Effect of Fentanyl for Preterm Infants on Mechanical Ventilation: A Systematic Review and Meta-Analysis

Introduction: Because excessive physical stress is harmful, reducing pain and discomfort in premature neonates during mechanical ventilation is a major challenge for physicians. There are no consensus and systematic review on the use of fentanyl, the most commonly used pain reliever in preterm neonates during mechanical ventilation. We aim to compare the benefits and harms of fentanyl versus placebo or no drug for preterm neonates receiving mechanical ventilation. Methods: A systematic review of randomized controlled trials (RCTs) was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions. The systematic review was reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Scientific databases such as MEDLINE, Embase, CENTRAL, and CINAHL were searched. All preterm infants on mechanical ventilation and enrolled in an RCT of fentanyl versus control were included. Results: Of 256 reports initially retrieved, 4 reports met the eligibility criteria. Fentanyl was not associated with mortality risk compared to the control (risk ratio: 0.72, 95% confidence intervals [CIs]: 0.36-1.44). No increase in ventilation duration (mean difference [MD]: 0.04, 95% CIs: -0.63-0.71) and no effect on hospital stay length (MD: 4.00, 95% CIs: -7.12-15.12) were found. Fentanyl intervention does not affect any other morbidities, including bronchopulmonary dysplasia, periventricular leukomalacia, patent ductus arteriosus, intraventricular hemorrhage (IVH), severe IVH, sepsis, and necrotizing enterocolitis. Conclusion: The present systematic review and meta-analysis failed to demonstrate the benefit of administering fentanyl to preterm infants on mechanical ventilation in mortality and morbidities. Follow-up studies are required to investigate the long-term neurodevelopment of the children.