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Section IICoredrugs in anaesthetic practiceHalothane
This halogenated hydrocarbon is unstable when exposed to light, and corrodes cer-
tain metals. It is stored with 0.01% thymol to prevent the liberation of free bromine.
It dissolves into rubber and may leach out into breathing circuits after the vaporizer
is turned off. Its physical properties are summarized in Table8.7.Effects
Respiratory – the minute ventilation is depressed largely due to a decreased tidal
volume. The normal responses to hypoxia and hypercarbia are also blunted and
these effects are more pronounced above 1 MAC. Bronchiolar tone is reduced and
it is useful in asthmatic patients. Owing to its sweet non-irritant odour it may be
used to induce anaesthesia.
Cardiovascular – halothane has significant effects on the heart. Bradycardia is pro-
duced by increased vagal tone, depressed sino-atrial and atrioventricular activ-
ity. It has direct myocardial depressant properties that reduce cardiac output. It
sensitizes the heart to catecholamines, which may lead to arrhythmias (especially
ventricular and bradyarrhythmias) and are more common than compared to other
agents. Where adrenaline is infiltrated to improve the surgical field less than 100
μg per 10 minutes should be given. Drugs that specifically reduce atrioventricu-
lar conductivity (e.g. verapamil) should be used with caution alongside halothane.
The systemic vascular resistance is reduced resulting in increased cutaneous blood
flow. However, due to a reduced cardiac output blood flow to the liver and kidneys
is reduced.
Central nervous system – halothane increases cerebral blood flow more than any
other volatile agent leading to significant increases in intracranial pressure above
0.6 MAC. Cerebral oxygen requirements are reduced.Metabolism
Upto 25% of inhaled halothane undergoes oxidative metabolism by hepatic
cytochrome P450 to produce trifluoroacetic acid, Br−and Cl−. However, reductive
metabolism producing F−and other reduced metabolites predominate when the
liver becomes hypoxic. While these reduced metabolites are toxic it is thought that
they are not involved in halothane hepatitis.Toxicity
Hepatic damage may take one of two forms:
Areversible form that is often subclinical and associated with a rise in hepatic
transaminases. This is probably due to hepatic hypoxia.
Fulminant hepatic necrosis (halothane hepatitis). Trifluoroacetyl chloride (an
oxidative metabolite of halothane) may behave as a hapten, binding covalently
with hepatic proteins, inducing antibody formation. The diagnosis of halothane