Effect of Fentanyl Boluses on Cerebral Oxygenation and Hemodynamics in Preterm Infants: A Prospective Observational Study

Abstract

<b><i>Background:</i></b> Fentanyl is a commonly used off-label medication for pain control and sedation in preterm infants. Yet, the effect of fentanyl on cerebral hemodynamics in preterm neonates remains unexplored. <b><i>Objective:</i></b> To evaluate the effect of a bolus dose of fentanyl on the regional cerebral oxygen saturation (RcSO<sub>2</sub>), cerebral fractional tissue oxygen extraction (cFTOE) and left ventricular output (LVO) as compared with pre-administration baseline in preterm infants. <b><i>Methods:</i></b> This was a prospective observational study conducted in a level III Canadian NICU from September 2017 to February 2019. Preterm infants born <37 weeks of gestation and scheduled to receive a fentanyl bolus (1–2 μg/kg/dose) were eligible. Infants with major congenital anomalies, medically unstable and those who had received fentanyl in the previous 48 h were excluded. <b><i>Outcomes:</i></b> The primary outcome was the difference between RcSO<sub>2</sub> measured 5 min prior to and RcSO<sub>2</sub> measured at defined time points after administration of fentanyl. <b><i>Results:</i></b> Twenty-eight infants were enrolled during the study period (median gestational age 28 weeks; interquartile range [IQR] 25–29 weeks; median birth weight 1,035 g [IQR 830–1,292 g]; median age 4 days [IQR 3–7 days]). Mean (±standard deviation) baseline RcSO<sub>2</sub> was 73.6% (±11.8), cFTOE was 21.9 (±11.2) and LVO was 380 (±147) mL/kg/min prior to fentanyl infusion. One-way ANOVA showed no statistically significant difference between baseline and any of the post-fentanyl cerebral oxygenation, tissue oxygen extraction or cardiac output measures (<i>p</i> > 0.05). <b><i>Conclusion:</i></b> Administration of fentanyl bolus for procedural pain and sedation was not shown to significantly affect cerebral oxygenation, cerebral tissue oxygen extraction or cardiac output in stable preterm infants.

Clinical Pharmacology of Fentanyl in Infants and Children

“…Fentanyl causes different adverse-effects in infants and children [4]. Fentanyl produces different effects in infants and children [14][15][16][17]. Intravenous fentanyl reduces pain and induces sedation in infants and does not affect cerebral oxygenation or cardiac output in preterm infants [14], and fentanyl co-administered with bupivacaine during labour does not depress neonatal respiratory or adversely affect neurobehavioral scores in infants [15].…”

“…Fentanyl produces different effects in infants and children [14][15][16][17]. Intravenous fentanyl reduces pain and induces sedation in infants and does not affect cerebral oxygenation or cardiac output in preterm infants [14], and fentanyl co-administered with bupivacaine during labour does not depress neonatal respiratory or adversely affect neurobehavioral scores in infants [15]. Intranasal fentanyl use during halothane or sevoflurane anaesthesia for tympanosotomy tube placement is associated reduced postoperative agitation without increase adverseeffects or discharge times [16].…”

“…Administration of fentanyl bolus for procedural pain and sedation is not shown to significantly affect cerebral oxygenation, cerebral tissue oxygen extraction, or cardiac output in stable preterm infants [14]. Fentanyl added to epidural bupivacaine infusions during labour does not depress neonatal respiration or adversely affect neurobehavioral scores and other indices of neonatal welfare [15].…”

Assessment and Management of Pain in Preterm Infants: A Practice Update

“…In a randomized trial comparing the pharmacokinetics of fentanyl across 100 neonates, serum fentanyl concentrations were steady in the infants receiving a continuous infusion (1 mcg/kg loading dose followed by 1 mcg/kg/hour infusion) in contrast to wide fluctuations in serum concentration with high-peak concentrations in infants receiving bolus administration (1 mcg/kg/dose administered every four hours) [ 168 ]. Fentanyl bolus administration (1–2 μg/kg/dose) prior to procedural pain was not found to significantly affect cerebral oxygenation, cerebral tissue oxygen extraction, or cardiac output in stable preterm infants ( n = 28) [ 169 ]. Similarly, in a large national cohort study examining the association of early continuous infusions of opioids and/or midazolam with survival and sensorimotor outcomes at age two years in very premature infants who were ventilated, infants either received continuous opioid and/or midazolam infusion in the first week of life ( n = 450) or no treatment ( n = 472).…”