Emerging therapies and management for neonatal encephalopathy-controversies and current approaches.

Neonatal encephalopathy (NE) continues to have a major impact on newborn survival and neurodevelopmental outcomes worldwide. In high-income settings, therapeutic hypothermia is the only established standard treatment for neonates with moderate-to-severe NE, with compelling evidence that cooling reduces mortality and major neurodevelopmental impairment in survivors. Despite therapeutic hypothermia, a significant proportion of cooled infants continue to suffer long-term disability from brain injury. Innovative therapies offer the possibility of further improving neurodevelopmental outcomes by working synergistically with therapeutic hypothermia to decrease hypoxia-ischemia-induced excitotoxicity, prevent progression to secondary energy failure, and in some cases, promote neuroregeneration in the developing neonatal brain. This review discusses emerging NE therapies currently under investigation, offers insight into controversies surrounding various approaches to clinical care during therapeutic hypothermia, and identifies ongoing knowledge deficits that hinder attainment of optimal outcomes for neonates with NE.

Opioid and benzodiazepine use during therapeutic hypothermia in encephalopathic neonates.

OBJECTIVES: To evaluate the use of sedatives and analgesics during therapeutic hypothermia in encephalopathic neonates and assess associations between medication exposure and hospital outcomes. STUDY DESIGN: We identified neonates ≥35 weeks gestational age treated with therapeutic hypothermia at 125 neonatal intensive care units between 2007 and 2015. We compared characteristics and hospital outcomes between unexposed neonates and neonates exposed to opioids and/or benzodiazepines. RESULTS: Opioids were administered to 1 677/2 621 (64%) neonates, and exposure increased from 38% in 2008 to 68% in 2015. Sedation/analgesia varied widely between centers. Opioid-exposed neonates experienced greater durations of respiratory support and were more likely to receive inotropes and inhaled nitric oxide. Mortality during postnatal days 0-3 was lower among opioid-exposed neonates (31/625 [5%]) than unexposed neonates (64/714 [9%]). CONCLUSIONS: Sedation/analgesia during therapeutic hypothermia is prevalent but not uniform across centers. Prospective studies are needed to assess if exposure independently predicts intensity and duration of physiologic support.