Intravenous anaesthetic agents can be used either to induce anaesthesia or for the maintenance of anaesthesia throughout surgery. Intravenous anaesthetics nearly all produce their effect in one arm-brain circulation time. Extreme care is required in surgery of the mouth, pharynx, or larynx where the airway may be difficult to maintain (e.g. in the presence of a tumour in the pharynx or larynx). To facilitate tracheal intubation, induction is usually followed by a neuromuscular blocking drug or a short-acting opioid.

The doses of all intravenous anaesthetic drugs should be titrated to effect (except when using ‘rapid sequence induction’); lower doses may be required in premedicated patients.

The following intravenous anaesthetic agents are highlighted as essential knowledge by the RCEM Basic Sciences Curriculum for the MRCEM examination:

• Thiopental sodium
• Etomidate
• Propofol
• Ketamine

Thiopental sodium

Thiopental sodium is a very short-acting barbiturate that is primarily used for the induction of anaesthesia.

Barbiturates are thought to act primarily at synapses by depressing post-synaptic sensitivity to neurotransmitters and by impairing pre-synaptic neurotransmitter release. 

Thiopental sodium binds at a distinct binding site associated with a chloride ionopore at the gamma-aminobutyric acid A (GABAA) receptor, increasing the duration of time for which the chloride ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged.

The dose for induction of anaesthesia is 2-7 mg/kg. Following intravenous injection, thiopental sodium rapidly reaches the brain and causes unconsciousness within 30-45 seconds, and the effects last 5-15 minutes. Its effects are cumulative with repeated administration. 

Thiopental sodium is negatively inotropic and decreases cardiac output by approximately 20%. It also decreases systemic vascular resistance. It is a potent respiratory depressant, and a period of apnoea may occur after administration. It also decreases renal blood flow and increases vasopressin secretion, resulting in a fall in urine output.

The main side effects of thiopental sodium are:

• Hypotension
• Arrhythmias
• Myocardial depression
• Laryngeal spasm
• Cough
• Headache
• Rash
• Hypersensitivity reactions

Etomidate 

Etomidate is a short-acting carboxylated imidazole derivate that is primarily used for the induction of anaesthesia.

It is thought to act upon GABA type A receptors to modulate fast inhibitory synaptic transmission within the central nervous system.

The dose for induction of anaesthesia is 0.3 mg/kg. Following intravenous injection, etomidate acts in 10-65 seconds, and its duration of action is 6-8 minutes. Its effects are non-cumulative with repeated administration.

Etomidate is notable for its relative cardiovascular stability. It causes less hypotension than thiopental sodium and propofol during induction. It is also associated with rapid recovery without a hangover effect.

Etomidate is a potent inhibitor of steroidogenesis. Adrenal 11 beta-hydroxylase and cholesterol cleavage enzymes are inhibited by the drug, resulting in depression of cortisol and aldosterone synthesis for 24 hours after administration. Because of this adrenocortical suppression, it should not be used for the maintenance of anaesthesia.

Other adverse effects associated with the use of etomidate include:

• Nausea and vomiting
• Pain on injection (in up to 50%)
• Phlebitis and venous thrombosis
• Arrhythmias and heart block
• Hyperventilation
• Respiratory depression and apnoea
• Can cause both hypo- and hypertension
• Increased mortality in critically ill patients

Propofol

Propofol (2,6-diisopropylphenol) is a short-acting phenol derivative that is primarily used for the induction of anaesthesia.

Its mechanism of action is unclear, but it is thought to act by potentiating the inhibitory neurotransmitters GABA and glycine, which enhances spinal inhibition during anaesthesia.

The dose for induction of anaesthesia is 1.5-2.5mg/kg. The dose for maintenance of anaesthesia is 4-12 mg/kg/hour. Following intravenous injection, propofol acts within 30 seconds, and its duration of action is 5-10 minutes.

Propofol produces a 15-25% decrease in blood pressure and systemic vascular resistance without a compensatory increase in heart rate. It is negatively inotropic and decreases cardiac output by approximately 20%.

The main side effects of thiopental sodium are:

• Pain on injection (in up to 30%)
• Hypotension
• Transient apnoea
• Hyperventilation
• Coughing and hiccough
• Headache
• Thrombosis and phlebitis

Ketamine

Ketamine is the only anaesthetic agent available that has analgesic, hypnotic, and amnesic properties. When used correctly, it is a very useful and versatile drug.

Ketamine acts by non-competitive antagonism of the NMDA receptor Ca2+ channel pore and also inhibits NMDA receptor activity by interaction with the phencyclidine binding site.

Ketamine can be used intravenously and intramuscularly. The intramuscular dose is 10 mg/kg, and when used by this route, it acts within 2-8 minutes and has a duration of action of 10-20 minutes. The intravenous dose is 1.5-2 mg/kg administered over a period of 60 seconds. When used intravenously, it acts within 30 seconds and has a duration of action of 5-10 minutes. Ketamine is also effective when administered orally, rectally, and nasally.

Ketamine causes tachycardia, an increase in blood pressure, central venous pressure, and cardiac output, secondary to an increase in sympathetic tone. Baroreceptor function is well maintained, and arrhythmias are uncommon.

The main disadvantage to the use of ketamine is the high incidence of hallucinations, nightmares, and other transient psychotic effects. These can be reduced by the co-administration of a benzodiazepine, such as diazepam or midazolam.

The main side effects of ketamine are:

• Nausea and vomiting
• Hypertension
• Nystagmus
• Diplopia
• Rash

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