Effect of dexmedetomidine on heart rate in neonates with hypoxic ischemic encephalopathy undergoing therapeutic hypothermia

Abstract

BACKGROUND: Sedation is recommended to optimize neuroprotection in neonates with hypoxic ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). Dexmedetomidine is an alternative agent to opioids, which are commonly used but have adverse effects. Both TH and dexmedetomidine can cause bradycardia. In this study, we describe our experience with dexmedetomidine and fentanyl in neonates undergoing TH for HIE, with a focus on heart rate (HR). METHODS: We performed a retrospective chart review from 2011–2019 at a level IV NICU comparing sedation with dexmedetomidine (n = 14), fentanyl (n = 120), or both (n = 32) during TH for HIE. HR trends were compared based on sedation and gestational age. Neonates were included if they underwent TH and received sedation and were excluded if cooling was initiated past 24 hours(h) of life or required ECMO. RESULTS: Of the 166 neonates included, 46 received dexmedetomidine, 14 as monotherapy and 32 in combination with fentanyl. Mean hourly HR from 12–36 h after birth was significantly lower for infants on dexmedetomidine versus fentanyl monotherapy (91±9 vs. 103±11 bpm, p < 0.002). Dexmedetomidine was decreased or discontinued in 22 (47.8%) neonates, most commonly due to inadequate sedation with a low HR. Lower gestational age was associated with higher HR but no significant difference in dexmedetomidine-related HR trends. CONCLUSIONS: Despite an association with lower HR, dexmedetomidine may be successfully used in neonates with HIE undergoing TH. Implementation of a standardized protocol may facilitate dexmedetomidine titration in this population.

Protective Effect of Dexmedetomidine against Hyperoxia-Damaged Cerebellar Neurodevelopment in the Juvenile Rat

“…DEX demonstrated a shorter treatment time per se, as well as a shorter time of mechanical ventilation, compared to fentanyl in premature infants [ 39 ]. Frequently, a reduction in additional midazolam or morphine administration can be detected [ 40 , 122 ], though the frequency of bradycardia in preterm infants has also increased [ 123 , 124 ]. Due to the discussed neuroprotective effect of DEX, an anti-oxidative effect should be primarily discussed.…”

Heart Rate and Pulse Oximetry Dynamics in the First Week after Birth in Neonatal Intensive Care Unit Patients and the Risk of Cerebral Palsy

“…Another clinical variable that we did not account for is therapeutic hypothermia which is used for term and late preterm infants with evidence of moderate-to-severe HIE, 35 36 which is associated with lower HR and might impact HR variability. 37 Additionally, our models only included clinical and demographic variables that were known at birth and did not account for clinical interventions including procedures, medications, and respiratory support or medical and neurological comorbidities that impact HR and SpO 2 dynamics. For example, preterm infants receive caffeine in the first week after birth to minimize central apnea and this might impact HR and SpO 2 patterns.…”

Effective Perturbations by Small-Molecule Modulators on Voltage-Dependent Hysteresis of Transmembrane Ionic Currents

“…Dexmedetomidine that viably and directly targets ionic channels [ 15 , 19 ] is therefore expected to have a significant therapeutic potential. However, whether dexmedetomidine-induced bradycardia or different cardioprotective action [ 20 ] is pertinent to its inhibitory effect on the magnitude and Hys (V) of I h intrinsically in heart cells warrants further investigations.…”