Effect of postoperative esketamine on depression after pancreatoduodenectomy: a randomized controlled trial

BACKGROUND: Pancreaticoduodenectomy (PD) can lead to major trauma in terms of patients' mental health, including severe postoperative depression. This study aimed to investigate the effects of supplementing patient-controlled analgesia with low-dose esketamine on postoperative depression among patients undergoing PD. METHODS: Eighty patients who were scheduled for PD were randomly assigned to either the control or esketamine groups. The control group received 2 µg/kg of sufentanil for patient-controlled analgesia (PCIA), whereas the esketamine group received a combination of 1.5 mg/kg esketamine and 2 µg/kg sufentanil. The primary outcome was the incidence of depression on the third postoperative day. The secondary outcomes included the Hamilton Depression Scale (HAMD-17) scores on the first, second, third, and fifth postoperative days; the severity of postoperative pain; the analgesic dosage; the incidence of postoperative adverse effects; the concentrations of plasma 5-hydroxytryptamine (5-HT), brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α); and the one-year survival rate. RESULTS: The incidence of depression on the third postoperative day did not differ significantly between the two groups (47.1% vs. 42.9%, P = 0.726). However, the change in the HAMD-17 score between baseline and the fifth postoperative day was significantly lower in the esketamine group (P = 0.029). The number of PCIA button presses was significantly lower in the esketamine group than in the control group (9.32 ± 6.48 vs. 6.54 ± 4.39, P = 0.040), and opioid usage was also significantly lower in the esketamine group (114.9 ± 23.32 vs. 100.9 ± 25.72, P = 0.021). Furthermore, esketamine decreased the plasma concentration of IL-6 on the first postoperative day (P < 0.05) and that of TNF-α on the fifth postoperative day (P < 0.05). CONCLUSION: The postoperative administration of esketamine may reduce the need for analgesics among patients undergoing PD, alleviate peripheral inflammation, and potentially improve postoperative depressive symptoms. TRIAL REGISTRATION: This trial was registered at http://www.chictr.org.cn (ChiCTR2200066303, Principal investigator: Yinqing Yin, Date of registration: 2022-11-30).