Effect of perioperative esketamine on postoperative recovery in breast cancer patients undergoing modified radical mastectomy: A systematic review and meta-analysis.

Abstract

e24074 Background: Modified radical mastectomy (MRM) is associated with significant acute postoperative and potential chronic pain. Esketamine offers potent analgesia with a theoretically more favorable side-effect profile than racemic ketamine, though its impact on recovery appears dependent on dosing strategies. This NMDA receptor antagonist may mitigate central sensitization, which is critical for preventing persistent post-surgical pain. This study evaluated the effect of esketamine on pain intensity, quality of recovery, and clinical efficiency in the context of MRM. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted, comparing perioperative esketamine to placebo or active control in patients undergoing MRM. Databases searched included PubMed, EMBASE, and Cochrane Library. Risk of bias was assessed using the Cochrane tool. Primary outcomes included 24-hour Visual Analogue Scale (VAS) pain scores and Day-1 Quality of Recovery-15 (QoR-15) scores. Secondary outcomes were the requirement for rescue analgesia, time to extubation, and duration of PACU stay. Random-effects models and subgroup analyses (bolus vs. infusion; dose levels) were utilized to investigate heterogeneity and clinical variables. Results: Nine RCTs (n = 749) met the inclusion criteria. Esketamine reduced 24-hour VAS scores (WMD -0.85; 95% CI -1.03 to -0.66). Subgroup stratification revealed this effect was associated with continuous infusion (WMD -1.07; 95% CI -1.20 to -0.94; I2 = 0%), whereas single-bolus administration showed no significant effect (WMD 0.01). Quality of recovery (QoR-15) scores improved (WMD 8.01; 95% CI 5.95 to 10.08), with greater improvements observed in low-dose protocols (WMD 11.50). Furthermore, low-dose esketamine did not increase the incidence of adverse psychotropic effects or postoperative nausea and vomiting. Esketamine was associated with a 69% reduction in the risk of requiring rescue analgesia (RR 0.31; 95% CI 0.16 to 0.60). Regarding efficiency, esketamine did not delay extubation (WMD -0.16 min). PACU stay duration exhibited a dose-dependent divergence: low-dose regimens shortened stays (WMD -2.85 min; P = 0.02), while high-dose combinations prolonged them (WMD 6.78 min; P < 0.00001). Conclusions: The data suggests that continuous intraoperative esketamine infusion, rather than single-bolus dosing, is associated with improved analgesic outcomes and quality of recovery in breast cancer surgery. Low-dose regimens appear to improve recovery metrics without delaying extubation or PACU discharge. These results emphasize the opioid-sparing potential of esketamine and advocate for standardized, weight-based infusion protocols. These findings support the consideration of low-dose esketamine infusions as a component of multimodal analgesia for mastectomy.