FORMATION AND TOXICITY OF ANESTHETIC DEGRADATION PRODUCTS

Toxic degradation products are formed from a range of old and modern anesthetic agents. The common element in the formation of degradation products is the reaction of the anesthetic agent with the bases in the carbon dioxide absorbents in the anesthesia circuit. This reaction results in the conversion of trichloroethylene to dichloroacetylene, halothane to 2-bromo-2-chloro-1,1-difluoroethylene, sevoflurane to 2-(fluoromethoxy)-1,1,3,3,3-pentafluoro-1-propene (Compound A), and desflurane, isoflurane, and enflurane to carbon monoxide. Dichloroacetylene, 2-bromo-2-chloro-1,1-difluoroethylene, and Compound A form glutathione S-conjugates that undergo hydrolysis to cysteine S-conjugates and bioactivation of the cysteine S-conjugates by renal cysteine conjugate β-lyase to give nephrotoxic metabolites. The elucidation of the mechanisms of formation and bioactivation of degradation products has allowed for the safe use of anesthetics that may undergo degradation in the anesthesia circuit.