Acute Colonic Pseudoobstruction (Acute Megacolon, Ogilvie Syndrome)

Megacolon, like megarectum, is a descriptive term. Megacolon denotes dilatation of the colon that is not caused by a mechanical obstruction. While the definition of megacolon has varied in the literature, most use a cecum measurement of greater than 12 cm in diameter to define megacolon. Adding to this definition, because the diameter of the large intestine is different in different areas, measurements of greater than 6.5 cm for the rectosigmoid region and greater than 8 cm for the ascending colon may also be significant.

Megacolon may be divided into three categories by acuity of onset, as follows: (1) acute megacolon (pseudoobstruction, Ogilvie syndrome); (2) chronic megacolon, which includes congenital, acquired, and idiopathic causes; and (3) toxic megacolon.

The Gastroenterology section of the Medscape Drugs & Diseases journal contains three articles devoted to megacolon, and they are separated based on the three aforementioned categories (see also Differentials). This article is devoted to the acute development of megacolon.

Acute colonic pseudoobstruction (ACPO) is a rare condition first reported in 1948 by Sir William Ogilvie. It is characterized by acute colonic dilatation in the absence of an intrinsic mechanical obstruction or an extrinsic inflammatory process (toxic megacolon).[1, 2]

The pathophysiology underlying acute colonic pseudoobstruction (ACPO) (acute megacolon, Ogilvie syndrome) remains unresolved. Limited human studies have investigated the pathophysiology underlying ACPO; few, if any, animal models have been found. However, multiple risk factors have been described that appear to be associated with ACPO, with the presumption that dysregulation of colonic motor activity as a possible underlying mechanism.[3]  It is well known that the colonic distensibility changes in the presence of luminal contents. For example, fatty acids infused into the cecum appear to reduce the volume of the proximal large bowel. Long-term opiate narcotic use (including diphenoxylate and loperamide) may lead to colonic dilatation and may limit the ability of the colon to contract when dilated.

Many pathophysiologic mechanisms have been proposed in an attempt to explain the altered motility seen in acute megacolon; these include the following[3] :

• Imalance of autonomic innervation (the most suggested mechanism): 1) Excess sympathetic motor input (failure to contract), 2) decrease in parasympathetic motor input to the distal colon (failure to relax and atonic segments), and 3) excess parasympathetic motor input (failure to relax)
• Disruption of colo-colonic (spinal and ganglionic) inhibitory reflex arcs: Abnormal motility in one colonic segment may lead to dilatation of other segments ^[4]
• Intrinsic colonic dysfunction (limited evidence): 1) impairment of the interstitial cells of Cajal (ICC) and enteric nervous system (ENS) function, and 2) dysregulation of nitric oxide neurotransmitter
• Excess stimulation of peripheral opioid receptors by endogenous and/or exogenous opioids (initially, excess activation, followed by prolonged inhibition)

Causes of acute megacolon (acute colonic pseudoobstruction [ACPO], Ogilvie syndrome) include, but are not limited to, the following:

• Metabolic abnormality(ies), including renal failure, hypothyroidism, and hyperthyroidism
• Electrolyte disturbances, which can alter autonomic function and predict poor clinical response to neostigmine
• Chronic illness/diseases which can dysregulate neurotransmitters and disrupt the interstitial cells of Cajal (ICC) and enteric nervous system (ENS)
• Medications, of which multiple drugs has been described that alter colonic motor activity, including anticholinergics, antidiarrheals, opioids, calcium channel blockers, antipsychotics, digitalis, clonidine, dexmedetomidine, and others
• Pregnancy and obstetric causes, which are most commonly associated with cesarian section surgery (possibly due to alteration of autonomic innervation); hormonal changes during pregnancy may have an effect on the colonic tone
• Inflammatory bowel disease, including ulcerative colitis and Crohn disease.
• Infections, including viral (herpes zoster, varicella zoster, cytomegalovirus, and severe dengue), Clostridioides difficile (pseudomembranous colitis), Trypanosoma cruzi (Chagas disease), and Entamoeba histolytica (amebic dysentery). ^{[5, 6, 7]}

Note that in any setting, a mechanical cause (eg, a tumor) and a toxic cause (eg, acute ulcerative colitis) must be first ruled out because the treatments are very different for these conditions.

Acute colonic pseudoobstruction (ACPO) (acute megacolon, Ogilvie syndrome) is rare disease. A national US hospital admissions database reported an estimated incidence rate of approximately 100 cases out of 100,000 inpatient admissions per year.[8]

Race-, sex-, and age-related demographics

Race has not been documented to play a role in acute megacolon.

Most patients are males over the age of 60 years[9] ; however, the increased incidence seen in older populations is more likely a reflection of their medical and surgical comorbidities rather than age alone.

Morbidity/mortality

Prognosis of patients with acute colonic pseudoobstruction (ACPO) (acute megacolon, Ogilvie syndrome) is determined in part by the underlying cause of the megacolon, the presence of any comorbidities, and the development of complications.

The mortality rate associated with ACPO declined from 9.4% in 1998 to 6.4% in 2011.[8]

In the absence of complications, mortality is approximately 15% as compared to up to 45% in patients with bowel ischemia or spontaneous perforation of nontoxic megacolon. However, most patients respond to treatment prior to the onset of this complication.[10, 11]

Complications

The most common complications of ACPO are bowel ischemia and perforation, which occur in up to 20% of cases. In a study by Vanek and Al-Salti, the perforation rates were 0% for cecal diameters of less than 12 cm, 7% for cecal diameters of 12-14 cm, and 23% for cecal diameters greater than 14 cm.[9]

Mortality has also been shown to increase with a delay of decompression therapy.

If surgical therapy is required, mortality increases based on older age, the presence of comorbidities, and decreased functional status.

The typical patient acute colonic pseudoobstruction (ACPO) (acute megacolon, Ogilvie syndrome) is an elderly person who is in the hospital, usually for an unrelated reason (eg, postoperative recovery), and may or may not already be taking oral feedings. Procedures that commonly predispose to ACPO include spinal and orthopedic surgery (1-2%), cardiovascular or lung surgery (up to 5%), cesarian delivery, and burn injuries (0.3%).[12, 13]

Acute megacolon can occur on the medical wards as frequently as on the surgical wards (eg, in patients with unrelated problems, such as pneumonia, sepsis, myocardial infarction, or stroke). Systemic diseases that affect the neuromuscular component of the GI tract, such as amyloidosis, may first present with an acute episode of pseudoobstruction.

The most common presenting symptom is abdominal distention (89%), but not having a past history of similar episodes of abdominal distention is common. Other common presenting symptoms include abdominal pain (60-80%), nausea and vomiting (13-60%), constipation (50%), and, paradoxically, secretory diarrhea (20-40%), as well as fever in patient with complications (ie, perforation).[14, 15, 16]

Physical examination findings in patients with acute colonic pseudoobstruction (acute megacolon, Ogilvie syndrome) may include the following:

• The vital signs can all be normal.
• Depending on the duration of the megacolon and the patient's fluid status, the patient may become tachycardic.
• With distention of the abdomen pushing on the lungs, the patient also may develop tachypnea. In this regard, the lung fields may be decreased.
• The abdomen is usually distended and tympanitic to percussion, with varying bowel sounds from absent to high-pitched. Serial measurement of the abdominal girth is routinely unreliable.
• Digital rectal examination should generally be performed to exclude fecal impaction.
• The presence of fever, severe tenderness, and peritoneal signs should raise the suspicion of colonic perforation or ischemia.

Laboratory studies are directed at establishing the etiology of the acute megacolon (acute colonic pseudoobstruction [ACPO], Ogilvie syndrome), assessing the patient’s fluid status, as well as evaluating the presence of any complications. These studies include the following:

• Complete blood cell (CBC) count
• Electrolyte levels (including calcium, magnesium, and phosphorus)
• Serum lactate level
• Blood urea nitrogen (BUN) and creatinine measurements
• Levels of aminotransferases, alkaline phosphatase, bilirubin, amylase, and lipase (to evaluate for other potential causes of abdominal pain)
• Thyroid studies
• Stool studies (including leukocytes, ova and parasites, and  C difficile toxin assay)
• Blood cultures

Imaging studies are used to determine the severity of acute colonic pseudoobstruction (ACPO) (acute megacolon, Ogilvie syndrome), to exclude free intraperitoneal air (perforation) as well as other etiologies (eg, extrinsic compression), and to follow the clinical course.[17]

Plain x-ray films of the abdomen demonstrate the massive gaseous distention of the colon. Generally, the small bowel is not seen. Dilation of all segments of the colon support the diagnosis of pseudoobstruction.

Other imaging studies, such as hypaque (water soluble radiopaque contrast material) enema, computed tomography (CT) scanning, or magnetic resonance imaging (MRI), may also be used to exclude obstruction.

Perform other tests only to rule out a mechanical obstruction. Depending on the setting, severity, and condition of the patient, these tests may include either a colonoscopic examination (which also may be therapeutic) or a water-soluble contrast enema. Colonoscopy is preferred because of its diagnostic and therapeutic potential.

Management of acute colonic pseudoobstruction (ACPO) (acute megacolon, Ogilvie syndrome) can be divided into a conservative or interventional approach. Conservative management can be as safe and effective as an interventional approach, with less likely ACPO syndrome-related complications in carefully selected patients.[18]  Interventional management has been recommended, especially for critically ill patients, and includes use of acetylcholinesterase inhibitors (neostigmine), gastrostomy tube placement, decompressive sigmoidoscopy/colonoscopy, and colostomy or colectomy.

A unique phenotype, secretory diarrhea and hypokalemia with colonic pseudoobstruction (SD-CPO), requires a distinct approach for management, as this condition  is more difficult to treat and carries a higher mortality as compared to the classic constipation-predominant form.[16]

Conservative management is preferred when the patient with acute colonic pseudoobstruction (ACPO) (acute megacolon, Ogilvie syndrome) is clinically stable. It can be continued for 24 to 48 hours in the absence of significant pain, extreme (>12 cm) colonic dilation, or evidence of peritonitis. Consider the following:

• Treat the underlying cause if possible, such as correction of any electrolyte/metabolic abnormalities and removal of medications that may decrease colonic motility (eg, narcotics, anticholinergic agents, calcium channel antagonists).
• Oral feeding should be discontinued, and intravenous fluids should be initiated.
• If nausea and vomiting are present, nasogastric decompression should be initiated.
• Encourage early ambulation when possible.

Decompression

Trans-anal rectal tube placement

Rectal tube can be placed with fluoroscopy guidance or during decompression colonoscopy. It has a 70% technical success and 50% clinical improvement rates. This tube may assist in the treatment only if the sigmoid colon is involved. When such tubes are used, anecdotal experience has demonstrated that frequent position changes for the patient may help improve decompression. Complications with these rectal tubes include tube obstruction and colonic/rectal ulceration.

Colonoscopic decompression

If the dilatation persists or worsens, colonoscopic decompression with or without placement of a tube in the right colon should be considered. Although the placement of a decompression tube per rectum is generally suggested, some experts believe that the tube often becomes obstructed with stool and ceases to work after a short time. Randomized controlled trials of the efficacy of colonoscopic decompression are lacking.  The therapeutic success rate of decompression colonoscopy can be enhanced form less than 50% to 88% by concurrent decompression tube placement.[19]  A retrospective study revealed that colonoscopic decompression is more effective as an initial therapy and at avoiding a second treatment modality compared to neostigmine.[19]  In patients with secretory diarrhea and hypokalemia with colonic pseudoobstruction (SD-CPO) a trial of concomitant colonic decompression and aldactone is warranted.[14, 20]  The resolution of ileus, perforation, and mortality rates are similar between endoscopic and conservative management.

Colonic decompression appears to be effective for proximal colonic dilation or ACPO-related symptoms relative to standard medical care alone.[21] A 2020 retrospective (2000-2016), propensity-matched study that evaluated the efficacy of colonic decompression with standard medical therapy (supportive care, pharmacotherapy) for treatment of inpatients with first diagnosis of ACPO versus standard medical therapy alone found no significant differences in mid or distal colon diameter reduction between the two groups. However, 47.7% of patients who underwent colonic decompression had complete resolution of ACPO, with a 15.7% 30-day readmission rate, compared to 19.9% of those who received standard care alone (P< 0.001), who had a 26.2% 30-day readmission rate. Moreover, the 30-day all-cause mortality for the colonic decompression group was lower versus the standard medical therapy group (8.4% vs 14.8%, respectively).[21]

Neostigmine

Neostigmine is an acetylcholinesterase inhibitor that has been demonstrated in a meta-analysis of randomized-controlled trials to be effective in 90% of treated patients compared to 15% in the control arm, with median time to response of 4 minutes (~3 to 30 minutes) and a number needed to treat (NNT) of 1.[22]

The major indication for its use is failure of conservative therapy after 24-48 hours or a cecal diameter of greater than 12 cm.

Contraindications include bradyarrhythmia, recent myocardial infarction, systolic blood pressure of less than 90 mm Hg, active bronchospasm, serum creatinine level of greater than 3 mg/dL, evidence of bowel perforation, or concomitant use of beta-blockers.

Adverse events include abdominal cramping (17%), excessive salivation (13%), transient bradycardia (6%), diaphoresis (4%), and nausea and vomiting (4%). Based on expert opinion, a starting dose of 0.5 -1 mg may reduce the likelihood of developing bradycardia.

Cardiac monitoring of patients during treatment with neostigmine is generally recommended, and atropine should be at the bedside.

A second dose of neostigmine (preferably after 24 hours) should be considered if there is a partial or minimal response to the initial administration.[23, 24, 25]

Of note, although neostigmine often induces clinical decompression, this decompression has not been shown to reduce perforation and mortality rates, and in patients with SD-CPO neostigmine appears to be relatively ineffective and may aggravate the diarrhea.[16]

Urgency

The urgency of management often depends on the size of the colon and the rate of change of the cecal diameter. Some experts believe that regardless of the criteria used for defining acute megacolon, the diameter of the cecum is the most important criterion because the cecum is generally the area that perforates. While the diameter at which the cecum perforates is variable, expert experience indicates that the cecum rarely perforates at a diameter of less than 12 cm.

Once acute megacolon (acute colonic pseudoobstruction [ACPO], Ogilvie syndrome) is relieved, close follow-up care, including physical examination and maintenance of a normal electrolyte balance, is important.

The use of polyethylene glycol electrolyte balanced solution can decrease the risk of recurrence.

Avoid using agents that slow transit time, such as opiates and anticholinergics.

Diet and activity

Most patients are in the hospital when acute pseudoobstruction is diagnosed, and bowel rest should be instituted. Parenteral nutrition may be considered depending on the patient's nutritional status.

Because many of the cases of acute pseudoobstruction occur postoperatively, the patients tend to be already at bed rest. Remembering to continue prophylaxis for deep venous thrombosis, per the individual physician's protocol, is important; however, if the patient is not severely ill, is not in severe pain, and is stable to ambulate, no reason exists for the patient to remain in bed.

In view of the high rate of recurrence of colonic dilation following medical and endoscopic therapies, other therapeutic modalities have been proposed for acute colonic pseudoobstruction (acute megacolon, Ogilvie syndrome).

Percutaneous cecostomy may successfully allow for colonic decompression, but complications with this procedure are high.

Surgical options include cecostomy, colostomy, or colectomy, although surgical therapies are associated with even poorer outcomes. A colectomy is indicated if perforation or colonic ischemia is present.[26, 27, 28, 29]

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Class Summary

Increase peristalsis and secretions in the intestine and relax the sphincter.

Neostigmine (Prostigmin)

Improves acute colonic megacolon; may increase cholinergic activity by reducing acetylcholine degradation.

Class Summary

Erythromycin

Response to treatment was inconsistent with gradual improvement over 24 hours.[30]

Methylnaltrexone

Resulted in successful decompression in one case with ACPO on opioids that was refractory to neostigmine. [31]