Chronic intestinal pseudo-obstruction (CIPO) belongs to a heterogeneous group of rare, severe, and potentially life-threatening disorders characterized by recurrent or chronic symptoms and signs of intestinal obstruction in the absence of any mechanical obstruction (1). It is characterized by profound impairment of gastrointestinal motility due to a variety of disorders affecting the enteric neuromuscular system. Chronic intestinal pseudo-obstruction is primarily a disorder of the small intestine, even if it can occur anywhere in the gastrointestinal tract, with variable phenotypic presentations. The precise incidence of pseudo-obstruction is not known, even if a national survey from North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition suggests that it occurs in approximately 1 in 40,000 live births, with clinical signs presenting most frequently in the neonatal period (2).
Based on histopathological assessment, CIPO can also be classified into 3 major entities: “neuropathies,” with the predominant involvement of enteric neurons, “mesenchymopathies,” involving the interstitial cells of Cajal, and “myopathies,” in which the involvement of smooth muscle prevails (3). All histopathological changes may contribute to gastrointestinal dysmotility either individually or in combination. Furthermore, CIPO may be primary or secondary to a large number of intestinal as well as extraintestinal conditions (ie, diseases affecting central autonomic and enteric nervous system, immune-mediated and collagen diseases, and endocrine and neuromuscular disorders). Indeed, every disorder affecting one of the control mechanisms of intestinal motility, including intrinsic and extrinsic neural supplies, as well as muscle cells, may be responsible for secondary and potentially curable forms of CIPO. However, pediatric CIPO presents most often as primary visceral myopathy or neuropathy, and it is generally sporadic, even if familial forms with autosomal dominant, autosomal recessive, and X-linked transmission have been widely described (4). In children, the disease is generally characterized by a particularly severe course, with mortality rates extremely high within the first year of life and ranging between 10% and 25% in older children, mainly due to complications of parenteral nutrition.
Treatment of CIPO is disappointing and frustrating for the physicians and the child, and remains extremely challenging even in referral centers. The management goals of CIPO are improving gastrointestinal motor activity, relieving symptoms, and restoring nutritional status and hydration. Unfortunately, the treatment of CIPO is mainly supportive because so far there are no motility agents in the market able to restore normal gastrointestinal motor function, particularly in those patients with a generalized motility disorder. However, even if drugs stimulating intestinal contractions are helpful only in a minority of children, a trial with prokinetics should always be attempted.
Chronic intestinal pseudo-obstruction is one of the most important causes of intestinal failure in childhood (15%), because affected patients are often unable to achieve normal growth and maintain a normal body weight, due to severe digestive symptoms triggered by food ingestion and presenting an adequate oral caloric intake. The severity of the clinical picture also contributes to the deterioration of quality of life. In this scenario, the aim of nutritional support is achieving an adequate nutritional status, preserving growth and development, and avoiding life-threatening complications. The oral intake of children with CIPO is influenced by the extent of gastrointestinal disease. For instance, patients with gastroparesis often complain of early satiety, bloating, and nausea and are likely to have more difficulty with oral intake than those with predominantly small bowel involvement. Small and soft frequent meals (up to 6 to 8 meals per day) are usually well tolerated in children with sufficient residual digestive function. A low-fiber, low-residue diet is helpful in minimizing intestinal gas, cramps and potential bezoar formation. Food with high concentrations of fat should be avoided in order to limit the delay in gastrointestinal transit. Patients with CIPO may also become deficient in essential vitamins as well as trace elements, and consequently multivitamins should be added to their diet. In order to meet an adequate caloric intake, hypercaloric formulae are available on the market and can be helpful if tolerated. In infants, protein hydrolyzed formulae are better tolerated than whole-protein formula because they are emptied from the stomach as fast as breast milk and faster than casein or whole-protein formulae.
In children with severe gastrointestinal motility dysfunctions who are not able to meet their caloric needs with oral nutrition alone and continue to lose weight, enteral nutrition is the following step. Before placing a permanent enteric feeding tube, it is appropriate to perform a 72-hour-long trial of naso-enteric feeding in order to confirm that the child is able to tolerate the formula and the rate of formula delivery. Percutaneous endoscopic gastrostomy should be placed in children who do not have significant gastroparesis. Alternatively, an artificial feeding device that bypasses the stomach should be preferred. Temporary or permanent small bowel access can be achieved by endoscopic, surgical, and radiological placement. Percutaneous endoscopic gastrostomy/jejunostomy is a dual system in which a jejunal tube is passed via a gastrostomy tube to a small bowel. The use of large diameter jejunal tubes allows both easy endoscopic tube placement and low incidence of tube migration. However, fluoroscopically guided or surgical tube placement may be alternatively performed. The success of jejunal feeding in children with CIPO varies and is unpredictable on the basis of signs and clinical symptoms. It has been clearly shown that jejunal feedings are more likely to be successful in children with phase 3 of the migrating motor complexes in duodenum or jejunum as compared with those without phase 3 of migrating motor complexes, supporting the view that the absence of a normal fasting motility is not compatible with enteral feeding and normal growth in children (5). Once appropriate enteral access has been achieved and the caloric needs of the patient have been estimated, tube feeding can be initiated. If the tube is placed in the stomach, gravity feeding may be used. However, because children frequently complain of abdominal bloating and nausea during gravity feeds, continuous infusion through a peristaltic pump is frequently required. On the other hand, in children with a tube placed in the small intestine, continuous feedings are necessary. Jejunal feedings in each child should be started with an elemental formula appropriate for the child's age, and the infusion volume should be progressively increased if the child is thriving and has mild or no symptoms.
In the most severe cases, parenteral nutrition (PN) becomes mandatory in order to satisfy nutritional requirements and manage appropriately obstructive episodes. Parenteral nutrition is defined as total parenteral nutrition (TPN) when it provides >50% of the caloric requirement and partial when it provides <50% of caloric needs. In the London experience at Great Ormond Street Hospital for Children more than 70% of children with severe CIPO needed long-term TPN, 60% for less than 6 months, whereas 25% had been successfully weaned off TPN, but still required TPN for short periods of time (usually <6 months) (6). Similar proportions of children requiring partial or total PN have been reported by other groups, corroborating the view that PN is the mainstay of management of pseudo-obstruction. To deliver adequate nutrition a tunneled central venous catheter should be placed under radiological control, because it is likely that the need for PN will continue for months. The use of a single lumen catheter with the line dedicated for the parenteral infusion only, and adequate training of all people involved in the handling of the catheter, seem to be crucial for safe management of PN and for the reduction of the episodes of septicemia. Home TPN tends to improve the quality of life of children with CIPO; however, it requires extensive family education and only if certain criteria are satisfied may the child be discharged home.
Although in the last decade the survival rate of children with CIPO on TPN has greatly increased, the latter is still the last desirable resource for achieving adequate nutritional needs. Prolonging the duration of use of PN may be associated with bacterial and fungal sepsis, liver disease, and other catheter-related complications that have adverse consequences for survival, duration of hospital stay, growth, and development. It has also been shown that even when PN provides adequate nutritional intake, the gastrointestinal tract does not grow or mature normally, unless enteral nutrition is also provided. The composition of enteral nutrients, the route of delivery, the ability of the nutrients to stimulate the release of endogenous peptides, and the presence of growth-promoting factors seem to represent a profound stimulus for morphological, biochemical, and functional gastrointestinal mucosal growth. Furthermore, the early exposure to enteral feeding of nutrients seems to be responsible of changes in maturation of the enteric nervous system, which parallel the development of gastrointestinal motility. Thus, these mucosal and nonmucosal activities may in turn result in better absorption and utilization of nutrients. It seems likely that an enteral formula contributing for more than 10% of the patient's caloric requirement is able to stimulate postprandial increase in both trophic factors, such as gastrin and splanchnic blow flow. Moreover, the mortality rate in children requiring PN for >50% of their caloric intake is significantly higher, as compared with those receiving more than 50% of their caloric requirement enterally (7). In this setting, if TPN is necessary, every effort should be made to establish some tolerance of enteral feeding and, ultimately, weaning off TPN.
In conclusion, CIPO is a rare, debilitating disorder with a multitude of etiologies. Even if in childhood the majority of cases are usually idiopathic, a greater awareness of the clinical features would help clinicians recognize possible underlying causes. Chronic intestinal pseudo-obstruction is an important cause of intestinal failure, because affected children are often unable to achieve normal growth and maintain normal body weight. The management goals of CIPO are to improve gastrointestinal motor activity, relieve symptoms, and restore nutrition and hydration. In the majority of cases, CIPO is difficult to treat and responds poorly to the available motility-modifying therapies. Nutritional therapy is still the mainstay of supportive care, and aims at maintaining a normal body weight and, thus, preserving growth and development.
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