Whole-Body Hypothermia for Neonates With Hypoxic???Ischemic Encephalopathy

This randomized, controlled trial had as its goal to determine whether whole-body cooling, begun within 6 hours of birth and continuing for 72 hours, reduces disability and mortality in term infants with moderate or severe encephalopathy. Infants entered into the study had a gestational age of 36 weeks or longer, were admitted with either severe acidosis or perinatal complications, and required resuscitation at birth. They were randomized to usual care or whole-body cooling and were reassessed neurodevelopmentally at age 18 to 22 months. The 102 infants assigned to hypothermia were placed on a blanket precooled to 5°C and the esophageal temperature, measured with a probe, was reduced to 33.5°C. A second blanket then was attached to the cooling system decrease variability in esophageal temperature. A skin probe monitored the temperature of the abdominal-wall skin. At both sites, temperature was monitored continuously and recorded every 15 minutes for 4 hours and then hourly for 8 hours. After 72 hours, the set point of the automatic control on the cooling system was increased by 0.5°C per hour. After 6 hours, the esophageal probe was removed and warming continued until the set point of the warmer reached 36.5°C. The 106 control infants were exposed to an overhead radiant warmer to maintain an abdominal-wall skin temperature of 36.5°C to 37.0°C. The incidence of death or moderate/severe disability was 44% in treated infants and 62% of control infants (risk ratio [RR], 0.72; 95% confidence interval [CI], 0.54–0.95). Approximately one fourth of actively treated infants (24%) and 37% of control infants died (RR, 0.68; 95% CI, 0.44–1.05). No increase in major disability was observed in surviving infants. Cerebral palsy occurred in 19% of the hypothermia group and 30% of control infants (RR, 0.68; 95% CI, 0.38–1.22). These results suggest that whole-body cooling, or hypothermia, is a safe and effective means of limiting mortality and reducing disability in newborn infants with moderate or severe encephalopathy.