Abstract
We conducted a systematic review and meta-analysis to assess the efficacy and safety of intranasal (IN) analgesic-dose ketamine as compared to IN fentanyl for pediatric acute pain management in the emergency department (ED). We searched PubMed, Embase, and Scopus for randomized controlled trials from inception to December 2019 without language restrictions. Reference lists of articles were hand searched. We conducted a meta-analysis and random-effects models to evaluate efficacy (pain reduction and rescue analgesia) and safety outcomes (rates of adverse events and sedation). We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method to evaluate the quality of evidence for each outcome. A total of 546 studies were screened and 56 selected for full-text review. A total of 4 randomized controlled trials were included. In the meta-analysis of 4 studies, IN ketamine had similar reductions in pain scores from baseline to all post-intervention times (10 to 15 minutes: weighted mean difference [WMD] -1.42, 95% confidence interval [CI] -9.95 to 7.10; 30 minutes: WMD 0.40, CI -6.29 to 7.10; 60 minutes: WMD 0.64, CI -6.76 to 5.47). The use of IN ketamine was associated with similar rates of rescue analgesia when compared to fentanyl (RR 0.74, CI 0.44 to 1.25). IN ketamine had a higher risk of non-serious adverse events (RR 2.00, CI 1.43 to 2.79), and no patients receiving ketamine had a serious adverse event. There was one serious adverse event (hypotension) in the fentanyl group that self-resolved. No patients receiving either IN fentanyl or ketamine had significant sedation (University of Michigan Sedation Score > 2). The certainty in the pooled estimates was deemed to be “High” for all outcomes except for the outcome of rescue analgesia, which was downgraded because of imprecision given its wide confidence interval. Intranasal analgesic-dose ketamine was found to be as efficacious as IN fentanyl in regards to pain reduction at all time points. Ketamine was associated with higher rates of non-serious adverse events. Intranasal analgesic-dose ketamine may be considered as an opioid alternative for acute pain management in children.
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