PREEMPTIVE ANALGESIA IN ANORECTAL SURGERY: RESULTS OF THE PROSPECTIVE, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

Aim: To assess the efficiency of preemptive analgesia with Ketoprofen 100 mg 2 hours before procedure per os to decrease postoperative pain. 
Methods: This prospective, randomized, double-blind study was conducted in the surgical department of the Lomonosov MSU Medical Center. Patients who were diagnosed with anorectal disease without contraindication to perform subarachnoid anesthesia or other somatic diseases and underwent anorectal procedure were included. After signing the consent all participants were randomly divided: the first group got a 100 mg Ketoprofen tablet, the second one got a starch tablet 2 hours before surgery. Following the procedure the primary and secondary outcomes were evaluated: opioid administration intake, the pain at rest and during defecation, duration and frequency of other analgesics intake, readmission rate, life quality, time to return to previous lifestyle, the complications rate. 
Results: 134 participants were included in the study: 68 in the main group, 66 in the control one. Postoperative pain syndrome was statistically less in the main group on the 4,5,7 days (p=0,035; p=0,023; p=0,046, respectively). Opioid intake after surgery was significantly lower in the main group (p=0.174). The side effects frequency, live quality, time to return to previous lifestyle also didn’t differ in both groups. 
Conclusion: Preoperative analgesia is safe and effective in reducing postoperative pain in anorectal surgery, reduces the opioid usе, doesn’t increase the ketoprophen side effects frequency. It should be a part of the routine patients’ multimodal management in anorectal surgery.

1. V. Poylin, J. Quinn, K. Messer, and D. Nagle, Gabapentin significantly decreases posthemorrhoidectomy pain: a prospective study, Int. J. Colorectal Dis., vol. 29, no. 12, pp. 1565–1569, 2014, https://doi.org/10.1007/s00384-014-2018-4

2. G. Gallo, Martellucci J., Sturiale A., Clerico G., Milito G., Marino F., Cocorullo G., Giordano P., Mistrangelo M., Trompetto M., Consensus statement of the Italian society of colorectal surgery (SICCR): management and treatment of hemorrhoidal disease, Techniques in Coloproctology, vol. 24, no. 2. 2020, https://doi.org/10.1007/s10151-020-02149-1

3. J. T. Van Backer, Jordan Matthew R., Leahy Danielle T., Moore Jesse S., Callas Peter, Dominick Timothy, Cataldo Peter A., Preemptive analgesia decreases pain following anorectal surgery: A prospective, randomized, double-blinded, placebo-controlled trial, Dis. Colon Rectum, vol. 61, no. 7, pp. 824–829, 2018, https://doi.org/10.1097/DCR.0000000000001069

4. B. Penprase, E. Brunetto, E. Dahmani, J. J. Forthoffer, and S. Kapoor, The efficacy of preemptive analgesia for postoperative pain control: A systematic review of the literature, AORN J., vol. 101, no. 1, pp. 94-105.e8, 2015, https://doi.org/10.1016/j.aorn.2014.01.030

5. Y. J. Huang, C. Y. Chen, R. J. Chen, Y. N. Kang, and P. L. Wei, Topical diltiazem ointment in post-hemorrhoidectomy pain relief: A meta-analysis of randomized controlled trials, Asian J. Surg., vol. 41, no. 5, 2018, https://doi.org/10.1016/j.asjsur.2017.06.002.

6. J. W. Liu, C. C. Lin, K. T. Kiu, C. Y. Wang, and K. W. Tam, Effect of Glyceryl Trinitrate Ointment on Pain Control after Hemorrhoidectomy: A meta-analysis of randomized controlled trials, World J. Surg., vol. 40, no. 1, 2016, https://doi.org/10.1007/s00268-015-3344-6

7. P.E. Frasco, J. Sprung, and T. L. Trentman, “The impact of the joint commission for accreditation of healthcare organizations pain initiative on perioperative opiate consumption and recovery room length of stay,” Anesth. Analg., vol. 100, no. 1, pp. 162–168, 2005, https://doi.org/10.1213/01.ANE.0000139354.26208.1C

8. I. M. Richman, Use of Toradol® in anorectal surgery, Dis. Colon Rectum, vol. 36, no. 3, 1993, https://doi.org/10.1007/BF02053515

9. G. Khalili, M. Janghorbani, H. Saryazdi, and A. Emaminejad, Effect of preemptive and preventive acetaminophen on postoperative pain score: A randomized, double-blind trial of patients undergoing lower extremity surgery, J. Clin. Anesth., vol. 25, no. 3, 2013, https://doi.org/10.1016/j.jclinane.2012.09.004

10. J. I. Wu, S. F. Lu, Y. Y. Chia, L. C. Yang, W. P. Fong, and P. H. Tan, Sevoflurane with or without antiemetic prophylaxis of dexamethasone in spontaneously breathing patients undergoing outpatient anorectal surgery, J. Clin. Anesth., vol. 21, no. 7, 2009, https://doi.org/10.1016/j.jclinane.2008.11.007

11. J. Y. Chen, Ko Tsung Lin, Wen Yeong Ray,Wu Shu Ching,Chou Yenn Hwei, Yien Hwey Wen, Kuo Cheng Deng, “Opioid-sparing effects of ketorolac and its correlation with the recovery of postoperative bowel function in colorectal surgery patients: A prospective randomized double-blinded study,” Clin. J. Pain, vol. 25, no. 6, 2009, https://doi.org/10.1097/AJP.0b013e31819a506b

12. F. Aubrun, O. Langeron, D. Heitz, P. Coriat, and B. Riou, Randomised, placebo-controlled study of the postoperative analgesic effects of ketoprofen after spinal fusion surgery, Acta Anaesthesiol. Scand., vol. 44, no. 8, pp. 934–939, 2000, https://doi.org/10.1034/j.1399-6576.2000.440807.x

13. D. Fletcher, Nègre I., Barbin C., François A., Carreres C., Falgueirettes C., Barboteu A., Samii K., Postoperative analgesia with iv propacetamol and ketoprofen combination after disc surgery, Can. J. Anaesth., vol. 44, no. 5, pp. 479–485, 1997, https://doi.org/10.1007/BF03011934

14. A. Hiller, O. A. Meretoja, R. Korpela, S. Piiparinen, and T. Taivainen, The analgesic efficacy of acetaminophen, ketoprofen, or their combination for pediatric surgical patients having soft tissue or orthopedic procedures, Anesth. Analg., vol. 102, no. 5, pp. 1365–1371, 2006, https://doi.org/10.1213/01.ane.0000204278.71548.bf

15. D. Oberhofer, J. Skok, and V. Nesek-Adam, Intravenous ketoprofen in postoperative pain treatment after major abdominal surgery, World J. Surg., vol. 29, no. 4, 2005, https://doi.org/10.1007/s00268-004-7612-0

16. H. Gaskell, S. Derry, P. J. Wiffen, and R. A. Moore, Single dose oral ketoprofen or dexketoprofen for acute postoperative pain in adults, Cochrane Database of Systematic Reviews, vol. 2017, no. 5. 2017, https://doi.org/10.1002/14651858.CD007355.pub3

17. S. A. Cooper, Ketoprofen in oral surgery pain: a review, Journal of clinical pharmacology, vol. 28, no. 12 Suppl. 1988, https://doi.org/10.1002/j.1552-4604.1988.tb05976.x

18. G. Velásquez, L. A. Cruz, and M. Espinoza, Ketoprofen Is More Effective Than Diclofenac After Oral Surgery When Used as a Preemptive Analgesic: A Pilot Study, J. Oral Facial Pain Headache, vol. 28, no. 2, 2014, https://doi.org/10.11607/ofph.1200

19. A. Sunshine and N. Z. Olson, Analgesic efficacy of ketoprofen in postpartum, general surgery, and chronic cancer pain, Journal of clinical pharmacology, vol. 28, no. 12 Suppl. 1988, https://doi.org/10.1002/j.1552-4604.1988.tb05977.x

20. G. A. Bjornsson, H. R. Haanæs, and L. A. Skoglund, Ketoprofen 75 mg qid versus acetaminophen 1000 mg qid for 3 days on swelling, pain, and other postoperative events after third-molar surgery, J. Clin. Pharmacol., vol. 43, no. 3, 2003, https://doi.org/10.1177/0091270002250603

21. R. J. Place, M. Coloma, P. F. White, P. J. Huber, J. Van Vlymen, and C. L. Simmang, Ketorolac improves recovery after outpatient anorectal surgery, Dis. Colon Rectum, vol. 43, no. 6, pp. 804–808, 2000, https://doi.org/10.1007/BF02238018

22. Mathiesen O, Dahl B, Thomsen BA, Kitter B, Sonne N, Dahl JB, Kehlet H. A comprehensive multimodal pain treatment reduces opioid consumption after multilevel spine surgery. Eur Spine J. 2013 Sep;22(9):2089-96. https://doi.org/10.1007/s00586-013-2826-1

23. Trabulsi EJ, Patel J, Viscusi ER, Gomella LG, Lallas CD. Preemptive multimodal pain regimen reduces opioid analgesia for patients undergoing robotic-assisted laparoscopic radical prostatectomy. Urology. 2010 Nov;76(5):1122-4. https://doi.org/10.1016/j.urology.2010.03.052

24. Tang R, Evans H, Chaput A, Kim C. Multimodal analgesia for hip arthroplasty. Orthop Clin North Am. 2009 Jul;40(3):377- 87. https://doi.org/10.1016/j.ocl.2009.04.001

25. Richman IM. Use of Toradol in anorectal surgery. Dis Colon Rectum. 1993 Mar;36(3):295-6. https://doi.org/10.1007/BF02053515