Pironi L, Corcos O, Forbes A, et al; ESPEN Acute and Chronic Intestinal Failure Special Interest Groups. Intestinal failure in adults: Recommendations from the ESPEN expert groups. Clin Nutr. 2018 Dec;37(6 Pt A):1798-1809. doi: 10.1016/j.clnu.2018.07.036. Epub 2018 Aug 18. PubMed PMID: 30172658.
Pironi L, Arends J, Bozzetti F, et al; Home Artificial Nutrition & Chronic Intestinal Failure Special Interest Group of ESPEN. ESPEN guidelines on chronic intestinal failure in adults. Clin Nutr. 2016 Apr;35(2):247-307. doi: 10.1016/j.clnu.2016.01.020. Epub 2016 Feb 8. Erratum in: Clin Nutr. 2017 Apr;36(2):619. PubMed PMID: 26944585.
Definition, Etiology, PathogenesisTop
Short bowel syndrome (SBS) develops after surgical resection or bypass of the small intestine, leading to reduced absorption of nutrients and water; in some SBS patients severe malabsorption can lead to intestinal failure such that the patient’s well-being cannot be maintained by oral or enteral nutrition alone. The incidence of SBS is ~2 per 1,000,000 per year and the prevalence is ~20 per 1,000,000.
Intestinal failure is unlikely in adults who retain >150 to 200 cm of functional small intestine but patients may tolerate more extensive loss if the colon remains in continuity, as this contributes substantially to the absorption of fluid and nutrients. Anatomically, patients with SBS at risk of intestinal failure may be assigned to one of 3 groups:
1) End jejunostomy (SBS-J) with no residual colon: The minimum length of residual small intestine required to maintain independence from parenteral nutrition is reported to be ~115 cm.
2) Jejunocolic anastomosis (SBS-JC) with anastomosis of the remnant jejunum to part of the colon (most frequently left colon): The minimum length of residual small intestine required to maintain independence from parenteral nutrition is reported to be ~60 cm.
3) Jejunoileal anastomosis (SBS-JIC) with an intact ileocecal valve and colon: The minimum length of residual small intestine required to maintain independence from parenteral nutrition is reported to be ~35 cm.
SBS is the most common cause of intestinal failure; the other 4 major pathophysiologic causes, which may be due to a variety of benign or malignant conditions, are intestinal fistula, intestinal dysmotility, mechanical obstruction, and extensive small bowel mucosal disease. Clinically, intestinal failure can be classified by duration:
1) Acute (type 1) intestinal failure usually occurs postoperatively and requires short-term IV fluid or nutritional support for days to weeks.
2) Prolonged acute (type 2) intestinal failure, in the presence of multiple complications, requires longer-term parenteral support for weeks to months pending resolution of the complications and intestinal adaptation.
3) Chronic (type 3) intestinal failure due to incomplete adaptation requires parenteral support for months to years or even permanently.
The most common causes of intestinal failure:
1) Extensive intestinal resection due to ischemia, Crohn disease, cancer, trauma, postoperative complications, intestinal torsion or strangulation and necrosis.
2) Extensive small bowel mucosal disease and dysfunction due to, for example, postradiation enteritis or refractory celiac disease.
3) Fistulae, which may be external (causing loss of bowel contents) or internal (bypassing sections of small bowel).
The initial signs and symptoms of SBS—diarrhea, dehydration, cachexia, and electrolyte disturbances—are primarily attributable to the malabsorption of fluid, electrolytes, and macronutrients, and their severity is proportional to the loss of small bowel function. Fluid and electrolyte disturbances are most severe in patients who have end jejunostomy. With time, malabsorption often leads to clinical or subclinical manifestations of vitamin and micronutrient deficiencies, including magnesium, calcium, phosphate, fat-soluble vitamins (A, D, and E, but rarely K), vitamin B12, folic acid, and trace elements (zinc, selenium, chromium, copper).
Long-term complications in patients with type 2 or 3 intestinal failure include:
1) Psychiatric, neurologic, and visual disturbances due to vitamin and essential fatty acid deficiencies (particularly vitamins A and E as well as B vitamins, including vitamin B12) exacerbated by bile acid loss after ileal resection. Neurologic disturbances may also occur in patients receiving long-term parenteral nutrition due to the accumulation of manganese (from trace element supplements) in the extrapyramidal system and aluminum (from IV water contaminants).
2) Arrhythmias, paresthesia, and muscle cramps due to potassium, magnesium, and calcium deficiency.
3) Heart failure and myositis due to selenium and thiamine (vitamin B1) deficiency.
4) Gallstones due to changes in bile composition and gallbladder emptying.
5) Kidney stones due to decreased urine volume and, in patients with a retained colon, excessive absorption of oxalate as a result of unabsorbed fatty acids binding to luminal calcium (to the extent that oxalates are absorbed freely from the colon and excreted in urine, where they bind to calcium, producing oxalate nephrolithiasis).
6) Ascending urinary tract infections, particularly in women, due to frequent profuse diarrhea and perineal contamination.
7) Altered mental status, seizures, and ataxia caused by D-lactic acidosis, predominantly in patients with a retained colon and fermentation of unabsorbed carbohydrates by gram-positive anaerobic bacteria that produce D-lactate.
8) Diarrhea, bloating, flatulence, anorexia, and malabsorption due to small bowel bacterial overgrowth caused by loss of the ileocecal valve after surgery.
9) Esophagitis, peptic ulcer disease, and upper gastrointestinal bleeding due to gastric hypersecretion caused by loss of neuroendocrine inhibitory feedback.
10) Anemia caused by impaired absorption of hematinics, including iron, vitamin B12, folic acid, and copper.
11) Metabolic bone disease and fractures caused by multiple factors, including impaired intake and metabolism of calcium, phosphate, magnesium, and vitamin D; abnormal parathyroid hormone secretion; and aluminum accumulation. These factors are exacerbated by protein-energy malnutrition, decreased exercise tolerance, and sarcopenia.
12) Intestinal failure–related liver disease, including cholestasis, hepatic steatosis, cirrhosis, and liver failure associated with decreased oral or enteral nutrient intake and parenteral lipid or glucose overload and exacerbated by sepsis and medications.
13) Blood stream infections, venous thrombosis, catheter breakage, and catheter occlusion, often due to nonadherence to strict management protocols for venous access management.
Treatment and PrognosisTop
Ideally, SBS should be managed by a multidisciplinary team with nursing, dietetic, and physician members in specialized centers to minimize the risk of catheter-related blood stream infections and ensure coordinated care for patients who often have complex medical problems in addition to the direct effects of small bowel loss. Patients with SBS require close monitoring of their oral intake, with tailored advice regarding the need for hyperphagia and appropriate oral hydration, including rehydration solutions and regular blood tests to ensure appropriate replacement of fluids, electrolytes, macronutrients, micronutrients, and trace elements. Almost all type 3 intestinal failure patients will require long-term parenteral support to provide adequate nutrition, fluid, and electrolytes; even if intestinal adaptation over a period of 6 months to 2 to 4 years permits discontinuation of parenteral support, most patients will require close follow-up. The management of underlying or concomitant conditions, including sepsis, stomas, and fistulae, is complicated by the presence of intestinal failure, while the absorption of oral drugs is often impaired, necessitating careful changes to the dose, formulation, and route of drug administration.
SBS is associated with significant morbidity and impairment of health-related quality of life, partly related to intestinal failure and malabsorption and partly related to the underlying disease as well as the effects of therapy. In general, the 2- and 5-year survival rates for SBS patients, in the absence of malignancy, are ~85% and 70% to 75%, respectively. Efforts to ameliorate the sequelae of intestinal failure have included small bowel transplant with or without other organs, surgical small bowel lengthening procedures, and most recently the administration of gut trophic hormone analogues. Small bowel transplant in adults is performed rarely and only at highly specialized centers; unfortunately, the long-term outcomes have been disappointing compared with other organ transplant procedures. Bowel lengthening procedures have been beneficial in some pediatric patients but there is limited data on their benefit in adults.
Glucagon-like peptide-2 (GLP-2), produced by enteroendocrine L cells in the ileum and colon, plays a key role in maintaining small bowel mucosal mass and function. Recent studies have reported that a long-acting GLP-2 analogue, teduglutide, reduces the need for parenteral support in patients with chronic intestinal failure, allowing up to one-third to discontinue parenteral support completely.Evidence 1Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness and imprecision. Schwartz LK, O'Keefe SJ, Fujioka K, et al. Long-Term Teduglutide for the Treatment of Patients With Intestinal Failure Associated With Short Bowel Syndrome. Clin Transl Gastroenterol. 2016 Feb 4;7:e142. doi: 10.1038/ctg.2015.69. PubMed PMID: 26844839; PubMed Central PMCID: PMC4817413.