Introduction

Intestinal failure (IF) was first described in 1981 by Fleming and Remington as the “reduction in gut mass resulting in the loss of the ability of digestion and absorption of food molecules [1].” Since then, the definition of IF has changed and been debated but now has been revised to encompass patients with insufficient intestinal capacity to fulfill nutritional demands resulting in the use of parenteral nutrition (PN). IF may be due to acquired or congenital, gastrointestinal or systemic, or benign or malignant diseases and can affect both adults as well as children [2, 3]. IF can have an abrupt onset and be self-limited, or it may develop as a chronic, slowly progressive disorder with long lasting affects (chronic intestinal failure (CIF)). Treatment of CIF is different than treatment of acute-onset IF and relies on intestinal rehabilitation programs that work to restore absorptive capacity of the bowel through nutrition, pharmacological, and/or surgical therapy [4]. If rehabilitation is unsuccessful, patients with CIF will require long-term PN or intestinal transplantation [5•]. The definition of IF has been revised by multiple sources [2–4, 5•, 6]; however, the European Society for Clinical Nutrition and Metabolism (ESPEN) is the first scientific society which has issued a formal definition for intestinal failure [7••]. The purpose of the current review will be to explore these new definitions as well as their potential clinical impact.

Prior Understanding and Challenges in Defining Intestinal Failure

The average small bowel length in a healthy adult human is approximately 600 cm [8]. The average intestinal length in men is felt to be 630 cm and in women 592 cm [7••]. For IF to occur, a reduction in the number of enterocytes may result in a loss of nutritional autonomy, where normal health and growth and/or development cannot be maintained without PN. The extent of nutritional deficiency and electrolyte imbalances depends on the anatomic segment (duodenum, jejunum, ileum, or colon), length of intestine resected, and the health of the remaining bowel. Therefore, the segment of bowel that is lost will have an impact on whether a patient will progress to IF.

Each segment of the intestine performs distinctly different functions. The proximal small intestine is responsible for absorption of various micronutrients including calcium, magnesium, phosphorous, iron, and folic acid [9]. The resection of the first 150 cm of the small intestine may result in severe metabolic derangements. In addition, the initial 100 to 200 cm of the jejunum is also responsible for the absorption of macronutrients including fats, carbohydrate, protein, micronutrients such as water-soluble vitamins, and water absorption given the large gaps in the intercellular junctions between jejunal epithelial cells [9]. The absorption of carbohydrates determines the osmotic forces and is primarily responsible for regulating fluid flow in the jejunum. In contrast to the jejunum, the ileum has decreased permeability because of tighter intracellular junctions [10] and the ileum relies on active transport of sodium and chloride for significant reabsorption and concentrative ability. The ileum is also the site for vitamin B12 and bile salt absorption, as well as feedback of cholecystokinin, peptide YY, and glucagon-like peptide 1 [11•]. If these regulatory hormones or the ability to reabsorb bile salts is lost with resection of the terminal segment of the small intestine, this results in increased intestinal transit due to hypertonic intestinal contents, increased intestinal secretion of water into the gut lumen, and therefore elevated stool output and risk of dehydration.

The ileocecal (IC) valve plays a crucial role in regulating the delivery of contents into the colon and serves as a mechanical barrier reducing reflux of contents and bacteria from the colon into the small intestine. Whether the ileocecal valve being resected or the length of ileum resected with the IC valve is related to whether a patient loses nutritional autonomy is not completely understood, but clearly resection of the IC valve is an independent predictor for achieving nutritional autonomy [12].

The colon’s main function is fluid and electrolyte reabsorption but does also have some role in energy absorption. It typically absorbs approximately 1 to 2 l per day but does have the ability to absorb up to 6 l [13]. In addition to fluid absorption, the colon assists in the conversion of undigested carbohydrates to absorbable short-chain fatty acids, an alternative energy source that can provide as many as 1000 cal per day in process called colonic salvage [14]. The preservation of the colon during surgical resection improves absorptive capacity of water as well as helps attain nutritional autonomy. In addition, placing the colon back in continuity with the small bowel may help wean PN dependent patients.

Depending on the health of the gut, the segment of intestine resected, and the length remaining after surgical resection, nutritional autonomy can be attained. If autonomy is not attained, patients are then diagnosed with IF. One of the difficulties of how IF has been defined previously is that it is often clinically recognized, but defining it has been difficult. Patients who are at risk for developing IF have an inadequate length of small bowel in continuity. This length is less than 35 cm of small bowel with a jejunoileal anastomosis and an intact colon, less than 60 cm of small bowel with a jejunocolic anastomosis, or less than 115 cm of small bowel with an end-jejunostomy [15]. While many providers may recognize features of intestinal failure, the definition of this syndrome has evolved through the years from the original definition by Remington and colleagues [2–4, 5•, 6]. In an effort to develop evidence driven consensus guidelines, ESPEN endorses guidelines to define and classify IF.

Recent Guidelines on Definition and Classification of Intestinal Failure

While IF is often well recognized by clinicians, it is agreed upon that firm definitions are lacking. In an effort to better delineate how it is that IF is diagnosed and categorized, ESPEN has put forth a set of guidelines to better address these issues. The ESPEN definition of IF concludes that IF only occurs when PN is given and uses the term intestinal insufficiency (or deficiency) for when health and growth are maintained with oral/enteral support [7••]. They conclude that the use of PN is an objective observation that helps better define when a patient has IF.

In addition to whether or not PN was in use to define IF, the new guideline wanted to define subtypes of IF based upon the volume and energy given in the PN. The ESPEN IF guideline committee agreed that comparing nutrient requirement and nutrient absorption would be an optimal way to not only identify but also actually quantify the nutrient need in a patient with IF [16]. However, given that very few medical centers have the facilities for the necessary testing to complete these metabolic studies, the use of PN/fluid supplementation would need to be a “surrogate diagnostic criterion” of IF. Micronutrients could not be mentioned in the definition in order to avoid misunderstanding about impaired gut absorption resulting in micronutrient deficiency alone. Micronutrient deficiency in and of itself would as not be considered IF [3, 5•, 6]. The new definition of IF proposes that two criteria must be present for the diagnosis to be made: a decreased absorption of macronutrients and/or water and electrolytes due to a loss of gut function and the need for PN or intravenous fluids. The guideline authors argue that by including both criteria in the new definition, this reduces ambiguity of true intestinal failure where a patient may have certain macronutrient deficiencies but then be able to be properly supplemented through targeted enteral feeding. The panel proposed that the term “intestinal insufficiency or intestinal deficiency” can be considered in the following conditions (Table 1); where there is reduced food intake but normal gut function, patients with altered gut function but conserved intestinal absorption, patients with inflammatory bowel disease treated with enteral nutrition, patients treated by PN because of refusal of otherwise effective enteral nutrition, patients with a reduction in gut function impairing intestinal absorption but in whom health and growth can be maintained by oral supplementation, enteral nutrition, re-feeding enteroclysis, or those who require only vitamins and trace element supplementation.

Table 1 Conditions of intestinal insufficiency
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The 16 subtype descriptors of IF in the new guidelines were determined by the use of previously proposed classification systems [3, 4, 17–21]. These classification systems describe functional and pathophysiological categories, as well as a clinical classification for CIF based on intravenous energy and volume requirements.

Functional Classification

The first section based on functional classification does so on the basis of onset, metabolic, and expected outcome criteria. Type I describes IF that is acute, short-term, and usually due to a self-limiting condition. Type II describes IF due to a prolonged acute condition, often in metabolically unstable patients who require complex multidisciplinary care and intravenous supplementation over periods of weeks or months. Type III describes IF due to a chronic condition, in metabolically stable patients, requiring intravenous supplementation over month or years. This classification may be reversible or irreversible. This set of subtypes, termed as “functional,” was also used in the UK project titled “A Strategic Framework for Intestinal Failure and Home Parenteral Nutrition Services for Adults in England” [4]. This system categorizes the medical care, professional expertise, management, and treatment setting as well as the organization and logistic issues required to treat IF.

Pathophysiological Classification

The subtypes based on pathophysiology were first described in 1991 [17] and revised multiple times to their most current version [21]. This system aims to underline the main mechanisms that alone or in association with one another can determine whether or not a patient will go on to develop IF. These subtypes are short bowel, intestinal fistula, intestinal dysmotility, mechanical obstruction, and extensive small bowel mucosal disease. These pathophysiologic descriptors are meant to allow providers a mechanism by which to communicate about etiologies for IF in a standardized fashion.

Clinical Classification

Lastly, the ESPEN panel agreed on the need for a clinical classification system for IF to facilitate communication and cooperation among healthcare providers. Clinical classification is based on the common experience of the panel of experts, and a consensus was reached on the clinical classification of CIF due to benign disease or active cancer. Clinical classification is based on intravenous energy and volume requirements. As was to be expected, CIF related to benign disease contained a wider range of patient distribution as benign disease has greater variability in the pathophysiological causes of IF and of activity-related energy expenditure. In patients with active cancer, intestinal dysmotility or mechanical obstruction due to cancer are the most frequent causes of IF.

Implication of ESPEN Definition and Classification System

The primary goal of the ESPEN definitions is to formally recognize and classify IF as an organ failure. One of the major benefits of these definitions and classifications is the potential facilitation of communication and cooperation among professionals who treat IF patients in clinical and research practice. Another major benefit of defining IF is the ability of clinicians to apply clinical treatment guidelines. ESPEN released guidelines on the treatment of CIF in 2016 (Table 2). The stated aim of these guidelines was to generate comprehensive recommendations for safe and effective management for CIF patients. Imagine the difficulty of creating and implementing such guidelines in clinical practice without a general working set of IF definitions and classifications. In fact, in these new 2016 treatment guidelines the definitions and classifications are extensively outlined in the introduction highlighting the importance of defining the disease state. Other benefits of defining IF as a disease state may include expanded insurance reimbursement to cover cost associated with IF and increased research funding.

Table 2 2016 ESPEN guideline statements for treatment of chronic intestinal failure with STRONG recommendations
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Other methods and criteria for defining and classifying IF are certainly possible, but there is currently no better-defined system. A significant critique that the ESPEN guideline authors attempt to address is the requirement of the need for PN in order for the diagnosis of IF to be made. The argument can be made that IF is a disorder encompassing a spectrum of severity as with renal and respiratory failure. Patients are still classified as being in renal failure before they reach an end-stage disease state and require dialysis. Much in the same, many patients are experiencing the spectrum of a failing digestive tract before they reach the need to PN. It may be that adding a definition for recognizing the continuum of the spectrum of IF may be helpful for future direction. While the current ESPEN guidelines are not perfect, they provide a frame work from which we as a clinical community may be able to better determine who needs treatment with PN. Without guidelines defining IF, it is very difficult to apply treatment guidelines to determine those patients who need PN and those who do not need PN.

Conclusions

The next step in the use of the ESPEN definition and classification guidelines is to demonstrate that when applied with the treatment guidelines they are effective in the safe management of IF patients . In addition, if these combined definition and treatment guidelines should be evaluated for effectiveness across different healthcare systems. It would be worth studying the use of this IF classification and treatment in the USA for example to better understand what differences in the healthcare system contribute to the how effective and consistent these guidelines are. There is also opportunity to determine how these guidelines impact management of patients and whether adverse events are reduced. It would be logical to postulate that a more structured approach to defining IF would lead to improved allocation of treatment and avoidance of the negative effects of treatments like PN. Better yet, could it be that a more organized definition for IF combined with treatment guidelines can lead to more appropriate allocation of resources like PN and intestinal transplantation. Both of these treatments are very costly to the healthcare system. This type of impact would not only be important to patients as individuals but to society as a whole.

As a community of clinicians, we are moving forward to better organize and structure the diagnosis of IF. This will help us move past a reliance on the subjective intuition of “knowing it when we see it.” A definition will give clinicians a framework by which to communicate with one another. By better defining IF, we can better study indications and impacts of treatment and transplantation on the individual patient as well the impact of resource utilization on society as a whole. As we begin to rely on this new set of guidelines, we will begin to identify in a systematic approach an improved care model for patients with IF.