Abstract

Acute pain is a common reason for pediatric emergency department presentation, yet it remains frequently undertreated. Intranasal fentanyl is an established initial analgesic in this setting, but concerns about opioid-related adverse effects have increased interest in opioid-sparing alternatives. Intranasal sub-dissociative ketamine has shown promise, although direct comparisons with fentanyl remain limited. This systematic review compared the efficacy, onset of analgesia, need for rescue medication, and side-effect profile of intra nasal ketamine versus intranasal fentanyl in children presenting to the emergency department with acute moderate to severe pain. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. PubMed, Web of Science, and EBSCO databases were searched up to March 30, 2026. Eligible studies were randomized controlled trials involving children aged 0-18 years, and risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Four randomized controlled trials, including 263 patients, were analyzed: the PICHFORK trial, PRIME trial. Both intranasal ketamine and intranasal fentanyl produced clinically meaningful pain reduction from baseline, with no statistically significant difference in primary analgesic outcomes. In the PRIME trial, ketamine was declared non-inferior to fentanyl, with a pain-score improvement difference of 1.3 mm, within the predefined 10-mm margin. Rescue analgesia use was similar between groups. Side effects were more frequent with ketamine but were minor, transient, and required no intervention. No serious adverse events occurred. Overall, intranasal ketamine appears to be a clinically effective and manageable opioid-sparing alternative to intranasal fentanyl in pediatric emergency pain management.

Key words: Intranasal ketamine, intranasal fentanyl, pediatric emergency department, acute pain, opioid-sparing, systematic review