Efficacy of Preemptive Ibuprofen Combined with Paracetamol in Lower Third Molar Surgery: A Double-blind Randomized Controlled Clinical Trial

Vittayakittipong Pichai, Areewattana Thippapa

Published Online: Jan 27, 2022 DOI 10.14456/cmdj.2022.6

Objectives: The aim of this study was to assess the preemptive analgesic efficacy of ibuprofen 400 mg combined with paracetamol 500 mg after lower third molar surgery.

Methods: A randomized double-blinded controlled clinical trial was conducted. Patients were randomized into the preemptive group (ibuprofen 400 mg combined with paracetamol 500 mg) and the control group (placebo) using block randomization. Preemptive drugs and the placebo were administered to patients orally 1 hour before undergoing lower third molar surgery. The following outcomes were assessed: postoperative pain assessed with visual analog scale (VAS), number of patients who received rescue medications, number of pain-free patients, time at first requirement for rescue medications, number of patients who received rescue medications, and drug satisfaction.

Results: The 48 patients were randomized, 24 to the control group and 24 to the preemptive group. The time until first requirement for rescue medications in the preemptive group was significantly longer than that of the control group (p=0.003). The other outcomes were not significantly different between groups.

Conclusions: Preemptive ibuprofen 400 mg combined with paracetamol 500 mg did not reduce postoperative pain after lower third molar surgery; however, the preemptive therapy delayed the time required for rescue medications.

ibuprofen lower third molar surgery paracetamol preemptive analgesic

1. Madani ZS, Moghadamnia AA, Panahi A, Poorsattar Bejeh Mir A. Analgesic effect of etoricoxib compared to ibuprofen on post endodontic pain. Oral Health Dent Manag. 2013; 12:186-90.. 2013; 12:186-90.

2. Yamaguchi A, Sano K. Effectiveness of preemptive analgesia on postoperative pain following third molar surgery: Review of literatures. Jpn Dent Sci Rev. 2013;49:131-8.

3. Lau SL, Chow RL, Yeung RW, Samman N. Pre-emptive ibuprofen arginate in third molar surgery: a double-blind randomized controlled crossover clinical trial. Aust Dent J. 2009;54:355-60.

4. Seymour RA, Meechan JG, Blair GS. An investigation into post-operative pain after third molar surgery under local analgesia. Br J Oral Maxillofac Surg.1985;23:410-8.

5. Mony D, Kulkarni D, Shetty L. Comparative evaluation of preemptive analgesic effect of injected intramuscular diclofenac and ketorolac after third molar surgery- a randomized controlled trial. J Clin Diagn Res. 2016;10:Zc102-6.

6. Moore PA, Hersh EV. Combining ibuprofen and acetaminophen for acute pain management after third-molar extractions: translating clinical research to dental practice. J Am Dent Assoc. 2013;144:898-908.

7. Altman RD. A rationale for combining acetaminophen and NSAIDs for mild-to-moderate pain. Clin Exp Rheumatol. 2004;22:110-7.

8. Mehlisch DR. The efficacy of combination analgesic therapy in relieving dental pain. J Am Dent Assoc. 2002;133:861-71.

9. Crile GW. The kinetic theory of shock and its prevention through anoci-association. Lancet. 1913;182:7–16.

10. Woolf CJ, Chong MS. Preemptive analgesia--treating postoperative pain by preventing the establishment of central sensitization. Anesth Analg. 1993;77:362-79.

11. Murayama T, Yamaguchi A, Nakano M, Sano K. Effect of acetaminophen (Caronal) for pre-emptive analgesia on postoperative pain after removal of impacted lower third molars. Oral Ther Pharmacol. 2009;28:130-6.

12. Negishi A, Tsuchiya A, Ishikita T, Yamaguchi T, Nakasone Y, Mogi K. Comparative study of the pre-emptive analgesic effects of nonsteroidal anti-inflammatory drugs having different mechanisms of action, for pain associated with extraction of impacted wisdom teeth. Kita Kanto Igaku. 2007;57:43-8.

13. Jung YS, Kim MK, Um YJ, Park HS, Lee EW, Kang JW. The effects on postoperative oral surgery pain by varying NSAID administration times: comparison on effect of preemptive analgesia. Oral Surg Oral Med Oral Pathol Oral Radiol. 2005;100:559-63.

14. Albuquerque AFM, Fonteles CSR, do Val DR, Chaves HV, Bezerra MM, Pereira KMA, et al. Effect of pre-emptive analgesia on clinical parameters and tissue levels of TNF-α and IL-1β in third molar surgery: a triple-blind, randomized, placebo-controlled study. Int J Oral Maxillofac Surg. 2017;46:1615-25.

15. Bauer HC, Duarte FL, Horliana AC, Tortamano IP, Perez FE, Simone JL, et al. Assessment of preemptive analgesia with ibuprofen coadministered or not with dexamethasone in third molar surgery: a randomized double-blind controlled clinical trial. Oral Maxillofac Surg. 2013;17:165-71.

16. Chiu WK, Cheung LK. Efficacy of preoperative oral rofecoxib in pain control for third molar surgery. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005:99: e47-e53.

17. Mehlisch DR, Aspley S, Daniels SE, Bandy DP. Comparison of the analgesic efficacy of concurrent ibuprofen and paracetamol with ibuprofen or paracetamol alone in the management of moderate to severe acute postoperative dental pain in adolescents and adults: a randomized, double-blind, placebo-controlled, parallel-group, single-dose, two-center, modified factorial study. Clin Ther. 2010;32:882-95.

18. Merry AF, Gibbs RD, Edwards J, Ting GS, Frampton C, Davies E, et al. Combined acetaminophen and ibuprofen for pain relief after oral surgery in adults: a randomized controlled trial. Br J Anaesth. 2010;104:80-8.

19. Kimiaei Asadi H, Jamalpour M R, Saeedi A. Clinical trial of combination of acetaminophen, ibuprofen and caffeine on pain relief and analgesic use after impacted lower third molar surgery. Shiraz E-Med J. 2017;18:e13092.

20. Bali A, Bali D, Sharma A, Verma G. Is pederson index a true predictive difficulty index for impacted mandibular third molar surgery? a meta-analysis. J Maxillofac Oral Surg. 2013;12:359-64.

21. Pell GJ, Gregory GT. Impacted mandibular third molars classification and modified technique for removal. Dent Dig. 1933;39:330-7.

22. Winter GB. Principles of exodontia as applied to the impacted mandibular third molar : a complete treatise on the operative technic with clinical diagnoses and radiographic interpretations, St. Louis, American Medical Book Company., 1926.

23. Seymour RA, Blair GS, Wyatt FAR. Post-operative dental pain and analgesic efficacy. Part I. Br J Oral Maxillofac Surg. 1983;21:290-7.

24. Jensen MP, Chen C, Brugger AM. Interpretation of visual analog scale ratings and change scores: a reanalysis of two clinical trials of postoperative pain. J Pain. 2003;4:407-14.

25. Morse Z, Tump A, Kevelham E. Ibuprofen as a pre-emptive analgesic is as effective as rofecoxib for mandibular third molar surgery. Odontology. 2006;94:59-63.

26. Al-Sukhun J, Al-Sukhun S, Penttilä H, Ashammakhi N, Al-Sukhun R. Preemptive analgesic effect of low doses of celecoxib is superior to low doses of traditional nonsteroidal anti-inflammatory drugs. J Craniofac Surg. 2012;23:526-9.

27. Costa FW, Soares EC, Esses DF, Silva PG, Bezerra TP, Scarparo HC, et al. A split-mouth, randomized, triple-blind, placebo-controlled study to analyze the pre-emptive effect of etoricoxib 120 mg on inflammatory events following removal of unerupted mandibular third molars. Int J Oral Maxillofac Surg. 2015;44:1166-74.

28. Lisboa AH, Pilatt GL. Pain control with dexamethasone, etoricoxib or ibuprofen associated with arginine in impacted third molar surgery. Rev Gaúch Odontol. 2013;61:335-40.

29. Chidchuangchai W, Kiatthaworncharoen S. Thai National Formulary 2016: Drugs used in Dentistry, Bangkok, National Drug Information, 2016.

30. Gutierrez KJ. Pharmacotherapeutics: Clinical reasoning in primary care. 2nd ed., Colorado, Elsevier, 2008.

31. Ong CKS, Seymour RA. Pathogenesis of postoperative oral surgical pain. Anesth Prog. 2003;50:5-17.

32. De Menezes SA, Cury PR. Efficacy of nimesulide versus meloxicam in the control of pain, swelling and trismus following extraction of impacted lower third molar. Int J Oral Maxillofac Surg. 2010;39:580-4.

33. Voutilainen A, Pitkäaho T, Kvist T, Vehviläinen-Julkunen K. How to ask about patient satisfaction? the visual analogue scale is less vulnerable to confounding factors and ceiling effect than a symmetric Likert scale. J Adv Nurs. 2016;72:946-57.

34. Rainsford KD. Ibuprofen: pharmacology, efficacy and safety. Inflammopharmacology. 2009;17:275-342.

35. Gerriets V, Anderson J, Nappe TM. Acetaminophen. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan- [updated 2021 July 3; cited 2021 Jan 7]. Available from: https://www.ncbi.nlm.nih. gov/books/NBK482369/

36. Pozzi A, Gallelli L. Pain management for dentists: the role of ibuprofen. Ann Stomatol (Roma). 2011;2:3-24.

37. Cho H, Lynham AJ, Hsu E. Postoperative interventions to reduce inflammatory complications after third molar surgery: review of the current evidence. Aust Dent J. 2017;62:412-9.

38. Kim K, Brar P, Jakubowski J, Kaltman S, Lopez E. The use of corticosteroids and nonsteroidal antiinflammatory medication for the management of pain and inflammation after third molar surgery: a review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;107:630-40.

Vittayakittipong P, Areewattana T. Efficacy of Preemptive Ibuprofen Combined with Paracetamol in Lower Third Molar Surgery: A Double-blind Randomized Controlled Clinical Trial: Original articles. CM Dent J [Internet]. 2022 Jan 27 [cited 2024 Apr 29];43(1):57-64. Available from: https://www.dent.cmu.ac.th/cmdj/frontend/web/?r=site/viewarticle&id=162

Vittayakittipong, P. & Areewattana, T. (2022). Efficacy of Preemptive Ibuprofen Combined with Paracetamol in Lower Third Molar Surgery: A Double-blind Randomized Controlled Clinical Trial. CM Dent J, 43(1), 57-64. Retrieved from: https://www.dent.cmu.ac.th/cmdj/frontend/web/?r=site/viewarticle&id=162

Vittayakittipong, P., and Areewattana Thippapa. 2022. "Efficacy of Preemptive Ibuprofen Combined with Paracetamol in Lower Third Molar Surgery: A Double-blind Randomized Controlled Clinical Trial." CM Dent J, 43(1), 57-64. https://www.dent.cmu.ac.th/cmdj/frontend/web/?r=site/viewarticle&id=162

Vittayakittipong, P. et al. 2022. 'Efficacy of Preemptive Ibuprofen Combined with Paracetamol in Lower Third Molar Surgery: A Double-blind Randomized Controlled Clinical Trial', CM Dent J, 43(1), 57-64. Retrieved from https://www.dent.cmu.ac.th/cmdj/frontend/web/?r=site/viewarticle&id=162

Vittayakittipong, P. and Areewattana, T. "Efficacy of Preemptive Ibuprofen Combined with Paracetamol in Lower Third Molar Surgery: A Double-blind Randomized Controlled Clinical Trial", CM Dent J, vol.43, no. 1, pp. 57-64, Jan. 2022.

Vittayakittipong Pichai, Areewattana Thippapa "Efficacy of Preemptive Ibuprofen Combined with Paracetamol in Lower Third Molar Surgery: A Double-blind Randomized Controlled Clinical Trial." CM Dent J, vol.43, no. 1, Jan. 2022, pp. 57-64, https://www.dent.cmu.ac.th/cmdj/frontend/web/?r=site/viewarticle&id=162