Journal of Parenteral and Enteral Nutrition

Short bowel syndrome (SBS) refers to the malabsorptive state caused by physical or functional loss of portions of the small intestine, most commonly following extensive intestinal resection. Such resections hinder absorption of adequate amounts of macronutrients, micronutrients, electrolytes, and water, resulting in malnutrition, diarrhea, and dehydration. Clinical features of SBS vary along a continuum, depending on the extent and anatomy of intestine lost and the ability of the patient and the remaining intestine to compensate for the loss. The impact of SBS can be extensive, leading to diminished health-related quality of life because of its many physical and psychological effects on patients. SBS is associated with decreased survival; risk factors for SBS-related mortality include very short remnant small bowel, end-jejunal remnant anatomy, and arterial mesenteric infarction as primary cause. Although parenteral nutrition and/or intravenous fluid (PN/IV) is a life-saving measure for many patients with SBS, patients with the most severe malabsorption (ie, dependent on PN/IV) are at risk for severe, chronic complications and death. Patients’ treatment needs vary depending on disease severity and resection type; thus, each patient should be individually managed. This review discusses the spectrum of disease in patients with SBS and presents common complications encountered by these patients to highlight the importance of individualized management and treatment.

The human small intestine is organized with a proximal-to-distal gradient of mucosal structure and nutrient processing capacity. However, certain nutrients undergo site-specific digestion and absorption, such as iron and folate in the duodenum/jejunum vs vitamin B₁₂ and bile salts in the ileum. Intestinal resection can result in short bowel syndrome (SBS) due to reduction of total and/or site-specific nutrient processing areas. Depending on the segment(s) of intestine resected, malabsorption can be nutrient specific (eg, vitamin B₁₂ or fat) or sweeping, with deficiencies in energy, protein, and various micronutrients. Jejunal resections are generally better tolerated than ileal resections because of greater postresection adaptive capacity than that of the jejunum. Following intestinal resection, energy scavenging and fluid absorption become particularly important in the colon owing to loss of digestive and absorptive surface area in the resection portion. Resection-induced alterations in enteroendocrine cell abundance can further disrupt intestinal function. For example, patients with end jejunostomy have depressed circulating peptide YY and glucagon-like peptide 2 concentrations, which likely contribute to the rapid intestinal transit and blunted intestinal adaptation observed in this population. SBS-associated pathophysiology often extends beyond the gastrointestinal tract, with hepatobiliary disease, metabolic bone disease, D-lactic acidosis, and kidney stone formation being chronic complications. Clinical management of SBS must be individualized to account for the specific nutrient processing deficit within the remnant bowel and to mitigate potential complications, both inside and outside the gastrointestinal tract.

Intestinal adaptation is a natural compensatory process that occurs following extensive intestinal resection, whereby structural and functional changes in the intestine improve nutrient and fluid absorption in the remnant bowel. In animal studies, postresection structural adaptations include bowel lengthening and thickening and increases in villus height and crypt depth. Functional changes include increased nutrient transporter expression, accelerated crypt cell differentiation, and slowed transit time. In adult humans, data regarding adaptive changes are sparse, and the mechanisms underlying intestinal adaptation remain to be fully elucidated. Several factors influence the degree of intestinal adaptation that occurs post resection, including site and extent of resection, luminal stimulation with enteral nutrients, and intestinotrophic factors. Two intestinotrophic growth factors, the glucagon-like peptide 2 analog teduglutide and recombinant growth hormone (somatropin), are now approved for clinical use in patients with short bowel syndrome (SBS). Both agents enhance fluid absorption and decrease requirements for parenteral nutrition (PN) and/or intravenous fluid. Intestinal adaptation has been thought to be limited to the first 1–2 years following resection in humans. However, recent data suggest that a significant proportion of adult patients with SBS can achieve enteral autonomy, even after many years of PN dependence, particularly with trophic stimulation.

Home parenteral nutrition (HPN) provides nourishment and hydration to patients with short bowel syndrome and intestinal failure and is thus a life-sustaining therapy for these patients. However, measures of quality of life (QOL) are lower among the HPN-dependent population than among patients with other intestinal diseases who do not require HPN. Multiple factors contribute to lower QOL in HPN-dependent patients, including fears surrounding the increased risk of HPN-associated adverse events, such as catheter-related complications, parenteral nutrition−associated liver disease, and metabolic bone disease. In addition, HPN-dependent patients report impaired sleep and daytime fatigue because of pump noises, equipment alarms, and nocturia. Psychosocial burdens on families of HPN-dependent patients include decreased social activities, disrupted family relationships and friendships, and depression. These families also face imposing financial constraints, including decreased employment and large out-of-pocket expenses for insurance premiums and nonreimbursed copayments, medications, and supplies. Furthermore, HPN technology and HPN-related complications and sequelae contribute to the rapid overall increase in the costs of healthcare systems. Additionally, family caregivers provide unpaid healthcare services for patients who require HPN, often to the detriment of their own physical and mental well-being. Nonetheless, patients dependent on HPN and their caregivers often demonstrate considerable resilience and are frequently able to normalize their response to illness and disability. Interventions that may improve QOL among HPN-dependent patients and caregivers include patient education, affiliation with support groups, treatment of concomitant symptoms, and pharmacotherapies that decrease HPN requirements.

Diarrhea associated with short bowel syndrome (SBS) can have multiple etiologies, including accelerated intestinal transit, gastric acid hypersecretion, intestinal bacterial overgrowth, and malabsorption of fats and bile salts. As a result, patients may need multiple medications to effectively control fecal output. The armamentarium of antidiarrheal drugs includes antimotility agents, antisecretory drugs, antibiotics and probiotics, bile acid–binding resins, and pancreatic enzymes. An antidiarrheal regimen must be individualized for each patient and should be developed using a methodical, stepwise approach. Treatment should be initiated with a single first-line medication at the low end of its dosing range. Dosage and/or dosing frequency can then be slowly escalated to achieve maximal effect while minimizing adverse events. If diarrhea remains poorly controlled, additional agents can be incorporated sequentially. If modification of the regimen is required, a single medication should be altered or exchanged at a time. After each adjustment of the regimen, sufficient time should be permitted to fully assess response (≥3–5 days) before initiating additional changes. SBS-associated malabsorption is a major obstacle to optimization of an antidiarrheal regimen because drug absorption is impaired. Patients may benefit from high dosages and/or frequent dosing intervals, liquid preparations, or nonoral routes of drug delivery. Although the diarrhea associated with SBS can be debilitating, effective pharmaceutical management has the potential to substantially improve health outcomes and quality of life for these patients.

A primary goal of intestinal rehabilitation programs is to facilitate intestinal adaptation. Adult patients with short bowel syndrome (SBS) who are dependent on parenteral nutrition and/or intravenous fluid (PN/IV) support have 2 hormonal pharmacologic treatment options available that may promote intestinal growth: a glucagon-like peptide 2 analog (teduglutide) and recombinant human growth hormone (somatropin). In two phase III clinical trials (N = 169), 24 weeks of teduglutide administered to outpatients with SBS resulted in significant decreases in PN/IV volume requirements of 2.5–4.4 L/wk. In an extension study of one of these trials, patients with SBS who completed 30 months of teduglutide experienced a mean PN/IV reduction of 7.6 L/wk from baseline. Furthermore, some patients achieved independence from PN/IV support. The most common adverse events associated with teduglutide treatment in clinical trials were gastrointestinal symptoms, including abdominal distension, abdominal pain, and nausea. This safety profile is consistent with the associated underlying diseases leading to SBS or the known mechanism of action of teduglutide. A single phase III study (N = 41) evaluated the safety and efficacy of a 4-week inpatient course of somatropin in combination with a glutamine-supplemented diet for adults with SBS. Somatropin treatment significantly reduced parenteral support requirements by 1.1 L/d in these patients. The most common adverse events were peripheral edema and musculoskeletal events. Large-scale, long-term follow-up studies of somatropin for SBS have not been conducted. Although treatment for patients with SBS must be individualized, teduglutide and somatropin are positive extensions to existing fluid and nutrient management strategies.

For patients with short bowel syndrome (SBS), surgery can play an important role in preventing, mitigating, and, in some cases, reversing intestinal failure (IF). During intestinal resection, bowel length should be conserved to the fullest extent possible to avoid dependence on parenteral nutrition (PN). Bowel salvage may be improved by initially preserving tissue of questionable viability and later reevaluating during “second-look” procedures. Once the patient is stabilized, ostomy reversal and recruitment of distal unused bowel should be prioritized whenever feasible. Following progression to IF, surgical management of SBS depends on the symptoms and anatomical characteristics of the individual patient. For carefully selected patients with rapid intestinal transit and dilated bowel, longitudinal intestinal lengthening and tailoring (LILT) and serial transverse enteroplasty (STEP) procedures may provide benefit. Outcomes following STEP and LILT are generally similar, and the choice between these procedures may rest on surgeon preference. For patients with rapid intestinal transit in the absence of bowel dilation, segmental reversal of the small bowel may reduce PN requirements. Intestinal transplantation is the standard of care for patients in whom intestinal rehabilitation attempts have failed and who are at risk of life-threatening complications of PN. Because patients awaiting isolated intestine transplant show increased survival compared with patients awaiting combined intestine-liver transplant, early referral of appropriate patients, before the development of advanced liver disease, is critical to enhancing patient outcomes.

Short bowel syndrome (SBS) is a heterogeneous disorder with broad variation in disease severity arising from different types of intestinal resection. The spectrum of malabsorption ranges from intestinal insufficiency to intestinal failure. Individualized patient strategies involving modifications of dietary macro- and micronutrients, fluid, and pharmacologic options are required to maximize health and quality-of-life outcomes and to minimize complications and SBS-associated mortality. Intestinal rehabilitation (IR) is an established but evolving approach to improving patient outcomes by decreasing long-term dependency on parenteral support (PS) for nutrition and fluid requirements. Specialized IR programs employ team-based interdisciplinary approaches to coordinate individualized patient care and treatment management through centralized facilities. Such facilities are often specialized intestinal care centers (ICCs) established at large medical centers. A multifaceted IR program offers the comprehensive interrelated services required by patients with SBS-associated intestinal failure throughout the course of disease. Components of interdisciplinary IR programs should include medical services offering diagnostics and monitoring, pharmacologic management, and symptom and complication control; nutrition services, including dietary modifications and interventions; and supportive psychosocial and educational services. A model of care centered on the IR concept means that long-term patient management, including decisions on long-term PS, is overseen by a member of the specialized care center. Rational, seamless, and timely communication among the patient’s network of home-based and ICC healthcare providers is crucial to the success of any IR program. This paradigm shift to specialized IR programs will likely result in improvements across the patient care continuum.