Effectiveness and safety of intranasal fentanyl for pain management in infants aged 0 to 6 months: a systematic review.

OBJECTIVE

The objective of this review was to evaluate the effectiveness and safety of intranasal fentanyl for the management of procedural pain in infants aged 0 to 6 months.

INTRODUCTION

Procedural pain in early infancy is frequently undertreated, with limitations in both pharmacological and non-pharmacological interventions. Retinopathy of prematurity screening is a painful procedure for infants, and although sucrose and topical anesthetics are standard, their analgesic effect is often inadequate. Intranasal fentanyl may offer an effective adjunct; however, its use in infants under 6 months has not been systematically reviewed.

ELIGIBILITY CRITERIA: This review included randomized controlled trials evaluating intranasal fentanyl in infants ≤6 months of corrected age undergoing painful procedures, compared with placebo, no treatment, or alternative analgesics. Studies with <20% of infants in this age range or that focused on chronic pain were excluded.

METHODS

This systematic review followed JBI methodology and was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A 3-step search strategy was performed in MEDLINE (Ovid), Embase, CINAHL (EBSCOhost), Scopus, and Cochrane CENTRAL, with a final search date of February 2025, with no date or language restrictions in the search. The studies were selected and critically appraised by 2 reviewers independently. Data were extracted and synthesized using a meta-analysis or narrative summary, as appropriate. The certainty of the evidence was assessed using a standardized approach. No deviations from the protocol were observed.

RESULTS

Two randomized controlled trials (n=153 preterm infants) evaluated intranasal fentanyl (2 mcg/kg) during retinopathy of prematurity screening. In one trial, adding intranasal fentanyl to sucrose (plus topical anesthetic and physical containment) reduced pain scores on the Premature Infant Pain Profile-Revised scale vs sucrose alone, whereas another trial found that intranasal (2 mcg/kg) and intravenous (1 mcg/kg) fentanyl without routine sucrose did not outperform sucrose. Serious adverse events were not observed; transient apnea/desaturation resolved with minimal stimulation. Certainty was low to moderate due to imprecision and inconsistency. Findings were specific to preterm infants undergoing retinopathy of prematurity screening.

CONCLUSIONS

Intranasal fentanyl may reduce procedural pain in stable preterm infants, with no serious safety concerns. However, the findings are based on 2 small trials with methodological limitations and moderate risk of bias. Further high-quality research is needed to confirm the efficacy, optimize dosing, and assess the safety in broader infant populations.

REVIEW REGISTRATION: PROSPERO CRD42024551524.