Intestinal Rehabilitation and Transplantation Joel Lim, MD Associate Professor of Pediatrics Children s Mercy Hospital University of Missouri in Kansas City
Objective: Intestinal Failure/Short Bowel Syndrome Medical Management - Enteral Nutrition - Parenteral Nutrition - Pharmacologic Therapy Surgical Management - Lengthening procedure - Intestinal transplantation
Intestinal Failure/Short Bowel Syndrome The reduction of gut function below the minimum necessary for the absorption of macronutrients and/or water and electrolytes such that intravenous supplementation is required to maintain health and/or growth. Pironi L, et al. Clin. Nutr 2015;34:171-80
Etiology: Anatomic short gut NEC and congenital malformations Functional- Pseudo- obstruction and congenital diarrhea syndromes Mixed - long segment hirschsprung s disease - Gastroschisis- atresia syndrome
iron carbohydrates, protein, fats, vitamins, minerals, trace elements water, electrolyte, vitamin B 12, bile salt, fat, fat soluble vitamins water, electrolytes, SCFA, oxalates
Evaluation of Length and Site Surgical measurement Radiologic evaluation UGI- SBFT Citrulline level
Nutritional Assessment Weight, height and head circumference Weight values may be underestimated due to fluid shift, ascites, ostomy output and organomegaly Mid- arm circumference and triceps skin fold thickness is important
MEDICAL MANAGEMENT Nutritional Pharmacologic
Nutritional Management Enteral Feeding - Initiated as soon as possible drip vs. bolus feeds What formula? - breast milk is still the most optimal Cow s milk/soy based formula Hydrolyzed formula Amino Acid based formula
When to Feed As soon as postoperative ileus resolves Prompt initiation of enteral feeding increases the rate of enteral autonomy and decrease duration of hospitalization 11
Oral vs Tube Feeding Macronutrient absorption in percent was significantly increased in Enteral tube feeding (ETF), and Oral continuous feeding (OCEF) vs. Oral feeding (oral feeding) Francisca J Gastroenterology 2009;136:824-831 12
Nutritional Management Fiber Insoluble fiber (wheat bran and psyllium) - gelatinize stool but no effect on bowel adaptation Soluble fiber (pectin and guar gum) - converted to short chain fatty acid (butyrate) - can cause osmotic diarrhea
Nutritional Management Monitoring - Iron deficiency - Zinc deficiency - Iodine deficiency - Calcium, chromium, copper, manganese, and selenium - Fat soluble vitamins - Water soluble vitamins
Parenteral Nutrition Life saving therapy Associated with complications - Intestinal Failure Associated Liver Disease (IFALD) - Central line infection - Vascular thrombosis
Predictors of ending PN Small bowel length - >40 cm - > or equal to 10% of expected small bowel length for gestational age - colon length greater than 50% - Retention of ICV ( after 1 year) - Combination of SB >20%+intact colon+icv - NEC and intestinal atresia best prognosis gastroschisis- atresia worst prognosis
Parenteral Nutrition Management of IFALD - Ursodeoxycholic acid - Limiting PN caloric intake to 90-100kcal/kg - Cycling PN - Limiting the fat - Aggressively treating infection - Advancing enteral nutrition - Fish oil (Omega 3 fatty acid)
Parenteral Nutrition Omegaven (Fish Oil) - Omega 3 fatty acids - Improved triglyceride clearance - Anti- inflammatory effect SMOF (Soy, MCT, Olive oil and Fish oil) - adequate balance of omega- 3 and omega- 6 fatty acids
Central Line Access (catheters) Central Line - Broviac - Hickmann - PICC line - Port- a- cath
Central Line Access (catheters) Placed by skilled team Proper position Smaller size Single lumen
Catheter Associated Complications Infection - prevalence is 1.4/1000 days - poor line care - bacterial translocation - Short gut patients have a 6 fold increase in infection - Catheter salvage rate is 42-52%
Catheter Associated Complications Prevention of Infection - Good line care - Appropriate antibiotic treatment - Antibiotic coated catheter - Antibiotic lock therapy - Ethanol lock therapy
Ethanol Lock Therapy 70% ethanol, Silicone lines 63% reduction in infection rates Adverse events are rare which include thrombosis Increase in catheter repair rate with ethanol
Catheter Associated Complications Thromboses - prevalence of 0.2/1000 days - Coagulation defect work- up - Anti- coagulation therapy?
Catheter Associated Complications Imaging Studies - Doppler Ultrasound - Standard Venography - CT Angiography - MRI with Feraheme
Thromboses
Pharmacologic Approach Antimicrobials - bacterial translocation - bacterial overgrowth - short courses (rotational) of oral antimicrobials - rifaximin, metronidazole, and oral gentamicin Lactobacillus rhamnosus GG (probiotics contraindicated with central lines) Pancreatic Enzymes H2 blockers and Proton pump inhibitors
Glucagon Like Peptide - 2 (GLP- 2) Synthesis confined to the ileum and right colon Inhibits apoptosis and stimulates proliferation of the small intestine Improves fluid and electrolytes absorption and citrulline levels Effects were only transient 12 week safety trial in pediatric population (2017)
Oral Insulin Present in breast milk Insulin receptors expressed in small bowel Increase cell proliferation Decrease enterocyte loss Multi- center study in Europe and North America
Surgical Management
Surgical Management Prevention and retention of intestinal length Restoration of Intestinal Continuity Lengthening procedures
LILT- Bianchi
Serial Transverse Enteroplasty Kim. J Pediatr Surg 2003
Tissue Bioengineering Intestinal lengthening is feasible In continuity expanders
Intestinal/Multivisceral Transplantation
History of Intestinal Transplantation Early 1950 s first reported transplantation in dogs 1990 s first successful transplantation due to discovery of more potent immunosuppression 2000 s Rapid increase in the number of intestinal transplantation 2010 s 25% decline in transplantation due to successful rehabilitation
Intestinal Transplantation (types)
Indication for Transplantation Severe intestinal failure associated liver disease Loss of venous access Recurrent central line infection (life threatening) Complete Mesenteric Thrombosis Extremely short residual bowel
Intestinal Transplants Performed 250 200 Number of Transplants 150 100 50 0 1985 1987 1989 1991 1993 1995 1997 1999 2001 2003 2005 2007 2009 2011 2013 Year of Transplant Children Adults
Pediatric Patient Survival by Transplant Type (2009-2014)
Transplantation Annual IT case volumes have leveled after a steep decline and seem to be increasing There is a trend to include the colon with the intestine graft, with evidence that this practice improves outcomes. There have been no major advances in IT graft survival rates for the past 5 years.
Interdisciplinary team Improves the outcome of patients with short gut syndrome (intestinal failure) Early referral is imperative before cholestasis and other complications set in
Take Home Message Aggressive early small bowel rehabilitation is needed (multidisciplinary team) Surgical lengthening should be considered Intestinal transplant is an emerging treatment for patients with intestinal failure
Intestinal Rehabilitation and Transplantation Association Encouraging membership of non- transplant programs Worldwide Pediatric Intestinal Failure Registry Looking for a center to represent Asia jdlim@cmh.edu