Comparison of Ibuprofen and Paracetamol combination with Ketorolac and Paracetamol combination in patients undergoing gynecologic surgery: a review of pain level, coagulation profile, and interleukin-6 levels

Introduction. Postoperative pain management in gynecological surgery remains a significant challenge, with many patients experiencing moderate-to-severe pain despite standard analgesic interventions. The risk of complications, such as bleeding and prolonged recovery, is heightened by the use of certain analgesics, emphasizing the need for optimal pain management strategies.

The objective was to compare the efficacy of two multimodal analgesic regimens: Ibuprofen– Paracetamol and Ketorolac- Paracetamol on pain, coagulation and IL-6 levels.

Materials and methods. A double-blind randomized trial was conducted with 40 patients who underwent gynecological surgery. Group 1 received IV Ibuprofen (400 mg) + Paracetamol (1000 mg); Group 2 received IV Ketorolac (30 mg) + Paracetamol (1000 mg). Pain (NRS), clotting time (CT), bleeding time (BT), and IL-6 were assessed at 6, 24, and 48 hours postoperatively.

Results. Pain scores and CT did not differ significantly between the groups. The Ketorolac group showed a significant increase in BT at 24 and 48 hours (p < 0.05), while the Ibuprofen group had significantly lower IL-6 levels at 24 hours (p < 0.05).

Conclusion. Both regimens were equally effective in pain control. However, Ketorolac- Paracetamol significantly prolonged the bleeding time, whereas Ibuprofen-Paracetamol was more effective in reducing inflammation by lowering IL-6 levels. These differences should be considered, especially in patients at risk of bleeding.

1. Aletaha D., Kerschbaumer A., Kastrati K. et al. Consensus statement on blocking interleukin-6 receptor and interleukin-6 in inflammatory conditions: an update. Ann Rheum Dis, 2023, vol. 82, no. 6, pp. 773–787. https://doi.org/10.1136/ard-2022-222784.

2. Botting R. M. Mechanism of action of acetaminophen: is there a cyclooxygenase 3? Clin Infect Dis, 2000, vol. 31. Suppl 5, S202–210. https://doi.org/10.1086/317520.

3. Douraiswami B., Dilip P. K., Harish B. N. et al. C-reactive protein and interleukin-6 levels in the early detection of infection after open fractures. J Orthop Surg (Hong Kong), 2012, vol. 20, no. 3, pp. 381–385. https://doi.org/10.1177/230949901202000325.

4. Erekson E. A., Yip S. O., Ciarleglio M. M. et al. Postoperative complications after gynecologic surgery. Obstetrics and Gynecology, 2011, vol. 118, no. 4, pp. 785–793. https://doi.org/10.1097/AOG.0b013e31822dac5d.

5. Fithri D., Wijaya D., Arifin H. Perbedaan nilai agregasi trombosit akibat pengaruh penggunaan analgesia ketorolak dan ibuprofen intravena pascaoperasi di RSUP haji adam malik medan. Jurnal Anestesi Perioperatif, 2017, vol. 5, no. 3, pp. 141–146. https://doi.org/10.1581/jap.v5n3.1166.

6. Goldenberg N. A., Jacobson L., Manco-Johnson M. J. Brief communication: duration of platelet dysfunction after a 7-day course of Ibuprofen. Ann Intern Med, 2005, vol. 142, no. 7, pp. 506–509. https://doi.org/10.7326/0003-4819-142-7-200504050-00009.

7. Horn R., Hendrix J. M., Kramer J. Postoperative Pain Control. In: StatPearls. StatPearls Publishing.; 2025. URL: https://pubmed.ncbi.nlm.nih.gov/31335018/ (accessed: 10.11.25).

8. Mahmoodi A. N., Patel P., Kim P. Y. et al. Ketorolac. In: StatPearls. StatPearls Publishing; 2025.

9. Martini W. Z., Deguzman R., Rodriguez C. M. et al. Effect of Ibuprofen dose on platelet aggregation and coagulation in blood samples from pigs. Mil Med, 2015, vol. 180, 3 Suppl, pp. 80–85. https://doi.org/10.7205/MILMED-D-14-00395.

10. Park A., Anderson D., Battaglino R. A. et al. Ibuprofen use is associated with reduced C-reactive protein and interleukin-6 levels in chronic spinal cord injury. J Spinal Cord Med, 2022, vol. 45, no. 1, pp. 117–125. URL: https://www.tandfonline.com/doi/full/10.1080/10790268.2020.1773029 (accessed: 10.11.25).

11. Rahim Muh. R., Musba A. M. T., Palinrungi A. S. et al. Perbandingan antara kombinasi ibuprofen dan parasetamol dengan ketorolak dan parasetamol intravena terhadap derajat nyeri dan rasio neutrofil limfosit pasca-functional endoscopic sinus surgery. Jurnal Anestesi Perioperatif, 2024, vol. 12, no. 3, pp. 161–8. https://doi.org/10.15851/jap.v12n3.3889.

12. Rose-John S. Local and systemic effects of interleukin-6 (IL-6) in inflammation and cancer. FEBS Lett, 2022, vol. 596, no. 5, pp. 557–566. https://doi.org/10.1002/1873-3468.14220.

13. Singh P., Rastogi S., Bansal M. et al. A prospective study to assess the levels of interleukin-6 following administration of Diclofenac, Ketorolac and Tramadol after surgical removal of lower third molars. J Maxillofac Oral Surg, 2015, vol. 14, no. 2, pp. 219–225. https://doi.org/10.1007/s12663-013-0609-1

14. Sun F., Zhang Y., Li Q. Therapeutic mechanisms of ibuprofen, prednisone and betamethasone in osteoarthritis. Mol Med Rep, 2017, vol. 15, no. 2, pp. 981–7. https://doi.org/10.3892/mmr.2016.6068.

15. Supermaniam S. Laparoscopic Surgery in Gynaecology. In: Laparoscopic Surgery in Gynaecology and Common Diseases in Women. 1st ed. Melaka, Malaysia: Adequate Wonder; 2016.

16. Wick E. C., Grant M. C., Wu C. L. Postoperativemultimodal analgesia pain management with nonopioid analgesics and techniques a review. JAMA Surg, 2017, vol. 152, no. 7, pp. 691–697. https://doi.org/10.1001/jamasurg.2017.0898.

17. Wittes J. Sample size calculations for randomized controlled trials. Epidemiol Rev, 2002, vol. 24, no. 1, pp. 39–53. https://doi.org/10.1093/epirev/24.1.39.

18. Younus L. A. The potential impact of Ibuprofen on level of IL-6. Maaen Journal for Medical Sciences, 2024, vol. 3, no. 1. https://doi.org/10.55810/2789-9136.1038.