Effects of Esketamine on Postoperative Delirium and Postoperative Cognitive Function in Elderly Gastrointestinal Tumor Patients with Preoperative Anxiety

Jin Zha,1,2,* Hao Chen,1,* Zijie Sun,3 Rui Shi,1 Rufang Yan,1 Longmei Guo,3 Xiaoshu Chen,1 Xiaoying Lan,1 Huansen Huang,1 Lingzhi Wang1 1Department of Anesthesiology, the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Anesthesiology, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 3The Second Clinical College of Guangzhou Medical University, Guangzhou, Guangdong, People’s Repulic of China*These authors contributed equally to this workCorrespondence: Lingzhi Wang, Email [email protected]: The aim of this study is to investigate the effects of administering low-dose esketamine during anesthesia induction on the occurrence of postoperative delirium (POD) and postoperative cognitive function in elderly patients with preoperative anxiety.Patients and Methods: Elderly patients aged 60– 80 years and with preoperative anxiety who were undergoing surgery for gastrointestinal tumors were enrolled. The patients were randomly divided into an esketamine group or a placebo group. Upon intravenous induction of general anesthesia, the placebo group received normal saline, while the esketamine group received a subanesthetic dose (0.25 mg/kg) of esketamine. The primary outcome was the incidence of POD and the Mini-Mental State Examination (MMSE) score within 7 days after the operation (d1 to d7). Secondary outcomes included perioperative hemodynamic adverse events, postoperative anxiety, postoperative pain score, and analgesic consumption.Results: 118 patients were screened for eligibility, and 100 were recruited and analyzed. The incidence of POD within 7 days after surgery in the esketamine group was significantly lower than the placebo group (24.00% vs 48.00%, P < 0.05). The MMSE scores at postoperative day1 (d1) were significantly higher in the esketamine group than placebo group (29.00 [28.00– 30.00] vs 27.25 [25.00– 29.00], Bonferroni-adjusted P = 0.0014). The esketamine group had a lower cumulative incidence of delayed neurocognitive recovery (dNCR) within 7 days after surgery (26.00% vs 54.00%, P < 0.05). When compared to the placebo group, esketamine group had lower incidence of bradycardia and hypotension events during anesthesia induction period (P < 0.05), and the visual analogue anxiety (VAS-A) score on d1 was lower (Bonferroni-adjusted P < 0.05). Moreover, the esketamine group had significantly lower plasma concentrations of serum levels of Interleukin-6 (IL-6) and S100 calcium-binding protein β (S100β) on d1 (Bonferroni-adjusted P < 0.05).Conclusion: In elderly patients with preoperative anxiety who undergo gastrointestinal tumor surgery, administering a low-dose intravenous esketamine injection (0.25 mg/kg) during anesthesia induction can decrease the incidence of POD and improve early postoperative cognitive function.Keywords: esketamine, preoperative anxiety, postoperative delirium, postoperative cognitive function, elderly patients