ArticleAnnals of medicine2026
Intraoperative esketamine for postoperative analgesia and depression in pancreatic cancer surgery: protocol for a multicenter randomized controlled trial.
Article in Annals of medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introductionPatients undergoing pancreatic cancer surgery frequently experience severe postoperative pain and a high prevalence of depression. Esketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, offers rapid-onset analgesic and antidepressant properties, yet its efficacy in this high-risk population remains unknown. We hypothesize that intraoperative esketamine infusion improves multidimensional analgesic benefit and reduces postoperative depression compared with placebo. PATIENTS AND
methodsThis prospective, multicenter, randomized, double-blind, placebo-controlled trial will be conducted at three tertiary hospitals in China. We will enroll 280 adult patients (aged 18-80 years, ASA physical status I-III) undergoing elective pancreatectomy for pancreatic cancer. Participants will be randomized (1:1) to receive either intraoperative intravenous esketamine (0.15 mg/kg/h, maximum 0.6 mg/kg over 4 h) or volume-matched 0.9% saline, stratified by center and surgical approach (open vs. laparoscopic). The co-primary endpoints are (1) the Overall Benefit of Analgesia Score at 24 h postoperatively and (2) the incidence of moderate-to-severe depression (Patient Health Questionnaire-9 ≥ 10) at 7 days postoperatively. A two-sided significance level is α = 0.025 for each primary endpoint with Bonferroni correction. Secondary endpoints include Numerical Rating Scale pain scores and the incidence of moderate-to-severe depression at 1 month and 3 months. Exploratory long-term endpoints are 5-year disease-free and overall survival. DISCUSSION: This trial will generate high-quality evidence on the use of esketamine as a dual-action perioperative intervention targeting both analgesic quality and psychological outcomes after pancreatic cancer surgery. The findings will inform enhanced recovery after surgery protocols and may provide mechanistic insights into NMDA receptor modulation in perioperative outcomes.
trial registrationChinese Clinical Trial Registry (ChiCTR2600119701; registered on March 2, 2026).
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