Relationship between PCO₂ and unfavorable outcome in infants with moderate-to-severe hypoxic ischemic encephalopathy

Background: Abnormal PCO ₂ is common in infants with hypoxic ischemic encephalopathy (HIE). The objective was to determine whether hypocapnia was independently associated with unfavorable outcome (death or severe neurodevelopmental disability at 18 mo) in infants with moderate-to-severe HIE. Methods: This was a post hoc analysis of the CoolCap Study in which infants were randomized to head cooling or standard care. Blood gases were measured at prespecified times after randomization. PCO₂ and follow-up data were available for 196 of 234 infants. Analyses were performed to investigate the relationship between hypocapnia in the first 72 h after randomization and unfavorable outcome. Results: After adjusting for pH, amplitude-integrated electroencephalogram background and seizures, birth weight, Apgar score at 5 min, cooling status, and Sarnat stage, PCO₂was inversely associated with unfavorable outcome (P < 0.001). The probability of unfavorable outcome was 0.20 ± 0.1 (point estimate ± SE), 0.53 ± 0.23 and 0.89 ± 0.16 for a PCO₂of 40, 30, and 20 mm Hg respectively and was greater in infants with severe HIE than with moderate HIE. Conclusions: Hypocapnia in infants with moderate-to-severe HIE was independently associated with unfavorable outcome. Future studies of controlled normocapnia will be important.