Early hyperbaric oxygen therapy is associated with favorable outcome in patients with iatrogenic cerebral arterial gas embolism: systematic review and individual patient data meta-analysis of observational studies

Background Iatrogenic cerebral arterial gas embolism (CAGE) caused by invasive medical procedures may be treated with hyperbaric oxygen therapy (HBOT). Previous studies suggested that initiation of HBOT within 6–8 h is associated with higher probability of favorable outcome, when compared to time-to-HBOT beyond 8 h. We performed a group level and individual patient level meta-analysis of observational studies, to evaluate the relationship between time-to-HBOT and outcome after iatrogenic CAGE. Methods We systematically searched for studies reporting on time-to-HBOT and outcome in patients with iatrogenic CAGE. On group level, we meta-analyzed the differences between median time-to-HBOT in patients with favorable versus unfavorable outcome. On individual patient level, we analyzed the relationship between time-to-HBOT and probability of favorable outcome in a generalized linear mixed effects model. Results Group level meta-analysis (ten studies, 263 patients) shows that patients with favorable outcome were treated with HBOT 2.4 h (95% CI 0.6–9.7) earlier than patients with unfavorable outcome. The generalized linear mixed effects model (eight studies, 126 patients) shows a significant relationship between time-to-HBOT and probability of favorable outcome ( p = 0.013) that remains significant after correcting for severity of manifestations ( p = 0.041). Probability of favorable outcome decreases from approximately 65% when HBOT is started immediately, to 30% when HBOT is delayed for 15 h. Conclusions Increased time-to-HBOT is associated with decreased probability of favorable outcome in iatrogenic CAGE. This suggests that early initiation of HBOT in iatrogenic CAGE is of vital importance.