Esketamine around surgery was associated with less delirium in older patients

Design

Systematic review and meta-analysis of randomised controlled trials

Population

17 RCTs, 2914 surgical patients aged ≥60 (11 trials in delirium analysis)

Primary outcome

Postoperative delirium

Effect

OR 0.57 (0.40–0.82); PONV OR 0.49 (0.32–0.75); psychiatric adverse events OR 1.41 (0.67–2.96)

This meta-analysis pooled 17 randomised trials (2914 participants aged 60 or over) of perioperative esketamine — the S-enantiomer of ketamine — with 11 trials contributing to the delirium analysis.

Esketamine-containing regimens were associated with less postoperative delirium (OR 0.57, 95% CI 0.40 to 0.82; I² 45.8%). Four small trials suggested less postoperative cognitive dysfunction (OR 0.39, 0.22 to 0.71), on very low-certainty evidence. Nausea and vomiting were also reduced (OR 0.49), and psychiatric adverse events were not significantly increased (OR 1.41, 0.67 to 2.96). There was no clear relationship between cumulative dose and delirium risk.

Most trials were Chinese, and perioperative care varied widely. The finding is encouraging but not yet a reason for geriatricians to ask for esketamine routinely; it is more useful as a prompt to discuss delirium prevention with the anaesthetic team before an older patient's operation. Esketamine availability in India is limited.

• Discuss a delirium prevention plan with the anaesthetist before surgery in any older patient at risk.
• Screen for delirium after surgery with the 4AT or CAM at least once per shift until postoperative day 5, as ESAIC guidance advises.
• Keep non-drug measures central: glasses, hearing aids, orientation, sleep, hydration, early mobilisation.
• Avoid benzodiazepines and strongly anticholinergic drugs perioperatively in older adults.
• Treat esketamine as a promising adjunct, not yet standard care.

Why it matters

Delirium after surgery drives long-term cognitive decline and institutionalisation, and drug prevention options are few.

Don't overread it

Heterogeneous, mostly single-country trials with retrospective protocol registration; the cognitive dysfunction finding is very low certainty.

The statistics, in plain English

An odds ratio of 0.57 means the odds of delirium were about 40% lower. If 20% of older patients would develop delirium without it, this corresponds to roughly 12–13% with it — about one fewer case per 13 to 15 patients treated.

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