Emergency Room

Toxicology
Joyce L. Flanagan, Ph.D., DABCC
Clinical Chemist
Toxicology Laboratory
April 7, 2010
ASCLS-WI State Convention

Outline
• Introduction
• Clinical approach to poisoned patients
• Laboratory role in managing poisoning
patients

Epidemiology of Poisoning
• In 2008, 2.5 million human exposures and
1315 deaths reported
• Children were involved in the majority of
exposures, however, they comprised just
2.0% of the exposure related fatalities
• 90% of the fatalities occurred in > 20 yr
individuals
• 75.2% intentional exposures
Source: American Association of Poison Control Centers, AAPCC, 2009 annual report

1
 50.4%
17.4%

Source: AAPCC 2009 Annual Report

Cause of Death
• 1066 pharmaceuticals
– 544 analgesics
• Acetaminophen, hydrocodone, methadone, oxycodone,
salicylate, morphine, fentanyl, propoxyphene
– 211 Sedative/hypnotics/anticonvulsants/muscle
relaxants
• Benzodiazepines, barbiturates
– 113 Cardiovascular drugs
• Verapamil, cardiac glycoside, beta blockers
– 111 Antidepressants
• TCAs, lithium, bupropion
– 87 stimulants/street drugs
• Cocaine, heroin, amphetamine, methamphetamine, MDMA

Cause of Death - continued

• 249 Non-pharmaceuticals
– 83 Volatiles
• 35 Ethanol
• 34 Ethylene glycol
• 12 methanol
• 2 isopropanol
– 72 Carbon monoxide/smoke related
– Rest including
• Metals: mercury
• Industrial solvents
• Farm chemicals

2
 Facts about Treating Poisoning
Cases
• Most acutely-poisoned patients are managed
within an Emergency Department
• Management decisions must be based primarily
on patients’ exposure history and presenting
signs and symptoms
• Antidotal therapy should be instituted
immediately; do not wait for laboratory
confirmation of the poison or the decreased
value of cholinesterase

Identification of the Toxin

Three Key Steps

• Exposure history
– What, when, and how much?
– Difficult to obtain such information from certain
patients: suicidal, unresponsive, distressed, pediatric
• Identification of the pill, product, or plant involved
– Clues from patient’s or family’s medical history are
often enlightening
– Help from poison control center
• Toxin-induced changes in vital signs

3
 Toxidromes

A constellation of sings and

symptoms that are typically
produced by particular toxins
– Narrows the differential
– Allows anticipation of clinical course
– Guides specific antidotal therapy

Classic Toxidromes
Opioid
Clinical Agents commonly
manifestations involved
Hypopnea or bradypnea Opioids
Lethargy Clonidine and
Obtundation Quanabenz
Miosis (pinpoint pupils) Phenothiazines
Hypothermia Hypoglycemic agents

Classic Toxidromes
Sympathomimetic
Clinical Agents commonly
manifestations involved
Hyperthermia Cocaine
Tachcardia Amphetamines
Hypertension Theophyline
Agitation Caffeine
Delirium Salicylates
Seizures Monoamine oxidase
Mydriasis inhibitors
Diaphoresis
Increased peristalsis
(bowel sounds)

4
 Classic Toxidromes
Anticholinergic
Clinical Agents commonly
manifestations involved
“Hot as Hades, mad as a Diphenhydramine,
hatter, blind as a bat, dry hydroxyxine
as a bone, and red as TCAs
beet” Antipsychotics
Hyperthermia, Benztropine
tachycardia,
hypertension, agitation, Many plants: Jimson
delirium, seizures, weed, deadly
mydriasis, decreased nightshade, henbane
peristalsis (bowel Hyoscyamine
sounds), dry, flushed Scopolomine
skin Atropine

Classic Toxidromes
Cholinergic
Clinical Agents commonly
manifestations involved
Bradycardia (muscarinic) Organophosphates
Tachycardia (nicotinic) Carbamates
Hypertension (nicotinic) Physostigmine
Pilocarpine
Miosis
Mushrooms
“SLUDGE” : Salivation,
Lacrimation, Urination,
Diarrhea,
Gastrointestinal upset,
and Emesis

Classic Toxidromes
Sedative-hypnotic
Clinical Agents commonly
manifestations involved
Hypothermia Ethanol
Bradypnea or hypopnea Benzodiazepines
Rarely hypotension Barbiturates
Lethargy Zolpidem
Stuppor Ethchlorvynol
Obtundation Meprobamate
Chloral hydrate
Glutethimide

5
 Case #1 History

• 17-yr-old male complaining of

weakness. Felt well until 2 hours
prior when he developed
lightheadedness. No history of
depression or overdose. No history
of OTC, herbal, or street drug use.

Case #1 Physical Examination

• Gen: well developed male slightly

pale and diaphoretic
• HR 50 beats/min, BP 110/70 mmHg

Approach to the Poisoned

Patient

1. Identify the most significant physical

finding/vital sign abnormality and
generate a differential diagnosis.

6
Case #1 Physical Examination

• Gen: well developed male slightly

pale and diaphoretic
• HR 50 beats/min, BP 110/70 mmHg
• Initial lab tests (suggested):
electrolytes-blood including calculated
anion gap, glucose, BUN, osmolality,
blood gases

Toxin-induced Bradycardia
• Cardiac glycosides
• Calcium channel antagonists
• β− Adrenergic antagonists
• Centrally acting α-agonists (imidazolines
including clonidine)
• Potent α-agonists (phenylpropanolamine)
• Organophosphates
• Antidysrhythmics
• Sedetive-hypnotics, opioids

Approach to the Poisoned

Patient

2. Refine the differential therapy

7
 Toxin-induced Bradycardia
• Cardiac glycosides
• Calcium channel antagonists
• β − Adrenergic antagonists
• Centrally acting α-agonists (imidazolines
including clonidine)
• Potent α-agonists (phenylpropanolamine): no
elevation in blood pressure
• Organophosphates: no other cholinergic signs
• Antidysrhythmics: no other signs
• Sedetive-hypnotics, opioids: patient not obtunded

Approach to the Poisoned

Patient

3. Develop an initial treatment strategy.

Case #1 Treatment

• Cardiac monitor
• External pacer placed / not activated
• Atropine (1 mg IV × 2)
– No effect

8
 Approach to the Poisoned
Patient

4. Identify the toxin by clarifying history,

following the clinical course, or by
focused analytical testing.

Case #1 ID the Toxin

• His friends secretly added a liquid into
his soda to “get him high.”
• Only liquid agent on our list is
imidazoline, tetrahydrozoline (Visine®)
which was the product they brought in.
• The pt was monitored for 16 hrs with
resolution of his symptoms /
bradycardia.

Case #2 History
• 2-yr-old toddler found obtunded in his
crib. He is currently being taken care
of by his grandmother who has a
history of hypertension and non-
insulin dependent diabetes mellitus.

9
Case #2 Physical Examination
• General: obtunded child w/ poor response
to painful stimuli
• HR 100, BP 70/35,
• RR 20 and shallow, T 96 °F
• Pupils 1–2 mm
• Normal heart, lung, abdomen

Case #2 Differential Diagnosis

• Miosis, respiratory and CNS depression is
toxidrome for:
– Opioids
– Clonidine (imidazolines)
– Phenothiazines (chlorpromazine)
– Organophosphates
– Hypoglycemia

Case #2 Refine the Differential

• Glucose 105 mg/dL
• No other cholinergic signs (SLUDGE)

10
Case #2 Initial Treatment Plan

• Slight arousal to 0.4 mg naloxone and

after repeat dose, completely alert.

Case #2 ID the Toxin

• Grandmother confessed to being opioid

dependent and storing a dose of
methadone in a baby juice jar in the
refrigerator “just in case.”
• Exposure confirmed with methadone in
child’s urine.
• 3 days in the ICU with naloxone
infusion.

Case History #3
• 28 yr white male, brought to ED shortly
after midnight by EMT. Police responded
to a call from girl friend reporting pt had
threatened suicide before walking out the
apartment after an argument with her.
Collapsed while walking out of the woods
when responding to police. He was
reported drinking earlier. Some pill bottles
and anti-freeze found in the garage.

11
 Case #3 Physical Examination
• Unresponsive, acute respiratory failure
and hypotensive.
• Initial ED lab results:
• Blood EtOH 0.145 g/dL; DAU screen: THC positive
• Salicylate and Acetaminophen negative
• Metabolic acidosis (pH= 7.15), low Ca, Osmo gap
= 38 (normal <10) , anion gap = 11 (normal 6 –
10).

Case #3 Refine the differential

diagnosis
• Unresponsive, acute respiratory failure and
hypotensive.
• Blood EtOH 0.145 g/dL; DAU screen: THC positive
• Salicylate and Acetaminophen negative
• Metabolic acidosis (pH= 7.15), low Ca, Osmp gap
= 38 (normal <10) , anion gap = 11 (normal 6 –
10).

DAU Tox Screen

• Screen - immunoassay
– POC Screening
• Understand the limitation
– Instrument based screen
• Determined by immuno-activity
• GC/MS
– Comprehensive
• Turn around time
• Sensitivity
• Targeted GC/MS confirmation
– Quantitative

12
Case #3 Refine the differential
diagnosis
• Unresponsive, acute respiratory failure and
hypotensive.
• Blood EtOH 0.145 g/dL; DAU screen: THC positive
• Salicylate and Acetaminophen negative
• Metabolic acidosis (pH= 7.15), low Ca, Osmp gap
= 38 (normal <10) , anion gap = 11 (normal 6 –
10).

Anion Gap Metabolic

Acidosis
M ethanol
U remia
D iabetic ketoacidosis (DKA), AKA
P henformin/metformin
I soniazid
L actate (seizure, shock, CO, CN)
E thylene glycol
S alicylates

Evaluation of MUDPILES
M ethanol — visual symptoms, level
U remia — BUN/creatinine
D KA, AKA — glucose, ketones
P henformin/metformin — history of diabetes, creatinine
I soniazid — history of seizure
L actate — level
E thylene glycol — crystaluria
S alicylates — respiratory alkalosis, ferric chloride, level

13
 Alcohol Toxicity

Metabolism of Toxic
Alcohols

glycolic acid
ethylene glycoaldehyde glyoxylic acid
glycol oxalic acid
alcohol aldehyde
dehydrogenase dehydrogenase

methanol formaldehyde formic acid

Methanol –Treatment
• If methanol ingestion is suspected, treatment
should start immediately while waiting for the
confirmation result from lab.
• Supported medical care
• Infusion of sodium bicarbonate to reverse
acidosis
• Administer Fomepizole, (or Ethanol is not
available), ADH inhibitor, to halt the metabolism
• Hemodialysis if blood methanol is > 20 mg/dL

14
 Ethylene Glycol Treatment
• Appropriate therapies: IV ETOH drip or
Fomepizole to saturate alcohol dehydrogenase;
NaHCO3, hemodialysis to remove EG and acid
metabolites
• Hemodialysis if blood EG is > 20 mg/dL

Ethylene Glycol Testing

• GC/MS
– EG Half-life ~ 2.5 hrs
– Sample should be drawn upon admission
– TAT Depending on the arrival time of the specimen
• Only 1 laboratory performs this test in Central WI
• REMEMBER: If history of EG ingestion is
very strong, suggest to physician to initiate
ETOH or Fomepizole therapy while EG levels
are being assayed in the lab.

Case #3 Treatment
• Sodium bicarbonate drip and monitor
• STAT volatile ordered
– Ethanol confirmed
– Methanol and Ethylene Glycol negative
• Full urine tox or methadone (? possible)
test was never ordered
• Formepizol not administered
• Pt discharged 2 days later

15
 Effective Clinical Use of
the Analytical Laboratory
• Clinical skills are essential
– “Can’t test for everything”
– Most treatments do not dependent upon
quantitative results
• There are very few lab drug tests
would impact the management of
poisoned patients

Quantitative Analysis
Affecting Acute Clinical
Management
• Initiation of specific antidotes
– Acetaminophen (N-acetylcysteine)
– Digoxin (digoxin specific antibody
fragments), e.g. Digibind
– Opioids – Naloxone
– Organophosphates –
Pralidoxime/Atropine
– Iron ? (deferoxamine)

Quantitative Analysis
Affecting Acute Clinical
Management
• Hemodialysis/hemoperfusion
– Theophylline
– Aspirin
– Lithium
– Methanol
– Ethylene glycol

16
 Clinical Toxicology
Principles
• Most drug deaths will occur within 4
hrs of patient’s admission.
• The best strategy is to use the
clinical history and signs and
symptoms to identify possible toxins
for the development of the initial
treatment plan.

Overall Approach for Poisoned

Patients
1. Identify the most significant physical/vital
sign abnormality and generate a differential
diagnosis
• Specimens should be obtained at the time of
admission
2. Refine the differential – suppl. lab results
3. Develop an initial treatment plan
4. Identify the toxin by clarifying the history, by
following the clinical course, or by
performing focused analytical testing

Thank you!

Questions?

17