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Systematic Reviews

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Application of opioid-free general anesthesia in laparoscopy: a meta-analysis of randomized controlled studies

  • Mei-hui Gao1,*,
  • Jin Meng1
  • Xu-ming Hu1
  • Jie Liu1

1Department of Anesthesiology, Sir Run Run Shaw Hospital Affiliated to Zhejiang University, 310016 Hangzhou, Zhejiang, China

DOI: 10.22514/sv.2024.050

Submitted: 22 August 2023 Accepted: 13 October 2023

Online publish date: 26 April 2024

*Corresponding Author(s): Mei-hui Gao E-mail:


Applying opioid-free general anesthesia (OFGA) in laparoscopy was controversial. A systematic review and meta-analysis were conducted to investigate the efficacy and safety of employing OFGA in laparoscopy. Relevant clinical trials to include in this systematic review and meta-analysis were scrutinized through electronic databases such as Embase, PubMed, Cochrane Library and Web of Science. The quality of selected randomized controlled trials (RCTs) was assessed by Cochrane Collaboration’s bias risk assessment tool. The meta-analysis was conducted on Review Manager 5.3. The quality of evidence was assessed in accordance with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. The analysis in this study included 14 RCTs involving 1042 patients. No notable variation examined in 24-hour postoperative pain score between the opioid-based and OFGA groups (mean difference = −0.43, 95% confidence interval (−1.08, 0.22); p = 0.19). However, OFGA application reduced the postoperative analgesic needs and the incidence of postoperative nausea and vomiting. The meta-analysis and systematic review findings indicated that OFGA could be effectively and safely used in laparoscopy.


Opioid-free general anesthesia; Laparoscopy; Meta-analysis

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Mei-hui Gao,Jin Meng,Xu-ming Hu,Jie Liu. Application of opioid-free general anesthesia in laparoscopy: a meta-analysis of randomized controlled studies. Signa Vitae. 2024.doi:10.22514/sv.2024.050.


[1] Buia A, Stockhausen F, Hanisch E. Laparoscopic surgery: a qualified systematic review. World Journal of Methodology. 2015; 5: 238.

[2] Kim SS, Donahue TR. Laparoscopic cholecystectomy. JAMA. 2018; 319: 1834.

[3] Farahat SM, Elbatarny A, Elshimy KM, Medhat S, Ismail KA, Arafa MA. Safe stapleless laparoscopic splenectomy; use of Hem-O-Lok to control the splenic hilum. The Journal of the Pakistan Medical Association. 2023; 73: S228–S232.

[4] Zeng M, Li J, Zheng T, Yan X, Yuan F, Xiang B. Electropress needle stimulation for the prevention of postoperative nausea and vomiting in patients undergoing laparoscopic sleeve gastrectomy: a prospective, randomized controlled trial. Obesity Surgery. 2023; 33: 2831–2840.

[5] De Cicco Nardone C, Ficarola F, Plotti F, Montera R, Feole L, Rampello S, et al. The role of peritoneal lavage in benign gynecologic laparoscopic surgery. European Review for Medical and Pharmacological Sciences. 2023; 27: 6800–6808.

[6] Guliev BG, Komyakov B, Avazkhanov Z, Shevnin M, Talyshinskii A. Laparoscopic ventral onlay ureteroplasty with buccal mucosa graft for complex proximal ureteral stricture. International Brazilian Journal of Urology. 2023; 49: 619–627.

[7] Durden L, Wilford BN. Identifying early opioid-induced respiratory depression and rapid response team activation. Pain Management Nursing. 2023; 24: 567–572.

[8] Suzuki N, Okuyama M, Kamiya K. Effects and limitations of Naldemedine for opioid-induced urinary retention: a case report. To be published in Journal of Palliative Medicine. 2023. [Preprint].

[9] Yu L, Yang Y, Wu H, Yu Y, Wang Y, Yan S, et al. Pupillary monitoring decreases remifentanil consumption during laparoscopic uterine surgery and improves postoperative recovery. Minerva Anestesiologica. 2023; 89: 859–866.

[10] Skolnick P. The opioid epidemic: crisis and solutions. Annual Review of Pharmacology and Toxicology. 2018; 58: 143–159.

[11] Kehlet H. Enhanced postoperative recovery: good from afar, but far from good? Anaesthesia. 2020; 75: e54–e61.

[12] Beloeil H. Opioid-free anesthesia. Best Practice & Research Clinical Anaesthesiology. 2019; 33: 353–360.

[13] Melucci AD, Dave YA, Lynch OF, Hsu S, Erlick MR, Linehan DC, et al. Predictors of opioid-free discharge after laparoscopic cholecystectomy. The American Journal of Surgery. 2023; 225: 206–211.

[14] Thiyagarajan D, Ragupathy R, Ganesh Prabhu S, Anto V. Opioid-free anaesthesia for laparoscopic surgeries—a prospective non-randomised study in a tertiary care hospital. Indian Journal of Anaesthesia. 2022; 66: 207.

[15] Hoffman C, Buddha M, Mai M, Sanjeevi S, Gutierrez R, O’ Neill C, et al. Opioid-free anesthesia and same-day surgery laparoscopic hiatal hernia repair. Journal of the American College of Surgeons. 2022; 235: 86–98.

[16] Conti D, Valoriani J, Gianesello L, Zini C, Ballo P, Pavoni V. Bilateral erector spinae plane block as part of an opioid-free anesthesia in enhanced recovery after surgery program in an unplanned open colorectal surgery. Minerva Anestesiologica. 2022; 88: 873–874.

[17] Shankar K, Rangalakshmi S, Kailash P, Priyanka D. Comparison of hemodynamics and opioid sparing effect of dexmedetomidine nebulization and intravenous dexmedetomidine in laparoscopic surgeries under general anesthesia. Asian Journal of Anesthesiology. 2022; 60: 33–40.

[18] Rajan S, Hutcherson MT, Sessler DI, Kurz A, Yang D, Ghobrial M, et al. The effects of dexmedetomidine and remifentanil on hemodynamic stability and analgesic requirement after craniotomy: a randomized controlled trial. Journal of Neurosurgical Anesthesiology. 2016; 28: 282–290.

[19] Polat R, Peker K, Baran I, Bumin Aydın G, Topçu Gülöksüz Ç, Dönmez A. Comparison between dexmedetomidine and remifentanil infusion in emergence agitation during recovery after nasal surgery: a randomized double-blind trial. Der Anaesthesist. 2015; 64: 740–746.

[20] Baishya M, Pandey RK, Sharma A, Punj J, Darlong V, Rewari V, et al. Comparative evaluation of the analgesic efficacy of ultrasound-guided erector spinae plane block versus intrathecal morphine in patients undergoing percutaneous nephrolithotomy surgery: a prospective randomized pilot study. International Journal of Urology. 2022; 29: 668–674.

[21] Bhoi D, Kalagara R, Baidya DK, Maitra S, Subramaniam R. Opioid free anaesthesia technique in patients undergoing laparotomy for gynaecological malignancy: a randomized controlled trial. Anesthesia and Analgesia. 2021; 133: 18–19.

[22] Aliev VA, Bashankaev BN, Loria IZ, Glabay VP, Yavorovsky AG, Shavgulidze KB, et al. Non-opioid multimodal anesthesia in the surgical treatment of colorectal cancer. Khirurgiia. 2019; 54–59. (In Russian)

[23] Araki M, Gu X, Raphaely S, Tinker T, Fitch J, Wong C. Opioid-free analgesia following robot-assisted laparoscopic prostatectomy (RALP): 10 case experience. Urology. 2012; 80: S304.

[24] Bachmann A, Giannini O, Wolff T, Dickenmann M, Ruszat R, Langer I, et al. Retroperitoneoscopic living donor nephrectomy: a comparison with the open approach in respect of early postoperative pain management. Transplantation Proceedings. 2005; 37: 609–612.

[25] Berlier J, Carabalona J, Tête H, Bouffard Y, Le-Goff M, Cerro V, et al. Effects of opioid-free anesthesia on postoperative morphine consumption after bariatric surgery. Journal of Clinical Anesthesia. 2022; 81: 110906.

[26] Campos-Pérez W, Ramírez-Plascencia L, Pérez-Robles M, Rivera-Valdés JJ, Sánchez-Muñoz P, Pérez-Vargas L, et al. A comparison of opioid-containing anesthesia versus opioid-free anesthesia using the Cortínez-Sepúlveda model on differential cytokine responses in obese patients undergoing gastric bypass surgery: a randomized controlled trial. BMC Anesthesiology. 2022; 22: 294.

[27] Misra S, Bhattacharya S, Saravanakumar S, Praveenraj P. RCT comparing opioid free vs. opiod anaesthesia for post operative pain control and intubation stress attenuation in laparoscopic sleeve gastrectomy. Obesity Surgery. 2019; 29: 255.

[28] Rodriguez-Guerrero T, Borrero-Cortes C. A completely opioid-free anesthesia for laparoscopic surgery in oncological patients. Anesthesia and Analgesia. 2021; 133: 823–824.

[29] Olausson A, Svensson CJ, Andréll P, Jildenstål P, Thörn S, Wolf A. Total opioid‐free general anaesthesia can improve postoperative outcomes after surgery, without evidence of adverse effects on patient safety and pain management: a systematic review and meta‐analysis. Acta Anaesthesiologica Scandinavica. 2022; 66: 170–185.

[30] Massoth C, Schwellenbach J, Saadat-Gilani K, Weiss R, Pöpping D, Küllmar M, et al. Impact of opioid-free anaesthesia on postoperative nausea, vomiting and pain after gynaecological laparoscopy—a randomised controlled trial. Journal of Clinical Anesthesia. 2021; 75: 110437.

[31] Menck JT, Tenório SB, de Oliveira RM, Strobel R, dos Santos BB, Junior AFF, et al. Opioid-free anesthesia for laparoscopic gastroplasty. a prospective and randomized trial. The Open Anesthesia Journal. 2022; 16: 1–7.

[32] Toleska M, Dimitrovski A, Dimitrovska NT. Postoperative nausea and vomiting in opioid-free anesthesia versus opioid based anesthesia in laparoscopic cholecystectomy. PRILOZI. 2022; 43: 101–108.

[33] Ahmed SA, Abdelghany MS, Afandy ME. The effect of opioid-free anesthesia on the postoperative opioid consumption in laparoscopic bariatric surgeries: a randomized controlled double-blind study. Journal of Opioid Management. 2022; 18: 47–56.

[34] An G, Wang G, Zhao B, Zhang X, Li Z, Fu J, et al. Opioid-free anesthesia compared to opioid anesthesia for laparoscopic radical colectomy with pain threshold index monitoring: a randomized controlled study. BMC Anesthesiology. 2022; 22: 241.

[35] Garg K, Bhardwaj S, Devgan S. Comparison of opioid-based and opioid-free TIVA for laparoscopic urological procedures in obese patients. Journal of Anaesthesiology Clinical Pharmacology. 2019; 35: 481.

[36] Chen J, Luo Q, Huang S, Jiao J. Effect of opioid-free anesthesia on postoperative analgesia after laparoscopic gynecologic surgery. Minerva Anestesiologica. 2022; 88: 439–447.

[37] Chen L, He WS, Liu X, Lv FH, Li YH. Application of opioid-free general anesthesia for gynecological laparoscopic surgery under ERAS protocol: a non-inferiority randomized controlled trial. BMC Anesthesiology 2023; 23: 34.

[38] Choi H, Song JY, Oh EJ, Chae MS, Yu S, Moon YE. The effect of opioid-free anesthesia on the quality of recovery after gynecological laparoscopy: a prospective randomized controlled trial. Journal of Pain Research. 2022; 15: 2197–2209.

[39] Greiss M, Ghobrial BB, Elmageed WMA, Elfawy DM, Mostafa RH. Dexmedetomidine versus fentanyl on stress response and pain control in adult patients undergoing laparoscopic surgery. Signa Vitae. 2022; 18: 116-124.

[40] Hakim KK, Wahba WB. Opioid-free total intravenous anesthesia improves postoperative quality of recovery after ambulatory gynecologic laparoscopy. Anesthesia: Essays and Researches. 2019; 13: 199–203.

[41] Ibrahim M, Elnabtity AM, Hegab A, Alnujaidi OA, El Sanea O. Combined opioid free and loco-regional anaesthesia enhances the quality of recovery in sleeve gastrectomy done under ERAS protocol: a randomized controlled trial. BMC Anesthesiology. 2022; 22: 29.

[42] Ramachandran R, Jebaraj B, Rewari V, Trikha A, Chandralekha, Kumar R, et al. Feasibility of dexmedetomidine as sole analgesic agent during robotic urological surgery: a pilot study. Journal of Anaesthesiology Clinical Pharmacology. 2017; 33: 187.

[43] Luong NV, Giang NT, V. Chuong H, Cuong NM, V. Dinh N, Anh V, et al. Evaluation of efficacy of free opioid anesthesia for laparoscopic cholecystectomy: a prospective, randomized double-blinded study. The Open Anesthesiology Journal. 2020; 14: 73–79.

[44] Soudi AM, Hammad RA, ElShafie MA, Ahmed IMAS, Alhadidy MA. Comparing opioid free general anesthesia to traditional balanced general anesthesia regarding achievement of enhanced recovery in laparoscopic bariatric surgeries. Ain-Shams Journal of Anesthesiology. 2022; 14: 24.

[45] Toleska M, Dimitrovski A. Is opioid-free general anesthesia more superior for postoperative pain versus opioid general anesthesia in laparoscopic cholecystectomy? PRILOZI. 2019; 40: 81–87.

[46] Van Loocke J, Heintz A, Mulier J. Impact of opoid free anesthesia on glycemia: a randomized controlled trial. Acta Anaesthesiologica Belgica. 2022; 73: 25–31.

[47] Techanivate A, Dusitkasem S, Anuwattanavit C. Dexmedetomidine compare with fentanyl for postoperative analgesia in outpatient gynecologic laparoscopy: a randomized controlled trial. Journal of the Medical Association of Thailand. 2012; 95: 383–390.

[48] Ripollés-Melchor J, Abad-Motos A, Zorrilla-Vaca A. Enhanced recovery after surgery (ERAS) in surgical oncology. Current Oncology Reports. 2022; 24: 1177–1187.

[49] Sao C, Chan-Tiopianco M, Chung K, Chen Y, Horng H, Lee W, et al. Pain after laparoscopic surgery. Journal of the Chinese Medical Association. 2019; 82: 819–826.

[50] McGrail K, Chapple AG, Stone G, Sutton EF, Chappell NR. Systematic review and meta-analysis of perioperative administration of acetazolamide for management of postoperative pain after laparoscopy. Journal of the Society of Laparoscopic & Robotic Surgeons. 2022; 26: e2022.00032.

[51] Frauenknecht J, Kirkham KR, Jacot‐Guillarmod A, Albrecht E. Analgesic impact of intra‐operative opioids vs. opioid‐free anaesthesia: a systematic review and meta‐analysis. Anaesthesia. 2019; 74: 651–662.

[52] Colvin LA, Bull F, Hales TG. Perioperative opioid analgesia—when is enough too much? A review of opioid-induced tolerance and hyperalgesia. The Lancet. 2019; 393: 1558–1568.

[53] Fletcher D, Martinez V. Opioid-induced hyperalgesia in patients after surgery: a systematic review and a meta-analysis. British Journal of Anaesthesia. 2014; 112: 991–1004.

[54] Liu X, Bae C, Liu B, Zhang Y, Zhou X, Zhang D, et al. Development of opioid-induced hyperalgesia depends on reactive astrocytes controlled by Wnt5a signaling. Molecular Psychiatry. 2023; 28: 767–779.

[55] Tedesco D, Gori D, Desai KR, Asch S, Carroll IR, Curtin C, et al. Drug-free interventions to reduce pain or opioid consumption after total knee arthroplasty. JAMA Surgery. 2017; 152: e172872.

[56] Mann GE, Flamer SZ, Nair S, Maher JN, Cowan B, Streiff A, et al. Opioid-free anesthesia for adenotonsillectomy in children. International Journal of Pediatric Otorhinolaryngology. 2021; 140: 110501.

[57] Gan TJ, Belani KG, Bergese S, Chung F, Diemunsch P, Habib AS, et al. Fourth consensus guidelines for the management of postoperative nausea and vomiting. Anesthesia and Analgesia. 2020; 131: 411–448.

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