Efficacy of opioid-sparing techniques on analgesia, complications and recovery outcomes in liver surgery: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

FU Anqi , HE Yi ,  ZUO Yunxia ,  SHEN Yu

Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;

Corresponding author：

ZUO Yunxia, Email: zuoyunxia@scu.edu.cn; SHEN Yu, Email: Dr.Shen@wchscu.edu.cn

Keywords：

Opioid-sparing; Liver surgery; Postoperative analgesia; Meta-analysis; Systematic review; Randomized controlled trial

DOI：

10.7507/1672-2531.202411135

Video：

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Objective To systematically review the efficacy of opioid-sparing analgesic techniques in terms of analgesic potential, incidence of complications and quality of recovery in liver surgery. Methods The PubMed, Embase and Cochrane Library databases were electronically searched to collect randomized controlled trials (RCTs) related to the objects from inception to August 2023. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed by using RevMan 5.3 software. Results A total of 20 RCTs involving 1 347 patients were included. The results of meta-analysis showed that opioid-sparing techniques could significantly reduce pain scores at rest and during movement from 2h to 48h postoperatively, opioid consumption within 24h (MD=−11.17, 95%CI −14.62 to −7.71, P<0.01) and 48h (MD=−7.19, 95%CI −10.06 to −4.33, P<0.01), postoperative nausea and vomiting (PONV) (OR=0.68, 95%CI 0.50 to 0.91, P=0.01) and wound infection (OR=0.42, 95%CI 0.18 to 0.98, P=0.04), as well as reduced time to bowel recovery (MD=−12.92, 95%CI −21.24 to −4.61, P<0.01) and decreased length of hospital stay (LOS) (MD=−0.90, 95%CI 1.32 to −0.49, P<0.01). No significant difference was observed between the two groups in the incidence of excessive sedation, pruritus, hypotension, headache and respiratory depression. Time to out-of-bed activity and patient satisfaction were also similar between groups. Conclusion Opioid-sparing techniques are effective in relieving postoperative pain and reducing opioid use, with additional potential in reducing postoperative nausea or vomiting, wound infection, time to bowel recovery and length of hospital stay.

1.	Behman R, Cleary S, McHardy P, et al. Predictors of post-operative pain and opioid consumption in patients undergoing liver surgery. World J Surg, 2019, 43(10): 2579-2586.
2.	Dudek P, Zawadka M, Andruszkiewicz P, et al. Postoperative analgesia after open liver surgery: systematic review of clinical evidence. J Clin Med, 2021, 10(16): 3662.
3.	Cannistrà M, Ruggiero M, Zullo A, et al. Hepatic ischemia reperfusion injury: a systematic review of literature and the role of current drugs and biomarkers. Int J Surg, 2016, 33(Suppl 1): S57-S70.
4.	Hasselström J, Eriksson S, Persson A, et al. The metabolism and bioavailability of morphine in patients with severe liver cirrhosis. Br J Clin Pharmacol, 1990, 29(3): 289-297.
5.	Pirie K, Traer E, Finniss D, et al. Current approaches to acute postoperative pain management after major abdominal surgery: a narrative review and future directions. Br J Anaesth, 2022, 129(3): 378-393.
6.	Stark N, Kerr S, Stevens J. Prevalence and predictors of persistent post-surgical opioid use: a prospective observational cohort study. Anaesth Intensive Care, 2017, 45(6): 700-706.
7.	Kambakamba P, Slankamenac K, Tschuor C, et al. Epidural analgesia and perioperative kidney function after major liver resection. Br J Surg, 2015, 102(7): 805-812.
8.	Joliat GR, Kobayashi K, Hasegawa K, et al. Guidelines for perioperative care for liver surgery: enhanced recovery after surgery (ERAS) society recommendations 2022. World J Surg, 2023, 47(1): 11-34.
9.	Myles PS, Myles DB, Galagher W, et al. Measuring acute postoperative pain using the visual analog scale: the minimal clinically important difference and patient acceptable symptom state. Br J Anaesth, 2017, 118(3): 424-429.
10.	Abdallah FW, MacLean D, Madjdpour C, et al. Pectoralis and serratus fascial plane blocks each provide early analgesic benefits following ambulatory breast cancer surgery: a retrospective propensity-matched cohort study. Anesth Analg, 2017, 125(1): 294-302.
11.	Sun JX, Bai KY, Liu YF, et al. Effect of local wound infiltration with ropivacaine on postoperative pain relief and stress response reduction after open hepatectomy. World J Gastroenterol, 2017, 23(36): 6733-6740.
12.	Fu J, Zhang G, Qiu Y. Erector spinae plane block for postoperative pain and recovery in hepatectomy: a randomized controlled trial. Medicine (Baltimore), 2020, 99(41): e22251.
13.	Ban M, Choi YS, Koo BN. Analgesic effect of intrathecal morphine combined with low-dose bupivacaine on postoperative analgesia after liver resection: a randomized controlled study. J Pers Med, 2022, 12(2): 211.
14.	Peres-Bachelot V, Blanc E, Oussaid N, et al. A 96-hour continuous wound infiltration with ropivacaine reduces analgesic consumption after liver resection: a randomized, double-blind, controlled trial. J Surg Oncol, 2019, 119(1): 47-55.
15.	Xin Y, Hong Y, Yong LZ. Efficacy of postoperative continuous wound infiltration with local anesthesia after open hepatectomy. Clin J Pain, 2014, 30(7): 571-576.
16.	Chan SK, Lai PB, Li PT, et al. The analgesic efficacy of continuous wound instillation with ropivacaine after open hepatic surgery. Anaesthesia, 2010, 65(12): 1180-1186.
17.	Wu YF, Li XP, Yu YB, et al. Postoperative local incision analgesia for acute pain treatment in patients with hepatocellular carcinoma. Rev Assoc Med Bras (1992), 2018, 64(2): 175-180.
18.	Dalmau A, Fustran N, Camprubi I, et al. Analgesia with continuous wound infusion of local anesthetic versus saline: Double-blind randomized, controlled trial in hepatectomy. Am J Surg, 2018, 215(1): 138-143.
19.	Kıtlık A, Erdogan MA, Ozgul U, et al. Ultrasound-guided transversus abdominis plane block for postoperative analgesia in living liver donors: a prospective, randomized, double-blinded clinical trial. J Clin Anesth, 2017, 37: 103-107.
20.	Kim D, Kim JM, Choi GS, et al. Ultrasound-guided erector spinae plane block for postoperative analgesia in laparoscopic liver resection: a prospective, randomised controlled, patient and observer-blinded study. Eur J Anaesthesiol, 2021, 38(Suppl 2): S106-S112.
21.	Zhang H, Du G, Liu YF, et al. Overlay of a sponge soaked with ropivacaine and multisite infiltration analgesia result in faster recovery after laparoscopic hepatectomy. World J Gastroenterol, 2019, 25(34): 5185-5196.
22.	Chen H, Liao Z, Fang Y, et al. Continuous right thoracic paravertebral block following bolus initiation reduced postoperative pain after right-lobe hepatectomy: a randomized, double-blind, placebo-controlled trial. Reg Anesth Pain Med, 2014, 39(6): 506-512.
23.	Guo JG, Li HL, Pei QQ, et al. The analgesic efficacy of subcostal transversus abdominis plane block with Mercedes incision. BMC Anesthesiol, 2018, 18(1): 36.
24.	Zhang J, Liu T, Zhou H, et al. The safety and efficacy of ultrasound-guided bilateral dual transversus abdominis plane (BD-TAP) block in ERAS program of laparoscopic hepatectomy: a prospective, randomized, controlled, blinded, clinical study. Drug Des Devel Ther, 2020, 14: 2889-2898.
25.	Apisutimaitri K, Thepsoparn M, Chairat S, et al. Comparison of intrathecal morphine and low-dose bupivacaine with intravenous morphine for postoperative analgesia in laparoscopic liver resection: a randomized controlled trial. Surg Endosc, 2023, 37(3): 2035-2042.
26.	Chen MT, Jin B, Du SD, et al. Role of a selective cyclooxygenase-2 inhibitor on pain and enhanced recovery after open hepatectomy: a randomized controlled trial. Trans Cancer Res, 2017, 6(4): 806-814.
27.	Karanicolas PJ, Cleary S, McHardy P, et al. Medial open transversus abdominis plane (MOTAP) catheters reduce opioid requirements and improve pain control following open liver resection: a multicenter, blinded, randomized controlled trial. Ann Surg, 2018, 268(2): 233-240.
28.	Wang RD, Zhu JY, Zhu Y, et al. Perioperative analgesia with parecoxib sodium improves postoperative pain and immune function in patients undergoing hepatectomy for hepatocellular carcinoma. J Eval Clin Pract, 2020, 26(3): 992-1000.
29.	Huang X, Wang J, Zhang J, et al. Ultrasound-guided erector spinae plane block improves analgesia after laparoscopic hepatectomy: a randomised controlled trial. Br J Anaesth, 2022, 129(3): 445-453.
30.	Cui XL, Xu N, Zhang ZY, et al. Ultrasound-guided continuous thoracic paravertebral block improves patient's quality of recovery after open hepatectomy: a randomized, double-blind, placebo-controlled trial. Chin Med Sci J, 2022, 37(1): 15-22.
31.	Bhushan S, Huang X, Su X, et al. Ultrasound-guided erector spinae plane block for postoperative analgesia in patients after liver surgery: a systematic review and meta-analysis on randomized comparative studies. Int J Surg, 2022, 103: 106689.
32.	Luo Z, Wang H, Huang D. The impact of parecoxib on pain management for laparoscopic cholecystectomy: a meta-analysis of randomized controlled trials. Surg Laparosc Endosc Percutan Tech, 2019, 29(2): 69-74.
33.	Hollmann MW, Durieux ME. Local anesthetics and the inflammatory response: a new therapeutic indication. Anesthesiology, 2000, 93(3): 858-875.
34.	Hopf HW, Hunt TK, West JM, et al. Wound tissue oxygen tension predicts the risk of wound infection in surgical patients. Arch Surg, 1997, 132(9): 997-1004.
35.	Kumar L, Anantharaman R, Thomas DE, et al. Evaluation of the analgesic efficacy of a low dose of intrathecal morphine in laparoscopic abdominal surgery: a randomised control trial. J Minim Access Surg, 2024, (11): 1.
36.	Chin KJ, El-Boghdadly K. Mechanisms of action of the erector spinae plane (ESP) block: a narrative review. Can J Anaesth, 2021, 68(3): 387-408.
37.	Forero M, Adhikary SD, Lopez H, et al. The erector spinae plane block: a novel analgesic technique in thoracic neuropathic pain. Reg Anesth Pain Med, 2016, 41(5): 621-627.
38.	Peng M, Wang YL, Wang FF, et al. The cyclooxygenase-2 inhibitor parecoxib inhibits surgery-induced proinflammatory cytokine expression in the hippocampus in aged rats. J Surg Res, 2012, 178(1): e1-e8.
39.	Rodrigues TFDC, Silveira B, Tavares FP, et al. Open, laparoscopic, and robotic-assisted hepatectomy in resection of liver tumors: a non-systematic review. Arq Bras Cir Dig, 2017, 30(2): 155-160.
40.	Jeong JS, Wi W, Chung YJ, et al. Comparison of perioperative outcomes between pure laparoscopic surgery and open right hepatectomy in living donor hepatectomy: Propensity score matching analysis. Sci Rep, 2020, 10(1): 5314.
41.	Hirata Y, Witt RG, Prakash LR, et al. Analysis of opioid use in patients undergoing open versus robotic gastrectomy. Ann Surg Oncol, 2022, 29(9): 5861-5870.
42.	Müller-Lissner S, Bassotti G, Coffin B, et al. Opioid-induced constipation and bowel dysfunction: a clinical guideline. Pain Med, 2017, 18(10): 1837-1863.
43.	de Oliveira CM, Issy AM, Sakata RK. Intraoperative intravenous lidocaine. Rev Bras Anestesiol, 2010, 60(3): 325-333.
44.	de Klaver MJM, Buckingham MG, Rich GF. Lidocaine attenuates cytokine-induced cell injury in endothelial and vascular smooth muscle cells. Anesth Analg, 2003, 97(2): 465-470.
45.	Ponce de León-Ballesteros G, Ramírez-Del Val A, Romero-Vélez G, et al. LAW trial - the impact of local anesthetics infiltration in surgical wound for gastrointestinal procedures (LAW): a double-blind, randomized controlled trial. J Invest Surg, 2022, 35(1): 98-103.
46.	Johnson SM, Saint John BE, Dine AP. Local anesthetics as antimicrobial agents: a review. Surg Infect (Larchmt), 2008, 9(2): 205-213.
47.	Sadik H, Watson N, Dilaver N, et al. The use of local anaesthetic wound catheter infiltration for post-operative pain after hepatic surgery: a systematic review and meta-analysis. Hpb, 2021, 23(Suppl 3): S969-S970.
48.	Xu Y, Ye M, Liu F, et al. Efficacy of prolonged intravenous lidocaine infusion for postoperative movement-evoked pain following hepatectomy: a double-blinded, randomised, placebo-controlled trial. Br J Anaesth, 2023, 131(1): 113-121.
49.	Jiang F, Wu A, Liang Y, et al. Assessment of ultrasound-guided continuous low serratus anterior plane block for pain management after hepatectomy: a randomized controlled trial. J Pain Res, 2023, 16: 2383-2392.

1. Behman R, Cleary S, McHardy P, et al. Predictors of post-operative pain and opioid consumption in patients undergoing liver surgery. World J Surg, 2019, 43(10): 2579-2586.
2. Dudek P, Zawadka M, Andruszkiewicz P, et al. Postoperative analgesia after open liver surgery: systematic review of clinical evidence. J Clin Med, 2021, 10(16): 3662.
3. Cannistrà M, Ruggiero M, Zullo A, et al. Hepatic ischemia reperfusion injury: a systematic review of literature and the role of current drugs and biomarkers. Int J Surg, 2016, 33(Suppl 1): S57-S70.
4. Hasselström J, Eriksson S, Persson A, et al. The metabolism and bioavailability of morphine in patients with severe liver cirrhosis. Br J Clin Pharmacol, 1990, 29(3): 289-297.
5. Pirie K, Traer E, Finniss D, et al. Current approaches to acute postoperative pain management after major abdominal surgery: a narrative review and future directions. Br J Anaesth, 2022, 129(3): 378-393.
6. Stark N, Kerr S, Stevens J. Prevalence and predictors of persistent post-surgical opioid use: a prospective observational cohort study. Anaesth Intensive Care, 2017, 45(6): 700-706.
7. Kambakamba P, Slankamenac K, Tschuor C, et al. Epidural analgesia and perioperative kidney function after major liver resection. Br J Surg, 2015, 102(7): 805-812.
8. Joliat GR, Kobayashi K, Hasegawa K, et al. Guidelines for perioperative care for liver surgery: enhanced recovery after surgery (ERAS) society recommendations 2022. World J Surg, 2023, 47(1): 11-34.
9. Myles PS, Myles DB, Galagher W, et al. Measuring acute postoperative pain using the visual analog scale: the minimal clinically important difference and patient acceptable symptom state. Br J Anaesth, 2017, 118(3): 424-429.
10. Abdallah FW, MacLean D, Madjdpour C, et al. Pectoralis and serratus fascial plane blocks each provide early analgesic benefits following ambulatory breast cancer surgery: a retrospective propensity-matched cohort study. Anesth Analg, 2017, 125(1): 294-302.
11. Sun JX, Bai KY, Liu YF, et al. Effect of local wound infiltration with ropivacaine on postoperative pain relief and stress response reduction after open hepatectomy. World J Gastroenterol, 2017, 23(36): 6733-6740.
12. Fu J, Zhang G, Qiu Y. Erector spinae plane block for postoperative pain and recovery in hepatectomy: a randomized controlled trial. Medicine (Baltimore), 2020, 99(41): e22251.
13. Ban M, Choi YS, Koo BN. Analgesic effect of intrathecal morphine combined with low-dose bupivacaine on postoperative analgesia after liver resection: a randomized controlled study. J Pers Med, 2022, 12(2): 211.
14. Peres-Bachelot V, Blanc E, Oussaid N, et al. A 96-hour continuous wound infiltration with ropivacaine reduces analgesic consumption after liver resection: a randomized, double-blind, controlled trial. J Surg Oncol, 2019, 119(1): 47-55.
15. Xin Y, Hong Y, Yong LZ. Efficacy of postoperative continuous wound infiltration with local anesthesia after open hepatectomy. Clin J Pain, 2014, 30(7): 571-576.
16. Chan SK, Lai PB, Li PT, et al. The analgesic efficacy of continuous wound instillation with ropivacaine after open hepatic surgery. Anaesthesia, 2010, 65(12): 1180-1186.
17. Wu YF, Li XP, Yu YB, et al. Postoperative local incision analgesia for acute pain treatment in patients with hepatocellular carcinoma. Rev Assoc Med Bras (1992), 2018, 64(2): 175-180.
18. Dalmau A, Fustran N, Camprubi I, et al. Analgesia with continuous wound infusion of local anesthetic versus saline: Double-blind randomized, controlled trial in hepatectomy. Am J Surg, 2018, 215(1): 138-143.
19. Kıtlık A, Erdogan MA, Ozgul U, et al. Ultrasound-guided transversus abdominis plane block for postoperative analgesia in living liver donors: a prospective, randomized, double-blinded clinical trial. J Clin Anesth, 2017, 37: 103-107.
20. Kim D, Kim JM, Choi GS, et al. Ultrasound-guided erector spinae plane block for postoperative analgesia in laparoscopic liver resection: a prospective, randomised controlled, patient and observer-blinded study. Eur J Anaesthesiol, 2021, 38(Suppl 2): S106-S112.
21. Zhang H, Du G, Liu YF, et al. Overlay of a sponge soaked with ropivacaine and multisite infiltration analgesia result in faster recovery after laparoscopic hepatectomy. World J Gastroenterol, 2019, 25(34): 5185-5196.
22. Chen H, Liao Z, Fang Y, et al. Continuous right thoracic paravertebral block following bolus initiation reduced postoperative pain after right-lobe hepatectomy: a randomized, double-blind, placebo-controlled trial. Reg Anesth Pain Med, 2014, 39(6): 506-512.
23. Guo JG, Li HL, Pei QQ, et al. The analgesic efficacy of subcostal transversus abdominis plane block with Mercedes incision. BMC Anesthesiol, 2018, 18(1): 36.
24. Zhang J, Liu T, Zhou H, et al. The safety and efficacy of ultrasound-guided bilateral dual transversus abdominis plane (BD-TAP) block in ERAS program of laparoscopic hepatectomy: a prospective, randomized, controlled, blinded, clinical study. Drug Des Devel Ther, 2020, 14: 2889-2898.
25. Apisutimaitri K, Thepsoparn M, Chairat S, et al. Comparison of intrathecal morphine and low-dose bupivacaine with intravenous morphine for postoperative analgesia in laparoscopic liver resection: a randomized controlled trial. Surg Endosc, 2023, 37(3): 2035-2042.
26. Chen MT, Jin B, Du SD, et al. Role of a selective cyclooxygenase-2 inhibitor on pain and enhanced recovery after open hepatectomy: a randomized controlled trial. Trans Cancer Res, 2017, 6(4): 806-814.
27. Karanicolas PJ, Cleary S, McHardy P, et al. Medial open transversus abdominis plane (MOTAP) catheters reduce opioid requirements and improve pain control following open liver resection: a multicenter, blinded, randomized controlled trial. Ann Surg, 2018, 268(2): 233-240.
28. Wang RD, Zhu JY, Zhu Y, et al. Perioperative analgesia with parecoxib sodium improves postoperative pain and immune function in patients undergoing hepatectomy for hepatocellular carcinoma. J Eval Clin Pract, 2020, 26(3): 992-1000.
29. Huang X, Wang J, Zhang J, et al. Ultrasound-guided erector spinae plane block improves analgesia after laparoscopic hepatectomy: a randomised controlled trial. Br J Anaesth, 2022, 129(3): 445-453.
30. Cui XL, Xu N, Zhang ZY, et al. Ultrasound-guided continuous thoracic paravertebral block improves patient's quality of recovery after open hepatectomy: a randomized, double-blind, placebo-controlled trial. Chin Med Sci J, 2022, 37(1): 15-22.
31. Bhushan S, Huang X, Su X, et al. Ultrasound-guided erector spinae plane block for postoperative analgesia in patients after liver surgery: a systematic review and meta-analysis on randomized comparative studies. Int J Surg, 2022, 103: 106689.
32. Luo Z, Wang H, Huang D. The impact of parecoxib on pain management for laparoscopic cholecystectomy: a meta-analysis of randomized controlled trials. Surg Laparosc Endosc Percutan Tech, 2019, 29(2): 69-74.
33. Hollmann MW, Durieux ME. Local anesthetics and the inflammatory response: a new therapeutic indication. Anesthesiology, 2000, 93(3): 858-875.
34. Hopf HW, Hunt TK, West JM, et al. Wound tissue oxygen tension predicts the risk of wound infection in surgical patients. Arch Surg, 1997, 132(9): 997-1004.
35. Kumar L, Anantharaman R, Thomas DE, et al. Evaluation of the analgesic efficacy of a low dose of intrathecal morphine in laparoscopic abdominal surgery: a randomised control trial. J Minim Access Surg, 2024, (11): 1.
36. Chin KJ, El-Boghdadly K. Mechanisms of action of the erector spinae plane (ESP) block: a narrative review. Can J Anaesth, 2021, 68(3): 387-408.
37. Forero M, Adhikary SD, Lopez H, et al. The erector spinae plane block: a novel analgesic technique in thoracic neuropathic pain. Reg Anesth Pain Med, 2016, 41(5): 621-627.
38. Peng M, Wang YL, Wang FF, et al. The cyclooxygenase-2 inhibitor parecoxib inhibits surgery-induced proinflammatory cytokine expression in the hippocampus in aged rats. J Surg Res, 2012, 178(1): e1-e8.
39. Rodrigues TFDC, Silveira B, Tavares FP, et al. Open, laparoscopic, and robotic-assisted hepatectomy in resection of liver tumors: a non-systematic review. Arq Bras Cir Dig, 2017, 30(2): 155-160.
40. Jeong JS, Wi W, Chung YJ, et al. Comparison of perioperative outcomes between pure laparoscopic surgery and open right hepatectomy in living donor hepatectomy: Propensity score matching analysis. Sci Rep, 2020, 10(1): 5314.
41. Hirata Y, Witt RG, Prakash LR, et al. Analysis of opioid use in patients undergoing open versus robotic gastrectomy. Ann Surg Oncol, 2022, 29(9): 5861-5870.
42. Müller-Lissner S, Bassotti G, Coffin B, et al. Opioid-induced constipation and bowel dysfunction: a clinical guideline. Pain Med, 2017, 18(10): 1837-1863.
43. de Oliveira CM, Issy AM, Sakata RK. Intraoperative intravenous lidocaine. Rev Bras Anestesiol, 2010, 60(3): 325-333.
44. de Klaver MJM, Buckingham MG, Rich GF. Lidocaine attenuates cytokine-induced cell injury in endothelial and vascular smooth muscle cells. Anesth Analg, 2003, 97(2): 465-470.
45. Ponce de León-Ballesteros G, Ramírez-Del Val A, Romero-Vélez G, et al. LAW trial - the impact of local anesthetics infiltration in surgical wound for gastrointestinal procedures (LAW): a double-blind, randomized controlled trial. J Invest Surg, 2022, 35(1): 98-103.
46. Johnson SM, Saint John BE, Dine AP. Local anesthetics as antimicrobial agents: a review. Surg Infect (Larchmt), 2008, 9(2): 205-213.
47. Sadik H, Watson N, Dilaver N, et al. The use of local anaesthetic wound catheter infiltration for post-operative pain after hepatic surgery: a systematic review and meta-analysis. Hpb, 2021, 23(Suppl 3): S969-S970.
48. Xu Y, Ye M, Liu F, et al. Efficacy of prolonged intravenous lidocaine infusion for postoperative movement-evoked pain following hepatectomy: a double-blinded, randomised, placebo-controlled trial. Br J Anaesth, 2023, 131(1): 113-121.
49. Jiang F, Wu A, Liang Y, et al. Assessment of ultrasound-guided continuous low serratus anterior plane block for pain management after hepatectomy: a randomized controlled trial. J Pain Res, 2023, 16: 2383-2392.

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