Significant
acute (<24h) hyponatraemia (>10mmol/L decline in serum Na+ or Na+
<120mmol/L) and severe symptomatic hyponatraemia require more
aggressive correction and monitoring. Seek expert help (see Box 9.8).
• Patients with cirrhosis and ascites and severe hyponatraemia should
have diuretics stopped, as diuretics worsen any reduction in tissue
perfusion and therefore reduce the ability to excrete free water.
• SIADH or other conditions associated with plasma volume expansion
can cause hypouricaemia (i renal clearance). Urate levels can therefore
be useful in differentiating hyponatraemia due to SIADH from other
causes of low Na+.
Hyponatraemia: causes
Decreased serum osmolarity
Hypovolaemia (hyponatraemia + hypovolaemia = salt depletion)
Renal losses (urinary Na+ Non-renal losses (urinary Na+
>20mmol/L) <20mmol/L)
• Diuretics. • GI losses (diarrhoea, vomiting).
• Addison’s disease. • Burns.
• Na+-losing nephropathies. • Fluid sequestration (e.g. peritonitis,
• Cerebral salt wasting. pancreatitis).
Normovolaemia (normal or mildly increased extracellular volume)
SIADH: urine osmolarity >100, serum osmolarity low (<280), urine Na+
>30mmol/L.
CNS disorders Malignancy Pulmonary disease
• Trauma. • Lung (oat cell). • Pneumonia.
• Stroke /SAH. • Pancreas. • TB.
• Malignancy (primary/ • Lymphoma or leukaemia. • Lung abscess.
secondary). • Prostate. • Cystic fibrosis.
• Vasculitis (e.g. SLE). • Urinary tract. • Lung vasculitis.
• Infection (abscess or • Head and neck
meningoencephalitis). carcinoma.
Drugs
(via SIADH ± i renal sensitivity to ADH or Na+ > water loss)
• Opiates. • Vasopressin. • Oxytocin.
• Haloperidol. • Thioridazine. • Chlorpropamide.
• Amitriptyline. • Carbamazepine. • Thiazides.
• Cyclophosphamide. • Clofibrate. • Vincristine.
Miscellaneous causes
• Severe myxoedema.
• Alcohol misuse.
• Psychogenic polydipsia.
Oedematous states
• CCF. • Cirrhosis with ascites.
• Severe renal failure. • Nephrotic syndrome.
Hyponatraemia: causes 565
56
Hyponatraemia: management
• Exclude pseudohyponatraemia: lipaemic serum will be obvious (ask the
biochemist). Calculate the osmolar gap to check there are no ‘hidden’
osmoles (E Hyponatraemia: causes, pp. 372–3). Always exclude the
possibility of artefactual Na+ from blood taken proximal to an IVI.
• The correction in Na+ concentration must not exceed 10mmol/
L in the first 24h and 8mmol/L per day thereafter. Rapid correction
of hyponatraemia must be avoided, as it can result in osmotic
demyelination known as ‘cerebral pontine myelinolysis’ (see Box 9.9).
• Chronic hyponatraemia can be corrected gradually.
• Symptomatic hyponatraemia (e.g. seizures or coma): requires a more
aggressive initial correction to increase serum Na+ concentration (see
Box 9.10). Seek expert help early.
• If volume-deplete (dehydrated): start an IVI of normal saline
(0.9% = 154mmol/L of Na+); insert a central venous line if indicated.
Monitor fluid output. Catheterize the bladder if there is renal
impairment. Watch out for heart failure.
• If not dehydrated: for patients with moderate SIADH, restrict fluid intake
to 500–1000mL/24h. Seek expert help.
• Remember that giving K+ can raise plasma Na+ levels in a hyponatraemic
subject. The increase in Na+ concentration caused by concurrent
K+ administration should be taken into account to avoid over-rapid
correction of hyponatraemia. Any K+ added to the infused solution
should be considered as Na+ in the equation below (see Box 9.10),
i.e.: change in [Na+] = {fluid [Na+ + fluid [K+]} − serum [Na+]/(total
body water + 1).
Hyponatraemia: management 567
Further reading
National Institute for Health and Care Excellence CKS (2015). Hyponatraemia. M http://cks.nice.
org.uk/hyponatraemia
Spasovski G, Vanholder R, Allolio B, et al.; Hyponatraemia Guideline Development Group. Clinical
practice guideline on diagnosis and treatment of hyponatraemia. Eur J Endocrinol 2014;170:G1–47.
M http://www.eje-online.org/content/170/3/G1.full.
568
Hypernatraemia
Abnormalities in serum Na+ are usually associated with changes in serum
osmolality and extracellular volume (ECV).
Presentation
Symptoms often relate to severe volume depletion: weakness, malaise, fa-
tigue, altered mental status, confusion, delirium, or coma.
Many patients with severe hypernatraemia are seen in intensive care,
often with an intracranial catastrophe. The cause or mechanism of
hypernatraemia in these patients is unknown.
Causes
• Osmotic diuresis (glycosuria), as seen in HHS.
• Critically ill with intracranial pathology.
• Diarrhoea/protracted vomiting.
• Burns.
• Diabetes insipidus (DI) (particularly when the patient becomes unwell
and is unable to keep up with oral fluids).
• Respiratory losses (hot, dry environment).
• Iatrogenic (administration of salt/saline or sodium bicarbonate).
• Mineralocorticoid excess (Conn’s, Cushing’s).
The way to determine the cause of abnormal serum Na+ is by:
• Careful assessment of the ECV [evaluation of neck veins, supine and
standing BP, any cardiac signs of fluid overload (e.g. S3, oedema), and
skin turgor], in association with:
• Measuring serum and urine osmolality. Serum osmolality may be
estimated by [2 × (Na+ + K+) + urea + glucose], but this is inaccurate
when there are other osmoles (e.g. ketones, ethanol, methanol,
ethylene glycol, renal failure) that contribute.
Serum Na+ >145mmol/L is always associated with hyperosmolarity.
Management
• Avoid rapid and extreme changes in serum Na+ concentration. It is safer
to change serum Na+ cautiously. Aim initially for no more than 10mmol
reduction in 24h.
• If there is hypovolaemia, start fluid replacement. Normal saline (0.9%)
contains elemental Na+ at 154mmol/L. Use this initially to correct
hypovolaemia, if present, then change to 5% glucose to replace water
and slowly correct Na+ concentration.
• If the patient is haemodynamically stable, encourage oral fluids.
• Monitor electrolytes twice daily initially, and more frequently if
hypernatraemia is known to be acute (<48h).
Hypernatraemia 569
570
Acute hypocalcaemia
Presentation
• Abnormal neurological sensations and neuromuscular excitability.
• Numbness around the mouth and paraesthesiae of the distal limbs.
• Hyper-reflexia.
• Carpopedal spasm.
• Tetanic contractions (may include laryngospasm).
• Focal or generalized seizures. Rarely extrapyramidal signs or
papilloedema.
• Hypotension, bradycardia, arrhythmias, and CCF.
• Chvostek’s sign is elicited by tapping the facial nerve just anterior to the
ear, causing contraction of the facial muscles (seen in 10% of normals).
• Trousseau’s sign is elicited by inflating a BP cuff for 3–5min 10–20mmHg
above the level of SBP. This causes mild ischaemia and unmasks
latent neuromuscular hyperexcitability, and carpal spasm is observed.
(Carpopedal spasm may also occur during hyperventilation-induced
respiratory alkalosis.)
Investigations
• Plasma Ca2+, PO43–, and albumin.
• Corrected Ca2+ = measured Ca2+ + [40 − serum albumin (g/L)] × 0.02.
• Plasma Mg2+.
• Vitamin D and ALP.
• U&Es.
• ECG (prolonged QT interval).
• Plasma PTH level.
• Skull X-ray (SXR) (intracranial calcification, especially
hypoparathyroidism).
Management
• The aim of acute management is to ameliorate the acute manifestations
of hypocalcaemia, and not necessarily to return Ca2+ to normal.
• For frank tetany, 10mL of 10% calcium gluconate (diluted in 100mL of
normal saline or 5% glucose) can be given by slow IV injection over
10min. NB: 10mL of 10% calcium chloride (9mmol) contains 74-fold more
Ca2+ than calcium gluconate. Calcium gluconate is preferred, as it causes
less tissue necrosis if it extravasates. IV Ca2+ should never be given
faster than this because of the risk of arrhythmia. This initial treatment
with IV calcium gluconate is followed with a slow infusion of calcium
gluconate—add 100mL of 10% calcium gluconate to 1L of normal saline
or 5% glucose. Start the infusion at 50mL/h, and titrate to maintain
serum Ca2+ in the low-normal range.
• Post-parathyroidectomy, mild hypocalcaemia normally ensues,
requiring observation only. In patients who have parathyroid bone
disease, however, ‘hungry bones’ may cause profound hypocalcaemia
shortly after the parathyroids are removed. This may cause severe and
prolonged hypocalcaemia which requires prolonged treatment.
Hypercalcaemia
Definition
• Mild—corrected Ca2+ 2.65–3mmol/L.
• Moderate—corrected Ca2+ 3.01–3.40mmol/L.
• Severe—>3.4mmol/L.
• The free (ionic) plasma Ca2+ concentration is dependent on both arterial
pH (increases with acidaemia due to d protein binding of ionized Ca2+)
and plasma albumin.
• Corrected Ca2+ = measured Ca2+ + [40 − serum albumin (g/L)] × 0.02;
for example, if measured Ca2+ = 2.10mmol/L and albumin = 30g/L,
corrected Ca2+ = 2.10 = [(40 − 30) × 0.02] = 2.30mmol/L.
• Most blood gas analysers now measure ionized Ca2+.
For causes of hypercalcaemia, see Box 9.13.
Presentation
• Routine biochemical screen in an asymptomatic patient.
• General: symptoms are often non-specific and include depression
(30–40%), weakness (30%), tiredness and malaise, itching, keratitis, and
corneal calcification.
• GI: constipation, anorexia, vague abdominal symptoms (nausea,
vomiting), weight loss.
• Renal: renal calculi (if long-standing); nephrogenic DI (20%); type 1 renal
tubular acidosis; pre-renal failure; chronic hypercalcaemic nephropathy,
polyuria, polydipsia, or dehydration.
• Neuropsychiatric: anxiety, depression, and cognitive dysfunction; coma or
obtundation.
• Cardiac: hypertension, cardiac dysrhythmias, short QT interval on ECG.
For investigations of hypercalcaemia, see Box 9.14.
Urgent treatment is required if
• Ca2+ >3.4mmol/L or if symptomatic, i.e.:
• Clouding of consciousness or confusion is present.
• Hypotension.
• Severe dehydration causing pre-renal failure.
Management
• Rehydrate patient with IV 0.9% saline. Aim for about 3–6L/24h,
depending on fluid status (CVP), urine output, and cardiac function.
• If the patient does not pass urine for 4h, pass a urinary catheter and a
central venous line to monitor CVP.
• Stop medications which may be contributing to hypercalcaemia, i.e.
thiazide diuretics.
• Diuretics: once the patient is rehydrated, continue 0.9% saline infusion
and consider adding furosemide with care. Avoid further dehydration,
and carefully monitor K+ and other electrolytes and replace if necessary.
The usual dose is 20mg every 4h (i.e. with each litre); however, some
patients may need a larger dose to avoid pulmonary oedema. Patients
need to have K+ added to all the bags to avoid hypokalaemia with
Hypercalcaemia 573
• Monitor electrolytes, especially K+ and Mg2+ which may fall rapidly with
rehydration and furosemide. Replace K+ (20–40mmol/L of saline) and
Mg2+ (up to 2mmol/L saline) IV.
• If this fails to reduce plasma Ca2+ adequately (Ca2+ still >2.8mmol/L),
then the following measures should be considered:
• Bisphosphonates: inhibit osteoclast activity, thereby causing a fall in
plasma Ca2+. Administer pamidronate at 30–60mg IV over 4–6h. (As a
general rule, give 30mg over 4h if Ca2+ is <3mmol/L or for all patients
with significant renal impairment, 60mg over 8h if Ca2+ is 3–4 mmol/
L.) Ca2+ levels begin to fall after 48h and remain suppressed for up to
14 days. Zoledronic acid has a shorter infusion time (15min) and is said
to more effective with a longer duration of action.
• Salmon calcitonin 400IU q8h. This has a rapid onset of action (within
hours), but its effect lasts only 2–3 days (tachyphylaxis). It may also
provoke nausea.
• Steroids (prednisolone 30–60mg PO od): most effective in
hypercalcaemia due to sarcoidosis, myeloma, or vitamin D intoxication.
• Consider use of the calcimimetic ‘cinacalcet’ if hypercalcaemia is due to
primary hyperparathyroidism not amenable to surgical treatment.
• Familial hypocalciuric hypercalcaemia: elevated Ca2+, normal 24h urinary
Ca2+. This causes few symptoms (mild fatigue or lethargy). PTH may be
raised, but the patient does not respond to parathyroidectomy.
• Dialysis may be considered in refractive hypercalcaemia or if large fluid
loads are not feasible.
For key points in the management of hypercalcaemia, see Box 9.15.
Further reading
National Institute for Health and Care Excellence CKS (2014). Hypercalcaemia. M http://cks.nice.
org.uk/hypercalcaemia
Hypercalcaemia 575
576
Hypophosphataemia
Plasma PO43– is normally 0.8–1.4mmol/L. Hypophosphataemia is common
and often unrecognized by clinicians. Most intracellular PO43– is present as
creatine phosphate or adenine phosphates [e.g. adenosine triphosphate
(ATP)], and in RBCs, the predominant species is 2,3-diphosphoglycerate.
Hypophosphataemia does not necessarily indicate PO43– deficiency; simi-
larly, PO43– deficiency may be associated with normal or high plasma PO43–
concentrations. See Box 9.16 for causes of hypophosphataemia.
Presentation
• Most cases of severe hypophosphataemia occur in very sick patients
(often in an ITU). Occasionally seen in asymptomatic patients.
• Coincident Mg2+ deficiency exacerbates PO43– depletion, and vice versa.
• Modest hypophosphataemia has no effect but warrants investigation.
Severe hypophosphataemia (<0.4mmol/L) may cause symptoms and
requires treatment.
See Box 9.17 for manifestations of severe hypophosphataemia.
Investigations
• Vitamin D and PTH.
• LFTs.
• Aldosterone.
• ABGs.
• Serum glucose.
• Serum and urine electrophoresis.
• 24h urine PO43–.
Treatment
• PO43– repletion should generally be reserved for patients with sustained
hypophosphataemia (e.g. ≤0.4mmol/L). Treatment of the underlying
cause (DKA, diarrhoea, vitamin D deficiency) will often correct
hypophosphataemia.
• Orally, give effervescent Phosphate Sandoz® two tablets tds or
potassium phosphate IV (9–18mmol/24h).
• IV PO43– replacement can be considered in severe deficiency but should
be used with care. Aggressive IV PO43– therapy can cause hypocalcaemia
with seizures and tetany, as well as renal impairment and potentially
arrhythmias. Serum PO43– and Ca2+ levels should be monitored 6-hourly
during PO43– infusion.
• Excessive PO43– replacement may cause hypocalcaemia and metastatic
calcification; monitor Ca2+, PO43–, K+, and other electrolytes.
• PO43– should not be infused with Ca2+, as this will cause Ca2+ to
precipitate.
For key points on the management of hypophosphataemia, see Box 9.18.
Hypophosphataemia 577
Addisonian crisis: assessment
Adrenocortical insufficiency may be subclinical for days or months in other-
wise well individuals. Stress, such as infection, trauma, or surgery, may pre-
cipitate an Addisonian crisis, with cardiovascular collapse and death if the
condition is not suspected (see Boxes 9.19 and 9.20). Crises may also occur
in patients with known Addison’s disease on replacement hydrocortisone if
they fail to increase their steroid dose with infections. For causes of adrenal
failure, see Box 9.19.
Presentation
• Hypotension and cardiovascular collapse (shock).
• Faintness, particularly on standing (postural hypotension).
• Anorexia, weight loss, nausea, vomiting, and abdominal pain.
• Hyponatraemia and hyperkalaemia.
• Dehydration (thirst may not be apparent because of low Na+).
• Salt cravings.
• Diarrhoea in 20% of cases.
• Symptoms of precipitant: fever, night sweats (infection), flank pain
(haemorrhagic adrenal infarction), etc. Note signs/symptoms of other
endocrinopathies.
• Non-specific: weight loss, fatigue, weakness, myalgia, low-grade fever,
headache, cramps, joint pain.
• Hyperpigmentation suggests chronic hypoadrenalism.
• Loss of axillary or pubic hair in women.
• Psychiatric features are common and include asthenia, depression,
apathy, and confusion (treatment with glucocorticoids reverses most
psychiatric features).
Autoimmune adrenalitis
Accounts for 70–90% of cases in developed countries. Look for clinical evi-
dence of other autoimmune disorders.
TB adrenalitis
Worldwide this is the most common cause of adrenal insufficiency.
Adrenal infiltration
Malignant secondaries may be present in the adrenals of a high percentage
of patients with lung cancer, breast tumours, and malignant melanomas.
Adrenal failure will only occur when over 90% of the gland is replaced by
metastases.
The adrenals may alternatively be infiltrated in primary adrenal lymphoma,
sarcoidosis, amyloidosis, and haemochromatosis.
Practice points
• Seventy-five per cent of patients with autoimmune adrenalitis have
one or more other autoimmune disorders such as polyglandular
autoimmune syndrome type 1 or 2.
• Never forget Addison’s disease in a sick patient when the diagnosis is
unclear.
• Patients with adrenal insufficiency should be informed of sick day rules
and should carry a steroid card or a MedicAlert bracelet/pendant.
Adrenal haemorrhage
This may complicate sepsis (meningococcal septicaemia, Waterhouse–
Friderichsen syndrome), traumatic shock, coagulopathies, and ischaemic
disorders.
• Severe stress substantially increases the arterial blood supply to the
adrenals. However, the adrenal gland has only one or two veins, making
it vulnerable to venous thrombosis.
• Blood tests: a precipitous drop in Hb, hyponatraemia, hyperkalaemia,
acidosis, uraemia, and neutrophilia.
• Waterhouse–Friderichsen syndrome is the association of bilateral adrenal
haemorrhage with fulminant meningococcaemia. Adrenal haemorrhage
can also be seen with other Gram –ve endotoxaemias such as Diplococcus
pneumoniae, Haemophilus influenzae B, and DF-2 bacillus infections.
Hypopituitarism
As there is no mineralocorticoid deficiency (the release of which is renin,
not ACTH-dependent), salt and water loss and shock are less profound
than in primary Addison’s disease.
Drugs
Rifampicin, phenytoin, and phenobarbital accelerate the metabolism of
cortisol and may precipitate an Addisonian crisis in partially compromised
individuals or in those on a fixed replacement dose. Most adrenal crises pre-
cipitated by rifampicin occur within 2 weeks of initiating therapy.
Addisonian crisis: management
Investigations
• U&Es Hyponatraemia and hyperkalaemia (rarely >6.0mmol/L).
High urea:creatinine ratio, indicative of hypovolaemia.
• FBC Anaemia [normal mean corpuscular volume (MCV)], mod-
erate neutropenia with relative eosinophilia/leucocytosis.
• Glucose Hypoglycaemia (rarely).
• Ca2+ May be high.
• Cortisol Baseline <400nmol/L. In sick patients, an expected cortisol level
is in the range of 1000nmol/L (NB may be difficult to interpret
in a patient on oestrogen therapy due to i binding proteins).
• ABG Mild metabolic acidosis, respiratory failure.
• Urine MC&S for infection; urinary Na+ may be high despite
hyponatraemia/hypovolaemia.
• CXR Previous TB, bronchial carcinoma.
• AXR Adrenal calcification.
Management
(See Box 9.21.)
• Treatment may be required before the diagnosis is confirmed.
• General measures include O2, continuous ECG monitoring, CVP
monitoring, urinary catheter (for fluid balance), and broad-spectrum
antibiotics for underlying infection.
• Treat shock (E Shock: management, pp. 332–3): give IV normal saline
for hypotension—1L stat, then depending on response and clinical signs.
Inotropic support may be necessary.
• Give IV glucose if hypoglycaemic.
• If an adrenal crisis is suspected, the patient needs glucocorticoids
urgently. Take blood for cortisol and ACTH measurement, and then
administer glucocorticoid. Use of dexamethasone is now generally
discouraged. Hydrocortisone should be administered IV (100mg qds
initially). Commencing hydrocortisone can do little harm and may be
lifesaving. The dose can later be reduced to an oral maintenance regime
once the patient has stabilized, which may be up to 72h.
• Short Synacthen® test (omit if the patient is known to have Addison’s
disease): take baseline blood sample (serum) and administer
tetracosactide (Synacthen®) 250 micrograms IM or IV. Take further
samples at 30 and 60min for cortisol assay.
• Fludrocortisone (50–100 micrograms daily PO) in patients with
adrenal insufficiency when stabilized on oral replacement doses of
hydrocortisone. Mineralocorticoid replacement is not initially required,
as large doses of glucocorticoids confer some mineralocorticoid activity.
Prevention
• Patients on long-term steroid therapy and/or known adrenocortical
failure should be instructed to increase steroid intake for predictable
stresses (e.g. elective surgery, acute illnesses with fever >38°C) or
planned excessive exertion.
• For mild illnesses, if not vomiting, double the oral dose. Vomiting
requires IV/IM therapy (hydrocortisone 50–100mg qds).
References
1. British National Formulary (1995). Section 6.3.2. Pharmaceutical Press, London; p. 615.
Further reading
National Institute for Health and Care Excellence (2016). Addison’s disease: management. M https://
cks.nice.org.uk/addisons-disease
Society for Endocrinology (2015). Adrenal insufficiency. Patient booklet. M https://www.endocrin-
ology.org/media/1767/16-04_adrenal-insufficiency.pdf
584
Myxoedema coma
A common precipitant of coma is the use of sedatives, and subsequent
hypothermia, in elderly ♀ patients with undiagnosed hypothyroidism.
Myxoedema coma has a high mortality (30–50%) if inadequately treated.
Presentation
• Altered mental status: disorientation, lethargy, frank psychosis.
• Coma (symmetrical, slow-relaxing reflexes; 725% have seizures).
• Hypothermia.
• Bradycardia, hypotension (rare).
• Hypoventilation.
• Hypoglycaemia.
Investigations
• U&Es Hyponatraemia is common (50%).
• Glucose Hypoglycaemia may occur.
• FBC Normocytic or macrocytic anaemia (there may be
coexisting pernicious anaemia).
• CK Often elevated due to myositis.
• TFT T4 and TSH.
• Cortisol There may be coexisting adrenal insufficiency.
• ABG Hypoventilation causing respiratory acidosis.
• Septic Blood and urine cultures—full examination essential, espe-
screen cially in the elderly.
• CXR Pericardial effusion may occur, also as part of septic screen.
• ECG Small complexes (pericardial effusion), prolonged QT
interval. MI can precipitate myxoedema coma in pre-
existing disease.
Poor prognostic indicators
• Hypotension: patients with hypothyroidism are usually hypertensive
due to high compensatory endogenous catecholamines. Reduced
BP indicates possible adrenal failure or cardiac disease. Response to
inotropes is poor, as patients are usually maximally vasoconstricted.
• Bradycardia.
• Hypothermia unresponsive to treatment.
• Sepsis.
• Reduced GCS scores and use of sedative medications.
• Hypoventilation and need for mechanical ventilation: is the most common
cause of death in patients with myxoedema coma. The hypoxia
responds poorly to O2 therapy which tends to exacerbate hypercapnia.
Management
(See Box 9.22.)
• Transfer the patient to ICU and monitor closely.
• Mechanical ventilation should be instituted for respiratory failure.
• CVP line: patients may be hypertensive and hypovolaemic, as chronic
myxoedema is compensated for by rising catecholamines.
Myxoedema coma 585
Thyrotoxic crisis: assessment
The term thyrotoxic crisis refers to a constellation of symptoms and signs
which together imply a poor prognosis. TFTs provide no discrimination be-
tween simple thyrotoxicosis and a thyrotoxic crisis (see Table 9.4). If the
diagnosis has not been made, look for clues such as a goitre or exophthalmic
Graves’ disease. The presentation may be confused with sepsis or malignant
hyperthermia. A thyrotoxic crisis carries a mortality rate of 30–50%.
Presentation
Cardiovascular symptoms GI symptoms
• Palpitations. • Diarrhoea.
• Tachycardia/tachyarrhythmias. • Vomiting.
• Cardiac failure/oedema. • Jaundice.
• Hypotension. • Abdominal pain.
• Arrhythmia.
• Cardiovascular collapse.
CNS symptoms General symptoms
• Anxiety/agitation. • Fever.
• Violent outbursts. • Hyperventilation.
• Psychosis/delirium. • Sweating.
• Fitting/coma. • Polyuria.
Rarely, patients may present with an apathetic thyroid storm and lapse into
a coma, with few other signs of thyrotoxicosis.
Precipitants of thyrotoxic crisis
• Thyroid surgery/general surgery.
• Withdrawal of antithyroid drug therapy/radioiodine therapy.
• Thyroid palpation.
• Iodinated contrast dyes.
• Infection.
• CVA/PE/MI.
• Parturition.
• DKA.
• Trauma or emotional stress.
• Burns.
Investigations
• TFTs (most labs can perform an urgent TSH/free T4 if needed).
• U&Es (? dehydration).
• Ca2+ (may be elevated).
• Glucose (may be low).
• FBC (may see raised WBC).
• LFTs (? jaundice, raised ALP).
• Blood and urine cultures.
• CXR (? pulmonary oedema or evidence of infection).
• ECG (rate ? AF).
Thyrotoxic crisis: management
Patients with a thyrotoxic crisis or impending crisis
(See Box 9.23.)
• Admit the patient to ICU.
• Fluid balance: CVP monitoring is essential to avoid precipitating or
worsening cardiac failure. In patients with arrhythmias, the CVP will
not accurately reflect left-sided pressures and PA pressure monitoring
should be considered. GI and insensible (pyrexia and excessive sweating)
fluid losses may exceed 5L/day and must be replaced.
• Fever should be treated with paracetamol and aggressive peripheral
cooling techniques. Dantrolene has been occasionally used to control
hyperthermia in a thyrotoxic crisis. Do not use salicylates which will
displace T4 from thyroxine-binding globulin (TBG) and can hence
worsen the storm.
• β-block the patient with propranolol 60–80mg q4h PO or 1mg
IV (repeated every 10min as necessary), with cardiac monitoring.
Propranolol also inhibits peripheral T4 to T3 conversion. Fever,
tachycardia, and tremor should respond immediately. An alternative is
esmolol (15–30mg as a bolus, followed by 3–6mg/min infusion).
• If β-blockade is contraindicated (e.g. asthma), consider a calcium
channel blocker such as diltiazem.
• Treat precipitating factors such as infection (e.g. cefuroxime 750mg IV tds).
• High-dose antithyroid drugs: propylthiouracil (PTU) (600mg loading
dose, then 200–300mg q4h PO/NG) is more effective than carbimazole
(20mg 4-hourly), as it inhibits peripheral T4 to T3 conversion.
• Consider bile acid sequestrants, e.g. colestyramine 2g qds, which can
increase faecal excretion of T4.
• Hydrocortisone: 100mg 6-hourly. This also inhibits conversion of
T4 to T3.
• Enoxaparin 20mg/day SC should be given to very sick patients at risk of
thromboembolism.
• Once organification of iodine has been blocked by antithyroid drugs,
iodine can be used to inhibit T4 release from the thyroid gland (Wolff–
Chaikoff effect). Lugol’s iodine contains 5% iodine and 10% potassium
iodide in water. Give 1mL PO every 6h. Do not give Lugol’s iodine until
at least 1h after the antithyroid drugs have been given. Any iodine given
prior to antithyroid medication may increase thyroid hormone stores.
Continue iodine-containing preparations for a maximum of 2 weeks
(lithium 300mg 8-hourly is an alternative to iodine in allergic patients).
• Monitor glucose levels 4-hourly and administer glucose 5–10% as
required. Hepatic glycogen stores are readily depleted during a
thyroid storm.
• Consider plasmapheresis if refractory to treatment.
Continuing treatment
• Response to treatment is gauged clinically and by serum T3 levels.
• Stop iodine/potassium iodide/lithium and β-blockers when controlled.
• Consider definitive treatment (e.g. surgery or radioactive iodine).
• Treat AF in the usual way (E Atrial fibrillation: assessment, pp. 76–7).
Higher doses of digoxin may be required, as its metabolism is i.
Amiodarone inhibits peripheral T4 to T3 conversion.
Further reading
American Thyroid Association. Hyperthyroidism (overactive). M https://www.thyroid.org/
hyperthyroidism
Carroll R, Matfin G. Endocrine and metabolic emergencies: thyroid storm. Ther Adv Endocrinol Metab
2010;1:139–45.
590
Pituitary apoplexy
Presentation
Pituitary infarction may be silent (‘subclinical pituitary apoplexy’). Apoplexy
implies the presence of symptoms. The clinical manifestations may be due
to leakage of blood/necrotic tissue into the subarachnoid space or rapid
expansion of a suprasellar mass and pressure on local structures. This may
be the presenting symptom of the pituitary tumour (see Box 9.24).
• Headache occurs in 95% of cases (sudden onset; variable intensity).
• Visual disturbance occurs in 70%, (usually bitemporal hemianopia).
• d level of consciousness.
• Ocular palsy (up to 70%) causing diplopia, unilateral or bilateral.
• Nausea/vomiting.
• Meningism (common).
• Hemiparesis or rarely seizures.
• Fever, anosmia, CSF rhinorrhoea, and hypothalamic dysfunction
(disturbed sympathetic autoregulation with abnormal BP control,
respiration, and cardiac rhythm) are all described but are rare.
• Altered mental state, lethargy, delirium, or coma.
• Symptoms of a preceding pituitary tumour.
• Acute hypopituitarism.
Clinically, pituitary apoplexy may be very difficult to distinguish from an
SAH, bacterial meningitis, midbrain infarction (basilar artery occlusion), or
cavernous sinus thrombosis. Transient neurological symptoms are common
in the preceding few days.
The clinical course is variable. Headache and mild visual disturbance may
develop slowly and persist for several weeks. In its most fulminant form,
apoplexy may cause blindness, haemodynamic instability, coma, and death.
Residual endocrine disturbance (panhypopituitarism) invariably occurs.
Investigations
• U&Es: hyper-or hyponatraemia may occur.
• Renal function, LFTs, clotting, and FBC.
• Endocrine function tests (save clotted blood): cortisol, TFTs, prolactin,
growth hormone (GH), IGF-1, luteinizing hormone (LH), follicle-
stimulating hormone (FSH). The short Synacthen® test is unreliable in
the first 2–3 weeks.
• CT head: pituitary cuts with IV contrast will reveal a tumour mass or
haemorrhage 24–48h after onset; however, CT is diagnostic in only
730% of patients.
• MRI (gadolinium-enhanced with pituitary views): is the investigation of
choice, and urgent MRI is warranted. May be more informative in the
subacute setting.
• Formal visual field assessment: preferably in the first 24h if the patient is
stable.
Management
(See Box 9.25.)
• Stabilize the patient (airway, breathing, circulation).
• Hydrocortisone 100mg IV should be given if the diagnosis is suspected,
after the blood samples above have been collected, and is particularly
Further reading
Rajasekaran S, Vanderpump M, Baldeweg S, et al. UK guidelines for the management of pituitary
apoplexy. Clin Endocrinol (Oxf ) 2011;74:9–20.
Hypopituitary coma
Hypopituitarism does not become evident until 75% of the adenohypophysis
is destroyed, and at least 90% destruction is required for total loss of pitu-
itary secretion. Complete loss of hormone secretion can rapidly become
life-threatening and requires immediate therapy. In a mild or incomplete
form, hypopituitarism can remain unsuspected for years.
Presentation
In the absence of stress, patients with severe hypopituitarism may have few
symptoms or signs.
The development of pituitary hormone deficiency tends to follow a
characteristic pattern, with GH and gonadotrophins lost early, followed by
ACTH and TSH at a later stage. Symptoms of prolactin deficiency are rarely
seen, except in the failure of lactation in Sheehan’s syndrome.
A general anaesthetic or infection may precipitate hypoglycaemia and
coma, due to the combination of a lack of GH, cortisol, and T4, all of
which have a counter-regulatory effect on insulin. See Box 9.26 for causes
of panhypopituitarism.
Clues from the history include:
• Known pituitary adenoma.
• Recent difficult delivery: pituitary infarction following postpartum
haemorrhage and vascular collapse is a recognized cause of
hypopituitarism. Features include failure of lactation (deficiency
of prolactin and oxytocin), failure of menstruation (lack of
gonadotrophins), non-specific features, e.g. tiredness, weakness, loss of
body hair, and loss of libido (due to ACTH deficiency, hypothyroidism,
and gonadotrophin deficiency).
• Men may give a history of impotence, lethargy, and loss of body hair.
• Women report loss of menstruation.
Examination
• Examination of the comatose patient is discussed under
E Coma: assessment, pp. 348–9.
• Examine specifically for secondary sexual characteristics and physical
signs of myxoedema.
• Consider other causes for coma (E Coma: assessment, pp. 348–9).
Investigations
• General investigations for patients in coma are discussed under
E Coma: assessment, pp. 348–9.
• Take blood for baseline cortisol (9 a.m.), ACTH, TFTs, LH, FSH,
prolactin, and GH.
• Short Synacthen® test can be performed to test for adrenocortical
reserve (E Addisonian crisis: management, pp. 582–3); however, a test
of ACTH reserve, such as the insulin tolerance test or glucagon stress
test, may be performed at a later date when the patient has stabilized.
• Luteinizing hormone-releasing hormone (LHRH) and thyrotropin-
releasing hormone (TRH) tests may be performed at the same time as
the short Synacthen® test but are rarely necessary.
Hypopituitary coma 595
Phaeochromocytomas: assessment
• Phaeochromocytomas are catecholamine-producing tumours usually
involving one or both adrenal glands. Bilateral tumours are more likely
to represent part of a familial syndrome, and tumour location, as well
as risk of malignancy, varies depending on the genetic defect. Therefore,
the previously described ‘rule of 10’ for phaeochromocytoma is no
longer applicable. Phaeochromocytomas usually secrete adrenaline
(AD) or noradrenaline (NA). A small proportion secrete dopamine
(DA), when hypotension may occur.
• Most are diagnosed during routine screening of hypertensive patients
(they are found in only 0.1% of hypertensives). Pure AD-producing
tumours may mimic septic shock due to AD-induced peripheral
vasodilatation (β2-receptors).
Presentation
• Classically a triad of episodic headaches, sweating, and tachycardia.
• Hypertension (mild to severe sustained or uncontrolled paroxysmal
hypertensive episodes) and orthostatic hypotension (low plasma
volume); 50% have sustained elevated BP and 50% have paroxysmal
elevations.
• Anxiety attacks, tremor, palpitations, cold extremities, and pallor.
• Cardiac dysrhythmias (including AF and VF) and dilated cardiomyopathy.
• Hypertensive crises may be precipitated by β-blockers, tricyclic
antidepressants, metoclopramide, and naloxone.
• Unexplained lactic acidosis.
• Triggers for hypertensive crises include surgery (particularly
manipulation of the tumour itself ), opiates, and contrast media.
See Box 9.27 for other causes of sympathetic overactivity.
Investigations
(See Box 9.28.)
• Two to three 24h urine collections for measurement of metanephrines.
These are more sensitive and specific than catecholamines, and false-
negative results are rare. Measurements of 24h urine catecholamines
remain useful and should be collected if metanephrine measurement is
unavailable.
• Urine should be collected in acid-containing bottles and kept
refrigerated, as catecholamines are more stable at low pH and low
temperature. Urine for metanephrines is collected in the same way.
• Urinary creatinine and volume should be measured to verify an
adequate (i.e. 24h) collection.
• In patients who are at high risk for phaeochromocytoma (i.e. familial
syndromes or previously surgically cured phaeochromocytoma
or paraganglioma), both urine and plasma free metanephrine
and normetanephrine should be measured if available (higher
sensitivity—799%).
• Certain drugs (e.g. tricyclic antidepressants, levodopa, prochlorperazine,
and calcium channel blockers) should be tapered and discontinued at
least 2 weeks before any biochemical tests.
Phaeochromocytomas: assessment 597
Phaeochromocytomas: management
Patients are usually volume-depleted at presentation and should be rehy-
drated prior to initiation of β-blockade; otherwise severe hypotension may
occur. β-blockade alone may precipitate a hypertensive crisis and must
never be given prior to adequate α-blockade. Labetalol is predominantly
a β-blocker and should not be used alone. Long-acting α-blockers prevent
escape episodes.
• Adequate fluid replacement with CVP monitoring.
• Acute hypertensive crises should be controlled with phentolamine
(0.5–1mg IV bolus, repeated as necessary every 15–30min).
Alternatively, start an infusion of nitroprusside (0.5–1.5 micrograms/
kg/min; typical dose 100 micrograms/min).
• Preparation for surgery:
• Initiate oral α-blockade: phenoxybenzamine 10mg bd, increasing
gradually to 20–30mg bd. Higher doses may be required. Monitor BP
closely. Tumour β-stimulation may produce excessive vasodilatation
and hypotension, requiring inotropic support. Recent studies have
shown that prazosin or doxazosin are equally effective and are being
used increasingly. α-blockade is necessary for several weeks prior to
surgery to allow for adequate circulating volume expansion.
• When the BP is controlled with phenoxybenzamine, add propranolol
10–20mg tds.
• Invasive monitoring [PA (Swan–Ganz) catheter and arterial line] is
mandatory.
• Hypotension commonly occurs intraoperatively when the tumour is
removed, and this should be managed with blood, plasma expanders,
and inotropes, as required. Inotropes should only be used when the
patient is appropriately fluid-replete. Expansion of intravascular volume
12h before surgery significantly reduces the frequency and severity of
post-operative hypotension. Angiotensin II should be available as an
alternative inotrope for cases of resistant hypotension.
For key points on the management of phaeochromocytomas, see Box 9.29.
Phaeochromocytomas: management 599
References
2. Society for Endocrinology (2010). Protocol using oral phenoxybenzamine to prepare patients with
catecholamine-secreting phaeochromocytoma and paraganglioma for surgery. M https://www.endo-
crinology.org/media/1780/10-10_protocol_using_oral_phenoxybenzamine.pdf
Further reading
Endobible. Phaeochromocytoma. M http://www.endobible.com/condition/phaeochromocytoma/
60
Polyuria
Definition: >3L of urine per day.
Presentation
• Confusion (hyponatraemia or dehydration).
• Coma.
• Proteinuria on screening.
• Depression or other psychiatric manifestations.
• Renal stones.
Causes
• Excessive fluid intake.
• Endocrine dysfunction (DM, DI, hypercalcaemia, hyperthyroidism).
• Hypokalaemia.
• Intrinsic renal disease (polycystic kidneys, analgesic nephropathy,
medullary cystic disease, amyloidosis) or renal recovery from ATN.
• Post-obstructive uropathy, e.g. after catheterization of a patient in
chronic retention.
• Post-renal artery angioplasty.
• Drugs (furosemide, alcohol, lithium, amphotericin B, vinblastine,
demeclocycline, cisplatin).
History
• Duration and severity (nocturia, frequency, water consumption at night).
• Family history of DM, polycystic kidneys, and renal calculi.
• Drug history (see E Causes, p. 600).
• Renal calculi (hypercalcaemia).
• Weakness (low K+), depression (hypercalcaemia).
• Psychiatric history (psychogenic polydipsia; medications, i.e. lithium).
• Endocrine history (menses, sexual function, lactation, pubic hair).
• Other significant pathology (e.g. causes of amyloid).
Investigations
• U&Es (renal disease, hypokalaemia).
• TFTs.
• Glucose (undiagnosed DM).
• Ca2+, PO43–, and ALP.
• Plasma and urine osmolality: a urine:plasma osmolality of <1.0 indicates
DI, intrinsic renal disease (including low K+), or hysterical drinking.
• AXR (nephrocalcinosis).
• Lithium levels, if appropriate.
• Dipstick protein and quantification, if indicated.
Management
• Assess fluid status ( JVP, BP, postural drop, weight charts, CVP).
• Strict fluid balance and daily weights.
• CVP line may be necessary.
• Measure urinary Na+ and K+ (random spot samples will give an
indication of the loss of Na+ or K+ initially, and if losses are great,
accurate timed samples of <6h are possible).
Polyuria 601
Malignant hyperthermia
Malignant hyperthermia is a drug-or stress-induced catabolic syndrome
characterized by excessive muscular contractions, a sudden rise in body
temperature, and cardiovascular collapse. It is often related to the use of
anaesthetic agents. The incidence is 1:15 000, with a mortality which has
significantly reduced from 80% down to <10% due to better treatment and
i awareness of the condition. The cause is unknown but may involve ab-
normal Ca2+ homeostasis in skeletal muscle cells. The condition seems to be
inherited in an autosomal dominant manner, with variable penetrance. Early
recognition of the condition is essential for treatment and survival.
See Box 9.32 for drugs precipitating malignant hyperthermia. See Box
9.33 for drugs considered safe in malignant hyperthermia.
Diagnosis
• Malignant hyperthermia most commonly presents in patients in their
early 20s. Early signs are muscular rigidity, sinus tachycardia and SVTs,
i carbon dioxide production with tachypnoea, and hypertension.
Patients may sweat profusely and exhibit skin mottling.
• Hyperthermia occurs late and may be rapidly followed by hypotension,
mixed respiratory and metabolic acidosis, and hyperkalaemia, which
gives rise to VT and cardiac arrest.
• The condition almost always occurs perioperatively.
• The differential diagnosis includes phaeochromocytoma, thyrotoxic
crisis, narcotic-induced hyperthermia in patients taking MAOIs, and drug-
induced hyperthermia [caused by cocaine, phencyclidine, amphetamine,
Further reading
Glahn KP, Ellis FR, Halsall PJ, et al. Recognizing and managing a malignant hyperthermia crisis: guide-
lines from the European Malignant Hyperthermia Group. Br J Anaesth 2010:105:417–20.
604
Chapter 10 607
Haematological
emergencies
Table 10.1 (Contd.)
Presentation Causes Timing
Transfusion-related acute lung Donor white cell antibodies Early
injury (TRALI) (rare) (min/h)
Non-cardiogenic
pulmonary oedema
Pyrexia
Cough
Breathlessness
CXR changes
Delayed haemolysis Minor red cell antibodies Late
Pyrexia (7–10 days)
Anaemia
Jaundice
Delayed thrombocytopenia Platelet antibody Late
Purpura (commonly anti-PlA1) (2–10 days)
Mucosal bleeding
Infection Hepatitis B/C, non-A/B/C, Late
CMV, EBV, HIV, HTLV, (days/months)
toxoplasmosis, malaria,
syphilis
Management
The main problem encountered in practice is differentiating a (common)
rise in temperature during a blood transfusion from (the rare, but poten-
tially lethal) major transfusion reactions. The common patterns of reactions
are outlined in Table 10.1.
Pointers to a severe reaction include:
• Symptoms: does the patient feel unwell?
• Pattern of temperature: a rapid rise in temperature to >38°C is
common in minor reactions.
• Hypotension or tachycardia.
(See Table 10.2 for the management of blood transfusion reactions.)
061
Sickle-cell crisis: presentation
A small percentage of sufferers with sickle-cell disease have recurrent crises
and repeated hospital admissions. There is an unwarranted tendency to
attribute this to a low pain threshold or to ‘dependence’ on opiates, rather
than to the severity of disease. Analgesia should never be denied to pa-
tients. This group of patients has the highest rate of serious complications
and mortality as a result of their severe disease. Sudden death is still a major
problem.
Painful (vaso-occlusive) crisis
• This is the most common presentation in adults and children.
• Severe/excruciating pain is felt at one or more sites, especially long
bones (small bones in children), back, ribs, and sternum.
• There may be associated pyrexia (usually <38.5°C), tenderness, local
warmth, and swelling, or there may be no objective features.
• Haemolysis may be i (i bilirubin, i LDH, fall in Hb) but is not a good
correlate.
• There are no reliable clinical markers for the severity of a crisis.
Chest crisis
• The most commont cause of mortality.
• Vaso-occlusion of the pulmonary microvasculature results in reduced
perfusion and local infarction.
• May be heralded by rib/sternal pain and/or falling SpO2.
• May be precipitated by a chest infection, pregnancy, surgery, and in
smokers.
• Prevented by: increasing HbF, with hydroxycarbamide, and incentive
spirometry.
• Symptoms (which may be minor initially) include pleuritic chest pain and
breathlessness.
• Signs are variable (often minimal) but can progress rapidly; usually
reduced air entry at lung bases.
• CXR is variable: uni-/bilateral consolidation, usually basal; ‘white-out’;
minimal changes.
• PaO2 is often markedly reduced. NB O2 delivery is low, given anaemia.
Cerebral infarction
• Usually in children <5 years, rare in adults.
• Presents as acute stroke.
• High risk of recurrence.
Splenic/hepatic sequestration
• Usually in children <5 years.
• RBCs trapped in the spleen and/or liver, usually causing organomegaly.
• Causes severe anaemia; circulatory collapse.
Aplastic crisis
• Usually in children, young adults.
• Mainly caused by parvovirus infection, exacerbated by folate deficiency.
• Occasionally when hydroxycarbamide dose has i.
• Sudden fall in Hb, inappropriately reduced/normal reticulocyte count.
Haemolytic crisis
• Often accompanies painful crises.
• Exacerbated by medications, including in those with G6PD (even in ♀).
• Fall in Hb; i reticulocyte count.
Cholecystitis/cholangitis/biliary colic
• Pigment stones common due to haemolytic anaemia and genetic
predisposing polymorphism associated with Gilbert’s syndrome.
• Can be misinterpreted as vaso-occlusive crisis.
Priapism
• Prolonged, painful erections due to local vaso-occlusion (1–24h long).
• Major crisis often preceded by ‘stuttering’ priapism episodes.
• May result in permanent impotence.
• This is a urological emergency. On-call urologists should be informed on
the patient’s arrival in casualty.
Infections/septic shock
• Any age group.
• Fever may not be prominent, and hypotension is a late sign in children.
• Osteomyelitis may not be apparent and may mimic veno-occlusive crises
and complicate leg ulcers.
• Patients receiving iron chelation therapy are at risk of Yersinia spp.
• Patients with long-term venous access devices (e.g. Portacath) are at risk
of Gram +ve infections.
461
Sickle-cell crisis: management
General measures
See NICE guidelines CG1431.
See Box 10.1 for management key points in sickle-cell crises.
Control pain
• This should be individualized; seek expert haematology input.
• Assess pain objectively with a score to assess treatment response.
• Have a low threshold to investigate for causes of pain not attributable
to veno-occlusive disease, especially if atypical for the patient.
• Usually parenteral opiates are necessary, often in high doses (depending
on previous opiate exposure). Start low and review in 0.5h, titrating to
response, e.g.
• Morphine 5–40mg IM every 2h.
• Diamorphine 5–25mg SC every 2h.
• Failure to control pain using these regimens usually indicates the need
for a continuous opiate infusion or a patient-controlled analgesia (PCA)
pump. Some patients prefer pethidine, but there is a risk of seizures as
the drug metabolites accumulate.
• Oral analgesia (dihydrocodeine/NSAIDs) may be sufficient for minor
crises, with regular paracetamol (IV preferred initially).
• Supplementary analgesics, such as diclofenac 50mg tds PO, may have a
small additional benefit.
Ensure hydration
• IV crystalloids are preferred, but venous access may be a problem.
• Aim for an input of 3–4L/day, with close monitoring of balance.
• Fluids can be oral where venous access is problematic.
Give oxygen
• Not of proven benefit (except in chest crises), but often provides
symptomatic relief.
• Incentive spirometry prevents chest crises.
• Monitor O2 saturations on air and O2; falling sats may be an early
indication of a chest crisis.
• In a severe chest crisis, CPAP/full ventilation may become necessary.
Transfer to ITU early.
Give folic acid
Give 5mg PO od (continue long term in all patients).
Review sources of sepsis
• Infections are frequent (at least partly due to hyposplenism).
• Penicillin prophylaxis and vaccination [pneumococcal, Haemophilus
influenzae b (Hib), meningococcal, influenza] do reduce the incidence,
but some penicillin-resistant organisms are emerging.
• If an infective precipitant, or component, of the crisis is suspected,
start ‘blind’ antibiotics (e.g. cefuroxime 750mg IV tds) after an infection
screen.
• Consider less common sources of sepsis (e.g. osteomyelitis,
Mycobacterium, etc.).
Give thromboprophylaxis
LMWH prophylaxis should be used routinely.
Give other supportive therapy
Laxatives, antiemetics, and anti-pruritics with opiates.
Investigations
(See Table 10.3.)
Exchange transfusion
The exchange can be performed on a cell separator. Aim for Hb of between
70 and 90g/L (end haematocrit of 0.34) in either case; a higher Hb can in-
crease blood viscosity and precipitate further sickling. In severe crises, red cell
exchange should be repeated until the HbS % is <30%. If a larger exchange
is not required or fluid balance is not precarious, manual venesection of
1–2U can be performed. Fluid replacement (normal saline 1L over 2–4h),
followed by transfusion of extended phenotype cross-matched blood.
Indications for urgent exchange transfusion
• Chest crisis.
• Cerebral infarction.
• Severe, persisting painful crisis.
• Priapism.
• Organ failure.
• Refractory ulceration.
• Preoperative.
61
References
1. National Institute for Health and Care Excellence (2012). Sickle cell disease: managing acute painful
episodes in hospital. Clinical guideline [CG143]. M https://www.nice.org.uk/guidance/CG143
• Examine the skin, oral mucosa, and fundi for evidence of fresh bleeding.
• Restore circulatory volume with IV crystalloid (colloids exacerbate
bleeding) if there is haemodynamic compromise, and consider blood
component transfusion.
Specific therapy
• Look for any local cause for the bleeding (e.g. oesophageal varices,
vascular damage causing epistaxis, chest infection causing haemoptysis)
that may be amenable to treatment.
• Stop any drug that may be exacerbating the bleeding (see Box 10.2).
• Correct coagulation abnormalities, if appropriate (E Abnormal
coagulation 1, p. 620).
• Correct platelet abnormalities, if appropriate (E Abnormal platelets,
pp. 622–3).
Abnormal coagulation 1
Common causes
• Anticoagulants.
• Liver disease.
• DIC.
• Massive transfusion.
Rarer causes
• Haemophilia A (acquired or congenital) and B.
• von Willebrand’s disease (vWD) (acquired or congenital).
• Amyloid (acquired factor X or IX deficiency with vasculopathy).
• α2-antiplasmin deficiency.
• Vitamin K deficiency:
• Obstructive jaundice.
• Small bowel disease.
Diagnosis
(See Table 10.4.)
The lupus anticoagulant usually confers a prothrombotic, rather than a bleeding, tendency.
*
Reptilase is a snake venom not inhibited by heparin. It converts fibrinogen to fibrin.
Abnormal coagulation 2
Management
Options are:
• FFP: indicated for treatment of acute DIC with bleeding, improving
haemostasis in decompensated liver failure if bleeding or prior to a
procedure, and emergency reversal of warfarin therapy if no PCC
available. Give 15mL/kg, i.e. 4–5U (7200mL/U). Watch for signs of fluid
overload, and give IV furosemide, if necessary.
• Vitamin K: phytomenadione 5–10mg IV slowly (daily for 3 days) if
deficiency is suspected; 2–5mg IV/PO will improve over-warfarinization
in 6–12h if no bleeding with low INR; 0.5–1mg for minor adjustment.
• Protamine sulfate (1mg IV neutralizes 100IU of heparin): is rarely used in
practice. Stopping a heparin infusion will normalize the APTT in 2–4h.
• Cryoprecipitate or fibrinogen concentrate: should be considered if
fibrinogen level is below 1–1.2g/L.
• Factor concentrates: can be used in the treatment of isolated factor
deficiencies, e.g. haemophilia A. Concentrates of factors II, VII, IX, and
X are also available in some centres for specific reversal of warfarin
effects (PCC).
• Antifibrinolytics: are used for the treatment of life-threatening bleeds
following thrombolytic therapy or major surgery (e.g. cardiac
surgery or prostatectomy), and in certain conditions associated with
hyperplasminaemia (e.g. acute promyelocytic leukaemia, certain
malignancies). Give tranexamic acid 0.5–1g slow IV injection tds.
• Miscellaneous: desmopressin and oestrogens are occasionally used for
haemophilia and renal failure.
Abnormal platelets
Causes
Thrombocytopenia
(See Table 10.5.)
Table 10.5 Thrombocytopenia
Increased platelet consumption Reduced platelet production
• Immune: • Myelosuppressant:
• Idiopathic (ITP) • Drugs, alcohol
• Drug-induced • Viral infections
• SLE • Marrow infiltration/failure
• HIV-related • B12 or folate deficiency
• Non-immune: • ITP (one-third of cases)
• Massive transfusion • Inherited disorders (rare)
• Hypersplenism
• DIC, TTP
Anticoagulant therapy
(See Table 10.6.)
• Asymptomatic patients with INR >5 should have warfarin withheld for
1–2 doses, and the maintenance dose should be reduced. The cause for
the elevated INR should be addressed.
Non-vitamin K antagonist oral anticoagulants
Renal impairment and drug interaction may exacerbate bleeding. Actively
look for occult GI bleeding in the presence of bleeding elsewhere due to a
NOAC. See Table 10.7 for possible coagulation screen results with NOACs.
• Stop the NOAC; activated charcoal can be used if ingested within 1–2h.
• PCC 50U/kg can be used, with variable success, with other haemostatic
measures and agents for major bleeding.
• In addition, dialysis and/or idarucizumab can be used for the direct thrombin
inhibitor dabigatran reversal, and andexanet for factor Xa inhibitor reversal.
• A normal PT for factor Xa inhibitors (rivaroxaban or apixaban) or
a normal TT (or APTT) for the direct thrombin inhibitor dabigatran
usually indicates a low drug activity level with most reagents.
• A normal dilute TT (or ECT) in the presence of a direct thrombin
inhibitor (dabigatran), or a normal anti-Xa activity in the presence
of a factor Xa inhibitor (rivaroxaban or apixaban), usually indicates
subclinical levels that do not require specific reversal therapy.
• Half-lives in descending order from up to 17h to 9h: dabigatran,
rivaroxaban, apixaban.
• NOACs are contraindicated when the creatinine clearance is
<15mL/min (or <30mL/min for dabigatran), for metal cardiac valves,
and during pregnancy and lactation.
Heparin
Risk factors for bleeding include age, recent surgery or trauma, renal or
liver failure, malignancy, APTT ratio >3, and a coexisting haematological
abnormality.
Management
• Stop heparin: the APTT usually normalizes in 2–4h.
• Protamine sulfate (1mg IV neutralizes 100U of heparin): may be used;
halve the dose if heparin has been turned off 1h previously.
• LMWHs: are thought to have fewer bleeding complications. However,
their plasma half-life is longer and they are less effectively reversed with
protamine. Treatment of OD is as described earlier, but note that the
APTT is usually normal on LMWH.
• Heparin-associated thrombocytopenia (E Abnormal platelets,
pp. 622–3).
62
Massive transfusion/cardiopulmonary
bypass
• Dilutional thrombocytopenia and coagulopathy usually occur once
red cell concentrates equivalent to 72 blood volumes have been
transfused. With cardiopulmonary bypass, the extracorporeal circuit
further damages the native platelets and depletes coagulation factors.
Furthermore, cold temperature also inactivates platelets.
• Abnormalities include i PT, i APTT, i FDPs, and d fibrinogen.
• Post-transfusion thrombocytopenia is a distinct disorder seen 8–10 days
following a transfusion and is due to a platelet-specific antibody
(E Blood transfusion reactions, pp. 608–9).
Management
Treatment should be discussed with the haematology team and involves
platelet transfusion to keep the platelet count >50– 75 × 109/L (or
>100 × 109/L for CNS lesions/multiple trauma), FFP (4–5U) if PT or APTT
>1.5 × control, and cryoprecipitate (10–15U) if fibrinogen <500g/L.
628
Desmopressin
• Indications: mild to moderate haemophilia A, especially in children, vWD
type 1 and some type 2. Most have previously responded to a challenge
test dose.
• Dosage: 0.3 micrograms/kg in 100mL of normal saline IV over 30min;
may be repeated 8–12h later. Alternatively, can be given SC at the same
dose or intranasally (300 micrograms for an adult). Peak haemostatic
effect in 60–90min.
• Monitor pulse and BP closely. Side effects include flushing, hypotension,
tachycardia, headache, and nausea; rare reports of MI (caution in
patients >60 years or with cardiac history). Temporary fluid restriction
may be necessary (especially in children) due to ADH effects and risk of
hyponatraemia.
Tranexamic acid
• Give with desmopressin in vWD or mild haemophilia A. Most useful in
mucosal bleeds. Avoid in renal tract bleeding (may cause clots).
• Dosage: 1g PO qds (adults). Mouthwash 4.8% q10min for oral bleeding.
Cryoprecipitate
• Give for severe bleeding in vWD if vWF concentrate is not available
and bleeding not responding to desmopressin and tranexamic acid.
• Dosage: 10–20U (bags) for 70kg adult.
For example, a 70kg man with a minor bleed who is known to have haemophilia B and usually
receives BeneFix® should receive 65 × 70 = 4550U (round to the nearest vial = 4500U).
632
Heparin-induced thrombocytopenia
and thrombosis (HITT)
• An idiosyncratic reaction seen in 1–5%. Much less common with
LMWHs (<1%).
• Type I: mild and transient seen in the first week, often resolving
spontaneously with continued therapy.
• Type II: late-onset thrombocytopenia seen 5 days to 2 weeks after
starting therapy and is caused by an IgG autoantibody that results in
platelet activation, and thromboembolic events in 40% if untreated.
• Bleeding is rare at presentation but will be i because of the need for
alternative anticoagulant therapy.
• Consider the diagnosis if the problem demanding heparinization does
not resolve or worsens while the patient is on heparin (e.g. propagation
of DVT) or a new thrombotic event takes place in a heparinized patient,
in association with a >50% fall in platelet count.
• Diagnosis is based on the 4T scoring system (see Table 10.10).
The 4T score is the sum of the values for each of the four categories. Scores
of 0–3, 4–5, and 6–8 are considered to correspond to a low, intermediate,
and high probability of HIT, respectively.
Management
• HIT can be excluded by a low pretest probability score, without the
need for laboratory investigation.
• If the pretest probability of HIT is not low, heparin should be stopped
and an alternative anticoagulant started in full dosage, while laboratory
tests are performed. Do not wait to see what happens to the
platelet count.
• An alternative anticoagulant [e.g. danaparoid, argatroban, fondaparinux
(pregnancy), bivalirudin (urgent PCI or surgery)] is usually indicated
for 3 months in the presence of thrombosis and 1 month without
thrombosis.
• LMWHs can have a crossover effect and perpetuate the problem.
• Do not start a coumarin (e.g. warfarin) until an alternative anticoagulant
has been instated and the platelet count has normalized.
• Do not give platelets to treat thrombocytopenia, as this can lead to
further platelet activation and thrombosis.
• Heparin re-exposure can occur after >3 months if the patient is IgG
antibody-negative.
Acute leukaemias: presentation
Types of acute leukaemia
Acute leukaemia
• Acute leukaemia is defined using the World Health Organization
(WHO) classification, which includes cytogenetic data and provides
useful clinical and prognostic information.
• Acute myeloid leukaemia (AML).
• Traditional French-American-British (FAB) classification (M0–M7).
• Acute promyelocytic leukaemia (APL; M3) is often associated with DIC
and a relatively low WCC.
• Monocytic differentiation often manifests with organ infiltration.
• WHO classification includes AML with characteristic genetic
abnormalities, AML with multilineage dysplasia, and AML with
myelodysplastic syndrome (MDS), therapy-related.
• Mainly adults, including the elderly.
• Acute leukaemias may occur de novo or may transform from chronic
myeloid leukaemia [to 70% AML, 30% acute lymphoblastic leukaemia
(ALL)]. MDS can also evolve into AML.
• ALL, usually precursor B-cell, and occasionally precursor T-cell, in origin
(FAB L1-2). Burkitt’s lymphoma (L3) is now separately classified.
• Acute biphenotypic leukaemia.
Poor prognostic factors
• Increasing age.
• High WCC at presentation.
• Prior MDS.
• Philadelphia chromosome-positive acute leukaemia (20% in adult ALL,
5% in children).
• Depends upon subclassification of leukaemia on the basis of
morphology, chromosomal abnormalities, and cell surface markers.
Presentation
Red cell problems
• Anaemia: caused by replacement of normal erythropoiesis by leukaemia
cells; also by bleeding due to low platelets or deranged clotting
(APL). The MCV is usually normal or high (MDS), unless blood loss is
predominant.
White cell problems
• High blast count: may cause ‘leucostasis’ (crudely, sludging of white cells
in small vessels), causing respiratory impairment, myocardial ischaemia/
MI, renal impairment, acute confusion, stroke, fits, and migraine.
• Leukaemia-related phenomena: pyrexia, malaise, muscle and joint pains.
• Neutropenia: secondary to marrow infiltration by leukaemic cells.
Platelet problems
• Thrombocytopenia due to myelosuppression by leukaemic infiltrate.
• Existing platelets may have sub-normal function. Risk of bleeding
increases if platelets are <10 × 109/L or <20 × 109/L if there is
concomitant sepsis or coagulation abnormality.
Coagulation problems
• Range from a prolongation of PT to DIC: may be due to sepsis or the
effects of leukaemia itself, especially APL.
Priorities
1 Stabilize the patient.
2 Treat immediate problems, e.g. bleeding, sepsis.
3 Confirm diagnosis (morphology, cytogenetics, and flow cytometry).
4 Define the treatment strategy, often urgently.
642
Acute leukaemias: management
Stabilize the patient
• Airway: stridor may be secondary to mediastinal obstruction in certain
cases of leukaemia, mainly T-ALL. If present, call the anaesthetist
immediately and arrange transfer to ITU to start treatment.
• Breathing: breathlessness may be due to infection (including atypical
organisms), leucostasis (high WCC), severe anaemia, cardiac failure
(leucostasis, severe sepsis), and pulmonary haemorrhage. Give
O2: where possible, use a pulse oximeter to monitor O2 saturation,
avoiding arterial puncture with thrombocytopenia. Leukapheresis may
be indicated (consider if WBC >100 with AML, >50 with ALL).
• Circulation: shock is usually secondary to sepsis, but consider the
possibility of blood loss if low platelets/clotting abnormalities or cardiac
failure from leucostasis.
• Restore circulatory volume with crystalloid and blood components.
• Give broad-spectrum antibiotics immediately (after blood cultures) if
sepsis suspected (E The febrile neutropenic patient 1, p. 648).
• Refer to a haematologist urgently.
Treat immediate problems
• Infection: until the blood film has been reviewed by a haematologist,
assume the patient is neutropenic and treat all infections aggressively
(E The febrile neutropenic patient 1, p. 648).
• Bleeding:
• Transfuse cross-matched blood components. Caution if high WCCs.
• If platelets <10 × 109/L, give one pool of platelets. If there is active
bleeding and platelet count <50 × 109/L, give platelets.
• If PT prolonged (>1.5 × control), give 4–5U of FFP.
• If fibrinogen <1–1.2g/L, consider cryoprecipitate in addition.
Transfusion in the presence of a high WCC is dangerous and can precipitate the
complications of leucostasis.
• High WCC: discuss with haematologists. May require urgent
leukapheresis, preferably in an ITU setting.
Confirmation of diagnosis
• Take a full history, looking for possible aetiological factors. Length of illness
(was there a preceding chronic condition, e.g. ? myelodysplasia). Past
medical history (? Down’s syndrome, radiation/chemotherapy exposure).
Occupation (? exposure to irradiation, benzenes, other mutagens). Family
history (rare familial syndromes, e.g. Fanconi’s anaemia).
• Examine the patient, looking for accessory clues to diagnosis (?
lymphadenopathy in ALL, hepatosplenomegaly, gum hyperplasia in
M5 monocytic leukaemias), splenomegaly in CML/non-Hodgkin’s
lymphoma (NHL)/myelofibrosis, and identifying potential sites for
infection (dental caries, skin lesions, etc.)
• Final confirmation then rests upon a bone marrow aspirate, with
samples being sent for morphology, chromosome analysis, and cell
surface markers.
Acute leukaemias: treatment
The treatment of acute leukaemia depends upon the type of leukaemia and
involves several courses of chemotherapy, taking months or even years to
complete. The prognosis has improved in recent years and depends upon
the exact diagnosis. Eighty per cent of children with ALL are now cured,
whereas only around 30–50% of adults with AML are cured, depending
on age. Most patients with APL survive long term if they do not succumb
to acute bleeding. The impact of the diagnosis on often young patients and
their families is devastating, and extensive time is needed in discussion; this
should be done by a haematologist. Before embarking on chemotherapy,
the following must be considered.
Sperm banking
Most forms of chemotherapy carry a risk of subsequent infertility. When
desired by the patient, every attempt must be made to provide for banking
of sperm collection prior to starting chemotherapy. Only 5–10% of men
subsequently utilize their banked sperm for assisted fertility. Unfortunately,
in practice, the presence of leukaemia itself often makes sperm non-viable,
and the need to start treatment precludes repeated collections.
Discussion about side effects
Patients need to be warned about hair loss, sterility, emesis (less of a
problem with current antiemetics but varies with individual), infections,
bleeding, mucositis, secondary cancers, etc. Patient-orientated literature is
available on acute leukaemia and chemotherapy, and may be helpful.
Other considerations
• LP (? CNS involvement). Indicated in:
• ALL (because of high risk of CNS relapse).
• AML if high WCC at presentation.
• Any neurological symptoms/signs.
• Human leucocyte antigen (HLA) typing of patient/siblings may be
considered, with a view to possible BMT in the future.
• CMV status should be determined, especially if BMT is an option, along
with a viral screen, e.g. HIV, etc.
Prior to commencement of chemotherapy
• Commence allopurinol 24h in advance. Rasburicase is used if there is
a high risk of tumour lysis syndrome (200 micrograms/kg IV od for
5–7 days); no G6PD.
• Prescribe regular antiseptic mouthwashes, to be used 4–5 times/day
in conjunction with antimicrobial prophylaxis (oral fluconazole,
ciprofloxacin, aciclovir).
• Ensure adequate hydration, aiming for 3L/day input.
• Give antiemetics before chemotherapy, and at regular intervals during
treatment with chemotherapy. Appropriate regimens include:
• Ondansetron 4 –8mg IV/PO bd
• Metoclopramide 10–20mg IV/PO plus dexamethasone 2–4mg IV/PO
4- to 8-hourly.
64
Interstitial shadowing on CXR
These may be diffuse or localized and associated with varying degrees of
fever, breathlessness, and hypoxia.
Causes
Pulmonary oedema [fluid overload, cardiac failure due to chemo-/radio-
therapy, non-cardiac (ARDS)—related to sepsis or drug toxicity]; infection
[bacterial, viral (especially CMV), fungal, Pneumocystis]; thromboembolic;
GVHD; pulmonary haemorrhage; idiopathic.
Management
Supportive treatment: O2, diuretics (if pulmonary oedema), and ventila-
tory support. CXR changes often minor if neutropenic, and so consider
HRCT early. Cover for infectious causes with broad-spectrum antibiotics,
antifungal agents, or occasionally antiviral agents (if viral respiratory tract
infection is suspected). PCP is unusual if the patient is on co-trimoxazole
prophylaxis. Consider bronchoscopy.
Early complications of BMT
• Skin rash.
• GI complications:
• Nausea and vomiting.
• Mucositis.
• Diarrhoea.
• Abnormal LFTs.
• Haemorrhagic cystitis.
• Interstitial shadowing on CXR.
• Cardiovascular complications:
• Cardiac failure.
• Hypertension.
• Deteriorating renal function.
• CNS complications.
• Sepsis.
• Drug toxicity.
64
Complications of BMT
Cardiac failure
• Cardiac toxicity may be secondary to high-dose cyclophosphamide, total
body irradiation, and/or previous anthracycline exposure.
• Transient ST-and T-wave abnormalities and LV dysfunction on Echo are
seen in up to 30%, following conditioning prior to BMT.
• Overt cardiac failure may be seen with repeated high-dose steroid
therapy that is required for episodes of GVHD.
Management
• Standard therapy with diuretics and ACEI.
Hypertension
• Very common in the early days post-BMT and due to ciclosporin
therapy ± renal impairment.
Treatment
• Calcium antagonists [e.g. nifedipine slow release (SR) 10–20mg PO bd].
Deteriorating renal function
Causes
• Drug therapy (ciclosporin, amphotericin, aminoglycosides,
chemotherapy, aciclovir, allopurinol).
• Pre-renal (dehydration, shock, bleeding).
• Tumour lysis syndrome (E Tumour lysis syndrome, p. 655).
• TTP (E Thrombotic thrombocytopenic purpura and haemolytic
uraemic syndrome, p. 654).
Haemorrhagic cystitis
Frequency, dysuria, and haematuria; commonly related to cyclophospha-
mide (caused by acreolin, a metabolite), but also seen with anthracyclines,
cytosine arabinoside, etoposide, adenovirus, and BK virus infection. Prevent
with mesna (see data sheet for dose).
Management
Supportive therapy with blood and platelet transfusion and hydration is usu-
ally sufficient. Discuss with urologists if severe, as more specialist interven-
tion, such as bladder irrigation, may be required.
CNS complications
Symptoms
• May include seizures, drowsiness/confusion, focal neurological signs,
stroke, and visual loss (cortical).
Causes
• Metabolic (d Mg2+, d Ca2+, hypoxia, liver failure, renal failure).
• Infection: bacterial, viral (e.g. HSV), fungal (especially Aspergillus),
Toxoplasma, Cryptococcus.
• Drug toxicity; ciclosporin can cause tremor, confusion, and seizures.
• Intracranial haemorrhage.
Complications of BMT 647
Notes
• Doses of vancomycin and gentamicin will need to be adjusted, according
to serum levels.
• Add metronidazole 500mg IV q8h to first-or second-line regimens if fever
persists and anaerobic infection possible (e.g. perineal sepsis or mucositis).
• Add amphotericin: most units use the lipid formulations Abelcet® or
AmBisome® for proven (or possible) fungal infection. Voriconazole
is used first line if Aspergillus is likely. Caspofungin or micafungin for
Candida. Posaconazole is an oral alternative.
• The change from first-to second-line therapy should be considered under
the following circumstances:
• Persistent pyrexia >48h (or less if the patient’s condition markedly
deteriorates).
• A new spike of temperature once the fever has settled on first-line
antibiotics (suggesting emergence of another resistant organism).
• Rising CRP in the face of apparently appropriate antibiotics.
• Choice of third-line antibiotics is often more arbitrary, and combinations
should again be discussed with haematology and microbiology. Duration
of neutropenia is an important factor, as fungal infections become more
likely the longer the period of neutropenia.
Particular situations
• Infections of the mouth, perianal area, or elsewhere in the GIT: consider
adding metronidazole for Bacteroides spp. and others.
• Suspected line infections: ensure good Gram +ve cover (vancomycin
or teicoplanin). Consider linezolid if vancomycin-resistant enterococci
(VRE) are present.
• Diarrhoea after prolonged antibiotic therapy: suspect C. difficile;
consider empirical oral vancomycin and/or metronidazole, while
awaiting stool toxin detection/culture results.
• Oropharyngeal mucositis due to reactivation of HSV is common. It is
effectively prevented and treated with aciclovir; the main complication is
bacterial super-infection.
• Pyrexia associated with a normal CRP virtually excludes bacterial or
fungal infection as a cause of the fever.
• Deteriorating renal function: avoid nephrotoxic agents, particularly in
combination (e.g. vancomycin, liposomal formulation of amphotericin,
gentamicin).
• Systemic candidiasis may be manifest only as fever unresponsive to
antibiotics: blood cultures are rarely positive; signs of local invasion (e.g.
endophthalmitis) are seen in a minority. Have a high index of suspicion
and treat aggressively with amphotericin or fluconazole. Hepatosplenic
disease is often diagnosed with imaging.
• Invasive aspergillosis presents with fever, abnormal CXR/HRCT,
and dyspnoea or sinusitis (invasive disease of the sinuses). There is
extensive local tissue destruction with cavitating lung lesions or bone
destruction of sinuses. Thoracic HRCT should be performed urgently.
Treat aggressively with IV AmBisome® or voriconazole/micafungin/
caspofungin/posaconazole.
• Granulocyte colony-stimulating factor (GCSF) may shorten a period
of neutropenia and may be used for certain patients. Discuss with
haematology.
When selecting an antimicrobial regimen, it is worthwhile reviewing all
recent microbiology results, including skin swabs (axilla, groin, perineal).
Review past microbiology for resistant organisms that may need to be
covered (e.g. MRSA, VRE, resistant Pseudomonas, E. coli, or Klebsiella).
Hyperviscosity syndrome
Causes
Increased cellularity Raised plasma proteins
• Polycythaemia (primary or • Waldenström’s
secondary): macroglobulinaemia:
• Haematocrit 50–60%. • IgM paraprotein level >30g/L.
• Leucocytosis (acute leukaemias): • Myeloma, usually IgA subtype:
• WCC >50–100 × 109/L. • Paraprotein level >80g/L.
• CML (>300 × 109/L).
Presentation
Most patients develop symptoms when serum viscosity reached 5–
6
centipoises (normal <1.8).
General features
• Muscle weakness.
• Lethargy, headache.
• Mental confusion, proceeding to coma.
• Visual disturbance.
• CCF.
• Fundoscopy:
• Engorgement and sludging in the veins.
• Haemorrhage, exudates.
• Papilloedema.
Specific features
The predominant symptoms vary with the underlying cause.
• Raised paraprotein:
• Bleeding/purpura: platelet dysfunction and factor deficiency.
• Neuropathies.
• Renal impairment.
• Cardiac conduction abnormalities.
• Leucostasis:
• Myocardial ischaemia/MI.
• Pulmonary infiltrates.
• Polycythaemia:
• Peripheral ischaemia.
• TIAs/strokes.
• MI.
Management
Arrange urgent intervention (same day), depending on the cause:
• Polycythaemia:
• Venesect 1–2U.
• Replace with normal saline.
• Leukaemia: leukapheresis or chemotherapy.
• High paraprotein: plasmapheresis.
Hypercalcaemia of malignancy
(See E Hypercalcaemia, pp. 572–4.)
• Urgent intervention required if Ca2+ >3mmol/L.
NB True Ca2+ = measured Ca2+ + [(40 − albumin) × 0.02].
Causes
• Bony metastases: probable local cytokine effect.
• Myeloma: secretion of an osteoclast-activating factor.
• Secretion of PTHrP (non-small cell lung cancer).
• T-ALL; NHL.
Presentation
• Nausea, vomiting, drowsiness, confusion, nocturia, polyuria, bone and
abdominal pains, constipation.
Management
• Hydration: 3–6L over 24h, continuing for 4–5 days. In the past, loop
diuretics (e.g. furosemide) were given routinely once fluid repletion had
been achieved, to further increase urinary Ca2+ excretion. This has fallen
out of favour due to the availability of drugs, such as bisphosphonates,
and the potential fluid and electrolyte complications resulting from
excessive diuresis, such as hypokalaemia, hypomagnesaemia, and
even volume depletion if the diuretic-induced losses are not replaced.
However, patients who are unable to excrete the administered salt
because of renal insufficiency are at risk of fluid overload and should
receive furosemide.
• Following overnight hydration, recheck Ca2+ and albumin. If symptoms
persist and/or Ca2+ remains >3mmol/L, give pamidronate disodium
IV—a maximum of 90mg over 4h. It can be given as an infusion of
60mg/h. Suspected or established renal failure—maximum rate
20mg/h. Pamidronate is well tolerated; however, there is a small
incidence of transient fever and flu-like symptoms.
• For myeloma, consider prednisolone 30–60mg PO daily. Start
chemotherapy if relapse.
Massive mediastinal mass
Presentation
• Dry cough, stridor, and dyspnoea, especially on lying flat.
Causes
• ALL (especially T-ALL with high WCC).
• High-grade NHL.
• Hodgkin’s disease.
• Germ cell tumour.
Management
Histological diagnosis (or cytological from pleural effusion if present):
• General anaesthetic carries considerable risk.
• Definitive treatment (radiotherapy or chemotherapy).
• Consider prednisolone 1mg/kg/day if urgent treatment is required.
658
Chapter 11 659
Rheumatological
emergencies
Acute monoarthritis: presentation
An acute monoarthritis should always be treated as septic arthritis until
proven otherwise. Failure to treat septic arthritis is negligent. If left un-
treated, joint destruction is fast—50% of cartilage proteoglycan is lost
within 48h; bone loss is evident within 7 days; mortality of Staphylococcus
aureus arthritis is 10%.
Presentation
• Hot, swollen, red joint.
• Joint line tenderness.
• Restricted range of movement.
• Systemic features of fever and malaise.
Assessment
Look for any risk factors for infection
• DM.
• Immunodeficiency state (inherent or iatrogenic).
• Underlying structural joint disease (e.g. RA, prosthesis, joint
replacement).
• High-risk sexual activity, IV drug abuse (predisposes to sacroiliitis and
acromioclavicular joint infection).
• TB needs to be considered in at-risk populations.
Ask for risk factors for gout
• Alcohol.
• High-purine diet (e.g. shellfish, meat).
• Drugs (e.g. thiazides, furosemide, pyrazinamide).
• High cell turnover states (e.g. lymphoma, polycythaemia, psoriasis).
• Tophi (at ears, elbows, Achilles tendon).
Examine for evidence for multisystem disease
• Rash.
• Ocular involvement.
• Oro-genital ulceration.
• GI symptoms.
• Renal involvement.
• Pulmonary manifestations.
Conditions that mimic monoarthritis
• Bone pain or fracture close to a joint.
• Tendinitis (especially at the wrist).
• Bursitis (commonly olecranon or pre-patellar bursae; no joint line
tenderness).
• Neuropathic pain.
• Soft tissue pain.
See Box 11.1 for the differential diagnosis of monoarthritis.
Practice points
• Always assume that a monoarthritis is due to sepsis until proven
otherwise.
• Perform a septic screen, including knee joint aspirate, immediately in
the emergency department, and antibiotics started thereafter. Never
aspirate a prosthetic joint. This should be discussed with orthopaedics.
62
Acute monoarthritis: investigations
Synovial fluid analysis
Aspirate the joint to dryness (E Joint aspiration, p. 852) and send fluid for:
• WBC: fluid may be placed in an EDTA tube.
• Microbiology: fluid into a sterile container and ideally a sample into blood
culture bottles and for AFB.
• Polarized microscopy: for crystals; fluid into a sterile container.
See Box 11.2 for indications for synovial fluid aspiration, and Box 11.3 for
contraindications to joint aspiration.
Take blood for
• Blood cultures.
• FBC: WBC high in infection and crystal arthritis.
• CRP/ESR: elevated with an inflammatory arthritis. Elevated ESR and
normal CRP suggest SLE.
• U&Es, LFTs: may be impaired with sepsis.
• Glucose: ? diabetic.
• Uric acid: ? gout. (NB Urate may be normal in acute gout.)
• Clotting: bleeding diathesis causing haemarthrosis.
• Immunology: rheumatoid factor (RhF), anti-CCP antibodies, ANA, anti-
dsDNA, complement levels (? RA or SLE).
X-ray of joint
• To exclude fracture. Chondrocalcinosis suggests pseudogout. (But not
helpful in the early diagnosis of septic arthritis, as the appearance may
be unchanged for up to 2 weeks in infection.)
Sepsis screen
• Chest radiograph; urine cultures; consider cervical, rectal, and
throat swabs.
Aspirate any cutaneous pustules for Gram stain in patients with suspected
gonococcal infection.
Septic arthritis
The most common pathogen in the UK is S. aureus (70%). Neisseria gonor-
rhoea is a common cause in the young, sexually active population. Other
important causes include Streptococcus. Haemophilus influenzae should be
considered in children.
Management
(See Box 11.4.)
• Admit and inform the orthopaedic team.
• Aspirate the joint to dryness (see Boxes 11.2 and 11.3 for indications
and contraindications for aspiration, respectively). Prosthetic joints
should be aspirated by the orthopaedic team in theatre—liaise with
them and consider early arthroscopy to facilitate effective joint washout,
especially if inflammatory markers are slow to fall.
• Full septic screen.
• Strict rest for the joint (bed rest); no weight-bearing on infected joints.
• Analgesics (NSAIDs). Consider adding a PPI if history of dyspepsia.
Antibiotics
• Initially IV for 2 weeks, then PO for a further 4 weeks.
• Empirically start with flucloxacillin 1g q6h and benzylpenicillin 1.2g q4h.
For penicillin allergy, use vancomycin and clindamycin. In young children,
use cefotaxime to cover H. influenzae.
(NB Aminoglycosides are not effective in the acidic pH of an infected joint;
erythromycin penetrates the synovial fluid poorly.)
• Review antibiotics when microbiology available.
• For gonococcal arthritis, treat with IV benzylpenicillin 1.2g q4h for 7 days
and then PO amoxicillin 500mg tds for 10 days. Remember to trace and
treat contacts (liaise with the GUM team).
Crystal arthropathy
Management
• May usually be managed as an outpatient (see Box 11.5).
• Bed rest.
• Analgesics: NSAIDs with PPI cover, e.g. naproxen 500mg bd. Use
cautiously in the elderly, patients with peptic ulceration, or patients with
asthma, cardiac failure, or renal or liver disease.
• Colchicine is a good alternative if NSAIDs are contraindicated. Give
500 micrograms every 4–6h, as tolerated, until pain settles. In renal
impairment, reduce the dose to 500 micrograms every 12h and monitor
renal function. Rheumatology consultation if symptoms fail to settle.
Intra-articular steroid injections may be given in patients who cannot take
NSAIDs or colchicine (e.g. those with renal failure) and only have one
or two actively inflamed joints. The diagnosis of acute gout should be
confirmed and septic arthritis must be excluded before giving steroids.
• Systemic steroids may be given in patients who cannot take NSAIDs or
colchicine and in whom intra-articular steroid injection is not an option
because of polyarticular disease. Oral prednisolone (20–30mg/day)
may be given for 3–5 days and then tapered over 7–10 days. Rebound
attacks may occur when steroids are withdrawn. IM steroids (e.g 120mg
IM depot methylprednisolone) may also be used as an alternative if
infection has been excluded.
• Allopurinol is contraindicated during acute gout, as it can exacerbate the
acute episode. However, once treatment with an antihyperuricaemic
drug (allopurinol or probenecid) has been started, it should not be
stopped during an acute attack.
• Allopurinol may be started for prophylaxis when the acute attack has
settled if the patient has had >2 attacks of acute gout in 1 calender
year, if tophi are present, or in cases of erosions or urate nephropathy.
Initiation of these drugs should be accompanied by either an NSAID
or colchicine (0.5mg bd) for 3–6 months, while the allopurinol dose is
being uptitrated to a target urate level of <0.35 mmol/L.
Management
General measures
• NSAIDs, e.g. naproxen 500mg bd, adjusting the dose according to
symptoms and response (caution in elderly patients, patients with
dyspepsia, asthmatics, and patients on anticoagulants).
• IM methylprednisolone (120mg) or PO prednisolone (e.g 20mg
prednisolone for 5 days) will settle most acute flares of RA/
inflammatory arthritis. Exclude infection first.
• Consider specific treatment of the underlying condition.
• Consider the need for physiotherapy and exercise regimens to reduce
long-term disability.
(See Table 11.1.)
Rheumatoid arthritis
Clinical features
• Typically young women (♀:♂—3:1).
• Symmetrical polyarthritis involving the small joints of the hands and feet.
• May present as relapsing or persistent monoarthritis.
• Signs most common in hands, feet, knees—but remember synovial joints
of the spine (and atlantoaxial joint/ligaments) and larynx (arytenoid
joints).
• Extra-articular manifestations: vasculitis, subcutaneous nodules,
lymphadenopathy, peripheral neuropathy, anaemia (normochromic
normocytic, iron deficiency, drug-induced aplasia, haemolytic), ocular
involvement (e.g. scleritis), pleurisy, pericarditis, pulmonary fibrosis.
Management
• General measures as before (E Polyarthritis, pp. 666–7).
• Early, intensive disease-modifying anti-rheumatic drugs (DMARDs)
reduce long-term joint damage. Most commonly methotrexate, but
others such as hydroxychloroquine, sulfasalazine, and leflunomide. Some
older patients may still be taking gold. Steroids are used as induction/
bridging therapy, while DMARDs are established.
• Biological therapies are increasingly used, e.g. anti-cytokine therapies
such as tumour necrosis factor (TNF)-α blockers (etanercept,
adalimumab, and infliximab), B-cell depletion (rituximab), interleukin
(IL)-6 receptor blockade (tocilizumab) and, more recently, small
molecules, e.g. Janus kinase ( JAK) inhibitors.
• Symptomatic treatment with NSAIDs.
Seronegative arthritides
(spondyloarthropathies)
Psoriatic arthropathy
Clinical features
• May present as an asymmetrical large-or small-joint oligoarthritis,
symmetrical polyarthritis, or a clinical picture similar to RA or ankylosing
spondylitis. Joint destruction may be extensive (arthritis mutilans).
• Look for rash (knees, elbows, scalp, behind the ears, umbilicus, natal
cleft) and nail changes (pitting, onycholysis, ridging).
Management
• Treatment is similar to that for RA, with DMARDs and biologics.
• Chloroquine and steroids may worsen psoriasis.
Reactive arthritis
Clinical features
• Typically young, sexually active individual with oro-genital ulcers
(painless), conjunctivitis (which may progress to iritis), and rash
(soles of feet—keratoderma blenorrhagica).
• May occur following non-specific urethritis or gastrointestinal infection,
e.g. with Shigella, Salmonella, Yersinia, or Campylobacter.
Treatment
• NSAIDs are the main therapy and treat underlying infection.
• GUM review.
See Box 11.1 for Reiter’s syndrome.
Practice points
Marked morning joint pain or stiffness is most likely to be due to inflam-
matory arthritis.
670
Reactive arthritis
Clinical features
• Comprises a triad of seronegative arthritis, non-specific urethritis, and
conjunctivitis.
• Skin lesions are psoriasiform (keratoderma blenorrhagicum) with brown
macules and pustules on the soles and palms.
• Arthritis usually begins 72 weeks after infection, and the lower limb
joints are most commonly affected (asymmetrical) and resolves over
months.
• It may be associated with a sterile urethral discharge and mild dysuria.
Erosive lesions may affect the penis (circinate balanitis) or mouth.
• Rarely progresses to give aortic incompetence, heart block, and
pericarditis.
Treatment
NSAIDs, and sometimes steroids, are the mainstay of therapy.
Ankylosing spondylitis
Clinical features
• Enquire about axial skeleton involvement (lower lumbar back pain, with
early morning stiffness, that improves with exercise).
• Peripheral joint involvement, uveitis, and anaemia of chronic disease may
be found.
Management
• NSAIDs for pain.
• Physiotherapy to try to prevent progressive immobility.
• Anti-TNF therapy or anti-IL17 (secukinumab) may be used for axial
disease.
• If there is peripheral arthritis—sulfasalazine or methotrexate.
• Refer to a rheumatologist for long-term management.
Infections 671
Enteropathic arthritis
• Large-joint arthritis often coincides with active IBD, but not always.
• Arthritis may predate the onset of intestinal symptoms; often there are
other extraintestinal manifestations (e.g. erythema nodosum and iritis).
• Treatment of colitis usually improves arthritic symptoms.
Infections
• Viral: rubella, parvovirus B19 (common, often presents with a generalized
rash), and HIV seroconversion.
• Bacterial: Gonococcus (rash, tenosynovitis, sexually active), Staphylococcus
(immunosuppressed, with septicaemia and seeding to several joints), IE
(vasculitic lesions, heart murmur).
• Treatment: see E Infectious diseases, pp. 469–503.
672
Vasculitis
The term vasculitis denotes an inflammatory reaction with destructive
changes of blood vessel walls. Vasculitides are classified into primary and
secondary (see Box 11.6) types.
Classification
(See Table 11.2.)
Presentation
• Arthralgia or arthritis, myalgia.
• PUO.
• Generalized systemic illness, e.g. weight loss, malaise.
• Rashes: splinter haemorrhages, nail fold infarcts, purpura, livedo
reticularis, nodules.
• Renal disease: haematuria, proteinuria, hypertension, renal failure (see
Box 11.7).
• Lung disease: haemoptysis, cough, breathlessness, pulmonary infiltrates
(see Box 11.7).
• Neurological disease: mononeuritis multiplex, sensorimotor
polyneuropathy, confusion, seizures, hemiplegia, acute cerebral
syndrome.
See Box 11.8 for patterns of ANCA.
Vasculitis 673
Practice points
SLE is often characterized by a high ESR and a normal CRP.
A raised CRP in SLE should make you think of infection, infection,
infection!
Other investigations
• Immunology: ANA, anti-dsDNa, ENA, anticardiolipin, anti-β2-
glycoprotein-1 antibody, lupus anticoagulant, complement levels.
• LFTs: usually normal.
• Viral: consider PCR for CMV.
• Urine: urine protein:creatinine ratio.
Points to note
• Immunology:
• >95% are ANA +ve (dsDNA antibody is almost pathognomonic
of SLE).
• Anti-dsDNA antibody titre may correlate with disease activity.
• Low complement levels correlate with disease activity (and renal
involvement).
• 40% are RhF-positive.
• Pneumococcal and meningococcal infections are more common in
patients with SLE as a consequence of either hereditary or acquired
deficiencies of components of the complement pathway.
• Immunosuppressive therapy renders patients susceptible to the usual
range of opportunistic infections, including Pneumocystis, CMV, and
mycobacteria.
• Chest and urine are the most common sources of infection in clinical
practice.
• Disease activity classically shows an elevated ESR, but a normal CRP.
An elevated CRP should alert you to look for an underlying infection.
Management
• Exclude infection.
• Prednisolone 20–30mg od.
• Additional immunosuppressive therapy, such as pulsed
methylprednisolone, or cyclophosphamide, should be given on
consultation with a rheumatologist.
• Antibiotics if infection is suspected.
• Hydroxychloroquine (200mg/day) may be added, especially if there is
cutaneous or joint involvement.
67
Points to note
• The ANCA test provides a rapid screening test and shows high
sensitivity for patients with small-vessel vasculitis.
• Patients with GPA are classically c-ANCA positive (cytoplasmic pattern
of immunofluorescence, antibody against elastase I), while patients with
microscopic polyangiitis may be either p-ANCA (perinuclear pattern of
immunofluorescence, antibody against myeloperoxidase) or c-ANCA
positive. A negative ANCA does not, however, preclude the diagnosis
of a small-vessel vasculitis.
• Underlying infection, especially IE and chronic meningococcaemia,
should always enter the differential diagnosis of a patient with small-
vessel vasculitis.
• An infectious episode, such as an URTI, often will precipitate the
presentation of a small-vessel vasculitis.
680
Cryoglobulinaemia
Cryoglobulins are Igs that precipitate at low temperatures and dissolve on
rewarming. They precipitate in the superficial capillaries or outside ves-
sels in the coldest part of the skin to produce microinfarcts or purpura.
Cryoglobulinaemia occurs in several conditions.
• Essential cryoglobulinaemia implies the absence of an identifiable cause.
• Renal disease is associated with all three types and is thought to involve
immune complex pathways.
• Mean age: 42–59 years; ♂:♀, 2:3.
Type 1 monoclonal
• Type 1 cryoglobulinaemia, or simple cryoglobulinaemia, is the result of a
monoclonal Ig, usually IgM or IgG.
• Associated with myelo-or lymphoproliferative disease.
• Heavy proteinuria, haematuria, and renal failure may occur (MPGN).
• Serum C4 and C1q are low.
Type 2 (mixed monoclonal) and type 3 (mixed polyclonal)
• Type 2 and type 3 cryoglobulinaemia (mixed cryoglobulinaemia) contain
RhFs (often IgM). These RhFs form complexes with the fragment,
the crystallizable (Fc) portion of polyclonal IgG. The actual RhF may
be monoclonal (in type 2 cryoglobulinaemia) or polyclonal (in type 3
cryoglobulinaemia) Ig.
• Type 2 is associated with immune complex vasculitis, and 50% have
evidence of renal disease. Many cases are associated with HCV
infection.
• Type 3 mixed polyclonal is associated with SLE and systemic infections
(post-streptococcal nephritis, leprosy, and syphilis). Renal involvement is
also seen.
Clinical features
• Renal involvement (haematuria, proteinuria, renal failure).
• Raynaud’s phenomenon.
• Purpura (especially legs).
• Arthralgia and fever.
• Confusion and weakness (secondary to hyperviscosity).
• Hepatosplenomegaly (probably a manifestation of the underlying
aetiology).
Management
• Treat the underlying cause (e.g. hepatitis C or haematological
malignancy).
• There is no specific treatment.
• Plasmapheresis and immunosuppressive therapy may be tried.
Cryoglobulinaemia 681
682
Further reading
Dasgupta B, Borg FA, Hassan N, et al. BSR and BHPR guidelines for the management of giant cell
arteritis. Rheumatology 2010;49(8):1594–7. https://doi.org/10.1093/rheumatology/keq039a
684
Polymyalgia rheumatica
PMR is a clinical syndrome characterized by an acute phase response (high ESR
or high CRP), which predominantly affects the elderly Caucasian population,
with a median age of onset of 70 years and an annual incidence of 71:2500.
Clinical features
• Proximal muscle stiffness and pain without weakness or wasting (see
Box 11.10).
• Systemic symptoms of malaise, fever, and weight loss.
Investigations
• FBC: normochromic normocytic anaemia.
• U&Es, LFTs: elevated ALP is common (50%).
• CK: normal (if high, consider myositis or hypothyroidism).
• ESR: high (>40mm/h initially).
• CRP: high.
• RhF and anti-CCP antibodies: PMR may be the presenting feature of RA.
• CXR: PMR symptoms may be the presenting feature of a neoplasm.
Treatment
• Steroids: prednisolone 15mg PO od initially, reducing to 5–10mg od over
2–3 months and very slow reduction thereafter. Some patients may
require treatment for years. Consider bone prophylaxis.
• Monitor response with symptoms and ESR.
Points to note
• PMR and giant cell arteritis form part of a clinical spectrum of disease,
and up to 40% of patients with biopsy-proven giant cell arteritis have
polymyalgic symptoms.
• Polymyalgic symptoms may be the presenting feature of an underlying
neoplasm or connective tissue disease.
• Polymyalgic symptoms should respond dramatically to prednisolone
within 7–10 days. Failure to respond should alert the clinician to the
possibility of an underlying neoplasm or connective tissue disease.
Practice points
• Never diagnose PMR in a patient <50 years old.
• Always consider paraneoplasia in PMR.
• Obtain a temporal artery biopsy ASAP after starting steroids for giant
cell arteritis.
68
Back pain
75% of all medical consultations in the UK are for back or neck pain. In the
majority of patients, no definite anatomical diagnosis is made (non-specific
back pain), but it is important not to miss the sinister causes of back pain
(see Boxes 11.11 and 11.12).
History
Is the pain likely to be mechanical, inflammatory, or sinister in origin?
• Mechanical back pain is exacerbated by prolonged sitting or standing and
can be precipitated by trauma.
• Inflammatory back pain is characterized by prolonged early morning
stiffness and is relieved by exercise.
• Sinister back pain (e.g. malignancy and infection) often leads to
pain at night, constant pain, and local bony tenderness, and may be
accompanied by other systemic symptoms.
• Are there any sensory or motor symptoms? Ask specifically for any
change in bowel or bladder function.
Back pain 687
Practice points
• Back pain at night suggests a sinister cause such as cancer or infection.
• Patients with acute onset of back pain and signs suggestive of a high
lesion (e.g. L1–L3/4) may have weak thighs and absent knee jerks, and
are unlikely to have a disc lesion and may have a tumour.
Examination
• General: look for evidence of malignancy.
• Spine (palpation for tenderness; muscle spasm; cervical spine flexion,
extension, rotation, and lateral flexion; thoracic spine rotation; lumbar
spine flexion, extension, and side flexion; compression of sacroiliac
joints).
• Neurological examination looking specifically for absent ankle jerks
(slipped disc) or long-tract signs in the legs. S1 nerve root signs and
symptoms can be produced by a lesion in the region of the upper
lumbar cord (central disc prolapse compressing the S1 nerve root).
• Always do a rectal examination and test perineal sensation.
Investigations
Patients with back pain occurring at night and patients with neurological
signs warrant investigation.
• X-rays of spine and CXR (? malignancy).
• FBC and ESR (elevated with sinister causes of pain).
• Biochemical profile (Ca2+, ALP, and PO43–).
• Igs and protein electrophoresis (? myeloma).
• PSA.
• Bence-Jones protein.
Further imaging
• CT or MRI scan (superior to CT for imaging the spinal cord and roots).
• Technetium bone scan for ‘hot spots’ (neoplastic or inflammatory).
Management
• Analgesics.
• Bed rest.
• Physiotherapy.
• Appropriate referral to a specialist.
68
Prolapsed intervertebral disc
Acute postero-lateral herniation of a lumbar disc, usually L4–L5 or L5–S1,
is a common cause of acute incapacitating lower back pain. There is often a
clear precipitating event (e.g. lifting), and pain may radiate in the distribution
of the L5 or S1 nerve root.
Patients should be examined carefully for:
• Paraspinal muscle spasm which is often prominent.
• Straight leg raising which is typically reduced on the affected side.
• Nerve root signs, and test sacral and perineal sensation; always do a
rectal examination.
• L5 lesion which leads to weakness of the extensor hallus longus,
ankle dorsiflexion, and ankle eversion; and altered sensation which is
perceived in the L5 dermatome.
• S1 lesion which leads to weakness of ankle plantar flexion, ankle
eversion, and a diminished or lost ankle jerk; and altered sensation
which is perceived in the S1 dermatome.
• Neurosurgical emergencies (see Box 11.13).
Treatment
• If the X-rays reveal a fracture, refer the patient to the orthopaedic
team; severe pain from inflammatory arthritides should be referred to
the rheumatologists.
• The majority of patients respond to conservative management.
• Rest until the acute pain subsides, followed by mobilization and
physiotherapy (patients may often be managed at home, with
instructions to return to the GP or doctor for review in 2–3 weeks).
• Non-steroidal anti-inflammatory agents.
• Physiotherapy.
Chapter 12 691
Dermatological
emergencies
Fig. 12.2 Erythema multiforme on the leg; note the presence of target lesions.
Reproduced from MacKie R. Clinical Dermatology, 2003, with permission from Oxford
University Press.
694
Points to note
• The ‘severe cutaneous adverse reactions’ (SCAR) refer to AGEP,
DRESS, SJS, and TEN. These are often grouped together, as they
are associated with systemic involvement, hospitalization, and high
morbidity/mortality.
• Peripheral drug eosinophilia is seen in certain drug reactions, such as
DRESS, but is uncommon across all cutaneous drug reactions.
• Parenteral drug administration is more commonly associated with
anaphylaxis.
• Cutaneous drug reactions are more common in patients with HIV.
Management
(See Box 12.1.)
• Severe angio-oedema and anaphylaxis require immediate treatment
(E Anaphylaxis, p. 342).
• Stop any responsible drugs, and prescribe an alternative if necessary.
Hospitalized patients receiving numerous drugs should be assessed
carefully, and all non-essential therapy discontinued.
• Most cutaneous drug reactions rapidly resolve on discontinuing the
causative medication. Symptoms can be alleviated and resolution
expedited with sedating/non-sedating antihistamines, a medium-potency
topical steroid, and frequent applications of emollients.
• If SCAR is considered, specialist advice should be sought urgently. The
patient will require assessment for systemic involvement, including
general examination and blood tests (FBC, U&Es, and LFTs), and may
require hospitalization. Oral steroids (prednisolone 0.5–1mg/kg/day)
may be required for EM, AGEP, or DRESS but should be given only
under specialist supervision. The management of SJS/TEN is considered
separately (E Stevens–Johnson syndrome and toxic epidermal
necrolysis, pp. 698–700).
• Pyrexia may occur with cutaneous drug reactions, but an underlying
infection should be excluded.
Management
• Anaphylactic reactions require immediate treatment (E Anaphylaxis,
p. 342).
• Lay the patient flat.
• Secure the airway and give O2.
• Establish cardiac/pulse oximetry monitoring.
• Give IM adrenaline 0.5mg (0.5mL of 1:1000 adrenaline injection), and
repeat every 5min according to BP, pulse, and respiratory function.
IV adrenaline may be required if the patient is severely ill with poor
circulation (E Anaphylaxis, p. 342).
• Establish IV access (large-bore), and start IV fluids if hypotensive.
• Give IV hydrocortisone 100–300mg and IV chlorphenamine 10–20mg.
Continue H1-antagonist (e.g. oral chlorphenamine 4mg every 4–6h)
for at least 24–48h, and continue if urticaria and pruritus persist.
• If the patient deteriorates, start IV aminophylline infusion (see
Box 2.6). Patients on β-blockers may not respond to adrenaline
injection and may require IV salbutamol infusion.
• Acute urticaria ± angio-oedema is usually not life-threatening, unless
associated with anaphylaxis or upper airway obstruction. If airway
obstruction, treat as anaphylaxis and get urgent specialist advice for
airway management. Otherwise:
• Give oral antihistamines such as hydroxyzine 25mg or
chlorphenamine 4mg.
• A single dose of oral prednisolone (0.5–1mg/kg) may be given but
should not be continued without specialist advice.
• When the patient’s condition has stabilized, discharge on regular
maintenance treatment with oral non-sedating antihistamine (nsAH)
(e.g. cetirizine 10mg/24h, levocetirizine 5mg/24h, desloratadine
5mg/24h, or fexofenadine 180mg/24h).
• Consider referral to a specialist for assessment (prick test) of IgE-
mediated hypersensitivity or if no clear trigger for acute urticaria/angio-
oedema established. Patch tests are not usually indicated in urticaria/
angio-oedema.
• Patients with contact sensitivity to latex should use alternatives such as
vinyl gloves. Such individuals should be warned to use only non-latex
polyurethane condoms.
• Chronic idiopathic urticaria/angio-oedema can often be managed with
long-term maintenance nsAH therapy. Treatment-resistant chronic
urticaria should be referred for specialist advice, to evaluate for other
causes and to guide management. Future treatment may include
high-dose/combination nsAH, leukotriene antagonists, or systemic
immunosuppressants, e.g. omalizumab (anti-IgE monoclonal antibody).
698
Management
(See Box 12.2.)
The priorities are:
1 To identify and discontinue the causative drug.
2 To get specialist advice and multidisciplinary assessment/care.
3 Supportive care.
4 Screening for, and treatment of, sepsis.
5 To limit future complications.
Identify the cause
• Document a thorough drug history from the patient (and/or relatives),
including over-the-counter and traditional/herbal medicines and
previous adverse reactions to medications. Document the chronological
association with the onset of symptoms (prodrome/rash).
• SJS/TEN usually develops 7–21 days after first administration of the
culprit drug, or within 48h if previously sensitized to the drug.
• Identify the causative agent and discontinue. If the patient is receiving
multiple drugs, stop all non-essential therapy.
Supportive care
Patients with SJS/TEN should be cared for by a multidisciplinary and multi-
professional team led by clinicians with experience in cutaneous medicine
and skin failure.
• Patients with significant epidermal loss (>10%) should be admitted to an
intensive care setting (ICU or burns unit) where they should be barrier-
nursed on a pressure-relieving mattress in a warm side room, with
regular monitoring of core temperature.
• Skin care:
Patients should be handled carefully, and unnecessary adhesive
•
• GI care:
• Oral mucosal surfaces should be cleaned every 4–6h with an
antiseptic (e.g. chlorhexidine) and an anti-inflammatory (e.g.
benzydamine).
• If there is extensive oral mucositis that limits food intake, nutritional
intake should be supported via NG feeding.
• Nasopharyngeal involvement may result in airway obstruction and
necessitate ventilation.
• Prophylactic H2-antagonist or PPI should be given to limit the risk of
gastritis/ulceration.
• Urogenital care:
• Catheterization should be considered if there is dysuria or
obstruction, to aid fluid management and limit stricture formation.
• Urogenital skin and mucosa should be regularly assessed.
• Fluid balance should be monitored closely, as there will be high
insensible losses. If possible, fluids should be administered PO or via an
NG tube. Avoid IV lines to reduce the risk of sepsis.
• Daily blood tests, including FBC, U&Es, LFTs, and glucose
(hyperglycaemia can cause an osmotic diuresis, increasing fluid loss).
• Prophylactic anticoagulation with LMWH, if not contraindicated.
Preventing infection
• SJS/TEN patients should be barrier-nursed in a side room.
• IV lines should be removed as soon as possible to reduce infection risk.
• Multiple skin sites, mucosal sites, sputum, and urine should be cultured
at least every 48h.
• Prophylactic antibiotics are only indicated if the risk of sepsis is
extremely high such as severe neutropenia or a heavy single-strain
bacterial colonization of the skin. Prophylactic topical antibiotics (e.g.
skin/eyes) are generally not recommended.
• If febrile, blood cultures should be taken daily; however, fever is a
common feature of TEN and does not always indicate an infection.
• Antibiotics should be started if there is positive blood, urine, or sputum
culture or indirect evidence of sepsis such as hypothermia, hypotension,
fever, decreasing level of consciousness, or reduced urinary output.
Specific systemic therapy
• Systemic treatments that have been used in SJS/TEN include
corticosteroids, ciclosporin, and IVIG; however, there is no clear
consensus from published studies that any of these improve outcome.
Further controlled trials are required to establish the role of these
treatments in SJS/TEN. Therefore, these treatments should only be
started following specialist advice, as local guidelines may vary.
The British Association of Dermatologists have published guidelines on the
management of SJS/TEN.2
References
1. Bastuji-Garin S, Fouchard N, Bertocchi M, Roujeau JC, Revuz J, Wolkenstein P. SCORTEN: a
severity-of-illness score for toxic epidermal necrolysis. J Invest Dermatol 2000;115:149–53.
2. Creamer D, Walsh SA, Dziewulski P, et al. U.K. guidelines for the management of Stevens–
Johnson syndrome/toxic epidermal necrolysis in adults 2016. Br J Dermatol 2016;174:1194–227.
702
Erythroderma
Presentation
• Exfoliative dermatitis affecting >90% of the body surface area. Can be
acute or chronic in presentation, with acute erythroderma more likely
to present as an emergency.
• Associated scale can be fine (pityriasiform) or coarse (psoriasiform).
• Itch is common.
• Patients may be febrile or hypothermic because of loss of temperature
control mechanisms.
• Chronic erythroderma may be associated with nail dystrophy, diffuse
hair loss, and ectropion. Palmo-plantar hyperkeratosis and peripheral
lymphadenopathy may be prominent.
Causes
Erythroderma can be the clinical presentation of a wide range of different
conditions:
• Common: dermatitis (atopic, contact, or seborrhoeic), psoriasis, drug
reaction, or idiopathic.
• Rare: cutaneous T-cell lymphoma, pityriasis rubra pilaris, autoimmune
bullous diseases, toxic shock syndrome, or paraneoplastic rash.
Investigations
• Monitor FBC, U&Es, albumin, Ca2+, and LFTs regularly.
• Blood cultures and skin swabs. Sustained pyrexia, hypotension, or
clinical deterioration should prompt a search for underlying sepsis.
• Skin biopsy should be performed, as histological features of the
underlying causative condition are often present.
• Indirect immunofluorescence of blood serum and/or direct
immunofluorescence of the skin biopsy should be performed in case of
autoimmune bullous disease.
Management
(See Box 12.3.)
General measures
• Discontinue all unnecessary medications.
• Nurse in a warm room, with regular monitoring of the core
temperature and fluid balance. Patients should be nursed on a pressure-
relieving mattress.
• Encourage oral fluids, a high-calorie diet, and protein supplements. NG
feeding may be required. Avoid IV cannulae, as they can be a source of
infection.
• Monitor fluid balance closely: daily weights and clinical examination
(as allowed by the exfoliation). Catheterize, if necessary, for fluid
management.
Erythroderma 703
Specific therapy
Liaise with a specialist early, as establishing a diagnosis will guide subsequent
management.
• Skin should be treated every 4–6h with greasy emollients such as 50%
white soft paraffin/50% liquid paraffin (‘50/50’).
• Wash with water and emollient soap substitutes.
• Oral sedating antihistamines such as hydroxyzine (25–100mg/24h in
divided doses) may be beneficial, with the dose adjusted according to
severity and weight.
• Application of topical steroids may be beneficial but should be initiated
only under specialist supervision.
• Depending on the underlying cause, early systemic treatment may
be required. For example, in erythrodermic atopic dermatitis, oral
corticosteroids may be indicated, whereas in erythrodermic psoriasis,
ciclosporin or a biologic medication may be indicated. Therefore,
specialist advice must be sought prior to initiating systemic treatment.
Complications
• Hypothermia.
• Infection.
• Hypoalbuminaemia.
• High-output cardiac failure.
Practice points
Most cases of erythroderma are due to an underlying skin condition or a
drug reaction. Therefore, take a careful history to establish any prior skin
disease(s), recent new medications, or dose changes.
704
Systemic therapy
• Systemic treatment may be required for long-term disease control (e.g.
ciclosporin or biologics) but should only be started under specialist
supervision.
• Bacterial infection should be treated with appropriate antibiotics.
Fig. 12.3 Blisters of bullous pemphigoid. Large, tense, raised lesions are seen on an
erythematous eczematized base.
Reproduced from MacKie R. Clinical Dermatology, 2003, with permission from Oxford
University Press.
Herpes zoster
See E Herpes zoster (shingles), p. 484.
Eczema herpeticum
Presentation
• Sudden onset of widespread umbilicated vesiculo-pustular lesions,
which are painful. Lesions progress to haemorrhagic crusts and leave
monomorphic punched-out erosions.
• Most common in patients with pre-existing atopic eczema but can occur
in other pre-existing skin conditions, e.g. ichthyosis vulgaris and mycosis
fungoides.
• Due to cutaneous HSV infection and may occur following a primary
episode of herpes labialis or after contact with an infected individual.
• Patients usually pyrexial and tachycardic; however, cardiorespiratory
collapse unusual.
• Lesions may also have a golden crust, as secondary staphylococcal
infection (‘impetiginization’) is common.
Management
• Early specialist advice is required, as patients may require hospitalization.
Can progress rapidly, so localized disease should be treated aggressively.
• Assess carefully for involvement of the ocular branch of the trigeminal
nerve if facial rash (i.e. associated involvement of the nose). If concern
of ocular involvement, liaise with the ophthalmologist urgently.
• Start high-dose IV aciclovir at the earliest opportunity (up to 10mg/kg
8-hourly in the immunocompromised). If IV therapy not possible, give
valaciclovir 500mg PO 12-hourly for 5–7 days.
• Use simple emollients. Aerosolized preparations are less painful to apply
and limit topical spread of infection.
• Chlorhexidine and potassium permanganate soaks once or twice daily
reduce excessive exudation.
• Secondary bacterial infection is common, so perform bacterial swabs
daily to guide treatment. If clinical concern, have a low threshold to
starting systemic antibiotic therapy.
• If concern of ocular involvement, liaise with the ophthalmologist early.
• Give oral nsAH for pruritus.
• If oral involvement, regular antiseptic and anti-inflammatory
mouthwashes, with good analgesia.
• Avoid topical steroids for active dermatitis for at least 3–5 days until the
infection is clinically resolving.
Practice points
Patients with severe atopic eczema should be advised about prompt
treatment of herpes labialis and to avoid contact with individuals with
active herpes simplex.
Patients with active herpes labialis should be advised to avoid contact
with individuals with atopic eczema.
071
Chapter 13 711
Psychiatric emergencies
Acute confusion: assessment
Acute confusional states, or delirium, are relatively common. They are par-
ticularly common in care of the elderly and on orthopaedic wards. Risk
factors include: age >65 years, prior cognitive impairment or dementia,
multiple comorbidities, psychoactive drug use, polypharmacy, previous his-
tory of delirium/falls/CVA, and gait disorder. Acute confusion may occur
on a background of chronic cognitive impairment (dementia) and may last
for a prolonged period of days or even weeks. Acute confusion may occur
as part of a mental illness or be secondary to organic disease (e.g. brain
tumour or encephalitis).
Common features of acute confusion
• Rapid onset.
• Fluctuation.
• Clouding of consciousness.
• Impaired recent and immediate memory.
• Disorientation.
• Perceptual disturbance, especially in visual or tactile modalities.
• Psychomotor disturbance (agitation or d movements).
• Altered sleep–wake cycle.
• Evidence of underlying cause.
Common causes of acute confusion
• Pain or discomfort (e.g. urinary retention, constipation).
• Hypoxia.
• Metabolic disorders (renal failure, liver failure, acidosis, hypercalcaemia,
hypoglycaemia) or endocrine disease (thyrotoxicosis, Addison’s
disease, DM).
• Infection (systemic or localized).
• Cardiac (MI, CCF, endocarditis).
• Neurological (head injury, subdural haematoma, CNS infection, post-
ictal states).
• Drugs [prescribed: benzodiazepines, opiates, digoxin, cimetidine, steroids,
anti-parkinsonian drugs, anticholinergics; or recreational: especially
stimulants, alcohol, gamma-butyrolactone (GBL), ketamine].
• Alcohol or drug withdrawal.
Detection of acute confusion
• The presence or absence of cognitive impairment may help distinguish
between organic and functional mental impairment.
• The 10-point Abbreviated Mental Test Score, 30-point Mini Mental State
Examination (MMSE), Montreal Cognitive Assessment (MoCA), or the
Confusion Assessment Method (short version) give a rapid estimate of
key cognitive functions.
• Take a clear history from friends or relatives, and try to determine
whether delirium is superimposed upon dementia.
Practice points
Patients with visual hallucinations usually have organic confusion.
Acute confusion: management
• Treat the cause. Always consider alcohol withdrawal. Ensure that common
problems like dehydration, pain, and constipation are adequately treated.
• It is often sufficient to manage the delirious patient’s behaviour
conservatively (non-pharmacologically), while treating the underlying
cause. Nurse in a well-lit, quiet room with familiar nursing staff or,
better still, a familiar person such as a family member or carer. Ensure
effective communication and reorientation, and provide reassurance to
patients with delirium.
• Occasionally, patients may refuse investigations or treatment. It may be
important to go ahead with baseline investigations in order to rule out
life-threatening causes for the confusion, and this may need to be done
under the Mental Capacity Act 2005 or common law (E The Mental
Health Act, p. 726; E Common law, pp. 730–1).
• If sedation is required, use small amounts of sedatives, given orally if
possible. Offer liquid preparations if tablets are refused. Parenteral
medication may be indicated if patients refuse or are particularly disturbed.
See E Sedation for patients with delirium, pp. 714–15 for drugs
and doses.
• Patients with ongoing disturbance may require regular sedation.
Sedation for patients with delirium
(See Box 13.1.)
• There are a few medication options here, so consider: the likely cause
of delirium, concomitant medication, and any underlying comorbidities
when choosing.
• Start with low doses, and titrate upwards according to clinical response.
• Antipsychotics are used, but not licensed for delirium, so this is off-label
prescribing. However, some such as haloperidol have a licence for
agitation in the elderly, and risperidone for short-term management of
aggression in dementia. Haloperidol 0.5–1mg PO bd, with additional
doses 4-hourly if needed. If using IM haloperidol 0.5–1mg, monitor for
1h and repeat if necessary. Remember it is recommended to have a
pre-haloperidol ECG recorded due to risk of QT prolongation. Avoid
haloperidol in neuroleptic malignant syndrome (NMS), anticholinergic
toxicity, and hepatic failure. Olanzapine 2.5–5mg PO bd (max 20mg/
24h) and risperidone 0.5mg bd (max 4mg/24h) can be used, but in the
elderly with underlying dementia, there is an i risk of CVA.
• Lorazepam 0.25–1mg PO/IM every 2–4h, as needed (half doses in the
elderly), but remember that benzodiazepines may exacerbate confusion.
• Diazepam 5–10mg PO (2mg starting dose in the elderly).
• In patients with Lewis body dementia or Parkinson’s disease, there
is a high risk of severe extrapyramidal side effects, so best to avoid
antipsychotics in these cases, and consider benzodiazepines.
• Some patients who are neuroleptic-naïve are extremely sensitive to
neuroleptics and may develop severe extrapyramidal side effects. Use
low doses of antipsychotics if you are unsure. Dystonic reactions should
be treated with anticholinergic drugs such as procyclidine.
• If parenteral medications are required, use lorazepam and/or
haloperidol (doses as listed earlier).
Practice points
Sudden onset of confusion and delirium with sweating and shaking, par-
ticularly in patients recently hospitalized, may indicate alcohol withdrawal.
Check the serum PO43– level, as it may be very low (<0.4mmol/L) in
acute alcohol withdrawal and lead to confusion or profound weakness. It
should be treated with IV phosphates to maintain a plasma concentration
of >0.4mmol/L.
720
*
Reproduced from Semple D, et al. Oxford Handbook of Psychiatry, 2013, with permission from
Oxford University Press.
72
Deliberate self-harm
Deliberate self-harm (DSH) is a common presenting complaint to A&E
and reason for admission. The severity and sequelae of DSH vary greatly,
from superficial cuts to serious ODs requiring prolonged spells in hospital.
Suicide is uncommon, but DSH increases the risk of subsequent suicide (1%
of those who commit acts of DSH kill themselves in the next year—100
times the general population risk), and 40–60% of suicides have a history
of DSH. Assessment of patients who have harmed themselves is important
in order to:
• Detect those at risk of subsequent DSH or suicide (see Box 13.3).
• Identify patients with significant mental health problems requiring
treatment.
• Plan aftercare in hospital or in the community.
Assessment by general medical staff
Assessment of DSH is normally done by a psychiatrist, specialist nurse, or
social worker experienced in the field. However, it is important for all staff
to be able to make a basic assessment of these patients, because patients
may refuse to see a mental health worker or may attempt to leave the ward
or department before a detailed assessment can be carried out.
What if a patient wants to leave before they are assessed
by a mental health professional?
• You have a duty of care to the patient that includes protecting them as
best you can from ongoing risk.
• Try to persuade the patient to stay for an assessment. If they agree,
refer to the psychiatric team and ask the nursing staff to monitor the
patient.
• If the patient refuses, then you will need to ask them to stay while you
make your own assessment of risk.
• If they will not stay, and you are concerned, you may need to detain
them under common law, pending a formal psychiatric assessment.
• If they agree to stay, make your assessment. Do not forget to enquire
about past episodes of self-harm and ongoing psychiatric problems, and
drug or alcohol problems, as well as the questions already detailed.
• If, after your assessment, you have concerns that require the patient
to see a mental health professional, try to persuade them to stay. If
they refuse, consider their capacity to decide to leave under the MCA
framework and whether you can use this to keep them from leaving,
or consider detaining them under common law, pending an urgent
psychiatric assessment.
• If you are satisfied that the ongoing risk is not of a magnitude that
requires them to be detained, then allow them to be discharged, but
ensure that the GP is informed.
• For detaining patients who will not stay in hospital, see E Patients who
do not wish to stay in hospital, p. 733.
• For guidelines on treatment for patients who are refusing treatment,
see E Mental Capacity Act 2005 (England and Wales), p. 728 and
E Common law, pp. 730–1.
Practice points
The phrase ‘detain under common law’ is contentious. While a doctor
who acted to prevent a patient from immediate harm, e.g. by stopping
an acutely suicidal patient from leaving A&E, is unlikely to be criticized
and could claim a common law defence of ‘necessity’ and ‘best interests’
if he were to, there is, strictly speaking, no power to detain under the
common law.
726
Common law
• This allows medical practitioners to act in the patient’s best interests
in emergency situations where they are unable to give consent (e.g. if
they are unconscious, or conscious but lack capacity—although if time
permits, in cases where patients lack capacity, then the Mental Capacity
Act framework should be used over common law).
• If in an emergency, it is deemed necessary to detain a patient pending
assessment, it may be done under common law.
• Treatment under common law is given in the best interests of the
patient if it is carried out to save life or to ensure improvement or
prevent deterioration of physical or mental health.
Always document in the notes that you are giving treatment in the patient’s
best interests under common law.
Common law principles for medical treatment decisions
• Act in accordance with the patient’s wishes: a fundamental principle of
the doctor–patient relationship. Doctors should, in general, respect the
patient’s autonomy in decision-making, only acting against the patient’s
wishes in very limited circumstances.
• Presume capacity in adults: a patient over the age of 16 is presumed to
have capacity to make treatment decisions, unless there is evidence to
the contrary (assessed on the balance of probabilities).
• Apply the ‘reasonableness’ test: a frequently used consideration in law
is the test of what a hypothetical ‘reasonable man’ would do in the
circumstances. For medical treatment decisions, the test is what the
‘reasonable doctor’ would have done in those circumstances.
• Act in the patient’s ‘best interests’: in emergency situations, it may not be
possible to obtain consent (e.g. in an unconscious RTA victim requiring
drainage of an extradural haematoma); here, it is accepted that the
doctor’s overriding duty is to preserve life.
• Doctrine of necessity: ‘necessity’ provides a defence against a potential
criminal charge that you have assaulted a patient by giving non-
consensual treatment. A doctor may therefore give emergency
treatment to preserve life and prevent significant deterioration in health.
• Act in accordance with a recognized body of opinion: it is accepted in law
that medicine is not an exact science—that, in any situation, multiple
courses of action may be potentially reasonable. However, there is an
expectation that any treatment decision is considered suitable by a body
of professional opinion (the ‘Bolam test’).
• Act in logically defensible manner: the Bolitho case added a consideration
to the Bolam test by stating that medical decisions made must, in
addition to being in accordance with a recognized body of opinion, be
logically defensible in the circumstances.
Common law 731
Practice points
It is best to detain people under common law if you do not think that
they should leave the A&E department (see E Common law, p. 730–1
for details of the principles used). You are unlikely to be criticized for this,
and you may ensure their safety in the short term.
Practice points
• Always find out what medication a psychiatrically disturbed patient is
taking. It is dangerous to stop certain psychotropic medications.
• New onset of confusion is organic until proven otherwise. Have a low
threshold for starting aciclovir or other antiviral therapy until herpes
encephalitis is excluded.
Further reading
Hughes R (2003). Neurological Emergencies, 4th edn. BMJ Books, London.
Lingford-Hughes AR, Welch S, Peters L, Nutt DJ; British Association for Psychopharmacology, Expert
Reviewers Group. BAP updated guidelines: evidence-based guidelines for the pharmacological
management of substance abuse, harmful use, addiction and comorbidity: recommendations from
BAP. J Psychopharmacol 2012;26:899–952.
Mental Capacity Act 2005. M https://www.legislation.gov.uk/ukpga/2005/9/section/1
National Institute for Health and Care Excellence (2010, updated 2017). Alcohol-use disorders: diag-
nosis and management of physical complications. Clinical guideline [CG100]. M https://www.nice.
org.uk/guidance/cg100
National Institute for Health and Care Excellence (2010). Delirium: prevention, diagnosis and manage-
ment. Clinical guideline [CG103]. M https://www.nice.org.uk/guidance/cg103
National Institute for Health and Care Excellence (2011). Alcohol-use disorders: diagnosis, assess-
ment and management of harmful drinking and alcohol dependence. Clinical guideline [CG115].
M https://www.nice.org.uk/guidance/cg115
Royal College of Psychiatrists and Royal College of Physicians (2003). The Psychological Care of
Medical Patients, A Practical Guide, 2nd edn. Royal College of Psychiatrists and Royal College of
Physicians, London.
Semple D, Smyth R (2013). Oxford Handbook of Psychiatry, 3rd edn. Oxford University Press, Oxford.
South London and Maudsley NHS Foundation Trust (2013). The Maze 2013: A Practical Guide to the
Mental Health Act 1983 (amended 2007), 3rd edn. South London and Maudsley NHS Foundation
Trust, Beckenham.
Taylor D, Barnes TRE, Young AH (2018). The Maudsley: Prescribing Guidelines in Psychiatry, 13th edn.
South London and Maudsley NHS Foundation Trust and Oxleas NHS Foundation Trust,
Wiley-Blackwell.
Wyatt JP, Illingworth RN, Graham CA, Clancy MJ, Robertson CE (2006). Oxford Handbook of
Accident & Emergency Medicine, 3rd edn. Oxford University Press, Oxford.
738
Chapter 14 739
Drug overdoses
Overdoses: general approach
• ODs account for 10–15% of acute medical emergencies and result in
140 000 admissions to hospital each year in England and Wales.
• In the last 15 years, the incidence of poisoning has i.
• Thirty per cent of self-poisonings involve multiple drugs.
• Fifty per cent of patients will have taken alcohol as well.
• It has been well documented that the history taken following an OD is
often inaccurate with regard to the dose and timing of ingestion.
• Question any witnesses or family about where the patient was found
and any possible access to drugs.
• Examination may reveal clues as to the likely poison (e.g. pinpoint pupils
with opioids). Signs of solvent or ethanol misuse and IV drug use should
be noted.
Management
• Priorities are to:
1 Resuscitate the patient.
2 Reduce absorption of the drug, if possible.
3 Give a specific antidote, if available.
• Secure the airway (place in the recovery position), and monitor
breathing, BP, temperature, acid–base, and electrolytes, and treat
seizures or dysrhythmias; check BM in all drowsy patients. Intubate if not
protecting the airway and not reversible with naloxone. Flumazenil should
not be used diagnostically in the unconscious patient (see Table 14.1).
• Take account of any active medical problems that the patient may have,
e.g. IVDUs may have concurrent septicaemia, hepatitis, endocarditis,
pulmonary hypertension, or HIV-related disease.
• Measures to reduce gut absorption include:
• Gastric lavage: has an extremely limited role and may be associated
with significant complications. It should only be used within 1h of
a potentially life-threatening OD by clinicians with sufficient clinical
experience. It is contraindicated in corrosive or hydrocarbon
ingestion to enable its use.
• Activated charcoal (50g as a single dose): will adsorb most drugs if
given within 1h of ingestion, although its effectiveness falls off rapidly
thereafter. Drugs not adsorbed by charcoal include iron, lithium,
alkalis, acids, alcohols (e.g. ethanol, methanol, ethylene glycol), and
organic solvents.
• Multiple-dose activated charcoal (50g every 4h or 25g every
2h): increases whole body clearance of some drugs by interrupting
enterohepatic or enteroenteric cycling, e.g. phenobarbital,
carbamazepine, dapsone, quinine, and theophylline. Multiple-dose
charcoal may also be used in slow-release drug OD (e.g. theophylline,
calcium channel blockers).
• Whole bowel irrigation: Klean-Prep®, a solution of polyethylene glycol
(not to be confused with ethylene glycol!!) is given PO or by NG tube
at 2L/h in adults. It is continued until the rectal effluent becomes clear.
• Indications: ingestion of sustained-release or enteric-coated
preparations of toxic drugs such as calcium channel blockers, lithium,
iron. Percutaneous endoscopic gastrostomy (PEG) bowel lavage
may be used in body packers to hasten the passage of packets of
illicit drugs.
• Contraindications: bowel obstruction, perforation, ileus, or in seriously
ill patients, e.g. haemodynamic instability.
• Ipecac-induced emesis: is no longer used.
Advice about management of the poisoned patient is available on
TOXBASE® (M http://www.toxbase.org), the online database of the
National Poisons Information Service (NPIS). For uncommon ODs or un-
stable patients, always seek telephone advice from the NPIS (telephone
number inside the front cover of the BNF and on TOXBASE®).
742
Acetylcysteine Paracetamol
Activated charcoal Many oral poisons
Atropine Organophosphorus or carbamate insecticides;
nerve agents
Bradycardia
Calcium chloride Calcium channel blockers
Systemic effects of hydrofluoric acid
Calcium gluconate gel Local infiltration for hydrofluoric acid
Dicobalt edetate Cyanide antidotes
Hydroxocobalamin O2 should be administered in all cases
(Cyanokit®) Dicobalt edetate is the antidote of choice in
Sodium nitrite severe cases when there is a high clinical suspicion
Sodium thiosulfate of cyanide poisoning, e.g. after cyanide salt
exposure
Hydroxocobalamin (Cyanokit®) should be
considered in smoke inhalation victims who
have severe lactic acidosis, are comatose, are in
cardiac arrest, or have significant cardiovascular
compromise
Sodium nitrite may be used if dicobalt edetate is
not available
Sodium thiosulfate is used generally as an adjuvant
to other antidotes.
Flumazenil Reversal of iatrogenic over-sedation with
benzodiazepines
Should not be used as a ‘diagnostic’ agent and is
contraindicated in mixed tricyclic antidepressant/
benzodiazepine ODs and in those with a history
of epilepsy
Glucagon β-adrenoceptor-blocking drugs
Other indications, e.g. calcium channel blocker/
tricyclic antidepressants
Intralipid® 20% Severe systemic local anaesthetic toxicity
Methylthioninium Methaemoglobinaemia
chloride (methylene
blue)
Naloxone Opioids
Procyclidine injection Dystonic reactions
Table 14.2 (Contd.)
Antidote/drug Indication
Anticonvulsant drugs
Phenytoin
Phenytoin is an anti-epileptic and a class Ib antiarrythmic, and it inhibits
voltage-dependent Na+ channels. It is highly protein-bound, and its metab-
olism via the liver demonstrates saturable (Michaelis–Menten) kinetics.
Presentation
• Nausea and vomiting are common early features.
• Horizontal nystagmus (the sine qua non of phenytoin toxicity) is seen, as
concentrations increase.
• Dysarthria, drowsiness, nystagmus, ataxia, tremor, hyper-/h yporeflexia,
and in significant poisoning coma, opisthotonus, vertical nystagmus, and
convulsions.
Cardiovascular effects are rare after oral phenytoin OD (they occur with
rapid IV phenytoin injection and are due to the propylene glycol diluent).
Management
• Activated charcoal (50g for adults) if the patient presents within 1h of
ingestion of a toxic amount. Evidence from volunteer studies suggests
that multiple-dose activated charcoal might provide some benefit,
but there are no controlled data in patients with phenytoin poisoning.
Plasma phenytoin concentrations can be helpful in monitoring patients
with significant poisoning managed with multiple-dose activated
charcoal; symptomatic toxicity generally occurs with phenytoin
concentrations >20mg/L and severe toxicity with concentrations
>40mg/L.
• Observe for a minimum of 4h.
• All patients should have a 12-lead ECG (measure QRS and QT), and
symptomatic patients should have bloods for U&Es, LFTs, and glucose.
• Seizures should be treated with IV diazepam in the first instance.
• Phenytoin is highly protein-bound, and so dialysis and plasmapheresis
have no place in management.
Carbamazepine
OD with carbamazepine causes primarily dose-dependent CNS toxicity.
Absorption is unpredictable, and it may take 6–12h for peak levels to be
reached; secondary peaks can occur in patients with significiant toxicity.
Presentation
• Nystagmus, dilated pupils, hyper-reflexia, ataxia, seizures, intention
tremor, and dysarthria are common. Coma may present 8–12h later and
may be cyclical and associated with respiratory depression and seizures.
• ECG abnormalities, including prolonged PR, QRS, and/or QTc,
can occur, and in patients with severe poisoning, arrhythmias and
hypotension can occur. Hyponatraemia and hypokalaemia can be
present in those with severe poisoning.
Anticonvulsant drugs 745
Management
• Multiple-dose activated charcoal is indicated if >20mg/kg have been
taken and/or in symptomatic patients.
• Observe for at least 6h after a non-sustained related ingestion and 12h
after a sustained-release ingestion.
• Plasma carbamazepine concentrations can be useful in patients treated
with multiple-dose activated charcoal (concentrations >40mg/L can be
associated with severe toxicity).
• All patients should have an ECG to look for AV block and QRS and/or
QTc prolongation. Patients with ECG abnormalities should be discussed
with a poisons centre or a clinical toxicologist.
• Charcoal haemoperfusion and/or haemodialysis may have a role in life-
threatening toxicity; these patients should be discussed with a poisons
centre or a clinical toxicologist.
Sodium valproate
ODs of <5g are unlikely to cause toxicity. Fatalities have occurred after in-
gestion of 20g. Plasma concentrations peak around 4h after dosing, but the
half-life will be prolonged in OD.
Presentation
• Drowsiness is common, and coma can occur in large ingestions.
• Nausea, vomiting, abdominal pain, diarrhoea, and hypotension.
• Unlike other anticonvulsants, nystagmus is uncommon.
• Electrolyte abnormalities include hypernatraemia, hypoglycaemia,
hyperammonaemia, and hypocalcaemia.
• Delayed-onset cerebral oedema can occur at 12–72h post-ingestion in
those with severe poisoning.
• Haemorrhagic pancreatitis can also occur.
Management
• Supportive care is likely to be all that is needed, unless the patient has
severe valproate poisoning. Activated charcoal (50g) can be given if OD
taken within an hour.
• Monitor U&Es, Ca2+, and glucose levels, and in those with severe
poisoning, check ammonia levels.
• Seizures should be treated with IV diazepam.
• Hypotension may need treatment with fluids ± inotropes/vasopressors.
• Consider giving levocarnitine in patients with hyperammonaemia or
hepatotoxicity.
• Haemodialysis may be of value in massive ODs.
Practice points
Unlike phenytoin toxicity, dysarthria, nystagmus, and ataxia are not seen
in sodium valproate toxicity.
746
Newer anticonvulsants
• Lamotrigine, levetiracetam, pregabalin, vigabatrin, topiramate, tiagabine,
oxcarbazepine, gabapentin.
Clinical presentation
• Drowsiness is found almost universally with these agents but is rarely
severe, although coma can occur with pregabalin.
• Gabapentin OD may cause nausea and vomiting.
• Ataxia may be seen in lamotrigine and topiramate OD.
• Seizures may occasionally be seen in toxicity with lamotrigine, tiagabine,
and topiramate.
Management
• Activated charcoal should be considered if the OD is taken within 1h.
• Monitor U&Es and glucose.
Antipsychotic drugs 747
Antipsychotic drugs
Chlorpromazine, haloperidol, risperidone, olanzapine
All of these drugs have antipsychotic activity with dopamine receptor antag-
onist activity. Their pattern of toxicity and management are similar.
Presentation
Includes drowsiness, coma, extrapyramidal features (oculogyric crises, tor-
ticollis, trismus, and orolingual dyskinesia), myoclonus, hypotension (or
rarely hypertension), and seizures. Many antipsychotic drugs cause QT pro-
longation and torsades de pointes (particularly amisulpride and haloperidol).
Management
Includes essential OD management and symptom-directed and supportive
treatment.
• Consider activated charcoal (50g for adults) if the patient presents within
1h of ingestion of a toxic amount.
• Treat hypotension with IV fluids and raising the foot of the bed. Some
patients may need inotrope/vasopressor support.
• Seizures usually respond to diazepam (5–10mg IV initially); resistant
seizures are likely to require barbiturates.
• Treat any ECG features, as required:
• For severe QRS prolongation (>160ms), give IV sodium bicarbonate
8.4% (50mL).
• For severe QT prolongation (>500ms), give IV magnesium sulfate
(2g) over 15min.
• For torsades de pointes, give IV magnesium sulfate (2g) or use
overdrive pacing.
• Treat extrapyramidal symptoms, e.g. acute dystonic reactions with
anticholinergic agents, e.g. procyclidine (5–10mg IV).
748
Aspirin
Aspirin is now less commonly ingested in OD. Occasionally, poisoning fol-
lows the topical application of salicylic acid in keratolytics or the ingestion
of methyl salicylate (‘oil of wintergreen’). Its primary toxic effect is to un-
couple oxidative phosphorylation.
Presentation
• The typical features of moderate salicylate toxicity are sweating,
vomiting, epigastric pain, tinnitus, and blurring of vision.
• In adults, there is also an early increase in RR, causing alkalosis that
precedes the later development of metabolic acidosis; children are
more likely to develop an early pure metabolic acidosis.
• In severe OD, acidosis reduces the ionization of salicylic acid, which
enhances tissue penetration. In the CNS, this presents as agitation,
tremor and fits, coma, and respiratory depression. This also decreases
renal salicylate clearance.
Complications
• Metabolic acidosis.
• Pulmonary oedema (non-cardiogenic, ARDS).
• ARF.
• Abnormal clotting due to hypoprothrombinaemia is very rare.
• Significant GI bleeding is surprisingly infrequent.
Prognostic features
• It is important that plasma salicylate concentrations are interpreted in
the context of clinical features and the patient’s acid–base status.
• Significant toxicity is unlikely at peak salicylate concentrations
<350mg/L.
• Salicylate concentrations of 500–750mg/L represent moderate toxicity,
and >750mg/L (5.4mmol/L) severe toxicity; but severe features can
be seen at lower salicylate concentrations in patients with metabolic
acidosis and in children (<10 years)/the elderly (>70 years).
• Severe metabolic acidosis is associated with a poor outcome.
Management
• Take blood for U&Es, PT, and salicylate (and paracetamol) concentration
at 4h after ingestion (repeat every 3–4h in symptomatic patients and
in those with a salicylate concentration of >350mg/L later to assess
continued absorption, as tablets may adhere to form large masses in the
stomach or some preparations are enteric-coated).
• Activated charcoal should be given if >125mg/kg of aspirin has been
taken in the last hour.
• If after 4h, salicylate levels are continuing to rise, a further dose of
activated charcoal may be given to patients to prevent late absorption.
• Check ABGs to assess the acid–base status.
• Mild or moderate salicylate OD requires only PO or IV rehydration,
with particular attention to K+ supplements.
Aspirin 749
Benzodiazepines
Deliberate OD with this group of compounds is very common. Unless
combined with other sedatives (e.g. alcohol, opioids, tricyclic antidepres-
sants), effects of a benzodiazepine OD are generally mild.
Presentation
• Drowsiness.
• Slurred speech.
• Hypotension (mild).
• Ataxia.
• Coma.
• Respiratory depression.
The elderly and those with chronic lung disease are generally more suscep-
tible to cardiorespiratory depression with benzodiazepine OD.
Management
• If patients present within 1h, give 50g of activated charcoal. Ensure the
patient can protect their airway.
• Flumazenil should not be used diagnostically in comatose patients
where the diagnosis is uncertain or if mixed ODs are a possibility,
as it may cause seizures, arrhythmias, or death—particularly if the
patient has co-ingested a proconvulsant or proarrhythmic drug (e.g.
dextropropoxyphene, theophylline, tricyclic antidepressants).
• If it is certain that a pure benzodiazepine OD has been taken, flumazenil
may be used to reverse significant cardiorespiratory depression in
severe OD, i.e. those with significant CNS depression associated with
respiratory depression and hypoxia. It should generally only be given
after consultation with a doctor experienced in its use or a poisons
centre/clinical toxicologist. Flumazenil is given as an IV bolus of 0.2mg. If
no response, give further IV bolus doses of 0.3mg and thereafter 0.5mg,
to a maximum of 3mg, until the patient has an adequate RR. Most
benzodiazepines have a substantially longer duration of action than
flumazenil, and an IVI of 0.1–0.4mg/h will be needed to prevent early
re-sedation.
• Avoid giving excess flumazenil to completely reverse the effect of
benzodiazepines. In chronic benzodiazepine users, this can precipitate
withdrawal.
Beta-blockers 751
Beta-blockers
These agents competitively antagonize the effects of endogenous cat-
echolamines. They cause profound effects on AV conduction and myo-
cardial contractility, and their effects are predictable based on their known
pharmacology.
Presentation
• Sinus bradycardia.
• Hypotension.
• Cardiac failure.
• Cardiac arrest (asystole or VF).
• Hypoglycaemia (rare).
• Bronchospasm (rare in non-asthmatics).
• Lipid-soluble β-blockers (e.g. propranolol, carvedilol, labetalol,
metoprolol, and pindolol) are more likely to cross the blood–brain
barrier, causing CNS features, e.g. drowsiness, confusion, seizures,
hallucinations, and coma.
• Sotalol causes QT prolongation and can cause torsades de pointes.
Prognostic features
• Subjects with pre-existing impaired myocardial contractility are less likely
to tolerate an OD of β-blockers.
Management
• Establish IV access.
• Check a 12-lead ECG, and then monitor ECG continuously for at least
6h (12h for sustained-release OD).
• Record the HR and BP regularly (at least every 15min).
• Consider activated charcoal (50g for adults) if the patient presents within
1h of ingestion.
• Hypotension: seek expert help early, with early admission to critical care;
raise the foot of the bed, and give an appropriate fluid challenge.
• If persistent hypotension, give IV glucagon (50–150 micrograms/kg,
followed by an infusion of 1–5mg/h). This peptide exerts an inotropic
effect, independent of β-receptor activation, by increasing myocardial
cyclic adenosine monophosphate (cAMP) levels.
• Use of an intra-aortic balloon or an alternative cardiac support device
may provide an adequate cardiac output, while the drug is metabolized
and excreted.
• Bradycardia: may respond to atropine (0.5–1.2mg for an adult, repeated
if required) or to glucagon in the doses discussed above. Pacing
may be required in patients with persistent bradycardia associated
with cardiovascular compromise (a high threshold is often required)
(E Pulmonary artery catheterization 1, pp. 800–1; E Pulmonary artery
catheterization 2, p. 802; E Pulmonary artery catheterization 3, p. 804).
• Convulsions: give diazepam 5–10mg IV initially (E Status epilepticus
(tonic–clonic) 1, pp. 408–9).
• Bronchospasm: treat initially with nebulized salbutamol (2.5mg).
• Monitor blood glucose regularly (hourly BMs) in symptomatic patients. If
hypoglycaemia develops, give PO or IV glucose.
752
Carbon monoxide
The most common sources are smoke inhalation, poorly maintained do-
mestic gas appliances, and deliberate inhalation of car exhaust fumes. CO
poisoning causes tissue hypoxia by two mechanisms. First, it interrupts
electron transport in mitochondria. Second, it reduces O2 delivery both by
competing with O2 for binding to Hb (its affinity for Hb is 220-fold that of
O2) and altering the shape of the HbO2 dissociation curve (making it shift
to the left).
Presentation
Carboxy-haemoglobin (COHb) levels correlate poorly with clinical features.
In general, levels of COHb of <30% cause only headache and dizziness.
Fifty to 60% produces syncope, tachypnoea, tachycardia, and fits. Levels of
>60% cause an increasing risk of cardiorespiratory failure and death.
Complications
• These are the predictable result of local hypoxia. Sites at particular
risk are: the CNS, affecting cerebral, cerebellar, or midbrain function
with confusion and incoordination; the myocardium with ischaemia and
infarction; skeletal muscle, causing rhabdomyolysis and myoglobinuria;
and skin involvement ranging from erythema to severe blistering.
• Long-term exposure can result in parkinsonism, ataxia, personality
change, poor memory, dementia, and peripheral neuropathy.
Management
• Ensure the patient is removed from the source; apply a tight-fitting face
mask, and give 100% O2.
• An ABG should be taken. Although PaO2 may be normal, it is important
to measure the COHb concentration on a co-oximeter. NB Monitoring
O2 saturation with a pulse oximeter is unhelpful, since it will not
distinguish HbO2 and COHb (hence the apparent O2 saturation will be
falsely high).
• O2 should be continued until COHb is <5%, which may take up to 20h.
• Check a 12-lead ECG, and continuously monitor the rhythm. Take
blood for FBC, U&Es, CPK, and troponin in symptomatic patients.
• If the patient is comatose, they should be intubated and ventilated with
100% FiO2 (this reduces the half-life of COHb to 80min, compared to
320min on room air). This should also be considered in all patients who
are severely acidotic or show evidence of myocardial ischaemia.
• Seizures should be controlled with IV diazepam (5–10mg).
• There is no evidence that hyperbaric O2 improves outcome; it may
be considered in those with severe poisoning (e.g. coma, neurological
signs)—these patients should be discussed with the NPIS.
• If the patient has been exposed to CO in a house fire, consider whether
they may have effects of soot inhalation or cyanide exposure.
• Ensure medical follow-up, as the neuropsychiatric sequelae may take
many weeks to evolve.
754
Cyanide
Poisoning is most commonly seen in victims of smoke inhalation [hydrogen
cyanide (HCN) is a combustion product of polyurethane foams]. Cyanide
derivatives are, however, widely employed in industrial processes, and sig-
nificant cyanide poisoning can occur in industrial accidents. Cyanide acts by
irreversibly blocking mitochondrial electron transport.
Presentation
HCN gas can lead to cardiorespiratory arrest and death within a few min-
utes. Onset of effects after ingestion or skin contamination is generally
much slower (up to several minutes or even hours). Note that the detec-
tion of the smell of bitter almonds is unhelpful.
Decisions regarding treatment are generally based on whether the pa-
tient is classified as having features of mild, moderate, or severe poisoning:
• Mild: nausea, dizziness, hyperventilation, and a lactate level of <10mmol/L.
• Moderate: reduced GCS scores or convulsions, vomiting, hypotension, a
lactate level of 10–15mmol/L.
• Severe: coma, fixed dilated pupils, cyanosis, cardiovascular instability or
respiratory failure, a lactate level of >15mmol/L.
Prognostic features
• Ingestion of a few hundred milligrams of a cyanide salt is usually fatal in
adults. Absorption can be delayed by a full stomach and high gastric pH
(e.g. antacids).
• Patients surviving to reach hospital after inhalation of HCN are unlikely
to have suffered significant poisoning.
Management
• Do not attempt mouth-to-mouth resuscitation. Give 100% O2 by a tight-
fitting face mask or ventilate via an ETT if necessary.
• Establish IV access.
• Check ABGs. Lactic acidosis indicates severe poisoning.
• Skin contamination requires thorough washing of the affected area with
soap and water.
• All cases of suspected cyanide poisoning should be discussed with a
poisons service or a clinical toxicologist before treatment.
• If mild features are present, then sodium thiosulfate can be used (25mL
of 50% sodium thiosulfate over 10 min).
• In moderate toxicity, sodium thiosulfate can also be given at the dose
above, with sodium nitrite (10mL of a 3% solution over 5–20min) or
hydroxocobalamin (5g over 15min).
• In severe toxicity, dicobalt edetate or hydroxocobalamin are recommended
if available. Dicobalt edetate is given at a dose of 300mg of Kelocyanor ®
IV over 1min, followed immediately by 50mL of 50% glucose; dicobalt
edetate can be very toxic and potentially fatal if cyanide is not present.
• A second dose of dicobalt edetate can be given if no response to
the first, but further doses can cause cobalt toxicity if the diagnosis
is incorrect. Alternatively, give sodium nitrite (10mL of a 3% solution
over 5–20min) and sodium thiosulfate (25mL of 50% solution).
Methaemoglobin levels should be measured if sodium nitrite is given.
Digoxin 755
Digoxin
Presentation
• Nausea, vomiting, confusion, and diarrhoea.
• Visual disturbance (blurring, flashes, disturbed colour vision).
• Cardiac dysrhythmias (tachyarrhythmias or bradyarrhythmias), hypotension.
Complications
• Hyperkalaemia.
• Cardiac dysrhythmias—any type of brady-or tachyarrhythmias can
occur in digoxin toxicity.
Management
• Take blood for a digoxin concentration (in patients not normally on
digoxin, this should be at least 6h post-ingestion) and U&Es.
• Baseline 12-lead ECG and continuous ECG monitoring.
• Activated charcoal should be given if the patient presents within 1h of
OD. Activated charcoal (25g) may be repeated every 2h, provided the
patient is not vomiting.
• Sinus bradyarrhythmias and AV block usually respond to atropine
(0.6mg IV, repeated to a total of 2.4mg). Asymptomatic ventricular
ectopics do not require specific treatment.
• If hyperkalaemia is present, treat in the first instance with insulin and
glucose, but a K+ level of >6.5 is an indication for antibody treatment.
Do not give calcium gluconate or chloride, as the increase in intracellular
Ca2+ can provoke arrhythmias and worsen digoxin-related hypotension.
• Ventricular tachyarrhythmias should be treated with magnesium sulfate
(8–10mmol IV).
• Indications for DigiFab® include haemodynamic instability, resistant
ventricular tachyarrhythmias, or high K+ levels requiring treatment with
digoxin-binding antibody fragments (see Box 14.1).
• The neutralizing dose for patients intoxicated during chronic therapy
is: (number of vials) = digoxin level (ng/mL) × weight (kg) × 0.01. Half this
dose should initially be given, and repeated if there is recurrence of toxicity.
Clinical effects, e.g. termination of VT, will take around 20–30min to occur.
K+ and free serum digoxin levels should be monitored for 24h after DigiFab®
therapy, but be aware that often the levels will rise, as most assays will
measure both bound and free digoxin levels. In patients with renal impairment,
this rebound is delayed and monitoring should be extended to 72h.
• Generally, pacing is best avoided, owing to the excitable myocardium
being more prone to arrhythmias, but if DigiFab® is not available, then a
transvenous pacing wire or overdrive pacing may be the only option available.
Ethanol: acute intoxication
Patients may present either with acute intoxication, withdrawal syndromes,
nutritional deficiency syndromes, or chronic toxicity (liver, CNS, peripheral
neuromyopathy, etc.).
Presentation
Alcohol intoxication results in disinhibition, euphoria, incoordination, ataxia,
stupor, and coma. Chronic alcoholics require higher blood ethanol levels
than ‘social’ drinkers for intoxication. Obtain a history from friends or re-
latives. Examine the patient for signs of chronic liver disease, trauma, or
signs of infection.
Complications
• Acute gastritis causes nausea and vomiting, abdominal pain, and GI
bleeding.
• Respiratory depression and arrest, inhalation of vomit (with ARDS), and
hypothermia may accompany profound sedation.
• Hypoglycaemia is common and should be excluded.
• Alcoholic ketoacidosis.
• Accidental injury, particularly head injury (subdural).
• Rhabdomyolysis and ARF.
• Infection (septicaemia, meningitis).
Management
• Mild to moderate intoxication usually requires no specific treatment—
the need for admission for rehydration and observation depends on the
individual patient. Admit all patients with stupor or coma.
• Check the airway is clear of vomitus and the patient is able to protect
their airway. Nurse in the recovery position.
• Gastric lavage or charcoal are not indicated.
• Take blood for U&Es, CPK, glucose, and amylase, and consider ethanol
levels and an ABG (acidosis). Consider the possibility of other drug OD.
• Monitor closely for respiratory depression, hypoxia, hypotension,
and withdrawal syndromes (E Acute alcohol withdrawal, pp. 436–7;
E Acute alcohol withdrawal, pp. 718–19).
• Check blood glucose. In comatose patients with hypoglycaemia,
give 25–50mL of 50% glucose, followed by an IVI of 10% glucose if
necessary. The only concern is that glucose may precipitate WE in
malnourished individuals. Therefore, ideally give a bolus of thiamine
1–2mg/kg IV before glucose.
• Rehydrate with IV fluids (avoid excessive use of saline in patients with
signs of chronic liver disease); monitor urine output.
• Rarely, haemodialysis is used if intoxication is very severe or in the
presence of acidosis.
• After recovery from the acute episode, arrange for a psychiatric
or medical assessment and follow-up and referral to an alcohol
rehabilitation programme if appropriate.
• For alcohol withdrawal and DT, see E Acute alcohol withdrawal,
pp. 436–7; E Acute alcohol withdrawal, pp. 718–19.
Hypoglycaemic agents
Insulin
Insulin poisoning is an important cause of hypoglycaemia that may be delib-
erate or accidental, and can result in life-threatening consequences and be
prolonged with long-acting insulin. If ingested, insulin is non-toxic.
Presentation
• Symptoms related to hypoglycaemia may present within 2h of
injection: nausea, vomiting, diaphoresis, tachycardia, palpitations,
agitation, and confusion related to cerebral oedema, followed by
seizures and coma.
• Electrolyte abnormalities may include low K+, Mg2+, and PO43–.
Practice points
Watch out for those on β-blockers that may present with minimal symp-
toms of hypoglycaemia.
Management
• Airway, breathing, and circulation if severe hypoglycaemia!
• Correct any hypoglycaemia rapidly with 50mL of 50% glucose/100mL
of 20% glucose or oral agents if alert.
• Commence a 10% glucose infusion, titrated to blood sugar levels, to
continue thereafter.
• Monitor: U&Es, ECG, lab glucose at least hourly, and capillary glucose
every 10–15min initially.
• Patients need to be observed for 6h after cessation of any glucose
infusion to ensure their glucose levels remain normal prior to discharge.
Metformin
Biguanide hypoglycaemic agents may cause type B lactic acidosis that is mild
at therapeutic doses but can be severe if taken in OD and/or in elderly pa-
tients with renal impairment.
Presentation
• Hypoglycaemia is uncommon but may occur.
• Abdominal pain, diarrhoea, and lactic acidosis may cause
hyperventilation, d GCS scores, and hypotension.
Management
• Consider activated charcoal (50g) if the patient presents within 1h.
• Monitor: U&Es, glucose, and venous bicarbonate.
• ABG in symptomatic patients. Any severe metabolic acidosis should be
corrected with 8.4% sodium bicarbonate.
• Haemodialysis: is the treatment of choice for persistent metabolic
acidosis and lactate levels consistently >10, especially if poor renal
function.
Hypoglycaemic agents 759
Iron
• The toxicity of a given iron preparation is dependent upon the
proportion of elemental iron contained within it.
• Greater than 20mg/kg of elemental iron is likely to cause toxicity, while
>200mg/kg may prove fatal.
• The early clinical features of iron toxicity are due to the corrosive
effects of iron, while the late effects are the result of disruption to
intracellular processes.
Presentation
• Early (30min onwards): vomiting, diarrhoea ± haematemesis and
melaena, abdominal pain
• Mid-latent phase (76–12h): the initial symptoms abate, and the patient
can deceptively appear to be improving.
• Late (from 12–48h): there might be a return of the initial symptoms,
together with hypotension, metabolic acidosis, evidence of
hepatocellular necrosis, including hypoglycaemia, jaundice,
encephalopathy, and coagulopathy. Respiratory and renal failure may
also occur.
• Very late (2–5 weeks): scarring from the initial corrosive effects of iron
can cause pyloric stenosis and small bowel strictures.
Investigations
• A serum iron level should be taken at 4h post-ingestion, if possible,
along with FBC, U&Es, LFTs, glucose, and clotting.
• If a sustained-release preparation has been taken, then a further iron
level should be taken at 6–8h.
• An ABG should be done if a significant OD is suspected.
• A plain AXR may be useful to assess the number of tablets ingested.
Management
• Give IV fluids and blood, as needed, but be careful not to fluid-overload
these patients.
• There is no place for activated charcoal in the management of these
patients, but whole bowel irrigation should be undertaken if sustained-
release tablets have been taken or tablets can be seen within the
stomach on X-ray.
• Parenteral chelation therapy: is indicated if the serum iron level is
>90micromol/L (5mg/L) or in patients who are shocked, convulsing, or
comatose.
• Give desferrioxamine IV initially at a rate of 15mg/kg/h. The generally
recommended maximum daily dose is 80mg/kg; however, higher doses
may be used in patients with severe poisoning—discuss with a poisons
centre or a clinical toxicologist. Desferrioxamine may cause hypotension
if infused more rapidly than recommended. Pulmonary oedema and
ARDS have been reported in patients treated at >80mg/kg/day
for >24h.
Iron 761
762
Lithium
Lithium has a low therapeutic index and is available in sustained-release
(most commonly) and non-sustained-release preparations. It is very im-
portant to distinguish between acute, acute-on-chronic, and chronic tox-
icity, as they are distinct clinical entities.
Clinical classification of lithium toxicity
Acute toxicity occurs in the context of an acute OD of lithium; lithium OD
in patients who are lithium-naïve is generally better tolerated than lithium
OD in those who take lithium therapeutically (acute-on-chronic OD).
Chronic toxicity tends to occur if there has been impairment of renal
function, dehydration, Na+ depletion, or in the context of drug interactions
with other drugs, e.g. ACEIs, NSAIDs, or diuretics.
There is a greater risk of neurological features and permanent impair-
ment in patients with chronic toxicity (E see Management, pp. 762–3), and
serum concentrations often correlate poorly with clinical features.
Presentation
• Thirst, polyuria, diarrhoea, vomiting, and fine tremor are common.
• In severe toxicity, the effects on the CNS generally predominate,
with impairment of consciousness, confusion, coarse tremor, choreo-
athetoid movements, urinary/faecal incontinence, hypertonia, and
seizures.
• Non-neurological features seen in severe poisoning include
hypernatraemia, cardiac arrhythmias, and hypotension.
Prognostic features
Features of toxicity are usually associated with lithium concentrations
>4–6mmol/L in acute lithium OD but can be seen at lower concentrations
(2–4mmol/L) in acute-on-chronic OD or chronic accumulation; however,
generally, clinical features are a more important prognostic marker than
lithium concentrations.
Management
• If slow-release preparations are involved in a significant acute or acute-
on-chronic OD, whole bowel irrigation with polyethylene glycol is
useful. (NB Activated charcoal does not adsorb lithium).
• Check serum lithium concentration at 6h, and repeat 6-to 12-hourly
(ensure the tube used does not contain lithium-heparin anticoagulant).
• Patients with slow-release lithium OD should be observed for 24h.
• Symptomatic patients should have an ECG.
• Check U&Es.
• Any diuretic (especially thiazides) or other drug likely to alter renal
handling of lithium (e.g. NSAIDs) should be stopped.
• Correct any fluid or electrolyte deficits, and ensure adequate hydration.
Forced diuresis should not be undertaken.
Lithium 763
Recreational drugs: stimulants
Broadly, recreational drugs can be divided into stimulants, hallucinogens,
and depressants.
Examples of stimulants: amphetamines (e.g. amphetamine, MDMA (3,4-
methylenedioxymethamphetamine), methamphetamine), cocaine, piperazines,
cathinones (e.g. mephedrone).
Amphetamines have been taken around the world for decades, but
recently there has been a new wave of substituted amphetamines and
phenylethylamines known as novel psychoactive substances (NPS), in
particular the cathinones which are β-keto derivatives of amphetamine.
A number of cathinones are used recreationally, including mephedrone,
methedrone, and methylone. Other NPS stimulants include indanes,
tetralines, pipradrols, and benofurans.
Common complications of stimulants include:
• Tachycardia, hypertension, and cardiac arrhythmias, often SVTs.
• Central effects (most relating to i sympathetic nervous system
stimulation): sweating, tremor, bruxism, mydriasis, seizures,
psychomotor agitation, anxiety, psychosis, and delusions.
• A hyperthermic syndrome which has some similarity to serotonin
syndrome: hyperthermia, hypertonia, nystagmus, clonus, autonomic
instability which may result in rhabdomyolysis, DIC, and ARF.
Less common complications include cardiomyopathy (after chronic use),
aortic dissection, and subarachnoid and intracerebral haemorrhage.
Psychotic symptoms may persist once the acute phase has passed, and it is
likely that chronic use is associated with a higher incidence of mental illness.
Cocaine
Cocaine may be used as cocaine powder (nasal insufflation or IV use) or as
crack cocaine (smoked or IV injection). Many of the features of acute co-
caine toxicity are similar to other stimulant recreational drugs (tachycardia,
hypertension, psychomotor agitation); in addition, cocaine can cause is-
chaemic stroke, intracerebral haemorrhage, arrhythmias related to cardiac
ion channel effects, and ACS.
Cocaine-related acute coronary syndrome and arrhythmias
• The mechanism of cocaine-related ACS (coronary artery
vasoconstriction) is different to classical ACS, and therefore
management is different.
• Na+ channel and/or K+/Ca2+ channel blockade can result in broad
complex tachyarrhythmias.
General management of stimulant toxicity
• Agitation may require diazepam (5–10mg IV initially); diazepam can also
help with cocaine-related ACS by action on peripheral benzodiazepine
receptors and coronary vasodilatation.
• Perform a 12-lead ECG for evidence of myocardial ischaemia (although
the ECG is less sensitive in the setting of acute cocaine toxicity) or
QRS/QTc prolongation (which indicates an i risk of ventricular
tachyarrhythmias).
Recreational drugs: hallucinogens
Examples: LSD, ketamine, glaucine, tryptamines, phencyclidine, cannabis,
mushrooms (Psilocybe semilanceata).
Ketamine
Usually used therapeutically as an anaesthetic and an analgesic. When used
as a recreational drug of abuse, it is usually snorted or taken orally. Onset
of effects is rapid, whatever method is used.
Presentation
• Vomiting, blurred vision, numbness, dizziness, and ataxia at low doses.
• Agitation, along with hallucinations and dissociation (‘out-of-body
experiences’), can be severe at moderate doses, together with mild
tachycardia and hypertension.
• Rarely, at high doses, respiratory depression and pulmonary oedema
can occur.
Magic mushrooms
The active ingredient is psilocybin, which is a 5-HT2A receptor agonist.
Presentation
• Vomiting, flushing, dilated pupils, abdominal pain, visual and auditory
hallucinations.
• Impairment of the ability to judge distances and height is common.
• Rarely, arrhythmias, MI, abnormal LFTs, and renal failure from
rhabdomyolysis can occur.
General management of hallucinogenic toxicity
• The patient should be nursed in a calm environment.
• Monitor BP, HR, temperature, and RR every 30min.
• Diazepam is the treatment of choice for significant agitation.
Recreational drugs: depressants
Opioids
Opioid toxicity may occur as a result of opioid or opiate misuse, commonly
heroin (taken IV, by skin-popping, smoked, or rarely snorted), or due to
deliberate self-poisoning or supratherapeutic excess of opioids used as
analgesics. It is important to remember that some opioids are present in
combination formulations with paracetamol, and so there is the potential
for paracetamol, in addition to opioid, toxicity. Some opioids, in particular
methadone, are long-acting and the half-life is even more prolonged in OD.
Presentation
Pinpoint pupils and respiratory system and CNS depression leading to coma
are typical. Both the RR and respiratory depth are d. The depressive effects
are exacerbated by alcohol or other CNS depressants such as benzodi-
azepines. BP may be low, but significant hypotension is rare in pure opioid
toxicity.
Prognostic features
• Non-cardiogenic pulmonary oedema carries a poor prognosis.
• Renal impairment reduces the elimination of many opiates and prolongs
their duration of action.
Management
• Monitor RR, depth of respiration, and pulse oximetry. Give O2 by mask.
• Establish IV access. If paracetamol–opioid combinations have
been ingested, measure a plasma paracetamol concentration
(E Paracetamol: assessment, p. 772).
• The specific antidote is naloxone (a pure opioid antagonist) which
should be given IV in boluses of 0.2–0.4mg at 1–2min intervals in
patients with respiratory depression/hypoxia until the patient has an
RR >12/min and adequate respiratory depth/O2 saturations. Avoid
giving sufficient naloxone to completely reverse the effect of opiates
in an opioid-dependent subject. This is likely to precipitate an acute
withdrawal reaction. The end-point of naloxone therapy is adequate
respiration.
• Doses of up to 2mg (and above) may be required, but if no response
is seen at this dose, then additional or alternative causes of the clinical
picture should be considered.
• The duration of action of naloxone is shorter than many opioids,
and so either repeated IV boluses of naloxone or a naloxone infusion
should be started to avoid re-sedation (starting with two-thirds of
the dose required to initially rouse the patient per hour and adjusting
as necessary). In the case of OD with long-acting opiates, such as
methadone, infusion of naloxone may be necessary for 48–72h.
Complications
• All opioids can cause non-cardiogenic pulmonary oedema, although it is
most frequently seen with IV heroin.
• Rhabdomyolysis can occur in opioid-induced coma but is not common.
• IVDUs may develop right-sided endocarditis and septic PEs (several
localized infiltrates on CXR).
Practice points
The respiratory depressant effects of buprenorphine are not fully reversed
by naloxone, and mechanical ventilation may be required in severe cases.
Paracetamol: assessment
In therapeutic doses, only a minor fraction of paracetamol is metabolized
to the reactive metabolite N-acetyl-p-benzoquinoneimine (NABQI), which
is detoxified by conjugation with glutathione. In OD, the normal metabolic
routes become saturated; therefore, an i fraction is metabolized via the
cytochrome P450 system to NABQI; hepatic glutathione stores become
depleted, and NABQI results in hepatocellular toxicity.
Paracetamol OD can be divided into an acute single OD and a staggered
OD in which the tablets are taken over 1h.
In September 2012, the Medicines and Healthcare Products Regulatory
Agency (MHRA) issued changes to the assessment and treatment of para-
cetamol poisoning with the antidote acetylcysteine in the UK. There is now
no risk stratification, and for patients with a single acute oral paracetamol
OD, there is just a single treatment line on the paracetamol nomogram
and staggered ODs should be treated at a threshold of 75mg/kg of para-
cetamol/day.
Presentation
• Apart from mild nausea, vomiting, and anorexia, patients presenting
within 24h of ingestion are generally asymptomatic.
• Hepatic necrosis becomes apparent in 24–36h, with vomiting, right
subchondral pain/tenderness, jaundice, acute liver failure, and
hypoglycaemia/encephalopathy.
• Encephalopathy may worsen over the next 72h, and oliguria and renal
failure can develop.
• Lactic acidosis: either <12h (very rare, in massive paracetamol
ingestions) or late in association with acute liver failure.
Paracetamol: assessment 773
74
Paracetamol: management
Single acute paracetamol overdoses
Early (<8h since paracetamol ingestion)
• Give activated charcoal 50g to patients presenting within 1h of a
significant (>150mg/kg) ingestion.
• Assess the need for treatment with the antidote acetylcysteine by
plotting the timed paracetamol concentration on the nomogram (see
Fig. 14.1). Take U&Es, LFTs, and INR at the same time as the plasma
paracetamol concentration.
• There is no need to start acetylcysteine before the 4h concentration is
known, as long as a result is known and acted upon within 8h.
• If the paracetamol concentration is on the line or within 10% of the line,
then it is advisable to treat with acetylcysteine (see Box 14.2).
Late (>8h since paracetamol ingestion)
• All patients with a significant OD of paracetamol (>75mg/kg) who
present 8–24h after ingestion should be treated with acetylcysteine until
levels are available.
• At presentation, take a plasma paracetamol concentration, along with
U&Es, LFTs, and INR, and plot the paracetamol concentration on
the nomogram. Continue acetylcysteine if the plasma paracetamol
concentration is above or within 10% of the nomogram. Acetylcysteine
can be stopped if the plasma paracetamol concentration is well below
the nomogram. Beware of interpretation of plasma paracetamol
concentrations in late-presenting patients (>14–16h), as the nomogram
treatment concentration is at or below the laboratory limit of detection.
• If there is doubt about whether or not to continue acetylcysteine,
discuss with a poisons centre or a clinical toxicologist.
Very late (>24–36h since paracetamol ingestion)
• If there is doubt about whether to treat or not, discuss the case with a
poisons centre or a clinical toxicologist.
• Treatment with acetylcysteine should NOT be started, unless there
is RUQ tenderness, jaundice, or clinical/biochemical evidence of liver
impairment.
• Bloods, as listed above, should be sent, including a plasma paracetamol
concentration.
• If paracetamol is detected, then there is the potential that there is an
inaccuracy in the history, and a full course of acetylcysteine should
be given.
• If the INR is >1.3 or the ALT is >3 times the upper limit of normal,
acetylcysteine should be started.
Staggered paracetamol overdoses
• There is no place for plasma paracetamol concentrations in the risk
assessment of staggered paracetamol ODs. The 2012 MHRA update on
the management of paracetamol poisoning suggests that all staggered
ODs with an ingestion of >75mg/kg over a 24h period should be
started on treatment.
Paracetamol: management 775
120 0.8
110
Treatment line 0.7
90 0.6
80
0.5
70
60 0.4
50
0.3
40
30 0.2
20
0.1
10
0 0
0 2 4 6 8 10 12 14 16 18 20 22 24
Time (hours)
Serotonin syndrome
Many drugs can cause serotonin syndrome, including serotonin-releasing
agents [e.g. SSRIs, e.g. paroxetine, fluoxetine, citalopram, sertraline;
serotonin– noradrenaline reuptake inhibitors (SNRIs), e.g. venlafaxine,
duloxetine; tricyclic antidepressants, e.g. clomipramine, imipramine; other
medications with serotonergic activity, e.g. opioids (tramadol, fentanyl),
St John’s wort; recreational drugs such as MDMA (ecstasy) and cathinones;
and MAOIs, e.g. phenelzine, tranylcypromine, moclobemide]. Serotonin
syndrome is more likely when an individual is exposed to two agents which
increase the serotonergic activity. Serotonin syndrome presents as a spec-
trum, from mild to potentially lethal, and may be associated with intentional
self-poisoning and inadvertent drug interactions, but it can also occur with
therapeutic use of serotonergic drugs.
Presentation
The majority of cases present within 24h (and most within 6h) of drug initi-
ation or dose changes. Typically, a triad of mental status changes (agitation,
confusion), autonomic hyperactivity (tachycardia, hypertension, hyper-
thermia), and neuromuscular excitation (clonus, hypertonia, hyper-reflexia)
is seen. Severe rigidity and hyperthermia can be associated with significant
complications, including rhabdomyolysis, AKI, metabolic acidosis, and DIC.
The Hunter criteria can be used to diagnose serotonin syndrome. To fulfil
the criteria, a patient must have taken a serotonergic agent and have one
of the following:
• Spontaneous clonus.
• Inducible clonus PLUS agitation or diaphoresis.
• Ocular clonus PLUS agitation or diaphoresis.
• Tremor PLUS hyper-reflexia.
• Hypertonia PLUS a temperature above 38°C PLUS ocular clonus or
inducible clonus.
Investigations
Serotonin syndrome is a clinical diagnosis based on a typical clinical pic-
ture, together with a drug history of recent exposure to one or more
serotonergic agents. Patients with significant serotonin syndrome, particu-
larly those with hyperthermia, should have a CK level, clotting, U&Es, LFTs,
and blood gas.
Differential diagnosis
• NMS:
• Slower onset and resolution (days), extrapyramidal features with no
clonus.
• Anticholinergic toxicity.
• Malignant hyperthermia.
• Sedative–hypnotic withdrawal.
• Meningitis/encephalitis.
Management
General supportive care
• Support the airway.
• Discontinuation of all serotonergic agents.
• IV crystalloid for volume replacement.
• Close monitoring of temperature, HR, and BP.
• Sedation with a benzodiazepine (e.g. IV lorazepam 2–4mg or PO
diazepam 5–10mg in adults).
Hyperthermia
Severe hyperthermia can lead to rhabdomyolysis, AKI, metabolic acidosis,
and DIC and should be aggressively managed with ice packs, cooling blan-
kets, or invasive cooling devices. Consider paralysis and tracheal intubation
if the temperature is >40–41°C. If benzodiazepines and supportive care
fail and the patient has ongoing hyperthermia, serotonin antagonists, such
as cyproheptadine or chlorpromazine, can be considered (these patients
should be discussed with a poisons centre or a clinical toxicologist, with
critical care support).
780
Toxic alcohols
Ethylene glycol and methanol
Ethylene glycol is present in antifreeze and is rapidly absorbed from the gut.
Peak concentrations occur 1–4h after ingestion. Ethylene glycol is metabol-
ized to glycolaldehyde, then to glycolic, glyoxylic, and oxalic acids which are
responsible for acidosis and the majority of the effects.
Methanol is metabolized to formaldehyde and then to formic acid which
causes the characteristic blindness of toxicity.
The initial steps in the metabolism of both ethylene glycol and methanol
are catalysed by alcohol dehydrogenase and can be blocked by competitive
antagonism with ethanol or fomepizole.
Presentation
• Impaired consciousness (‘inebriation’ without alcohol on breath) in the
early phase prior to metabolism of ethylene glycol/methanol.
• Nausea, vomiting, and abdominal pain may occur in the first few hours
post-ingestion.
• Metabolic acidosis is usually delayed until 6–18h after ingestion. Initially,
this is a non-lactic high-anion-gap metabolic acidosis.
• In methanol toxicity, visual symptoms present with falling visual acuity,
photophobia, and the sensation of ‘being in a snow storm’. Up to one-
third of patients are left with permanent visual loss.
• CNS features, including seizures, are generally delayed by >24h and may
signify the start of the development of severe features that can lead to
coma and death.
• Oliguria suggestive of AKI typically occurs 24–48h post-ingestion.
• Late cranial neuropathies can be seen up to 20 days post-ingestion.
Prognostic features
• As little as 30mL of a toxic alcohol can be fatal in adults. However,
toxic effects can be averted, even with massive ingestions, if specific
treatment is started early.
• Co-ingestion of ethanol can actually be protective by blocking the
metabolism of ethylene glycol/methanol to toxic metabolites.
• The degree of acidosis is the best indicator of a poor outcome. The
presence of coma has also been shown to predict poor outcome.
Complications
• Severe metabolic acidosis.
• Oliguric renal failure.
• Cerebral oedema.
• Hypotension.
• Non-cardiogenic pulmonary oedema.
• Blindness (methanol).
• Convulsions.
Tricyclic antidepressants
First-generation agents (e.g. amitriptyline, imipramine, and dosulepin) are
the most likely to cause lethal intoxication. The newer second-generation
tricyclics (e.g. lofepramine) and tetracyclics are generally much safer in OD.
Presentation
• Anticholinergic features are prominent early on, with dry mouth, dilated
pupils, blurred vision, sinus tachycardia, urinary retention, myoclonic
jerking, agitation, and hallucinations.
• Cardiac arrhythmias chiefly arise from the blockade of inactivated fast
Na+ channels in the heart. Hypotension can also occur as a result of α1
adrenergic blockade and impaired cardiac contractility.
• Convulsions and coma with respiratory depression may precede the
cardiac effects, and death can occur only a few hours after ingestion.
• Metabolic and respiratory acidosis can, in turn, worsen cardiotoxicity.
Complications
• Hypothermia, skin blistering (cf. barbiturates), and rhabdomyolysis are
also reported.
Prognostic features
• Significant clinical features can be seen with ingestion of >5–10mg/kg.
• QRS prolongation is associated with an i risk of convulsions and
arrhythmias.
Management
• Patients with significant tricyclic antidepressant toxicity should be
monitored closely in an ITU or a high-dependency area.
• Activated charcoal should be given PO (50g) within 1h.
• Record a 12-lead ECG, and monitor for a minimum of 6h
post-ingestion.
• Alkalinization with boluses of 50mmol 8.4% sodium bicarbonate IV,
aiming for an arterial pH of 7.45–7.55, is the initial treatment for
patients with prolonged QRS duration, metabolic acidosis, hypotension,
or arrhythmias.
• Severe hypotension may be treated with IV glucagon; inotropes or
vasopressors may be required (E Hypovolaemic shock, p. 333).
• Control seizures with diazepam (5–10mg IV) in the first instance; the
second-line treatment for seizures is phenobarbital.
• Arrhythmias should be treated with hypertonic sodium bicarbonate.
Antiarrhythmics should be avoided.
• Tricyclic coma may last 24–48h. In some patients, recovery is marked by
agitation and myoclonic jerks.
Chapter 15 783
Practical procedures
Needle
Catheter
30–45°
Artery
(a)
Blood
(b)
(c)
Needle removed
(d)
Pulsatile blood
flow seen
(e)
(f)
(g)
Apply pressure
(h)
Needle
Catheter
30–45°
Artery
(a)
Blood
(b)
10–15°
(c)
(d)
Apply pressure
(e)
Sternal head
Sternal
head Sternocleidomastoid
muscle
Clavicular
head
External jugular
vein
(a) Surface anatomy of external and internal jugular veins
(b) Anterior approach: the chin is in the midline and the skin puncture
is over the sternal head of the SCM muscle
(c) Central approach: the chin is turned away and the skin puncture is
between the two heads of the SCM muscle
Subclavian
vein 1st rib
2nd rib
3rd rib
US equipment
• Ensure that the display can be seen.
• The sheath is opened (operator) and the gel squirted in (assistant). A
generous amount of gel ensures good contact and air-free coupling between
the probe tip and the sheath. Too little may compromise the image quality.
• The probe and connecting cable are lowered into the sheath (assistant),
which is then unrolled along them (operator).
• A rubber band secures the sheath to the probe.
• The sheath over the probe tip is smoothed out (wrinkles will degrade
the image quality).
• Apply liberal amounts of gel to the sheathed probe tip for good US
transmission and i patient comfort during movement.
798
• Flush all the lumens of the PA catheter, and attach the distal lumen to
the pressure transducer. Check the transducer is zeroed (conventionally
to the mid-axillary point). Check the integrity of the balloon by inflating
it with the syringe provided (2mL of air), and then deflate the balloon.
• The procedure is detailed under E Pulmonary artery catheterization 2,
p. 802 and E Pulmonary artery catheterization 3, p. 804.
(See Fig. 15.5.)
(a)
(b)
(c)
60
50
(mmHg)
40
30
20
10
0
Right atrium Right ventricle Pulmonary Wedge position
artery (PCWP)
Indications for temporary pacing
1 Following acute MI
• Asystole.
• Symptomatic CHB (any territory).
• Symptomatic secondary heart block (any territory).
• Trifascicular block:
• Alternating LBBB and RBBB.
• First-degree heart block + RBBB + left axis deviation.
• New RBBB and left posterior hemiblock.
• LBBB and long PR interval.
• After anterior MI:
• Asymptomatic CHB.
• Asymptomatic second-degree (Mobitz II) block.
• Symptomatic sinus bradycardia unresponsive to atropine.
• Recurrent VT for atrial or ventricular overdrive pacing.
2 Unrelated to MI
• Symptomatic sinus or junctional bradycardia unresponsive to atropine
(e.g. carotid sinus hypersensitivity).
• Symptomatic secondary heart block or sinus arrest.
• Symptomatic CHB.
• Torsades de pointes tachycardia.
• Recurrent VT for atrial or ventricular overdrive pacing.
• Bradycardia-dependent tachycardia.
• Drug OD (e.g. verapamil, β-blockers, digoxin).
• Permanent pacemaker box change in a patient who is pacing-dependent.
3 Before general anaesthesia
• The same principles as for acute MI (see earlier).
• Sinoatrial disease and secondary (Wenckebach) heart block only need
prophylactic pacing if there are symptoms of syncope or pre-syncope.
• CHB.
Transvenous temporary pacing
• The technique of temporary pacing is described on E Temporary
cardiac pacing: ventricular pacing, pp. 808–9.
• The most commonly used pacing mode and the mode of choice for life-
threatening bradyarrhythmias is ventricular demand pacing (VVI) with
a single bipolar wire positioned in the RV (see E Temporary cardiac
pacing: ventricular pacing, pp. 808–9 for an explanation of common
pacing modes).
• In critically ill patients with impaired cardiac pump function and
symptomatic bradycardia (especially with RV infarction), cardiac output
may be i by up to 20% by maintaining AV synchrony. This requires two
pacing leads, one atrial and one ventricular, and a dual pacing box.
Epicardial temporary pacing
Following cardiac surgery, patients may have epicardial wires (attached to
the pericardial surface of the heart) left in for up to 1 week in case of post-
operative heart block or bradyarrhythmia. These may be used in the same
way as the more familiar transvenous pacing wires, but the threshold may
be higher.
AV sequential pacing
In critically ill patients with impaired cardiac pump function and symptom-
atic bradycardia (especially with RV infarction), cardiac output may be i by
up to 20% by maintaining AV synchrony. This requires two pacing leads, one
atrial and one ventricular, and a dual pacing box.
Patients most likely to benefit from AV sequential pacing
• Acute MI (especially RV infarction).
• ‘Stiff ’ LV (aortic stenosis, hypertrophic cardiomyopathy, hypertensive
heart disease, amyloidosis).
• Low cardiac output states (cardiomyopathy).
• Recurrent atrial arrhythmias.
80
• Cover the wire with the plastic sheath, and suture the sheath and wire
securely to the skin. Loop the rest of the wire, and fix to the patient’s
skin with adhesive dressing.
• When the patient returns to the ward, obtain a CXR to confirm
satisfactory positioning of the wire and to exclude a pneumothorax.
RV
Tricuspid valve
IVC
SVC
Aorta Main pulmonary
artery
Too shallow
Right atrial
appendage
Ideal position
Too much
slack in lead Position of
tricuspid
valve
Diaphragmatic pacing
• High-output pacing (10V), even with a satisfactory position of the
ventricular lead, may cause pacing of the left hemidiaphragm. At low
voltages, this suggests perforation (see E Perforation, p. 812).
• Right hemidiaphragm pacing may be seen with atrial pacing and
stimulation of the right phrenic nerve.
• Reposition the wire if symptomatic (painful twitching, dyspnoea).
Pericardial aspiration 1
Equipment
Establish peripheral venous access, and check that full facilities for resusci-
tation are available. Pre-prepared pericardiocentesis sets may be available.
You will need:
• A trolley, as for central line insertion, with iodine or chlorhexidine for
the skin, dressing pack, sterile drapes, local anaesthetic (lidocaine 2%),
syringes (including a 50mL), needles (25G and 22G), a No. 11 blade, and
silk sutures.
• Pericardiocentesis needle (15cm, 18G) or similar Wallace cannula.
• J-guidewire (≥80cm, 0.035in diameter).
• Dilators (up to 7F).
• Pigtail catheter (≥60cm with multiple sideholes, a large Seldinger-type
CVP line can be used if no pigtail is available).
• Drainage bag and connectors.
• Facilities for fluoroscopy or echocardiographic screening.
Technique
(See Fig. 15.9.)
• Position the patient at 730°. This allows the effusion to pool inferiorly
within the pericardium.
• Sedate the patient lightly with midazolam and fentanyl if necessary. Use
with caution, as this may drop the BP in patients already compromised
by the effusion.
• Put on a sterile gown and gloves; clean the skin from mid chest to mid
abdomen, and place the sterile drapes on the patient.
• Infiltrate the skin and subcutaneous tissues with local anaesthetic,
starting 1–1.5cm below the xiphisternum and just to the left of the
midline, aiming for the left shoulder and staying as close to the inferior
border of the rib cartilages as possible.
• The pericardiocentesis needle is introduced into the angle between the
xiphisternum and the left costal margin, angled at >30°. Advance slowly,
aspirating gently and then injecting more lidocaine every few millimetres,
aiming for the left shoulder.
• As the parietal pericardium is pierced, you may feel a ‘give’ and fluid will
be aspirated. Remove the syringe, and introduce the guidewire through
the needle.
• Check the position of the guidewire by screening. It should loop within
the cardiac silhouette only and not advance into the SVC or PA.
• Remove the needle, leaving the wire in place. Enlarge the skin incision
slightly, using the blade, and dilate the track.
• Insert the pigtail over the wire into the pericardial space, and remove
the wire.
• Take specimens for microscopy, culture (and inoculate a sample into
blood culture bottles), cytology, and haematocrit if bloodstained (an
FBC tube; ask the haematologists to run on a Coulter counter for a
rapid estimation of Hb).
Pericardial aspiration 2
Aftercare
• Closely observe the patient for recurrent tamponade (obstruction of
the drain), and repeat Echo.
• Discontinue anticoagulants.
• Remove the drain after 24h or when drainage stops.
• Consider the need for surgery (drainage, biopsy, or pericardial window)
or specific therapy (chemotherapy if malignant effusion, antimicrobials if
bacterial, dialysis if renal failure, etc.).
See Box 15.4 for complications of pericardiocentesis.
Tips and pitfalls
If the needle touches the heart’s epicardial surface
You may feel a ‘ticking’ sensation transmitted down the needle—withdraw
the needle a few millimetres; angulate the needle more superficially, and try
cautiously again, aspirating as you advance.
If you do not enter the effusion
• Withdraw the needle slightly and advance again, aiming slightly deeper,
but still towards the left shoulder.
• If this fails, try again, aiming more medially (mid-clavicular point or even
suprasternal notch).
• Consider trying the apical approach (starting laterally at the cardiac apex
and aiming for the right shoulder) if Echo confirms sufficient fluid at the
cardiac apex.
Difficulty in inserting the pigtail
• This may be because of insufficient dilatation of the tract.
• Hold the wire tort (by gentle traction), while pushing the catheter; take
care not to pull the wire out of the pericardium.
Haemorrhagic effusion versus blood
• Compare the Hb of the pericardial fluid to venous blood Hb.
• Place some of the fluid in a clean container; blood will clot, whereas
a haemorrhagic effusion will not, as the ‘whipping’ action of the heart
tends to defibrinate it.
• Confirm the position of the needle by first withdrawing some fluid
and then injecting 10–20mL of contrast; using fluoroscopy, see if the
contrast stays within the cardiac silhouette.
• Alternatively, if using Echo guidance, inject 5–10mL of saline into the
needle, looking for ‘microbubble contrast’ in the cavity containing
the needle tip. Injecting 20mL of saline rapidly into a peripheral vein
will produce ‘contrast’ in the RA and RV and may allow them to be
distinguished from the pericardial space.
• Connect a pressure line to the needle; a characteristic waveform will
confirm penetration of the RV (see Fig. 15.6).
DC cardioversion 1
Relative contraindications
• Digoxin toxicity.
• Electrolyte disturbance (dNa+, dK+, dCa2+, dMg2+, acidosis).
• Inadequate anticoagulation and chronic AF.
See Box 15.5 for complications of DC cardioversion.
Checklist for DC cardioversion
• Defibrillator: Check this is functioning, with a fully equipped arrest
trolley to hand in case of an arrest.
• Informed consent: (Unless life-threatening emergency.)
• 12-lead ECG: AF, flutter, SVT, VT, signs of ischaemia or digoxin. If
the ventricular rate is slow, have an external (transcu-
taneous) pacing system nearby in case of asystole.
• NBM: For at least 4h.
• Anticoagulation: Does the patient require anticoagulants? Is the INR
>2.0? (Has it been so for >3 weeks?)
• K+: Check this is >3.5mmol/L.
• Digoxin: Check there are no features of digoxin toxicity and
recent digoxin levels are normal. If there are frequent
ventricular ectopics, give IV Mg2+ 8mmol.
• Thyroid function: Treat thyrotoxicosis or myxoedema first.
• IV access: Peripheral venous cannula.
• Sedation: Short general anaesthesia (propofol) is preferable to
sedation with benzodiazepine and fentanyl. Bag the
patient with 100% O2.
• Select energy: See Table 15.2.
• Synchronization: Check this is selected on the defibrillator for all shocks
(unless the patient is in VF or haemodynamically un-
stable). Adjust the ECG gain, so that the machine is
only sensing QRS complexes, and not P or T waves.
• Paddle placement: Most centres now use ‘hands-free’ adhesive paddles
for DC cardioversion. Some continue with the
traditional handheld paddles.
Conductive gel pads should be placed between the right
of the sternum and the other to the left of the left nipple
(anterior to mid-axillary line). Alternatively, place one
anteriorly just left of the sternum, and one posteriorly to
the left of the midline. There is some evidence that the
anteroposterior (AP) position is superior for AF.
• Cardioversion: Check no one is in contact with the patient or with
the metal bed. Ensure your own legs are clear of the
bed! Apply firm pressure on the paddles if using the
handheld device.
• Unsuccessful: Double the energy level, and repeat up to 360J.
Consider changing the paddle position (see E ‘Paddle
placement’ earlier in the table). If prolonged sinus
pause or ventricular arrhythmia during an elective
procedure, stop.
DC cardioversion 1 819
DC cardioversion 2
Notes
Anticoagulation
The risk of thromboembolism in patients with chronic AF and dilated car-
diomyopathy is 0–7%, depending on the underlying risk factors.
Increased risk
• Prior embolic event.
• Mechanical heart valve.
• Mitral stenosis.
• Dilated LA.
Low risk
• Age <60 years.
• No heart disease.
• Recent-onset AF (<3 days).
Anticoagulate patients at risk with warfarin for at least 3–4 weeks. For
recent-onset AF (1–3 days), anticoagulate with IV heparin for at least
12–24h and, if possible, exclude an intracardiac thrombus with TOE prior
to DC shock. If there is a thrombus, anticoagulate with warfarin, as de-
scribed earlier. For emergency cardioversion of AF (<24h), heparinize prior
to shock.
The risk of systemic embolism with cardioversion of atrial flutter and
other tachyarrhythmias is very low, provided there is no ventricular
thrombus, since the coordinated atrial activity prevents the formation of a
clot. Routine anticoagulation with warfarin is not necessary, but we would
recommend heparin before DC shock, as the atria are often rendered
mechanically stationary for several hours after shock, even though there is
coordinate electrical depolarization.
After successful cardioversion, if the patient is on warfarin, continue
anticoagulation for at least 3–4 weeks. Consider indefinite anticoagulation if
there is intrinsic cardiac disease (e.g. mitral stenosis) or recurrent AF.
Special situations
Pregnancy
DC shock during pregnancy appears to be safe. Auscultate the fetal heart
before and after cardioversion and, if possible, the fetal ECG should be
monitored.
Pacemakers
There is a danger of damage to the pacemaker generator box or the junc-
tion at the tip of the pacing wire(s) and endocardium. Position the paddles
in the AP position, as this is theoretically safer. Facilities for backup pacing
(external or transvenous) should be available. Check the pacemaker post-
cardioversion—both early and late problems have been reported.
DC cardioversion 2 821
82
Coronary
perfusion
Mechanical ventilation
Negative pressure ventilation (NPV)
• This works by ‘sucking’ out the chest wall and is used in chronic
hypoventilation (e.g. polio, kyphoscoliosis, or muscle disease). Expiration
is passive.
• These techniques do not require tracheal intubation. However, access
to the patient for nursing care is difficult.
Intermittent positive pressure ventilation (IPPV)
Indications
Deteriorating gas exchange due to a potentially reversible cause of respira-
tory failure:
• Pneumonia.
• Head injury.
• Exacerbation of COPD.
• Cerebral hypoxia.
• Massive atelectasis (e.g. post-cardiac arrest).
• Respiratory muscle weakness.
• Intracranial bleed.
• Myasthenia gravis.
• Raised ICP.
• Acute infective polyneuritis.
• Major trauma or burns.
Ventilation of the ill patient on the ITU is via either an ETT or a trache-
ostomy. If ventilation is anticipated to be needed for >1 week, consider a
tracheostomy.
There are two basic types of ventilator.
• Pressure-cycled ventilators deliver gas into the lungs until a prescribed
pressure is reached, when inspiratory flow stops and, after a short
pause, expiration occurs by passive recoil. This has the advantage
of reducing the peak airway pressures without impairing cardiac
performance in situations such as ARDS. However, if the airway
pressures increase or compliance decreases, the tidal volume will fall, so
patients need to be monitored closely to avoid hypoventilation.
• Volume-cycled ventilators deliver a preset tidal volume into the lungs over
a predetermined inspiratory time (usually 730% of the breathing cycle),
hold the breath in the lungs (for 710% of the cycle), and then allow
passive expiration as the lungs recoil.
Nasal ventilation
• NIPPV delivers positive pressure for a prescribed inspiratory time, when
triggered by the patient initiating a breath, allowing the patient to exhale
to atmospheric pressure.
• The positive pressure is supplied by a small machine via a tight-fitting
nasal mask.
• It is generally used as a method of home nocturnal ventilation
for patients with severe musculoskeletal chest wall disease (e.g.
kyphoscoliosis) or with OSA.
• It has also been used, with modest success, as an alternative to formal
ventilation via ETT in patients where positive expiratory pressure is
not desirable, e.g. acute asthma, COPD with CO2 retention, and as a
weaning aid in those in whom separation from a ventilator is proving
difficult.
• The system is relatively easy to set up by experienced personnel, but
some patients take to it better than others. It should not be commenced
by inexperienced personnel.
830
Pressure support
• Positive pressure is added during inspiration to relieve part or all of the
work of breathing.
• This may be done in conjunction with an SIMV mode of ventilation or as
a means of supporting entirely spontaneous patient-triggered ventilation
during the process of weaning.
• It allows the patients to determine their own RR and should ensure
adequate inflation of the lungs and oxygenation. It is, however, only
suitable for those whose lung function is reasonably adequate and who
are not confused or exhausted.
Positive end-expiratory pressure
• PEEP is a preset pressure added to the end of expiration only, to
maintain the lung volume, prevent airway or alveolar collapse, and
open up atelectatic or fluid-filled lungs (e.g. in ARDS or cardiogenic
pulmonary oedema).
• It can significantly improve oxygenation by making more of the lung
available for gas exchange. However, the trade-off is an increase in
intrathoracic pressure, which can significantly decrease venous return
and hence cardiac output. There is also an i risk of pneumothorax.
• ‘Auto-PEEP’ is seen if the patient’s lungs do not fully empty before the
next inflation (e.g. asthma).
• In general, PEEP should be kept at a level of 5–10cmH2O, where
required, and the level adjusted in 2–3cmH2O intervals every 20–30min,
according to a balance between oxygenation and cardiac performance.
• Measurement and interpretation of PCWP in patients on PEEP depend
on the position of the catheter. PCWP will always reflect pulmonary
venous pressures if they are greater than PEEP. If the catheter is in an
apical vessel where the PCWP is normally lower, due to the effects of
gravity, the pressure measured may be the alveolar (PEEP) pressure,
rather than the true PCWP; in a dependent area, the pressures
are more accurate. Removing PEEP during measurement alters the
haemodynamics and oxygenation, and the pressures do not reflect the
state once back on the ventilator.
832
Percutaneous cricothyrotomy
Indications
• To bypass upper airway obstruction (e.g. trauma, infections, neoplasms,
post-operative, burns, and corrosives) when oral or nasotracheal
intubation is contraindicated.
• In situations when ET intubations fail (e.g. massive nasopharyngeal
haemorrhage, structural deformities, obstruction due to foreign
bodies, etc.).
Percutaneous cricothyrotomy
The Seldinger technique is quicker, may be performed by non-surgeons at
the bedside, and is safer (see Fig. 15.11). After anaesthetizing the area, a
needle is used to puncture the cricothyroid membrane, and, through this, a
guidewire is introduced into the trachea. Over this, a series of dilators and
a tracheostomy tube can be safely positioned.
Complications of cricothyrotomy
• Haemorrhage.
• Subglottic stenosis.
• Hoarseness.
• Laryngotracheal-cutaneous fistula.
(a)
(b)
(c)
Endotracheal intubation
This is the best method for providing and maintaining a clear airway for
ventilation, protection against aspiration, and suctioning and clearing lower
respiratory tract secretions. The most common indication for urgent in-
tubation by a physician is cardiac arrest. This is not a technique for the
inexperienced—the description given here is not intended as a substitute
for practice under supervision of a skilled anaesthetist.
You will need
• Laryngoscope, usually with a curved blade (Macintosh).
• ETT (8–9mm internal diameter for ♂ and 7–8mm for ♀) and
appropriate adaptors.
• Syringe for cuff inflation, and clamp to prevent air escaping from the cuff
once inflated.
• Scissors and tape or bandage to secure the tube.
• Lubricating jelly (e.g. K-Y® jelly).
• Suction apparatus with rigid (Yankauer) and long, flexible catheters.
Potential problems during intubation
• Certain anatomical variations (e.g. receding mandible, short neck,
prominent incisors, high-arched palate), as well as stiff neck or trismus,
may make intubation complicated; summon experienced help.
• Vomiting: suction if necessary. Cricoid pressure may be useful.
• Cervical spine injury: immobilize the head and neck in line with the body,
and try not to extend the head during intubation.
• Facial burns or trauma may make orotracheal intubation impossible.
Consider cricothyrotomy (E Percutaneous cricothyrotomy, p. 832).
Procedure
(See Fig. 15.12.)
• Place the patient with the neck slightly flexed and the head extended.
Take care if cervical injury is suspected.
• Cricoid pressure: the oesophagus can be occluded by compressing
the cricoid cartilage posteriorly against the body of C6. This prevents
passive regurgitation into the trachea, but not active vomiting. Ask your
assistant to maintain pressure until the tube is in place and the cuff
inflated.
• Pre-oxygenate the patient by hyperventilation with ≥85% O2 for 15–30s.
Suction the throat to clear the airway.
• With the laryngoscope in your left hand, insert the blade on the right
side of the mouth. Advance to the base of the tongue, identifying the
tonsillar fossa and the uvula. Push the blade to the left, moving the
tongue over. Advance the blade until the epiglottis comes into view.
• Insert the blade tip between the base of the tongue and the epiglottis,
and pull the whole blade (and larynx) upwards along the line of the
handle of the laryngoscope to expose the vocal cords. Brief suction may
be necessary to clear the view.
• Insert the ETT between the vocal cords, and advance it until the cuff is
just below the cords and no further. Inflate the cuff with air.
Tongue
Vocal cords
Trachea
Uvula
Aspiration of pneumothorax
If the pneumothorax is <75% and the patient is haemodynamically stable,
it is reasonable to attempt aspiration of the pneumothorax in the first in-
stance (E Pneumothorax: assessment, pp. 210–11).
You will need
• 10mL and 50mL syringes with green (18G) and orange (25G) needles.
• Dressing pack (swabs, sterile drapes, antiseptic) and sterile gloves.
• 19G Venflon® or alternative cannula.
• Local anaesthetic (e.g. 2% lidocaine).
• A 3-way tap.
Procedure
• One assistant is required.
• Sit the patient up, propped against pillows, with their hand behind their
head; ensure you are comfortable and on a similar level.
• Select the space to aspirate—the second intercostal space in the
mid-clavicular line. Confirm with a CXR that you are aspirating the
correct side (a surprisingly common cause of disasters is aspirating the
normal side).
• Clean the skin and use an aseptic technique.
• Connect a 50mL syringe to a 3-way tap in readiness, with the line which
will be connected to the patient turned ‘off ’ so that no air will enter the
pleural cavity on connecting the apparatus.
• Infiltrate 5–10mL of lidocaine from the skin to pleura, just above
the upper border of the rib in the space you are using. Confirm the
presence of air by aspirating 75mL via a green needle.
• Insert a 16G or larger IV cannula into the pneumothorax, preferably
while aspirating the cannula with a syringe, so that entry into the pleural
space is confirmed. Allow the tip of the cannula to enter the space
by 71cm.
• Ask the patient to hold their breath, and remove the needle. Swiftly
connect the 3-way tap. Aspirate 50mL of air/fluid, and void it through
the other lumen of the tap. Repeat.
• Aspiration should be stopped when resistance to suction is felt, the
patient coughs excessively, or ≥2.5L of air has been aspirated.
• Withdraw the cannula, and cover the site with a dressing plaster (e.g.
Elastoplast™ or Band-Aid™)
• Check a post-procedure CXR. If there is significant residual
pneumothorax, insert a chest drain.
• Gently tighten the skin sutures, but do not knot. The drain should be
secured with several other stitches and copious amounts of adhesive
tape. They are very vulnerable to accidental traction.
• Wrap adhesive tape around the join between the drain and the
connecting tubing.
• Prescribe adequate analgesia for the patient for when the local
anaesthetic wears off.
• Arrange for a CXR to check the position of the drain.
• Do not drain off >1L of pleural fluid/24h to avoid re-expansion
pulmonary oedema.
(a) (b)
(c)
Ascitic tap 841
Ascitic tap
Indications
• To diagnose or exclude SBP.
• To obtain ascites for measurement of protein, albumin, or amylase
(pancreatic ascites).
• Ascitic cytology may require 100mL of fluid.
• Stain and culture for AFBs; lymphocytes: >500 cells/mm3).
• To drain cirrhotic or malignant ascites.
Relative contraindications
• Previous abdominal surgery increases the risk of perforation (due to
adhesion of underlying bowel to the abdominal wall).
• Massive hepatomegaly or splenomegaly (avoid the same side).
• Massive ileus with bowel distension.
NB There are no clinical data to support avoiding paracentesis in severe
coagulopathy (platelets <20 000, INR >4.0), but most clinicians should be
cautious and consider correcting coagulopathy.
Procedure
• Lie the patient supine and tilted slightly to one side.
• Select the site for paracentesis (e.g. on a horizontal line across the
umbilicus, and 4cm lateral to a line passing to the mid-inguinal point).
Clean the area with chlorhexidine. Avoid surgical scars (see Fig. 15.14).
• Use a 20mL syringe with a 18G (green) needle. In obese patients, use
a longer needle (e.g. 18G Abbocath®). Infiltrate the area with local
anaesthetic. Insert the needle slowly into the abdomen, while aspirating
until fluid is obtained.
• Inoculate 5mL of the fluid into each bottle of a set of blood culture
bottles, and send 5mL in a sterile bottle for microscopy and protein
determination. Add 2mL of ascites to an EDTA tube (contains
anticoagulant), and send to haematology for cell count.
• Remove and apply a sterile plaster over the puncture site.
842
Total paracentesis
Daily small-volume paracentesis increases the risk of complications such as
infection and ascitic leakage. The risk of infection is high if a peritoneal drain
is left in situ in cirrhotic ascites. It is safer to drain the ascites to dryness.
The rate of fluid drainage can be fast, and it is generally safe to drain
>3–5L/h. During the first 3–6h of paracentesis, there is a significant in-
crease in cardiac output, a decrease in SVR, and a modest fall in MAP (by
5–10mmHg). Tense ascites increases the RA pressure, which falls acutely
following paracentesis.
Indications
• Tense or gross ascites.
Mortality
The paracentesis-related mortality rate is 70.02% (1 in 5000).
Relative contraindications
• Previous abdominal surgery and scarring. Be cautious—avoid scars, and
use USS guidance.
• Patients with clinically apparent DIC or fibrinolysis and oozing from
needle-sticks.
• Paracentesis should not be performed in patients with a massive ileus
with bowel distension without imaging guidance.
• Platelet count <20. Ignore the INR (FFP not required).
• Renal failure: the risk of bleeding is i in renal failure, although this is
NOT a contraindication, and diagnosis of infected ascites is important in
this group of patients.
• It is important to avoid puncturing the superficial inferior epigastric
artery, which runs just lateral to the umbilicus from the mid-inguinal
point (see Fig. 15.14). Avoid any visible superficial veins.
• For USS-guided paracentesis, mark the spot prior to the procedure.
• The skin should be cleaned and sterilized. Use chlorhexidine pads.
Anaesthetize the area (see ‘X’ in Fig. 15.14) with a small volume of
lidocaine.
• Do NOT go too lateral, and the patient should be supine and leaning
slightly to one side.
• Beware of patients with a very large spleen or very large liver, and avoid
going too close to either structure. Use USS guidance, if possible.
• To avoid the catheter blocking due to omentum plugging the end, use a
catheter with side-holes.
Insertion of drainage catheter and draining the ascites
• You will need to gown up with a sterile gown.
• Monitor the BP before, and hourly for the first 6h.
• Insert the drainage catheter with multiple side-holes provided (attached
to a 20mL syringe), aspirating as one advances the cannula. When ascitic
fluid is obtained, advance the needle 3–4cm more, and then advance the
plastic cannula into the abdomen and attach the drainage system.
• Secure into place with adhesive tape, and leave on free drainage.
• Ask the patient to lie to one side, so that the drainage side is downmost
(left or right).
• Allow all ascites to drain as quickly as it will come, regardless of the
volume. When the ascites stops draining or slows down, move the
patient from side to side and lie towards the drainage site.
• When complete, remove the catheter; apply plaster, and lie the patient
with the drainage site uppermost for at least 4h (7100mL of 20% albumin
for every 2.5L removed).
• Replace albumin with an infusion of 20% albumin to give 8g of albumin
for every litre of ascites removed. It is usually best to start the albumin
infusion after paracentesis is complete, but if there is a significant drop in
BP, it can be started earlier.
• Try and ensure that all fluid is drained, as incomplete paracentesis
increases the risk of leakage post-procedure.
• Measure the volume of ascites drained.
• Always remove the drainage catheter within 6h of insertion to decrease
the risk of sepsis.
Insertion of Sengstaken–Blakemore tube
The Sengstaken–Blakemore tube is inserted to control variceal bleeding
when endoscopic therapy or IV terlipressin have failed. It should not be
used as primary therapy, since it is unpleasant and increases the risk of oe-
sophageal ulceration and aspiration.
Seek experienced or specialist help early. Balloon tamponade is a tem-
porary procedure to prevent exsanguination.
Procedure
• It is assumed that the patient is undergoing resuscitation and has
received IV terlipressin. To reduce the risk of aspiration, the patient
should be intubated and ventilated.
• The Sengstaken tube should be stored in the fridge (to maximize
stiffness) and removed just before use. Familiarize yourself with the
ports before insertion. Check the integrity of the balloons before you
insert the tube.
• Place an endoscope protection mouthguard in place (to prevent biting
of the tube). Cover the end of the tube with lubricating jelly, and, with
the patient in the left semi-prone position, push the tube down, asking
the patient to swallow (if conscious). If the tube curls up in the mouth,
try again.
• Estimate the length of the tube to be inserted by measuring from the
bridge of the nose to the earlobe and adding the distance from the nose
to the xiphoid process. This should equate to at least 50–60cm; make
sure that the tube is not coiled up in the back of the mouth.
• Inflate the gastric balloon with 250mL of water. Clamp the balloon
channel. Then gently pull back on the tube until the gastric balloon abuts
the gastro-oesophageal junction (resistance felt), and then pull further
until the patient is beginning to be tugged by pulling. Note the position
at the edge of the mouthpiece (mark with a pen), and attach with a
sticking plaster to the side of the face.
• Tip: if the above fails, place the tube through the mouthguard to the
back of the throat, and then follow with an endoscope. The endoscope
will push the tube down the oesophagus and can be retroverted to
directly visualize the gastric balloon being filled, before being removed.
• In general, the oesophageal balloon should never be used. Virtually
all bleeding varices occur at the oesophagogastric junction and are
controlled using the gastric balloon.
• Do not leave the balloon inflated for >12h, since this increases the risk
of oesophageal ulceration.
• Obtain a CXR to check the position of the tube.
• The gastric channel should be aspirated continuously.
Percutaneous liver biopsy
This should only be done by experienced doctors.
Procedure
Patients should be warned of the risk of bleeding, pneumothorax, gall
bladder puncture, failed biopsy, and shoulder tip pain, which may last sev-
eral hours. The mortality is 71:10 000.
Relative contraindications
• PT >3s prolonged.
• Platelet count <80 × 109/L or bleeding diathesis.
• Ascites.
• Liver cancer (risk of tumour seeding).
Premedicate the patient with analgesia (e.g. 30–60mg of dihydrocodeine)
before the procedure. The patient lies supine, with their right hand behind
their head. Always carry out the liver biopsy under US guidance, especially
if the liver is small and cirrhotic. The skin is cleaned, local anaesthetic infil-
trated down to the liver capsule, and a liver biopsy needle is inserted when
the breath is held in expiration. The biopsy itself takes about 5–10s and may
cause shoulder tip pain.
A plugged biopsy can be performed when the PT is up to 6s prolonged,
with a platelet count of >40 000mm3. The biopsy is done through a sheath,
and the tract embolized using Gelfoam® to prevent bleeding.
Transjugular liver biopsy
This liver biopsy is taken through the hepatic vein, with secondary bleeding
occurring into the circulation. It is not without risk, as the hepatic capsule
may be punctured, leading to bleeding. It is used for patients in whom a pro-
longed PT or low platelet count precludes a normal liver biopsy.
A large introducer is placed into the IJV. A catheter is introduced through
this and manipulated into the hepatic vein. The catheter is removed, leaving
a guidewire in situ. A metal transjugular biopsy needle is passed over the
wire and advanced into the hepatic vein. One has to avoid being too per-
ipheral (risk of capsular puncture). The wire is removed, and the needle
advanced while suction is applied. A biopsy is obtained by the ‘Menghini’
technique. The biopsies obtained are smaller and more fragmented than
those obtained by conventional techniques.
846
Peritoneal dialysis
Rarely used but does not require vascular access or anticoagulation.
A clearance rate of 710mL/min may be achieved.
It requires:
• A peritoneal dialysis (PD) catheter (inserted under local anaesthesia).
• An intact peritoneal cavity free of infection, herniae, and adhesions.
Complications
Peritonitis occurs at 0.8 episode per patient per year.
Assessment
• Features of peritonitis are: cloudy PD bag (99%), abdominal pain (95%),
and abdominal tenderness (80%).
• Other features include: fever (33%), nausea and vomiting (30%),
leucocytosis (25%), and diarrhoea or constipation (15%).
• Investigations: PD effluent cell count (peritonitis if >100 neutrophils/
mm3); culture PD fluid (inoculate a blood culture bottle); Gram-stain PD
fluid; FBC (for leucocytosis); blood cultures.
Management
• All patients require antibiotics but may not require admission. The
antibiotics used depend on Gram stain and culture results. A typical
protocol would be ciprofloxacin or vancomycin, plus metronidazole.
Patients with high fever with leucocytosis and/or who are systemically
unwell warrant IV antibiotics.
• Gram –ve infection, in particular Pseudomonas, is associated with more
severe infection.
• Peritonitis can lead to the development of an ileus.
• Patients may lose up to 25g of protein/day in severe cases and should
receive adequate nutritional support.
• If the infection is resistant to treatment, consider removal of the
Tenckhoff catheter and atypical organisms (e.g. fungi).
• Consider an underlying GI pathology, especially if multibacterial, Gram –
ve organisms, or other symptoms.
Other problems
Mild cases of fluid overload may respond to hypertonic exchanges (6.36%
or 4.25% glucose), fluid restriction (1L/day), and large doses of diuretics
(e.g. furosemide 500mg bd).
Other problems include poor exchanges, malposition of the catheter,
omental blocking, fibrin deposition, and hyperglycaemia.
84
Intermittent haemodialysis
A blood flow of 250–300mL/min is needed across the dialysis membrane
and leads to a clearance of 20mL/min.
• Vascular access: vascular access may be obtained using an arteriovenous
shunt involving the radial artery or, more commonly, by using a Vascath
which uses venous, rather than arterial, blood.
• Anticoagulation: heparin is normally used. If contraindicated, e.g.
recent haemorrhage, then epoprostenol may be used but may cause
hypotension and abdominal cramps.
• Haemodynamic stability: patients with MOF commonly develop
hypotension during haemodialysis. This may be ameliorated by high-
sodium dialysate and priming the circuit with 4.5% human albumin
solution.
Complications of haemodialysis
Hypotension
Usually occurs within the first 15min of commencing dialysis. It probably
involves activation of circulating inflammatory cells by the membrane, os-
motic shifts, and possibly loss of fluid. Treatment: cautious fluid replacement
and inotropes (watch for pulmonary oedema if overtransfused).
Dialysis disequilibrium
This occurs during the initial dialysis, especially in patients with marked ur-
aemia, and is more common in patients with pre-existing neurological dis-
ease. Clinical features: headache, nausea and vomiting, fits, cerebral oedema.
Treatment: treat cerebral oedema as described under E Intracerebral
haemorrhage, pp. 398–9. Short and slow initial dialyses may prevent this.
Dialyser reaction
This is caused by an IgE or complement response against the ethylene oxide
component (sterilizing agent) or the cellulose component. Use of ‘biocom-
patible’ membranes, e.g. polysulfone, polyacrylonitrile (PAN), or dialysers
sterilized by steam or gamma-irradiation may prevent further reactions.
Haemofiltration
Continuous arteriovenous haemofiltration (CAVH) implies bulk solute
transport across a membrane and replacement. Continuous arteriovenous
haemodiafiltration (CAVHD) involves pumping of dialysate across the
other side of the membrane. For both, arterial blood (driven by arterial
pressure) is continuously filtered at a relatively low flow rate (50–100mL/
min). Continuous venovenous haemofiltration (CVVH) and continuous
venovenous haemodiafiltration (CVVHD) involve pumping blood from a
venous access to the dialysis membrane (150–200mL/min). The equivalent
GFR obtained by these are 15–30mL/min. These are used most commonly
on ITU. Both of these methods cause less haemodynamic instability and are
particularly useful in patients with MOF.
Plasmapheresis 849
Plasmapheresis
A therapy directed towards removal of circulating high-molecular-weight
compounds not removed by dialysis. Particularly used in the removal of
antibodies or lipoproteins.
Indications
• Myasthenia gravis.
• GBS.
• Goodpasture’s syndrome.
• TTP.
• HUS.
• Severe hyperlipidaemia
• Multisystem vasculitis.
• Hyperviscosity syndrome (e.g. Waldenström’s macroglobulinaemia).
• HLA antibody removal.
Method
Requires central venous access with a large- bore, dual-lumen cannula.
Usually five treatment sessions are given on consecutive days. Plasma is
removed and replaced with typically 2U of FFP and 3L of 4.5% albumin.
IV Ca2+ (10mL of 10% calcium gluconate) should be given with the FFP.
Febrile reactions may occur, as with other blood products. Plasmapheresis
has no effect on the underlying rate of antibody production but is a useful
treatment in acute situations such as Goodpasture’s syndrome and myas-
thenia gravis.
• For HUS and TTP, one must use FFP only (preferably cryodepleted),
usually a minimum of 3L/day (E Thrombotic thrombocytopenic
purpura and haemolytic uraemic syndrome, p. 634).
• For hyperviscosity syndrome, a centrifugation system is required, rather
than a plasma filter (E Hyperviscosity syndrome, p. 654).
• For lipopheresis, there may be severe reactions if the patient is on
an ACEI.
• An alternative to plasmapheresis is immunoabsorption, in which two
columns are used in parallel. This may be used in the removal of HLA
antibodies, anti-GBM disease, or multisystem vasculitis.
850
Renal biopsy
Indications
Biopsy is now performed using real-time US guidance by trained doctors
(see Box 15.6).
Contraindications
• Bleeding diathesis—unless correctable prior to biopsy.
• Solitary functioning kidney.
• Uncontrolled hypertension, i.e. DBP >100mmHg.
• Urinary tract obstruction.
• Small kidneys, since it is unlikely to be helpful.
Prior to biopsy
• Check Hb, clotting screen, G&S serum.
• Ensure IVU or USS has been carried out to determine the presence and
size of the two kidneys.
• Consent the patient; >1% risk of bleeding requiring transfusion.
Technique
• The biopsy is taken with the patient prone on the bed, with pillows
under the abdomen. The lower pole of either kidney is visualized by
US. A trucut biopsy is taken from the lower renal pole under sterile
conditions with local anaesthesia. The biopsy is taken with the patient
holding their breath at the end of inspiration (displaces the kidney
inferiorly). Following biopsy, they should have bed rest for 24h to
minimize the risk of bleeding, and the BP and pulse monitored half-
hourly for 2h, 1-hourly for 4h, then 4-hourly for 18h.
• Send renal biopsy tissue for light microscopy, immunofluorescence, EM,
and special stains (e.g. Congo red).
Complications
• Bleeding: microscopic haematuria is usual; macroscopic haematuria in
5–10%; bleeding requiring transfusion in 1%.
• Formation of an intrarenal arteriovenous fistula may occur.
• Severe loin pain suggests bleeding.
• Pneumothorax and ileus are rare.
Renal transplant biopsy
Indications
• Decline in transplant function.
• Primary non-function post-transplant.
Procedure
Biopsy may be taken from either the upper or the lower pole. Some centres
find fine-needle aspiration biopsy (FNAB) useful in the diagnosis of trans-
plant rejection.
Joint aspiration
Many synovial joints can be safely aspirated by an experienced operator.
Knee effusions are common, and aseptic aspiration can be safely performed
in the emergency department. The risk of inducing septic arthritis is <1 in
10 000 aspirations, but certain rules should be followed:
• Anatomical landmarks are identified.
• The skin is cleaned with alcohol or iodine.
• Local anaesthetic is applied to the area.
• A no-touch technique is essential.
• Aspirate the joint to dryness, by leaving the needle in the joint space and
changing syringes.
Indications for synovial fluid aspiration in casualty
• Suspected septic arthritis.
• Suspected crystal arthritis.
• Suspected haemarthrosis.
• Relief of symptoms by removal of effusion in degenerative arthritis.
Contraindications to joint aspiration
• Overlying sepsis—never insert a needle through an area of cellulitis, as
there is a risk of introducing infection into the joint.
• Bleeding diathesis.
• Prosthetic joints—must be aspirated in theatre by the orthopaedic
surgeons
Knee joint
The patient lies with the knee slightly flexed and supported. The joint space
behind the patella either medially or laterally is palpated, the skin cleaned,
and a needle (18G, green) inserted horizontally between the patella and the
femur using a no-touch technique. There is a slight resistance, as the needle
goes through the synovial membrane. Aspirate on the syringe until fluid is
obtained. (See Fig. 15.15a, b.)
Elbow joint
Flex the elbow to 90°, and pass the needle between the proximal head of
the radius (locate by rotating the patient’s hand) and the lateral epicondyle;
or the needle can be passed posteriorly between the lateral epicondyle and
the olecranon. (See Fig. 15.15c.)
Ankle joint
Plantarflex the foot slightly; palpate the joint margin between the extensor
hallucis longus (lateral) and the tibialis anterior (medial) tendons just above
the tip of the medial malleolus. (See Fig. 15.15d.)
When synovial fluid is obtained:
• Note the colour and assess the viscosity.
• Microscopy for cell count and crystals (see Table 15.3).
• Gram stain and culture.
• AFB for suspected TB (although synovial fluid is usually non-diagnostic,
and a synovial biopsy should be performed).
Head of
radius
Lateral
epicondyle
Complications
• Infection (up to 5%).
• Bleeding (local, subdural, extradural, or intracerebral).
• CSF leak.
• Seizures.
• Misreading of ICP.
856
Lumbar puncture 1
Contraindications
• Raised ICP (falling level of consciousness with falling pulse, rising BP,
vomiting, focal signs, papilloedema). A CT scan should be carried out
prior to an LP to exclude an obstructed CSF system or SOL (E Raised
intracranial pressure, pp. 388–90).
• Coagulopathy or d platelets (<50 × 109/L).
You will need
• Spinal needles and a manometer for measuring the opening CSF
pressure.
• Dressing pack (gauze, drapes, antiseptic, gloves, plaster).
• Local anaesthetic (e.g. 2% lidocaine), three sterile bottles for collecting
CSF, and a glucose bottle.
Procedure
(See Fig. 15.16.)
Give antibiotics first if suspected meningitis (E Acute bacterial menin-
gitis: assessment, p. 371).
• Explain the procedure to the patient.
• Position the patient. This is crucial to success. Lie the patient on their left
side if you are right-handed or on their right side if you are left-handed,
with their back on the edge of the bed, fully flexed (knees to chin), with
a folded pillow between their legs, keeping the back perpendicular to
the bed. Flexion separates the interspaces.
• The safest site for LP is the L4–L5 interspace (the spinal cord ends at
L1–L2). An imaginary line drawn between the iliac crests intersects
the spine at the L4 process or L4–L5 space exactly. Mark the L4–5
intervertebral space.
• Clean the skin, and place the sterile drapes over the patient.
• Inject and anaesthetize the deep structures with 2% lidocaine.
• Insert the spinal needle (stilette in place) in the midline, aiming slightly
cranially (towards the umbilicus), horizontal to the bed. Do not advance
the needle without the stylet in place.
• You will feel the resistance of the spinal ligaments, and then the dura,
followed by a ‘give’ as the needle enters the subarachnoid space.
Replace the stylet before advancing.
• Measure the CSF pressure with the manometer and 3-way tap. Normal
opening pressure is 7–20cmCSF. CSF pressure is i with anxiety, SAH,
infection, SOL, benign intracranial hypertension (BIH), and CCF.
• Collect 0.5–1.5mL of fluid in three serially numbered bottles, including a
glucose bottle.
• Send specimens promptly for microscopy, culture, protein, glucose (with
a simultaneous plasma sample for comparison), and, where appropriate,
virology, syphilis serology, cytology for malignancy, AFB, oligoclonal
bands (MS), CrAg, India ink stains, and fungal culture.
• Remove the needle, and place a plaster over the site.
• The patient should lie flat for at least 6h and have hourly neurological
observations and BP measurements.
Position the patient so that the line joining the iliac crests is perpendicular
to the bed.
(b)
Ask the patient to curl up with a pillow between the knees to open the
interspace. Point the needle cranially and advance gently.
Lumbar puncture 2
Complications of lumbar puncture
• Headache: common (up to 25%). Typically present when the patient is
upright and better when supine. May last for days. Thought to be due
to CSF depletion from a persistent leak from the LP site. Prevented by
using finer spinal needles; keep the patient supine for 6–12h post-LP, and
encourage fluids. Treat with analgesia, fluids, and reassurance.
• Trauma to nerve roots: rarer, but seen if the needle does not stay in the
midline. The patient experiences sharp pains or paraesthesiae down
the leg. Withdraw the needle, and if the symptoms persist, stop the
procedure and seek expert help.
• Bleeding: minor bleeding may occur with a ‘traumatic tap’ when a small
spinal vein is nicked. The CSF appears bloody (see E CSF analysis, p. 858),
but the bleeding stops spontaneously and does not require specific
therapy. Coagulopathy, severe liver disease, or thrombocytopenia
carries the risk of subarachnoid/subdural bleeding and paralysis.
• Coning: herniation of cerebellar tonsils with compression of the medulla
is very rare, unless the patient has raised ICP. Always get a CT brain
scan prior to LP, and review this yourself if possible. Mortality is high,
but the patient may respond to standard measures for treating this
(E Raised intracranial pressure, pp. 388–90).
• Infection: rare if a proper sterile technique used.
CSF analysis
(See Table 15.4.)
• Normal values:
• Lymphocytes <4/mm3; polymorphs 0/mm3.
• Protein <0.4g/L.
• Glucose >2.2mmol/L (or >70% plasma glucose).
• Opening pressure <20cmCSF.
• A bloody tap is indicated by progressively fewer red cells in successive
bottles and no yellowing of CSF (xanthochromia). The true WCC may
be estimated by:
• True CSF WCC = CSF WCC –(blood WCC × CSF RBC)/
blood RBC
• If the patient’s blood count is normal, subtract 71 WBC for every 1000
RBCs). To estimate the true protein level, subtract 10mg/L for every
1000 RBCs/mm3 (be sure to do the count and protein estimation on
the same bottle).
• SAH: (E Subarachnoid haemorrhage: assessment, p. 402)
xanthochromia (yellowing of CSF); red cells in equal numbers in all
bottles. The RBCs will excite an inflammatory response (increasing CSF
WCC), most marked after 48h.
• Very high CSF protein: a marked increase in CSF protein—acoustic
neuroma and spinal tumours; GBS (E Guillain–Barré Syndrome,
pp. 452–3).
Needle-stick injuries
Occupational exposures to bloodborne viruses (BBVs) in health- care
workers can be divided into two groups: percutaneous (needle-stick) and
mucocutaneous (e.g. through broken skin or via splashes into the eyes).
High-risk body fluids include: blood, pleural fluid, peritoneal fluid, pericar-
dial fluid, synovial fluid, amniotic fluid, human breast milk, CSF, saliva (in
dentistry), semen, vaginal secretions, and unfixed tissues and organs (vomit,
faeces, and urine only when contaminated with blood).
The major pathogens associated with needle- stick injuries and
mucocutaneous exposures are:
• HBV.
• HCV.
• HIV.
Occupational exposures to BBVs can be caused by certain work practices
such as:
• Not properly disposing of used needles.
• Recapping needles.
• Not using protective equipments, e.g. eye protection.
Prevention
Assume that every patient is potentially infected with a bloodborne infec-
tion. The same precautions should be taken for every patient and every
procedure.
• Cover skin cuts and abrasions with waterproof dressings.
• Never recap needles or pass sharps hand to hand.
• Always dispose of used needles promptly in sharps disposal containers
at the point of use.
• Never leave sharps to be cleared up by others.
• Use eye protection. Ordinary spectacles offer inadequate protection.
Use safety glasses, which fit over spectacles.
• Double-gloving reduces the risk of BBV transmission from a sharp injury.
• Use safer sharp devices; according to Health and Safety (Sharp
Instruments in Healthcare) Regulations 2013: ‘the employer must
substitute traditional, unprotected sharps with a “Safer Sharp” where it
reasonably practicable to do so’.
Management of exposure incidents
• If the mouth or eyes are involved, wash thoroughly with water.
• If the skin is punctured, let the wound bleed and wash it with soap
and water.
• Report to the occupational health department to arrange immediate
assessment or, if out of hours, attend the A&E department.
Assessment of the risk of bloodborne virus transmission
Estimated seroconversion risks are:
• HBV: 30% for percutaneous exposure of a non-immune individual to
HBsAg-and HBeAg-positive source.
• HCV: 1.9% for percutaneous exposure to HCV-infected blood with
detectable HCV RNA.
• HIV: 0.3% for percutaneous exposure to HIV-infected blood.
Chapter 16 863
Differential diagnosis
of common presentations
Introduction 864
Systemic enquiry 865
Abdominal pain 1 866
Abdominal pain 2 868
Abdominal pain (referred) 869
Abdominal distension 869
Back pain 870
Blackouts 870
Breathlessness/dyspnoea 871
Chest pain 872
Chest pain (pleuritic) 872
Collapse 872
Confusion 873
Constipation 873
Cough 873
Cutaneous manifestations of internal malignancy 874
Diarrhoea 875
Diarrhoea (bloody) 875
Dysphagia 876
Falls 876
Fever 876
Fever in a traveller 877
Fits 877
Haematemesis and melaena 877
Haematuria 878
Haemoptysis 879
Headache 879
Hemiparesis 880
Hoarseness 880
Itching/pruritus 881
Joint pain/swelling 882
Leg swelling 883
Melaena 883
Muscle weakness 884
Nausea 886
Palpitations 886
Seizures 886
Tremor 887
Unconsciousness/reduced consciousness 888
Vomiting 888
Weak legs 888
Wheeze 889
864
Introduction
It is often said that 80% of the diagnosis depends on a good history. The
differential diagnosis formed from the history can then be narrowed down
by physical examination and investigations.
The history of the presenting complaint is a key component of establishing
a diagnosis and should be divided into three subsections to ensure that the
most crucial points in the history are dealt with at an early stage.
About the symptom
That is, what, where (including radiation), when (onset, duration, course),
how bad (severity), exacerbating/relieving factors, etc.
About the most relevant organ system
(For example, questions relating to the respiratory and cardiovascular sys-
tems for a patient presenting with breathlessness.) It is important to ask
about the most relevant organ systems and common ‘associated symp-
toms’ during the initial history, rather than during the systemic enquiry. See
E Systemic enquiry, p. 865 for a summary of the most important questions.
Risk factors
Go through your list of differential diagnoses for the presenting complaint
(see next sections), and ask questions about the various differentials and
risk factors that increase the likelihood of their development. For example,
if a patient presents with diarrhoea, the list of differential diagnoses includes
infection. Therefore, risk factors such as contacts, food history, recent
travel, etc. should be addressed.
The following pages will outline relatively short/memorable lists of dif-
ferential diagnoses for the most common presenting symptoms. These lists
are not comprehensive but are a good starting point. Each list of differential
diagnoses can be used as a guide for asking the important questions about
each differential and the risk factors.
See the appropriate sections in the rest of this book for further informa-
tion on the clinical signs and the specific investigations needed to exclude
or confirm a diagnosis.
Systemic enquiry
General questions
Fever, sweats, fatigue, malaise, loss of appetite, weight loss, lumps.
Cardiovascular
Chest pain, palpitation, breathlessness (exertional, at rest, orthopnoea, par-
oxysmal nocturnal dyspnoea), ankle swelling, dizziness.
Respiratory
Wheeze, breathlessness, cough, sputum, haemoptysis, chest pain, calf
pain/swelling.
Gastrointestinal
Loss of appetite/weight, nausea/vomiting, dysphagia, indigestion/heart-
burn, abdominal pain, change of bowel habit (diarrhoea or constipation),
bloating, blood/mucus PR, melaena or haematemesis, jaundice, pruritus,
dark urine, pale stool.
Urogenital
Urinary frequency, urgency, dysuria, haematuria, loin pain, vaginal/penile
discharge, periods/sexual problems.
Neurological
Cognitive impairment or reduced consciousness (from collateral history),
visual disturbance, hearing loss, speech/swallowing problems, headache,
neck/back pain, weakness, paraesthesiae, balance/coordination problems,
bowel/bladder control.
Rheumatological
Morning stiffness, joint pain/swelling/stiffness, deformity, malaise/fatigue/
weight loss, arthralgia, myalgia, rash, Raynaud’s phenomenon, hair loss, red
or sore or dry eyes, dry mouth, oral ulcers, genital ulcers.
Diabetes and endocrine
Polyuria, polydipsia, fatigue, weight loss, neck swelling or tenderness,
tremor, heat/cold intolerance, sweating, changes in hair, skin, voice, face,
hands, or feet appearance, pigmentation.
Ear, nose, and throat
Ear pain/discharge, nasal discharge/crusting, sore throat.
86
Abdominal pain 1
(See Fig. 16.1.)
Abdominal pain 1 867
Epigastric pain
• Peptic ulcer
• Pancreatitis
• Reflux oesophagitis
• Acute gastritis
• Malignancy: gastric, pancreatic
• Pain from adjacent areas: e.g. right upper
quadrant, central abdominal pain,
cardiac/pulmonary/pleural pathology,
e.g. MI, pericarditis, pneumonia
• Functional disorders: non-ulcer dyspep-
sia, irritable bowel syndrome.
Abdominal pain 2
Loin pain
• Infection: UTI (pyelonephritis), perinephric abscess/pyonephrosis.
• Obstruction: in the lumen, e.g. stones, tumour, blood clots; in the
wall, e.g. stricture (ureteric/urethral); pressure from the outside, e.g.
prostatic/pelvic mass, retroperitoneal fibrosis.
• Other: renal carcinoma, renal vein thrombosis, polycystic kidney
disease, pain from the vertebral column.
Groin pain
• Renal stones (pain radiating from loin to groin).
• Testicular pain, e.g. torsion, epididymo-orchitis (pain radiating from
scrotum to groin). Hernia (inguinal), hip or pelvic pathology, e.g.
fracture.
Diffuse abdominal pain
• Gastroenteritis.
• Peritonitis.
• Intestinal obstruction.
• IBD.
• Mesenteric ischaemia.
• Medical causes.
• Irritable bowel syndrome.
Medical causes
Most causes of abdominal pain are surgical. However, occasionally there
may be a ‘medical cause’ of abdominal pain:
• Cardiovascular/respiratory: MI, pneumonia, Bornholm’s disease
(Coxsackie B virus infection).
• Metabolic: DKA, Addisonian crisis, hypercalcaemia, uraemia, porphyria,
phaeochromocytoma, lead poisoning.
• Neurological: herpes zoster.
• Haematological: sickle-cell crisis, retroperitoneal haemorrhage (e.g.
anticoagulants), lymphadenopathy.
• Inflammatory: vasculitis (e.g. Henoch–Schönlein purpura, PAN), familial
Mediterranean fever.
• Infections: intestinal parasites, TB, malaria, typhoid fever.
• Irritable bowel syndrome.
Shoulder
(from undersurface
of diaphragm)
Shoulder blade Epigastrium
(from gall bladder) (from heart)
Left chest
Abdomen (from spleen)
(from lung Umbilicus
and pleura) (from appendix,
pancreas)
Testis
(from ureter)
Abdominal distension
• Fat (obesity).
• Fluid (ascites, fluid in the obstructed intestine).
• Flatus (intestinal obstruction).
• Faeces.
• Fetus.
• Giant organomegaly (e.g. ovarian cystadenoma, lymphoma).
• Small bowel: adhesions, herniae, Crohn’s disease, gallstone ileus, foreign
body, tumour, TB.
• Large bowel: cancer, volvulus, diverticulitis, faeces.
870
Back pain
All patients
• Strenuous activity, muscle spasm, trauma, fractures.
• Infection: TB or bacterial osteomyelitis of vertebra, disciitis.
• Malignancy: metastasis, multiple myeloma, malignant lumbosacral
plexopathy (with colorectal and gynaecologic tumours, sarcomas,
lymphomas).
• Spinal cord compression.
• Infection: epidural abscesses (IV users, vertebral osteomyelitis,
haematogenous spread)—common pathogens: Staphylococcus aureus,
Mycobacterium tuberculosis.
• Malignancy: myeloma, metastases (vertebral, spinal cord).
• Inflammatory: RA, sarcoidosis, or tophaceous gout.
• Other: haematomas (bleeding disorders, anticoagulant therapy),
arteriovenous malformation.
Younger patients (≤40 year)
• Prolapsed disc, ankylosing spondylitis, spondylolisthesis.
Older patients (≥40 year)
• Osteoarthritis, spinal stenosis, and spinal claudication.
• Osteoporotic fractures, Paget’s disease of bone.
Blackouts
Cardiovascular (due to transient reduction in blood flow
to the brain)
• Arrhythmia: bradycardia (heart block), tachycardia.
• Outflow obstruction: aortic stenosis, hypertrophic obstructive
cardiomyopathy, PE, pulmonary stenosis.
• Postural hypotension: hypovolaemia, autonomic neuropathy (e.g. DM),
antihypertensive medications (e.g. ACEIs).
• MI, aortic dissection, and any other condition that may cause a sudden
reduction in cardiac output.
Neurological
• Epilepsy, stroke/TIA (rarely).
Neurocardiogenic (vasovagal) syncope and carotid sinus
hypersensitivity
Vasovagal syncope may be induced by prolonged standing, cough, mictur-
ition, venepuncture, heat exposure, or painful stimuli. There may be no
identifiable cause, especially in the elderly. Blackouts due to carotid sinus
hypersensitivity may be produced by head turning, tight-fitting collars, or
shaving.
Metabolic
• Hypoglycaemia (E Hypoglycaemia: assessment, pp. 556–7).
Breathlessness/dyspnoea 871
Breathlessness/dyspnoea
The causes of breathlessness are best classified according to rapidity of
onset. However, although the onset gives a significant clue, the following
lists are not mutually exclusive.
Acute (seconds)
• PE.
• Pneumothorax.
• Foreign body.
• Anaphylaxis.
• Anxiety.
Subacute (minutes to hours)
• Acute LVF (pulmonary oedema).
• Asthma exacerbation.
• COPD exacerbation.
• Pneumonia (bacterial, viral, fungal, TB).
• Metabolic acidosis.
Chronic (days to weeks)
• Anaemia.
• Thyrotoxicosis.
• Recurrent PEs.
• Cardiac disease (chronic cardiac failure, arrhythmias, valvular heart
disease).
• Asthma.
• COPD.
• Non-resolving pneumonia.
• Bronchiectasis.
• Lung cancer.
• Interstitial lung disease/pulmonary fibrosis (cryptogenic, connective
tissue diseases, drugs, environmental/occupational lung disease).
• Pulmonary hypertension.
• Pleural effusion.
• Neuromuscular disorders, chest wall deformities.
872
Chest pain
Some causes of chest pain
Chest wall
• Ribs: fracture or neoplasm.
• Intercostal muscle: spasm, inflammation (Bornholm’s disease).
• Costochondritis.
• Herpes zoster.
• Thoracic vertebral pain.
• Thoracic nerve root pain.
Pleura
• Pleurisy (infectious, neoplastic, vasculitic, irritative).
Lung vasculature
• Pulmonary infarction.
• Pulmonary hypertension.
Mediastinal structures
• Lymph nodes (lymphoma, cancer).
• Oesophagitis.
• Aortic dissection.
• Tracheobronchitis.
• Pericarditis.
• Myocardial pain (angina, ACS).
Extrathoracic
• Cervical arthritis.
• Subdiaphragmatic disease (e.g. hepatitis, splenic infarction, pancreatitis,
peptic ulcer, gallstones).
• Migraine.
Collapse
See E Blackouts, p. 870.
Cough 873
Confusion
• Hypoglycaemia.
• Hypoxia: cardiac arrest, shock (hypovolaemic, septic), respiratory
failure.
• Vascular: intracranial haemorrhage/infarction.
• Infection: extracranial (most commonly UTI and pneumonia in the
elderly); intracranial (meningitis, encephalitis).
• Inflammation (cerebral vasculitis).
• Trauma (head injury).
• Tumour (i ICP).
• Toxic: drugs, e.g. opiates, alcohol, anxiolytics, antidepressants.
• Metabolic: liver failure, renal failure, electrolyte (Na+, K+, Ca2+, Mg2+)
disturbances, endocrinopathies, e.g. myxoedema coma, vitamin
deficiencies (e.g. thiamine, B12), hypothermia.
• Post-ictal.
Constipation
• Drugs: opiates, anticholinergics (tricyclics, phenothiazines), iron tablets.
• Immobility, old age.
• GI/surgical.
• Intestinal obstruction (strictures, IBD, cancers, diverticulosis, pelvic
mass, e.g. fibroids).
• Pseudo-obstruction in scleroderma.
• Anorectal disease (fissure, stricture, rectal prolapse).
• Post-operative.
• Endocrine: hypothyroidism, hypercalcaemia, hypokalaemia, porphyria,
lead poisoning.
• Neurological/neuromuscular: autonomic neuropathy, spinal/pelvic
nerve injury, Hirschsprung’s disease, Chagas’ disease.
Cough
• URTI.
• All lung diseases:
• Asthma, COPD, PEs, infection (viral/bacterial/fungal/TB pneumonia),
bronchiectasis, malignancy, interstitial lung disease, sarcoidosis,
pneumoconiosis.
• Other causes:
• Post-nasal drip.
• Gastro-oesophageal reflux disease.
• ACEIs.
• Cardiac failure.
• Psychogenic.
874
Diarrhoea
Infection
• Viral: adenovirus, astrovirus, calciviruses (norovirus and related viruses),
rotavirus.
• Bacterial: Campylobacter, Salmonella, Shigella, haemorrhagic Escherichia
coli, Clostridium difficile, Yersinia enterocolitica, Clostridium perfringens,
Vibrio cholerae, Vibrio parahaemolyticus.
• Parasites: cryptosporidia, Giardia, Entamoeba histolytica.
• AIDS: AIDS enteropathy, cryptosporidia, microsporidia, CMV.
• IBD.
• Malabsorption: small intestine disease/resection, biliary or pancreatic
disease.
• Medication: laxatives, antibiotics.
• Overflow diarrhoea: secondary to constipation.
• Endocrine: thyrotoxicosis, VIPomas.
NB Staphylococcus aureus and Bacillus cereus mainly present with vomiting
1–6h after ingestion of prepared food, e.g. salad, dairy, meat (S. aureus) and
rice and meat (B. cereus).
Diarrhoea (bloody)
• Infective colitis: Campylobacter, haemorrhagic E. coli, Salmonella, Shigella,
E. histolytica, CMV in the immunocompromised.
• IBD.
• Ischaemic colitis.
• Diverticulitis.
• Malignancy.
876
Dysphagia
Mechanical obstruction of the oesophagus
• Congenital stricture.
• Corrosive stricture.
• Foreign body.
• Carcinoma of the oesophagus or stomach.
• External compression (e.g. aortic aneurysm).
• Oesophageal divertula or pouch.
• Reflux oesophagitis with stricture.
Dysphagia secondary to pain
• Pharyngitis.
• Laryngitis.
Neurologic dysfunction of the oesophagus
• Bulbar paralysis.
• Syphilis.
• Lead poisoning.
• Tetanus.
• Rabies.
• Parkinson’s disease.
• Botulism.
• Myasthenia gravis.
• Achalasia.
• Plummer–Vinson syndrome.
• Hysteria.
Falls
• Sensory (visual, hearing, proprioception) impairment.
• Gait/balance problem.
• Muscle weakness/rigidity.
• Urinary incontinence/frequency/urgency.
• Medications: psychotropic, opiates.
• Cognitive impairment.
• Home hazards (especially in the elderly).
Fever
• Infection: abscesses (e.g. subphrenic, liver, pelvis); bacterial—infective
endocarditis, pneumonia, UTI, biliary infection, osteomyelitis, TB,
brucellosis, viral (e.g. HIV, CMV, EBV), malaria, etc.
• Inflammation/connective tissue disease: e.g. RA, SLE, sarcoidosis,
vasculitides, polymyalgia rheumatica.
• Malignancy: lymphomas, leukaemia, renal cell, hepatocellular, or
pancreatic carcinoma.
• Metabolic: thyrotoxicosis.
• Drugs: e.g. antibiotics, allopurinol, phenytoin, interferon.
• NMS, malignant hyperthermia, serotonin syndrome.
• Familial Mediterranean fever, familial periodic fever.
Fits
• Vascular: haemorrhage, infarction, cortical venous thrombosis, vascular
malformation.
• Trauma: head injury.
• Tumours.
• Toxic: alcohol, drugs, lead, CO.
• Metabolic: hypoxia, hypoglycaemia, electrolyte disturbances (i or d
Na+, K+, Ca2+, Mg2+), renal/hepatic failure, endocrine disorders (e.g.
myxoedema), vitamin deficiency.
• Infection: meningitis, encephalitis, abscess, TB, cysticercosis, HIV.
• Inflammation: MS, vasculitis, SLE, sarcoidosis.
• Malignant hypertension.
Haematuria
(See Fig. 16.3.)
Systemic causes
Infective endocarditis
Coagulopathy
Acute febrile infections
Exercise
Scurvy
Headache 879
Haemoptysis
NB Nasal or upper respiratory tract and GI bleeding may be confused with haemoptysis
Infectious
• Acute bronchitis.
• Pneumonia.
• Bronchiectasis.
• Lung abscess.
• Mycobacterial infection.
• Fungal infection (histoplasmosis, coccidiomycosis, aspergillosis).
• Parasites (paragonimiasis, schistosomiasis, ascariasis, amoebiasis,
echinococcus, strongyloidiasis, etc.).
Neoplastic
• Bronchogenic carcinoma.
• Bronchial adenoma.
• Metastatic deposits.
Traumatic
• Lung contusion.
• Bronchial rupture.
• Post-endotracheal intubation.
Vascular
• Pulmonary infarction.
• Pulmonary vasculitis.
• Arteriovenous fistula.
Cardiovascular
• Pulmonary oedema.
Parenchymal
• Diffuse interstitial fibrosis.
• Systemic diseases and vasculitis (WG, RA, SLE, Goodpasture’s, etc.).
• Sarcoidosis.
Headache
Serious causes to exclude
• Head injury.
• Meningitis/encephalitis.
• Vascular: haemorrhage (subarachnoid, intracranial), cerebral venous
thrombosis, pituitary apoplexy.
• Dissection (carotid/vertebral artery).
• Acute angle closure glaucoma.
• Giant cell arteritis.
• Other causes: malignant hypertension, drugs (e.g. GTN, Ca2+ channel
antagonists), infections (bacterial, viral illnesses, etc.), electrolyte imbalances
(e.g. hyponatraemia), hyperviscosity syndromes (e.g. polycythaemia),
reduced ICP (e.g. post-LP), migraine, migrainous neuralgia.
80
Hemiparesis
• Vascular: infarction, haemorrhage.
• Infection: brain abscess from local (e.g. middle ear, sinuses) or
distant (e.g. lung) infections, in the immunocompromised—TB,
toxoplasmosis, PML.
• Inflammation: demyelination, cerebral vasculitis.
• Trauma: extradural or subdural haemorrhage (a history of trauma may
not be apparent in the latter).
• Tumours: primary (e.g. meningioma, glioma), metastases, lymphoma.
• Metabolic: hypoglycaemia (transient).
• Other causes of transient hemiparesis: epileptic seizures (Todd’s
paralysis), migraine.
Hoarseness
Traumatic
• Foreign body.
• External injury to the larynx.
• Voice abuse (‘singer’s nodules’).
• Irritant gases (tobacco and other smoke).
• Aspiration (acid, alcohol).
Infections
• Viral.
• Diphtheria.
• Syphilis.
• Leprosy.
Idiopathic
• Sarcoidosis.
• Lupus erythematosus.
• Cricoarytenoid ankylosis in RA.
Neurological
• Recurrent laryngeal palsy.
• Bulbar palsy.
• Myasthenia gravis.
Other
• Weakness.
• Myxoedema.
• Acromegaly.
Itching/pruritus 881
Itching/pruritus
Causes of pruritus with visible skin disease
Rashes with excoriation
• Eczematous diseases (atopic, contact dermatitis, stasis dermatitis,
anogenital pruritus, seborrhoeic dermatitis).
• Scabies.
• Dermatitis herpetiformis.
• Psoriasis.
• Superficial fungal disease (especially feet and intertriginous areas).
• Pinworm infestation (perianal).
• Psychogenic causes.
Rashes with little or no excoriation
• Urticaria.
• EM.
• Lichen planus.
• Drug reactions.
• Pityriasis rosea.
• Urticaria pigmentosa (mastocytosis).
• Pruritic papules of pregnancy.
Causes of pruritus without visible skin disease
Associated with internal disease
• Uraemia.
• Liver disease (biliary cirrhosis, obstructive jaundice).
• Lymphoma.
• Polycythaemia.
• Pregnancy.
• Miscellaneous (e.g. occasionally seen with DM, thyroid disease,
parathyroid disease, iron deficiency, internal malignancy, etc.).
Not associated with internal disease
• Pediculosis pubis.
• Pinworm infestation.
• Xerosis.
• Psychogenic.
82
Joint pain/swelling
Single joint
• Infection: septic arthritis (staphylococci, gonococci, Gram –ve bacilli, TB,
Lyme disease).
• Trauma, haemarthrosis (haemophilia).
• Gout/pseudogout.
• RA, osteoarthritis.
• Seronegative arthritides: reactive arthritis, enteropathic arthritis (IBD,
Whipple’s disease), ankylosing spondylitis, psoriatic arthritis.
• Systemic: SLE, Sjögren’s syndrome, sarcoidosis, Behçet’s disease,
vasculitides.
• Malignancy.
Multiple joints
• Infection: disseminated septic arthritis (e.g. staphylococcal, gonococcal),
viral (e.g. enteroviruses, EBV, HIV, hepatitis B, mumps, rubella),
rheumatic fever, Lyme disease, TB.
• Gout/pseudogout.
• RA, osteoarthritis (generalized).
• Seronegative arthritis: reactive/Reiter’s, enteropathic (Whipple’s, IBD),
ankylosing spondylitis, psoriatic arthritis.
• Systemic diseases: SLE, sarcoid, Sjögren’s, Behçet’s, primary vasculitides,
polymyalgia rheumatica.
• Other: haemochromatosis, sickle cell, malignancy (hypertrophic
pulmonary osteoarthropathy).
Melaena 883
Leg swelling
Bilateral
• Cardiac failure.
• Liver failure.
• Other causes of hypoalbuminaemia (malnutrition, malabsorption,
nephrotic syndrome, protein-losing enteropathy).
• Renal failure.
• Hypothyroidism.
• Iatrogenic: oestrogens, Ca2+ channel blockers, ‘glitazones’, NSAIDs, fluid
overload.
• Venous insufficiency: acute (prolonged sitting), chronic venous
obstruction, e.g. pelvic mass, pregnancy, IVC/bilateral iliac vein
obstruction.
Unilateral
• Acute.
• DVT.
• Cellulitis.
• Compartment syndrome, trauma.
• Baker’s cyst rupture.
Chronic
• Varicose veins.
• Lymphoedema (non-pitting): primary, lymph node involvement
[radiotherapy, infection (filariasis), malignant infiltration, excision].
• Immobility.
Melaena
See E Haematemesis and melaena, p. 877.
84
Muscle weakness
Congenital
• Muscular dystrophies: (limb-girdle, facioscapulohumoral, Duchenne,
myotonic).
• Glycogen storage diseases.
• Inherited spinal muscular atrophies.
Infectious
• Viral (e.g. influenza).
• Bacterial (e.g. TB, syphilis).
• Parasites (e.g. trichinosis, toxoplasmosis, trypanosomiasis).
Toxic
• Alcohol.
• Heavy metals (e.g. mercury, lead, arsenic).
• Corticosteroids.
• Organophosphates.
• Drugs (vincristine, doxorubicin, heroin).
• Botulism.
Traumatic
• Exercise.
• Injury.
• Seizure.
Metabolic
• Hyper-or hypothyroidism.
• Hypokalaemia.
• Hypophosphataemia.
• Hypocalcaemia..
• Hypomagnesaemia.
• Hypoglycaemia.
• DM.
• Cushing’s disease.
• Addison’s disease.
• Hyperparathyroidism.
• Hyperaldosteronism.
• Acromegaly.
• Malnutrition.
Vascular insufficiency
Immune/idiopathic
• Myasthenia gravis.
• Scleroderma.
• SLE.
• PAN.
• RA.
• PMR.
• Sarcoidosis.
• Polymyositis/dermatomyositis.
Neoplastic
• Carcinomatous myopathy.
• Eaton–Lambert syndrome.
• Carcinoid myopathy.
86
Nausea
See E Vomiting, p. 888.
Palpitations
• Fever, dehydration, exercise, anaemia, pregnancy.
• Drugs (caffeine, nicotine, salbutamol, anticholinergics, vasodilators,
cocaine).
• Cardiac: any arrhythmia (e.g. AF, extrasystoles, SVT, VT), valvular
disease, cardiomyopathy, septal defects, atrial myxoma.
• Endocrine: thyrotoxicosis, phaeochromocytomas, hypoglycaemia,
mastocytosis.
• Psychiatric: panic attacks, generalized anxiety disorder.
Seizures
See E Fits, p. 877.
Tremor 887
Tremor
See Table 16.1.
Unconsciousness/reduced consciousness
• Hypoglycaemia.
• Hypoxia: cardiac arrest, shock (hypovolaemic, septic), respiratory
failure.
• Vascular: intracranial haemorrhage/infarction.
• Infection: meningitis, encephalitis.
• Inflammation (cerebral vasculitis).
• Trauma (head injury).
• Tumour (i ICP).
• Toxic: drugs, e.g. opiates, alcohol, anxiolytics, antidepressants.
• Metabolic: liver failure, renal failure, electrolyte (Na+, K+, Ca2+, Mg2+)
disturbances, endocrinopathies, e.g. myxoedema coma, vitamin
deficiencies (e.g. thiamine, B12), hypothermia.
• Epilepsy (post-ictal).
Vomiting
• Drugs, poisoning, alcohol.
• Abdominal pathology (GI, hepatic, gynaecological).
• Metabolic/endocrine: DKA, Addisonian crisis, hypercalcaemia, uraemia,
pregnancy.
• i ICP (infection, SOL, BIH).
• Acute labyrinthitis.
• Acute angle closure glaucoma.
Weak legs
Spastic paraparesis
• Inflammation: demyelination, transverse myelitis (post-infectious, e.g.
viral infections, Mycoplasma), vasculitides, sarcoidosis, SLE.
• Infection: epidural abscess, tuberculous abscess, HIV, HTLV-1 (tropical
spastic paraparesis), syphilis.
• Trauma: vertebral fractures/dislocation, disc protrusion (usually
spontaneous, rather than traumatic).
• Tumours: vertebral metastases, intrinsic cord tumours (ependymoma,
glioma, metastases), extrinsic tumours (neurofibroma, meningioma),
parasagittal meningioma.
• Metabolic: vitamin B12 deficiency (subacute combined degeneration).
• Degenerative: of the spine (spondylosis with cord compression); in the
cord: motor neuron disease.
• Congenital: hereditary spastic paraparesis, Friedreich’s ataxia.
• Other: syringomyelia
Flaccid paraparesis
• Polyneuropathies.
• Myopathies.
• Anterior spinal artery syndrome (spinal cord infarction).
Wheeze 889
Wheeze
• Angio-oedema/anaphylaxis.
• Asthma.
• Bronchitis.
• Bronchiectasis.
• Cardiac wheeze (pulmonary oedema).
• Cancer (lung).
• Carcinoid syndrome.
• Pulmonary eosinophilia.
890
Chapter 17 891
Assessing frailty
Frailty is the clinical state of i vulnerability related to age-associated decline
in physiological reserve. Frailty is not an inevitable part of ageing and can
manifest in a variety of ways.
Be careful in judging frailty based on initial impressions and partial
information—the fit older person with an acute illness, once stuck in a bed
and hospital gown, looks very similar to the frail older patient in the same
outfit.
In the acute setting, it is most likely that frailty will present with a ‘frailty
syndrome’—an acute event that has been exacerbated by their underlying
vulnerability. These syndromes can often mask a serious acute medical
condition (such as MI, stroke, or sepsis). Remember that all of these ‘syn-
dromes’ can occur in the absence of frailty.
The frailty syndromes
• Falls.
• Delirium/acute confusion.
• Reduced mobility.
• Polypharmacy/i susceptibility to medication side effects.
• Incontinence.
• Exacerbation of chronic conditions.
These presentations are umbrella terms encompassing a myriad of aetiolo-
gies. Frequently used unhelpful terms, such as ‘acopia’ and ‘off legs’, detract
from the possibility of a serious underlying condition and should be avoided
when describing a presenting complaint.
Frailty screening
Active screening can be performed in those in whom frailty is suspected,
with many tests available. Frailty is best tested for in the outpatient setting,
once a patient is at their ‘baseline’ function.
Examples include:
• Timed up and go test:2 the time taken to stand up out of a chair, walk 3m
and back again, with >10s suggesting frailty.
• Gait speed:3 <0.8m/s measured over 4–6m.
• Frailty scores: need to be calculated and interpreted by those trained in
their use.
• Polypharmacy: taking >5 medications can be an indicator of frailty.
Inappropriate prescribing should be looked for and medications
screened for justification, net benefit, and effectiveness. (It should
be noted that some conditions call for an appropriately heavier ‘pill
burden’.)
References
2. Podsiadlo D, Richardson S. The timed ‘Up & Go’: a test of basic functional mobility for frail elderly
persons. J Am Geriatr Soc 1991;39:142–8.
3. Abellan van Kan G, Rolland Y, Houles M, Gillette-Guyonnet S, Soto M, Vellas B. The assessment
of frailty in older adults. Clin Geriatr Med 2010;26:275–86.
Muskuloskeletal
Osteoarthritis or rheumatological conditions causing deformities, muscle
wasting, and weight loss, joint stiffness. Pressure sores. Assessing functional
ability is important.
Investigations
• Blood tests, e.g. FBC (anaemia), U&Es (renal disease, dehydration),
LFTs, glucose (hypo-/hyperglycaemia), vitamin B12 (peripheral
neuropathy, nutritional), folate, ferritin, Ca2+ (malignancy, arrhythmia,
weakness), vitamin D, TFTs (arrhythmia, myxoedema, anaemia), can all
be useful.
• ECG (AV block, arrhythmia, MI, prolonged QTc).
• The following should be guided by history/examination:
• Echo (if signs of valvular heart disease or CCF).
• 24h ECG monitor—not routine, only if suspicion of paroxysmal
arrhythmia.
• Tilt table testing.
• Investigations for infection/sepsis—CXR, urine dip, blood cultures,
lactate, CRP.
• CT head if focal neurological signs (malignancy, stroke, SAH, subdural
haematoma, normal pressure hydrocephalus) or head injury on
anticoagulants.
• CXR if any signs of hypoxia (underlying chronic lung disease, PE,
pneumothorax).
• Toxicology (paracetamol and salicylate levels, ECG, urine toxicology)
if OD suspected.
Management
Treat any underlying cause found, and consider referral to specialist falls
services.
Medication review
Polypharmacy increases the risk of side effects such as reduced awareness/
reactions, postural hypotension, hypoglycaemia, and ECG abnormalities.
Multidisciplinary team approach
Elderly care physician, physiotherapist, occupational therapist, dietician,
psychiatrist (dementia, depression), speech and language therapists, social
services.
Refer to a specialist, as indicated by above (cardiology, neurology, on-
cology, audiology, ophthalmology). Consider ongoing rehabilitation with the
multidisciplinary team.
89
Fragility fractures
A fall from standing height or less resulting in a fracture is defined as a fra-
gility fracture. Hip fractures account for three-quarters of fragility fractures
in the elderly, and there is a delay in diagnosis in up to 10% (undisplaced
fractures, patient unable to give a history). The mortality and morbidity
with a hip fracture is high (up to 13% at 30 days), and these patients should
be admitted under an orthopaedic team and operated on within 48h. It is
important to always consider a hip fracture in a frail patient, particularly fol-
lowing a fall. These patients should ideally be reviewed by an orthogeriatric
specialist prior to theatre.
Non-hip fragility fractures are often encountered on medical units, e.g.
vertebral crush fractures, pubic ramus fractures, and wrist fractures. Often
there is an underlying osteoporotic process, and surgical techniques can be
ineffective. Specialist orthopaedic opinion is key, and in the absence of a
surgical option, the following should be considered:
• Analgesia: effective pain relief can avoid complications associated with
immobility. Regular paracetamol and low-dose opiates can be effective.
Consider topical analgesic patches and non-pharmacological approaches
[heat patches, transcutaneous electrical nerve stimulation (TENS)].
Prolonged NSAID use is to be avoided.
• Non-surgical options: immobilization with plaster/orthopaedic aids helps
with analgesia and effective healing.
• Secondary prevention: Ca2+ and vitamin D replacement should be offered
to those who are deficient.
• Bisphosphonates should be prescribed for patients:
• 75 years or over without the need for a dual-energy X-ray
absorptiometry (DXA) scan.
• 65–74 years if osteoporosis is confirmed by DXA (T-score –2.5).
• <65 years if: T-score –3.0 standard deviation (SD) or below, or
T-score –2.5 SD plus one or more additional age-independent risk
factors.
• Alternatives to oral bisphosphonates are available.
• Consider referral to specialist osteoporosis services.
• Underlying causes: assessment of falls risk, as described under
E Falls and collapse, pp. 896–7. Smoking cessation and safe alcohol
consumption advice. Review medications—long-term steroids, in
particular.
• Rehabilitation: early mobilization reduces risks of immobility (VTE,
pressure ulcers). Ongoing support from physiotherapists and
occupational therapists. May need inpatient rehabilitation at a specialist
facility, otherwise consider early supported discharge home with active
rehabilitation.
Investigations
History (including collateral history)
• Assessment of cognitive history: timescale of decline, temporal fluctuation
of confusion, previous diagnosis of dementia.
• Assessment for risk factors: drug history and recent drug changes,
alcohol use, features of infection (lower urinary tract symptoms, cough,
vomiting, fever).
• Co-morbidities: e.g. DM, Parkinson’s disease, depression, psychiatric
diagnoses, chronic lung disease, epilepsy.
Examination
A full general examination should be performed, with particular focus
on signs of infection, dehydration, focal neurological signs (including
meningism), abdominal pain, and constipation.
A measurement of cognitive function, such as the Abbreviated Mental
Test (AMTS)4 should be performed at this stage to provide a baseline for
clinicians assessing the patient’s cognition at a later date.
Further tools, such as the confusion assessment method (CAM)5 or 4AT,
can help distinguish between delirium and dementia, and can be used after
a formal assessment of attention and cognition has been performed. These
tests should be used by those trained in their use but can identify key fea-
tures of delirium and dementia.
Focused investigation
• FBC (raised WCC), U&Es (dehydration, AKI), glucose (hypo-/
hyperglycaemia), Ca2+ (hypercalcaemia and dehydration), CRP
(inflammation), TFTs (myxoedema), LFTs (hepatic encephalopathy),
drug levels (e.g. valproate, phenytoin), vitamin B12.
• ABG (if hypoxia/hypercapnia suspected).
• CXR (hypoxia, concerns about malignancy—symptomatic
hyponatraemia in small cell lung carcinoma).
• ECG (electrolyte disturbances).
• CT head if neurological signs present (stroke, encephalitis, subdural
haematoma, SOL).
• LP if encephalitis or meningitis suspected (but do not delay antibiotics).
• EEG (non-convulsive status epilepticus).6
Management strategies
• Treat any acute medical issues identified.
• Medication review: address polypharmacy; reduce or stop any
psychoactive medication (or note any missing medications, e.g. ‘PRN’
sleeping tablet actually taken every night).
• Improve sensory impairment: address visual and auditory deficiencies to
improve orientation.
• Ensure the patient’s safety: avoid bed rails, restraints, ‘boxing gloves’,
and sedation (which will add to the confusion and increase the falls
risk).7 Use de-escalation techniques, and provide one-to-one nursing
care if the patient is at risk of falling or hurting themselves. Discuss
with nursing and therapy staff about strategies to maintain calmness—
this may include walking with the patient around the ward (if safe to
mobilize), rather than trying to continually try to sit them down.
902
Further reading
Abellan van Kan G, Rolland Y, Houles M, Gillette-Guyonnet S, Soto M, Vellas B. The assessment of
frailty in older adults. Clin Geriatr Med 2010;26:275–86.
British Geriatrics Society (2010). Comprehensive assessment of the frail older patient. Good practice
guide. British Geriatrics Society, London.
British Geriatrics Society (2017). Fit for frailty Part 1. Consensus best practice guidance for the care of
older people living in community and outpatient settings. M https://www.bgs.org.uk/sites/default/
files/content/resources/files/2018-05-23/fff_full.pdf
British Medical Association, Resuscitation Council (UK), Royal College of Nursing (2016). Decisions
relating to cardiopulmonary resuscitation, 3rd edn, 1st revision. M https://www.resus.org.uk/
dnacpr/decisions-relating-to-cpr
Health Protection Agency, British Infection Association (2011). Diagnosis of UTI: quick reference guide
for primary care. Health Protection Agency, London.
Hodkinson HM. Evaluation of a mental test score for assessment of mental impairment in the elderly.
Age Ageing 1972;1:233–8.
Inouye SK, van Dyke CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying confusion: the confusion
assessment method. A new method for detection of delirium. Ann Intern Med 1990;113:941–8.
Inouye SK, Westendorp RGJ, Saczynski JS. Delirium in elderly people. Lancet 2014;383:911–22.
Mody L, Juthani- Mehta M. Urinary tract infections in older women: a clinical review. JAMA
2014;311:844–54.
Naeije G, Pepersack T. Delirium in elderly people. Lancet 2014;383:2044–5.
Royal College of Physicians (2006). The prevention, diagnosis and management of delirium in older
people. Royal College of Physicians, London.
906
907
Appendix
908 Appendix
Reference intervals
Biochemistry (always consult your local laboratory)
(See Table A1.)
Table A1
Substance Reference interval
ACTH <80ng/L
ALT Men <31IU/L
Women <19IU/L
Albumin 35–50g/L
Aldosterone1 100–500pmol/L
ALP 30–300IU/L (adults)
α-fetoprotein <10kU/L
Amylase 0–180 Somogyi U/dL
Angiotensin II1 5–35pmol/L
ADH 0.9–4.6pmol/L
AST 5–35IU/L
Bicarbonate 24–30mmol/L
Bilirubin 3–17micromol/L (0.25–1.5mg/dL)
Calcitonin <0.1 micrograms/L
Ca2+ (ionized) 1.0–1.25mmol/L
Ca2+ (total) 2.12–2.65mmol/L
Chloride 95–105mmol/L
Total cholesterol 3.9–5.5mmol/L
LDL cholesterol 1.55–4.4mmol/L
HDL cholesterol 0.9–1.93mmol/L
Cortisol (a.m.) 450–700nmol/L
Cortisol (midnight) 80–280nmol/L
CK Men 25–195IU/L
Women 25–170IU/L
Creatinine 70 to ≤130micromol/L
CRP 0–10
Ferritin 12–200 micrograms/L
Folate 5–6.3nmol/L (2.1–2.8 micrograms/
L)
GGT Men 11–51IU/L
Women 7–33IU/L
Table A1 (Contd.)
Substance Reference interval
Glucose (fasting) 3.5–5.5mmol/L
Glycosylated haemoglobin (HbA1c) 5–8%
GH <20mU/L
Iron Men 14–31micromol/L
Women 7–33IU/L
LDH 70–250IU/L
Mg2+ 0.75–1.05mmol/L
Osmolality 278–305mOsmol/kg
PTH <0.8–8.5pmol/L
PO43– (inorganic) 0.8–1.45mmol/L
K+ 3.5–5.0mmol/L
Prolactin Men <450U/L; women <600U/L
PSA 0–4ng/mL
Protein (total) 60–80g/L
Red cell folate 0.36–1.44micromol/L (160–640
micrograms/L)
Renin (erect/recumbent)1 2.8–4.5/1.1–2.7pmol/mL/h
Na+ 135–145mmol/L
TSH 0.3–3.8mU/L
Thyroxine (T4) 70–140nmol/L
Thyroxine (free) 10.0–26.0pmol/L
Triglyceride (fasting) 0.55–1.90mmol/L
Tri-iodothyronine (T3) 1.2–3.0nmol/L
Urea 2.5–6.7mmol/L
Urate Men 0.21–0.48mmol/L
Women 0.15–0.39mmol/L
Vitamin B12 0.13–0.68nmol/L (>150ng/L)
1
The sample requires special handling—contact the lab.
091
910 Appendix
Urine
(See Table A2.)
Table A2
Substance Reference interval
Adrenaline 0.03–0.10micromol/
24h
Cortisol (free) ≤280nmol/24h
Dopamine 0.65–2.70micromol/
24h
Hydroxyindole acetic acid (HIAA) 16–73micromol/24h
Hydroxymethylmandelic acid (HMMA, VMA) 16–48micromol/24h
Metanephrines 0.03–0.69micromol/
mmol creatinine
Noradrenaline 0.12–0.5micromol/24h
Osmolality 350–1000mOsmol/kg
PO43– (inorganic) 15–50mmol/24h
K+ 14–120mmol/24h
Na+ 100–250mmol/24h
Cerebrospinal fluid
See E Lumbar puncture 2, p. 858.
Haematology
(See Table A3.)
Table A3
Measurement Reference interval
WBC 3.2–11.0 × 109/L
RBC Men 4.5–6.5 × 1012/L
Women 3.9–5.6 × 1012/L
Hb Men 13.5–18.0g/dL
Women 11.5–16.0g/dL
Haematocrit (Hct) or packed cell Men 0.4–0.54L/L
volume (PCV)
Women 0.37–0.47L/L
MCV 82–98fL
Mean cell haemoglobin (MCH) 26.7–33.0pg
Mean cell haemoglobin 31.4–35.0g/dl
concentration (MCHC)
Platelet count 120–400 × 109/L
Neutrophils 40–75%
Abs. no. 1.9–7.7 × 109/L
Monocytes 3.0–11.0%
Abs. no. 0.1–0.9 × 109/L
Eosinophils 0.0–7.0%
Abs. no. 0.0–0.4 × 109/L
Basophils 0.0–1.0%
Abs. no. 0.2–0.8 × 109/L
Lymphocytes 20–45%
Abs. no. 1.3–3.5 × 109/L
Reticulocyte count1 0.8–2.0% (25–100 × 109/L)
ESR Depends on age (and i in anaemia)
Men (age in years)/2
Women (age in years + 10)/2
PT—factors II, VII, and X 10–14s
APTT—factors VIII, IX, XI, and XII 35–45s
1
Only use percentages if the red cell count is normal; otherwise use absolute values.
291
912 Appendix
Table A4
INR Clinical condition
2.0–3.0 Treatment of DVT, PE, TIAs; chronic AF
3.0–4.5 Recurrent DVTs and PEs; arterial grafts and arterial disease
(including MI); prosthetic cardiac valves
160
8 2.9 340
150
6 8 200 2.8 320
140
2.7 300
4
190 2.6 130
2 280
2.5
120
6 0 2.4 260
180 2.3 110
10 240
2.2 105
8 220 100
170 2.1 95
5 6 2.0 200
165 90
4 190 85
160 1.9
180 80
2 1.8 170
155 75
5 0 1.7 160
150 70
150
10 1.6 65
145 140
8 1.5 60
130
140
4 6 1.4 120 55
135
110 50
4 1.3
130
100 45
2 1.2
125
90 40
4 0
120 1.1
80
10 35
115 1.0
70
8
110 30
0.9
3 6 60
105
25
4 0.8
100 50
2
95 0.7 20
3 0 40
90
0.6
2 10
85 0.58 15
Height Body Weight
ft/in cm surface m2 Ib kg
914 Appendix
Useful contacts
Liver units
Royal Free Hospital, London 0207 794 0500
Addenbrooke’s Hospital, Cambridge 01223 245 151
Freeman Hospital, Newcastle 0191 233 6161
Queen Elizabeth Hospital, Birmingham 0121 472 1311
St James Hospital, Leeds 0 113 243 3144
Edinburgh Royal Infirmary, Edinburgh 0131 536 1000
Kings College Hospital, London 0207 737 4000
Organ donation and transplantation
ODT 0117 975 7575
Poisons units
National Poisons Information Service 0344 892 0111
Drug and chemical exposure in pregnancy
UK Teratology Information Service 0344 892 0909
Tropical and infectious diseases
Hospital for Tropical Diseases, 020 3456 7890: ask for
London the tropical medicine
registrar (or 24h HTD
registrar on-call: 07908
250924)
Northwick Park, London 0208 864 3232 (bleep in-
fectious diseases registrar)
Liverpool 0151 705 3100 during
working hours (out of
hours: 0151 706 2000 and
ask for the tropical medi-
cine physician on-call)
Anti-venom kits for snakebites
For information on identification and management, contact:
Liverpool 0151 705 3100
London 0207 188 0500
Virus reference laboratory
Colindale, London 0208 200 4400
915
Index
Note: Pages dealing with the management of drug overdose are shown in bold type. Main ref-
erences to drugs with dosages have been included in the index. Tables, figures, and boxes are
indicated by an italic t, f, and b following the page number.
916 INDEX
INDEX 917
918 INDEX
INDEX 919
920 INDEX
INDEX 921
922 INDEX
INDEX 923
924 INDEX
INDEX 925
926 INDEX
INDEX 927
928 INDEX
INDEX 929
930 INDEX
INDEX 931
932 INDEX
INDEX 933
934 INDEX
INDEX 935
936 INDEX
INDEX 937
938 INDEX
R
seconds (50 mm/sec)
Q S QT 0.35–0.42
QRS
1.2
ECG measurements Complex QRS 0.08–0.11
QT Interval