Pharmacology for Anaesthesia and Intensive Care

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Section IICoredrugs in anaesthetic practice

Kinetics

Following an intravenous dose the plasma concentration falls in a bi-exponential

fashion. The initial fall is due to distribution across lipid membranes while the slower

phase is due to hepatic metabolism. Ketamine is the least protein bound (about 25%)

of the intravenous anaesthetics and is demethylated to the active metabolite norke-

tamine by hepatic P450 enzymes. Norketamine (which is 30% as potent as ketamine)

is further metabolized to inactive glucuronide metabolites. The conjugated metabo-

lites are excreted in the urine.

Etomidate

Etomidate is an imidazole derivative and an ester. While it continues to be used

infrequently in the UK it has been withdrawn in North America and Australia.

Presentation

Etomidate is prepared as a 0.2% solution at pH of 4.1 and contains 35% v/v propylene

glycol to improve stability and reduce its irritant properties on injection. A lipid

formulation is now also available.

Uses

Etomidate is used for the induction of general anaesthesia at a dose of 0.3 mg.kg−^1.

Effects

Atfirst glance etomidate would appear to have some desirable properties, but due

to its side effects its place in anaesthesia has remained limited.


Cardiovascular – of the commonly used intravenous anaesthetics it produces

the least cardiovascular disturbance. The peripheral vascular resistance may fall

slightly (but less so than with other induction agents), while myocardial oxygen

supply, contractility and blood pressure remain largely unchanged. Hypersensitiv-

ity reactions are less common following etomidate and histamine release is rare.


Metabolic – it suppresses adrenocortical function by inhibition of the enzymes

11 β-hydroxylase and 17α-hydroxylase, resulting in inhibition of cortisol and aldos-

terone synthesis. It was associated with an increase in mortality when used as an

infusion to sedate septic patients in intensive care. Single doses can influence

adrenocortical function but are probably of little clinical significance in otherwise

fit patients. However it is it unlikely to be used to induce elective patients. In other

words the situation in which it has the best cardiovascular profile is the unwell

patient in whom the consequences of steroid inhibition are likely to be the most

detrimental.