P0736 - Heart Rate Characteristics in Infants with Hypoxic Ischemic Encephalopathy: Effects of Dexmedetomidine and Gestational Age

Purpose: Therapeutic hypothermia is used in neonates with hypoxic ischemic encephalopathy (HIE) to mitigate neurologic damage due to asphyxia. Prior studies have shown that infants with more severe encephalopathy have lower heart rate variability, reflecting autonomic nervous system dysfunction. If heart rate characteristics (HRC) are to be useful as an early biomarker for severity of encephalopathy, it is important to consider how other clinical variables impact HRC. Two variables of interest are gestational age (GA), since cooling practices have expanded to include late preterm infants, and the effect of sedation medications. Our institution changed from fentanyl to dexmedetomidine as the first line agent in an effort to avoid adverse effects of opioids and due to some reports of neuroprotective effects of dexmedetomidine through alpha2 adrenergic agonists.

The objectives of our study were 1) Describe the effects of dexmedetomidine versus fentanyl on HRC in neonates undergoing therapeutic hypothermia for HIE and 2) Determine whether HRC are predictive of severity of HIE irrespective of gestational age and sedation medication.

Methods: We performed a retrospective review of infants undergoing therapeutic hypothermia for HIE from March 2011-October 2019 at our institution. Infants were excluded if they were cooled after 24 hours from birth, required ECMO, or did not have at least 4 hours of HR data available. We recorded time of fentanyl and dexmedetomidine use and dose changes. HR was measured continuously through 96 hours of age and four HRC (mean, standard deviation, skewness and kurtosis) were measured from 12-24 hours after birth and compared between GA, EEG encephalopathy, and sedation groups.

Results: There were 231 infants cooled, with 168 meeting inclusion criteria (34 GA 34-36w, 134 GA >=37 weeks). Moderate/severe encephalopathy on 24-hour EEG was found in 62%. All but three infants received sedation during cooling. Fentanyl was the first-line sedative in 72% and dexmedetomidine initially in 28%, but ultimately 19% received both drugs during cooling. Dexmedetomidine was discontinued or decreased in 48% due to bradycardia or inadequate sedation. An example of heart rate trend on dexmedetomidine is shown in Figure 1. HRC are shown in Table 1. There were no statistically significant differences in HRC between late preterm versus term groups. Infants receiving dexmedetomidine had significantly lower heart rate (p=0.004), skewness (p=0.011) and kurtosis (p=0.031) from 12-24h after birth compared to infants receiving exclusively fentanyl.

Conclusions: In this cohort, dexmedetomidine dose was often limited or discontinued due to concern for worsening bradycardia or inadequate sedation, ultimately requiring a different sedating agent. Use of these HRC as biomarkers for degree of encephalopathy was not impacted by GA, but was impacted by dexmedetomidine.