Anesthesia and analgesia
October 16, 2026 · via Europe PMC
Effects of Ketamine and Esketamine on Postoperative Delirium After General Anesthesia: A Meta-Analysis and Meta-Regression Analysis.
Li S, Zhou W, Li P, Hu Y
AI summary — for doctors, generated from the abstract only
Ketamine and esketamine may reduce postoperative delirium, but evidence is inconclusive.
What was studied
A meta-analysis of 25 RCTs (3344 patients).
Key findings
- Ketamine RR 0.69 (95% CI 0.49-0.98); esketamine RR 0.58 (0.36-0.95)
- Effect seen at 2 to 7 days but not within 24 hours
- Dizziness increased (RR 1.45, 95% CI 1.14-1.84)
- Trial sequential analysis indicated insufficient information size
Clinical relevance
Not enough to recommend routine use; dizziness is a cost.
Who should care
Limitations
Heterogeneity, TSA shows inconclusive evidence, and depressive symptom finding rests on 2 studies.
A potential signal needing large RCTs.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
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.
DOI
10.1213/ANE.0000000000008380
PMID
42887017
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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