- Design
- Systematic review and meta-analysis of 25 RCTs with trial sequential analysis
- Population
- 3,344 surgical patients receiving ketamine or esketamine vs control
- Primary outcome
- Postoperative delirium incidence
- Effect
- Ketamine RR 0.69 (95% CI 0.49–0.98); esketamine RR 0.58 (0.36–0.95)
This meta-analysis pooled 25 randomised trials (3,344 patients) of perioperative ketamine (9 trials) or esketamine (16) against placebo or standard care, with postoperative delirium as the primary outcome.
Both were associated with less delirium: ketamine RR 0.69 (95% CI 0.49 to 0.98) and esketamine RR 0.58 (0.36 to 0.95). The effect appeared larger with higher doses, bolus-plus-infusion and major surgery, and was seen when delirium was assessed on days 2 to 7 but not within 24 hours. Dizziness increased (RR 1.45). Two small studies suggested fewer depressive symptoms.
Trial sequential analysis judged the evidence inconclusive: there are not yet enough patients to be confident. The authors themselves do not recommend routine use. Esketamine is not widely available in India, while racemic ketamine is.
- Do not add ketamine routinely to prevent delirium; the evidence is not yet conclusive.
- Consider it where it already has an analgesic role in a high-risk older patient, recognising the delirium signal is uncertain.
- Warn patients about dizziness, which was more common.
- Keep established non-drug delirium prevention as the foundation.
Why it matters
It explains why a drug many already give for analgesia cannot yet be credited with preventing delirium.
Don't overread it
Trial sequential analysis judged the evidence insufficient; this does not establish that ketamine prevents delirium.
The statistics, in plain English
Risk ratios of 0.58–0.69 suggest about a third fewer cases, but the upper limits are close to 1. Trial sequential analysis asks whether enough patients have been studied to trust the result; here the answer was no.
Read the rest in the app
You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.
Scan to keep reading on your phone. No account needed to start.
Tomorrow morning, before your first patient
One edition a day for anaesthesiology, written by the desk, every claim tied to its paper. Six minutes.
Get the app — free