MALABSORPTION

Intestinal failure and short

bowel syndrome

Whats new?
New data, from the use of growth hormone and
glucagon-related trophic factors, show promise in
improving adaptation and reducing the need for artificial
nutrition

Alastair Forbes

The increasing recognition that nutritional support may

be necessary in the absence of anatomical short bowel
syndrome is steadily enlarging the number of patients
recognized to have intestinal failure

Abstract
Intestinal failure is best defined as the reduction of intestine function
so that fluids and nutrients given by the enteral route are needed to
maintain health. It usually follows major resection (e.g. in short bowel
syndrome [SBS]), but also occurs when intact intestine is unable to function due to inflammation or disorders of motility. In many patients, both
causes coexist. Intestinal failure is rare; with a prevalence of 12 per
100,000 and an incidence of 12 per 1,000,000. Adaptation occurs in
the first month after injury and comprises hyperplasia and hypertrophy;
this is potentially responsive to trophic factor. In SBS, intestinal volume
losses may exceed 5 litres/day. The biggest challenge in intestinal failure
management is preventing consumption of excess free fluid orally, as
this is sodium free and drives intestinal secretion. Initial therapeutic
steps include intravenous saline, reduced oral intake of hypotonic fluid,
increased sodium intake and high-energy foods. Formula feeds should
be polymeric with additional sodium and magnesium. Useful drugs
include loperamide, codeine and proton pump inhibitors. Somatostatin
agents are not especially helpful, but growth hormone and GLP-2 may
become important. Parenteral nutrition should be avoided, if possible,
but when essential, follows a routine format. The riskbenefit equation
is beginning to favour intestinal transplantation in selected patients, and
complete failure of intravenous nutrition should no longer be awaited.

Intestinal transplantation is more widely available, and

for some diagnoses the mortality is no longer greater
than that from home parenteral nutrition

cases in the UK (Figure 1). Intestinal failure is best managed when

anticipated (e.g. in any patient with an ileostomy and <200cm of
small bowel, <150 cm of small bowel if it is anastomosed to the
colon, or stoma or fistula output >1.5 l/day).

Fluid balance and the intestine

Normal intestinal fluid volumes are shown in Table 1. It is
clearly an over-simplification to state that all intake and secretion
reaches the mid-point of the small bowel and that all absorption
is more distal, but net fluid shifts largely follow this paradigm.
In most situations, GI output is directly proportional to jejunal
length; positive fluid balance requires about 100 cm.

Causes of intestinal failure at St Marks Hospital,

Harrow, UK

Keywords Crohns disease; glucagons; intestinal transplant; short

bowel syndrome

Intestinal failure may be defined as the presence of inadequate

functional intestine to maintain health by ordinary food and drink
intake (usually extended to include nutrients given enterally).
It is similar, but not identical, to short bowel syndrome (SBS),
which the definition includes.1 Intestinal failure usually follows
major small bowel resection, or can occur when intact intestine
is unable to function because of severe inflammation or motility
disorders. In many patients, both causes are present. Established
intestinal failure is rare; the prevalence is between 1 and 2 per
100,000 population, and the annual incidence is about one-tenth
of this. Crohns disease accounts for more than a third of long-term
Crohns disease
Vascular
Motility
Surgical
Radiation

Alastair Forbes FRCP ILTM is Professor of Gastroenterology and

Clinical Nutrition at University College London. He is Chairman-elect
for Education at ESPEN. He was previously consultant at St.
Marks Hospital, Secretary of the BSG and Chairman of BAPEN. His
interests are in inflammatory bowel disease, nutrition, and intestinal
regeneration. Competing interests: none declared.

MEDICINE 35:4

Progressive systemic sclerosis

Familial adenomatous polyposis
Malignancy
Others

Figure 1

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MALABSORPTION

Management of intestinal failure

Normal gastrointestinal volumes

Food and drink
Saliva
Gastric secretion
Biliary secretion
Pancreatic secretion
Jejunal secretion
Total
Stool liquid

1500
750
1250
1000
1000
2500
8000
150

ml
ml
ml
ml
ml
ml
ml
ml

Water/electrolyte deficit

Nutrient deficit

Fluid restriction

Encourage food

Oral rehydration solution

+ antisecretory agents

Sip feeds

Table 1

The colon is inessential to health and has little direct

nutritional impact, but in SBS it becomes crucial for fluid
balance in this respect it may be equivalent to up to 50 cm of
small intestine. The fermentation of non-absorbed carbohydrates
by colonic bacteria may also yield additional usable nutrients
(up to as much as 1000 kcal/day).
The effluent from a proximal stoma or fistula may exceed
5 l/day. Patients readily develop negative fluid balance, which
provokes thirst, and this aggravates the problem because most
of these individuals are net secretors. Because of the virtual
absence of sodium from fluids that are normally consumed, the
inevitable response to drinking is an increase in output greater
than the additional input, caused by sodium-linked movement of
water across the intestinal wall into the lumen. Recognition of this
paradox is vital to the understanding of SBS, and education (of
staff and patients) is the most important aspect of management.

Overnight tube feed

?Gastrostomy

?Gastrostomy

Intravenous
(subcutaneous) fluid
nightly

Intravenous nutrition
37 nights per week

Figure 2

without major intestinal losses) need intravenous nutrients alone

and may be given an infusion three or four times per week.
In the acute situation, it may be necessary to resuscitate
the patient with intravenous saline, but in most cases this is a
temporary intervention. The next step is reduction of oral intake
of hypotonic fluid typically to no more than 500 ml of free
fluids every 24 hours. In addition, sodium intake should be
increased, and appropriate dietary measures instituted. Rigorous
attention to this regimen can be expected to reduce GI efflux by
about 50% or by around 2 litres. In patients with particularly
high outputs, this is the most profound intervention-induced
change that can normally be achieved.

Investigations
In possible intestinal failure, some physicians tend to rely too
heavily on serum electrolytes, plasma osmolality, serum urea or
creatinine, and full blood count. These are abnormal in advanced
fluid depletion and malnutrition, but are not sensitive. Earlier
indications of disturbed fluid balance come from regular body
weight estimation and random urine sodium. In SBS, the urine
sodium is reduced because of the kidneys avidity for sodium to
maintain an effective circulating volume. Levels below 20 mmol/l
indicate impending hypovolaemic renal failure and a need for
action. Apparently reassuring, but misleading, levels of over
20 mmol/l occur only in established renal failure and in patients on
diuretics (almost always contraindicated in SBS). Low magnesium
is common in SBS and is the usual cause of tetany in these patients.
Low calcium almost always results from low magnesium.

Enteral nutrition food

Regular intake of food should be encouraged in patients with SBS
(Table 2). There may be only modest nutritional gain in severely
affected patients, but pleasure and psychological advantages should
not be underestimated. Eating little and often is usually best, and
intestinal losses tend to be lessened if solid food is separated from
liquid. Most patients will need to avoid certain problem foods, but
in general an energy-rich diet should be advocated. Advice on enteral
fat intake depends partly on the presence or absence of the colon. In
patients with no colon, a high fat intake is useful because it is rich
in energy and should cause no problems. In those with a colon, a
tendency to steatorrhoea may limit fat tolerance. Additionally, the
use of a fat-predominant energy source diminishes the availability
of unabsorbed carbohydrate for colonic bacterial fermentation, and
thus the subsequent availability of nutritionally useful substrates.

Management
The principal aims of management are to:
minimize sodium-poor fluid intake
reduce gut secretion
slow intestinal transit
overcome nutritional deficiencies.
It is useful to consider patients with intestinal failure on two
parallel algorithms (Figure 2). Most require fluids, electrolytes,
and nutrients, but some need daily intravenous fluids with no
nutrients, and others (mostly those with motility disorders and

MEDICINE 35:4

Overnight tube oral

rehydration solution

Enteral nutrition formula feeds

Formula feeds may be useful to increase nutrient assimilation
outside mealtimes. These should not be of an elemental nature;
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MALABSORPTION

Enteral therapy in short bowel syndrome

Oral rehydration solution

Limit free fluid intake to 500 ml/day

Oral rehydration solution ad libitum
Antisecretory regimen
Encourage oral feeding
Consider formula feed
Consider enteral tube delivery of feed and/or oral rehydration
Additional magnesium and specific micronutrients as required

In 1 litre of water (not necessarily sterile):

20 g glucose
3.5 g sodium chloride
2.5 g sodium bicarbonate (or sodium citrate)
Yields sodium 90 mmol/l
Table 3

be sufficient to allow a nights sleep with no need for a change of

stoma bag, and it is therefore a worthwhile intervention.
Experience with somatostatin, octreotide and lanreotide is less
encouraging than might be expected. Output is reduced by about
500 ml/day in trials, but this is seldom replicated in clinical practice. A 72-hour trial of octreotide, 300 g/day is worthwhile. If this
is clinically effective, conversion to the longer-acting lanreotide is
warranted; if there is no obvious response, this drug group can be
abandoned. Fewer than 5% of patients gain prolonged benefit.
Low-dose human growth hormone has now been shown to
yield useful results, reducing stomal losses and promoting an
anabolic state, even many months after adaptation would have
been expected to be complete.2 However, the effects are modest
in magnitude and its use has not yet become routine.

Table 2

the high osmolality and volume, low energy density, and poorer
palatability of such feeds render them ill-suited to the particular
problems of SBS. Polymeric feeds are not obviously inferior to
semi-digested formulations, and there is no clear advantage to
the use of modified/supplemented feeds such as those containing extra glutamine or nucleotides. The choice between regular
(1 kcal/ml) and high-energy (1.5 kcal/ml) feeds is determined
by the patients needs and the degree of tolerance of the higher
osmolality of the latter (which may aggravate the volume of
intestinal losses). Addition of sodium will often be needed
because of the particularly high requirements in SBS. Although
ordinary table salt can be used, it is often more practical to
use vials of strong NaCl (e.g. 5% = 830 mmol/litre). (Generally speaking patients who need additional magnesium will be
dependent on parenteral fluids.) Overnight tube feeding (nasogastric or gastrostomy) is helpful in increasing the number
of absorptive hours in borderline patients and in those who
cannot tolerate the formulae orally.
Oral rehydration solution is needed in patients whose fluid
balance remains marginal despite the above measures. It does
not reduce effluent volumes, but renders them safe because
sodium influx and efflux are nearer to equal. A concentration
of about 100 mmol/l is required for sodium balance in the jejunum, but many proprietary solutions are low in sodium and
none contain more than 60 mmol/l. The heritage WHO solution
contained 90 mmol/l of sodium, but had unnecessary amounts
of potassium and was adapted, with a gain in palatability, to
produce the St Marks formula (Table 3). The choice between
bicarbonate and citrate may be the patients decision. The solution may be flavoured with small amounts of fruit squash concentrate or lemon juice, and is better tolerated if served straight
from the refrigerator (or kept in a vacuum flask). Some patients
benefit from overnight enteral tube delivery of the solution.

Parenteral therapy
Despite best efforts, in some patients fluid restriction and enteral
therapy are insufficient to restore and maintain sodium, fluid or
calorie balance. Parenteral therapy then becomes essential. All
components of the enterally-based regimen should be continued,
but may be applied less rigidly.
Subcutaneous fluids may be considered in patients with
modest fluid, sodium and/or magnesium deficit in whom the
parenteral fluid requirement is less than 1 litre/day. Placement
of a subcutaneous cannula each night (610 hours) normally
permits the administration of at least 500 ml of fluid, which can
accommodate 75 mmol sodium and at least 4 mmol magnesium.
Patients should be warned that a swelling may develop; this acts
as a depot, diminishing over the following hours.
The intravenous catheter
An intravenous approach is necessary in patients requiring
nutrients or larger quantities of fluid or electrolytes. Care must
be taken when establishing venous access. Use of a subcutaneous
tunnel reduces infective complications and the risk of cannula
displacement. Strict aseptic technique must be observed; feeding
cannulae should not be handled without sterile gloves or used for

Pharmacological measures
A so-called antisecretory drug regimen is normally administered
in short bowel syndrome (Table 4). This regimen is not strictly
antisecretory, because the main action of the opioid component
(acting via receptors) is to delay transit, but the reduction in gastric secretion volume achieved by the inclusion of a proton pump
inhibitor (most gastric secretion is acid) is beneficial. Anticholinergics are not favoured; their common side-effect of dry mouth may
cause clinical confusion with respect to hydration status. In combination with restriction of sodium-free fluids, this regimen can be
expected to reduce gastrointestinal efflux by about 20% (around
5001000 ml/day). Although only a modest improvement, this may

MEDICINE 35:4

The antisecretory regimen

Opioids
Loperamide, 1664 mg/day
Codeine phosphate, 120480 mg/day
Proton pump inhibitor, standard full dose or double dose
Occasional use of somatostatin-like agents

Table 4

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MALABSORPTION

any purpose other than the provision of nutritional fluids. With

these precautions, the complication rate is very low (an average
of one episode of line sepsis every three years). In specialist centres, the average catheter lifetime is more than 3 years, but careful
patient training is required: at least 3 weeks is thought necessary,
but American data suggest that, with appropriate support, the
training time can be substantially reduced without risk.

Summary of current indications for intestinal

transplantation (American Gastroenterological
Association)
1 Failure of home parenteral nutrition (HPN)
Impending or overt liver failure due to parenteral nutritionrelated liver injury
Central venous catheter-related thrombosis of 2 or more
central veins
Frequent or severe central line sepsis
Frequent severe dehydration despite intravenous fluid in
addition to HPN

The intravenous regimen

In the intravenous regimen used for SBS, the quantities of sodium
and magnesium, and the volume of fluid required are greater than
in conventional post-operative intravenous nutrition. In all forms of
intestinal failure requiring intravenous nutrition, the provision of
lipids should be limited to no more than 2 g/kg/week (~1 litre 20%
lipid emulsion/week), to avoid the cholestasis of long-term intravenous nutrition.3 Vitamin and trace element replacement are obligatory. Glutamine has been shown to be ineffective and need not be
added.4 It should be emphasized also, that intestinal failure patients
can, and should, eat even when intravenous nutrition has become
necessary. Substantial (though inadequate) nutrient absorption can
be achieved. Patients dependent on long-term intravenous nutrition
may need as little as 30% of their daily requirements intravenously
(5060% would be typical). The term total parenteral nutrition is
a misnomer and should be avoided in this context.

2 High risk of death otherwise attributable to the underlying

disease, including:
Desmoid tumours associated with familial adenomatous
polyposis
Congenital mucosal disorders (microvillus inclusion, tufting
enteropathy)
Ultra short bowel syndrome (<10 cm in infants; <20 cm in
adults)
3 Intestinal failure with high morbidity or low acceptance of HPN
Table 6

Predicting the need for intravenous nutrition

Long-term intravenous nutrition is more likely to be necessary in
certain predictable circumstances (Table 5); referral to a specialist
centre should then be considered. Referral is also warranted for
patients with multiple fistulae, laparostomy wounds, persistent
intra-abdominal sepsis, venous access problems, unresponsive
hypoalbuminaemia, or associated hepatic or renal dysfunction.
Low plasma citrulline is an additional independent marker of the
need for intravenous support.5

should be more generally adopted to ensure that patients do not

deteriorate to the point at which surgery is precluded or that liver
as well as small bowel grafting becomes necessary. Early assessment of these patients at specialist centres is recommended.

The future
Newer agents with true antisecretory effects are under develop
ment and should soon be available. These include drugs acting
on the delta opioid receptor and those directly affecting the
enterocyte chloride channel. Manipulation of the intestinal
serotinergic system may also prove to be of value.
Research into ways of promoting intestinal adaptation continues. Adaptation occurs mainly in the first 6 months after injury;
it involves both hyperplasia and hypertrophy, and is probably
responsive to trophic factors, as suggested by the growth hormone data. It may be reinvoked or prolonged by administration
of glucagon-like peptide 2 (GLP-2). The first human experiments
with a more stable analogue (teduglutide) indicate that GLP-2
reduces the magnitude of salt and water loss and contributes to
energy conservation.8,9
The place of intestinal transplantation is increasing, and
it is probable that the criteria for its use will continue to be
broadened.

Intestinal transplantation
Transplantation of the small intestine has been feasible for some
time, but has not been felt sufficiently safe to be justified in most
patients with intestinal failure. This situation is gradually changing, and in the two busiest North American centres, mortality
rates at one year are now no worse than those for unselected
patients on home parenteral nutrition (HPN).6,7 It will be understood that this is not an entirely balanced comparison, as the
HPN figures include patients with neoplasia, scleroderma and
chronic abdominal sepsis who have high mortality and who
would not be considered for transplantation. Nonetheless, the
current criteria for consideration for transplantation (Table 6)

Situations in which long-term i.v. nutrition is required

Very short bowel syndrome (<80 cm terminating in stoma,
<50 cm anastomosed to colon)
Proximal fistula
High output (>1.5 litres/day) despite full enteral therapy
Patients with intestinal failure in whom eating provokes pain
Patients with low circulating citrulline concentration

References
1 Nightingale J, ed. Intestinal failure. London: Greenwich Medical,
2001.
2 Seguy D, Vahedi K, Kapel N, Souberbielle JC, Messing B. Low-dose
growth hormone in adult home parenteral nutrition-dependent
short bowel syndrome patients: a positive study. Gastroenterology
2003; 124: 293302.

Table 5

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3 Cavicchi M, Beau P, Crenn P, et al. Prevalence of liver disease and

contributing factors in patients receiving home parenteral nutrition
for permanent intestinal failure. Ann Intern Med 2000; 132: 52532.
4 Culkin A, Gabe S, Bjarnasson I, Grimble G, Forbes A. A double-blind
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Survival analysis in a cohort of adult patients on home parenteral

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nutrition. Prognostic factors related to early and overall mortality.

Clin Nutr 2003; 23: 17.
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peptide 2 improves nutrient absorption and nutritional status in
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80615.
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clinical applications. Clinical significance of GLP-2 in short-bowel
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