Aetna considers intestinal rehabilitation programs or individual components of such programs (e.g., glutamine) experimental and investigational because these interventions have not been shown to be effective.  These programs have been used for persons with anatomical loss of their intestine secondary to extensive surgical resection (e.g., short-bowel syndrome) or with functional loss (e.g., Crohn's disease, ischemic disease, radiation injury, and ulcerative colitis).

See CPB 0170 - Growth Hormone (GH) and Growth Hormone Antagonists for policy on growth hormone therapy for short-bowel syndrome.

See also CPB 0605 - Intestinal Transplantation for criteria for intestinal transplantation for persons who have failed total parenteral nutrition.

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.