Effects of ketamine on postoperative cognition: a scoping review

Postoperative delirium and other forms of perioperative neurocognitive deficits occur commonly in older adult patients. Ketamine, administered either before or during general anaesthesia, may have cognitive-sparing properties owing to its ability to reduce neuroinflammation, increase neurotrophin levels, or allow reductions in the doses of other general anaesthetic drugs. However, the efficacy of ketamine in preventing perioperative neurocognitive disorders remains highly controversial. This scoping review summarises clinical studies that examined the cognitive-sparing properties of ketamine in adult surgical patients. Clinical trials and retrospective cohort analyses that assessed cognition in adult patients after treatment with racemic (R,S) ketamine, esketamine, or arketamine were identified through a systematic search of the Embase and Embase Classic databases (from 1947 to 2025). Overall, we identified 58 studies involving 6830 patients. Most studies (n=31) evaluated postoperative delirium and, of these, most used a derivative of the Confusion Assessment Method as the primary measurement tool (81%). Thirty-nine studies evaluated other types of perioperative neurocognitive disorders; of these, 24 (62%) used the Mini Mental State Examination and six (15%) used the Montreal Cognitive Assessment. Ketamine produced no cognitive benefits in 35 of the 58 studies (60%), whereas 23 studies (40%) reported a reduced incidence or duration of perioperative neurocognitive disorders, or both. There were no clear trends in terms of the doses, enantiomeric formulations, or timing of ketamine administration associated with favourable cognitive outcomes. However, ketamine studies that evaluated cognition at only early postoperative timepoints were more likely to report no cognitive benefit. Most trials were underpowered to detect changes in cognitive endpoints, and study populations and methods were too heterogeneous to support meaningful meta-analyses. Although the current results summarised in this extensive review are inconsistent, the data nevertheless support the need for larger, well-designed trials to determine whether subgroups of patients that undergo specific types of surgeries might benefit from ketamine. Recommendations regarding the direction of future research are proposed.