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.