186 - Infants Receiving Whole Body Cooling Exposed to Opioids, Benzodiazepines, and Dexmedetomidine: A Secondary Analysis of the HEAL Trial

Infants with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia remain at high risk of neurodevelopmental impairment. While limited information exists regarding factors that may modify outcomes in these patients, opioid and benzodiazepine exposure have been associated with an increased risk for adverse outcomes in various neonatal populations.

Objective:

To describe the exposures to opioids, benzodiazepines, and dexmedetomidine in a contemporary clinical trial population and the relationship between medication exposures with short and long-term outcomes.

Design/Methods:

A secondary analysis of the High Dose Erythropoietin for Asphyxia and Encepalopathy (HEAL) Trial, a randomized controlled multi-center trial of erythropoietin or placebo for neuroprotection in infants receiving therapeutic hypothermia. Infants were enrolled from January 2017 through October 2019 across 17 sites involving 23 hospitals. We used descriptive statistics and graphic illustrations to describe baseline maternal and infant characteristics. Exposures to any sedatives (benzodiazepines, opioids, and/or dexmedetomidine) were classified as none, short (£ 4 days) or long ( > 4 days). Cognitive, language, and motor developmental outcomes were assessed using the Bayley Scales of Infant Development-Third Edition.

Results: Of 500 patients, 50 (10%) had no exposure, 262 (52%) had 1 – 4 days, and 188 (38%) had > 4 days of exposure to sedatives. We found no demographic differences between the groups (Table 1). Infants without sedating drug exposure were more likely to be inborn, less likely to receive therapy for hypotension, fluid boluses, or requiring intubation. Infants receiving > 4 days of medications more frequently required therapy for pulmonary hypertension (Table 1).

We found significant site variability in the use of sedatives (Figure 1).  Dexmedetomidine was only utilized by 9/17 centers whereas opioids and benzodiazepines exposure occurred at all sites, with morphine and midazolam the most frequently used medications. There was no significant association between total duration of exposure to sedatives and Bayley sub-scores at 2-years of age and found no significant association (Figure 2).

Conclusion(s):

Significant site variability exists in the utilization of opioids, benzodiazepines, and dexmedetomidine for infants requiring therapeutic hypothermia. We found no clear association exists between total duration of exposure for sedatives and 2-year neurodevelopmental outcomes.