Alterations in pharmacokinetics of carboxyhemoglobin produced by oxygen under pressure

Abstract

The pharmacokinetic effect of elevated oxygen partial pressures in the elimination of carboxyhemoglobin (COHb) by O2 administration was studied in an inflatable hyperbaric chamber. A double crossover prospective analysis between the modified Gamow bag and non-rebreather (NRB) mask O2 was conducted among 12 healthy, adult volunteers who smoked five cigarettes sequentially within a 60-min period. COHb levels were measured using co-oximetry before and after smoking. Subjects inspired hyperbaric oxygen (HBO2) and normobaric oxygen (NBO2) in separate trials for 40 min. Mean COHb levels (1.16 +/- 0.28 g/dl) post-smoking were representative of low-level poisoning. NBO2 consisted of a NRB mask at a rate of 15 liter/min outside the Gamow bag. HBO2 was delivered inside the Gamow bag with a demand valve regulator mask at a Po2 of 1.58 atm abs. A significant increase in the half-life (t 1/2) of COHb was observed for each subject in the Gamow bag (P < 0.05; repeated measures analysis of variance). Average t 1/2 for COHb was 26.3 +/- 3.7 min (n = 12) and 71.3 +/- 9.9 min (n = 12) while breathing HBO2 and NBO2, respectively. Pharmacokinetic modeling was performed using PCNONLIN software for each subject. Both zero and first order elimination kinetics were tested and the model of best fit determined using the Akaike Information Criterion for each subject. A significant shift in COHb elimination from a zero to first order mechanism with elevation in O2 partial pressure was observed (P = 0.002; McNemar's test). HBO2 provides a pharmacokinetic advantage over NRB mask O2 in eliminating mild carboxyhemoglobinemia.