Daniel Peckham and Alison Morton. July, 2003. Treatment of Distal Intestinal Obstruction Syndrome [online]. Seacroft and St James's University Hospitals, UK. Available from http://www.cysticfibrosismedicine.com

Introduction

The distal intestinal obstruction syndrome (DIOS) (previously known as meconium ileus equivalent, MIE) is a unique condition to cystic fibrosis (CF). It occurs due to the accumulation of viscous mucous and faecal material in the terminal ileum, caecum and ascending colon. Typically patients develop progressive symptoms of recurrent colicky abdominal pain, bloating, nausea and anorexia, and signs of small intestinal obstruction. It has not been described in other forms of pancreatic insufficiency although it has been reported in patients with cystic fibrosis who are pancreatic sufficient and have normal fat absorption (Millar-Jones et al, 1995, Davidson et al, 1987).

The syndrome is relatively common, occurring in about 10-20% of patients (Penketh et al, 1987, Davidson et al, 1987, Rubinstein et al, 1986). It may present either acutely or chronically and can be easily misdiagnosed by those who are unaware of the condition. DIOS may occur at any time after the neonatal period and the incidence appears to increase with age and to be more common in adolescent and adult patients. Contributing factors include fat malabsorption (Andersen et al, 1990), abnormal intestinal mucins, low duodenal pH, low dietary fibre intake, possibly a prolonged transit time, previous meconium ileus, abnormal intestinal water and electrolyte transport, and anticholinergic drugs (Eggermont 1996, Wilschanski et al, 1998). Dehydration associated with the development of diabetes mellitus may also precipitate DIOS (Hodson et al, 1976).

Transplantation

DIOS is a well recognised complication in the early post transplant period. It occurs with increasing frequency due to dehydration and drug therapy. Effective preventative measures and early treatment are important if severe complications are to be avoided (Gilljam et al, 2003).

Analgesia

Dehydration and opiate analgesics can potentiate acute and chronic attacks of DIOS. Appropriate preventative measure such as good hydration and prophylactic laxative therapy should be considered.

Clinical presentation

Patients may have intermittent acute exacerbations or chronic symptoms (Zentler-Munro, 1987). In the acute form the patient frequently presents with acute lower abdominal pain, diarrhoea and a tender mass in the right iliac fossa. In the chronic form, DIOS can present in a more indolent fashion with symptoms such as anorexia, colicky abdominal pain, abdominal distension, fatty stools and constipation.

Investigations

Investigation of patients who are prone to attacks of DIOS should include a plain abdominal X-ray, which typically shows faecal loading in the right iliac fossa, (often granular or bubbly in appearance), dilatation of the ileum and an empty distal colon. Fluid levels and a variable degree of small bowel dilatation may be seen during acute attacks (Agrons et al, 1996 ). Serum amylase and electrolytes should be checked and an abdominal ultrasound may be helpful in identifying the obstructing mass, but cannot be relied upon to exclude other serious causes of pain and obstruction such as intussusception (Dik 1995). If the condition is recurrent or unresponsive to medical treatment, a contrast enema or colonoscopy should be performed.

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Differential diagnosis

DIOS may mimic or be mimicked by other conditions such as simple constipation (Rubinstein et al, 1986), appendicitis (may be atypical in CF) (Sheilds et al, 1990; Coughlin et al 1990), an appendix mass, ovarian cyst, fibrosing colonopathy (Smyth et al, 1994; Smyth et al, 1995), pancreatitis (Shwachman et al, 1975), inflammatory bowel disease (Lloyd-Still, 1990) ,volvulus, intussusception, (Holmes et al, 1991),bowel adhesions (eg previous surgery for meconium ileus) (Littlewood, 1995). and gastrointestinal malignancy.

Chronic management

A number of studies have suggested that DIOS occurs more frequently in patients on inadequate pancreatic enzyme replacement. Review by an experienced dietitian to ensure that pancreatic enzyme dose is titrated to fat intake and to encourage adherence to routine dietetic management is essential. Care should be taken when increasing pancreatic enzyme supplementation in patients with abdominal pain and constipation as it is likely to worsen their symptoms, unless fat malabsorption is confirmed (Littlewood 1995). An increase in fluid intake should be recommended and a review of dietary fibre intake may be beneficial it is not always appropriate to increase the dietary fibre intake in all patients as this may lead to a reduction in the energy density of the diet. Timing of enzyme therapy with respect to meals and snacks and method of taking pancreatic enzymes should also be reviewed. An experienced CF dietitian should undertake this review (Littlewood & Wolfe, 2000).

Faecal chymotrypsin is low in untreated pancreatic insufficient patients with CF and can be useful for monitoring enzyme therapy with low values suggesting inadequate therapy possibly due to poor adherence ( Littlewood & Wolfe, 2000). . Measuring chymotrypsin levels may be inaccurate during acute attacks of DIOS when associated with diarrhoea.

In addition to assessment of enzyme therapy, assessment of malabsorption and/or steatorrhoea is valuable. The 72 hour faecal fat collection is the gold standard for assessing fat absorption however faecal fat microscopy has been shown as a useful tool to detect steatorrhoea. Fat microscopy shows some correlation between microscopic grading and severity of steatorrhoea and has been validated by comparison with quantitative measurements (Walters et al, 1990).

Reduction of gastric acid or acid suppression as a means of improving enzyme efficacy with a proton pump inhibitor has been reported and the addition of ranitidine, omeprazole or lansoprazole to reduce gastric acid secretion (Heijerman et al, 1990; Heijerman et al, 1993) or taurine (Smith et al, 1994) may help to improve absorption.

Several studies have suggested that the pro-kinetic drug, cisapride (Janssen-Cilag Ltd) can be used to improve the symptoms of chronic DIOS, although its use has been discontinued in many CF centres following the suspension of the product licence due to concern about prolongation of the QT interval and ventricular arrhythmias (Koletzko et al, 1990). In selected cases this drug may still be used on a named patient basis and with appropriate monitoring.

Patients with mild episodes of DIOS often respond to laxatives such as lactulose (20 mls twice a day and senna). Some centres use Sodium picosulphate or high dose Movicol (Norgine). Prolonged maintenance therapy with N-acetylcysteine (Celltech) can be used in patients with chronic DIOS (acetylcystein sachet 400 mg twice or three times a day or Parvolex liquid (horrid taste) –children; 5-10 ml qds in orange juice. Adults; 30 ml tds with 120 ml water or orange juice). Alternatively some patients appear to respond to intermittent courses of either gastrografin (Schering), Fabrol or Klean Prep(Norgine) as long as it is administered with appropriate fluids.

Acute DIOS

If there are signs of peritoneal irritation or complete obstruction then surgical review is recommended and patient should be placed nil by mouth, given intravenous fluids and nasogastric aspiration (drip and suck).

All patient presenting with acute DIOS should be well hydrated, intravenously if necessary. Pain relief with non-opiod analgesia is recommended and an antiemetic is often given.

There are variable treatment options and preparations may be administered either orally or via nasogastric tube. These include ;

1) High dose oral gastrografin (gastrografin, <15kg 15-30 ml, < 25kg 50mL, >25kg 100mL once daily in 4 times the volume of water or fruit juice ie for adults 100ml gastrografin in 400 ml water or juiceon day one and half doses on day 2 and 3. For children the weight appropriate dose taken with four times the volume of water or juice on day one and half doses on day 2 and 3) (O’Halloran et al, 1986; shah et al 1993, Zentler-Munro et al, 1987). Gastrografin may also be administerd by enema under radiological supervision (100 ml diluted 3 to 5 times with water up to twice in 24 hours – variable between units with doses of 500 ml 50% gastrografin having been used)
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2) Alternatively the intestines can be flushed out using a balanced electrolyte solution such as Klean-Prep, which may need to be given via nasogastric tube (Davidson et al, 1987, Davis et al, 1980, Koletzko et al, 1988, Cleghorn et al, 1986). Klean Prep – may be administered at 10 ml kg/hour for the first 30 minutes, followed by 20 ml/kg/hour for 30 minutes, and then increased to 25 ml/kg/hr if well tolerated. Maximum volume over 4 hours: 100 ml/kg or 4 litres. A further 4 hours of treatment may be necessary if the output is not clean. However in practice it is unusual to prescribe more than 4 litres a day. Our standard adult dose is 2 litres on two successive days.

3) Treatment with oral N-acetylcysteine is used by some centres as it acts as a mucolytic and can help break up the protein matrix of the inspissate. (N-acetylcysteine (acetylcystein sachet 400 mg twice or three times a day or Parvolex liquid (horrid taste) –children; 5-10 ml qds in orange juice. Adults; 30 ml tds with 120 ml water or orange juice).

In the more severe case, DIOS can be successfully treated using gastrografin directed into the lumen of the ascending colon by means of either an enema or colonoscopy (500 ml of 50% gastrografin (Agrons et al, 1996, Shidrawi et al, 2002). In a few refractory cases, surgical decompression may be required but carries a high post operative mortality. In one case of DIOS resistant to conventional therapy, a modified antegrade continence enema technique, creating a continent stoma proved an effective alternative to more conventional surgery (Clifton et al, 2003).

Post operative

In the event of laparotomy and surgical decompression, it is recommend that a small dose of pancreatin is started even if patient is nil by mouth to avoid further obstruction.

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