AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Toxic megacolon is the clinical term for an acute toxic colitis with dilatation of the colon. The dilatation can be either total or segmental. A more contemporary term for toxic megacolon is simply toxic colitis, because patients may develop toxicity without megacolon. For purposes of this article, the term toxic megacolon is used, but either toxicity or megacolon can occur exclusively of each other.

The hallmarks of toxic megacolon, a potentially lethal condition, are nonobstructive colonic dilatation larger than 6 cm and signs of systemic toxicity. Toxic megacolon was recognized in 1950 by Marschak et al. Jalan et al described the diagnostic criteria. The first criterion is radiographic evidence of colonic dilatation. The second criterion is any 3 of the following: fever (>101.5°F), tachycardia (>120), leukocytosis (>10.5), or anemia. The third criterion is any 1 of the following: dehydration, altered mental status, electrolyte abnormality, or hypotension.

Toxic megacolon was first thought to be a complication of ulcerative colitis. In fact, toxic megacolon may complicate any number of colitides, including inflammatory, ischemic, infectious, radiation, and pseudomembranous. The incidence of toxic megacolon is expected to increase due to the rising prevalence of pseudomembranous colitis. Colonic dilatation may be present in other conditions, such as Hirschsprung disease, idiopathic megacolon/chronic constipation, and intestinal pseudoobstruction (Ogilvie syndrome). However, these patients do not develop signs of systemic toxicity and, therefore, do not fall into the category of having toxic megacolon.

Pathophysiology

Although the precise pathophysiology of toxic megacolon is unproven, several factors may contribute to its development and precipitation. Signs and symptoms of acute colitis may be present for as long as a week before dilatation develops.

Often, triggering or predisposing factors can be identified. While the risk of toxic megacolon increases with the severity of colitis, rapid tapering or abrupt discontinuation of medications such as steroids, sulfasalazine, and 5-aminosalicylic acid may precipitate toxemia and dilatation. Medications that negatively impact bowel motility also are implicated in the development of toxic megacolon. These include, but are not limited to, anticholinergics, antidepressants, loperamide, and opioids. Procedures such as barium enema or colonoscopy may cause distension, may impair blood supply, or may exacerbate a microperforation and cause subsequent toxemia.

In cases of uncomplicated colitis, the inflammatory response is confined to the mucosa. The microscopic hallmark of toxic megacolon is inflammation extending beyond the mucosa into the smooth-muscle layers and serosa. Myenteric plexus involvement is not consistent and probably does not contribute to dilatation.

As inflammation progresses into the smooth-muscle layers of the colon, nitric oxide appears to be involved in the pathogenesis of toxic megacolon. Nitric oxide inhibits smooth-muscle tone and is generated by inflammatory cells such as neutrophils and macrophages in the inflamed portions of the colon. Studies performed by Mourelle et al. have shown increased amounts of inducible nitric oxide synthetase in the muscularis propria of patients with toxic megacolon. Inflammation and up-regulated nitric oxide synthetase are thought to increase local nitric oxide, which inhibits colonic smooth muscle and causes dilatation.

Frequency

International

The incidence cited in the literature of toxic megacolon depends on the etiology. The lifetime risk of toxic megacolon in ulcerative colitis has been estimated to be 1-2.5%. In one series of 1936 patients admitted to the hospital over a 19-year period, toxic megacolon was present in 6% of patients, specifically 10% of ulcerative colitis admissions and 2.3% of Crohn disease admissions. Toxic megacolon occurs in approximately 5% of severe attacks of ulcerative colitis. In pseudomembranous colitis, toxic megacolon is reported to occur in 0.4-3% of patients. This number is expected to increase in proportion to the increasing prevalence of pseudomembranous colitis. This increasing prevalence is felt to be due to increased use of broad-spectrum antibiotics.

Mortality/Morbidity

Mortality rates for toxic megacolon have improved substantially over the past few decades, from 20% in 1976 to 4-5% currently. The decrease is a result of earlier recognition, intensive medical management, early surgical consultation, and improved surgical technique and postoperative care.

Race

In the United States, Jewish people are more prone to ulcerative colitis than people who are not Jewish. In Israel, Ashkenazi Jewish people have a higher incidence of ulcerative colitis than Sephardic Jewish people. No data exist regarding race and the incidence of toxic megacolon.

Sex

Regarding ulcerative colitis, most studies demonstrate that both sexes are affected equally.

Age

Regarding ulcerative colitis, young adults (aged 20-40 y) primarily are affected, but it may present at any age. With toxic megacolon, no predilection appears to exist for any particular age group. All ages may be affected. Many individuals present with toxic megacolon during their first flare. The mean duration of disease has been reported to be 3-5 years.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Patients typically have signs and symptoms of acute colitis that may be refractory to treatment. Common complaints include diarrhea, abdominal pain, rectal bleeding, tenesmus, vomiting, and fever. The patient may already have a diagnosis of inflammatory bowel disease or another cause of colitis (see Causes). In some patients, toxic megacolon may be the initial presentation of inflammatory bowel disease.
• A careful history may reveal recent travel, antibiotic use, chemotherapy, or immunosuppression. Patients usually are very ill, with the toxic definition including some or all of the following symptoms:
• • High fever
  • Abdominal pain and tenderness
  • Tachycardia
  • Dehydration
• The diagnostic criteria developed by Jalan et al may be helpful to guide the history. They are as follows:
• • Radiographic evidence colonic dilatation (classic finding is > 6 cm in the transverse colon)
  • Three of the following - Fever (>101.5°F), tachycardia (>120), leukocytosis (>10.5), or anemia
  • One of the following - Dehydration, altered mental status, electrolyte abnormality, or hypotension

Physical

• Vital signs generally reveal tachycardia and fever. If severe, the patient may be hypotensive or tachypneic.
• In inflammatory colitides (ie, ulcerative colitis, Crohn colitis), physical findings may be minimal because high-dose steroids routinely are used; however, the abdomen maybe distended, and bowel sounds usually are decreased.
• With toxemia, patients may be obtunded.
• The presence of an increased white blood cell count also contributes to the diagnosis of toxic megacolon. While most believe that the absence of a high white blood cell count makes defining the disease as toxic megacolon difficult, an abnormally low, or even a white blood cell count that is within normal limits, does not rule out toxic megacolon.
• Peritoneal signs may indicate perforation. They include the following:
• • Rebound
  • Rigidity
  • Peritoneal irritation
• The form of megacolon usually associated with ulcerative colitis is defined by a transverse colon that is 6 cm or more in diameter, with loss of haustration.
• The signs of perforation may be masked by high-dose steroids, as in inflammatory bowel disease.

Causes

• The classic etiologies of toxic megacolon include the following inflammatory causes:
• • Ulcerative colitis
  • Crohn colitis
  • Pseudomembranous colitis
• The many causes of infectious colitis, including the following, may lead to toxic megacolon:
• • Salmonella species
  • Shigella species
  • Campylobacter species
  • Yersinia species
  • Clostridium difficile
  • Entamoeba histolytica
  • Cytomegalovirus
• Toxic megacolon also may be caused by the following:
• • Radiation colitis
  • Ischemic colitis
  • Nonspecific colitis secondary to chemotherapy

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• CBC count
• • Patients may develop leukocytosis with a left shift.
  • Additionally, bloody diarrhea results in anemia.
  • In immunosuppressed or extremely toxic patients, the white count actually may be normal or low.
• Chemistry panel
• • Electrolyte disturbances are very common secondary to inflammatory diarrhea, steroid use, and ongoing GI losses.
  • The inflamed colon is unable to reabsorb salt and water.
• Nutritional and coagulation panel
• • A coagulation panel should be ordered in the event that surgery is required.
  • A nutrition panel, in accordance with the physician's practice, is helpful to determine treatment (eg, albumin vs prealbumin) and to assess nutritional status.
• Other
• • Erythrocyte sedimentation rate and C-reactive protein usually are elevated.
  • While these findings may support the diagnosis, they are not specific.

Imaging Studies

• Plain abdominal radiographs are essential for the diagnosis and management of toxic megacolon. Repeated abdominal plain films are necessary to evaluate the efficacy and progress of treatment.
• Radiographic findings include the following:
• • Dilated (>6 cm) transverse colon
  • Loss of colonic haustrations, possible "thumbprinting"
  • Presence of intraluminal soft-tissue masses, ie, pseudopolyps
  • Free intraperitoneal air - Possible finding, best seen on upright chest x-ray or left lateral decubitus abdominal film
• Comparison with old baseline films, if available, is helpful.
• Avoid barium studies in a patient who is severely toxic. The potential for perforation is considerable.
• A CT should probably be obtained in patients for whom the diagnosis of toxic megacolon is considered. A CT scan may identify a local or contained perforation. If the diagnosis remains unclear or the cause of toxicity is thought to be an abscess, a CT scan may be helpful. There is little literature on the role of CT scan in toxic megacolon, but further studies may help further define its role in diagnosis and prognosis.

Procedures

• If the diagnosis is in doubt and the patient is not toxic or unstable, endoscopy may be attempted by appropriately trained personnel.
• • Endoscopy may take the form of flexible sigmoidoscopy or colonoscopy. If clinical concern of toxic megacolon exists, the examination should not progress beyond sigmoidoscopy, if at all. The scope should only be advanced as far as is needed for diagnosis. Air insufflation should be a minimal. According to some experts, colonoscopy generally is justified only if the patient has no or minimal inflammation of the sigmoid or rectum.
  • Perforation is an obvious potential complication with this approach.

Histologic Findings

Pathology demonstrates acute inflammation involving all layers of the colon. Variable amounts of necrosis and degeneration are present. Infiltration by inflammatory cells (neutrophils, macrophages, and lymphocytes) is noted. The myenteric and submucosal plexi usually are preserved.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Treatment of toxic colitis includes 3 main goals: (1) reduce colonic distension to prevent perforation, (2) correct fluid and electrolyte disturbances, and (3) treat toxemia and precipitating factors. Careful and frequent monitoring of the patient is required, and, initially, complete blood counts, electrolytes, and abdominal radiographs should be checked every 12 hours.

• During the initial resuscitation, fluid replacement, electrolyte repletion, and transfusion should be aggressive. Broad-spectrum intravenous antibiotics with coverage equivalent to ampicillin, gentamicin, and metronidazole should be initiated. All medications that may affect colonic motility must be stopped. These include narcotics, antidiarrheals, and anticholinergic agents. The patient should be put on bowel rest, and a nasogastric tube or long intestinal tube should be placed to assist with GI decompression. Long suction tubes may be more helpful for colonic decompression but should be placed under fluoroscopic guidance into the ileum.
• The patient should be started on intravenous steroids. Intravenous hydrocortisone is necessary for patients who are taking corticosteroids or who have been treated with corticosteroids recently.
• Importantly, recognize that, while symptomatic improvement may correspond to improvement in the disease process, this is not always the case. Cessation of bowel movements may indicate worsening of the patient's condition. Including repeated abdominal plain films in the evaluation of the clinical picture remains essential.
• Any possible triggers should be stopped, including narcotics, antidiarrheals, and anticholinergics. Rolling techniques (knee-elbow and prone) may be performed to assist in redistribution of colonic gas and decompression.
• If the patient is malnourished, consider parenteral nutrition.
• Some reports indicate that cyclosporin A may be beneficial in the treatment of severe ulcerative colitis or toxic megacolon. Data suggest that cyclosporin may provide an initial response rate of as high as 80%. After a variable follow-up period, the durable response rate decreases to approximately 40%. Cyclosporin does have significant adverse effects, including immunosuppression and opportunistic infections, hypertension, renal toxicity, and neurological complications. Although further studies are needed, cyclosporin therapy may obviate the need for an urgent colectomy such that an elective subtotal colectomy or proctocolectomy may be performed under more controlled circumstances.
• Some experimental therapies under study may help patients with toxic megacolon to avoid surgery. A recent case report showed that the use of infliximab, an anti-TNF-alpha monoclonal antibody, was successful in the treatment of toxic megacolon in a patient who failed to respond to usual treatment and refused surgery.
• Leukocytapheresis (LCAP) has been reported in the treatment of toxic megacolon. A series of 6 patients were enrolled in this study. All patients had failed to improve after treatment with antibiotics and high-dose steroids. In 4 cases, their toxic megacolon resolved by the morning after initiation of treatment with LCAP. In 2 patients, their megacolon resolved approximately 40 hours later. Improvement continued in 4 of the 6 patients.
• Hyperbaric oxygen has also been reported to be of use in the treatment of toxic megacolon. Further studies are needed to confirm these results.

Surgical Care

Early surgical consultation is essential. Indications for urgent operative intervention include free perforation, massive hemorrhage (6-8 U packed red cells), increasing toxicity, and progression of colonic dilatation. Most authors recommend colectomy if persistent dilatation is present or if no improvement is observed on maximal medical therapy after 24-72 hours. The rationale for early intervention is based on a 5-fold increase in mortality after free perforation. Some physicians provide up to 7 days of medical therapy if the patient demonstrates clinical improvement despite persistent colonic dilatation. The authors recommend a strategy of early surgical intervention to minimize the incidence of colonic perforation.

• If no improvement occurs over 48-72 hours with medical therapy, perform surgical resection.
• • This strategy minimizes the incidence of colonic perforation. Perforation increases the chances of mortality from toxic megacolon by 5-fold.
  • Whether to perform a total proctocolectomy or subtotal colectomy with the rectum left behind is debated. The preference in the literature is to perform a subtotal colectomy because (1) the patient usually is very ill and not lengthening the operation is prudent if at all possible, (2) it preserves the possibility for an ileal pouch anal anastomosis, and (3) approximately 50% of patients with Crohn disease have minimal involvement of the rectum. Performance of a total proctocolectomy in a patient who is acutely ill and toxic and on high-dose steroids would increase the risk of complications, morbidity, and likely mortality.
  • Terminate the resection at the sacral promontory, and perform either a mucus fistula or a stapled rectal stump. If the latter is performed, keeping a rectal tube in place for 2-3 days may reduce the incidence of rectal stump blowout.

Consultations

• Consultation with a gastroenterologist and surgeon is required.
• Depending on the health care setting, other consultations that may be needed include a nutritionist and an infectious disease specialist.

Diet

• Patients with toxic megacolon should be at complete bowel rest.
• Parenteral nutrition should be considered in patients with toxic megacolon.

Activity

• Patients with toxic megacolon should primarily be at bed rest. As previously mentioned, position changes, such as the prone position and the knee-elbow position, should be used to aid in colonic gas redistribution.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Start the patient on antibiotics to cover the colonic bacterial flora. Any number of antibiotics that primarily cover gram-negative and anaerobic bacteria can be administered. Also begin administration of steroids. Either hydrocortisone 100 mg IV piggy-back (IVPB) q6h or methylprednisolone 60 mg IVPB q24h is acceptable. The latter has greater relative anti-inflammatory potency and less relative mineralocorticoid potency.

Drug Category: Corticosteroids

Have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

Drug Category: Immunosuppressant agents

These agents inhibit immune reactions resulting from diverse stimuli.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Complications

• The complication one must constantly be alert for is perforation, even in the absence of colonic dilatation.
• Numerous studies have demonstrated that classic physical signs of peritonitis were absent in the majority of patients with free perforation, possibly because of the effects of steroids.

Prognosis

• The survival prognosis should be excellent in the absence of perforation. If perforation occurs, the mortality is approximately 20%.
• In the case of ulcerative colitis, a proctocolectomy cures patients of the disease.
• In the case of Crohn disease, proctocolectomy does not necessarily cure the patient because Crohn disease can occur in any portion of the GI tract.

Patient Education

• Educating the patient about toxic megacolon is crucial.
• First, educate the patient about the disease and the causes of the disease.
• • The most common cause of toxic megacolon is inflammatory bowel disease. However, with the rising incidence of C difficile, pseudomembranous colitis must always be considered, even in patients with inflammatory bowel disease.
  • Educate the patient about ulcerative colitis, Crohn disease, and indeterminate colitis.
  • The patient should be clearly informed that, if an operation is required for this acute problem, an ostomy likely will be the procedure needed, regardless of the cause.
• Secondly, educate the patient about the operation.
• • Patients require at least a temporary, and possibly a permanent, ostomy.
  • Most patients require a thoughtful compassionate discussion regarding this aspect. Psychological aspects of dealing with an ostomy can be extremely difficult.
• Finally, educate patients so they understand that this disease is a process that may require several months to overcome if an operation is needed and that a 2-stage or 3-stage procedure usually is required.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Communicating with the patient and patient's family at all times is imperative. This disease can be fatal, and clear lines of communication are essential.
• Because the surgical treatment for this disease requires an ostomy, the patient must give clear informed consent. In addition, discussing the implications of an ostomy with the patient and the patient's family is helpful. Also, telling the patient that that surgical treatment may be staged such that reoperation is required in the future is important.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Actis GC, Ottobrelli A, Pera A, et al. Continuously infused cyclosporine at low dose is sufficient to avoid emergency colectomy in acute attacks of ulcerative colitis without the need for high-dose steroids. J Clin Gastroenterol. Jul 1993;17(1):10-3. [Medline].
• Bartlett JG, Perl TM. The new Clostridium difficile--what does it mean?. N Engl J Med. Dec 8 2005;353(23):2503-5.
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• Greenstein AJ, Sachar DB, Gibas A. Outcome of toxic dilatation in ulcerative and Crohn''s colitis. J Clin Gastroenterol. Apr 1985;7(2):137-43. [Medline].
• Guslandi M. Nitric oxide and inflammatory bowel diseases. Eur J Clin Invest. Nov 1998;28(11):904-7.
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• Mourelle M, Vilaseca J, Guarner F, et al. Toxic dilatation of colon in a rat model of colitis is linked to an inducible form of nitric oxide synthase. Am J Physiol. Mar 1996;270(3 Pt 1):G425-30. [Medline].
• Panos MZ, Wood MJ, Asquith P. Toxic megacolon: the knee-elbow position relieves bowel distension. Gut. Dec 1993;34(12):1726-7.
• Present DH. Toxic megacolon. Med Clin North Am. Sep 1993;77(5):1129-48.
• Present DH, Wolfson D, Gelernt IM, et al. Medical decompression of toxic megacolon by "rolling". A new technique of decompression with favorable long-term follow-up. J Clin Gastroenterol. Oct 1988;10(5):485-90.
• Roy MA. Inflammatory bowel disease. Surg Clin North Am. Dec 1997;77(6):1419-31.
• Sawada K, Egashira A, Ohnishi K. Leukocytapheresis (LCAP) for management of fulminant ulcerative colitis with toxic megacolon. Digestive Diseases and Sciences. 2005;50:767-773.
• Sheth SG, LaMont JT. Toxic megacolon. Lancet. Feb 14 1998;351(9101):509-13.
• Shimada Y, Iiai T, Okamoto H. Toxic megacolon associated with cytomegalovirus infection in ulcerative colitis. J Gastroenterol. 2003;38(11):1107-8. [Medline].
• Sriram PV, Reddy KS, Rao GV. Infliximab in the treatment of ulcerative colitis with toxic megacolon. Indian J Gastroenterol. Jan-Feb 2004;23(1):22-3.
• Weissleder, R, Rieumont MJ, Wittenberg J. Primer of Diagnostic Imaging. St. Louis, Mo: Mosby; 1997:. 192.
• Wodzinski MA, Snowden JA, Reilly JT. Toxic megacolon complicating chemotherapy for acute myeloid leukaemia. Postgrad Med J. Dec 1994;70(830):921-3.

Article Last Updated: Jul 5, 2006