Apolipoprotein E genotype and response of carbon monoxide poisoning to hyperbaric oxygen treatment

Rationale: Hyperbaric oxygen (HBO2) reduced the incidence of cognitive sequelae 6 weeks after carbon monoxide (CO) poisoning compared with normobaric oxygen (NBO2). The apolipoprotein (APOE) epsilon 4 allele predicts unfavorable neurologic outcome after brain injury and stroke. Objectives: To assess the effects of the epsilon 4 allele on 6-week cognitive sequelae after CO poisoning. Methods: We tested APOE genotypes in 86 of 152 CO-poisoned patients from our randomized trial. Logistic regression was used to control for risk factors while testing for effects with the epsilon 4 allele or interactions with epsilon 4 and treatment on 6-week and 6- and 12-month cognitive sequelae. Measurements and Main Results: We enrolled 86 patients: 44 received HBO2 and 42 NBO2 therapy. A total of 31 (36%) patients had at least one epsilon 4 allele. Six-week cognitive sequelae rates for patients treated with HBO2 and NBO2, respectively: epsilon 4 allele absent, 11% (3/27) and 43% (12/28); epsilon 4 allele present, 35% (6/17) and 29% (4/14). The epsilon 4 allele was not associated with 6-week cognitive sequelae, 27% (15/ 55) without and 32% (10/31) with the epsilon 4 allele (P = 0.323). The interaction between the epsilon 4 allele and treatment was significantly associated with 6-week cognitive sequelae (P = 0.048). The interaction between the epsilon 4 allele and treatment was not associated with 6- and 12-month cognitive sequelae. Conclusions: HBO2 therapy reduces cognitive sequelae after CO poisoning in the absence of the epsilon 4 allele. Because apolipoprotein genotype is unknown at the time of poisoning, we recommend that patients with acute CO poisoning receive HIBO2.