Adjuvant Continuous Infusion of Nefopam Versus Standard of Care in Mechanically Ventilated Critically Ill Patients: Randomized Double-blind Controlled Study

Summary

The aim of this prospective, randomized, active control, double blinded study is to assess the effect and safety of continuous infusion nefopam in mechanically ventilated ICU patients compared to standard of care. It is being hypothesized that continuous infusion nefopam will reduce opioid use with acceptable safety profile compared to standard of care.

Timeline

Start

2021-10-01

Primary completion

2023-03-01

Completion

2023-03-31

Publications

• Background Loeser JD, Treede RD. The Kyoto protocol of IASP Basic Pain Terminology. Pain. 2008 Jul 31;137(3):473-477. doi: 10.1016/j.pain.2008.04.025. Epub 2008 Jun 25. No abstract available.
• Background Chanques G, Sebbane M, Barbotte E, Viel E, Eledjam JJ, Jaber S. A prospective study of pain at rest: incidence and characteristics of an unrecognized symptom in surgical and trauma versus medical intensive care unit patients. Anesthesiology. 2007 Nov;107(5):858-60. doi: 10.1097/01.anes.0000287211.98642.51. No abstract available.
• Background Puntillo KA, Max A, Timsit JF, Vignoud L, Chanques G, Robleda G, Roche-Campo F, Mancebo J, Divatia JV, Soares M, Ionescu DC, Grintescu IM, Vasiliu IL, Maggiore SM, Rusinova K, Owczuk R, Egerod I, Papathanassoglou ED, Kyranou M, Joynt GM, Burghi G, Freebairn RC, Ho KM, Kaarlola A, Gerritsen RT, Kesecioglu J, Sulaj MM, Norrenberg M, Benoit DD, Seha MS, Hennein A, Periera FJ, Benbenishty JS, Abroug F, Aquilina A, Monte JR, An Y, Azoulay E. Determinants of procedural pain intensity in the intensive care unit. The Europain(R) study. Am J Respir Crit Care Med. 2014 Jan 1;189(1):39-47. doi: 10.1164/rccm.201306-1174OC.
• Background Chapman CR, Tuckett RP, Song CW. Pain and stress in a systems perspective: reciprocal neural, endocrine, and immune interactions. J Pain. 2008 Feb;9(2):122-45. doi: 10.1016/j.jpain.2007.09.006. Epub 2007 Dec 21.
• Background Tennant F. The physiologic effects of pain on the endocrine system. Pain Ther. 2013 Dec;2(2):75-86. doi: 10.1007/s40122-013-0015-x. Epub 2013 Aug 20.
• Background Sigakis MJ, Bittner EA. Ten Myths and Misconceptions Regarding Pain Management in the ICU. Crit Care Med. 2015 Nov;43(11):2468-78. doi: 10.1097/CCM.0000000000001256.
• Background Chanques G, Viel E, Constantin JM, Jung B, de Lattre S, Carr J, Cisse M, Lefrant JY, Jaber S. The measurement of pain in intensive care unit: comparison of 5 self-report intensity scales. Pain. 2010 Dec;151(3):711-721. doi: 10.1016/j.pain.2010.08.039. Epub 2010 Sep 16.
• Background Devlin JW, Skrobik Y, Gelinas C, Needham DM, Slooter AJC, Pandharipande PP, Watson PL, Weinhouse GL, Nunnally ME, Rochwerg B, Balas MC, van den Boogaard M, Bosma KJ, Brummel NE, Chanques G, Denehy L, Drouot X, Fraser GL, Harris JE, Joffe AM, Kho ME, Kress JP, Lanphere JA, McKinley S, Neufeld KJ, Pisani MA, Payen JF, Pun BT, Puntillo KA, Riker RR, Robinson BRH, Shehabi Y, Szumita PM, Winkelman C, Centofanti JE, Price C, Nikayin S, Misak CJ, Flood PD, Kiedrowski K, Alhazzani W. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018 Sep;46(9):e825-e873. doi: 10.1097/CCM.0000000000003299.
• Background Gelinas C, Fillion L, Puntillo KA, Viens C, Fortier M. Validation of the critical-care pain observation tool in adult patients. Am J Crit Care. 2006 Jul;15(4):420-7.
• Background Benyamin R, Trescot AM, Datta S, Buenaventura R, Adlaka R, Sehgal N, Glaser SE, Vallejo R. Opioid complications and side effects. Pain Physician. 2008 Mar;11(2 Suppl):S105-20.
• Background Wibbenmeyer L, Sevier A, Liao J, Williams I, Light T, Latenser B, Lewis R 2nd, Kealey P, Rosenquist R. The impact of opioid administration on resuscitation volumes in thermally injured patients. J Burn Care Res. 2010 Jan-Feb;31(1):48-56. doi: 10.1097/BCR.0b013e3181c7ed30.
• Background Kohler M, Chiu F, Gelber KM, Webb CA, Weyker PD. Pain management in critically ill patients: a review of multimodal treatment options. Pain Manag. 2016 Nov;6(6):591-602. doi: 10.2217/pmt-2016-0002. Epub 2016 May 18.
• Background Kumar K, Kirksey MA, Duong S, Wu CL. A Review of Opioid-Sparing Modalities in Perioperative Pain Management: Methods to Decrease Opioid Use Postoperatively. Anesth Analg. 2017 Nov;125(5):1749-1760. doi: 10.1213/ANE.0000000000002497.
• Background Payen JF, Genty C, Mimoz O, Mantz J, Bosson JL, Chanques G. Prescribing nonopioids in mechanically ventilated critically ill patients. J Crit Care. 2013 Aug;28(4):534.e7-12. doi: 10.1016/j.jcrc.2012.10.006. Epub 2013 Mar 19.
• Background Gregori-Puigjane E, Setola V, Hert J, Crews BA, Irwin JJ, Lounkine E, Marnett L, Roth BL, Shoichet BK. Identifying mechanism-of-action targets for drugs and probes. Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11178-83. doi: 10.1073/pnas.1204524109. Epub 2012 Jun 18.
• Background 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 Jun;42(3):684-92. doi: 10.1177/0300060514525351. Epub 2014 Apr 1.
• Background Moon JY, Choi SS, Lee SY, Lee MK, Kim JE, Lee JE, Lee SH. The Effect of Nefopam on Postoperative Fentanyl Consumption: A Randomized, Double-blind Study. Korean J Pain. 2016 Apr;29(2):110-8. doi: 10.3344/kjp.2016.29.2.110. Epub 2016 Apr 1.
• Background Sessler CN, Gosnell MS, Grap MJ, Brophy GM, O'Neal PV, Keane KA, Tesoro EP, Elswick RK. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002 Nov 15;166(10):1338-44. doi: 10.1164/rccm.2107138.
• Background Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, Truman B, Speroff T, Gautam S, Margolin R, Hart RP, Dittus R. Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA. 2001 Dec 5;286(21):2703-10. doi: 10.1001/jama.286.21.2703.
• Background Mimoz O, Chauvet S, Gregoire N, Marchand S, Le Guern ME, Saleh A, Couet W, Debaene B, Levy RH. Nefopam pharmacokinetics in patients with end-stage renal disease. Anesth Analg. 2010 Nov;111(5):1146-53. doi: 10.1213/ANE.0b013e3181f33488.
• Background Du Manoir B, Aubrun F, Langlois M, Le Guern ME, Alquier C, Chauvin M, Fletcher D. Randomized prospective study of the analgesic effect of nefopam after orthopaedic surgery. Br J Anaesth. 2003 Dec;91(6):836-41. doi: 10.1093/bja/aeg264.
• Background Chawla LS, Russell JA, Bagshaw SM, Shaw AD, Goldstein SL, Fink MP, Tidmarsh GF. Angiotensin II for the Treatment of High-Output Shock 3 (ATHOS-3): protocol for a phase III, double-blind, randomised controlled trial. Crit Care Resusc. 2017 Mar;19(1):43-49.
• Abdelraouf MG, Farid SF, Mukhtar AM, Sabry NA. Adjuvant nefopam versus standard of care in mechanically ventilated surgical critically ill patients: A randomized, double-blind controlled study. Anaesth Crit Care Pain Med. 2025 May;44(3):101518. doi: 10.1016/j.accpm.2025.101518. Epub 2025 Apr 16.

Drugs

Indications

No indication recorded.