J Dent Anesth Pain Med.  2019 Feb;19(1):55-66. 10.17245/jdapm.2019.19.1.55.

Effects on postoperative nausea and vomiting of nefopam versus fentanyl following bimaxillary orthognathic surgery: a prospective double-blind randomized controlled trial

• Choi E
• Karm MH
• So E
• Choi YJ
• Park S
• Oh Y
• Yun HJ
• Kim HJ
• Seo KS

• KMID: 2439036
• DOI: http://doi.org/10.17245/jdapm.2019.19.1.55

Abstract

BACKGROUND
Postoperative nausea and vomiting (PONV) frequently occurs following bimaxillary orthognathic surgeries. Compared to opioids, Nefopam is associated with lower incidences of PONV, and does not induce gastrointestinal tract injury, coagulopathy, nephrotoxicity, or fracture healing dysfunction, which are common side effects of Nonsteroidal anti-inflammatory drugs. We compared nefopam- and fentanyl-induced incidence of PONV in patients with access to patient-controlled analgesia (PCA) following bimaxillary orthognathic surgeries.
METHODS
Patients undergoing bimaxillary orthognathic surgeries were randomly divided into nefopam and fentanyl groups. Nefopam 120 mg or fentanyl 700 µg was mixed with normal saline to a final volume of 120 mL. Patients were given access to nefopam or fentanyl via PCA. Postoperative pain intensity and PONV were measured at 30 minutes and 1 hour after surgery in the recovery room and at 8, 24, 48, and 72 hours after surgery in the ward. The frequency of bolus delivery was compared at each time point.
RESULTS
Eighty-nine patients were enrolled in this study, with 48 in the nefopam (N) group and 41 in the fentanyl (F) group. PONV occurred in 13 patients (27.7%) in the N group and 7 patients (17.1%) in the F group at 8 hours post-surgery (P = 0.568), and there were no significant differences between the two groups at any of the time points. VAS scores were 4.4 ± 2.0 and 3.7 ± 1.9 in the N and F groups, respectively, at 8 hours after surgery (P = 0.122), and cumulative bolus delivery was 10.7 ± 13.7 and 8.6 ± 8.5, respectively (P = 0.408). There were no significant differences in pain or bolus delivery at any of the remaining time points.
CONCLUSION
Patients who underwent bimaxillary orthognathic surgery and were given nefopam via PCA did not experience a lower rate of PONV compared to those that received fentanyl via PCA. Furthermore, nefopam and fentanyl did not provide significantly different postoperative pain control.

Keyword

Fentanyl; Nefopam; Patient-Controlled Analgesia; Postoperative Nausea And Vomiting

MeSH Terms

Analgesia, Patient-Controlled
Analgesics, Opioid
Fentanyl*
Fracture Healing
Gastrointestinal Tract
Humans
Incidence
Nefopam*
Orthognathic Surgery*
Pain, Postoperative
Passive Cutaneous Anaphylaxis
Postoperative Nausea and Vomiting*
Prospective Studies*
Recovery Room
Analgesics, Opioid
Fentanyl
Nefopam

Figure

• 

  Fig. 1 Consolidated Standards of Reporting Trials (CONSORT) flow diagram of patients in this trial. Eighty-nine patients were randomly assigned to the Nefopam (n = 48) or Fentanyl (n = 41) groups. At 72 hours after the procedure, 31 and 34 patients remained in each arm, respectively.

Reference

1. Silva AC, O'Ryan F, Poor DB. Postoperative nausea and vomiting (ponv) after orthognathic surgery: A retrospective study and literature review. J Oral Maxillofac Surg. 2006; 64:1385–1397. PMID: 16916674.

2. Frost CM, Frost DE. Nursing care of patients in intermaxillary fixation. Heart Lung. 1983; 12:524–528. PMID: 6554262.

3. Niederhagen B, Braumann B, Dierke-Dzierzon C, Albrecht S. [postoperative pain after interventions in the area of the mouth-jaw-face]. Mund Kiefer Gesichtschir. 1997; 1:229–234. PMID: 9410633.

4. Park S, Chi SI, Seo KS, Kim HJ. Circadian variation of iv pca use in patients after orthognathic surgery - a retrospective comparative study. J Dent Anesth Pain Med. 2015; 15:141–146. PMID: 28879271.

5. Aoki Y, Yoshida K, Nishizawa D, Kasai S, Ichinohe T, Ikeda K, et al. Factors that affect intravenous patient-controlled analgesia for postoperative pain following orthognathic surgery for mandibular prognathism. PLoS One. 2014; 9:e98548. PMID: 24893040.

6. Ballantyne JC, Carr DB, Chalmers TC, Dear KB, Angelillo IF, Mosteller F. Postoperative patient-controlled analgesia: Meta-analyses of initial randomized control trials. J Clin Anesth. 1993; 5:182–193. PMID: 8318237.

7. Walder B, Schafer M, Henzi I, Tramer MR. Efficacy and safety of patient-controlled opioid analgesia for acute postoperative pain. A quantitative systematic review. Acta Anaesthesiol Scand. 2001; 45:795–804. PMID: 11472277.

8. George JA, Lin EE, Hanna MN, Murphy JD, Kumar K, Ko PS, et al. The effect of intravenous opioid patient-controlled analgesia with and without background infusion on respiratory depression: A meta-analysis. J Opioid Manag. 2010; 6:47–54. PMID: 20297614.

9. 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; 20:990–992. PMID: 14690106.

10. Rohm KD, Riechmann J, Boldt J, Schuler S, Suttner SW, Piper SN. Physostigmine for the prevention of postanaesthetic shivering following general anaesthesia - a placebo-controlled comparison with nefopam. Anaesthesia. 2005; 60:433–438. PMID: 15819761.

11. Myles PS, Wengritzky R. Simplified postoperative nausea and vomiting impact scale for audit and post-discharge review. Br J Anaesth. 2012; 108:423–429. PMID: 22290456.

12. McLintock TT, Kenny GN, Howie JC, McArdle CS, Lawrie S, Aitken H. Assessment of the analgesic efficacy of nefopam hydrochloride after upper abdominal surgery: A study using patient controlled analgesia. Br J Surg. 1988; 75:779–781. PMID: 3167526.

13. Lee JH, Kim JH, Cheong YK. The analgesic effect of nefopam with fentanyl at the end of laparoscopic cholecystectomy. Korean J Pain. 2013; 26:361–367. PMID: 24156002.

14. Kim YA, Kweon TD, Kim M, Lee HI, Lee YJ, Lee KY. Comparison of meperidine and nefopam for prevention of shivering during spinal anesthesia. Korean J Anesthesiol. 2013; 64:229–233. PMID: 23560188.

15. Bhatt AM, Pleuvry BJ, Maddison SE. Respiratory and metabolic effects of oral nefopam in human volunteers. Br J Clin Pharmacol. 1981; 11:209–211. PMID: 6783057.

16. 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. 2014; 42:684–692. PMID: 24691459.

17. Yoon JU, Byeon GJ, Cheon JH, Choi YM, Ri HS, Baik SW. Post-operative intravenous patient-controlled analgesic efficacy of morphine with ketorolac versus nefopam after laparoscopic gynecologic surgery: A randomized noninferiority trial. Korean J Anesthesiol. 2016; 69:161–166. PMID: 27066208.

18. Su B, O'Connor JP. Nsaid therapy effects on healing of bone, tendon, and the enthesis. J Appl Physiol (1985). 2013; 115:892–899. PMID: 23869068.

19. Marquez-Lara A, Hutchinson ID, Nunez F Jr, Smith TL, Miller AN. Nonsteroidal anti-inflammatory drugs and bone-healing: A systematic review of research quality. JBJS Rev. 2016; 4.

20. Baht GS, Nadesan P, Silkstone D, Alman BA. Pharmacologically targeting beta-catenin for nf1 associated deficiencies in fracture repair. Bone. 2017; 98:31–36. PMID: 28254468.

21. Grass JA. Patient-controlled analgesia. Anesth Analg. 2005; 101:S44–S61. PMID: 16334492.

22. Dawson R, von Fintel N, Nairn S. Sedation assessment using the ramsay scale. (cover story). Emergency Nurse. 2010; 18:18–20.

23. Precious DS, Multari J, Finley GA, McGrath P. A comparison of patient-controlled and fixed schedule analgesia after orthognathic surgery. J Oral Maxillofac Surg. 1997; 55:33–39. discussion 40. PMID: 8994466.

24. Shin TJ, Park Y, Seo K-S, Han HJ, Kim HJ. Surgical invasiveness is important for determining severity of postoperative pain after oral & maxillofacial surgery. J Korean Dent Soc Anesthesiol. 2011; 11:9–15.

25. Gold BS, Kitz DS, Lecky JH, Neuhaus JM. Unanticipated admission to the hospital following ambulatory surgery. JAMA. 1989; 262:3008–3010. PMID: 2810644.

26. Rodrigo C, Campbell R, Chow J, Tong A. The effect of a 4-mg preoperative intravenous dose of ondansetron in preventing nausea and vomiting after maxillofacial surgery. J Oral Maxillofac Surg. 1996; 54:1171–1175. PMID: 8859234.

27. Gray AM, Nevinson MJ, Sewell RD. The involvement of opioidergic and noradrenergic mechanisms in nefopam antinociception. Eur J Pharmacol. 1999; 365:149–157. PMID: 9988097.

28. Rosland JH, Hole K. The effect of nefopam and its enantiomers on the uptake of 5-hydroxytryptamine, noradrenaline and dopamine in crude rat brain synaptosomal preparations. J Pharm Pharmacol. 1990; 42:437–438. PMID: 1979627.

29. Fuller RW, Snoddy HD. Evaluation of nefopam as a monoamine uptake inhibitor in vivo in mice. Neuropharmacology. 1993; 32:995–999. PMID: 7507578.

30. Dordoni PL, Della Ventura M, Stefanelli A, Iannace E, Paparella P, Rocca B, et al. Effect of ketorolac, ketoprofen and nefopam on platelet function. Anaesthesia. 1994; 49:1046–1049. PMID: 7864317.

31. Michael R, Younan N, Aziz M, Mostafa N, Ghobriel A, Gintautas J. Effect of a non-opiate analgesic, nefopam hydrochloride, on stress gastric ulcer in rats. Proc West Pharmacol Soc. 2001; 44:109–111. PMID: 11793953.

32. Alfonsi P, Adam F, Passard A, Guignard B, Sessler DI, Chauvin M. Nefopam, a nonsedative benzoxazocine analgesic, selectively reduces the shivering threshold in unanesthetized subjects. Anesthesiology. 2004; 100:37–43. PMID: 14695722.

33. Kim KH, Abdi S. Rediscovery of nefopam for the treatment of neuropathic pain. Korean J Pain. 2014; 27:103–111. PMID: 24748937.

34. 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. 2003; 91:836–841. PMID: 14633755.

35. 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; 56:520–525. PMID: 11412156.

36. Kapfer B, Alfonsi P, Guignard B, Sessler DI, Chauvin M. Nefopam and ketamine comparably enhance postoperative analgesia. Anesth Analg. 2005; 100:169–174. PMID: 15616073.

37. Heel RC, Brogden RN, Pakes GE, Speight TM, Avery GS. Nefopam: A review of its pharmacological properties and therapeutic efficacy. Drugs. 1980; 19:249–267. PMID: 6991238.

38. Djerada Z, Fournet-Fayard A, Gozalo C, Lelarge C, Lamiable D, Millart H, et al. Population pharmacokinetics of nefopam in elderly, with or without renal impairment, and its link to treatment response. Br J Clin Pharmacol. 2014; 77:1027–1038. PMID: 24252055.

39. Evans MS, Lysakowski C, Tramer MR. Nefopam for the prevention of postoperative pain: Quantitative systematic review. Br J Anaesth. 2008; 101:610–617. PMID: 18796441.

40. Oh CS, Jung E, Lee SJ, Kim SH. Effect of nefopamversus fentanyl-based patient-controlled analgesia on postoperative nausea and vomiting in patients undergoing gynecological laparoscopic surgery: A prospective double-blind randomized controlled trial. Curr Med Res Opin. 2015; 31:1599–1607. PMID: 26047392.

41. Jin HS, Kim YC, Yoo Y, Lee C, Cho CW, Kim WJ. Opioid sparing effect and safety of nefopam in patient controlled analgesia after laparotomy: A randomized, double blind study. J Int Med Res. 2016; 44:844–854. PMID: 27358262.

42. Kim SY, Huh KH, Roh YH, Oh YJ, Park J, Choi YS. Nefopam as an adjunct to intravenous patient-controlled analgesia after renal transplantation: A randomised trial. Acta Anaesthesiol Scand. 2015; 59:1068–1075. PMID: 25903742.

43. 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; 29:110–118. PMID: 27103966.

44. Tirault M, Derrode N, Clevenot D, Rolland D, Fletcher D, Debaene B. The effect of nefopam on morphine overconsumption induced by large-dose remifentanil during propofol anesthesia for major abdominal surgery. Anesth Analg. 2006; 102:110–117. PMID: 16368814.