Uses: Induction and maintenance of general anaesthesia.
Chemical: Halogenated hydrocarbon.
Presentation: Clear colourless liquid with a sweet smell, (should be protected from light). The commercial preparation contains 0.01% thymol which prevents decomposition on exposure to light.
Mode of action: Mechanism of general anaesthesia remains unclear.
Routes: Inhalation, via a calibrated vaporiser. Induction dose 2-4%, maintenance 0.5-2%.
Cardiovascular system: Causes a dose-related decrease in myocardial contractility and cardiac output, with a decrease in cardiac work and myocardial oxygen consumption, by inhibition of calcium ion flux within myocardial cells. Heart rate decreases due to vagal stimulation; the SVR is decreased by 15% thus leading to a decrease in mean arterial pressure. Causes a marked sensitisation of the myocardium to catecholamines.
Respiratory system: Respiratory depressant. Decreases tidal volume, although may increase respiratory rate. Decreases response to hypoxia and hypercapnia. Non-irritant to the respiratory tract and causes bronchodilatation by a direct effect on bronchial smooth muscle.
Central nervous system: Principal effect is general anaesthesia; little if any analgesic effect. Causes cerebral vasodilatation, leading to increased cerebral blood flow. Decreases cerebral oxygen consumption. Causes a centrally mediated decrease in skeletal muscle tone.
Abdominal system: Decreases salivation and gastric motility; decreases splanchnic blood flow due to hypotension.
Genitourinary system: Decreases renal blood flow by 40% and glomerular filtration rate by 50%. Tone of pregnant uterus is reduced.
Toxicity: Potent trigger agent for malignant hyperthermia. May also cause the appearance of myocardial dysrhythmias, particularly in conjunction with hypoxia, hypercapnia or excessive catecholamine concentrations.
Two major types of hepatotoxicity are associated with halothane administration. The two forms appear to be unrelated and are termed type I (mild) and type II (fulminant). Type I hepatotoxicity is benign, self-limiting, and relatively common (up to 25-30% incidence). This type is marked by mild, transient increases in serum transaminase and glutathione S-transferase concentrations and by altered postoperative drug metabolism. Type I probably results from reductive (anaerobic) biotransformation of halothane rather than the normal oxidative pathway. It does not occur following administration of other volatile anaesthetics because they are metabolised to a lesser degree and by different pathways than halothane.
Type II hepatotoxicity is associated with massive centrilobular liver cell necrosis that leads to fulminant liver failure. No histopathologic findings are specific to this condition. Type II hepatotoxicity is characterised clinically by fever, jaundice and grossly elevated serum transaminase levels. It appears to be immune mediated and is initiated by oxidative halothane metabolism to an intermediate compound. This compound then binds to trifluoroacetylate proteins in the hepatic endoplasmic reticulum. Type II hepatotoxicity is thought to occur in genetically predisposed individuals. Approximately 20% of halothane is oxidatively metabolised, compared with only 2% of enflurane and 0.2% of isoflurane. The occurrence of type II hepatotoxicity after enflurane or isoflurane administration is extremely rare.
The Committe on Safety of Medicines in 1986 recommended the avoidance of halothane following:
-history of previous adverse reactions, previous exposure within 3 months unless the indications are clinically overriding (the safe time interval is not known), history of unexplained jaundice/pyrexia after previous exposure to halothane.
Absorption: Coefficients - Blood/gas: 2.4, oil/gas: 225; minimum alveolar concentration: 0.76. Halothane is relatively insoluble in blood; alveolar concentration therefore reaches inspired concentration very rapidly, resulting in a rapid induction of anaesthesia.
Distribution: Initially to areas of high blood flow (brain, heart, liver and kidney). Later to less well-perfused organs.
Metabolism: 20% of dose is metabolised in the liver (oxidation/dehalogenation to yield trifluoroacetic acid, trifluoroacetylethanolamide, chlorobromidifluorethylene, and chloride and bromide radicals.
Excretion: 60-80% is exhaled unchanged; the metabolites are excreted in the urine.
Special points: Potentiates action of non-depolarising muscle relaxants.
[i] Halothane: the end of an era?
Anesth Analg 2002; 95(6): 1471.
[ii] Identification of the enzyme responsible for oxidative halothane metabolism: implications for prevention of halothane hepatitis.
Kharasch ED et al.
Lancet 1996; 347(9012): 1367-71.
Related examination questions
a) has a marked arrhythmogenic potential compared with other currently used volatiles
b) is a racemic mixture of optical isomers
c) has a minimum alveolar concentration of 0.29 in 70% of nitrous oxide
d) is metabolised to the greatest extent amongst currently available agents
e) sensitises the myocardium to endogenous or exogenous catecholamines