title: Efficacy and safety of continuous infusion of fentanyl for pain control in preterm newborns on mechanical ventilation.
abstract: OBJECTIVE
  To evaluate the analgesic superiority and the safety equivalence of continuous fentanyl infusions versus fentanyl boluses in preterm infants on mechanical ventilation.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Neonatology and Neonatal Intensive Care Unit, Department of Women's, Child's and Adolescent's Health, Sant'Orsola-Malpighi Hospital, Bologna, Italy. gina.ancora@libero.it
authors.forename: Gina
authors.initials: G
authors.lastname: Ancora
authors.forename: Paola
authors.initials: P
authors.lastname: Lago
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Garetti
authors.forename: Anna
authors.initials: A
authors.lastname: Pirelli
authors.forename: Daniele
authors.initials: D
authors.lastname: Merazzi
authors.forename: Maura
authors.initials: M
authors.lastname: Mastrocola
authors.forename: Luca
authors.initials: L
authors.lastname: Pierantoni
authors.forename: Giacomo
authors.initials: G
authors.lastname: Faldella
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000628:therapy*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D016015:Logistic Models; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D012121:Respiration, Artificial / Q000009:adverse effects*; D012131:Respiratory Insufficiency / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D005283:Fentanyl
keywords: EDIN; Echelle Douleur Inconfort Nouveau-Né; GA; Gestational age; NICU; Neonatal intensive care unit; PIPP; Premature Infant Pain Profile