INTRODUCTION: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: Administration of ketamine via nebulization for patients with acute painful conditions provided equivalent analgesia with similar safety profile when compared to active controls.
CLINICALTRIALS: gov Registration: N/A.
| Discipline Area | Score |
|---|---|
| Physician |  |
Physician rater
This is a useful source of available studies for practitioners interested in the topic. The clinical impact of the reported findings is unclear.
Physician rater
This systematic review and meta-analysis evaluated the analgesic efficacy and incidence of adverse effects of nebulized ketamine. The search was exhaustive and found 13 studies with 2496 participants overall, which showed equal efficacy of ketamine compared with intravenous (IV) morphine or IV ketamine, inhaled nitrous oxide, or inhaled dexmedetomidine. There were no serious adverse events in patients given ketamine and no difference in incidence of non-serious adverse events between the ketamine and other groups. Thus, administering ketamine via nebulization for patients with acute painful conditions provided equivalent analgesia with a similar safety profile compared with active controls.
Physician rater
This meta-analysis shows equivalent efficacy and safety of nebulized ketamine for pediatric emergency procedures.
Physician rater
Very useful study but, unfortunately very little Paediatric data available.
Physician rater
Intranasal ketamine may be a useful alternative to opioids and NSAIDs in the ED setting, but methodologically robust, multicenter, multi-arm trials are needed first.
Physician rater
No prior registration of the systematic review protocol. Very limited data in pediatric patients (2 case series).
, McMaster University