Acute Colonic Pseudo-Obstruction

Introduction

Acute colonic pseudo-obstruction (ACPO) is a disorder characterized by massive dilation of the colon in the absence of mechanical obstruction. This severe motility disturbance, also known as Ogilvie's syndrome, usually develops in hospitalized patients, and is associated with various medical and surgical conditions. The tension on the colon wall resulting from the extreme dilation can lead to ischemic necrosis and perforation, especially in the cecum. The rate of spontaneous perforation has been reported to be 3% to 15%, with an attendant 40% to 50% mortality rate. Despite the potential risk of perforation, approximately 75% of patients with ACPO recover over an average of 3 to 5 days when treated using a variety of conservative measures. During the sometimes prolonged recovery phase, however, ACPO contributes greatly to patients' discomfort and immobilization, and prevents institution of enteral nutrition.

The risk of major complications/mortality and the morbidity of the long recovery led to a search for effective and safe therapies, not only to prevent ischemia and perforation but also to speed resolution. Very few controlled trials have evaluated the standard therapies used for ACPO. Nonetheless, conservative management strategies such as nasogastric (NG) suction and measures taken to correct precipitating factors have been the mainstay of treatment.

For the minority (approximately 25%) of patients who fail to respond to conservative therapy and for patients who have severe or prolonged colonic dilation risking perforation, more active interventions are instituted. In the past, surgical cecostomy and hemicolectomy were the main options for severe or refractory cases. Subsequently, colonoscopy and various radiologic procedures were reported to help decompress the colon. Medications such as neostigmine have also been shown to be effective. The timing and combination of conservative and more active interventions must be individualized according to the severity of ACPO and the patient's comorbidities.

Epidemiology

ACPO is relatively uncommon. It can be triggered by various acute medical and surgical illnesses. Typically, rapid-onset abdominal distension begins within a few days of the start of the underlying illness. Because ACPO is uncommon, one must look at reviews that examine several years of reported cases before one can draw conclusions about the epidemiology of the condition. Numerous case reports and reviews describe specific triggers. However, each proposed underlying condition seems to be associated with the development of ACPO in only a very small percentage of cases ( Table 35.1 ). ACPO has been reported after various surgeries, including orthopedic, urologic, gynecologic, and neurologic surgeries, as well as organ transplants. It is seen in obstetrics after vaginal deliveries and cesarean sections. Trauma and burn patients sometimes develop ACPO. Various medical illnesses are known to cause ACPO, including sepsis, respiratory failure, mechanical ventilation, renal failure, myocardial infarction, vascular emergencies, sickle cell crisis, and cancer. Many medications can precipitate or worsen ACPO, especially narcotic analgesics and any medication that decreases peristalsis, such as tricyclic antidepressants or anticholinergic drugs. Although the connection between any of these causes and ACPO is most likely through a disturbance in the autonomic innervation of the bowel, other variables, such as patient age, comorbidities, and factors such as immobility, medications, and electrolyte imbalances, are contributing factors.

In one review of 351 ACPO cases from 1948 to 1980, 88% followed surgery, trauma, or acute medical illness. The remaining 12% were classified as idiopathic. This review reported a 15% perforation rate, with a 45% mortality in patients with colonic perforation. This high mortality was attributed in part to the fact that these patients already had serious underlying medical or surgical problems.

In another review of 400 patients from 1970–1985, 95% of the cases had identifiable underlying medical, surgical, or obstetric conditions ; this left only 5% to be categorized as idiopathic. ACPO usually developed within 5 days of onset of the underlying condition. The median patient age was approximately 60 years, and the male-to-female ratio was 1.5 : 1. The perforation rate was 20%, and mortality in patients with perforation was approximately 40%. Overall, mortality in the group was 15%. The mortality rate was affected by age, cecal diameter, length of dilation of colon, presence of ischemia in the bowel wall, and patient comorbidities. One important observation in this review was that patients with a cecal diameter of 8 to 25 cm usually had viable colon without significant ischemia. Thus, cecal size alone is not the only factor in the risk of perforation. Other variables, such as the acuity of the onset and the duration of distention, were also potentially important factors.

A more recent review by Ross et al (2016) of over 100,000 cases from 1998–2011 found a higher rate of ACPO incidence than previously reported (approximately 100/100,000 adult inpatients/year). They noted that, although the incidence rate has increased, the overall mortality has decreased. They found a 7.7 % overall mortality. There was, as expected, much higher mortality in those that failed medical therapy and needed endoscopy or surgery.

Pathogenesis

In 1948, Ogilvie first described massive colonic distention in two patients who exhibited onset of abdominal distention over a few weeks, rather than the more acute presentation that we currently refer to as Ogilvie's syndrome. Ironically, by today's criteria, neither patient would be categorized as having ACPO. Both patients were ultimately found to have widespread intraabdominal malignancy with retroperitoneal involvement of nerve plexuses, leading Ogilvie to speculate that disruption of the autonomic innervation of the colon was the underlying cause of the disorder.

Despite the wide variety of possible triggers for ACPO, the presentation is remarkably consistent. Generally, patients develop severe abdominal distention within 5 days of the onset of the medical or surgical insult. The intestinal dilation is usually most pronounced in the colon, especially proximal to the splenic flexure. On x-ray examination, the appearance is very similar to that of a patient who actually has an obstruction near the upper left colon/splenic flexure, leading to the term pseudo-obstruction . These facts led to the hypothesis that the final common pathway of the development of the disease is an acute cessation of effective colonic motility resulting from a disruption of the autonomic supply of the left side of the colon. One hypothesis was that excess sympathetic stimulation of the colon was inhibiting contraction. This hypothesis seemed to be supported by the observation that ACPO can occur in any sort of severe physical stress. In addition, epidural anesthesia to decrease sympathetic output has been reported to be beneficial for ACPO. However, when guanethidine was used to block sympathetic tone, there was very little effect on colonic function in patients with ACPO.

The leading current theory about the pathogenesis of ACPO is that a decrease in parasympathetic stimulation of the colon is more important than an excess of sympathetic input. In the study of guanethidine mentioned previously, patients were first given guanethidine and then treated with neostigmine to block acetylcholinesterase. Patients had a prompt return of colonic function only after receiving the neostigmine, leading to the idea that a loss of parasympathetic tone is important in the development of ACPO. Some authors speculate that the parasympathetic deficiency is most pronounced in the left colon because of disruption of supply from the sacral plexus; this may explain why the left colon is contracted and aperistaltic in ACPO. Since these pioneering studies, the one medical treatment that has had the most consistent success in treatment of ACPO has been the use of neostigmine to cause a sudden increase in acetylcholine concentration at parasympathetic nerve synapses and an increase in colon peristalsis. However, there are other complex mechanisms that are thought to contribute to ACPO, including changes in nitric oxide release, stimulation of opioid receptors on the bowel wall, reflex inhibition of colonic motility caused by stretch-sensitive mechanoreceptors in the gut wall once severe dilation has occurred, etc.

Other factors that likely contribute to the pathogenesis of ACPO are chronic underlying bowel motility disorders and constipation, patient immobility, electrolyte imbalance, medications such as narcotics, and mechanical ventilation. These other factors may worsen the autonomic imbalance, directly suppress muscular function of the colon, or simply increase the amount of gas that is entering the digestive tract, as occurs with mechanical ventilation. At least 50% of patients with ACPO have significant electrolyte abnormalities, especially low potassium, magnesium, and calcium. Secretory diarrhea (with high potassium and low sodium concentration in the stool) can occur in ACPO. This is thought to be due to the effects of autonomic nervous system disturbance and colonic distension on the activity of the apical (BK) potassium channels in the colonic mucosa.

The most feared complication of ACPO is colon perforation. When perforation occurs, it is usually in the right colon, especially the cecum. This relates to the high wall tension in the cecum leading to ischemic necrosis and wall disruption. The right side of the colon, which naturally has a thinner wall and a larger diameter than the left side, has the highest wall tension when the colon is distended. This occurrence is described well by Laplace's law: T = P × R/2d, where T is wall tension, P is pressure in colon lumen, R is radius of the colon, and d is the thickness of the colonic wall. This equation helps explain how small changes in colonic radius in the setting of severe distention of the thin-walled cecum can lead to relatively large changes in wall tension and increase the risk of perforation.

Usually the perforation risk is not very high in patients with a cecal diameter of less than 12 cm. Nonetheless, studies have shown that patients with ACPO and a cecal diameter greater than 25 cm can recover without incident, and that this may also occur in patients with prior or chronic dilation. Other variables, such as elasticity of the muscle wall, adequacy of blood supply, and time course of distention, must be important as well in determining whether the colon remains viable. Some studies indicate an association between the duration of ACPO and perforation risk, and indicate that patients with persistence of distention for more than 5 days have higher perforation rates.