Effects of Ketamine and Esketamine on Postoperative Delirium After General Anesthesia: A Meta-Analysis and Meta-Regression Analysis
In brief
Ketamine and esketamine were linked to 31% and 42% less postoperative delirium
A meta-analysis of 25 randomized trials involving 3,344 patients found lower delirium risk with ketamine and esketamine, especially with higher doses, combined bolus and infusion, and major surgery; no benefit appeared when delirium was assessed within 24 hours. Evidence remains inconclusive, dizziness increased, and larger trials are needed before routine use can be recommended.
- Journal
- Anesthesia and analgesia (Q1)
- Published
- 16 October 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Shuying Li, Wenqin Zhou, Ping Li, Yajiao Hu
- PMID
- 42887017
- DOI
- 10.1213/ANE.0000000000008380
Why clinicians should know about it
- Picked for Anesthesiology and Pain Medicine (paper of the day, 18 October 2026): Ketamine/esketamine effect on postoperative delirium
Abstract
BACKGROUND: Postoperative delirium (POD) is a frequent and serious complication, particularly in older adults undergoing major surgery. Pharmacologic prevention remains limited. This study aimed to evaluate whether perioperative ketamine or esketamine reduces POD incidence and to explore optimal administration strategies. METHODS: We systematically searched PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to January 2025 for randomized controlled trials (RCTs) comparing perioperative ketamine or esketamine with placebo or standard care. The primary outcome was POD incidence (risk ratio [RR]). Subgroup, meta‑regression, and trial sequential analysis (TSA) were performed. Sensitivity analyses addressed active comparators and unit‑of‑analysis issues. RESULTS: Twenty-five RCTs (3344 patients) were included (ketamine: 9; esketamine: 16). Both agents reduced POD risk versus control (ketamine: RR 0.69, 95% CI, 0.49-0.98, P = .04; esketamine: RR 0.58, 95% CI, 0.36-0.95, P = .03). Benefit was 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. The effect was observed when POD was assessed 2 to 7 days postoperatively, but not within 24 hours. TSA indicated that current evidence remains inconclusive due to insufficient information size. Dizziness risk increased (RR 1.45, 95% CI, 1.14-1.84, P = .002), while postoperative depressive symptoms decreased (RR 0.78, 95% CI, 0.63-0.96, P = .02; based on 2 studies, 493 patients). CONCLUSIONS: 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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.