Intestinal failure - Clinical Tree

Introduction

Intestinal failure (IF) is defined as the reduction of gut function below the minimum necessary for the absorption of macronutrients and/or fluid and electrolytes, such that intravenous supplementation is required to maintain health and/or growth. ^,

IF can be classified on the basis of onset, metabolic and expected outcome criteria: ^,

Type 1: acute, short-term, without significant intestinal pathology and usually self-limiting. The vast majority of IF cases are type 1 and frequently occur secondary to post-operative ileus. They are routinely managed in general surgical units.
Type 2: prolonged acute condition requiring artificial nutrition for more than 28 days, often in metabolically unstable patients, requiring complex multi-disciplinary care and intravenous supplementation over periods of weeks or months. This type is considered potentially reversible.
Type 3: chronic, in metabolically stable patients, requiring intravenous supplementation over months or years and, in a subset of patients, permanently.

Types 2 and 3 are distinguished by loss of functional gut due to massive intestinal loss following surgery, or loss of functioning intestine available for absorption, as can occur after development of enterocutaneous fistula (ECF).

Patients with Type 1 and a subset of patient with Type 2 IF would be expected to return to full enteral autonomy in time.

Management of these cases may be complex, prolonged and expensive, in terms of financial cost and clinical input. The care of these patients should therefore be in a specialist IF unit. Such a unit should include a nutrition support team with the capacity to facilitate transition of the patient’s care from a hospital environment to a home environment. The care of patients with IF is prolonged and involves specialist gastroenterological, surgical, nursing, pharmacy, dietetic and psychological input. Surgical treatment is generally the last of many steps in the management but accounts for an important part of the workload of specialised IF units.

The nursing staff on the ward and in clinic, specialist nutrition nurses and the home parenteral nutrition (PN) team are the backbone of delivery of care to these patients and their families. The different functions of each of these groups and their separate locations make it imperative that all are coordinated in their approach to each patient. Failure to achieve this results in confusion and demoralisation of this psychologically vulnerable group of patients, who are faced with prolonged hospital admission, debilitating illness, the prospect of no longer being able to eat normally (or at all) and the likelihood of incomplete functional recovery. Those who survive find it difficult to accept the major limitations to their opportunities in life, especially in the case of young adults who constitute a significant proportion of these patients. A high level of technical training of patient and family (where necessary) is required, which necessitates a specialist centre to maintain the technical base to these skills.

Guidelines on surgical management have been published by the Association of Surgeons of Great Britain and Ireland and the European Society of Coloproctology. ^, The National Health Service has set up and funded two national reference centres in England through the National Specialist Commissioning Advisory Body. One is at St Mark’s Hospital in London, the other is at Salford Royal Hospital in Salford. Currently, a national procurement process for severe IF is underway, aiming to set up and fund home PN centres, integrated care centres (for the joint medical and surgical management of IF) and national reference centres (the two existing national units).

Epidemiology

The prevalence of IF is unknown, but estimates can be made by considering those who require home PN. The incidence of home PN in Europe is estimated to be 3 per million population and the prevalence at 4 per million population, of whom 35% have short-bowel syndrome (SBS). ^, In the USA the use of home PN is estimated to be 120 per million population, of whom approximately 25% have SBS. Such data do not include the patients who have not required home PN or those who have been successfully weaned off home PN. In the UK the estimated incidence of IF requiring treatment at a specialised unit is 5.5 per million population.

As SBS is an uncommon condition, specialised centres with expertise in SBS have been created. ^, ^, A recent study showed an overall survival rate of 86% in patients undergoing autologous surgical reconstruction in a specialised unit at a median follow-up period of 2 years. Similar results have been achieved in other units and highlight the importance of multi-disciplinary care. ^,

Causes

IF can be caused by the following major pathophysiological conditions, which may originate from various gastrointestinal or systemic diseases:

1.
Loss of intestinal length: SBS.
2.
Loss of functional intestinal length: intestinal fistula.
3.
Loss of intestinal function: intestinal dysmotility and mechanical obstruction.
4.
Loss of intestinal absorptive capacity: extensive small-bowel mucosal disease.

Loss of intestinal length

In the adult population, IF is most commonly related to a loss of intestinal length as a result of multiple resections or one massive intestinal resection. ^, Multiple resections are most common in recurrent Crohn’s disease; an isolated massive enterectomy usually follows a vascular catastrophe, such as mesenteric arterial thrombosis or embolism or a venous thrombosis. Massive resection can also be necessary in cases of volvulus, trauma or, in the case of children, necrotising enterocolitis or gastroschisis.

The relation between the amount of bowel removed and the degree of IF is variable, influenced by the age of the patient, the site of resection and the presence or absence of colon. The normal small bowel is around 600 cm in length but may range between 300 and 800 cm. The important figure is not how much small bowel is removed but how much remains.

Post-operative small bowel anatomy can broadly speaking be categorised in three different groups for which the prognosis differs according to the surgical anatomy and the length of remaining small bowel:

Group 1: small bowel ending in an end jejunostomy; long-term IF mostly associated with <100 cm residual small bowel
Group 2: jejunocolic anastomosis; long-term IF mostly associated with <50 cm residual small bowel anastomosed to complete colon; more small bowel is required where there is less colon
Group 3: jejuno-ileal anastomosis with preservation of the ileocaecal junction: long-term IF mostly associated with <30–50cm residual small bowel.

Children may function with shorter bowel as small bowel adaptation (see later) can be more dramatic. The function of the remaining bowel may also be influenced by the presence of active Crohn’s disease as well as the presence or absence of colon, as this may have a significant absorptive function.

Loss of functional absorptive capacity

ECF or entero-atmospheric fistula (EAF) is the commonest cause of IF where the mechanism is loss of functional absorptive capacity. Fistulous disease commonly bypasses otherwise normal functional small intestine. This is usually the result of an ECF, but entero-enteric or enterocolic fistulae (such as those seen in certain Crohn’s phenotypes) may also be responsible.

At a specialised IF unit, 42% of patients had Crohn’s disease and the commonest complication necessitating admission was formation of ECFs (in 44% of patients). The second most common cause of fistulae is abdominal surgery: in non-Crohn’s patients, ECFs most commonly result as a post-operative complication from either partial breakdown of an intestinal anastomosis or inadvertent bowel injury. ^, Risk factors for this include the age of the patient, the state of the bowel undergoing anastomosis, pre-operative nutritional status and the site of anastomosis. When associated with malignancy, factors including tumour fixity, presence of obstruction, previous radiotherapy, associated abscess and surgical technique all affect the risk. Non-absorbable mesh can erode into the bowel and cause fistula, particularly where there is fragile post-operative or diseased bowel. The use of vacuum-assisted closure (VAC) systems in the open abdomen can result in fistula when applied next to the bowel wall. In patients with intestinal or peritoneal inflammation and/or multi-organ failure, there is a 20% rate of intestinal fistulisation associated with the use of a VAC system. Irrespective of VAC dressings or mesh, the inappropriate formation of a laparostomy (i.e., leaving the abdomen open without a plan for short-term primary fascial closure) is in itself fistulogenic. ^,

Other causes of fistula formation include colorectal cancer, diverticular disease and radiation. Fistulae resulting from radiation damage are usually complex and carry a high mortality. Rarer conditions include trauma and congenital fistulae, such as a patent vitellointestinal tract. Tuberculosis may fistulate as a complication of an ileal mass, and actinomycosis is an alternative possibility. Ulcerative colitis may fistulate, but this is more common post-operatively, and occasionally, the diagnosis needs reviewing with regard to the possibility of Crohn’s disease.

Loss of intestinal function

In the acute setting, post-operative ileus is the commonest reason for loss of intestinal function, but this is usually self-limiting and does not require more than short-term supportive treatment. More chronic conditions, such as pseudo-obstruction, gastroparesis, visceral myopathy or autonomic neuropathy, can result in functional disability and present a significant challenge for management.

Loss of intestinal absorptive capacity

Inflammatory conditions of the small bowel can result in non-functioning enterocytes that reduce absorptive capacity. Such conditions include inflammatory bowel disease, scleroderma, amyloid, coeliac disease and radiation enteritis.

Pathophysiology

The three stages of intestinal failure

Following the initiating event, intestinal ‘recovery’ results in three recognisable phases that have implications for management.

Stage I: hypersecretory phase

Of the 7 litres secreted daily by the duodenum, stomach, small intestine, pancreas and liver, about 6 litres are reabsorbed proximal to the ileocaecal valve and a further 800 mL are reabsorbed in the colon, leaving just 200 mL of water in the faeces.

Lack of absorption results in large volume losses. This phase can last 1–2 months and is characterised by copious diarrhoea and/or high stoma or fistula outputs. The main focus of treatment is on fluid and electrolyte replacement, while PN may be required to maintain nutrition.

Stage II: adaptation phase

The process of intestinal adaptation involves a series of histological changes in the intestinal mucosa that permit enhanced mucosal absorption within the residual intestine. The triggers for adaptation are the maintenance of fluid and electrolyte balance and the gradual introduction of enteral feeding. The process of adaptation takes 3–12 months and the degree of adaptation varies with age (more adaptation occurs in the paediatric population), underlying disease extent, and the site of resection (ileum has better capacity for adaptation than jejunum).

Stage III: stabilisation phase

Maximum intestinal adaptation may take up to 1–2 years and the extent and route of nutritional support will vary. The overall goal for the patient is to achieve as normal a lifestyle as possible, which means achieving stability at home.

Normal physiological functioning of the intestine involves complex fluid, electrolyte and nutrient exchanges to maintain homeostasis. Interruption of this can result in gross imbalances that require supplementation enterally or parenterally. The normal physiology of the intestine is discussed later.

Fluid and electrolytes

Sodium absorption in the small bowel is actively linked to the absorption of glucose and certain amino acids. Water absorption is passive and follows the sodium. The jejunum is freely permeable to water, so the contents remain isotonic.

Movement of sodium into the lumen occurs if luminal sodium concentration is low, and absorption of sodium, and hence water, occurs only when the concentration is greater than 100 mmol/L.

Sodium absorption normally occurs in the ileum and colon. In the absence of the absorptive capacity of the ileum and colon, the net sodium losses are expectedly high. This occurs in the presence of a high fistula or jejunostomy; the daily net loss of sodium and net loss of water from the body will be approximately 300–400 mmol and 3–4 L, respectively. This highlights the importance of sodium replacement when there is a high jejunostomy or fistula. Oral fluid concentrated in sodium will help reduce enteric fluid losses. The minimum required daily oral sodium replacement is 100 mmol. The sodium concentration that is absorbable is limited by palatability.

The colon has a significant absorptive capacity, amounting to 6–7 L of water, up to 700 mmol of sodium and 40 mmol of potassium per day. Connection of colon in continuity with the residual small bowel will significantly reduce water and sodium losses.

Potassium absorption is usually adequate unless there is less than 60 cm of small bowel. In this scenario, standard daily intravenous requirements of potassium are 60–100 mmol. Magnesium is usually absorbed in the distal jejunum and ileum. Loss of these will result in significant magnesium loss and deficiency. Magnesium deficiency may precipitate calcium deficiency because hypomagnesaemia impairs the release of parathyroid hormone.

Nutrients

Carbohydrates, proteins and water-soluble vitamins

The upper 200 cm of jejunum absorbs most carbohydrates, protein and water-soluble vitamins. Nitrogen is the macronutrient least affected by a decrease in the absorptive surface and utilisation of peptide-based diets rather than protein-based ones has demonstrated no benefit. Water-soluble vitamin deficiencies are rare in patients with SBS, although thiamine deficiency has been reported.

Fat, bile salts and fat-soluble vitamins

Fat and the fat-soluble vitamins (A, D, E and K) are absorbed over the length of the small intestine, hence loss of ileum will impair absorption. Bile salts are also reabsorbed in the ileum and bile salt deficiency will contribute to reduced fat absorption. However, bile salt sequestrants such as cholestyramine have shown no benefit and may worsen steatorrhoea due to binding of dietary lipid and may also worsen fat-soluble vitamin deficiency. In view of multifactorial metabolic bone disease, vitamin D ₂ supplements are often given empirically along with calcium supplements. Vitamin A and E deficiencies have been reported, but usually an awareness that visual or neurological symptoms may indicate deficiency, combined with infrequent monitoring of serum levels, are all that is necessary. If the patient is wholly dependent on PN, then replacement along with vitamin K injections is required. Most patients have lost their terminal ileum and so require vitamin B ₁₂ replacement. Trace elements appear not to be a problem, with normal levels being found in patients on long-term PN.

Loss of bowel results not only in decreased absorptive capacity but also rapid transit. Reduced time for absorption will exacerbate nutritional deficiencies.

Adaptation

Following massive small-bowel resection, there are changes in the mucosal surface of the remaining small intestine. Most experimental work has been in small animals such as rats. It appears that adaptation will occur only if there is enteral feeding. Patients who are wholly dependent on PN have mucosal atrophy, which is reversed on re-feeding enterally. The mechanism for this is at present unknown, but various trophic factors have been proposed. Current theory is that increased crypt cell proliferation leads to lengthening of villi and deepening of crypts, so resulting in increased surface area. Because the ileum has shorter villi, it is able to adapt further, but is unfortunately more frequently resected. The stimulation to adapt appears to be threefold: (i) direct absorption of enteral nutrients leading to local mucosal hyperplasia; (ii) enteral nutrition resulting in the release of trophic hormones and a paracrine effect; and (iii) increased fluid and protein secretion with subsequent resorption, leading to increased enterocyte workload and adaptation.

Another form of adaptation occurs in neonates, infants and young children, where continued developmental growth of the small intestine may make the difference between dependence on PN and managing with an enteral diet.

Role of the colon in short-bowel syndrome

The colon has significant absorptive capacity, not only for fluid and electrolytes as described earlier, but also for short-chain fatty acids. ^, These are an energy substrate and in the region of 500 kcal may be derived in this way. It is estimated that having a colon is the equivalent of approximately 50 cm of small bowel for energy purposes. The colon will also slow intestinal transit, particularly if the ileocaecal valve is present, which will improve absorption.

Having overcome the immediate problems of fluid balance and nutritional replacement, a frequent problem for those patients who still have their large bowel in continuity is diarrhoea. Excessive carbohydrate entry into the colon may result in osmotic diarrhoea. ^, Alternatively, choleric diarrhoea may be brought on by failure to reabsorb bile salts completely. Colonic bacteria deconjugate and dehydroxylate these into bile acids, which stimulate water and electrolyte secretion. In more extreme cases of SBS, bile salt depletion may occur that will give rise to steatorrhoea from incompletely digested long-chain fatty acids. Bile salts increase colonic permeability to oxalate. As the undigested fatty acids bind calcium in preference to oxalate, there is a resultant increase in enteric oxalate uptake and hence increased renal stone formation.

There is an increased frequency of mixed gallstones, possibly because of interruption of the enterohepatic circulation.

Lastly, d -lactate acidosis is a rare syndrome that comprises headache, drowsiness, stupor, confusion, behavioural disturbance, ataxia, blurred vision, ophthalmoplegia and/or nystagmus. It only occurs in patients with a short bowel and a preserved colon. Colonic bacteria may degrade a surplus of fermentable carbohydrate to form d -lactate, which is absorbed but not easily metabolised. In addition to a metabolic acidosis with a large anion gap, increased concentrations of d -lactate are found in blood and urine. Treatment involves restricting mono and oligosaccharides and encouraging the more slowly digestible polysaccharides (starch), thiamine supplements, and broad spectrum antibiotics. In rare cases, the patient may need to fast while receiving PN.

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