Esketamine-sufentanil PCA reduces postoperative depression state in elderly colorectal cancer patients: a randomized controlled trial

Elderly colorectal cancer (CRC) patients face high risks of postoperative depression state, inadequately addressed by opioid-based analgesia. Esketamine, an NMDA receptor antagonist with rapid antidepressant effects, offers potential benefits but lacks evidence in this population. This double-blind RCT enrolled 99 elderly (≥ 65 years) CRC resection patients, randomized to three postoperative PCA groups: C: Sufentanil (2 µg/kg) + saline placebo, ES1: Sufentanil + esketamine 1 mg/kg, ES2: Sufentanil + esketamine 2 mg/kg. Primary outcomes were anxiety/depression (HAMA/HAMD scores) at 24 h postoperatively. Secondary outcomes included VAS pain scores, patient satisfaction, and adverse events. Depression/Anxiety: Both esketamine groups showed significantly lower HAMD/HAMA scores vs. control at 24 h and 72 h (e.g., 24 h HAMD: ES1 6.16 ± 2.16, ES2 7.10 ± 2.55 vs. C 9.87 ± 3.67; p < 0.001), with no dose-dependent difference (p > 0.05 ES1 vs. ES2). Pain Control: No intergroup differences in resting/activity VAS scores or rescue analgesia demands (p > 0.05). Satisfaction: Higher satisfaction rates in ES1 (77.4%) and ES2 (90.0%) vs. C (50.0%) (p = 0.002). Safety: Comparable adverse events across groups (p > 0.05). Low-dose esketamine (1 mg/kg) adjunct to sufentanil PCA significantly reduces postoperative depression and anxiety state in elderly CRC patients without enhancing analgesia or increasing adverse events. Its profound psychological benefits and high patient satisfaction support its integration into enhanced recovery protocols for this vulnerable cohort. Registry: Chinese Clinical Trial Registry(chictr.org.cn), TRN: ChiCTR2300070763, Registration date: 23 April 2023.