Intestinal rehabilitation is the process of intestinal adaptation through which the remaining small intestine gradually increases its absorptive capacity.

Short-bowel syndrome is the mal-absorptive state that follows extensive resection of the small intestine. Although the remaining bowel undergoes morphological and functional adaptation, often these changes are inadequate to support the individual by enteral feedings. Ambulatory total parenteral nutrition (TPN) then becomes a requirement to prevent dehydration, electrolyte disturbances, and malnutrition on a chronic basis. Complications of long-term TPN include sepsis, thrombosis, parenteral nutrition-induced liver disease, nutrient deficiency states, and, frequently, small bowel bacterial over-growth. Several surgical procedures have been performed, either to decelerate intestinal transit or to increase the area of intestinal absorption with overall unsatisfactory results. However, in the presence of small-bowel dilatation, promising surgical results (tapering, stricturoplasty, intestinal lengthening) have been achieved. Although bowel transplantation has recently reached clinical application with 1-year survival rate of intestinal grafts approaching 50 to 70 %, the ultimate role of intestinal transplantation is still undergoing evaluation.

Potential long-term survival without parenteral nutrition heavily depends on stimulation of the process of intestinal adaptation. Substances such as glutamine and fiber exert bowel-specific trophic effects and have been used to either directly or indirectly influence nutrient absorption. Such therapy supposedly enhances growth of villi in the intestine and prolongs the time it takes for food to pass through the intestine, thereby promoting absorption of nutrients and fluids across the remaining bowel.

Although early studies appeared to show that this type of intestinal rehabilitation was beneficial, recent randomized controlled trials reported that glutamine and low-fat/high-carbohydrate diet are ineffective in enhancing the gastro-intestinal function of patients with short-gut syndrome. In a randomized, double-blind, placebo-controlled cross-over study, Scolapio and associates (2001) found 8 weeks of treatment with oral glutamine and a low-fat/high-carbohydrate diet did not significantly improve intestinal morphology, gastro-intestinal transit, D-xylose absorption and stool losses in short-bowel patients.

Luis et al (2007) analyzed their findings in the management of intestinal failure (IF) with a multi-disciplinary approach including optimized parenteral nutrition (PN), reconstructive surgery and intestinal transplantation (ITx). These researchers included all patients evaluated by their team with the diagnosis of IF. They assessed outcome, mortality and complications in children that achieved adaptation and those listed for ITx. A total of 71 children (31 girls, 40 boys) were evaluated between 1997 and 2006 because of IF. Forty eight (76 %) were referred from other institutions. In 56 cases (80 %), IF began in the newborn period. Causes of IF were: short-bowel syndrome (SBS, n = 52) intestinal motility disorders (n = 16) and intestinal epithelial disorders (n = 3). Median birth weight in the group of SBS was 2.2 kg and prematurity was an associated condition in 15 % of them. Overall, 14 patients (20 %) achieved intestinal adaptation with progressive weaning from PN, the management of these children consisted of optimized parenteral and enteral nutrition and autologous intestinal reconstructive surgery. Nine (13 %) were stable under home PN regimen. Eight children (11 %), all of them listed for liver and small-bowel transplantation, died in the waiting list after a mean waiting time of more than 300 days, with a median of 4 laparotomies and 4 episodes of catheter-related sepsis. Four children (5.6 %) died in the adaptation process or before their inclusion on the waiting list. Finally, 25 (35.2 %) children underwent 28 intestinal transplantation: 9 isolated small-bowel transplantation (SBTx), 16 combined liver and small bowel (CLSB) and 3 multi-visceral (MVTx). Among transplanted patients, 9 (36 %) died, (3 MVTx, 1 SBTx and 8 CLSB) and 4 were re-transplanted. The authors concluded that intestinal transplantation is an established alternative to PN in the treatment of IF, although complications and mortality rates are still considerable, especially MVTx and CLSBTx. Mortality in children listed for intestinal transplantation remains also high. Intestinal adaptation can be achieved with adequate rehabilitation therapy even in some cases with apparently irreversible intestinal transplantation. Early referral before liver failure or other complications arise is crucial in order to improve the outcome of these patients.

Diamond and colleagues (2007) compared the preliminary outcomes of neonates with SBS before with those after the establishment of a formalized IF program (Group for the Improvement of Intestinal Function and Treatment [GIFT]). These investigators conducted a retrospective analysis of their IF registry comparing pre-GIFT (1997 to 1999) with GIFT (2003 to 2005) outcomes. A total of 54 patients (mean gestational age = 33.5 weeks) were included in the GIFT cohort, and 40 patients (mean gestational age = 30.7 weeks) formed the pre-GIFT cohort. Overall mortality rates (33.3 % versus 37.5 %, p = 0.84) were equivalent in the 2 cohorts, although fewer patients died of liver failure after the establishment of the GIFT. Among those with liver failure, the mortality in the pre-GIFT group was 9/10 as compared with that of 6/13 in the GIFT group (p = 0.03). The decrease in liver-related deaths was partly attributable to earlier referral for and increased survival to transplant (4 for the GIFT group versus 0 for the pre-GIFT group). The authors concluded that analysis of the preliminary outcomes of the GIFT program suggested that the natural history of neonatal SBS remains unaltered to date despite a coordinated approach to care. However, improved communication and integration with the transplant service have resulted in earlier assessment, increased rates of transplantation, and decreased mortality from liver failure.

Sigalet and colleagues (2011) described the results of a systematic, protocol-driven management strategy by a multi-disciplinary team for patients with intestinal failure (IF). Intestinal failure was defined as bowel length of less than 40 cm or PN for more than 42 days. A multi-disciplinary team and protocol to prevent PN-associated liver disease (PNALD) were instituted in 2006. Data were gathered prospectively with consent and ethics board approval. From 1998 to 2006, 33 patients were treated (historical cohort) with an overall survival of 72 %. Rotating prophylactic antibiotics for bacterial over-growth were given to 27 % of patients; 6 % had lipid-sparing PN, and none received fish oil-based lipids. Median time to intestinal rehabilitation was 7 +/- 3.1 months, and 27 % of patients who developed PNALD died. From 2006 to 2009, 31 patients were treated. Seventy-seven percent received pre-albumin; 60 %, lipid-sparing PN; and 47 %, parenteral fish oil emulsion. Eighty-seven percent weaned from PN at 3.9 +/- 3.8 months, and no patients developed PNALD with 100 % survival. Novel lipid therapies were associated with changes in essential fatty acid profile and 1 case of clinical essential fatty acid deficiency. The authors stated that the institution of a multi-disciplinary team and a protocol-driven strategy to prevent PNALD improves survival in IF. Moreover, they stated that further studies are recommended.

The American Society for Enteral and Parenteral Nutrition (ASPEN) Clinical Guideline Support of Pediatric Patients With Intestinal Failure at Risk of Parenteral Nutrition–Associated Liver Disease (Wales et al, 2014) includes the following recommendation regarding intestinal rehabilitation programs: "A suggestion is made to refer patients with PN-dependent intestinal failure to multidisciplinary intestinal rehabilitation programs. The evidence on this topic is of very low quality, but the improvement in survival is compelling, and the risk to the child of treatment with multidisciplinary practice is not increased". The guidelines note that the evidence for this recommendation is "very low" and the strength of this recommendation was "weak". The guidelines explain that the data supporting this recommendation are based on comparisons of clinical outcomes after the establishment of multidisciplinary intestinal rehabilitation programs relative to historical controls in the same 3 sites and with a total of 133 children included. The guidelines reference a meta-analysis of these 3 studies by Stanger et al (2013) which found that the relative risk of survival from intestinal failure was 1.22 (95 % confidence interval [CI]: 1.06 to 1.40), favoring the post-multidisciplinary team practice. The guidelines note, however, that these findings may also be influenced by factors other than the multidisciplinary team practice that have changed over the same window in time. The guidelines state that the meta-analysis by Stanger et al found another 12 articles that were descriptive in design outlining clinical improvement in patients with intestinal failure after initiation of an intestinal rehabilitation program, but no control group was included. The guidelines note, in addition, that interpretation of the literature is made difficult due to heterogeneity of patient populations, the intestinal rehabilitation program construct at different institutions, variable treatment protocols, and inconsistent definitions of key clinical outcomes. The guidelines state that the literature would be improved if investigators could reach consensus on definitions of specific outcomes such as short bowel syndrome/intestinal failure, cholestasis, liver failure, sepsis, and parenteral nutrition independence. The guidelines state that further research is likely to change this recommendation.

The ASPEN guidelines (Wales et al, 2014) state that a number of related questions remain to be answered. What characteristics of nutrition supportive care employed by these programs are associated with improved clinical outcomes? Can key practice protocols derived from these groups be translated broadly to improve the care of children who are not able to access a multidisciplinary program? What is the prevalence of other chronic health concerns, such as metabolic bone disease, in long-term survivors of intestinal failure? The guidelines state that, now that mortality risk has diminished with establishment of intestinal rehabilitation programs, future research should address the impact of other comorbidities on outcome, long-term neurodevelopmental outcomes, quality of life of patients receiving chronic parenteral nutrition and after intestinal transplantation, and economic evaluation of intestinal rehabilitation programs.

Scope of Policy

This Clinical Policy Bulletin addresses intestinal rehabilitation programs.

Medical Necessity

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Experimental and Investigational