Patient analysis and case-control investigation for high-output ileostomy control with glucagon (PACIFHIC-G) like peptide-1 analogues: a case control study
DOI:
https://doi.org/10.18203/2320-6012.ijrms20233162Keywords:
Ileostomy, High-output stoma, GLP-1, Intestinal failure, Ileo-colonic break, LiraglutideAbstract
Background: High ostomy losses (HOL) in the early postoperative (PO) period after an ileal resection are in an adaptation phase. After resection of the terminal ileum or proximal colon L cells are lost, this reduces the synthesis of glucagon-like peptide (GLP), its loss accelerates intestinal transit and gastric acid hypersecretion. An adequate adaptation phase is induced by enterotrophic hormones such as GLP. In this case control study, we performed an analysis of clinical outcomes with a conventional treatment compared with liraglutide intervention, a GLP-1 analogue.
Methods: A single center, case-control study, from January 2021 to April 2023, patients had an ileal resection >20 cm, >18 years old, previously treated with loperamide 12 mg and omeprazole 80 mg, continued >1500 ml output at 48 hours PO, 30 patients where collected, 15 patients followed with a watch and wait approach and 15 patients treated 0.6 mcg of liraglutide every day for 8 weeks.
Results: Clinical outcomes were followed for 6 months. Centimeters of resection had a statistically significant difference p<0.001 (control 20-180 cm vs. liraglutide 20-330 cm). Clinical outcomes with a significant difference where hospital length stay p<0.01 (control 4-133 days vs. 1-51 days) and hypovolemic shock p<0.05 (control 5 patients vs. 0 patients). Kaplan-Meier curve an 80% vs 100% 30 day survival rate in controls and liraglutide respectively.
Conclusions: This is the first study with patients with HOL using liraglutide as an adaptation therapy. Patients had better clinical outcomes in mortality, length stay and hypovolemic shock.
References
Nightingale JM, Lennard-Jones JE, Gertner DJ, Wood SR, Bartram CI. Colonic preservation reduces need for parenteral therapy, increases incidence of renal stones, but does not change high prevalence of gall stones in patients with a short bowel. Gut. 1992;33(11):1493-7.
Drucker DJ, Erlich P, Asa SL, Brubaker PL. Induction of intestinal epithelial proliferation by glucagon-like peptide 2. Proceed Natnl Acad Sci. 1996;93(15):7911-6.
Jeppesen PB. Elevated plasma glucagon-like peptide 1 and 2 concentrations in ileum resected short bowel patients with a preserved colon. Gut. 2000;47(3):370-6.
Bremholm L, Hornum M, Andersen UB, Hartmann B, Holst JJ, Jeppesen PB. The effect of Glucagon-Like Peptide-2 on mesenteric blood flow and cardiac parameters in end-jejunostomy short bowel patients. Regul Pept. 2011;168(1-3):32-8.
Madsen KB, Askov-Hansen C, Naimi RM, Brandt CF, Hartmann B, Holst JJ, et al. Acute effects of continuous infusions of glucagon-like peptide (GLP)-1, GLP-2 and the combination (GLP-1+GLP-2) on intestinal absorption in short bowel syndrome (SBS) patients. A placebo-controlled study. Regul Pept. 2013;184:30-9.
Hvistendahl M, Brandt CF, Tribler S, Naimi RM, Hartmann B, Holst JJ, et al. Effect of liraglutide treatment on jejunostomy output in patients with short bowel syndrome: an open‐label pilot study. J Parent Ent Nutri. 2018;42(1):112-21.
Wøjdemann M, Har AW. Glucagon-like peptide-2 inhibits centrally induced antral motility in pigs. Scand J Gastroenterol. 1998;33(8):828-32.
Wøjdemann M, Wettergren A, Hartmann B, Hilsted L, Holst JJ. Inhibition of Sham feeding-stimulated human gastric acid secretion by glucagon-like peptide-2. J Clin Endocrinol Metab. 1999;84(7):2513-7.
Cani PD, Possemiers S, Van de Wiele T, Guiot Y, Everard A, Rottier O, et al. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut. 2009;58(8):1091-103.
Guan X, Karpen HE, Stephens J, Bukowski JT, Niu S, Zhang G, et al. GLP-2 receptor localizes to enteric neurons and endocrine cells expressing vasoactive peptides and mediates increased blood flow. Gastroenterology. 2006;130(1):150-64.
Nagell CF, Wettergren A, Pedersen JF, Mortensen D, Holst JJ. Glucagon‐like peptide‐2 inhibits antral emptying in man, but is not as potent as glucagon‐like peptide‐1. Scand J Gastroenterol. 2004;39(4):353-8.
Washizawa N, Gu LH, Gu L, Openo KP, Jones DP, Ziegler TR. Comparative effects of glucagon-like peptide-2 (GLP-2), growth hormone (GH), and keratinocyte growth factor (KGF) on markers of gut adaptation after massive small bowel resection in rats. J Parenter Enter Nutr. 2004;28(6):399-409.
Litvak D. Glucagon-like peptide 2 is a potent growth factor for small intestine and colon. J Gastroint Surg. 1998;2(2):146-50.
Tsai CH, Hill M, Asa SL, Brubaker PL, Drucker DJ. Intestinal growth-promoting properties of glucagon-like peptide-2 in mice. Am J Physiol Endocrinol Metabol. 1997;273(1):77-84.
Kunkel D, Basseri B, Low K, Lezcano S, Soffer EE, Conklin JL, et al. Efficacy of the glucagon-like peptide-1 agonist exenatide in the treatment of short bowel syndrome. Neurogastroenterol Motil. 2011;23(8):739.
Spiller RC, Trotman IF, Adrian TE, Bloom SR, Misiewicz JJ, Silk DB. Further characterisation of the “ileal brake” reflex in man--effect of ileal infusion of partial digests of fat, protein, and starch on jejunal motility and release of neurotensin, enteroglucagon, and peptide YY. Gut. 1988;29(8):1042-51.
Nightingale JM, Kamm MA, van der Sijp JR, Morris GP, Walker ER, Mather SJ, et al. Disturbed gastric emptying in the short bowel syndrome. Evidence for a “colonic brake”. Gut. 1993;34(9):1171-6.
Chandankhede SR. Acute intestinal failure. Ind J Critic Care Med. 2020;24(S4):168-74.
Allan P, Lal S. Intestinal failure: a review. F1000 Res. 2018;7:85.
Daoud DC, Joly F. The new place of enterohormones in intestinal failure. Curr Opin Clin Nutr Metab Care. 2020;23(5):344-9.
Aksan A, Farrag K, Blumenstein I, Schröder O, Dignass AU, Stein J. Chronic intestinal failure and short bowel syndrome in Crohn’s disease. World J Gastroenterol. 2021;27:3440-65.
Tappenden KA. Intestinal adaptation following resection. J Parenter Enter Nutr. 2014;38(1):23-31.
Nightingale JMD. How to manage a high-output stoma. Frontline Gastroenterology. BMJ Publishing Group; 2022: 140-51.
Hunt JE, Holst JJ, Jeppesen PB, Kissow H. GLP-1 and intestinal diseases. Biomedicines. 2021;9(4):383.
Brandt CF, Tribler S, Hvistendahl M, Staun M, Brøbech P, Jeppesen PB. Single-center, adult chronic intestinal failure cohort analyzed according to the ESPEN-endorsed recommendations, definitions, and classifications. J Parenter Enter Nutr. 2017;41(4):566-74.
