Ketamine and esketamine may cut postoperative delirium, at a dizziness cost

Design

Meta-analysis of 25 randomised trials with trial sequential analysis

Population

3,344 adults having general anaesthesia

Primary outcome

Postoperative delirium incidence

Effect

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

A meta-analysis pooled 25 randomised trials (3,344 patients) of perioperative ketamine (9 trials) or esketamine (16) against placebo or usual care.

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). Benefit was clearer with higher doses (bolus over 0.5 mg/kg ketamine or 0.25 mg/kg esketamine), bolus plus infusion, and major surgery, and appeared when delirium was assessed over days 2 to 7 rather than the first 24 hours. Dizziness increased (RR 1.45). Trial sequential analysis judged the evidence inconclusive.

These results sit uneasily with the large PODCAST trial, which found no delirium benefit from intraoperative ketamine in older adults. Most trials here are small and many come from single regions.

This is a signal worth a large trial, not a reason to add ketamine routinely for delirium prevention.

• Do not add ketamine routinely for delirium prevention on this evidence.
• Continue proven delirium measures: orientation, sleep, hydration, mobilisation and avoiding deliriogenic drugs.
• If using ketamine for analgesia, warn about dizziness.
• Watch for a large multicentre trial before changing protocols.

Why it matters

Delirium prevention lacks a drug that works, and this keeps ketamine in question without settling it.

Don't overread it

Trial sequential analysis says the evidence is insufficient, and the largest earlier trial was negative.

The statistics, in plain English

A risk ratio of 0.69 means delirium was about 31% less common with ketamine, but the upper bound of 0.98 is close to no effect. Trial sequential analysis estimates how much evidence is needed for a firm conclusion; here it has not been reached.

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