Oxygen Exposure During Cardiopulmonary Resuscitation Is Associated With Cerebral Oxidative Injury in a Randomized, Blinded, Controlled, Preclinical Trial

BACKGROUND: Hyperoxia during cardiopulmonary resuscitation (CPR) may lead to oxidative injury from mitochondrial‐derived reactive oxygen species, despite guidelines recommending 1.0 inspired oxygen during CPR. We hypothesized exposure to 1.0 inspired oxygen during CPR would result in cerebral hyperoxia, higher mitochondrial‐derived reactive oxygen species, increased oxidative injury, and similar survival compared with those exposed to 21% oxygen. METHODS AND RESULTS: Four‐week‐old piglets (n=25) underwent asphyxial cardiac arrest followed by randomization and blinding to CPR with 0.21 (n=10) or 1.0 inspired oxygen (n=10) through 10 minutes post return of spontaneous circulation. Sham was n=5. Survivors received 4 hours of protocolized postarrest care, whereupon brain was obtained for mitochondrial analysis and neuropathology. Groups were compared using Kruskal‐Wallis test, Wilcoxon rank‐sum test, and generalized estimating equations regression models. Both 1.0 and 0.21 groups were similar in systemic hemodynamics and cerebral blood flow, as well as survival (8/10). The 1.0 animals had relative cerebral hyperoxia during CPR and immediately following return of spontaneous circulation (brain tissue oxygen tension, 85% [interquartile range, 72%–120%] baseline in 0.21 animals versus 697% [interquartile range, 515%–721%] baseline in 1.0 animals; P=0.001 at 10 minutes postarrest). Cerebral mitochondrial reactive oxygen species production was higher in animals treated with 1.0 compared with 0.21 (P<0.03). Exposure to 1.0 oxygen led to increased cerebral oxidative injury to proteins and lipids, as evidenced by significantly higher protein carbonyls and 4‐hydroxynoneals compared with 0.21 (P<0.05) and sham (P<0.001). CONCLUSIONS: Exposure to 1.0 inspired oxygen during CPR caused cerebral hyperoxia during resuscitation, and resultant increased mitochondrial‐derived reactive oxygen species and oxidative injury following cardiac arrest.