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

54

Background: Modified radical mastectomy (MRM) causes significant acute postoperative and potential chronic pain. Esketamine offers potent analgesia with fewer side effects than racemic ketamine, though its recovery impact varies by dosing. This study evaluated esketamine's efficacy on pain, recovery quality, and efficiency in MRM. Methods: A systematic review and meta-analysis of RCTs compared perioperative esketamine to placebo/control in MRM. Primary outcomes were 24-hour Visual Analogue Scale (VAS) pain and Day-1 Quality of Recovery-15 (QoR-15). Secondary outcomes: rescue analgesia, extubation, and PACU stay. Random-effects models and subgroup analyses (bolus vs. infusion; dosing) were utilized to investigate heterogeneity. Results: Nine RCTs (n=749) were included. Esketamine significantly reduced 24-hour VAS scores (WMD -0.85; 95% CI -1.03 to -0.66). Stratification revealed this benefit was driven exclusively by continuous infusion (WMD -1.07; 95% CI -1.20 to -0.94; I ² =0%), whereas single-bolus administration showed no significant effect (WMD 0.01). Quality of recovery (QoR-15) improved significantly (WMD 8.01; 95% CI 5.95 to 10.08), with greater benefits observed in low-dose protocols (WMD 11.50) compared to high-dose regimens. Esketamine reduced the risk of requiring rescue analgesia by 69% (RR 0.31; 95% CI 0.16 to 0.60). Regarding efficiency, esketamine did not delay extubation (WMD -0.16 min) after excluding trials with background dexmedetomidine confounding. PACU stay duration exhibited a dose-dependent divergence: low-dose regimens shortened stay (WMD -2.85 min; P=0.02), whereas high-dose/sedative combinations prolonged it (WMD 6.78 min; P<0.00001). Conclusions: Continuous intraoperative esketamine infusion provides robust analgesic efficacy and enhances quality of recovery in breast cancer surgery, whereas single-bolus dosing does not. Importantly, low-dose regimens improve recovery metrics without delaying extubation or PACU discharge. These findings support the integration of low-dose esketamine infusions into multimodal analgesic regimens for mastectomy.