Dexmedetomidine versus opioids for sedation during therapeutic hypothermia in neonatal HIE: efficacy, safety, and dose-response relationship.

Abstract

Therapeutic hypothermia (TH) is the standard of care for neonates with hypoxic-ischemic encephalopathy (HIE), but effective sedation remains a challenge. Opioids are widely used but are associated with respiratory depression, delayed enteral feeding, and neurodevelopmental concerns. This study assessed the efficacy, safety, and dose-response profile of dexmedetomidine as an alternative sedative. In this single-center retrospective cohort study, 163 neonates with HIE receiving TH between 2018 and 2024 were evaluated. Outcomes were compared between those receiving dexmedetomidine-based sedation (n = 61) versus opioid-only sedation (n = 102). Primary outcomes included cumulative opioid dose, sedation adequacy (NPASS), bradycardia <80 bpm incidence, and respiratory support needs. Dexmedetomidine was associated with 50% lower cumulative opioid exposure (46 vs. 95 μg/kg, p < 0.001), fewer rescue doses (3.3 vs. 5.0), shorter time to full enteral feeding (6 vs. 7 days, p < 0.001), and reduced mechanical ventilation (8.5% vs. 17%, p = 0.14). Sedation scores and hemodynamics were comparable. Bradycardia occurred in 41% of dexmedetomidine-treated neonates, leading to discontinuation in 30%. Dose-response analysis suggested efficacy plateaued above 0.5 μg/kg/hr, with increasing bradycardia risk. Dexmedetomidine was effective and generally well tolerated during TH. Infusion rates between 0.25 and 0.5 μg/kg/hr may optimize the balance of efficacy and safety. Dexmedetomidine use during therapeutic hypothermia in neonates with HIE reduced opioid exposure by 50% while maintaining sedation efficacy. Associated with earlier achievement of full enteral feeding and lower rates of mechanical ventilation compared with opioid-only sedation. Dose-response analysis identified an infusion range (0.25-0.5 μg/kg/hr) balancing sedation efficacy with bradycardia risk. Findings support dexmedetomidine as a viable first-line sedative during therapeutic hypothermia and inform safer dosing strategies.