Association between sedation–analgesia and neurodevelopment outcomes in neonatal hypoxic-ischemic encephalopathy

Objectiveto evaluate the association between sedation–analgesia (sa) during initial 72 h and death/disability at 18 months of age in neonatal hypoxic-ischemic encephalopathy (hie).designthis was a secondary analysis of the nichd therapeutic hypothermia (th) randomized controlled trial in moderate or severe hie. receipt of sa and anticonvulsant medications at five time points were considered: prior to and at baseline, 24, 48, and 72 h of th or normothermia. disability was defined as mental developmental index <85, cerebral palsy, blindness, hearing impairment, or gross motor function classification system 2–5.resultsof the 208 rct participants, 38 (18%) infants had no exposure to sa or anticonvulsants at any of the five time points, 20 (10%) received sa agents only, 81 (39%) received anticonvulsants only, and 69 (33%) received both sa and anticonvulsants. sa category drugs were not administered in 57% of infants while 18% received sa at ≥3 time points; 72% infants received anticonvulsants during 72 h of intervention. at 18 months of age, disability among survivors and death/disability was more frequent in the groups receiving anticonvulsants, with (48 and 65%) or without (37 and 58%) sa, compared to groups with no exposure (14 and 34%) or sa (13 and 32%) alone. severe hie (aor 3.60; 1.59–8.13), anticonvulsant receipt (aor 2.48; 1.05–5.88), and mechanical ventilation (aor 7.36; 3.15–17.20) were independently associated with 18-month death/disability, whereas th (aor 0.28; 0.13–0.60) was protective. sa exposure showed no association with outcome.conclusionsthe risk benefits of sa in hie need further investigation.