Research Progress of Postoperative Ileus Mechanisms_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Li , TONG Weidong.

Department of General Surgery, Daping Hospital, The Third Military Medical University, Chongqing 400042, China;

Corresponding author：

Keywords：

Postoperative ileus; Inflammatory response; Nerve reflex; Drugs effect; Gastrointestinal motility

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ObjectiveTo summarize the recent advancements in the researches on the pathogenesis of postoperative ileus and explain the clinical significances of postoperative ileus mechanisms for the diagnosis, treatment, and prevention. MethodsRelevant literatures about the postoperative ileus mechanism published recently were collected and reviewed. ResultsThe occurrence of postoperative ileus were related to postoperative nerve reflex inhibition, inflammatory response, effects of drugs, and other factors, it was a variety of mechanisms modulating each other. ConclusionThe gastrointestinal motility of postoperative ileus is mainly regulated by neural reflexes, inflammatory reactions, and drug interactions, three of which act differently but as a whole in different time segments while the inflammatory response play a key role of postoperative ileus persistence.

Citation： WANG Li,TONG Weidong.. Research Progress of Postoperative Ileus Mechanisms. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2011, 18(10): 1114-1117. doi: Copy

1.	Carroll J, Alavi K. Pathogenesis and management of postoperative ileus [J]. Clin Colon Rectal Surg, 2009, 22(1): 4750.
2.	Boeckxstaens GE, de Jonge WJ. Neuroimmune mechanisms in postoperative ileus [J]. Gut, 2009, 58(9): 13001311.
3.	Mueller MH, Karpitschka M, Xue B, et al. Intestinal afferent nerve sensitivity is increased during the initial development of postoperative ileus in mice [J]. J Gastrointest Surg, 2009, 13(3): 423431.
4.	Boeckxstaens GE, Hirsch DP, Kodde A, et al. Activation of an adrenergic and vagallymediated NANC pathway in surgeryinduced fundic relaxation in the rat [J]. Neurogastroenterol Motil, 1999, 11(6): 467474.
5.	Korolkiewicz RP, SeinAnand J, Ruczyński J, et al. The role and interactions of nitric oxide (no), carbon monoxide (CO), and prostanoids in the pathogenesis of postoperative ileus in rats [J]. J Gastrointest Surg, 2004, 8(3): 346357.
6.	Boeckxstaens GE, Hollmann M, Heisterkamp SH, et al. Evidence for VIP(1)/pacap receptors in the afferent pathway mediating surgeryinduced fundic relaxation in the rat [J]. Br J Pharmacol, 2000, 131(4): 705710.
7.	Gao Z, Müller MH, Karpitschka M, et al. Role of the vagus nerve on the development of postoperative ileus [J]. Langenbecks Arch Surg, 2010, 395(4): 407411.
8.	Doherty TJ. Postoperative ileus: pathogenesis and treatment [J]. Vet Clin North Am Equine Pract, 2009, 25(2): 351362.
9.	Kalff JC, Buchholz BM, Eskandari MK, et al. Biphasic response to gut manipulation and temporal correlation of cellular infiltrates and muscle dysfunction in rat [J]. Surgery, 1999, 126(3): 498509.
10.	Kalff JC, Schraut WH, Simmons RL, et al. Surgical manipulation of the gut elicits an intestinal muscularis inflammatory response resulting in postsurgical ileus [J]. Ann Surg, 1998, 228(5): 652663.
11.	Kalff JC, Carlos TM, Schraut WH, et al. Surgically induced leukocytic infiltrates within the rat intestinal muscularis mediate postoperative ileus [J]. Gastroenterology, 1999, 117(2): 378387.
12.	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 [J]. Gastroenterology, 2003, 125(4): 11371147.
13.	The FO, de Jonge WJ, Bennink RJ, et al. The ICAM1 antisense oligonucleotide ISIS3082 prevents the development of postoperative ileus in mice [J]. Br J Pharmacol, 2005, 146(2): 252258.
14.	The FO, Bennink RJ, Ankum WM, et al. Intestinal handlinginduced mast cell activation and inflammation in human postoperative ileus [J]. Gut, 2008, 57(1): 3340.
15.	de Jonge WJ, The FO, van der Coelen D, et al. Mast cell degranulation during abdominal surgery initiates postoperative ileus in mice [J]. Gastroenterology, 2004, 127(2): 535545.
16.	Schwarz NT, BeerStolz D, Simmons RL, et al. Pathogenesis of paralytic ileus:intestinal manipulation opens a transient pathway between the intestinal lumen and the leukocytic infiltrate of the jejunal muscularis [J]. Ann Surg, 2002, 235(1): 3140.
17.	Wehner S, Behrendt FF, Lyutenski BN, et al. Inhibition of macrophage function prevents intestinal inflammation and postoperative ileus in rodents [J]. Gut, 2007, 56(2): 176185.
18.	Bauer AJ. Mentation on the immunological modulation of gastrointestinal motility [J]. Neurogastroenterol Motil, 2008, 20 Suppl 1: 8190.
19.	Türler A, Schnurr C, Nakao A, et al. Endogenous endotoxin participates in causing a panenteric inflammatory ileus after colonic surgery [J]. Ann Surg, 2007, 245(5): 734744.
20.	Ohama T, Hori M, Ozaki H. Mechanism of abnormal intestinal motility in inflammatory bowel disease: how smooth muscle contraction is reduced？ [J]. J Smooth Muscle Res, 2007, 43(2): 4354.
21.	Kalff JC, Schraut WH, Billiar TR, et al. Role of inducible nitric oxide synthase in postoperative intestinal smooth muscle dysfunction in rodents [J]. Gastroenterology, 2000, 118(2): 316327.
22.	Kreiss C, Birder LA, Kiss S, et al. Cox2 dependent inflammation increases spinal Fos expression during rodent postoperative ileus [J]. Gut, 2003, 52(4): 527534.
23.	Korolkiewicz R, SeinAnand J. Cox2 inhibitors and postoperative ileus [J]. Colorectal Dis, 2007, 9(9): 856857.
24.	Mueller MH, Glatzle J, Kampitoglou D, et al. Differential sensitization of afferent neuronal pathways during postoperative ileus in the mouse jejunum [J]. Ann Surg, 2008, 247(5): 791802.
25.	Johnson MD, Walsh RM. Current therapies to shorten postoperative ileus [J]. Cleve Clin J Med, 2009, 76(11): 641648.
26.	Viscusi ER, Gan TJ, Leslie JB, et al. Peripherally acting muopioid receptor antagonists and postoperative ileus: mechanisms of action and clinical applicability [J]. Anesth Analg, 2009, 108(6): 18111822.
27.	Iyer S, Saunders WB, Stemkowski S. Economic burden of postoperative ileus associated with colectomy in the United States [J]. J Manag Care Pharm, 2009, 15(6): 485494.
28.	Kraft M, Maclaren R, Du W, et al. Alvimopan (entereg) for the management of postoperative ileus in patients undergoing bowel resection [J]. P T, 2010, 35(1): 4449.
29.	Becker G, Blum HE. Novel opioid antagonists for opioidinduced bowel dysfunction and postoperative ileus [J]. Lancet, 2009, 373(9670): 11981206.
30.	Erowele GI. Alvimopan (entereg), a peripherally acting muopioid receptor antagonist for postoperative ileus [J]. P T, 2008, 33(10): 574583.
31.	Karuppiah S, Farrah R. Alvimopan (entereg) for the treatment of postoperative ileus [J]. Am Fam Physician, 2011, 83(8): 978979.
32.	Delaney CP, Weese JL, Hyman NH, et al. Phase Ⅲ trial of alvimopan, a novel, peripherally acting, mu opioid antagonist, for postoperative ileus after major abdominal surgery [J]. Dis Colon Rectum, 2005, 48(6): 11141125.
33.	Herzog TJ, Coleman RL, Guerrieri JP Jr, et al. A doubleblind, randomized, placebocontrolled phase III study of the safety of alvimopan in patients who undergo simple total abdominal hysterectomy [J]. Am J Obstet Gynecol, 2006, 195(2): 445453.
34.	Asantila R, Eklund P, Rosenberg PH. Continuous epidural infusion of bupivacaine and morphine for postoperative analgesia after hysterectomy [J]. Acta Anaesthesiol Scand， 1991， 35(6): 513517.
35.	Jrgensen H, Fomsgaard JS, Dirks J, et al. Effect of peri and postoperative epidural anaesthesia on pain and gastrointestinal function after abdominal hysterectomy [J]. Br J Anaesth， 2001， 87(4): 577583.
36.	Liu SS, Carpenter RL, Mackey DC, et al. Effects of perioperative analgesic technique on rate of recovery after colon surgery [J]. Anesthesiology, 1995, 83(4): 757765.
37.	Holte K, Kehlet H. Epidural anaesthesia and analgesia-effects on surgical stress responses and implications for postoperative nutrition [J]. Clin Nutr, 2002, 21(3): 199206.

1. Carroll J, Alavi K. Pathogenesis and management of postoperative ileus [J]. Clin Colon Rectal Surg, 2009, 22(1): 4750.
2. Boeckxstaens GE, de Jonge WJ. Neuroimmune mechanisms in postoperative ileus [J]. Gut, 2009, 58(9): 13001311.
3. Mueller MH, Karpitschka M, Xue B, et al. Intestinal afferent nerve sensitivity is increased during the initial development of postoperative ileus in mice [J]. J Gastrointest Surg, 2009, 13(3): 423431.
4. Boeckxstaens GE, Hirsch DP, Kodde A, et al. Activation of an adrenergic and vagallymediated NANC pathway in surgeryinduced fundic relaxation in the rat [J]. Neurogastroenterol Motil, 1999, 11(6): 467474.
5. Korolkiewicz RP, SeinAnand J, Ruczyński J, et al. The role and interactions of nitric oxide (no), carbon monoxide (CO), and prostanoids in the pathogenesis of postoperative ileus in rats [J]. J Gastrointest Surg, 2004, 8(3): 346357.
6. Boeckxstaens GE, Hollmann M, Heisterkamp SH, et al. Evidence for VIP(1)/pacap receptors in the afferent pathway mediating surgeryinduced fundic relaxation in the rat [J]. Br J Pharmacol, 2000, 131(4): 705710.
7. Gao Z, Müller MH, Karpitschka M, et al. Role of the vagus nerve on the development of postoperative ileus [J]. Langenbecks Arch Surg, 2010, 395(4): 407411.
8. Doherty TJ. Postoperative ileus: pathogenesis and treatment [J]. Vet Clin North Am Equine Pract, 2009, 25(2): 351362.
9. Kalff JC, Buchholz BM, Eskandari MK, et al. Biphasic response to gut manipulation and temporal correlation of cellular infiltrates and muscle dysfunction in rat [J]. Surgery, 1999, 126(3): 498509.
10. Kalff JC, Schraut WH, Simmons RL, et al. Surgical manipulation of the gut elicits an intestinal muscularis inflammatory response resulting in postsurgical ileus [J]. Ann Surg, 1998, 228(5): 652663.
11. Kalff JC, Carlos TM, Schraut WH, et al. Surgically induced leukocytic infiltrates within the rat intestinal muscularis mediate postoperative ileus [J]. Gastroenterology, 1999, 117(2): 378387.
12. 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 [J]. Gastroenterology, 2003, 125(4): 11371147.
13. The FO, de Jonge WJ, Bennink RJ, et al. The ICAM1 antisense oligonucleotide ISIS3082 prevents the development of postoperative ileus in mice [J]. Br J Pharmacol, 2005, 146(2): 252258.
14. The FO, Bennink RJ, Ankum WM, et al. Intestinal handlinginduced mast cell activation and inflammation in human postoperative ileus [J]. Gut, 2008, 57(1): 3340.
15. de Jonge WJ, The FO, van der Coelen D, et al. Mast cell degranulation during abdominal surgery initiates postoperative ileus in mice [J]. Gastroenterology, 2004, 127(2): 535545.
16. Schwarz NT, BeerStolz D, Simmons RL, et al. Pathogenesis of paralytic ileus:intestinal manipulation opens a transient pathway between the intestinal lumen and the leukocytic infiltrate of the jejunal muscularis [J]. Ann Surg, 2002, 235(1): 3140.
17. Wehner S, Behrendt FF, Lyutenski BN, et al. Inhibition of macrophage function prevents intestinal inflammation and postoperative ileus in rodents [J]. Gut, 2007, 56(2): 176185.
18. Bauer AJ. Mentation on the immunological modulation of gastrointestinal motility [J]. Neurogastroenterol Motil, 2008, 20 Suppl 1: 8190.
19. Türler A, Schnurr C, Nakao A, et al. Endogenous endotoxin participates in causing a panenteric inflammatory ileus after colonic surgery [J]. Ann Surg, 2007, 245(5): 734744.
20. Ohama T, Hori M, Ozaki H. Mechanism of abnormal intestinal motility in inflammatory bowel disease: how smooth muscle contraction is reduced？ [J]. J Smooth Muscle Res, 2007, 43(2): 4354.
21. Kalff JC, Schraut WH, Billiar TR, et al. Role of inducible nitric oxide synthase in postoperative intestinal smooth muscle dysfunction in rodents [J]. Gastroenterology, 2000, 118(2): 316327.
22. Kreiss C, Birder LA, Kiss S, et al. Cox2 dependent inflammation increases spinal Fos expression during rodent postoperative ileus [J]. Gut, 2003, 52(4): 527534.
23. Korolkiewicz R, SeinAnand J. Cox2 inhibitors and postoperative ileus [J]. Colorectal Dis, 2007, 9(9): 856857.
24. Mueller MH, Glatzle J, Kampitoglou D, et al. Differential sensitization of afferent neuronal pathways during postoperative ileus in the mouse jejunum [J]. Ann Surg, 2008, 247(5): 791802.
25. Johnson MD, Walsh RM. Current therapies to shorten postoperative ileus [J]. Cleve Clin J Med, 2009, 76(11): 641648.
26. Viscusi ER, Gan TJ, Leslie JB, et al. Peripherally acting muopioid receptor antagonists and postoperative ileus: mechanisms of action and clinical applicability [J]. Anesth Analg, 2009, 108(6): 18111822.
27. Iyer S, Saunders WB, Stemkowski S. Economic burden of postoperative ileus associated with colectomy in the United States [J]. J Manag Care Pharm, 2009, 15(6): 485494.
28. Kraft M, Maclaren R, Du W, et al. Alvimopan (entereg) for the management of postoperative ileus in patients undergoing bowel resection [J]. P T, 2010, 35(1): 4449.
29. Becker G, Blum HE. Novel opioid antagonists for opioidinduced bowel dysfunction and postoperative ileus [J]. Lancet, 2009, 373(9670): 11981206.
30. Erowele GI. Alvimopan (entereg), a peripherally acting muopioid receptor antagonist for postoperative ileus [J]. P T, 2008, 33(10): 574583.
31. Karuppiah S, Farrah R. Alvimopan (entereg) for the treatment of postoperative ileus [J]. Am Fam Physician, 2011, 83(8): 978979.
32. Delaney CP, Weese JL, Hyman NH, et al. Phase Ⅲ trial of alvimopan, a novel, peripherally acting, mu opioid antagonist, for postoperative ileus after major abdominal surgery [J]. Dis Colon Rectum, 2005, 48(6): 11141125.
33. Herzog TJ, Coleman RL, Guerrieri JP Jr, et al. A doubleblind, randomized, placebocontrolled phase III study of the safety of alvimopan in patients who undergo simple total abdominal hysterectomy [J]. Am J Obstet Gynecol, 2006, 195(2): 445453.
34. Asantila R, Eklund P, Rosenberg PH. Continuous epidural infusion of bupivacaine and morphine for postoperative analgesia after hysterectomy [J]. Acta Anaesthesiol Scand， 1991， 35(6): 513517.
35. Jrgensen H, Fomsgaard JS, Dirks J, et al. Effect of peri and postoperative epidural anaesthesia on pain and gastrointestinal function after abdominal hysterectomy [J]. Br J Anaesth， 2001， 87(4): 577583.
36. Liu SS, Carpenter RL, Mackey DC, et al. Effects of perioperative analgesic technique on rate of recovery after colon surgery [J]. Anesthesiology, 1995, 83(4): 757765.
37. Holte K, Kehlet H. Epidural anaesthesia and analgesia-effects on surgical stress responses and implications for postoperative nutrition [J]. Clin Nutr, 2002, 21(3): 199206.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Research Progress of Postoperative Ileus Mechanisms

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