TOPLINE

Perioperative administration of ketamine and esketamine was associated with a reduced risk for postoperative delirium among adult patients undergoing various surgical procedures under general anesthesia. However, trial sequential analysis (TSA) revealed that the current evidence remains insufficient to draw firm conclusions.

METHODOLOGY

• Researchers conducted a meta-analysis of 25 randomized controlled trials involving 3344 adult patients undergoing general anesthesia for various surgical procedures.
• Ketamine was studied in nine trials and esketamine in 16 trials, comparing perioperative administration of these agents vs placebo (saline) or standard analgesic or anesthetic therapy.
• The main outcome was the incidence of postoperative delirium assessed using validated tools such as the Confusion Assessment Method (CAM), CAM-ICU, or others.
• Subgroup analyses were conducted by type of drugs, age of patients (< 60 vs ≥ 60 years), dosing regimens (high vs low single dose and cumulative dose), route of administration (bolus only vs bolus plus infusion), surgical type (major vs minor), and the time of assessment of postoperative delirium.
• TSA was performed to determine whether the cumulative evidence was robust.

TAKEAWAY

• Both ketamine and esketamine were associated with a reduced risk for postoperative delirium vs control regimens (risk ratio [RR], 0.69; P = .04; I² = 47% and RR, 0.58; P = .03; I² = 52%, respectively).
• High-dose regimens with a single bolus of ketamine at more than 0.5 mg/kg or esketamine at more than 0.25 mg/kg were associated with a reduced risk for postoperative delirium (RR, 0.59; P = .008), with similar findings for a cumulative dose of more than 1.0 mg/kg ketamine or more than 0.5 mg/kg esketamine (RR, 0.60; P = .02).
• Administration via bolus plus infusion was associated with a lower risk for postoperative delirium (RR, 0.58; P = .001). The risk was also reduced with the assessment of delirium at 2-7 days (RR, 0.71; P = .01).
• The intervention was also associated with an elevated risk for dizziness (RR, 1.45; P = .002; I² = 0%). TSA findings indicated that the current evidence is inconclusive.

IN PRACTICE

"[W]hile perioperative ketamine and esketamine show a potential signal for reducing POD [postoperative delirium] in high-risk surgical patients when administered via optimized, high-dose regimens, the current evidence is inconclusive. The potential benefit must be carefully weighed against the increased risk of dizziness and possible dissociation. Taken together, these findings suggest a rational framework for future Phase III trials," the researchers wrote.

SOURCE

The study was led by Shuying Li, MD, of the Department of Anesthesiology at the West China Second Hospital of Sichuan University in Chengdu, China. It was published online on October 16 in Anesthesia & Analgesia.

LIMITATIONS

The analysis relied on numerous small, underpowered trials with notable heterogeneity in methodology, including variations in delirium assessment tools and the time and frequency of assessment. Subgroup analyses, though prespecified, retain study-level observational characteristics. Safety evaluation focused on adverse events at a short term; neurocognitive and psychological effects in the long term remain uncertain.

DISCLOSURES

The study did not receive any specific funding. The authors reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.