Perioperative Esketamine and Postoperative Delirium in Older Adults
Postoperative delirium remains one of the perioperative complications that most alters a family’s hospital experience, and it is among 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, and the caveats are equally important.
Seventeen randomized trials were included, with about 2,914 participants aged 60 and older or otherwise labeled older by the investigators. Across the eleven trials reporting postoperative delirium (POD), esketamine-containing regimens were associated with lower odds of POD than control (OR about 0.57, 95% CI 0.40 to 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, and sensitivity analyses restricted to placebo-controlled trials remained in the same direction.
Where this fits in my practice
I read this review as support for considering low-dose esketamine as one adjunct within a multimodal plan for selected higher-risk older patients. It does not make esketamine 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 that of a strategy rather than a purified molecule. All included trials were conducted in China, and many were single-center, which limits how confidently the estimate can be exported to every U.S. operating room.
In my own approach, non-pharmacologic prevention still comes first: orientation, sleep, early mobilization, sensory aids, careful opioid stewardship, and avoidance of unnecessary deliriogenic drugs. Esketamine may help through analgesia, opioid sparing, and possible anti-inflammatory or glutamatergic effects, although in these trials those mechanisms remain more hypothesis than proven pathway. 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.
Implications for practice
In older adults, pooled RCTs associated perioperative esketamine-containing strategies with a lower incidence of postoperative delirium, with moderate-certainty evidence in this review. Longer-term cognitive outcomes remain uncertain, and we should not over-promise prevention of lasting cognitive decline. Because background anesthesia and analgesia differed across trials, the benefit is best interpreted as part of multimodal care. Psychiatric adverse events were not clearly increased here, but monitoring and patient selection still matter.
Non-drug delirium prevention remains the foundation. I consider esketamine selectively, when its analgesic and opioid-sparing effects and the local protocol fit the individual 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.