Perioperative Esketamine and Postoperative Delirium in Older Adults
Postoperative delirium remains one of the perioperative complications that most changes a family’s hospital experience—and one of the hardest to prevent with a single drug. A September 14, 2026 open-access systematic review and meta-analysis in BMC Geriatrics asked whether perioperative esketamine-containing strategies reduce delirium in older surgical patients. The pooled signal is interesting; the caveats are equally important.
Seventeen randomized trials (about 2,914 participants aged 60 and older, or otherwise labeled older by investigators) were included. Across eleven trials reporting postoperative delirium (POD), esketamine-containing regimens were associated with lower POD odds versus control (OR about 0.57, 95% CI 0.40–0.82; moderate GRADE certainty). A smaller set of trials suggested a possible reduction in early postoperative cognitive dysfunction or delayed neurocognitive recovery, but certainty was very low. PONV was lower with esketamine strategies; psychiatric adverse events were not clearly increased, though event counts were sparse. Exploratory dose–response work did not show a clean relationship between cumulative esketamine exposure and POD risk. Sensitivity analyses restricted to placebo-controlled trials remained in the same direction.
What this changes—and what it doesn’t
I read this as supportive of considering low-dose esketamine as one adjunct inside a multimodal plan for selected higher-risk older patients—not as a stand-alone delirium vaccine. The authors themselves stress that many protocols bundled esketamine with other analgesic or anesthetic choices, so the pooled effect is the effect of a strategy, not a purified molecule. All included trials were conducted in China and many were single-center, which limits how confidently we export the estimate to every U.S. OR.
Non-pharmacologic prevention still comes first in my mental model: orientation, sleep, early mobilization, sensory aids, careful opioid stewardship, and avoiding unnecessary deliriogenic drugs. Esketamine may help via analgesia, opioid sparing, and possible anti-inflammatory or glutamatergic effects—but those mechanisms are still more hypothesis than proven pathway in these trials. I also keep the older ketamine literature in view: prior large work on intraoperative ketamine for delirium prevention has been mixed, so humility is warranted even when a newer enantiomer looks promising in pooled smaller trials.
Clinical takeaways
- Pooled RCTs in older adults associated perioperative esketamine-containing strategies with lower postoperative delirium incidence (moderate-certainty evidence in this review).
- Longer-term cognitive outcomes remain uncertain; do not over-promise prevention of lasting cognitive decline.
- Interpret the benefit as part of multimodal care—background anesthesia and analgesia differed across trials.
- Psychiatric adverse events were not clearly increased here, but monitoring and patient selection still matter.
- Keep non-drug delirium prevention as the foundation; consider esketamine selectively when analgesia, opioid sparing, and local protocol fit the patient.
Source
- Qi R, et al. Perioperative esketamine-containing strategies and postoperative neurocognitive outcomes in older surgical patients: a systematic review and meta-analysis of randomized controlled trials with certainty assessment. BMC Geriatrics. Published September 14, 2026. Article (PROSPERO CRD420261370159)
This post is clinician commentary for educational discussion. It is not medical advice for any reader’s personal care. Anesthesia and perioperative decisions should be made with the treating clinician based on the individual patient’s circumstances.