Ketamine and esketamine were linked to less delirium, but the evidence is not yet settled

Design

Meta-analysis and meta-regression of 25 randomised trials, with trial sequential analysis

Population

3,344 patients having surgery under general anaesthesia

Primary outcome

Incidence of postoperative delirium

Effect

Ketamine RR 0.69 (0.49–0.98); esketamine RR 0.58 (0.36–0.95); dizziness RR 1.45

This meta-analysis pooled 25 randomised trials of 3,344 patients comparing perioperative ketamine (9 trials) or esketamine (16 trials) with placebo or usual care, with delirium as the primary outcome.

Both were associated with less postoperative delirium: ketamine RR 0.69 (95% CI 0.49 to 0.98) and esketamine RR 0.58 (0.36 to 0.95). The effect was clearer with higher doses (single bolus above 0.5 mg/kg ketamine or 0.25 mg/kg esketamine), with bolus plus infusion, and in major surgery, and appeared when delirium was assessed from day 2 to day 7 rather than in the first 24 hours. Dizziness increased (RR 1.45). Trial sequential analysis judged the total evidence too small to be conclusive.

This is a signal, not a recommendation. Many of the trials are small and single-centre, and the largest earlier trial of intraoperative ketamine for delirium was negative. Ketamine remains a reasonable part of opioid-sparing analgesia; adding it solely to prevent delirium is not yet supported.

• Do not add ketamine solely to prevent delirium until larger trials report.
• Where ketamine is already part of multimodal analgesia, a delirium benefit is possible but unproven.
• Expect more dizziness; consider this in older patients at risk of falls.
• Screen high-risk patients for delirium daily from day 1 to day 7, not only in recovery.
• Keep non-drug prevention measures as the foundation.

Why it matters

A cheap drug already in theatre shows a possible delirium benefit, which raises the stakes for a definitive trial.

Don't overread it

Trial sequential analysis found the evidence inconclusive, and the dose findings come from subgroup analyses.

The statistics, in plain English

An RR of 0.69 means about 31% fewer cases in relative terms. The ketamine interval's upper limit (0.98) sits close to 1.0, so the true effect could be small. Trial sequential analysis asks whether enough patients have been studied to trust a result; here the answer was no.

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