Nebulized ketamine for acute pain management in the Emergency Department: A systematic review and meta-analysis

Ketamine administered in sub-dissociative doses has been effective in managing a variety of painful conditions in the emergency department (ED) and pre-hospital settings. The inhalation route of ketamine administration has gained traction over the past 5 years.

We conducted a systematic review and meta-analysis to evaluate the analgesic efficacy and incidence of adverse effects of nebulized ketamine. We searched Ovid CENTRAL, EMBASE, and MEDLINE databases for randomized controlled trials (RCTs) and observational studies from inception to January 2025, assessing pain reduction, rescue analgesia, and occurrences of adverse effects. We used the Cochrane Collaboration tool and a modified Newcastle-Ottawa Scale to evaluate the risk of bias and the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation) to evaluate the confidence in the evidence. Mean differences with 95 % confidence intervals (CI) using random effects were used for the meta-analyses.

Thirteen studies met the inclusion criteria. Nebulized ketamine had equivalent efficacy to active controls in 8 RCT's. Four RCTs (n = 601) demonstrated no difference in pain reduction between nebulized ketamine and IV morphine with mean difference (MD) 0.28 (CI -0.18 to 0.73) at 30 min, and similar rates of rescue analgesia (16.9 % vs. 17.4 %). Eleven studies reported absence of serious events and no difference in non-serious adverse events (39.1 % ketamine and 37.8 % controls). The level of confidence for the outcomes was deemed to be very low.

Administration of ketamine via nebulization for patients with acute painful conditions provided equivalent analgesia with similar safety profile when compared to active controls.

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