Preemptive Ketamine versus Dexamethasone for the Prevention of Postoperative Pain and Nausea Following Laparoscopic Cholecystectomy: A Triple-Blind Randomized Controlled Trial
,
Abstract
Background: Postoperative pain and nausea/vomiting remain common and clinically significant complications following laparoscopic cholecystectomy. Although both ketamine and dexamethasone have demonstrated preemptive analgesic and antiemetic properties, direct comparative evidence between these agents is limited. The objective is to compare the effectiveness of preemptive ketamine versus dexamethasone in reducing postoperative pain, nausea, and vomiting after laparoscopic cholecystectomy.
Methods: In this triple-blind randomized controlled trial, 102 patients undergoing elective laparoscopic cholecystectomy at Alzahra Hospital (Isfahan, Iran) in 2024 were randomly assigned to receive intravenous ketamine (0.75 mg/kg), dexamethasone (0.1 mg/kg), or placebo immediately after surgical incision. The main outcomes focused on patients' recovery experience, including the level of postoperative pain measured on a 0-10 scale, the severity of nausea assessed on a 0-10 visual analog scale, and the frequency of vomiting during the recovery period.Secondary outcomes included rescue analgesic requirements and adverse events.
Results: All 102 randomized participants (34 per group) completed the study. At recovery room admission, mean pain scores were significantly lower in the ketamine group (3.4 ± 1.8) compared with the dexamethasone (4.5 ± 1.9) and placebo
(6.2 ± 2.1) groups (p < 0.001). In contrast, mean nausea scores were significantly lower in the dexamethasone group (2.3 ± 1.7) compared with the ketamine (4.1 ± 2.2) and placebo (5.8 ± 2.4) groups (p < 0.001). Vomiting incidence was lowest with dexamethasone (23.5%) relative to ketamine (44.1%) and placebo (70.6%)
(P < 0.001). Rescue morphine use was required in 55.9% of ketamine, 64.7% of dexamethasone, and 82.4% of placebo recipients (p = 0.029). No serious adverse events were observed.
Conclusion: Preemptive ketamine provides superior postoperative analgesia, whereas dexamethasone offers superior antiemetic efficacy compared with placebo in patients undergoing laparoscopic cholecystectomy. Selection between these agents should be individualized based on whether postoperative pain or prevention of nausea/vomiting is the primary clinical priority.
[2] Panda A, Mishra JC, Panigrahi A, Kandregula S, Majumder R. Early postoperative pain intensity after laparoscopic cholecystectomy and associated risk factors. Indian J Public Health Res Dev. 2020; 11:517-22.
[3] Jamtsho P, Dorjey Y, Dorji N, Tshering S, Wangmo KP, et al. Factors associated with postoperative nausea and vomiting after laparoscopic cholecystectomy at the National Referral Hospital, Bhutan: a cross-sectional study. BMC Anesthesiol. 2024; 24(1):248.
[4] Barazanchi AWH, MacFater WS, Rahiri JL, Tutone S, Hill AG, et al. Evidence-based management of pain after laparoscopic cholecystectomy: a PROSPECT review update. Br J Anaesth. 2018; 121(4):787-803.
[5] Arslan M, Ciçek R, Kalender HÜ, Yilmaz H. Preventing postoperative nausea and vomiting after laparoscopic cholecystectomy: a prospective, randomized, double-blind study. Curr Ther Res Clin Exp. 2011; 72(1):1-12.
[6] Bayoumi HM, Abdelaziz DH, El Said NO, Boraii S, Bendas ER. Postoperative pain management following laparoscopic cholecystectomy-non-opioid approaches: a review. Future J Pharm Sci. 2024; 10(1):125.
[7] Katz J, Clarke H, Seltzer Z. Review article: Preventive analgesia: quo vadimus? Anesth Analg. 2011; 113(6):1475.
[8] Zhao C, Liao Q, Yang D, Yang M, Xu P. Advances in perioperative pain management for total knee arthroplasty: a review of multimodal analgesic approaches. J Orthop Surg Res. 2024; 19(1):843.
[9] Grape S, Tramèr MR. Do we need preemptive analgesia for the treatment of postoperative pain? Best Pract Res Clin Anaesthesiol. 2007; 21(1):51-63.
[10] Cao L, Yang T, Hou Y, Yong S, Zhou N. Efficacy and Safety of Different Preemptive Analgesia Measures in Pain Management after Laparoscopic Cholecystectomy: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials. Pain Ther. 2024; 13(6):1471-1497.
[11] Singh H, Kundra S, Singh RM, Grewal A, Kaul TK, et al. Preemptive analgesia with Ketamine for Laparoscopic cholecystectomy. J Anaesthesiol Clin Pharmacol. 2013; 29(4):478-84.
[12] Jain S, Nazir N, Mustafi SM. Preemptive low-dose intravenous ketamine in the management of acute and chronic postoperative pain following laparoscopic cholecystectomy: a prospective randomized control study. Med Gas Res. 2022; 12(4):141-145.
[13] Ye F, Wu Y, Zhou C. Effect of intravenous ketamine for postoperative analgesia in patients undergoing laparoscopic cholecystectomy: A meta-analysis. Medicine (Baltimore). 2017; 96(51):e9147.
[14] Jamil K, Qaisar R. The Effect of Dexamethasone on Postoperative Pain in Patients After Laparoscopic Cholecystectomy. Cureus. 2022; 14(11):e32067.
[15] Lim SH, Jang EH, Kim MH, Cho K, Lee JH, et al. Analgesic effect of preoperative versus intraoperative dexamethasone after laparoscopic cholecystectomy with multimodal analgesia. Korean J Anesthesiol. 2011; 61(4):315-9.
[16] Charan J, Biswas T. How to calculate sample size for different study designs in medical research? Indian J Psychol Med. 2013; 35(2):121-6.
[17] Sakpal TV. Sample size estimation in clinical trial. Perspect Clin Res. 2010; 1(2):67-9.
[18] Laskowski K, Stirling A, McKay WP, Lim HJ. A systematic review of intravenous ketamine for postoperative analgesia. Can J Anaesth. 2011; 58(10):911-23.
[19] Akram U, Fatima E, Ashraf H, Rehman KA, Raza MA, Qazi MS, et al. Perioperative ketamine or esketamine for acute postoperative pain after laparoscopic cholecystectomy: a systematic review and meta-analysis with meta-regression. Anaesth Crit Care Pain Med. 2026;45(3):101762.
[20] Zhu J, Xie H, Zhang L, Chang L, Chen P. Efficiency and safety of ketamine for pain relief after laparoscopic cholecystectomy: a meta-analysis from randomized controlled trials. Int J Surg. 2018; 49:1-9.
[21] Peltoniemi MA, Hagelberg NM, Olkkola KT, Saari TI. Ketamine: A Review of Clinical Pharmacokinetics and Pharmacodynamics in Anesthesia and Pain Therapy. Clin Pharmacokinet. 2016; 55(9):1059-77.
[22] Sridharan K, Sivaramakrishnan G. Drugs for preventing post-operative nausea and vomiting in patients undergoing laparoscopic cholecystectomy: network meta-analysis of randomized clinical trials and trial sequential analysis. Int J Surg. 2019; 69:1-12.
[23] Polderman JA, Farhang-Razi V, Van Dieren S, Kranke P, DeVries JH, et al. Adverse side effects of dexamethasone in surgical patients. Cochrane Database Syst Rev. 2018; 11:CD011940.
[24] De Oliveira GS Jr, Castro-Alves LJ, Ahmad S, Kendall MC, et al. Dexamethasone to prevent postoperative nausea and vomiting: an updated meta-analysis of randomized controlled trials. Anesth Analg. 2013; 116(1):58-74.
[25] Grape S, Kirkham KR, Frauenknecht J, Albrecht E. Intra-operative analgesia with remifentanil vs. dexmedetomidine: a systematic review and meta-analysis with trial sequential analysis. Anaesthesia. 2019; 74(6):793-800.
[26] Brinck ECV, Tiippana E, Heesen M, Bell RF, Straube S, Moore RA, Kontinen V. Perioperative intravenous ketamine for acute postoperative pain in adults. Cochrane Database Syst Rev. 2018;12(12):CD012033.
[27] Safavi M, Honarmand A, Habibabady MR, Baraty S, Aghadavoudi O. Assessing intravenous ketamine and intravenous dexamethasone separately and in combination for early oral intake, vomiting and postoperative pain relief in children following tonsillectomy. Med Arh. 2012;66(2):111-115.
[28] Weibel S, Jelting Y, Pace NL, Helf A, Eberhart LH, et al. Continuous intravenous perioperative lidocaine infusion for postoperative pain and recovery in adults. Cochrane Database Syst Rev. 2018; 6(6):CD009642.
[29] Kurdi MS, Theerth KA, Deva RS. Ketamine: Current applications in anesthesia, pain, and critical care. Anesth Essays Res. 2014; 8(3):283-90.
[30] Toner AJ, Ganeshanathan V, Chan MT, Ho KM, et al. Safety of Perioperative Glucocorticoids in Elective Noncardiac Surgery: A Systematic Review and Meta-analysis. Anesthesiology. 2017; 126(2):234-248.
| Files | ||
| Issue | Article in Press |
|
| Section | Research Article(s) | |
| Keywords | ||
| Laparoscopic cholecystectomy Preemptive analgesia Ketamine Dexamethasone Postoperative pain Postoperative nausea and vomiting | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
