Halothane

Overview
Halothane vapour (or Fluothane) is an inhalational general anaesthetic. Its systematic name is 2-Bromo-2-chloro-1,1,1-trifluoroethane. It is the only inhalational anaesthetic agent containing a bromine atom. It is colourless and pleasant-smelling, but unstable in light. It is packaged in dark-coloured bottles and contains 0.01% thymol as a stabilising agent.

Adverse effects
All volatile anaesthetics such as halothane can trigger malignant hyperthermia in genetically susceptible individuals. The caffeine-halothane contracture test was developed to directly test muscle biopsy specimens for this susceptibility. This test may be replaced by genetic testing in the future.

Related substances
Chemically, halothane is not an ether. Attempts to find anaesthetics with less metabolism led to halogenated ethers such enflurane and isoflurane. The incidence of hepatic reactions with these agents is less. The degree of hepatotoxic potential of enflurane is controversial, although it is minimally metabolised. Isoflurane is essentially not metabolised and reports of associated liver injury are quite rare.

History
This halogenated hydrocarbon was first synthesised by C. W. Suckling of Imperial Chemical Industries (ICI) in 1951 and was first used clinically by M. Johnstone in Manchester in 1956. Halothane became popular as a nonflammable general anaesthetic replacing other volatile anaesthetics such as diethyl ether and cyclopropane. Use of the anesthetic was phased out during the 1980s and 1990s as newer anesthetic agents became popular. Halothane retains some use in veterinary surgery and in the Third World because of its lower cost.

Halothane was given to many millions of adult and pediatric patients worldwide from its introduction in 1956 through the 1980s. Its properties include cardiac depression at high levels, cardiac sensitisation to catecholamines such as norepinephrine, and potent bronchial relaxation. Its lack of airway irritation made it a common inhalation induction agent in pediatric anaesthesia. Due to its cardiac depressive effect, it was contraindicated in patients with cardiac failure. Halothane was also contraindicated in patients susceptible to cardiac arrythmias, or in situations related to high catecholamine levels such as pheochromocytoma.

Repeated exposure to halothane in adults was noted in rare cases to result in severe liver injury. This occurred in about 1 in 35,000 exposures. The resulting syndrome was referred to as halothane hepatitis, and is thought to result from the metabolism of halothane to trifluoroacetic acid via oxidative reactions in the liver. About 20% of inhaled halothane is metabolised by the liver and these products are excreted in the urine. The hepatitis syndrome had a mortality rate of 30% to 70%. Concern for hepatitis resulted in a dramatic reduction in the use of halothane for adults. It was replaced in the 1980s by enflurane and isoflurane. By the year 2005 the common volatile anaesthetics in use were isoflurane, sevoflurane, and desflurane. Since the risk of halothane hepatitis in children was substantially lower than in adults, halothane saw continued use in pediatrics in the 1990s. However, by the year 2000 sevoflurane had largely replaced the use of halothane in children.