Perioperative medicine & outcomes
Effects of Ketamine and Esketamine on Postoperative Delirium After General Anesthesia: A Meta-Analysis and Meta-Regression Analysis
Authors' conclusion
Perioperative ketamine and esketamine show a potential signal for POD reduction, particularly with optimized dosing in high-risk patients. However, the evidence is currently inconclusive, and increased dizziness risk precludes routine recommendation. Large, multicenter RCTs are urgently needed.
Study context
- Population
- Patients undergoing surgery under general anesthesia in randomized controlled trials (RCTs) comparing perioperative ketamine or esketamine with placebo or standard carepatients in twenty-five RCTs · ketamine RCTs 9 · esketamine RCTs 16
- Participants
- 3,344 patients
- Comparison
- Perioperative ketamine or esketamine vs placebo or standard care
- Outcome
- POD incidence
Methodological detailssystematic search, subgroup analysis, trial sequential analysis, sensitivity analyses
- Systematic search
- Subgroup analysis
- Trial sequential analysis
- Sensitivity analyses
Pooled result
As reported in the abstract
Each group vs controlRelative risk (95% CI)P value
Ketamine
0.69(0.49–0.98)
P = 0.04Esketamine
0.58(0.36–0.95)
P = 0.03Further pooled results
| Outcome | RR (95% CI) | P value | |
|---|---|---|---|
| Postoperative depressive symptomsKetamine or esketamine vs control · based on 2 studies, 493 patients | 0.78 (0.63–0.96) | P = 0.02 | |
| 0.512Relative risk (log scale) |
Postoperative delirium (POD), subgroups
- Benefit more evident with high-dose regimens (single bolus: ketamine >0.5 mg/kg or esketamine >0.25 mg/kg; cumulative dose: ketamine >1.0 mg/kg or esketamine >0.5 mg/kg), bolus-plus-infusion, and in major surgery
- Effect observed when POD assessed 2 to 7 days postoperatively, but not within 24 hours
Trial sequential analysis
- Current evidence remains inconclusive due to insufficient information size
Safety
| Outcome | RR (95% CI) | P value | |
|---|---|---|---|
| DizzinessKetamine or esketamine vs control | 1.45 (1.14–1.84) | P = 0.002 | |
| 0.512Relative risk (log scale) |
Original publication
Effects of Ketamine and Esketamine on Postoperative Delirium After General Anesthesia: A Meta-Analysis and Meta-Regression Analysis. Anesth Analg. Published 16 October 2026. doi:10.
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