Intraoperative and Postoperative Nefopam Administration for Video-assisted Thoracoscopic Lobectomy Pain: A Multicenter, Randomized, Controlled Trial

Chaowanan Khamtuikrua; Sirilak  Suksompong; Punnarerk  Thongcharoen; Suparauk Geanphun; Ratchaya  Weerayutwattana; Sira Laohathai; Thanapat   Vanichnatee; Non  Singpan; Chompunoot  Pathonsamit

doi:10.33192/smj.v77i10.274325

Authors

Chaowanan Khamtuikrua Department of Anesthesiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Sirilak Suksompong Department of Anesthesiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
Punnarerk Thongcharoen Division of Cardiothoracic Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Suparauk Geanphun Division of Cardiothoracic Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Ratchaya Weerayutwattana Department of Anesthesiology, Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand
Sira Laohathai Cardiothoracic Surgery Unit, Department of Surgery, Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand
Thanapat Vanichnatee Department of Anesthesiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
Non Singpan Department of Anesthesiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
Chompunoot Pathonsamit Department of Anesthesiology, Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand

DOI:

https://doi.org/10.33192/smj.v77i10.274325

Keywords:

Video-assisted thoracoscopic surgery, nefopam, postoperative pain, lobectomy

Abstract

Objective: Intraoperative nefopam infusion was documented as safe and viable for supplemental pain management, alongside opioids following surgery. Postoperative pain control with nefopam after video-assisted thoracoscopic surgery (VATS) is not well understood. This study assessed the effects of nefopam towards postoperative morphine requirements and pain intensity 24 hours after VATS lobectomies.

Materials and Methods: This multicenter, double-blind, randomized, controlled trial enrolled 18-70-year-old elective VATS lobectomy patients. Patients were randomized 1:1, receiving nefopam or normal saline solution (NSS) administered during the maintenance of anesthesia and 24-hour postoperative period. All received multimodal analgesia, including paracetamol, ibuprofen, and intercostal nerve blocks. Postoperative morphine was administered via patient-controlled analgesia (PCA) devices and recorded at 10 and 30 minutes, and 1, 2, 6, 12, 18 and 24 hours.
Postoperative pain was graded at rest and during deep breathing using numeric rating scale (NRS) scores 1, 2, 12, and 24 hours.

Results: Of 72 enrolled patients, 70.8% were female, with a mean (± standard deviation) age of 56.5 ± 10.4 years. No significant postoperative difference was observed between groups for: total median (P25, P75) morphine amounts administered over 24 hours (nefopam, 14 [8, 24] mg; control, 8 [4.5, 19] mg; p = 0.17); NRS pain scores during rest (p = 0.98) or deep breathing (p = 0.82) 1, 2, 12, and 24 hours

Conclusion: Intraoperative and postoperative nefopam infusion, including multimodal analgesia, did not reduce morphine consumption or NRS pain scores in VATS lobectomy, but may have prolonged the duration of pain relief.

References

Sihoe ADL. Video-assisted thoracoscopic surgery as the gold standard for lung cancer surgery. Respirology. 2020;25(S2):49-60.

Bishnoi S, Puri HV, Asaf BB, Pulle MV, Parikh MBK, Patel MV, et al. Video-assisted thoracoscopic surgery: The preferred method to manage pulmonary sequestration. J Minim Access Surg. 2022;18(2):230-4.

Flores RM, Park BJ, Dycoco J, Aronova A, Hirth Y, Rizk NP, et al. Lobectomy by video-assisted thoracic surgery (VATS) versus thoracotomy for lung cancer. J Thorac Cardiovasc Surg. 2009;138(1):11-8.

Landreneau RJ, Hazelrigg SR, Mack MJ, Dowling RD, Burke D, Gavlick J, et al. Postoperative pain-related morbidity: video-assisted thoracic surgery versus thoracotomy. Ann Thorac Surg. 1993;56(6):1285-9.

Pan H, Chen H, Kong W, Ning J, Ge Z, Tian Y, et al. Video-assisted thoracoscopic surgery versus thoracotomy following neoadjuvant immunochemotherapy in resectable stage III non-small cell lung cancer among Chinese populations: a multi-center retrospective cohort study. Clin Lung Cancer. 2024;25(5):395-406.e5.

Zhang G, Fan J, Yu Z, Chai Y, Zhang S, Wu M, et al. Video-assisted thoracoscopic treatment as two-day surgery for lung neoplasms: a propensity-matched analysis. BMC Cancer. 2022;22(1):832.

Sabra MJ, Alwatari Y, Bierema C, Wolfe LG, Cassano AD, Shah RD. Five-year experience with VATS versus thoracotomy segmentectomy for lung tumor resection. Innovations. 2020;15(4):346-54.

Ng A, Swanevelder J. Pain relief after thoracotomy: is epidural analgesia the optimal technique? Br J Anaesth. 2007;98(2):159-62.

Goto T. What is the best pain control after thoracic surgery? J Thorac Dis. 2018;10(3):1335-8.

Soto RG, Fu ES. Acute pain management for patients undergoing thoracotomy. Ann Thorac Surg. 2003;75(4):1349-57.

Piccioni F, Segat M, Falini S, Umari M, Putina O, Cavaliere L, et al. Enhanced recovery pathways in thoracic surgery from Italian VATS Group: perioperative analgesia protocols. J Thorac Dis. 2018;10(Suppl 4):S555-S63.

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

Heel RC, Brogden RN, Pakes GE, Speight TM, Avery GS. Nefopam: a review of its pharmacological properties and therapeutic efficacy. Drugs. 1980;19(4):249-67.

Kim EM, Jeon JH, Chung MH, Choi EM, Baek SH, Joen PH, et al. The Effect of Nefopam Infusion during Laparascopic Cholecystectomy on Postoperative Pain. Int J Med Sci. 2017;14(6):570-7.

Du Manoir B, Aubrun F, Langlois M, 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(6):836-41.

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.

McLintock TTC, Kenny GNC, 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. 2005;75(8):779-81.

Batchelor TJP, Rasburn NJ, Abdelnour-Berchtold E, Brunelli A, Cerfolio RJ, Gonzalex M, et al. Guidelines for enhanced recovery after lung surgery: recommendations of the Enhanced Recovery After Surgery (ERAS®) Society and the European Society of Thoracic Surgeons (ESTS). Eur J Cardiothorac Surg. 2018;55(1):91-115.

Na HS, Oh AY, Ryu JH, Koo BW, Nam SW, Jo J, et al. Intraoperative Nefopam Reduces Acute Postoperative Pain after Laparoscopic Gastrectomy: a Prospective, Randomized Study. J Gastrointest Surg. 2018;22(5):771-7.

Lee S, Lee S, Kim H, Oh C, Park S, Kim Y, et al. The Analgesic Efficacy of Nefopam in Patient-Controlled Analgesia after Laparoscopic Gynecologic Surgery: A Randomized, Double-Blind, Non-Inferiority Study. J Clin Med. 2021;10(5):1043.

Guerra-Londono CE, Privorotskiy A, Cozowicz C, Hicklen RS, Memtsoudis SG, Mariano ER, et al. Assessment of Intercostal Nerve Block Analgesia for Thoracic Surgery: A Systematic Review and Meta-analysis. JAMA Netw Open. 2021;4(11):e2133394.

Bolotin G, Lazarovici H, Uretzky G, Zlotnick AY, Tamir A, Saute M. The efficacy of intraoperative internal intercostal nerve block during video-assisted thoracic surgery on postoperative pain. Ann Thorac Surg. 2000;70(6):1872-5.

Ki H-S, Shim J-G, Choi H-K, Ryu KH, Kang Dy, Park J, et al. Nefopam as a multimodal analgesia in thoracoscopic surgery: a randomized controlled trial. J Thorac Dis. 2024;16(6):3644-54.

Jahangiri Fard A, Farzanegan B, Khalili A, Ahmadabad NE, Kakhaki AD, Parsa T, et al. Paracetamol Instead of Ketorolac in Post-Video-Assisted Thoracic Surgery Pain Management: A Randomized Trial. Anesthe Pain Med. 2016;6(6):e39175.

Seers K. Review: single dose, oral paracetamol reduces moderate to severe postoperative pain. Evid Based Nurs. 2004;7(3):84.

Derry C, Derry S, Moore RA, McQuay HJ. Single dose oral ibuprofen for acute postoperative pain in adults. Cochrane Database Syst Rev. 2009;2009(3):CD001548.

Derry CJ, Derry S, Moore RA. Single dose oral ibuprofen plus paracetamol (acetaminophen) for acute postoperative pain. Cochrane Database Syst Rev. 2013;2013(6):CD010210.

Suksompong S, Chaikittisilpa N, Wanchiange S, Poolsuppasit S, Thongcharoen P, Limratana P. Low dose intraoperative ketamine infusion with multilevel paravertebral block for pain after video-assisted thoracic surgery: a randomized-controlled study. Ann Palliat Med. 2021;10(7):7258-69.

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(1):37-43.

Jirakulsawat A, Noocharoen N, Somnuke P. Prehabilitation in Clinical Practice: A Review of Concepts and Implementation in Enhancing Postoperative Outcomes. Siriraj Med J. 2024;76(9):646-54.