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Multimodal analgesia for postoperative pain in Asia: a review of evidence with clinical focus on dexketoprofen and tramadol/dexketoprofen fixed-dose combination

  • Maria Dolma Santos1
  • Kim Soon Oh2
  • Giustino Varrassi3
  • Dinesh Nagrale4

1Department of Anesthesiology, Asian Hospital and Medical Center, 1780 Manila, Philippines

2Department of Orthopedics, Island Hospital, 10450 Penang, Malaysia

3President, Paolo Procacci Foundation (FPP), 00193 Rome, Italy

4Regional Asia Pacific Menarini Medical Team, 117440 Singapore, Singapore

DOI: 10.22514/sv.2021.210 Vol.17,Issue 6,November 2021 pp.1-7

Submitted: 19 July 2021 Accepted: 25 August 2021

Published: 08 November 2021

*Corresponding Author(s): Giustino Varrassi E-mail:


The majority of patients who have undergone surgery experience moderate-to-severe postoperative pain. Asian patients tend to under-report pain and are consequently under-treated. Poor postoperative pain management increases the risk of morbidity, prolonged opioid use, lower quality of life outcomes and the risk of chronic post-surgical pain. Multimodal analgesia is the cornerstone of postoperative pain management. Non-steroidal anti-inflammatory drugs are considered a core component of multimodal analgesia due to their anti-inflammatory and analgesic properties. Use of a consistent non-steroidal anti-inflammatory throughout the postoperative period can help to achieve and maintain adequate pain relief. This review investigates the use of multimodal analgesia in postoperative pain management in Asia, with a focus on clinicians’ experience with dexketoprofen as a non-steroidal anti-inflammatory therapy throughout the postoperative period and its combination as fixed dose with Tramadol, a centrally acting synthetic opioid analgesic, in Asian patients, when necessary.


Multimodal analgesia; Dexketoprofen; Tramadol; Fixed dose combination; Asia

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Maria Dolma Santos,Kim Soon Oh,Giustino Varrassi,Dinesh Nagrale. Multimodal analgesia for postoperative pain in Asia: a review of evidence with clinical focus on dexketoprofen and tramadol/dexketoprofen fixed-dose combination. Signa Vitae. 2021. 17(6);1-7.


[1] Chou R, Gordon DB, de Leon-Casasola OA, Rosenberg JM, Bickler S, Brennan T, et al. Management of Postoperative Pain: a Clinical Practice Guideline from the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists’ Committee on Regional Anesthesia, Executive Committee, and Administrative Council. The Journal of Pain. 2016; 17: 131–157.

[2] Goren A, Mould-Quevedo J, daCosta DiBonaventura M. Prevalence of Pain Reporting and Associated Health Outcomes across Emerging Markets and Developed Countries. Pain Medicine. 2014; 15: 1880–1891.

[3] Wang H, Li S, Liang N, Liu W, Liu H, Liu H. Postoperative pain experiences in Chinese adult patients after thoracotomy and video-assisted thoracic surgery. Journal of Clinical Nursing. 2017; 26: 2744–2754.

[4] Yin HH, Tse MMY, Wong FKY. Postoperative pain experience and barriers to pain management in Chinese adult patients undergoing thoracic surgery. Journal of Clinical Nursing. 2012; 21: 1232–1243.

[5] Berry P. Pain: Current understanding of assessment, management and treatments. Glenview IL: USA. 2001.

[6] Gan TJ. Poorly controlled postoperative pain: prevalence, consequences, and prevention. Journal of Pain Research. 2017; 10: 2287–2298.

[7] Tan M, Law LS, Gan TJ. Optimizing pain management to facilitate Enhanced Recovery after Surgery pathways. Canadian Journal of Anaesthesia. 2015; 62: 203–218.

[8] Gupta A, Kaur K, Sharma S, Goyal S, Arora S, Murthy RSR. Clinical aspects of acute post-operative pain management & its assessment. Journal of Advanced Pharmaceutical Technology & Research. 2010; 1: 97–108.

[9] Kuusniemi K, Pöyhiä R. Present-day challenges and future solutions in postoperative pain management: results from PainForum 2014. Journal of Pain Research. 2016; 9: 25–36.

[10] Schug SA, Palmer GM, Scott DA, Alcock M, Halliwell R, Mott JF. APM:SE Working Group of the Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine. Acute Pain Management: Scientific Evidence. 5th edition. ANZCA & FPM, Melbourne. 2020.

[11] European Society of Regional Anesthesia and Pain Therapy. PROSPECT. 2021. Available at: 21 May 2021).

[12] European Society of Regional Anesthesia and Pain Therapy. Overall PROSPECT Recommendations – Algorithm for the management of post-operative pain. 2019. Available at: https://archive.postoppain. org/sections/?root_id=27963§ion=4# (Accessed: 21 May 2021).

[13] Bhatia A, Buvanendran A. Anesthesia and postoperative pain control-multimodal anesthesia protocol. Journal of Spine Surgery. 2019; 5: S160–S165.

[14] de Leon JRC, Espinosa E. Pattern of pain management practices of Filipino surgeons. Oncology. 2008; 74: 40–45.

[15] Ng JJ, Leong WQ, Tan CS, Poon KH, Lomanto D, So JBY, et al. A Multimodal Analgesic Protocol Reduces Opioid-Related Adverse Events and Improves Patient Outcomes in Laparoscopic Sleeve Gastrectomy. Obesity Surgery. 2017; 27: 3075–3081.

[16] Low SJ, Wong SSC, Qiu Q, Lee Y, Chan TCW, Irwin MG, et al. An Audit of Changes in Outcomes of Acute Pain Service: Evolution over the last 2 Decades. Medicine. 2015; 94: e1673.

[17] Choi SW, Cho HK, Park S, Yoo JH, Lee JC, Baek MJ, et al. Clinical Medicine Multimodal Analgesia (MMA) Versus Patient-Controlled Analgesia (PCA) for One or Two-Level Posterior Lumbar Fusion Surgery. Journal of Clinical Medicine. 2020; 9: 1087.

[18] Barra M, Remák E, Liu DD, Xie L, Abraham L, Sadosky AB. A cost-consequence analysis of parecoxib and opioids vs opioids alone for postoperative pain: Chinese perspective. ClinicoEconomics and Outcomes Research. 2019; 11: 169–177.

[19] Li J, Ma Y, Xiao L. Postoperative Pain Management in Total Knee. Orthopaedic Surgery. 2019; 11: 755–761.

[20] Fusco M, Skaper SD, Coaccioli S, Varrassi G, Paladini A. Degenerative Joint Diseases and Neuroinflammation. Pain Practice. 2017;17:522-532.

[21] Varrassi G, Hanna M, Macheras G, Montero A, Montes Perez A, Meissner W, et al. Multimodal analgesia in moderate-to-severe pain: a role for a new fixed combination of dexketoprofen and tramadol. Current Medical Research and Opinion. 2017; 33: 1165–1173.

[22] Garimella V, Cellini C. Postoperative pain control. Clinics in Colon and Rectal Surgery. 2013; 26: 191–196.

[23] Zhao-Fleming H, Hand A, Zhang K, Polak R, Northcut A, Jacob D, et al. Effect of non-steroidal anti-inflammatory drugs on post-surgical complications against the backdrop of the opioid crisis. Burns & Trauma. 2018; 6: 25.

[24] Varrassi G, Yeam CT, Rekatsina M, Pergolizzi JV, Zis P, Paladini A. The Expanding Role of the COX Inhibitor/Opioid Receptor Agonist Combination in the Management of Pain. Drugs. 2020; 80: 1443–1453.

[25] Gaskell H, Derry S, Wiffen PJ, Moore RA. Single dose oral ketoprofen or dexketoprofen for acute postoperative pain in adults. The Cochrane Database of Systematic Reviews. 2017; 5: CD007355.

[26] Hanna M, Moon JY. A review of dexketoprofen trometamol in acute pain. Current Medical Research and Opinion. 2019; 35: 189–202.

[27] Jiménez-Martínez E, Gasco-García C, Arrieta-Blanco JJ, Gomez del Torno J, Bartolome Villar B. Study of the analgesic efficacy of Dexketoprofen Trometamol 25 mg. vs. Ibuprofen 600 mg. after their administration in patients subjected to oral surgery. Medicina Oral. 2004; 9: 138–148.

[28] Açmaz G, Aksoy H, Özoğlu N, Aksoy Ü, Albayrak E. Effect of paraceta-mol, dexketoprofen trometamol, lidocaine spray, and paracervical block application for pain relief during suction termination of first-trimester pregnancy. BioMed Research International. 2013; 2013: 869275.

[29] Scott LJ, Perry CM. Tramadol: a review of its use in perioperative pain. Drugs. 2000; 60: 139–176.

[30] Kotake RO, Siguan SS. A Retrospective Study on Common Practices in Post-operative Pain Assessment and Control Among Adult Patients Who Underwent Major/Medium Surgeries at the Cebu Velez General Hospital, January to Jun 2014. Portuguese Journal of Social Science. 2014; 69: 11–17.

[31] Ho KY, Wang EH, Salud JA, Cheung CW, Syfu F, Chong KW. Real-world experience with tramadol plus dexketoprofen fixed-dose combination in postoperative pain management: A series of case studies from Asia. Clinical Case Reports and Reviews. 2020; 6: 1–7.

[32] Varrassi G, Coaccioli S, De-Andrés J, Hanna M, Macheras G, Montero A, et al. Expert Consensus on Clinical Use of an Orally Administered Dexketoprofen Plus Tramadol Fixed-Dose Combination in Moderate-to-Severe Acute Pain: a Delphi Study. Advances in Therapy. 2019; 36: 3174–3185.

[33] Derry S, Cooper TE, Phillips T. Single fixed-dose oral dexketoprofen plus tramadol for acute postoperative pain in adults. Cochrane Database of Systematic Reviews. 2016; 9: CD012232.

[34] McQuay HJ, Moore RA, Berta A, Gainutdinovs O, Fülesdi B, Porva-neckas N, et al. Randomized clinical trial of dexketoprofen/tramadol 25 mg/75 mg in moderate-to-severe pain after total hip arthroplasty. British Journal of Anaesthesia. 2016; 116: 269–276.

[35] Moore RA, McQuay HJ, Tomaszewski J, Raba G, Tutunaru D, Lietuviete N, et al. Dexketoprofen/tramadol 25 mg/75 mg: randomised double-blind trial in moderate-to-severe acute pain after abdominal hysterectomy. BMC Anesthesiology. 2016; 16: 9.

[36] Moore RA, Gay-Escoda C, Figueiredo R, Tóth-Bagi Z, Dietrich T, Milleri S, et al. Dexketoprofen/tramadol: randomised double-blind trial and confirmation of empirical theory of combination analgesics in acute pain. The Journal of Headache and Pain. 2015; 16: 60.

[37] Gay-Escoda C, Hanna M, Montero A, Dietrich T, Milleri S, Giergiel E, et al. Tramadol/dexketoprofen (TRAM/DKP) compared with tra-madol/paracetamol in moderate to severe acute pain: Results of a randomised, double-blind, placebo and active-controlled, parallel group trial in the impacted third molar extraction pain model. BMJ Open. 2019; 9: e023715.

[38] Montero Matamala A, Bertolotti M, Contini MP, Guerrero Bayón C, Nizzardo A, Paredes Lario I, et al. Tramadol hydrochloride 75 mg/dexketoprofen 25 mg oral fixed-dose combination in moderate-to-severe acute pain: sustained analgesic effect over a 56-h period in the postoperative setting. Drugs of Today. 2017; 53: 339.

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