The Effect of Low-Dose Esketamine on Postoperative Neurocognitive Dysfunction in Elderly Patients Undergoing General Anesthesia for Gastrointestinal Tumors: A Randomized Controlled Trial

Overview

Journal Drug Des Devel Ther

Specialty Pharmacology

Date 2023 Jul 6

PMID 37408867

Authors

Jiamin Ma

Fuquan Wang

Jingxu Wang

Pengcheng Wang

Xiaoke Dou

Shanglong Yao

Yun Lin

Affiliations

Soon will be listed here.

Abstract

Purpose: This study aims to evaluate the effects of the intraoperative application of low-dose esketamine on postoperative neurocognitive dysfunction (PND) in elderly patients undergoing general anesthesia for gastrointestinal tumors.

Methods: Sixty-eight elderly patients were randomly allocated to two groups: the esketamine group (group Es) (0.25 mg/kg loading, 0.125mg/kg/h infusion) and the control group (group C) (received normal saline). The primary outcome was the incidence of delayed neurocognitive recovery (DNR). The secondary outcomes were intraoperative blood loss, the total amount of fluid given during surgery, propofol and remifentanil consumption, cardiovascular adverse events, use of vasoactive drugs, operating and anesthesia time, the number of cases of sufentanil remedial analgesia, the incidence of postoperative delirium (POD), the intraoperative hemodynamics, bispectral index (BIS) value at 0, 1, 2 h after operation and numeric rating scale (NRS) pain scores within 3 d after surgery.

Results: The incidence of DNR in group Es (16.13%) was lower than in group C (38.71%) ( <0.05). The intraoperative remifentanil dosage and the number of cases of dopamine used in group Es were lower than in group C ( <0.05). Compared with group C, DBP was higher at 3 min after intubation, and MAP was lower at 30 min after extubation in group Es (0.05). The incidence of hypotension and tachycardia in group Es was lower than in group C (0.05). The NRS pain score at 3 d after surgery in group Es was lower than in group C ( 0.05).

Conclusion: Low-dose esketamine infusion reduced to some extent the incidence of DNR in elderly patients undergoing general anesthesia for gastrointestinal tumors, improved intraoperative hemodynamics and BIS value, decreased the incidence of cardiovascular adverse events and the intraoperative consumption of opioids, and relieved postoperative pain.

Citing Articles

Identification of Key Genes in Esketamine's Therapeutic Effects on Perioperative Neurocognitive Disorders via Transcriptome Sequencing.

Hu W, Luo J, Li H, Luo Y, Zhang X, Wu Z Drug Des Devel Ther. 2025; 19:981-1000.

PMID: 39974608 PMC: 11836629. DOI: 10.2147/DDDT.S510752.

Effect of perioperative esketamine use on emergency delirium in children undergoing tonsillectomy and adenoidectomy: a systematic review and meta-analysis of randomized controlled trials.

Liu J, Liu J, Sun H, Cheng X, Wang C, Lei D Front Med (Lausanne). 2025; 12:1505408.

PMID: 39944481 PMC: 11814166. DOI: 10.3389/fmed.2025.1505408.

Effect of Esketamine on Cognitive Recovery After Propofol Sedation for Outpatient Colonoscopy: A Randomized Clinical Trial.

Liu D, Gao X, Zhuo Y, Cheng W, Yang Y, Wu X Drug Des Devel Ther. 2025; 19:425-437.

PMID: 39867863 PMC: 11762454. DOI: 10.2147/DDDT.S503129.

Effect of subanesthetic dose of esketamine on early postoperative depression in elderly patients with Sarcopenia.

Fang Y, Cao G, Hu S, Cheng J, Wang Y J Orthop Surg Res. 2024; 19(1):881.

PMID: 39725976 PMC: 11670516. DOI: 10.1186/s13018-024-05388-2.

Influence of preoperative comprehensive education on anxiety, depression, pain, and sleep in elderly patients operated under general anesthesia.

Qu L, Ma R, Ma Y, Zhao X, Jin J, Zhu Q World J Psychiatry. 2024; 14(12):1845-1853.

PMID: 39704354 PMC: 11622012. DOI: 10.5498/wjp.v14.i12.1845.

References

Zhang Y, Bao H, Lv Y, Si Y, Han L, Wang H . Risk factors for early postoperative cognitive dysfunction after colorectal surgery. BMC Anesthesiol. 2019; 19(1):6. PMC: 6325738. DOI: 10.1186/s12871-018-0676-4. View

Dekker E, Tanis P, Vleugels J, Kasi P, Wallace M . Colorectal cancer. Lancet. 2019; 394(10207):1467-1480. DOI: 10.1016/S0140-6736(19)32319-0. View

Tu W, Yuan H, Zhang S, Lu F, Yin L, Chen C . Influence of anesthetic induction of propofol combined with esketamine on perioperative stress and inflammatory responses and postoperative cognition of elderly surgical patients. Am J Transl Res. 2021; 13(3):1701-1709. PMC: 8014402. View

Tsai T, Sands L, Leung J . An Update on Postoperative Cognitive Dysfunction. Adv Anesth. 2010; 28(1):269-284. PMC: 2998043. DOI: 10.1016/j.aan.2010.09.003. View

Uchino H, Nagashima F, Nishiyama R, Ishida Y, Saiki I, Yara M . [Pathophysiology and mechanisms of postoperative cognitive dysfunction]. Masui. 2015; 63(11):1202-10. View

Keum N, Giovannucci E . Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol. 2019; 16(12):713-732. DOI: 10.1038/s41575-019-0189-8. View

Roach G, Newman M, Murkin J, Martzke J, RUSKIN A, Li J . Ineffectiveness of burst suppression therapy in mitigating perioperative cerebrovascular dysfunction. Multicenter Study of Perioperative Ischemia (McSPI) Research Group. Anesthesiology. 1999; 90(5):1255-64. DOI: 10.1097/00000542-199905000-00006. View

Wu C, King A, Geiger T, Grant M, Grocott M, Gupta R . American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Perioperative Opioid Minimization in Opioid-Naïve Patients. Anesth Analg. 2019; 129(2):567-577. PMC: 7261519. DOI: 10.1213/ANE.0000000000004194. View

Andrade C . Ketamine for Depression, 3: Does Chirality Matter?. J Clin Psychiatry. 2017; 78(6):e674-e677. DOI: 10.4088/JCP.17f11681. View

10.

Amat-Foraster M, Jensen A, Plath N, Herrik K, Celada P, Artigas F . Temporally dissociable effects of ketamine on neuronal discharge and gamma oscillations in rat thalamo-cortical networks. Neuropharmacology. 2018; 137:13-23. DOI: 10.1016/j.neuropharm.2018.04.022. View

11.

Gill H, Gill B, Rodrigues N, Lipsitz O, Rosenblat J, El-Halabi S . The Effects of Ketamine on Cognition in Treatment-Resistant Depression: A Systematic Review and Priority Avenues for Future Research. Neurosci Biobehav Rev. 2020; 120:78-85. DOI: 10.1016/j.neubiorev.2020.11.020. View

12.

Liu X, Xie G, Zhang K, Song S, Song F, Jin Y . Dexmedetomidine vs propofol sedation reduces delirium in patients after cardiac surgery: A meta-analysis with trial sequential analysis of randomized controlled trials. J Crit Care. 2016; 38:190-196. DOI: 10.1016/j.jcrc.2016.10.026. View

13.

Steiner L . Postoperative delirium. Part 1: pathophysiology and risk factors. Eur J Anaesthesiol. 2011; 28(9):628-36. DOI: 10.1097/EJA.0b013e328349b7f5. View

14.

Ohgi Y, Futamura T, Hashimoto K . Glutamate Signaling in Synaptogenesis and NMDA Receptors as Potential Therapeutic Targets for Psychiatric Disorders. Curr Mol Med. 2015; 15(3):206-21. DOI: 10.2174/1566524015666150330143008. View

15.

Malenka R, Bear M . LTP and LTD: an embarrassment of riches. Neuron. 2004; 44(1):5-21. DOI: 10.1016/j.neuron.2004.09.012. View

16.

Wang J, Huang J, Yang S, Cui C, Ye L, Wang S . Pharmacokinetics and Safety of Esketamine in Chinese Patients Undergoing Painless Gastroscopy in Comparison with Ketamine: A Randomized, Open-Label Clinical Study. Drug Des Devel Ther. 2019; 13:4135-4144. PMC: 6902860. DOI: 10.2147/DDDT.S224553. View

17.

Folstein M, Folstein S, McHugh P . "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975; 12(3):189-98. DOI: 10.1016/0022-3956(75)90026-6. View

18.

Monk T, Weldon B, Garvan C, Dede D, van der Aa M, Heilman K . Predictors of cognitive dysfunction after major noncardiac surgery. Anesthesiology. 2007; 108(1):18-30. DOI: 10.1097/01.anes.0000296071.19434.1e. View

19.

Bornemann-Cimenti H, Wejbora M, Michaeli K, Edler A, Sandner-Kiesling A . The effects of minimal-dose versus low-dose S-ketamine on opioid consumption, hyperalgesia, and postoperative delirium: a triple-blinded, randomized, active- and placebo-controlled clinical trial. Minerva Anestesiol. 2016; 82(10):1069-1076. View

20.

Scholz A, Oldroyd C, McCarthy K, Quinn T, Hewitt J . Systematic review and meta-analysis of risk factors for postoperative delirium among older patients undergoing gastrointestinal surgery. Br J Surg. 2015; 103(2):e21-8. DOI: 10.1002/bjs.10062. View