Co-Chief, Division of Neonatology Children's Hospital of Michigan Central Michigan University, Mount Pleasant, MI Detroit, Michigan, United States
Background: Limited preclinical data suggest that the efficacy of therapeutic hypothermia (TH) in HIE may be improved with sedation-analgesia but concerns exist about the potential adverse effects of opioid exposure.
Objective: To assess the association between opioid exposure during TH for perinatal HIE and short-term outcomes.
Design/Methods: The Children's Hospitals Neonatal Database (CHND) was used to identify infants (≥36 weeks gestational age [GA], birthweight ≥1800g, born from 1/2010-1/2017) with HIE, who underwent TH at participating sites. CHND data were linked to the Pediatric Health Information Systems (PHIS) to evaluate opioid use during TH. To focus on opioid use primarily for sedation during TH, we excluded infants who received opioids beyond 5 days. Infants were categorized as No (NOG) opioid, Low (1-2 days) (LOG) and High (3-5 days) (HOG) opioid groups. The primary outcome was survival with normal MRI; length of stay and ventilation among survivors were secondary outcomes. Statistical analyses included Chi-square and Kruskal-Wallis tests; logistic regression and generalized linear models for gamma distribution and log link were developed after adjusting for center, HIE severity, antiepileptic (AED) and sedative days.
Results: Among 1,484 infants, 240 (16.2%) received no opioids, 574 (38.7%) were in the LOG and 670 (45.2%) infants were in the HOG respectively. Fewer neonates in the NOG received delivery room chest compressions, and epinephrine, and had 10-minute Apgar scores <5, although proportion of moderate/severe HIE was higher, compared to the opioid-exposed groups [Table 1]. Infants in the HOG underwent head cooling and transport TH more often while the NOG had higher sedative (benzodiazepine) costs [Table 2]. The NOG had higher survival with normal MRI and received G-tube and oxygen at discharge less frequently [Table 3]. There was no interaction between opioid exposure and HIE severity nor between opioid and sedative use. On logistic regression (AUC =0.776), HIE severity was associated with the primary outcome but opioid exposure was not. Opioid use, HIE severity and AED days were all significantly associated with prolonged hospital stay and ventilation [Table 4]. Conclusion(s): The vast majority (84%) of a large multicenter cohort of infants with HIE received opioids during TH. Opioid exposure was associated with higher adjusted odds of prolonged hospital stay and ventilation, without an improvement in survival with normal MRI. These data suggest the need for judicious use of opioids in HIE.
Table 1: Comparison of baseline characteristics of infants in the No Opioid (NOG), Low Opioid (LOG) and High Opioid (HOG) groups
Table 2: Comparison of TH-related data in the NOG, LOG and HOG
Table 3: Comparison of short-term outcomes in the NOG, LOG and HOG
Table 4: Logistic regression for survival with normal MRI and generalized linear models for gamma distribution and log link for length of stay and ventilation
Authors/Institutions: Girija Natarajan, Children's Hospital of Michigan, Detroit, Michigan, United States; Shannon E. Hamrick, Emory University, Atlanta, Georgia, United States; Isabella Zaniletti, Children's Hospital Association, Lenexa, Kansas, United States; Robert DiGeronimo, Seattle Children's Hospital/University of Washington, Seattle, Washington, United States; Maria L. Dizon, Northwestern University, Chicago, Illinois, United States; John Flibotte, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States; Kyong-Soon Lee, Hospital for Sick Children, Toronto, Ontario, Canada; Ulrike Mietzsch, Seattle Children's Hospital/University of Washington, Seattle, Washington, United States; Karna Murthy, Northwestern University, Chicago, Illinois, United States; Eric S. Peeples, University of Nebraska Medical Center, Omaha, Nebraska, United States; Priscilla Joe, UCSF Benioff Children's Hospital Oakland, Oakland, California, United States; Danielle L. Smith, Children's Hospital of Colarado, Denver, Colorado, United States; Tai-Wei Wu, Children's Hospital Los Angeles, Los Angeles, California, United States; Toby D. Yanowitz, university of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States; An N. Massaro, Childrens National Health Systems, Washington, DC, District of Columbia, United States; Rakesh Rao, Washington University in St. Louis, St. Louis, Missouri, United States