1.1 Aim

This guideline aims to help clinicians manage patients who have or are thought to have severe small intestinal dysmotility that is causing malnutrition. It gives a logical guidance to determining the underlying diagnosis and shows how, knowing this, treatments may be tailored for each individual patient. It also aims to present some of the other factors contributing to the presentation and progress of the illness.

1.2 Development

The preliminary guidelines were compiled from the literature and a first document was drafted by Dr Nightingale and modified by members of the Neuro-gastroenterology and Motility Committee of the British Society of Gastroenterology (BSG) and by the Small Bowel and Nutrition Committee of the BSG. The article was reviewed by the patient organisation PINNT (Support and Advocacy group for people on home artificial nutrition) and modifications made to result in the current document.

The guidelines have applied the GRADE system.1 Strength of recommendation can be strong, moderate or weak. The evidence was graded according to the Oxford Centre for Evidence-based Medicine.2 Level 1 includes systematic reviews with homogeneity, individual randomised controlled trials (RCTs); level 2 includes systematic reviews of cohort studies, low quality RCTs and outcomes research; level 3 includes systematic reviews with heterogeneity and individual case–control studies; level 4 includes poor quality cohort or case series; and level 5 includes expert opinion without critical appraisal.

1.3 Scheduled review

The content and evidence base for these guidelines should be reviewed within 5 years of publication. We recommend that these guidelines are audited and request feedback from all users.

1.4 Service delivery

• Patients with severe chronic small intestinal dysmotility are not common but should be managed by a multidisciplinary team headed by a clinician with expertise in managing these patients. If managed appropriately, particularly if receiving parenteral nutrition (PN), there may be an improved quality of safe care and also considerable cost savings. (Grade of evidence level 4, Strength of recommendation strong)

• Any surgical procedure should be performed after extensive local/regional multidisciplinary team (MDT) discussions at hospitals with surgeons and histopathologists experienced in managing these patients. (Grade of evidence level 5, Strength of recommendation strong)

• Patients being considered for PN or a surgical bypass/resection should be seen at a dedicated PN centre or by an integrated intestinal failure (IF) unit respectively. (Grade of evidence level 5, Strength of recommendation strong)

• Regional networks may be established to ensure expertise is available to all and a national research forum may be established. (Grade of evidence level 5, Strength of recommendation strong)

1.5 Patients' experience

• Patients with a severe chronic small intestinal dysmotility causing malnutrition should be managed as individuals; other factors including opioid use and psychosocial circumstances must be taken into account. (Grade of evidence level 5, Strength of recommendation strong)

• Patients will become experts in coping with their condition and management. All decisions should be made in conjunction with them. They are often more knowledgeable about their condition and treatments than the clinicians, nurses and dietitians and this should be respected. (Grade of evidence level 5, Strength of recommendation strong)

• Facilities for looking after these patients should be able to deal with physical, emotional, psychological, social and quality of life issues. (Grade of evidence level 5, Strength of recommendation strong)

• Patients should be referred rapidly to places of more advanced expertise if management is difficult or unsuccessful. There should be a clinician, specialist nurse and/or a dietitian available and a psychologist/psychiatrist to discuss the patients. The healthcare professionals should be familiar to the patient and know their history, thus eliminating the need for lengthy, time-consuming explanations. (Grade of evidence level 5, Strength of recommendation strong)

• The patients should be managed on wards or IF/home parenteral nutrition (HPN) units where the healthcare professionals are familiar with their specialist needs, especially if receiving PN. (Grade of evidence level 5, Strength of recommendation strong)

• Patients, especially if receiving HPN, should have access to a helpline (ideally 24 hours) so that emergencies are dealt with appropriately and quickly. (Grade of evidence level 5, Strength of recommendation strong)

• Written and audiovisual materials that explain and support the training techniques in enteral and PN should be available. (Grade of evidence level 5, Strength of recommendation strong)

• Meeting other patients with similar problems may improve the way in which a patient copes with their condition. (Grade of evidence level 5, Strength of recommendation strong)

• Where appropriate, patients should be offered contact numbers for the relevant support group that represents their specific disease. (Grade of evidence level 5, Strength of recommendation strong)

• Follow-up appointments should be as deemed appropriate to the MDT and patient, and ideally the patient should not have to travel long distances for appointments. The appointment should be with experienced and familiar staff, thus enabling continuity of care. (Grade of evidence level 5, Strength of recommendation strong)

• Staff should be aware of the latest research and developments and should make patients aware of any which may apply to them. (Grade of evidence level 5, Strength of recommendation strong)

Phrases that may be found on investigations

Radiology

• slow transit

• dilated bowel

• no transitional zone

Scintigraphy

• slow transit (gastric emptying, small bowel or colon) of liquid/solid

Manometry

• propulsive failure

• giant contractions

• no migrating motor complexes (MMCs)

Pathological

• neuropathy

• plexitis, leiomyositis

• myopathy

In this document the term 'intestinal dysmotility' is used to cover all conditions in which there is a failure to propel the luminal contents without there being an organic obstructing lesion. The intestinal dysmotility is considered severe when nutritional or fluid support is needed due to objective evidence of malnutrition, dehydration or electrolyte disturbance.

This guideline relates to adults and does not cover acute pseudo-obstruction (eg, ileus).

5.1 Organic obstruction

A major problem, that is often not diagnosed, is a localised bowel obstruction as a result of adhesion formation. This may be suspected clinically when a patient has had a number of abdominal operations (with or without extensive adhesion division).7 A history of intermittent colicky abdominal pain with abdominal distension, loud bowel sounds, no bowel or stoma action and vomiting suggest this. A distal obstruction is suggested if the vomit is faeculent, while a more proximal one by green/yellow vomit. During an obstructive episode the bowel secretes more fluid, and when the obstruction resolves, diarrhoea follows (or a high stomal output). If a patient sticks to a low residue diet or even a liquid diet, the obstructive episodes may reduce or even be abolished. This approach, if successful, can be a useful supportive diagnostic test.

Radiologically, the clue to an organic obstruction is the demonstration of a distinct transition point between dilated and normal sized bowel, but this may not be apparent either because the obstruction has resolved or the bowel is fixed by adhesions and thus cannot dilate. It can be helpful to obtain an abdominal CT scan when the patient has an episode of severe pain. Contrast follow through studies or MRI scans, although useful when positive, may not be tolerated in the acute setting and do not always demonstrate the obstruction. Unsuspected diagnoses may be revealed (eg, small bowel volvulus from a band adhesion or an intussusception). Further clues to an organic obstruction are visible small bowel peristalsis, worse pain after prokinetic drugs or giant jejunal contractions on manometry.8 9

Multiple laparotomies themselves may result in secondary dysmotility, especially if the bowel becomes encased in fibrous tissue as can occur with sclerosing peritonitis. In addition, upper gut surgery (eg, a vagotomy, Whipple’s resection, gastro-enterostomy, bariatric procedures or any bowel anastomosis) can result in secondary small bowel dysmotility.10

Radiation damage can cause strictures and a localised obstruction and/or a generalised secondary dysmotility. Problems caused by radiation damage tend to be progressive over many years.

5.2 Opioid and other drug effects on the bowel

Opioid-induced bowel dysfunction can result from both opioid withdrawal and chronic opioid usage and manifests with features of dysmotility (especially constipation) when pain is not the dominant issue. The narcotic bowel syndrome may result from chronic usage and is defined as chronic, worsening or frequently occurring abdominal pain despite continued or escalating doses of narcotics in addition to dysmotility.11 The opioid usage induces a hyperalgesic effect. It may be becoming more prevalent but it is often not recognised by clinicians.12 13 In addition to being acknowledged to occur in patients with gastrointestinal disease (functional or organic), it also occurs in patients with no pre-existing gastrointestinal problems who take high doses of the opioids for other painful conditions (eg, joint problems or following surgery).

The components of therapy for narcotic bowel syndrome are recognition of the disorder, a trusting therapeutic relationship with the patient, replacement using neuropathic type pain drugs and controlled reduction in the opioid dose.14 Specific drug treatments have been tried for opioid-induced bowel dysfunction and narcotic bowel syndrome and include clonidine (to reduce withdrawal symptoms) and peripheral mu opioid antagonists (naloxone, methylnaltrexone, alvimopan).15–17

Opioids inhibit intestinal motility and so invalidate the tests of small bowel motility. They may also increase the risk of line infections in patients on long-term PN.

Survivors of cancer treatment may have bowel dysmotility which may be due to chemotherapy or opioid medication. Their management may require a wider MDT input.

Cyclizine is both an antihistamine and anticholinergic drug which acts as a centrally acting anti-emetic. There are many reports of it being taken for its euphoric effect, which is most marked when taken intravenously. In addition to causing addictive behaviour, it is of a low pH and so damages veins. It is not recommended for long-term use, especially in patients receiving PN.18

Other drugs such as anticholinergics, antidepressants, calcium channel blockers, chronic laxative abuse or some chemotherapeutic drugs (eg, vincristine) may also cause reduced gut propulsion.

5.3 Functional gastrointestinal disorders

Many of the symptoms of small intestinal dysmotility are the same as for patients with other functional abdominal gastrointestinal disorders (eg, irritable bowel syndrome, functional dyspepsia, cyclical vomiting, functional bloating/distension, functional constipation/diarrhoea and centrally mediated disorders of gastrointestinal pain).19

The differentiation and overlap with these functional gastrointestinal disorders is difficult. They all may have genetic and psychosocial influences (early life trauma, life stresses, coping mechanisms, lack of social support, etc). In addition, bacterial flora, inflammation, visceral sensation and motility may all contribute to the symptoms. In irritable bowel syndrome there may be an overlap with enteric neuropathy as increased lymphocytes have been observed in the jejunal myenteric plexus.20 However, significant malnutrition is rarely a consequence of these disorders.

The treatment—as for all dysmotility problems—is to identify and treat the main symptom. If weight loss has occurred, then the same therapies as for intestinal dysmotility may be tried at the same time as nutritional support is given. Significant caution should be exercised, however, to avoid escalating to more invasive forms of nutrition support in patients with functional symptoms, especially in pain predominant presentations, in the absence of objective features of biochemical disturbance or those who have a high or normal BMI. Such escalation of invasive intervention in these patients is subject to risks of iatrogenesis, and in clinical practice experience does not appear to improve global function, quality of life or symptoms.

5.4 Psychological/psychiatric problems

5.5 Effect of undernutrition on gut function

Malnutrition itself can impair gut function and cause malabsorption with mucosal atrophy, reduced gastric acid and pancreatic enzyme secretion and more bacterial colonisation of the upper gut.29 30 The effects of undernutrition on gut motility and histological appearance are uncertain.

There is literature on the superior mesenteric artery syndrome (Wilkie's syndrome) in which the third part of the duodenum is compressed between the superior mesenteric artery and the aorta (when the left renal vein is compressed it is referred to as ‘nutcracker syndrome’). It is reported to be prevalent in patients who have suddenly lost weight and reported to improve when either the patient becomes better nourished or a duodeno-jejunostomy (bypass) is formed to avoid the obstruction. The symptoms attributed to this are postprandial epigastric pain, nausea/vomiting and loss of weight.31–35 Whether this is a cause or consequence of malnutrition and whether it is a radiological rather than true clinical entity remains contentious and some clinicians dispute its existence and think it is over diagnosed. Thus the risks of any surgery should be very carefully considered, especially as the benefits of surgery are not always predictable or clear.

5.6 Hypermobile Ehlers–Danlos syndrome (EDS) (joint hypermobility syndrome or Ehlers–Danlos syndrome hypermobility type)

Hypermobile Ehlers–Danlos syndrome (EDS) with its gastrointestinal associations is difficult to classify as most patients with EDS do not have a dysmotility of the small bowel, merely visceral hypersensitivity. Its symptoms may mimic dysmotility (neuropathy) and the presence of EDS can contribute to dysmotility, usually if postural tachycardia syndrome (PoTS) or other associated factors such as opiates are present. According to the 2017 classification, patients previously diagnosed with joint hypermobility syndrome and Ehlers–Danlos syndrome hypermobility type were reclassified as hypermobile Ehlers–Danlos syndrome (hEDS) if they met the strict criteria or Hypermobile Spectrum Disorders (HSD) if they had many but not all of the characteristics of hEDS.36 Patients with hEDS and HSD represent a third of patients referred to a tertiary neurogastroenterology clinic and these patients tend to be young, female with a poorer quality of life.37 hEDS/HSD is associated with a range of gut disorders (acid reflux, abdominal pain (especially typical is pain after eating or when any food arrives in the gut even from an enteral feed) and constipation).38 There is often autonomic dysregulation, particularly PoTs,37 chronic urinary retention due to a failure of the urethral sphincter to relax (Fowler’s syndrome) and hypoglycaemia.37 Mast cell activation disorder39 is being increasingly reported (most commonly in those having PoTs). An increasing number of patients with joint hypermobility and gut dysmotility are being seen by nutrition support teams because of weight loss and malnutrition. This group seems especially sensitive to opioids and cyclizine, both of which can exacerbate all of their symptoms.18 It is currently unclear the degree to which the association of hEDS with gut symptoms encompasses specifically any greater degree of chronic small intestinal dysmotility, or whether there are any different treatment approaches to patients without hEDS who have the same functional symptoms. The same cautions therefore should apply when considering escalating invasiveness of nutrition support in this group as to that of functional gastrointestinal disorders in general, especially if there is a pain predominant presentation.

6.1 Myopathies

Primary myopathies most commonly occur in children and young adults and are often familial (genetic). Myopathies often have multivisceral involvement and thus a relatively high mortality. They are characteristically associated with massive gut dilatation. Many predominantly affect the circular muscle (except hollow visceral myopathy). Primary myopathies are more common in children whereas secondary myopathies are more common in adults. Some causes will remain idiopathic.

6.2 Neuropathies

An enteric neuropathy may occur as a primary pathology (congenital, autoimmune or infective), secondary to a generalised neurological disorder, paraneoplastic process, metabolic disorder (eg, diabetes) or drugs/toxins or as a developmental abnormality. Visceral neuropathy is less well reported in the literature than visceral myopathy. Visceral neuropathy is commonly acquired in adulthood or in old age and is associated with a high morbidity usually due to factors other than the neuropathy. Luminal dilatation is rarely seen except at the end stage of the disease.

Two forms of pathology are found—either enteric neural degeneration (in the absence of inflammation) or inflammatory.62 Degenerative neuropathies can result from mitochondrial dysfunction and the pathological findings include neuronal swelling, intranuclear inclusions, axonal degeneration and hypoganglionosis. The aetiology of many degenerative enteric neuropathies will remain idiopathic. Inflammatory neuropathies may include both plexitis and neuritis and can be lymphocytic or less commonly eosinophilic, the former promoting autoimmune screening, the latter investigation for parasites.

6.3 Idiopathic

In the majority of patients and in most centres, the precise aetiology of chronic severe dysmotility is not characterised histopathologically and remains based on the clinical presentation, physiological testing and exclusion of obstructive and mucosal disease. This in part reflects a low uptake of full thickness biopsies outside of the context of stoma formation or other surgical intervention. In selected populations of PN dependent patients with dysmotility, high rates of full thickness biopsies were associated with high rates of neuromuscular abnormalities of which two-thirds were primary and one-third were secondary causes, although not all biopsies yielded a diagnosis. The threshold and acceptability of full thickness biopsy testing, especially as most will not lead to a change in management, has not currently achieved consensus. There also remain some unresolved issues for gastrointestinal neuromuscular pathology standardisation and interpretation.59 For the near future, therefore, it is likely that the aetiology in the majority of dysmotility patients will remain idiopathic.

7.1 Impairment of coordinated gut contractions and the migrating myoelectric complex (MMC)

If the MMC is impaired, then the small bowel will not be cleared of debris predisposing to gut stasis and bacterial overgrowth. With enteric neuropathies, gut coordination is disrupted and the presence of chyme in the small bowel can cause severe painful non-propulsive large contractions. This is one of the causes of abdominal pain shortly after eating.

7.2 Gut stasis

The failure of forward propulsion may also cause constipation and this is often the first symptom. Gut stasis results in abdominal distension and, if much fluid accumulates (oral intake and normal gut secretions), it may produce a large volume vomit. The vomit may be faeculent and contain food debris from several days previously.

7.3 Bacterial overgrowth and malabsorption

The combination of a dilated gut with reduced propulsion and ineffective MMC allows anaerobic bacteria to proliferate in stagnant loops of bowel. This bacterial overgrowth results in bile salts being deconjugated, less effective secondary bile acids (eg, lithocolic acid) being made and pancreatic enzyme degradation occurs so that steatorrhoea and malnutrition may occur. Associated with steatorrhoea is malabsorption of the fat soluble vitamins A and E (less so D and rarely K) with deficiency symptoms (night blindness, poor colour vision, dry flaky skin and ataxia). Vitamin B₁₂ may be malabsorbed but both folic acid and vitamin K can be manufactured by the bacteria and so may give rise to high serum levels.

Occasionally the bacteria can manufacture D-lactic acid (normally L-isomer) giving rise to D-lactic acidosis (high anion gap acidosis) and other bacteria can manufacture ammonia which may appear in high levels in the blood.

Small intestinal bacterial overgrowth (SIBO) is when excess micro-organisms are present in the small intestine and lead to a malabsorption syndrome with occasionally a protein losing enteropathy. Subtotal villous atrophy may be found on histology. There are several endogenous mechanisms for preventing bacterial overgrowth: gastric acid secretion, intestinal motility, intact ileo-caecal valve, intestinal immunoglobulin secretion and bacteriostatic properties of pancreatic and biliary secretions. The aetiology of SIBO is usually complex, associated with disorders of these mechanisms. In some patients more than one factor may be involved.

There is currently no gold standard for the diagnosis of SIBO and the commonly available methodologies (the culture of jejunal aspirates and a variety of breath tests) are limited by large variations in their performance and interpretation.78

7.4 Problems of undernutrition

Patients who rapidly lose more than 10% of their body weight frequently have demonstrable physiological changes which include skeletal and cardiac muscle weakness, poor concentration and mental function including memory, prolonged sleeping, reduced sexual function, a low body temperature and a propensity to develop infections which are potentially severe.79 In the gut, malabsorption with mucosal atrophy, reduced gastric acid and pancreatic enzyme secretion and more bacterial colonisation of the upper gut can occur although the experimental backing for this is inferred from studies in patients with anorexia nervosa.22–26

8.1 History, examination and blood tests

The features of patients with a myopathy are summarised in table 1. The clinical history and examination should determine if there are associated systemic neuromuscular, connective tissue or endocrine diseases (muscular diseases, neurological disease, storage diseases, systemic sclerosis, diabetes mellitus, irradiation, etc) and thus if the myopathy or neuropathy is a primary or secondary disorder. Exploring the family history will detect some congenital diseases, as will asking about foreign travel (Chagas' disease). Examination especially includes the neuromuscular system and testing for joint hypermobility. Autonomic neuropathy should be considered if orthostatic, pupillary or sudomotor (sweating) dysfunction accompanies dysmotility. Simple clinical bedside assessment of orthostatic pulse rate change (lying to standing) may identify PoTs (box 3).52

Symptoms need to be listed in order of importance to the patient, and a record made of all the drugs currently taken or that have been taken for long periods (especially opioids and cyclizine).

A basic nutritional assessment will include measuring the patient’s height and weight and asking their usual weight in health and their weight change over the last 2 weeks, 3 and 6 months. From these their BMI and percentage weight loss can be calculated. In addition they are asked about recent changes in their food intake.

Tests to help make the diagnosis are summarised in box 4. Blood tests will include routine blood count, renal (including potassium and magnesium), liver, bone chemistry, thyroid function, glucose, myeloma screen, anti-tissue transglutaminase (for coeliac disease). Nutritional measures if undernourished or steatorrhoea include vitamin A, E, D, INR, iron, ferritin. B₁₂, red blood cell folate, selenium, zinc and copper. Consideration is given to requesting auto-antibodies (especially antineuronal antibodies (see section 6.2 and box 4).

In MNGIE, direct evidence is provided by a plasma thymidine concentration greater than 3 µmol/L and a plasma deoxyuridine concentration greater than 5 µmol/L. Thymidine phosphorylase enzyme activity in leukocytes will be less than 10% of the control mean. Molecular genetic testing of TYMP, the gene encoding thymidine phosphorylase, detects mutations in affected individuals.

Rectal examination with an unprepared sigmoidoscopy will identify stool consistency and colour and permit biopsy for amyloid. Steatorrhoea will be detected and constipation/diarrhoea confirmed. Basic tests of autonomic function include lying and standing systolic blood pressure and heart rate with ECG confirmation.

8.2 Radiological tests

The diagnosis is usually first suspected after plain abdominal radiographs have shown a dilated small and large bowel. Once suspected, investigations aim to confirm that there is impaired transit of luminal contents, to identify the region of the bowel affected, ideally to identify the propulsive abnormality and to show a specific pathology.6 Investigations help establish the presence of intestinal pseudo-obstruction and may delineate an underlying cause. In practice the diagnosis is often presumed after several laparotomies have excluded a physical obstruction, although CT/barium follow-through/MR enterography excluding a transition point in a diffusely distended small bowel suggests CIPO and may prevent unnecessary laparotomy. CT may also help distinguish severe dysmotility from functional bloating due to abdomino-phrenic dysinergia.81 Dynamic MRI of the small bowel is becoming increasingly helpful,82 83 though is less established. MRI brain can be helpful in the diagnosis of MNGIE.59

The measurement of whole gut time can be measured by serial X-rays of ingested radio-opaque markers (small lengths of barium-impregnated polyvinyl tubing).

Small bowel transit using a barium follow-through examination will usually give some indication of accelerated or delayed transit and a dilated duodenal loop (megaduodenum) may be one of the earliest signs of visceral myopathy.83 In addition, in HVM there may be oesophageal aperistalsis and variable dilatation of the small and large bowel.

8.3 Radioisotopic investigations

Gastric emptying can be measured using gamma scintigraphy to obtain serial images of labelled solid (scrambled eggs, liver or pancake), semi-solid (thick soup) or liquid (orange juice) meals in the stomach. Gastric emptying measurements may be helpful in determining whether the stomach is involved in a generalised disorder of propulsion or a localised one (eg, Chagas' disease). These isotopic meals can be extended to measuring the transit of the meal through the small bowel and, if the isotope has a long half-life, orocaecal and colonic transit may be determined. Liquid meals may not clearly demonstrate an abnormality.

8.4 Endoscopic tests

Jejunal aspirate for bacterial overgrowth is infrequently performed but usually by endoscopy (or fluoroscopy with jejunal intubation). A clinically significant overgrowth is when counts exceed 10⁵/mL (usual is less than 10⁴/mL). Common species include Bacteroides, Enterococcus and Lactobacillus. However, most of the bacteria likely to be relevant in causing symptoms cannot be cultured. Endoscopy also has a role in mucosal sampling and palliative venting. Capsule endoscopy examination can sometimes give transit information but is rarely used due to the risk of the capsule being retained and some regard it as contraindicated.

8.5 Non-invasive investigations of gut transit

Orocaecal transit can be measured using the rise in breath hydrogen due to the degradation of ingested polysaccharides (eg, lactulose). In health this is caused by caecal bacteria fermenting the ingested agent, but this is unhelpful if there is propulsive failure as small bowel bacterial overgrowth is common and is not a recommended test for this application.84 85 It is also unhelpful following a significant small bowel resection or if there is an enteric fistula.

Breath tests to diagnose bacterial overgrowth may be misleading and produce false negative results compared with culture of small bowel aspirate.78 86 This has in part been due to broad variations in how these tests are performed and interpreted. Recent work in the UK and USA has taken place to develop evidence-based consensus guidelines for breath testing in terms of dose of substrate (75 g glucose, 10 g lactulose) and cut-off values. In addition, while hydrogen only breath testing was previously used, modern testing protocols have incorporated the measurement of methane. Increased intestinal methane levels have been associated with delayed small bowel transit as measured by scintigraphy and therefore should be measured in patients with suspected small bowel dysmotility to improve the test's utility.86 Other tests that may indicate bacterial overgrowth include raised urinary indicans, blood D-lactate or alcohol levels.

8.6 Manometry

Intraluminal pressure sensors incorporated into a catheter can detect the patterns of contractile events. For the diagnosis of pseudo-obstruction, the logical investigation is small bowel manometry. Small bowel motor activity was initially studied using multi-lumen perfused tube systems, with a pump and strain gauge transducer external to the patient.87 This gave information on motor activity in the antrum and proximal duodenum, and detected abnormal motility88 and some types of pseudo-obstruction.89 90 This technique required the patient to remain in a laboratory attached to a machine for more than 6 hours and was not good at recording fasting, and postprandial activity.91

An alternative is the wireless motility capsule (WMC) which is an ambulatory, minimally invasive diagnostic modality that allows continuous assessment of intraluminal pH, temperature and pressure during its transit through the gastrointestinal tract. The technology allows for both measurement of transit times in multiple regions of the upper and lower gastrointestinal tract, as well as pressure profiles in the antro-duodenum. The standardised equipment and procedures in WMC allow the comparisons of data across multicentres. The role of the technology has been best established in the evaluation of a large number of healthy volunteers92 and in patients with suspected gastroparesis and suspected chronic constipation. The worry with this technique in these patients is that the capsule may remain in the bowel and not be passed. However, a study in patients with Crohn’s disease has shown that the same precautions used when considering patients for capsule endoscopy (ie, clinical and radiological assessment and use of a patency capsule) can mitigate much of the risk in potential WMC patients.93

Twenty-four hour ambulatory jejunal manometry94 uses a catheter with built-in miniature strain gauge transducers95 and records data to a solid-state digital recorder.96 The digital encoding of pressure data simplifies the analysis of continuous 24-hour recordings by computer software.97 98 This technique has proved useful in several conditions99 100 including pseudo-obstruction. During nocturnal sleep, normal stereotypic MMC activity is clearly evident101 and in some patients with pseudo-obstruction the abnormal contractile activity of the small bowel results in distortion of the fasting MMC pattern. Manometry of patients with pseudo-obstruction can be difficult in the later stages of disease because the peristaltic activity required to propel a manometry catheter into position in the proximal jejunum is lacking, and endoscopic assistance may be needed. A patient with a neuropathy may have a normal diameter gut but it may be hyperactive with many uncoordinated and often strong contractions (bursts).90

The effect of any drugs the patient may be taking must be taken into account in interpreting any results (eg, opioids, anticholinergics and cyclizine). Manometry does not always produce results that are clinically helpful.90

8.7 Pathology and histology

The biochemical examinations recommended are listed in box 4.

Adequate biopsy material is not often available and few laboratories have an experienced gastrointestinal neuropathologist. There also remain some additional pitfalls for collecting and analysing samples including sampling error, effects of bowel handling, sparsity of normal data and specificity. Good histological samples are needed to make a firm diagnosis. Close liaison between the surgeon and pathology laboratory is crucial so that a full thickness specimen of bowel is immediately processed. The samples should be divided. In an ideal situation some is snap-frozen in liquid nitrogen and the main portion fixed for routine histology and electron microscopy. In practice the latter two may be the best option. The immediate processing of samples is important if a detailed examination of the nerves, ganglia and muscle tissue is to be carried out. Diagnosis of a neuropathy may be difficult in conventionally orientated and stained sections of gut, and whole mount plexus assessment is a research tool. The most important element is to ensure that enough sections and material is examined in a centre with experience of dysmotility.

A full thickness jejunal biopsy is usually taken laparoscopically and is often helpful diagnostically, but the procedure in centres without much experience can be unhelpful and have a significant risk. Published data from centres with expertise suggest a median operating time of 50 min, conversion rate to open operation 2% and length of stay 1 day with an 8% readmission rate for obstructive symptoms.102 In myopathies the diagnosis may be established. A neuropathy in general shows either degenerative changes or inflammation.

All full thickness biopsies should be stained with Congo red stains to look for the presence of amyloid. As full thickness jejunal biopsies may not change the clinical management and are associated with risks, they are often performed when a laparotomy does not find an organic cause of obstruction or when the patient happens to be undergoing surgery for another reason (eg, a jejunal tube placement).103

MNGIE can be diagnosed with a skeletal muscle biopsy in addition to the blood and genetic testing.

9.1 Underlying condition

An underlying disease may need to be treated (eg, connective tissue disorder, enteric myositis, neoplastic disease or myotonic dystrophy). Diabetic control should be very good and may necessitate an insulin pump. Electrolyte, mineral or endocrine abnormalities should be prevented and treated when detected.

Immunosuppressive treatment has a small evidence base restricted to case series or reports. Prednisolone and ciclosporin have been reported to be of particular benefit in autoimmune myopathy.104 There is a case report of an improvement with initially prednisolone 1 mg/kg and azathioprine 2 mg/kg/day, then subsequently the prednisolone was replaced with budesonide 9 mg/day.52

There must always be awareness that organic obstruction can be missed as a diagnosis and, if a prokinetic drug105 makes pain worse, then an organic obstruction must be considered. Similarly, a successful trial of a low fibre or liquid diet suggests an organic obstruction.

Some metabolic storage disorders can be treated with specific enzyme replacement therapy.61

9.2 Specific drug treatments of symptoms

No treatment is ideal, and even though some help to correct physiological abnormalities, they may not affect the patient’s symptoms (boxes 3 and 5).

Drug therapy106 can be difficult and often drugs with conflicting actions are used (prokinetic for constipation and anticholinergic for colicky pain). Essentially, the drug therapy is targeted at the symptom perceived as most important by the patient.

Prokinetic treatments are used to try and improve the dysmotility itself and can return some of the measured abnormalities towards normal. They may especially help with vomiting and constipation. Prokinetic drugs are generally not used after a bowel anastomosis. Some of the previously used prokinetic drugs have been withdrawn or can only be used with extreme caution. They include domperidone and metoclopramide (D₂ dopamine receptor antagonists) which stimulate gastric emptying and small intestinal transit, and enhance the strength of oesophageal sphincter contraction. Metoclopramide also increases the release of acetylcholine from some enteric nerves. Domperidone is a selective antagonist of peripheral D₂ dopamine receptors, which does not have the acetylcholine-like effect of metoclopramide. National Patient Safety Agency (NPSA) alerts have been issued for domperidone highlighting problems with prolonged QTc, therefore long-term use should be subject to QTc monitoring. The extrapyramidal side effects of metoclopramide (especially in children) and the potentially irreversible tardive dyskinesia in elderly subjects, together with no evidence of consistent benefit in gastroparesis, caused the European Medicines Agency’s Committee to recommend that metoclopramide is not used in the long term.107 Cisapride, a 5-HT₄ agonist, enhances acetylcholine release in the myenteric plexus without having anti-dopaminergic effects and may have been of particular benefit if MMCs were present on small intestinal manometry. In a 6-week double-blind, placebo-controlled trial in 26 patients, cisapride helped abdominal pain, improved solid gastric emptying and the MMC.105 Unfortunately, due to an increased risk of fatal cardiac arrhythmias (probably relating to a prolonged QT interval) in patients taking other medications or suffering from underlying conditions known to increase the risk of cardiac arrhythmias, cisapride was withdrawn. Tegaserod, a 5-HT₄ receptor partial agonist, increased stool frequency in irritable bowel syndrome108 109 and improved the symptoms in functional dyspepsia,110 but was withdrawn due to an increased risk of heart attacks or strokes.

Prucalopride, a high affinity selective 5HT₄ receptor agonist, has been used for constipation and appears not to have the cardiac risks of cisapride or tegaserod as it does not affect the QT interval. This is by having no significant action on the 5-HT_1B/D and on the cardiac human ether-a-go-go K⁺ channels.111

Erythromycin, a motilin agonist, is potentially useful112 if there are absent or impaired antroduodenal migrating complexes but is subject to tachyphylaxis. Doses of 900 mg/day have been recommended.113 Azithromycin may be more effective for small bowel dysmotility.114

A somatostatin analogue (octreotide), given by a relatively painful subcutaneous injection, may be dramatically beneficial, especially in systemic sclerosis when other treatments have failed.115–117 It can improve vomiting and pain, partly because octreotide (in normal subjects) reduces the perception of volume distension due to inhibition of sensory afferent pathways.115 Octreotide may cause low amplitude MMCs to return.117 Octreotide may have a beneficial effect when erythromycin has been unsuccessful; its effect (50–100 μg once or twice a day) is apparent within 48 hours and is maintained for more than 2 years. It may be more effective when combined with erythromycin.118

The parasympathomimetics bethanechol, distigmine, neostigmine and pyridostigmine enhance parasympathetic activity in the gut and increase intestinal motility. They are rarely used because of both their gastrointestinal and cardiovascular side effects (diarrhoea and severe bradycardia). Pyridostigmine has, however, been shown to help refractory constipation (including in diabetes) and was well tolerated using a stepped dosing regimen.119 120

Naloxone 1.6 mg given subcutaneously each day or methylnaltrexone given subcutaneously on alternate days may be beneficial in blocking dysmotility effects of opioids or in improving motility through blocking endogenous opioids.121

9.3 Neuromodulation (pacemakers)

There is some limited evidence for gastric electrical stimulation (gastric pacing) to improve vomiting symptoms where gastroparesis is prominent and small bowel function relatively intact.129–131 Patients with diabetic gastroparesis respond best and, in general, responders tend to have more severe vomiting. Patients with idiopathic gastroparesis have a potentially higher rate of poor response to gastric electrical stimulation.132 Non-invasive vagal nerve stimulation has shown some promise both for improving gastroduodenal motility and reducing pain sensitivity.133

The dorsal column pathways are involved in the transmission of visceral pelvic pain. Spinal cord stimulation suppresses the visceral response to colon distension in an animal model and therefore may be an effective therapy for chronic pelvic pain of visceral origin. There has been success reported in one study of 35 patients in whom the catheter tip was situated at the T5 position for a median of 9 days (range 4–14).134 The Cochrane database concludes that more studies are needed.135

Sacral nerve stimulation uses electrical stimulation applied to the sacral nerves, eliciting a physiological effect on the lower bowel, anal sphincter and pelvic floor, and has shown some success in treating faecal incontinence and constipation.136–138 A Cochrane review concluded that from three studies there was “very limited evidence that sacral nerve stimulation can improve continence in selected people with faecal incontinence, and reduce symptoms in selected people with constipation” and larger “good quality randomised crossover trials are needed”.139 There is no evidence that sacral nerve stimulation helps any of the symptoms in patients with CIPO.

Small intestinal electrical stimulation is at an experimental stage.

9.4 Nutritional support

Nutritional assessment and support is an important aspect of management. With appropriate therapy, many patients with CIPO manage to maintain their nutritional status through the oral/enteral route without the need for PS.

9.5 Surgical options

Surgery is to be avoided in this group of patients who are at high risk of iatrogenic injury; however, judicious palliative surgical intervention (resection, bypass or stoma formation) can improve symptoms and quality of life.147 148 If constipation is difficult to manage and high volume saline washouts are needed, then colectomy with ileorectal anastomosis or ileostomy may be necessary but diarrhoea or continuing episodes of obstruction may remain a problem. Adhesiolysis in the absence of a clear focal obstruction carries a high risk of severe complications and morbidity with ultimately more adhesion recurrence and worsening pain. Urology is often needed to help with neuromuscular disorders of the urinary tract (dilated ureters and bladder) and stents and/or a suprapubic catheter may need to be inserted. Especially in women, there may be fertility problems due to dilated non-functioning fallopian tubes. Often the pains experienced result in gynaecological referrals.

9.6 Psychosocial treatments

Psychological support from nurses, physicians and psychologists is important. Vigilance needs to be maintained for the presence of psychopathology even in patients with a strong suspicion of gastrointestinal neuromuscular disorder. In one case series, six patients diagnosed initially with IF had significant psychopathology requiring specialised psychiatric unit treatment.25 In addition to psychological distress including anxiety and depression, other psychological problems encountered can include somatisation disorder, personality disorders, substance misuse and disordered eating (see also section 5.4). Dysmotility disorders can also be associated with a risk of self-harm including suicide. Clinical psychology and liaison psychiatry provide overlapping but complementary approaches and ideally a MDT involving both specialties should be available.