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Short bowel syndrome and nutritional consequences. Alastair Forbes University College London. Intestinal failure. Inadequate functional intestine to allow health to be maintained by ordinary food and drink. Intestinal failure . - PowerPoint PPT Presentation
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Short bowel syndrome and nutritional consequences
Alastair Forbes University College London
Intestinal failure
Inadequate functional intestine to allow health to be maintained by ordinary food and drink
Intestinal failure
• Critical reduction of functional gut mass below the minimum amount necessary for adequate digestion and absorption to satisfy body nutrient and fluid requirements
• Jan DM, in Intestinal failure, Ed: Langnas et al
Acute intestinal failure
• Usually follows major resection• May be exacerbated by coexistent
intestinal dysfunction because of severe inflammation or disorders of motility
• (Post-operative ileus)• Type 2 intestinal failure
Intestinal failure
• rare: prevalence 1-2 per 100,000 incidence
1-5 per 1,000,000 • Crohn's, ischaemia, and surgical mishap
account for most benign long-term cases• more common if cancer cases included
Intestinal failure: adaptation• Mostly in first 6 months• Hyperplasia and hypertrophy• Ileum better at this than jejunum• Possibly responsive to trophic factors
Intestinal failure: adaptation• Mostly in first 6 months• Hyperplasia and hypertrophy• Ileum better at this than jejunum• Possibly Responsive to trophic factors
Intestinal failure
Ileostomy and <200cm small bowel<150cm with colonStoma or fistula output >1.5L/day
Intestinal losses
Output proportional to jejunal lengthPositive fluid balance requires ~1mConcept of net absorber/net secretorIf high/normal secretion and poor
absorption, output may be dramatic
Net absorber/net secretor ?
Normal person is net absorberDrink more absorb more
Net absorber/net secretor ?
Normal person is net absorber
Dehydration Thirst Drinking Increased fluid retention Resolution
Normal physiology
Osmosis and sodium gradientsProximal intestinal response is secretoryThreshold about 100mmol/L
Net absorber/net secretor ?
If <1.5m small intestine Normal proximal secretion is not
compensated by distal absorption
Net absorber/net secretor ?
Drink more absorb LESS
Net absorber/net secretor ?
Dehydration Thirst Drinking Increased fluid loss Deterioration
Net secretor and fluid restriction
Fluid restriction is central challenge
Thirst requires LESS drinkingsevere - iv saline moderate - oral rehydration solutionsmild - limit (sodium-free) fluids
The colon in short bowel
Retained colon (>half) equivalent to ~50cm small intestine
Value mainly in fluid balanceSome nutritional gain from fermentation
Assessment
ObservationsSerum electrolytesPlasma osmolaritySerum urea nitrogen/creatinineComplete blood picture Serum magnesium
Urine sodium
Marked sodium retention in dehydrationVery early featureSimple untimed sample sufficient<20 mmol/L almost diagnostic
Unreliable if renal failure or diuretics
Short bowel syndrome management
Scan for sepsisSkin careNutritional careAssessmentPlan for future surgery
Short bowel syndrome management
Scan for sepsisSkin careNutritional care SSNAPAssessmentPlan for future surgery
Short bowel syndrome management
Resuscitate if necessary with iv salineReduce oral intake of low sodium fluidIncrease sodium intakeDon’t render nil per os / nil by mouth
Food selection
Regular foodEncourage high energy densitySeparate food from liquidAvoid fluids (as low Na+)Little and often
Enteral fat intakeIf no colon
useful : energy denseIf retained colon
may give steatorrhoeafat less utilized than carbohydrateless (beneficial) fermentation
Formula feeds in SBS
NOT elemental - becausehigh osmolalitylow energy densityhigh volumepoor palatability
Polymeric not inferior to semi-digestedNo advantage to modified/supplemented
feedsRegular (1kcal/ml) or high energy
(1.5kcal/ml) determined by needs and tolerance of osmolality
Formula feeds in SBS
Simple electrolyte mix
20g glucose3.5g NaCl 2.5g NaHCO3 (or citrate)
Na+ = 90mmol/L
glucose
salt
bicarbonate or citrate
SBS: enteral therapy
Limit “free” fluid intake to 500ml/dayOral rehydration solution (>60mmol/l) ad
libitumAntisecretory regimeEncourage oral feeding
± formula feed± tube feed
Intestinal failure: pharmacological therapy
Proton pump inhibitors reduce gastric secretionLoperamide reduces speed of transit
Intestinal failure: pharmacological therapy
Proton pump inhibitors reduce gastric secretionLoperamide reduces speed of transit
Codeine less favored – sedativeAnticholinergics less favored – dry mouthSomatostatin and derivatives disappointingTeduglutide (GLP-2) great promiseCitrulline - interesting
Intestinal failure parenteral nutrition
Continue all components of enterally based regime (but less rigidly)
Always aim for maximal possible enterallyUsually give more nutrition than estimated
or measured because of malabsorption
Intestinal failure: parenteral nutrition
Usually give more nutrition than predicted Example: patient needs 2000 kcal/day But has SBS and absorption of 50% Eats 2000kcal - absorbs 1000kcal Needs 1000kcal parenterallyTotal 3000kcal administered Correct 2000kcal received
Intestinal failure: parenteral nutrition
Usually give more nutrition than predicted Example: patient needs 2000 kcal/day But has SBS and absorption of 50% Eats 2000kcal - absorbs 1000kcal Needs 1000kcal parenterallyTotal 3000kcal administered Correct 2000kcal received Same applies to other nutrients
Intestinal failure research • New forms of assessment• Modified parenteral feeds• Drugs and trophic factors• Surgical options• The artificial intestine?
Growth hormone• Uniquely approved by the FDA for use in SBS• Mediates its trophic effects through IGF-1• Increases serum IGF-1 and IGF-1 in intestine• Increases crypt cell proliferation• inhibits apoptosis in intestine • Enhances intestinal absorption of nutrients• Best in combination with a optimal SBS care
Glucagon-like peptide 2• Intestinal trophic activities recognized 1996• From intestinal L cells exposed to luminal nutrients• Degraded by DPP IV, t½ 7 min• Increases crypt cell proliferation• Inhibits villous apoptosis• Enhanced digestive and absorptive function• Reduces gastric secretion and slows emptying• Increases intestinal blood flow • Rapidly reversible changes
Teduglutide • Longer acting analogue of GLP-2
– 1 amino acid alteration – enzyme resistant
• More effective than native ?– growth of juvenile primate small bowel
• Particular benefit for fluid balance• Mean of 800mL/d reduction in Phase II
Jeppesen Gut 2005
Teduglutide
Phase 3 study – 24 week evaluation• n=83 • End-point = 20% reduction in PN• Placebo, 0.05/kg, 0.1/kg• 15/16; 27/35 & 29/32 completed • AEs few - 1, 5 and 2 drop-outs
Jeppesen 2009
Teduglutide Weight change• Placebo: 61.5 61.6• Low dose: 57.2 59.7• High dose: 59.5 61.4
Teduglutide Weight change• Placebo: 61.5 61.6• Low dose: 57.2 59.7• High dose: 59.5 61.4Response• Placebo: 1/16 6%• Low dose: 16/35 46% p=0.005• High dose: 8/32 25%• Combined: 24/67 36% p=0.077
Citrulline in intestinal failure
• Produced by intestine (only)• Degraded/excreted by kidneys • Excellent marker of intestinal integrity
Paris group
Citrulline in intestinal failure
• Produced by intestine (only)• Degraded/excreted by kidneys • Excellent marker of intestinal integrity• In various conditions and
independent of inflammation• Clinically predictive
Paris groupLondon/Parma/Zambia group
Therapeutic citrulline in intestinal failure ?
• A “safer” arginine donor• Preserves nitrogen balance in resected
rats (Gut 2004)
• Reduces splanchnic sequestration of amino acids
• Treatment for sarcopenia in rats (AJPEM 2006)
• Prevents TPN muscle atrophy (Clin Sci 2008)Paris/Warsaw group
Osowska et al
The Bianchi Operation
From Thomson 2004
STEP - serial transverse enteroplasty procedure
From Thomson 2004
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1 5 15 20 years10
Transplantation or HPN
HPN vs “best” Tp2007
Mange Takk