Perioperative ketamine administration to prevent delirium and neurocognitive disorders after surgery: a systematic review and meta-analysis

BACKGROUND: Surgery induces high rates of cognitive disorders, persisting for up to 12 months in elderly adults. This review aimed to assess the currently debated preventive effect of perioperative ketamine on postoperative delirium and postoperative neurocognitive disorders (POND). MATERIALS AND METHODS: Systematic review and meta-analysis including all randomized controlled trials investigating the effects of perioperative ketamine administration in adult patients compared to placebo or no intervention on postoperative delirium and/or POND between January 2007 and April 2022. Database searches were conducted in PubMed, Medline, Embase, Scopus, and Central. Random effects models were used to pool overall estimates. The GRADE approach was used to assess the quality of the evidence. RESULTS: From 1379 records screened, 14 randomized controlled trials with 1618 patients randomized met our inclusion criteria with a high level of consensus among reviewers, amongst whom 50% were at low-moderate risk of bias. There was no between-group difference in postoperative delirium [8 trials, 1265 patients, odds ratio (OR) 0.93, 95% CI (0.51–1.70), I (2)=28%] and POND [5 trials, 494 patients, OR 0.52, 95% CI (0.15–1.80); I (2)=78%]. There was no significant between-group difference in postoperative psychological adverse effects, level of pain, hospital length of stay, or mortality. Between-group subgroup analyses showed no difference in delirium or POND incidence according to surgical setting, ketamine dose, mode of administration, combination or not with other drug(s), and assessment timing or definition of cognitive disorders. CONCLUSION: Perioperative ketamine does not prevent postoperative delirium or POND. Significant study heterogeneity suggests that standardized measures for POND assessment and a specific focus on patients at high risk for POND should be used to improve the comparability of future studies.