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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Transplantation or HPN

HPN vs “best” Tp2007

Mange Takk