Evidence regarding the analgesic efficacy of intraoperative low-dose ketamine in opioid-naïve patients remains inconsistent.

To evaluate the effects of intraoperative low-dose ketamine on postoperative pain outcomes in opioid-naïve patients.

We conducted a pre-registered systematic review and meta-analysis of randomized controlled trials identified through searches to August 2024. Two reviewers independently performed study selection and data extraction, assessed risk of bias using RoB 2, and rated certainty of evidence using GRADE.

A total of 18 randomized controlled trials involving 1339 participants were included. Compared with placebo, ketamine reduced resting pain scores at 1 h (SMD = −1.51, 95% CI − 2.25 to −0.77; GRADE: low), 6 h (SMD = −0.92, 95% CI − 1.51 to −0.23; GRADE: very low), and 24 h postoperatively (SMD = −0.62, 95% CI − 0.92 to −0.31; GRADE: low). Ketamine was also associated with reduced opioid consumption at 24 h (SMD = −1.69, 95% CI − 3.22 to −0.15; GRADE: low), but not at 48 h (SMD = −0.19, 95% CI − 0.46 to 0.07; GRADE: very low). In addition, the risk of requiring rescue analgesia was lower in the ketamine group (RR = 0.31, 95% CI 0.23 to 0.41; GRADE: moderate).

In opioid-naïve patients, intraoperative low-dose ketamine may provide analgesic benefit mainly in the early postoperative period, although the clinical benefit at 24 h appears limited. Its opioid-sparing effect does not appear sustained at 48 h. Given the substantial heterogeneity and low certainty of evidence, these findings should be interpreted with caution.