MECHANISTIC ASPECTS OF CARBON-MONOXIDE FORMATION FRONT VOLATILE ANESTHETICS

Background Desflurane, enflurane and isoflurane can be degraded to car bon monoxide (CO) by carbon dioxide absorbents, whereas sevoflurane an d halothane form negligible amounts of CO. Carbon monoxide formation i s greater with drier absorbent, and with barium hydroxide, than with s oda lime, The mechanism, role of absorbent composition and water, and anesthetic structures determining CO formation are unknown. This inves tigation examined sequential steps in anesthetic degradation to CO. Me thods: Carbon monoxide formation from anesthetics and desiccated bariu m hydroxide lime or soda Lime was determined at equimole and equiMAC c oncentrations. Carbon monoxide formation from deuterium-substituted an esthetics was also quantified. Proton abstraction from anesthetics by strong base was determined by deuterium isotope exchange. A reactive c hemical intermediate was trapped and identified by gas chromatography- mass spectrometry, The source of the oxygen in CO was identified by O- 18 incorporation. Results: Desflurane, enflurane, and isoflurane (difl uoromethyl-ethyl ethers), but not sevoflurane (monofluoromethyl ether) , methoxyflurane (methyl-ethyl ether), or halothane (alkane) were degr aded to CO, The amount of CO formed was desflurane greater than or equ al to enflurane > isoflurane at equiMAC and enflurane > desflurane > i soflurane at equimole concentrations. Proton abstraction from the difl uoromethoxy carbon was greater with potassium than with sodium hydroxi de, but unmeasurable with barium hydroxide. Carbon monoxide formation was correlated (r = 0.95-1.00) with difluoromethoxy (enflurane > desfl urane > isoflurane greater than or equal to methoxyflurane = sevoflura ne = 0) but not ethyl carbon proton abstraction. Deuterium substitutio n on enflurane and desflurane diminished CO formation. Chemical trappi ng showed formation of a difluorocarbene intermediate from enflurane a nd desflurane. Incorporation of (H2O)-O-18 in barium hydroxide Lime re sulted in (CO)-O-18 formation from unlabeled enflurane and desflurane. Conclusions: A difluoromethoxy group is a structural requirement for haloether degradation to CO, Results are consistent with initial base- catalyzed difluoromethoxy proton abstraction (potassium > sodium hydro xide, thus greater CO formation with barium hydroxide lime vs. soda Li me) forming a carbanion (reprotonated by water to regenerate the anest hetic, hence requirements for relatively dry absorbent), carbanion dec omposition to a difluorocarbene, and subsequent difluorocarbene reacti on to form CO.