Halothane

Halothane (2-bromo-2-chloro-1,1,1-trifluoroethane; CAS 151-67-7; molecular formula C2HBrClF3; molecular weight 197.38) is a halogenated alkane volatile anesthetic synthesized by Charles Suckling at ICI in 1951 and introduced clinically by Michael Johnstone in 1956. Halothane was the first non-flammable volatile to displace diethyl ether and chloroform as the dominant inhalational agent and remained in widespread use through the 1980s before isoflurane and the newer ethers superseded it. The minimum alveolar concentration (MAC) at age 40 is 0.75 percent in oxygen; the blood-gas partition coefficient is 2.4, slower than the modern ether agents. Mechanism is the standard volatile profile (GABA-A potentiation, K2P channel activation, glycine and NMDA modulation). Cardiovascular effects include dose-dependent myocardial depression with preserved or modestly reduced systemic vascular resistance, sensitization to catecholamine-induced arrhythmias (a clinically important interaction with epinephrine), and bradyarrhythmia. The principal limitations that drove displacement are halothane hepatitis (immune-mediated hepatic necrosis with an incidence of approximately 1 in 35,000 cases, attributed to trifluoroacetyl protein adducts generated by 20 percent hepatic metabolism through CYP2E1), and the negative inotropic and arrhythmogenic profile relative to the ether agents. Halothane remains the dominant inhalational anesthetic in lower-resource settings owing to acquisition cost (manufacturer-stated cost approximately one-third of isoflurane). Veterinary use persists in some jurisdictions. The global warming potential is moderate (GWP100 approximately 50). Pediatric induction was a historical strength owing to the non-pungent character; sevoflurane has displaced halothane for this indication in most jurisdictions.