Intestinal Pseudo-Obstruction

Etiology

Although the exact cause of acute intestinal pseudo-obstruction is unknown, current theories suggest that the inhibition of parasympathetic activity, dysregulation of stretch receptors, and decreased ganglion cells in the colonic smooth muscle play an important role. Specifically, decreased parasympathetic activity, which plays an excitatory role for colonic motility, from the sacral plexus is thought to play a role in colonic atony.[1] Other possible contributors to intestinal pseudo-obstruction include decreased splanchnic perfusion, anticholinergic medications, opiates, hypokalemia, and uremia.[2]

The pathophysiology of chronic intestinal pseudo-obstruction (CIPO) is better understood with multiple causes identified. Neuropathies, myopathies, or abnormalities of the interstitial cells of Cajal have all been attributed to CIPO.[3][4] Known diseases that compromise the neuromuscular pathway include Hirschsprung disease, Parkinson disease, scleroderma, diabetes, Ehlers-Danlos syndrome, Fabry disease, and Chagas disease. Most cases are sporadic; however, rare genetic causes have been also associated with CIPO.  Additionally, paraneoplastic syndromes from small cell lung cancers, carcinoid tumors, and thymomas have been associated with CIPO due to an antineuronal nuclear antibody (anti-Hu) that possibly shares an epitope with the enteric nervous system causing inflammation and infiltration.[5]

Epidemiology

Acute intestinal pseudo-obstruction is more common in men and patients over the ages of 60. The annual incidence is estimated to be around 100/100,000 for every inpatient admission.[6] Cases are typically found in hospitalized patients after surgery or after a severe illness. Medications, metabolic imbalances, non-operative trauma, surgery, and cardiac disease have all been associated with intestinal pseudo-obstruction.[1] CIPO can develop in children and adults.[4] Many patients with CIPO also have underlying degenerative neuropathic and myopathic conditions. It is estimated that 20% of patients on home parenteral nutrition have CIPO. Limited epidemiological studies characterized CIPO in the U.S. Studies from Japan have reported a prevalence of 0.8 and 1.0 and an incidence of 0.21 and 0.24 cases per 100,000 adult men and women, respectively.[7]

Pathophysiology

The exact mechanism of acute intestinal pseudo-obstruction is still unknown. However, the relationship between trauma, spinal anesthesia, and certain medications suggests a possible impairment of the autonomic nervous system.[1] All of the proposed mechanisms describe the pathogenesis of a lack of colonic motility.[8] The major concern for intestinal pseudo-obstruction is bowel dilatation, which can lead to ischemia and perforation. The cecum, because of its larger diameter compared to the rest of the bowel, requires the least amount of pressure to distend as described in the law of Laplace. Under normal circumstances, the cecal diameter is less than 9 cm. The risk for ischemia and perforation increases after 10 cm with impending perforation when the diameter is greater than 12 cm for longer than six days.[9] It is not only the diameter and the duration of distension that increase the risk of perforation but the acceleration of the distension.

Chronic intestinal pseudo-obstruction has been associated with a myriad of diseases. Neuropathies such as Parkinson disease and diabetes mellitus have been implicated in the degeneration of the signaling pathway of the enteric nervous system causing CIPO.[10] Scleroderma, lupus, and paraneoplastic syndromes have been associated with immune-mediated CIPO damaging the enteric nerves and smooth muscle cells of the gastrointestinal tract.[10] The most common infectious etiology is Chagas disease, where inflammatory changes of the enteric neural pathways to the gastrointestinal tract are altered.[11] There are many genetic disorders (e.g., Fabry disease, Ehler Danlos Syndrome, Hirschsprung disease) under investigation for their involvement in CIPO.[4]

History and Physical

Abdominal distension is the key clinical feature in intestinal pseudo-obstruction occurring in about 80% of cases.[1] Nausea, vomiting, early satiety, constipation, and generalized abdominal pain can also be observed.[12] These symptoms can be acute, chronic, or recurrent. Patients may also exhibit symptoms from a neuromuscular disease that is associated with CIPO.

In ACPO, patients are typically already hospitalized with a severe illness or after surgery.[13] The findings of abdominal distension can occur rapidly or after several days. Patients presenting with fever, severe abdominal tenderness, or peritonitis may have progressed to bowel ischemia or perforation from the increased distension.

Evaluation

The key feature of intestinal pseudo-obstruction is abdominal distension. As the differential for a distended abdomen is broad, imaging is useful in establishing a diagnosis. X-rays of the abdomen will demonstrate air-fluid levels with dilated loops of bowel. The pathognomonic finding for ACPO is a dilated colon from the cecum to the splenic flexure or even the rectum. Findings of a dilated colon are nonspecific, and thus further investigation beyond x-ray is required to confirm the diagnosis.

Abdominal CT scans are much more specific than abdominal x-rays. CT will also demonstrate dilated loops of bowel, air-fluid levels, or specifically proximal colonic dilatation from the cecum to the splenic flexure or even the rectum. No mechanical obstruction must be identified, such as closed-loop obstructions, hernias, strictures, or masses. In the acute setting, contrast enemas and small bowel follow-throughs can be essential adjuncts to rule out these obstructions.

Although no specific labs will suggest intestinal pseudo-obstruction, a liver profile and lipase should be obtained to rule out other causes of abdominal pain. A complete blood count and serum lactate should also be obtained as leukocytosis, and elevated serum lactate can be increased in cases of bowel ischemia and perforation. In patients with chronic symptoms, vitamin B12, folate, TSH, and celiac serology should be ordered to assess for metabolic and autoimmune abnormalities. Additionally, serologic testing for herpes simplex virus, cytomegalovirus, and Epstein-Barr virus can assist in the diagnosis as viruses may cause inflammation of the enteric nervous system causing CIPO.  Finally, antineuronal antibodies (ANNA-1/anti-Hu) can also be analyzed to assess for paraneoplastic immune-mediated pseudo-obstruction.[12]

Patients with a dilated colon and rectum raise suspicion for toxic megacolon. Stool cultures and stool evaluation for Clostridioides difficile toxin should be obtained, especially in patients with diarrhea. As metabolic abnormalities, including hypokalemia, hypomagnesemia, and hypocalcemia, have been associated with intestinal pseudo-obstruction, a metabolic panel should be obtained so that these may be repleted.

Patients with chronic symptoms may undergo further testing to identify the cause of symptoms. An upper endoscopy and colonoscopy should be performed to identify and locate any pathology or areas of obstruction. If an endoscopy demonstrates no abnormalities, scintigraphy, which assesses the motility of the gastrointestinal tract, may be employed. With scintigraphy, patients ingest resin pellets and undergo a series of imaging to assess the transit time. If an abnormality is seen on scintigraphy, a manometry study of the esophagus, stomach, and small intestine can delineate an underlying diagnosis and differentiate between myopathic and neuropathic disorders based on the pattern and amplitude of contraction.

As many neurological disorders are known to cause gastrointestinal dysmotility, autonomic function testing can differentiate peripheral neuropathy from central lesions.[5] In patients with severe dysmotility and known diagnosis, a full-thickness biopsy can be used to identify abnormalities in the enteric nervous system.

Treatment / Management

Treatment of ACPO involves decompression of the dilated colon to prevent bowel ischemia and perforation. Initial management in a stable patient may be conservative with serial x-rays of the abdomen to evaluate colonic diameter.[14] During this time, underlying causes should be treated and corrected.  These causes include electrolyte abnormalities, infections, and medication side effects (e.g., anticholinergics and opiates). A nasogastric tube connected to intermittent suction can be placed to assist in decompression and prevent aspiration. A rectal tube to dependent drainage can also be placed to assist in decompression. If no improvement is seen after 48-72 hours, neostigmine may be administered.[14](A1)

Neostigmine is an acetylcholinesterase inhibitor that exhibits a parasympathomimetic effect by increasing the amount of available acetylcholine and indirectly stimulating muscarinic and nicotinic receptors.  These receptors, which are located on the smooth muscle of bowel mucosa, cause muscle contraction. The initial dose is 2 mg, administered slowly over 5 minutes.[15] Due to the side effect of bradycardia from neostigmine, patients should be placed in a monitored bed with telemetry and with atropine available at the bedside. A reduced dose should be used in patients with a history of heart block.

If the pharmacologic approach is unsuccessful or contraindicated, colonoscopic decompression should be considered. The colonoscope is advanced to the dilated bowel, and the air is suctioned. A decompression tube can also be placed up to the transverse colon with the aid of a guidewire to prevent re-occurrence.[13](B2)

Surgery remains the final option when the above measures have failed or if the patient's condition continues to worsen. Options include placing a cecostomy tube or performing a colectomy.[16] A cecostomy involves placing a tube in the cecum which can drain and decompress outside of the abdomen. Alternatively, the dilated portion of the bowel can be resected with primary anastomosis or an ostomy. Any patient who develops peritonitis or becomes hemodynamically unstable presumably from bowel ischemia or perforation requires surgical evaluation and resection of the compromised bowel.(A1)

For patients with chronic symptoms, prokinetic agents can help treat oral intake intolerance. Erythromycin is useful in treating acute exacerbations by stimulating motilin receptors in the bowel.[17] This is useful in the hospitalized setting but has not been shown to be effective for long-term treatment.[18] For patients that cannot tolerate erythromycin, metoclopramide has proven to be effective. However, like erythromycin, it has not been proven effective for long-term treatment. Prucalopride and cisapride are prokinetic agents currently being investigated to improve gastric emptying and symptomatic relief.[19][20](B3)

Proper nutritional assessment is also imperative for patients with CIPO.  Patients with oral intake intolerance should employ strategies such as small, frequent meals, and high-calorie drinks. If these adjuncts are unsuccessful in achieving caloric goals, feeding tube access through a gastrostomy tube. A jejunostomy may be indicated if there is evidence of gastroparesis in conjunction with CIPO.  Finally, patients with severe symptoms may require parenteral nutrition.

Differential Diagnosis

Mechanical Obstructions

Mechanical obstructions will present as dilation of bowel proximal to the obstructed point. Mechanical obstructions include incarcerated hernia, stricture, volvulus, or mass. Typically a "transition point" will be observed where proximal bowel is dilated and distal bowel compressed. If contrast is administered either by mouth or by enema, a cut-off may be seen.

Toxic Megacolon

In addition to abdominal distension on physical exam and abdominal radiograph, patients with toxic megacolon typically exhibit systemic inflammatory response syndrome (SIRS) criteria including fever, tachycardia, tachypnea, and altered mental status. The patients also more commonly have abdominal pain and bloody diarrhea. Toxic megacolon is commonly seen with ulcerative colitis but may also be seen with other types of colitis, e.g., ischemic, infectious, pseudomembranous. Clinical deterioration requires surgical evaluation for total colectomy with end ileostomy. 

Fecal Impaction

A dilated rectum and colon is commonly seen with fecal impaction. Patients with these findings should have a digital rectal exam to rule out impacted stool. Additionally, fecal matter can be seen on radiograph and CT imaging. Once the impaction is resolved, patients typically have a resolution of their symptoms.

Prognosis

The mortality rate for adult patients with CIPO is approximately 10%. One-third of patients with CIPO will require parenteral nutrition with its associated complications, which are estimated between 45% to 80%.[21]

In children, mortality rates range from 10% to 40%, with parenteral nutrition dependence as high as 60% to 80%.[22]

In ACPO, the prognosis is predicated on the development of bowel ischemia or perforation, which occurs in 3% to 15% of cases. The mortality rate with ischemic bowel or perforation is 40% versus 15% without perforation.[23][24]

Complications

Failure to address the colonic distension for intestinal pseudo-obstruction can result in the major complications of bowel ischemia or perforation, which may require urgent surgical intervention. As discussed previously, if a mechanical obstruction is not ruled out, the administration of neostigmine in a patient with a bowel obstruction can result in a catastrophic perforation.