Efficacy of nefopam in postoperative pain management: A systematic review of opioid consumption

Nagla Abdelmonim Bader; Mohammad M. Al-Ahmad; Waiel Al Naeem; Mohammed Gamal Amer

doi:10.7324/JAPS.2025.203223

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Abstract

Previous research assessing the role of nefopam in postoperative pain management has yielded mixed results, with more evidence supporting a beneficial effect. This systematic review examines the efficacy of nefopam in reducing opioid consumption in postoperative patients and includes patient satisfaction measures and the frequency of adverse events. A comprehensive search strategy was performed in the following databases: PubMed, Web of Science, and Cochrane Library. Search terms used included “postoperative pain management” AND “nefopam”, “nefopam” AND “opioid consumption”, and “nefopam” AND “analgesia” OR “postoperative pain management”. Studies involving postoperative adult patients receiving nefopam and compared with a control group were included. A risk of bias assessment was performed using the Cochrane ROB-2 tool. 17 articles passed the inclusion criteria. Findings indicated that nefopam significantly reduces opioid consumption in postoperative patients by an average of 38%. The overall analgesic effect of nefopam was superior to that of opioids alone, with a good margin of safety and a high degree of satisfaction in most patients. Nausea, sweating, and postoperative tachycardia were common in the treatment groups. From the findings, the study concludes that nefopam is an effective adjunctive postoperative analgesic that has a significant positive impact on pain management and reduction of opioid consumption. The study was registered on PROSPERO (ID: CRD42022364446).

Keyword: Nefopam postoperative pain management opioids opioid consumption analgesia

Citation:

Bader NA, Al-Ahmad MM, Al Naeem W, Amer MG. Efficacy of nefopam in postoperative pain management: A systematic review of opioid consumption. J Appl Pharm Sci. 2025. Online First. http://doi.org/10.7324/JAPS.2025.205927

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Reference

1. Choi SK, Yoon MH, Choi JI, Kim WM, Heo BH, Park KS, et al. Comparison of effects of intraoperative nefopam and ketamine infusion on managing postoperative pain after laparoscopic cholecystectomy administered remifentanil. Korean J Anesthesiol. 2016;69(5):480-6. https://doi.org/10.4097/kjae.2016.69.5.480
2. Charoenpol FN, Khampitak N, Aimnang C, Pachirat K, Sirithanaphol W, Rompsaithong U, et al. Single-dose intravenous nefopam on postoperative catheter-related bladder discomfort in patients undergoing transurethral resection of prostate: a randomized, double-blind placebo-controlled trial. J Anesth. 2023;37(1):72-8. https://doi.org/10.1007/s00540-022-03130-y
3. Franzese A, Borrelli O, Corrado G, Rea P, Di Nardo G, Grandinetti AL, et al. Domperidone is more effective than cisapride in children with diabetic gastroparesis. Aliment Pharmacol Ther. 2002;16:951-7. https://doi.org/10.1046/j.1365-2036.2002.01240.x
4. du Manoir B, Aubrun F, Langlois M, le Guern ME, Alquier C, Chauvin M, et al. Randomized prospective study of the analgesic effect of nefopam after orthopaedic surgery. Br J Anaesth [Internet]. 2003 [cited 2023 Jan 5];91(6):836-41. https://doi.org/10.1093/bja/aeg264
5. Evans MS, Lysakowski C, Tramèr MR. Nefopam for the prevention of postoperative pain: quantitative systematic review. Br J Anaesth. 2008;101(5):610-7. https://doi.org/10.1093/bja/aen267
6. Mimoz O, Incagnoli P, Josse C, Gillon MC, Kuhlman L, Mirand A, et al. Analgesic efficacy and safety of nefopam vs. propacetamol following hepatic resection. Anaesthesia. 2001;56(6):520-5. https://doi.org/10.1046/j.1365-2044.2001.01980.x
7. Mitra S, Carlyle D, Kodumudi G, Kodumudi V, Vadivelu N. New advances in acute postoperative pain management. Curr Pain Headache Rep. 2018;22:1. https://doi.org/10.1007/s11916-018-0690-8
8. Girard P, Chauvin M, Verleye M. Nefopam analgesia and its role in multimodal analgesia: a review of preclinical and clinical studies. Clin Exp Pharmacol Physiol. 2016;43(1):3-12. https://doi.org/10.1111/1440-1681.12506
9. Hariton E, Locascio JJ. Randomised controlled trials-the gold standard for effectiveness research. BJOG. 2018;125(13):1716. https://doi.org/10.1111/1471-0528.15199
10. Kim KH, Abdi S. Rediscovery of nefopam for the treatment of neuropathic pain. Korean J Pain [Internet]. 2014 [cited 2023 Jan 5];27(2):103. https://doi.org/10.3344/kjp.2014.27.2.103
11. Kim K, Kim WJ, Choi DK, Lee YK, Choi IC, Sim JY. The analgesic efficacy and safety of nefopam in patient-controlled analgesia after cardiac surgery: a randomized, double-blind, prospective study. J Int Med Res [Internet]. 2014 [cited 2023 Jan 5];42(3):684-92. https://doi.org/10.1177/0300060514525351
12. Jung KT, So KY, Kim SC, Kim SH. Effect of nefopam-based patient-controlled analgesia with and without fentanyl on postoperative pain intensity in patients following laparoscopic cholecystectomy: a prospective, randomized, controlled, double-blind non-inferiority trial. Medicina [Internet]. 2021 [cited 2023 Jan 5];57(4):316. https://doi.org/10.3390/medicina57040316
13. Martinez V, Beloeil H, Marret E, Fletcher D, Ravaud P, Trinquart L. Non-opioid analgesics in adults after major surgery: systematic review with network meta-analysis of randomized trials. Br J Anaesth. 2017;118(1):22-31. https://doi.org/10.1093/bja/aew391
14. Barazanchi AWH, MacFater WS, Rahiri JL, Tutone S, Hill AG, Joshi GP, et al. Evidence-based management of pain after laparoscopic cholecystectomy: a PROSPECT review update. Br J Anaesth. 2018;121(4):787-803. https://doi.org/10.1016/j.bja.2018.06.023
15. Zhao T, Shen Z, Sheng S. The efficacy and safety of nefopam for pain relief during laparoscopic cholecystectomy: a meta-analysis. Medicine. 2018;97(10):e0089. https://doi.org/10.1097/MD.0000000000010089
16. Higgins JP, Savovi? J, Page MJ, Elbers RG, Sterne JA. Assessing risk of bias in a randomized trial. In: Higgins JPT, Thomas J, Chandler J, Li MCT, Page MJ, Welch VA, editors. Cochrane handbook for systematic reviews of interventions. Hoboken, NJ: Wiley-Blackwell; 2019 Sep 23. pp. 205-28. https://doi.org/10.1002/9781119536604.ch8
17. DistillerSR.com. Literature review software. Available from: https://www.distillersr.com/products/distillersr-systematic-review-software
18. Stoll CRT, Izadi S, Fowler S, Green P, Suls J, Colditz GA. The value of a second reviewer for study selection in systematic reviews. Res Synth Methods. 2019;10(4):539-45. https://doi.org/10.1002/jrsm.1369
19. Kapfer B, Alfonsi P, Guignard B, Sessler DI, Chauvin M. Nefopam and ketamine comparably enhance postoperative analgesia. Anesth Analg [Internet]. 2005 Jan [cited 2023 Jan 5];100(1):169. https://doi.org/10.1213/01.ANE.0000138037.19757.ED
20. Richebé P, Picard W, Rivat C, Jelacic S, Branchard O, Leproust S, et al. Effects of nefopam on early postoperative hyperalgesia after cardiac surgery. J Cardiothorac Vasc Anesth. 2013;27(3):427-35. https://doi.org/10.1053/j.jvca.2012.08.015
21. Moon JY, Choi SS, Lee SY, Lee MK, Kim JE, Lee JE, et al. The effect of nefopam on postoperative fentanyl consumption: a randomized, double-blind study. Korean J Pain. 2016;29(2):110-8. https://doi.org/10.3344/kjp.2016.29.2.110
22. Son JS, Doo A, Kwon YJ, Han YJ, Ko S. A comparison between ketorolac and nefopam as adjuvant analgesics for postoperative patient-controlled analgesia: a randomized, double-blind, prospective study. Korean J Anesthesiol. 2017;70(6):612-8. https://doi.org/10.4097/kjae.2017.70.6.612
23. Nair A. Nefopam: another pragmatic analgesic in managing chronic neuropathic pain. Indian J Palliat Care [Internet]. 2019 Jul 1 [cited 2023 Jan 5];25(3):482. https://doi.org/10.4103/IJPC.IJPC_215_18
24. Na HS, Oh AY, Koo BW, Lim DJ, Ryu JH, Han JW. Preventive analgesic efficacy of nefopam in acute and chronic pain after breast cancer surgery: a prospective, double-blind, and randomized trial. Medicine. 2016;95(20):e3705. https://doi.org/10.1097/MD.0000000000003705
25. Pasutharnchat K, Wichachai W, Buachai R, Yuen Ho K, Hadi Mohamed A. Analgesic efficacy of nefopam for cancer pain: a randomized controlled study. F1000Res. 2020 [cited 2023 Jan 5];9:378. https://doi.org/10.12688/f1000research.23455.1
26. Lekprasert V, Yapanan L, Ittichaikulthol W, Buachai R, Soisod P, Sophonsritsuk A. Perioperative intravenous patient-controlled analgesic efficacy of morphine with combined nefopam and parecoxib versus parecoxib in gynecologic surgery: a randomized, double-blind study. Anesthesiol Res Pract. 2021;2021:5461890. https://doi.org/10.1155/2021/5461890
27. Chalermkitpanit P, Limthongkul W, Yingsakmongkol W, Thepsoparn M, Pannangpetch P, Tangchitcharoen N, et al. Analgesic effect of intravenous nefopam for postoperative pain in minimally invasive spine surgery: a randomized prospective study. Asian Spine J. 2022;16(5):651. https://doi.org/10.31616/asj.2021.0337
28. Yoon S, Lee HB, Na KJ, Park S, Bahk J, Lee HJ. Effect of continuous infusion of intravenous nefopam on postoperative opioid consumption after video-assisted thoracic surgery: a double-blind randomized controlled trial. Pain Physician. 2022;25(6):491-500.
29. Lavand'homme P, Steyaert A. Opioid-free anesthesia opioid side effects: tolerance and hyperalgesia. Best Pract Res Clin Anaesthesiol. 2017;31(4):487-98. https://doi.org/10.1016/j.bpa.2017.05.003
30. Stephan BC, Parsa FD. Avoiding opioids and their harmful side effects in the postoperative patient: exogenous opioids, endogenous endorphins, wellness, mood, and their relation to postoperative pain. Hawaii J Med Public Health. 2016;75(3):63-7.
31. Li Y, Dong H, Tan S, Qian Y, Jin W. Effects of thoracic epidural anesthesia/analgesia on the stress response, pain relief, hospital stay, and treatment costs of patients with esophageal carcinoma undergoing thoracic surgery: a single-center, randomized controlled trial. Medicine. 2019;98(7):e14362. https://doi.org/10.1097/MD.0000000000014362
32. Weber L, Yeomans DC, Tzabazis A. Opioid-induced hyperalgesia in clinical anesthesia practice: what has remained from theoretical concepts and experimental studies?. Curr Opin Anaesthesiol. 2017;30(4):458-65. https://doi.org/10.1097/ACO.0000000000000485
33. Tramoni G, Viale JP, Cazals C, Bhageerutty K. Morphine-sparing effect of nefopam by continuous intravenous injection after abdominal surgery by laparotomy. Eur J Anaesthesiol. 2003;20(12):990-2. https://doi.org/10.1097/00003643-200312000-00013
34. Moussa MK, Lefevre N, Valentin E, Meyer A, Grimaud O, Bohu Y, et al. Dynamic intermittent compression cryotherapy with intravenous nefopam results in faster pain recovery than static compression cryotherapy with oral nefopam: post-anterior cruciate ligament reconstruction. J Exp Orthop. 2023;10(1):72. https://doi.org/10.1186/s40634-023-00639-3

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1. Choi SK, Yoon MH, Choi JI, Kim WM, Heo BH, Park KS, et al. Comparison of effects of intraoperative nefopam and ketamine infusion on managing postoperative pain after laparoscopic cholecystectomy administered remifentanil. Korean J Anesthesiol. 2016;69(5):480-6. https://doi.org/10.4097/kjae.2016.69.5.480

2. Charoenpol FN, Khampitak N, Aimnang C, Pachirat K, Sirithanaphol W, Rompsaithong U, et al. Single-dose intravenous nefopam on postoperative catheter-related bladder discomfort in patients undergoing transurethral resection of prostate: a randomized, double-blind placebo-controlled trial. J Anesth. 2023;37(1):72-8. https://doi.org/10.1007/s00540-022-03130-y

3. Franzese A, Borrelli O, Corrado G, Rea P, Di Nardo G, Grandinetti AL, et al. Domperidone is more effective than cisapride in children with diabetic gastroparesis. Aliment Pharmacol Ther. 2002;16:951-7. https://doi.org/10.1046/j.1365-2036.2002.01240.x

4. du Manoir B, Aubrun F, Langlois M, le Guern ME, Alquier C, Chauvin M, et al. Randomized prospective study of the analgesic effect of nefopam after orthopaedic surgery. Br J Anaesth [Internet]. 2003 [cited 2023 Jan 5];91(6):836-41. https://doi.org/10.1093/bja/aeg264

5. Evans MS, Lysakowski C, Tramèr MR. Nefopam for the prevention of postoperative pain: quantitative systematic review. Br J Anaesth. 2008;101(5):610-7. https://doi.org/10.1093/bja/aen267

6. Mimoz O, Incagnoli P, Josse C, Gillon MC, Kuhlman L, Mirand A, et al. Analgesic efficacy and safety of nefopam vs. propacetamol following hepatic resection. Anaesthesia. 2001;56(6):520-5. https://doi.org/10.1046/j.1365-2044.2001.01980.x

7. Mitra S, Carlyle D, Kodumudi G, Kodumudi V, Vadivelu N. New advances in acute postoperative pain management. Curr Pain Headache Rep. 2018;22:1. https://doi.org/10.1007/s11916-018-0690-8

8. Girard P, Chauvin M, Verleye M. Nefopam analgesia and its role in multimodal analgesia: a review of preclinical and clinical studies. Clin Exp Pharmacol Physiol. 2016;43(1):3-12. https://doi.org/10.1111/1440-1681.12506

9. Hariton E, Locascio JJ. Randomised controlled trials-the gold standard for effectiveness research. BJOG. 2018;125(13):1716. https://doi.org/10.1111/1471-0528.15199

10. Kim KH, Abdi S. Rediscovery of nefopam for the treatment of neuropathic pain. Korean J Pain [Internet]. 2014 [cited 2023 Jan 5];27(2):103. https://doi.org/10.3344/kjp.2014.27.2.103

11. Kim K, Kim WJ, Choi DK, Lee YK, Choi IC, Sim JY. The analgesic efficacy and safety of nefopam in patient-controlled analgesia after cardiac surgery: a randomized, double-blind, prospective study. J Int Med Res [Internet]. 2014 [cited 2023 Jan 5];42(3):684-92. https://doi.org/10.1177/0300060514525351

12. Jung KT, So KY, Kim SC, Kim SH. Effect of nefopam-based patient-controlled analgesia with and without fentanyl on postoperative pain intensity in patients following laparoscopic cholecystectomy: a prospective, randomized, controlled, double-blind non-inferiority trial. Medicina [Internet]. 2021 [cited 2023 Jan 5];57(4):316. https://doi.org/10.3390/medicina57040316

13. Martinez V, Beloeil H, Marret E, Fletcher D, Ravaud P, Trinquart L. Non-opioid analgesics in adults after major surgery: systematic review with network meta-analysis of randomized trials. Br J Anaesth. 2017;118(1):22-31. https://doi.org/10.1093/bja/aew391

14. Barazanchi AWH, MacFater WS, Rahiri JL, Tutone S, Hill AG, Joshi GP, et al. Evidence-based management of pain after laparoscopic cholecystectomy: a PROSPECT review update. Br J Anaesth. 2018;121(4):787-803. https://doi.org/10.1016/j.bja.2018.06.023

15. Zhao T, Shen Z, Sheng S. The efficacy and safety of nefopam for pain relief during laparoscopic cholecystectomy: a meta-analysis. Medicine. 2018;97(10):e0089. https://doi.org/10.1097/MD.0000000000010089

16. Higgins JP, Savovi? J, Page MJ, Elbers RG, Sterne JA. Assessing risk of bias in a randomized trial. In: Higgins JPT, Thomas J, Chandler J, Li MCT, Page MJ, Welch VA, editors. Cochrane handbook for systematic reviews of interventions. Hoboken, NJ: Wiley-Blackwell; 2019 Sep 23. pp. 205-28. https://doi.org/10.1002/9781119536604.ch8

17. DistillerSR.com. Literature review software. Available from: https://www.distillersr.com/products/distillersr-systematic-review-software

18. Stoll CRT, Izadi S, Fowler S, Green P, Suls J, Colditz GA. The value of a second reviewer for study selection in systematic reviews. Res Synth Methods. 2019;10(4):539-45. https://doi.org/10.1002/jrsm.1369

19. Kapfer B, Alfonsi P, Guignard B, Sessler DI, Chauvin M. Nefopam and ketamine comparably enhance postoperative analgesia. Anesth Analg [Internet]. 2005 Jan [cited 2023 Jan 5];100(1):169. https://doi.org/10.1213/01.ANE.0000138037.19757.ED

20. Richebé P, Picard W, Rivat C, Jelacic S, Branchard O, Leproust S, et al. Effects of nefopam on early postoperative hyperalgesia after cardiac surgery. J Cardiothorac Vasc Anesth. 2013;27(3):427-35. https://doi.org/10.1053/j.jvca.2012.08.015

21. Moon JY, Choi SS, Lee SY, Lee MK, Kim JE, Lee JE, et al. The effect of nefopam on postoperative fentanyl consumption: a randomized, double-blind study. Korean J Pain. 2016;29(2):110-8. https://doi.org/10.3344/kjp.2016.29.2.110

22. Son JS, Doo A, Kwon YJ, Han YJ, Ko S. A comparison between ketorolac and nefopam as adjuvant analgesics for postoperative patient-controlled analgesia: a randomized, double-blind, prospective study. Korean J Anesthesiol. 2017;70(6):612-8. https://doi.org/10.4097/kjae.2017.70.6.612

23. Nair A. Nefopam: another pragmatic analgesic in managing chronic neuropathic pain. Indian J Palliat Care [Internet]. 2019 Jul 1 [cited 2023 Jan 5];25(3):482. https://doi.org/10.4103/IJPC.IJPC_215_18

24. Na HS, Oh AY, Koo BW, Lim DJ, Ryu JH, Han JW. Preventive analgesic efficacy of nefopam in acute and chronic pain after breast cancer surgery: a prospective, double-blind, and randomized trial. Medicine. 2016;95(20):e3705. https://doi.org/10.1097/MD.0000000000003705

25. Pasutharnchat K, Wichachai W, Buachai R, Yuen Ho K, Hadi Mohamed A. Analgesic efficacy of nefopam for cancer pain: a randomized controlled study. F1000Res. 2020 [cited 2023 Jan 5];9:378. https://doi.org/10.12688/f1000research.23455.1

26. Lekprasert V, Yapanan L, Ittichaikulthol W, Buachai R, Soisod P, Sophonsritsuk A. Perioperative intravenous patient-controlled analgesic efficacy of morphine with combined nefopam and parecoxib versus parecoxib in gynecologic surgery: a randomized, double-blind study. Anesthesiol Res Pract. 2021;2021:5461890. https://doi.org/10.1155/2021/5461890

27. Chalermkitpanit P, Limthongkul W, Yingsakmongkol W, Thepsoparn M, Pannangpetch P, Tangchitcharoen N, et al. Analgesic effect of intravenous nefopam for postoperative pain in minimally invasive spine surgery: a randomized prospective study. Asian Spine J. 2022;16(5):651. https://doi.org/10.31616/asj.2021.0337

28. Yoon S, Lee HB, Na KJ, Park S, Bahk J, Lee HJ. Effect of continuous infusion of intravenous nefopam on postoperative opioid consumption after video-assisted thoracic surgery: a double-blind randomized controlled trial. Pain Physician. 2022;25(6):491-500.

29. Lavand'homme P, Steyaert A. Opioid-free anesthesia opioid side effects: tolerance and hyperalgesia. Best Pract Res Clin Anaesthesiol. 2017;31(4):487-98. https://doi.org/10.1016/j.bpa.2017.05.003

30. Stephan BC, Parsa FD. Avoiding opioids and their harmful side effects in the postoperative patient: exogenous opioids, endogenous endorphins, wellness, mood, and their relation to postoperative pain. Hawaii J Med Public Health. 2016;75(3):63-7.

31. Li Y, Dong H, Tan S, Qian Y, Jin W. Effects of thoracic epidural anesthesia/analgesia on the stress response, pain relief, hospital stay, and treatment costs of patients with esophageal carcinoma undergoing thoracic surgery: a single-center, randomized controlled trial. Medicine. 2019;98(7):e14362. https://doi.org/10.1097/MD.0000000000014362

32. Weber L, Yeomans DC, Tzabazis A. Opioid-induced hyperalgesia in clinical anesthesia practice: what has remained from theoretical concepts and experimental studies?. Curr Opin Anaesthesiol. 2017;30(4):458-65. https://doi.org/10.1097/ACO.0000000000000485

33. Tramoni G, Viale JP, Cazals C, Bhageerutty K. Morphine-sparing effect of nefopam by continuous intravenous injection after abdominal surgery by laparotomy. Eur J Anaesthesiol. 2003;20(12):990-2. https://doi.org/10.1097/00003643-200312000-00013

34. Moussa MK, Lefevre N, Valentin E, Meyer A, Grimaud O, Bohu Y, et al. Dynamic intermittent compression cryotherapy with intravenous nefopam results in faster pain recovery than static compression cryotherapy with oral nefopam: post-anterior cruciate ligament reconstruction. J Exp Orthop. 2023;10(1):72. https://doi.org/10.1186/s40634-023-00639-3