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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
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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
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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 colon
Stoma or fistula output >1.5L/day
Intestinal losses
Output proportional to jejunal length
Positive fluid balance requires ~1m
Concept of net absorber/net secretor
If high/normal secretion and poor
absorption, output may be dramatic
Net absorber/net secretor ?
Normal person is net absorber
Drink more  absorb more
Net absorber/net secretor ?
Normal person is net absorber
Dehydration  Thirst  Drinking 
Increased fluid retention  Resolution
Normal physiology
Osmosis and sodium gradients
Proximal intestinal response is secretory
Threshold 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 drinking
severe - iv saline
moderate - oral rehydration solutions
mild - limit (sodium-free) fluids
The colon in short bowel
Retained colon (>half) equivalent to ~50cm
small intestine
Value mainly in fluid balance
Some nutritional gain from fermentation
Assessment
Observations
Serum electrolytes
Plasma osmolarity
Serum urea nitrogen/creatinine
Complete blood picture
Serum magnesium
Urine sodium
Marked sodium retention in dehydration
Very early feature
Simple untimed sample sufficient
<20 mmol/L almost diagnostic
Unreliable if renal failure or diuretics
Short bowel syndrome
management
Scan for sepsis
Skin care
Nutritional care
Assessment
Plan for future surgery
Short bowel syndrome
management
Scan for sepsis
Skin care
Nutritional care
Assessment
Plan for future surgery
SSNAP
Short bowel syndrome
management
Resuscitate if necessary with iv saline
Reduce oral intake of low sodium fluid
Increase sodium intake
Don’t render nil per os / nil by mouth
Food selection
Regular food
Encourage high energy density
Separate food from liquid
Avoid fluids (as low Na+)
Little and often
Enteral fat intake
If no colon
useful : energy dense
If retained colon
may give steatorrhoea
fat less utilized than carbohydrate
less (beneficial) fermentation
Formula feeds in SBS
NOT elemental - because
high osmolality
low energy density
high volume
poor palatability
Formula feeds in SBS
Polymeric not inferior to semi-digested
No advantage to modified/supplemented
feeds
Regular (1kcal/ml) or high energy
(1.5kcal/ml) determined by needs and
tolerance of osmolality
Simple electrolyte mix
20g glucose
3.5g NaCl
2.5g NaHCO3 (or citrate)
Na+ = 90mmol/L
glucose
bicarbonate
or citrate
salt
SBS: enteral therapy
Limit “free” fluid intake to 500ml/day
Oral rehydration solution (>60mmol/l) ad
libitum
Antisecretory regime
Encourage oral feeding
± formula feed
± tube feed
Intestinal failure:
pharmacological therapy
Proton pump inhibitors reduce gastric secretion
Loperamide reduces speed of transit
Intestinal failure:
pharmacological therapy
Proton pump inhibitors reduce gastric secretion
Loperamide reduces speed of transit
Codeine less favored – sedative
Anticholinergics less favored – dry mouth
Somatostatin and derivatives disappointing
Teduglutide (GLP-2) great promise
Citrulline - interesting
Intestinal failure
parenteral nutrition
Continue all components of enterally based
regime (but less rigidly)
Always aim for maximal possible enterally
Usually 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 parenterally
Total 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 parenterally
Total 3000kcal administered
Correct 2000kcal received
Same applies to other nutrients
Intestinal failure research
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New forms of assessment
Modified parenteral feeds
Drugs and trophic factors
Surgical options
The artificial intestine?
Growth hormone
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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
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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:
• Low dose:
• High dose:
61.5  61.6
57.2  59.7
59.5  61.4
Teduglutide
Weight change
• Placebo:
• Low dose:
• High dose:
Response
• Placebo:
• Low dose:
• High dose:
• Combined:
61.5  61.6
57.2  59.7
59.5  61.4
1/16
16/35
8/32
6%
46% p=0.005
25%
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
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Produced by intestine (only)
Degraded/excreted by kidneys
Excellent marker of intestinal integrity
In various conditions and
independent of inflammation
• Clinically predictive
Paris group
London/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
Transplantation or HPN
100
90
HPN vs “best” Tp
2007
80
70
60
50
40
30
20
10
0
1
5
10
15
20 years
Mange Takk