Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Anesthesiology
Published in: BMC Anesthesiology 1/2023

Open Access 01-12-2023 | Esketamine | Research

The ED50 and ED95 of esketamine for preventing early postoperative pain in patients undergoing laparoscopic cholecystectomy: a prospective, double-blinded trial

Authors: Zhongling Xu, Yantao Lang, Xiaolei Xu, Linjuan Deng, Hengya Song, Dekun Yin

Published in: BMC Anesthesiology | Issue 1/2023

Login to get access

Abstract

Background

This study aims to estimate the safety, efficacy, and median effective dose (ED50) of esketamine for preventing early postoperative pain in patients undergoing laparoscopic cholecystectomy.

Methods

54 patients undergoing laparoscopic cholecystectomy were prospectively randomized into two groups (group C and group E). Different doses of esketamine were intravenously administered before the skin incision in Group E. The patients in group C received the same dose of saline at the same time. General population characteristics were recorded. The median effective dose (ED50) and 95% effective dose (ED95) were calculated using Dixon’s up-and-down method. Hemodynamic parameters were monitored, and pain intensity was assessed using a visual analog scale. We also recorded the condition of anesthesia recovery period and postoperative adverse reactions.

Results

The ED50 of esketamine for preventing early postoperative pain was 0.301 mg/kg (95%CI: 0.265-0.342 mg/kg), and the ED95 was 0.379 mg/kg (95%CI: 0.340-0.618 mg/kg), calculated by probability unit regression. Heart rate (HR) was significantly lower in the esketamine group compared to the control at the skin incision (p < 0.05). The total VAS score at resting was significantly lower in the esketamine group compared to the control group during the awakening period (p < 0.05). There was no significant difference between the two groups regarding the incidence of adverse reactions (p > 0.05).

Conclusions

In this study, esketamine can prevent early postoperative pain effectively. The ED50 and ED95 of esketamine for controlling early postoperative pain were 0.301 mg/kg and 0.379 mg/kg, respectively.

Trial registration

ChiCTR2200066663, 13/12/2022.
Literature
1.
Bittner R. Laparoscopic surgery–15 years after clinical introduction. World J Surg. 2006;30(7):1190–203.PubMedCrossRef
2.
Ros A, Gustafsson L, Krook H, Nordgren CE, Thorell A, Wallin G, Nilsson E. Laparoscopic cholecystectomy versus mini-laparotomy cholecystectomy: a prospective, randomized, single-blind study. Ann Surg. 2001;234(6):741–9.PubMedPubMedCentralCrossRef
3.
Bisgaard T, Kehlet H, Rosenberg J. Pain and convalescence after laparoscopic cholecystectomy. Eur J Surg. 2001;167(2):84–96.PubMedCrossRef
4.
Hang LH, Shao DH, Gu YP. The ED50 and ED95 of ketamine for prevention of postoperative hyperalgesia after remifentanil-based anaesthesia in patients undergoing laparoscopic cholecystectomy. Swiss Med Wkly. 2011;141:w13195.PubMed
5.
Mitra S, Khandelwal P, Roberts K, Kumar S, Vadivelu N. Pain relief in laparoscopic cholecystectomy–a review of the current options. Pain Pract. 2012;12(6):485–96.PubMedCrossRef
6.
Koc M, Ertan T, Tez M, Kocpinar MA, Kilic M, Gocmen E, Aslar AK. Randomized, prospective comparison of postoperative pain in low- versus high-pressure pneumoperitoneum. ANZ J Surg. 2005;75(8):693–6.PubMedCrossRef
7.
8.
Blichfeldt-Eckhardt MR, Ording H, Andersen C, Licht PB, Toft P. Early visceral pain predicts chronic pain after laparoscopic cholecystectomy. Pain. 2014;155(11):2400–7.PubMedCrossRef
9.
Gebhart GF. Visceral pain-peripheral sensitisation. Gut 2000, 47 Suppl 4(Suppl 4):iv54-55; discussion iv58.
10.
Sengupta JN. Visceral pain: the neurophysiological mechanism. Handb Exp Pharmacol. 2009;194:31–74.CrossRef
11.
Cervero F. Visceral versus somatic pain: similarities and differences. Dig Dis. 2009;27(Suppl 1):3–10.PubMedCrossRef
12.
Fletcher D, Martinez V. Opioid-induced hyperalgesia in patients after Surgery: a systematic review and a meta-analysis. Br J Anaesth. 2014;112(6):991–1004.PubMedCrossRef
13.
Koo CH, Yoon S, Kim BR, Cho YJ, Kim TK, Jeon Y, Seo JH. Intraoperative naloxone reduces remifentanil-induced postoperative hyperalgesia but not pain: a randomized controlled trial. Br J Anaesth. 2017;119(6):1161–8.PubMedCrossRef
14.
Sridharan K, Sivaramakrishnan G. Comparison of Fentanyl, Remifentanil, Sufentanil and Alfentanil in Combination with Propofol for General Anesthesia: a systematic review and Meta-analysis of Randomized controlled trials. Curr Clin Pharmacol. 2019;14(2):116–24.PubMedPubMedCentralCrossRef
15.
Angst MS, Koppert W, Pahl I, Clark DJ, Schmelz M. Short-term infusion of the mu-opioid agonist remifentanil in humans causes hyperalgesia during withdrawal. Pain. 2003;106(1–2):49–57.PubMedCrossRef
16.
Leal PC, Salomao R, Brunialti MK, Sakata RK. Evaluation of the effect of ketamine on remifentanil-induced hyperalgesia: a double-blind, randomized study. J Clin Anesth. 2015;27(4):331–7.PubMedCrossRef
17.
Lin HQ, Jia DL. Effect of preemptive ketamine administration on postoperative visceral pain after gynecological laparoscopic Surgery. J Huazhong Univ Sci Technolog Med Sci. 2016;36(4):584–7.PubMedCrossRef
18.
Sen H, Sizlan A, Yanarates O, Emirkadi H, Ozkan S, Dagli G, Turan A. A comparison of gabapentin and ketamine in acute and chronic pain after hysterectomy. Anesth Analg. 2009;109(5):1645–50.PubMedCrossRef
19.
Zhu Y, Li Q, Liu G, Sheng F, Zhang X, Jiang L, Li S, He J, Zou Z, Zhang B, et al. Effects of esketamine on postoperative rebound pain in patients undergoing unilateral total knee arthroplasty: a single-center, randomized, double-blind, placebo-controlled trial protocol. Front Neurol. 2023;14:1179673.PubMedPubMedCentralCrossRef
20.
Lei Y, Liu H, Xia F, Gan S, Wang Y, Huo W, Wang Q, Ji F. Effects of Esketamine on Acute and Chronic Pain after Thoracoscopy Pulmonary Surgery under General Anesthesia: a Multicenter-Prospective, randomized, Double-Blind, and controlled trial. Front Med (Lausanne). 2021;8:693594.PubMedCrossRef
21.
Zhu M, Xu S, Ju X, Wang S, Yu X. Effects of the different doses of esketamine on postoperative quality of recovery in patients undergoing modified radical mastectomy: a Randomized, Double-Blind, controlled trial. Drug Des Devel Ther. 2022;16:4291–9.PubMedPubMedCentralCrossRef
22.
Wang P, Song M, Wang X, Zhang Y, Wu Y. Effect of esketamine on opioid consumption and postoperative pain in thyroidectomy: a randomized controlled trial. Br J Clin Pharmacol. 2023;89(8):2542–51.PubMedCrossRef
23.
Su M, Zhu Y, Liu S, Song L, Qu J, Zhang Y, Zhang Q. Median effective dose (ED(50)) of esketamine combined with propofol for children to inhibit response of gastroscope insertion. BMC Anesthesiol. 2023;23(1):240.PubMedPubMedCentralCrossRef
24.
25.
Zhou D, Liu F, Jiang F, Ye X, Gong X, Zhang M. Sub-anesthesia Dose of S-Ketamine reduces Postoperative Pain and anxiety in patients receiving breast and thyroid Surgery: a Randomized, Controlled Trial. Pain Physician. 2023;26(3):257–64.PubMed
26.
Zheng Y, Xu Y, Huang B, Mai Y, Zhang Y, Zhang Z. Effective dose of propofol combined with a low-dose esketamine for gastroscopy in elderly patients: a dose finding study using dixon’s up-and-down method. Front Pharmacol. 2022;13:956392.PubMedPubMedCentralCrossRef
27.
28.
Schug SA, Zech D, Grond S. Adverse effects of systemic opioid analgesics. Drug Saf. 1992;7(3):200–13.PubMedCrossRef
29.
Mion G, Villevieille T. Ketamine pharmacology: an update (pharmacodynamics and molecular aspects, recent findings). CNS Neurosci Ther. 2013;19(6):370–80.PubMedPubMedCentralCrossRef
30.
Ma X, Peng J, Chen Y, Wang Z, Zhou Q, Yan J, Jiang H. Esketamine anesthetizes mice with a similar potency to racemic ketamine. Dose Response. 2023;21(1):15593258231157563.PubMedPubMedCentralCrossRef
31.
Massoth C, Schwellenbach J, Saadat-Gilani K, Weiss R, Popping D, Kullmar M, Wenk M. Impact of opioid-free anaesthesia on postoperative nausea, vomiting and pain after gynaecological laparoscopy - A randomised controlled trial. J Clin Anesth. 2021;75:110437.PubMedCrossRef
32.
Tan M, Zhang C, Zeng W, Chen M, Huang Z, Huang D. Determining the effective dose of esketamine for mitigating pain during propofol injection by Dixon’s up-and-down method: a double-blind, prospective clinical study of drug dose response. BMC Anesthesiol. 2022;22(1):368.PubMedPubMedCentralCrossRef
33.
Ren YL, Yuan JJ, Xing F, Zhu LN, Zhang W. Effects of different doses of Esketamine on Pain Sensitivity of patients undergoing thyroidectomy: a Randomized Controlled Trial. Pain Ther. 2023;12(3):739–50.PubMedPubMedCentralCrossRef
34.
Arroyo-Novoa CM, Figueroa-Ramos MI, Miaskowski C, Padilla G, Stotts N, Puntillo KA. Acute wound pain: gaining a better understanding. Adv Skin Wound Care. 2009;22(8):373–80. quiz 381 – 372.PubMedCrossRef
35.
Bisgaard T. Analgesic treatment after laparoscopic cholecystectomy: a critical assessment of the evidence. Anesthesiology. 2006;104(4):835–46.PubMedCrossRef
36.
Fu H, Zhong C, Fu Y, Gao Y, Xu X. Perioperative Analgesic effects of preemptive ultrasound-guided Rectus Sheath Block Combined with Butorphanol or Sufentanil for single-incision laparoscopic cholecystectomy: a prospective, randomized, clinical trial. J Pain Res. 2020;13:1193–200.PubMedPubMedCentralCrossRef
37.
38.
Cortelli P, Pierangeli G. Chronic pain-autonomic interactions. Neurol Sci. 2003;24(Suppl 2):68–70.CrossRef
39.
Benson S, Siebert C, Koenen LR, Engler H, Kleine-Borgmann J, Bingel U, Icenhour A, Elsenbruch S. Cortisol affects pain sensitivity and pain-related emotional learning in experimental visceral but not somatic pain: a randomized controlled study in healthy men and women. Pain. 2019;160(8):1719–28.PubMedCrossRef
40.
Burkle H, Dunbar S, Van Aken H. Remifentanil: a novel, short-acting, mu-opioid. Anesth Analg. 1996;83(3):646–51.PubMedCrossRef
41.
Moon YE, Kim MH, Lee HM, Yoon HM, Jeon YJ. Preventative effect of ketamine on post-surgical hyperalgesia induced at a body part remote from the surgical site. Minerva Anestesiol. 2018;84(4):481–7.PubMedCrossRef
42.
Liu F, Kong F, Zhong L, Wang Y, Xia Z, Wu J. Preoperative esketamine alleviates Postoperative Pain after Endoscopic plasma adenotonsillectomy in children. Clin Med Res. 2023;21(2):79–86.PubMedPubMedCentralCrossRef
43.
Del Sant LC, Sarin LM, Magalhaes EJM, Lucchese AC, Tuena MA, Nakahira C, Fava VAR, Delfino R, Surjan J, Steiglich MS, et al. Effects of subcutaneous esketamine on blood pressure and heart rate in treatment-resistant depression. J Psychopharmacol. 2020;34(10):1155–62.PubMedCrossRef
44.
Baraka A, Harrison T, Kachachi T. Catecholamine levels after ketamine anesthesia in man. Anesth Analg. 1973;52(2):198–200.PubMedCrossRef
Metadata
Title
The ED50 and ED95 of esketamine for preventing early postoperative pain in patients undergoing laparoscopic cholecystectomy: a prospective, double-blinded trial
Authors
Zhongling Xu
Yantao Lang
Xiaolei Xu
Linjuan Deng
Hengya Song
Dekun Yin
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Anesthesiology / Issue 1/2023
Electronic ISSN: 1471-2253
DOI
https://doi.org/10.1186/s12871-023-02357-w

Other articles of this Issue 1/2023

BMC Anesthesiology 1/2023 Go to the issue

Research

Cognitive function in older patients and their stress challenge using different anesthesia regimes: a single center observational study

Research

Development and assessment of the performance of a shared ventilatory system that uses clinically available components to individualize tidal volumes

Research

Comparison of post-auricular and frontal bispectral index values obtained during renal surgeries

Research

Effect of superior laryngeal nerve block in alleviating sore throat after application of i-gel supraglottic airway: a randomized controlled trial

Research

Correlation and influencing factors of preoperative anxiety, postoperative pain, and delirium in elderly patients undergoing gastrointestinal cancer surgery

Research

Intraoperative circulatory arrest secondary to high-risk pulmonary embolism. Case series and updated literature review