Pharmacology for Anaesthesia and Intensive Care

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Section IICoredrugs in anaesthetic practice

hepatitis is based on the exclusion of all other forms of liver damage. The incidence

in children is between 1 in 80 000–200 000 while in the adult it is 1 in 2500–35 000.

The following are risk factors: multiple exposures, obesity, middle age and female

sex. The mortality rate is 50–75%.

Halothane should be avoided if administered within the previous 3 months, there

is a history of a previous adverse reaction to halothane or pre-existing liver disease.

Enflurane has also been reported to cause hepatic necrosis. Its incidence is much

lower due to its lower rate of metabolism. In theory the other volatile agents may

cause a similar reaction but due to their even lower rates of metabolism this becomes

increasingly unlikely.

Enflurane

This halogenated ethyl methyl ether is a structural isomer of isoflurane. Its use is

decreasing due to newer agents with more favourable profiles.

Effects


Respiratory – enflurane causes more depression of ventilation than the other

agents. The minute volume decreases and the PaCO 2 will rise. The ventilatory

response to hypoxia and hypercarbia are also blunted.


Cardiovascular – while the heart rate increases, cardiac output, contractility and

blood pressure fall along with a small fall in systemic vascular resistance. The heart

is not sensitized to catecholamines, and arrhythmias are relatively uncommon.


Central nervous system – high concentrations of enflurane in the presence of

hypocarbia produce a 3 Hz spike and wave pattern on the EEG consistent with

grand mal activity. While there is no evidence that these changes are seen more

frequently in epileptics, enflurane is usually avoided in this group of patients. The

increase in cerebral blood flow and accompanying increase in intracranial pressure

lie between those observed with halothane and isoflurane.

Metabolism

Only 2% is metabolized by hepatic cytochrome P450. F−ions are produced but rarely

reach the levels (>40μmol.l−^1 )known to produce reversible nephropathy. It is usually

avoided in patients with renal impairment.

Toxicity

Hepatic damage may occur (cf. halothane metabolism).

Desflurane

Desflurane (a fluorinated ethyl methyl ether) was slow to be introduced into anaes-

thetic practice due to difficulties in preparation and administration. It has a boil-

ing point of 23.5◦C, which renders it extremely volatile and, therefore, dangerous

to administer via a conventional vaporizer. It is, therefore, administered via the