PREANAESTHETIC MEDICATION

& GENERAL ANAESTHETIC

AGENTS
 Preanaesthetic medication

 “It is the term applied to the

administration of drugs prior to general
anaesthesia so as to make anaesthesia
safer for the patient”

 Ensures comfort to the patient & to

minimize adverse effects of
anaesthesia
 Aims

 Relief of anxiety & apprehension

preoperatively & facilitate smooth induction

 Amnesia for pre- & post-operative events

 Potentiate action of anaesthetics, so less

dose is needed
 Aims(contd.)
 Antiemetic effect extending to post-
operative period

 Decrease secretions & vagal stimulation

caused by anaesthetics

 Decrease acidity & volume of gastric juice

to prevent reflux & aspiration pneumonia
Drugs used for preanesthetic
medication

 Anti-anxiety drugs-

- Provide relief from apprehension & anxiety

- Post-operative amnesia
e.g. Diazepam (5-10mg oral), Lorazepam (2mg
i.m.) (avoided co-administration with
morphine, pethidine)
Sedatives-hypnotics

 e.g. Promethazine (25mg i.m.) has

sedative, antiemetic & anticholinergic
action

 Causes negligible respiratory depression

& suitable for children
Opioid analgesics

 Morphine (8-12mg i.m.) or Pethidine (50-

100mg i.m.) used one hour before surgery

 Provide sedation, pre-& post-operative

analgesia, reduction in anaesthetic dose

 Fentanyl (50-100μg i.m. or i.v.) preferred

nowadays (just before induction of anaesthesia)
Anticholinergics-

 Atropine (0.5mg i.m.) or Hyoscine (0.5mg

i.m.) or Glycopyrrolate (0.1-0.3mg i.m.) one
hour before surgery(not used nowadays)

 Reduces salivary & bronchial secretions,

vagal bradycardia, hypotension

 Glycopyrrolate(selective peripheral action)

acts rapidly, longer acting, potent
antisecretory agent, prevents vagal
bradycardia effectively
Antiemetics-

 Metoclopramide (10mg i.m.) used as antiemetic

& as prokinetic gastric emptying agent prior to
emergency surgery

 Domperidone (10mg oral) more preferred (does

not produce extrapyramidal side effects)

 Ondansetron (4-8mg i.v.), a 5HT3 receptor

antagonist, found effective in preventing post-
anaesthetic nausea & vomiting
Drugs reducing acid secretion

 Ranitidine (150-300mg oral) or Famotidine

(20-40mg oral) given night before & in morning
along with Metoclopramide reduces risk of
gastric regurgitation & aspiration pneumonia

 Proton pump inhibitors like Omeprazole

(20mg) with Domperidone (10mg) is preferred
nowadays
 Stages of General Anesthesia
Stage I: It is the state of analgesia, because sensory
transmission in spino-thalamic tract is inhibited. There is no
amnesia. Consciousness and sense of touch are present, while
sense of hearing is enhanced.
Stage II: It is the state of excitement and delirium. The patient
shows violent behaviour and is amnesic. There is irregular rise
in blood pressure and respiratory rate. To avoid these
symptoms, a short acting barbiturate like thiopental sodium is
given intravenously before administration of inhalation
anaesthetic.

Stage III: It is the stage of surgical anaesthesia. Regular

respiration and relaxation of skeletal muscle occurs during this
stage. It is divided in to following four planes.
Stage III
 Plane 1: During this plane, there are revolving movements of
eye balls which while attaining plane 3 get fixed. Respiration
and skeletal muscle tone are normal.
 Plane 2: Most surgical procedures are performed during this
plane. There is progressive loss of corneal, light and laryngeal
reflexes. Respiration is slow but regular.
 Plane 3: It is a plane of marked muscle relaxation. Respiration
is abdominal. Eye ball movement is absent. Pupils are dilated.
Light, corneal and laryngeal reflexes are absent
 Plane 4: It is a plane of complete muscle relaxation. Pupils are
dilated. There is complete loss of light, corneal and laryngeal
reflexes. Respiration is abdominal.
 Stage IV
 It is a stage of medullary paralysis. It appears due to
overdose of the general anaesthetic.
 During this stage, there is severe depression of respiratory
centre and vasomotor centre in medulla.
 The stage is fatal causing death of the patient. The most
reliable index for attainment of stage III is loss of corneal
reflex and establishment of regular respiratory pattern. A
fall in BP, cardiac and respiratory depression are the signs
of deep anaesthesia.
 As against this, resistance to insertion of endotracheal tube
is the sign of light anaesthesia. Monitoring of vital signs
reduces the dose requirement of general anaesthetic which
contributes to rapid recovery from general anaesthesia.
 GENERAL ANESTHETICS

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 Isoflurane
 It is a structural derivative of enflurane.
 It does not cause dilation of pupils and light reflex is not lost.
Hence, hepatotoxicity and nephrotoxicity is less.
 It depresses cortical EEG activity and is preferred for
neurosurgery. It is also a muscle relaxant. It is a potent
coronary vasodilator. It irritates upper airway, but it is a
bronchodilator.
 It has a pungent odour and causes bronchial irritation.
Hence, induction is unpleasant.
 Being a vasodilator, it causes hypotension and reflex
tachycardia. Isoflurane is available as inhalant liquid in a
pack of 30 ml, 100 ml or 250 ml: FORANE, ISORANE,
SOFANE.
Volatile liquids
 Halothane :
 It is a poor analgesic and poor muscle relaxant. It may
be used along with nitrous oxide/opioids and skeletal
muscle relaxants.
 It abolishes pharyngeal and laryngeal reflexes.
 It is a bronchodilator and is preferred for asthmatic
patients.
 It inhibits intestinal and uterine contractions and can be
used for assisting external or internal version of foetus
during late pregnancy. Recovery from halothane is
smooth except for shivering, nausea and vomiting.
 GENERAL ANAESTHETICS

 General Anaesthetics (GA) are drugs

which produce reversible loss of all
sensation & consciousness

 Neurophysiologic state produced by

general anaesthetics characterized by five
primary effects:
• Unconsciousness
• Amnesia
• Analgesia
• Inhibition of autonomic reflexes
• Skeletal muscle relaxation .
Ideal anaesthetic-

- Rapid induction
- Smooth loss of consciousness
- Rapidly reversible upon
discontinuation
- Possess a wide margin of safety

 The cardinal features of general anaesthesia are:

• Loss of all sensation, especially pain

• Sleep (unconsciousness) & amnesia
• Immobility & muscle relaxation
• Abolition of somatic & autonomic reflexes
 Development of intravenous anaesthetic
agents such as Propofol
Combined with Midazolam,
Dexmedetomidine & Remifentanyl

Led to the use of total intravenous

anaesthesia (TIVA) as clinically useful tool in
modern anaesthetic practice.
Intravenous Anaesthetics

a. Fast inducers –
i.) Thiopental, Methohexital
ii.) Propofol, Etomidate
b. Slow inducers –
i.) Benzodiazepines – Diazepam,
Lorazepam & Midazolam

c. Dissociative anaesthesia – Ketamine

d. Opioid analgesia – Fentanyl

 Pharmacokinetics
Procedure for producing anaesthesia
involves smooth & rapid induction

Maintenance

Prompt recovery after discontinuation

Induction –

 “Time interval between the administration of

anaesthetic drug & development of stage of
surgical anaesthesia”

 Fast & smooth induction desired to avoid

dangerous excitatory phase
 Thiopental or Propofol often used for rapid
induction
 Unconsciousness results in few minutes after
injection

 Muscle relaxants(Pancuronium or
Atracurium) co-administered to facilitate
intubation

 Lipophilicity is key factor governing

pharmacokinetics of inducing agents
Maintenance

 Patient remains in sustained stage of

surgical anaesthesia(stage 3 plane 2)

 Depth of anaesthesia depends on

concentration of anaesthetic in CNS

 Usually maintained by administration of

gases or volatile liquid anaesthetics (offer
good control over depth of anaesthesia)
Recovery

 Recovery phase starts as anaesthetic drug is

discontinued (reverse of induction)

 In this phase, nitrous oxide moves out of blood

into alveoli at faster rate (causes diffusion
hypoxia)
 Oxygen given in last few minutes of anaesthesia
& early post-anaesthetic period

 More common with gases relatively insoluble in

blood
 Mechanism of Anaesthesia
 Non-selective in action

 At molecular level, anaesthetics interact with

hydrophobic regions of neuronal membrane proteins

 Inhaled anaesthetics, Barbiturates, Benzodiazepines,

Etomidate & propofol facilitate GABA-mediated
inhibition at GABAA receptor sites & increase Cl- flux

 Ketamine blocks action of glutamate on NMDA

receptor
 General anaesthetics disrupt neuronal firing
& sensory processing in thalamus, by
affecting neuronal membrane proteins

 Motor activity also reduced – GA inhibit

neuronal output from internal pyramidal layer
of cerebral cortex
 Intravenous anaesthetics
Thiopentone sodium

Ultrashort acting thiobarbiturate, smooth

induction within one circulation time
Crosses BBB rapidly
Diffuses rapidly out of brain, redistributed
to body fats, muscles & other tissues
Typical induction dose is 3-5mg/kg
Metabolised in liver
 Cerebral vasoconstriction, reducing cerebral
blood flow & intracranial pressure(suitable for
patients with cerebral oedema & brain tumours)
 Laryngospasm on intubation

 No muscle relaxant action

 Barbiturates in general may precipitate Acute

intermittent porphyria (hepatic ALA synthetase)
 Reduces respiratory rate & tidal volume
 Propofol
 Available as 1% or 2% emulsion in oil

 Induction of anaesthesia with 1.5-2.5mg/kg within 30 sec & is

smooth & pleasant

 Low incidence of excitatory voluntary movements

 Rapid recovery with low incidence of nausea &

vomiting(antiemetic action)

 Non-irritant to respiratory airways

 No analgesic or muscle relaxant action

 Anticonvulsant action

 Preferred agent for day care surgery

 Apnoea & pain at site of injection are common

after bolus injection

 Produces marked decrease in systemic blood

pressure during induction(decreases peripheral
resistance)

 Bradycardia is frequent
 Ketamine
 Phencyclidine derivative

 Dissociative anaesthesia: a state characterized by

immobility, amnesia and analgesia with light sleep and
feeling of dissociation from surroundings

 Primary site of action – cortex and limbic system –

acts by blocking glutamate at NMDA receptors

 Highly lipophilic drug

 Dose: 1-2mg/kg i.v.
 Only i.v. anaesthetic possessing significant analgesic
properties & produces CNS stimulation
 Increases heart rate, blood pressure & cardiac output

 Markedly increases cerebral blood flow & ICP

 Suitable for patients of hypovolaemic shock

 Recovery associated with “emergence delirium”, more in

adults than children

 Use of diazepam or midazolam i.v. prior to administration of

ketamine, minimises this effect
 Fentanyl

 Potent, short acting (30-50min), opioid analgesic

 Generally given i.v.

 Reflex effects of painful stimuli are abolished

 Respiratory depression is marked but

predictable
 Decrease in heart rate, slight fall in BP

 Nausea, vomiting & itching often occurs

during recovery

 Also employed as adjunct to spinal & nerve

block anaesthesia & to relieve
postoperative pain
 Complications of Anaesthesia

During anaesthesia:
After anaesthesia:
Respiratory depression
Nausea and vomiting
Salivation, respiratory
Persisting sedation
secretions Pneumonia
Cardiac arrhythmias
Organ damage – liver,
Fall in BP
kidney
Aspiration
Nerve palsies
Laryngospasm and asphyxia
Emergence delirium
Awareness
Cognitive defects
Delirium and convulsion
Fire and explosion
 Balanced anaesthesia
 General anaesthetics rarely given as sole agents

 Anaesthetics adjuvants used to augment specific components

of surgical anaesthesia, permitting lesser doses of GA

 General anaesthetic drug regimen for balanced anaesthesia:

Thiopental + Opioid analgesic(pethidine or fentanyl/

benzodiazepine) + Skeletal muscle relaxant
(pancuronium) & Nitrous oxide along with inhalation
anaesthetic(Halothane/other newer agents )
 Summary
Anaesthetics Characteristics

Nitrous oxide Highest MAC, Second gas effect, Diffusion hypoxia

Halothane Used in bronchial asthma, Malignant Hyperthermia

Ether Safest in unskilled hands, highly inflammable

Sevoflurane Agent of choice for induction in children
Isoflurane Neurosurgery
Ketamine Dissociative anaesthesia, used in CHF & shock
Thiopentone Epilepsy, thyrotoxicosis
Propofol Day care anaesthesia, i.v. Anaesthetic of choice in
patients with Malignant Hyperthermia

Etomidate Aneurysm surgeries & cardiac diseases

Thank You