Postoperative ileus and possibilities of pharmacological intervention

Česká verzia

Authors: L. Urbánek ¹; P. Urbánková ²; T. Trávníček ³
Authors place of work: I. chirurgická klinika LF MU, a FN u sv. Anny v Brně ¹; Klinika otorinolaryngologie, a chirurgie hlavy a krku LF MU, a FN u sv. Anny v Brně ²; Oddělení klinické farmacie, Nemocniční lékárna, FN u sv. Anny v Brně ³
Published in the journal: Rozhl. Chir., 2024, roč. 103, č. 9, s. 346-350.
Category: Review
doi: https://doi.org/10.48095/ccrvch2024346

Summary

Introduction: Postoperative ileus is a severe condition occurring especially in high-risk patients following acute and prolonged surgical procedures. Multiple factors are described as important in etiology, such as inflammation as well as neurological, hormonal and pharmacological influences. In prevention and treatment, we try to apply non-pharmaceutical procedures, to influence reversible etiological factors and, in postoperative period, to implement and use ERAS procedures. Drugs are the other possibility how to influence this pathology. Short-term impairment of intestinal motility following the most of the intraabdominal surgeries must be also taken in count in the differential diagnosis and treatment.

Study aim: We try to describe all possibilities of pharmacological treatment and prevention of the postoperative ileus. Effectiveness of drugs used in present praxis, especially group of so-called prokinetics is analyzed.

Conclusion: Postoperative ileus is still recognized as severe complication. Pharmacological treatment options are limited, only a few substances have evident positive impact (neostigmin for treatment and alvimopan – not registered in the Czech Republic for prevention). More evidence is necessary for positive effect of 5-hydroxytryptamine 4 (5HT4) agonists, and the effect of selective COX-2 inhibitors is still controversial.

Keywords:

neostigmine – postoperative ileus – PAMORA – serotonin agonists

Zdroje

1. Wolthuis AM, Bislenghi G, Fieuws S et al. Incidence of prolonged postoperative ileus after colorectal surgery: a systematic review and meta-analysis. Colorectal Dis 2016; 18(1): O1–O9. doi: 10.1111/codi.13210.

2. Ramirez JA, McIntosh AG, Strehlow R et al. Definition, incidence, risk factors, and prevention of paralytic ileus following radical cystectomy: a systematic review. Eur Urol 2013; 64(4): 588–597. doi: 10.1016/j.eururo.2012.11.051.

3. van Bree SH, Bemelman WA, Hollmann MW et al. Identification of clinical outcome measures for recovery of gastrointestinal motility in postoperative ileus. Ann Surg 2014; 259(4): 708–714. doi: 10.1097/SLA.0b013e318293ee55.

4. Iyer S, Saunders WB, Stemkowski S. Economic burden of postoperative ileus associated with colectomy in the United States. J Manag Care Pharm 2009; 15(6): 485–494. doi: 10.18553/jmcp.2009.15.6.485.

5. Vather R, Trivedi S, Bissett I. Defining postoperative ileus: results of a systematic review and global survey. J Gastrointest Surg 2013; 17(5): 962–972. doi: 10.1007/s11605-013-2148-y.

6. Peters EG, Pattamatta M, Smeets BJJ et al. The clinical and economical impact of postoperative ileus in patients undergoing colorectal surgery. Neurogastroenterol Motil 2020; 32(8): e13862. doi: 10.1111/nmo.13862.

7. Schwarz NT, Kalff JC, Türler A et al. Selective jejunal manipulation causes postoperative pan-enteric inflammation and dysmotility. Gastroenterology 2004; 126(1): 159–169. doi: 10.1053/j.gastro.2003.10.060.

8. de Jonge WJ, van den Wijngaard RM, The FO et al. Postoperative ileus is maintained by intestinal immune infiltrates that activate inhibitory neural pathways in mice. Gastroenterology 2003; 125(4): 1137–1147. doi: 10.1016/s0016-5085(03)01197-1.

9. Engel DR, Koscielny A, Wehner S et al. T helper type 1 memory cells disseminate postoperative ileus over the entire intestinal tract. Nat Med 2010; 16(12): 1407–1413. doi: 10.1038/nm.2255.

10. Maruna P, Gürlich R, Frasko R. Pathophysiology of postoperative dysfunctions of the intestinal motility. A review. Rozhl Chir 2005; 84(7): 356–362.

11. Andrews JM, Dent J. Small intestinal motor physiology. In: Sleisenger and Fordtran‘s gastrointestinal and liver disease. Pathophysiology/diagnosis/management. Philadelphia: Saunders 2002.

12. Artinyan A, Nunoo-Mensah JW, Balasubramaniam S et al. Prolonged postoperative ileus-definition, risk factors, and predictors after surgery. World J Surg 2008; 32(7): 1495–1500. doi: 10.1007/s00268-008-9491-2.

13. Svatek RS, Fisher MB, Matin SF et al. Risk factor analysis in a contemporary cystectomy cohort using standardized reporting methodology and adverse event criteria. J Urol 2010; 183(3): 929–934. doi: 10.1016/j.juro.2009.11.038.

14. Makino T, Shukla PJ, Rubino F et al. The impact of obesity on perioperative outcomes after laparoscopic colorectal resection. Ann Surg 2012; 255(2): 228–236. doi: 10.1097/SLA.0b013e31823dcbf7.

15. Morimoto Y, Takahashi H, Fujii M et al. Visceral obesity is a preoperative risk factor for postoperative ileus after surgery for colorectal cancer: single-institution retrospective analysis. Ann Gastroenterol Surg 2019; 3(6): 657–666. doi: 10.1002/ags3.12291.

16. Kronberg U, Kiran RP, Soliman MS et al. A characterization of factors determining postoperative ileus after laparoscopic colectomy enables the generation of a novel predictive score. Ann Surg 2011; 253(1): 78–81. doi: 10.1097/SLA.0b013e3181fcb83e.

17. Delaney CP, Senagore AJ, Viscusi ER et al. Postoperative upper and lower gastrointestinal recovery and gastrointestinal morbidity in patients undergoing bowel resection: pooled analysis of placebo data from 3 randomized controlled trials. Am J Surg 2006; 191(3): 315–319. doi: 10.1016/j.amjsurg.2005.10.026.

18. Resnick J, Greenwald DA, Brandt LJ. Delayed gastric emptying and postoperative ileus after nongastric abdominal surgery: part I. Am J Gastroenterol 1997; 92(5): 751–762.

19. Corcoran T, Rhodes JE, Clarke S et al. Perioperative fluid management strategies in major surgery: a stratified meta-analysis. Anesth Analg 2012; 114(3): 640–651. doi: 10.1213/ANE.0b013e318240d6eb.

20. Satinský I, Havel E, Bezděk K et al. Klinická výživa v chirurgii – doporučení ESPEN (European Society for Parenteral and Enteral Nutrition) s konsenzuálním hlasováním pracovní skupiny SKVIMP (Společnost klinické výživy a intenzivní metabolické péče). Anest Intenziv Med 2019; 30(2): 104–110.

21. Seta ML, Kale-Pradhan PB. Efficacy of metoclopramide in postoperative ileus after exploratory laparotomy. Pharmacotherapy 2001; 21(10): 1181–1186. doi: 10.1592/phco.21.15.1181.33888.

22. Bungard TJ, Kale-Pradhan PB. Prokinetic agents for the treatment of postoperative ileus in adults: a review of the literature. Pharmacotherapy 1999; 19(4): 416–423. doi: 10.1592/phco.19.6.416.31040.

23. Davidson ED, Hersh T, Brinner RA et al. The effects of metoclopramide on postoperative ileus. A randomized double-blind study. Ann Surg 1979; 190(1): 27–30. doi: 10.1097/00000658-197907000-00006.

24. Itoh Z, Nakaya M, Suzuki T et al. Erythromycin mimics exogenous motilin in gastrointestinal contractile activity in the dog. Am J Physiol 1984; 247(6 Pt1): G688–694. doi: 10.1152/ajpgi.1984.247.6.G688.

25. Dolina J, Hep A, Kunovský L et al. Prokinetics and their use in gastroenterology. Vnitr Lek 2018; 64(6): 673–678.

26. Hawkyard CV, Koerner RJ. The use of erythromycin as a gastrointestinal prokinetic agent in adult critical care: benefits versus risks. J Antomicrob Chemother 2007; 59(3): 347–358. doi: 10.1093/jac/dkl537.

27. Smith AJ, Nissan A, Lanouette NM et al. Prokinetic effect of erythromycin after colorectal surgery: randomized, placebo-controlled, double-blind study. Dis Colon Rectum 2000; 43(3): 333–337. doi: 10.1007/BF02258298.

28. Bonacini M, Quiason S, Reynolds M et al. Effect of intravenous erythromycin on postoperative ileus. Am J Gastroenterol 1993; 88(2): 208–211.

29. Traut U, Brügger L, Kunz R et al. Systemic prokinetic pharmacologic treatment for postoperative adynamic ileus following abdominal surgery in adults. Cochrane Database Syst Rev 2008; 23(1): CD004930. doi: 10.1002/14651858.CD004930.pub3.

30. van der Spoel JI, Oudemans-van Straaten HM, Stoutenbeek CP et al. Neostigmine resolves critical illness-related colonic ileus in intensive care patients with multiple organ failure – a prospective, double-blind, placebo-controlled trial. Intensive Care Med 2001; 27(5): 822–827. doi: 10.1007/s001340100926.

31. Kram B, Greenland M, Grant M et al. Efficacy and safety of subcutaneous neostigmine for ileus, acute colonic pseudo-obstruction, or refractory constipation. Ann Pharmacother 2018; 52(6): 505–512. doi: 10.1177/1060028018754302.

32. Liao Y, Yang Li, Wen Ouyang. Effects and safety of neostigmine for postoperative recovery of gastrointestinal function: a systematic review and meta-analysis. Ann Palliat Med 2021; 10(12): 12507–12518. doi: 10.21037/apm-21-3291.

33. Fanaei SA, Khatami SM, Ziaee SA. Neostigmine in unavoidable post operative ileus: a randomized clinical trial. J Clin Diagn Res 2008; 2(6): 1163–1168. doi: 10.7860/JCDR/2008/.372.

34. İlban O, Cicekci F, Celik JB et al. Neostigmine treatment protocols applied in acute colonic pseudo-obstruction disease: a retrospective comparative study. Turk J Gastroenterol 2019; 30(3): 228–233. doi: 10.5152/tjg.2018.18193.

35. Smedley LW, Foster DB, Barthol CA et al. Safety and efficacy of intermittent bolus and continuous infusion neostigmine for acute colonic pseudo-obstruction. J Intensive Care Med 2020; 35(10): 1039–1043. doi: 10.1177/0885066618809010.

36. White L, Sandhu G. Continuous neostigmine infusion versus bolus neostigmine in refractory Ogilvie syndrome. Am J Emerg Med 2011; 29(5): 576.e1–576.e3. doi: 10.1016/j.ajem.2010.06.006.

37. Nguyen DL, Maithel S, Nguyen ET et al. Does alvimopan enhance return of bowel function in laparoscopic gastrointestinal surgery? A meta-analysis. Ann Gastroenterol 2015; 28(4): 475–480.

38. Xu LL, Zhou XQ, Yi PS et al. Alvimopan combined with enhanced recovery strategy for managing postoperative ileus after open abdominal surgery: a systematic review and meta-analysis. J Surg Res 2016; 203(1): 211–221. doi: 10.1016/j.jss.2016.01.027.

39. Viscusi ER, Rathmell JP, Fichera A et al. Randomized placebo-controlled study of intravenous methylnaltrexone in postoperative ileus. J Drug Assess 2013; 2(1): 127–134. doi: 10.3109/21556660.2013.838169.

40. Beavers J, Orton L, Atchison L et al. The efficacy and safety of methylnaltrexone for the treatment of postoperative ileus. Am Surg 2022; 88(3): 409–413. doi: 10.1177/00031348211048825.

41. Yu CS, Chun HK, Stambler N et al. Safety and efficacy of methylnaltrexone in shortening the duration of postoperative ileus following segmental colectomy: results of two randomized, placebo-controlled phase 3 trials. Dis Colon Rectum 2011; 54(5): 570–578. doi: 10.1007/DCR.0b013e3182092bde.

42. Gong J, Xie Z, Zhang T et al. Randomised clinical trial: prucalopride, a colonic pro-motility agent, reduces the duration of post-operative ileus after elective gastrointestinal surgery. Aliment Pharmacol Ther 2016; 43(7): 778–789. doi: 10.1111/apt.13557.

43. Toyomasu Y, Mochiki E, Morita H et al. Mosapride citrate improves postoperative ileus of patients with colectomy. J Gastrointest Surg 2011; 15(8): 1361–1367. doi: 10.1007/s11605-011-1567-x.

44. Drake TM, Ward AE. Pharmacological management to prevent ileus in major abdominal surgery: a systematic review and meta-analysis. J Gastrointest Surg 2016; 20(6): 1253–1264. doi: 10.1007/s11605-016-3140-0.

45. Hawkins AT, McEvoy MD, Wanderer JP et al. Ketorolac use and anastomotic leak in elective colorectal surgery: a detailed analysis. Dis Colon Rectum 2018; 61(12): 1426–1434. doi: 10.1097/DCR.0000000000001244.

46. Raju DP, Hakendorf P, Costa M et al. Efficacy and safety of low-dose celecoxib in reducing post-operative paralytic ileus after major abdominal surgery. ANZ J Surg 2015; 85(12): 946–950. doi: 10.1111/ans.12475.

47. Milne TGE, Jaung R, O‘Grady G et al. Nonsteroidal anti-inflammatory drugs reduce the time to recovery of gut function after elective colorectal surgery: a systematic review and meta-analysis. Colorectal Dis 2018; 20(8): O190–O198. doi: 10.1111/codi.14268.

48. Huang Y, Tang SR, Young CJ. Nonsteroidal anti-inflammatory drugs and anastomotic dehiscence after colorectal surgery: a meta-analysis. ANZ J Surg 2018; 88(10): 959–965. doi: 10.1111/ans.14322.

49. Weibel S, Jelting Y, Pace NL et al. Continuous intravenous perioperative lidocaine infusion for postoperative pain and recovery in adults. Cochrane Database Syst Rev 2018; 6(6): CD009642. doi: 10.1002/14651858.CD009642.pub3.

MUDr. Libor Urbánek, Ph.D.

I. chirurgická klinika

LF MU a FN u sv. Anny v Brně

Pekařská 664/53

602 00 Brno

libor.urbanek@fnusa.cz