Efficacy and safety of continuous infusion of fentanyl for pain control in preterm newborns on mechanical ventilation

J Pediatr. 2013 Sep;163(3):645-51.e1. doi: 10.1016/j.jpeds.2013.02.039. Epub 2013 Apr 10.


Objective: To evaluate the analgesic superiority and the safety equivalence of continuous fentanyl infusions versus fentanyl boluses in preterm infants on mechanical ventilation.

Study design: 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.

Results: 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).

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT00571636.

Keywords: EDIN; Echelle Douleur Inconfort Nouveau-Né; GA; Gestational age; NICU; Neonatal intensive care unit; PIPP; Premature Infant Pain Profile.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / adverse effects
  • Analgesics, Opioid / therapeutic use
  • Double-Blind Method
  • Female
  • Fentanyl / administration & dosage*
  • Fentanyl / adverse effects
  • Fentanyl / therapeutic use
  • Follow-Up Studies
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases / therapy*
  • Infusions, Intravenous
  • Injections, Intravenous
  • Logistic Models
  • Male
  • Pain / drug therapy*
  • Pain / etiology
  • Pain Measurement
  • Respiration, Artificial / adverse effects*
  • Respiratory Insufficiency / therapy*
  • Treatment Outcome


  • Analgesics, Opioid
  • Fentanyl

Associated data

  • ClinicalTrials.gov/NCT00571636