Efficacy and Safety of Continuous Infusion of Fentanyl for Pain Control in Preterm Newborns on Mechanical Ventilation

Abstract

To evaluate the analgesic superiority and the safety equivalence of continuous fentanyl infusions versus fentanyl boluses in preterm infants on mechanical ventilation. In this multicenter, double-blind, randomized controlled trial, mechanically ventilated newborns (≤ 32(+6) weeks gestational age) were randomized to fentanyl (continuous infusion of fentanyl plus open-label boluses of fentanyl) or placebo (continuous infusion of placebo plus open-label boluses of fentanyl). The primary endpoint was analgesic efficacy, as evaluated by the Echelle Douleur Inconfort Nouveau-Né (EDIN) and Premature Infant Pain Profile scales. Safety variables were evaluated as well. Sixty-four infants were allocated to the fentanyl group, and 67 were allocated to the placebo group. The need for open-label boluses of fentanyl was similar in the 2 groups (P = .949). EDIN scores were comparable in the 2 groups; 65 of 961 (6.8%) EDIN scores were >6 in the fentanyl group and 91 of 857 (10.6%) in the placebo group (P = .003). The median Premature Infant Pain Profile score was clinically and statistically higher in the placebo group compared with the fentanyl group on days 1, 2, and 3 of treatment (P < .05). Mechanical ventilation at age 1 week was required in 27 of 64 infants in the fentanyl group (42.2%), compared with 17 of 67 infants in the placebo group (25.4%) (P = .042). The first cycle of mechanical ventilation was longer and the first meconium passage occurred later in the fentanyl group (P = .019 and .027, respectively). In very preterm infants on mechanical ventilation, continuous fentanyl infusion plus open-label boluses of fentanyl does not reduce prolonged pain, but does reduce acute pain and increase side effects compared with open-label boluses of fentanyl alone.