Toxic Megacolon

Toxic megacolon is a life-threatening condition characterized by nonobstructive segmental or pancolonic dilatation of at least 6 cm with systemic toxicity.[1] It was recognized by Marshak and Lester in 1950.[2] Although inflammatory bowel disease (IBD) is a common reason for toxic megacolon, other etiologies including infections, inflammation, bowel ischemia, radiation, and certain medications can lead to the development of this condition.[3, 4, 5] See the following images.

It is important to differentiate toxic megacolon from other conditions that present with megacolon without systemic toxicity such as Hirschsprung disease,[6] idiopathic megacolon/chronic constipation, chronic long-standing constipation of any etiology, and intestinal pseudo-obstruction (Ogilvie syndrome).[1]  Patients with these conditions do not develop signs of systemic toxicity and, therefore, do not fall into the category of having toxic megacolon (see the image below). (See also Etiology, Presentation, and Workup.)

Although the precise pathophysiology of toxic megacolon is unproven, several factors may contribute to its development and precipitation. 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 muscularis propria. Whereas the typical ulcerative colitis inflammatory response is limited to the mucosa, toxic megacolon is characterized by severe inflammation extending into the smooth muscle layer, thus paralyzing the colonic smooth muscle and leading to dilatation. The extent of dilatation seems to be correlated with the depth of inflammation and ulceration.[1]

Studies by Mourelle et al showed significantly increased amounts of inducible nitric oxide (NO) synthetase in the muscularis propria of patients with toxic megacolon, particularly in the more dilated colonic segments.[7, 8, 9]

As inflammation progresses into the smooth-muscle layers of the colon, NO and local inflammatory modulators appear to be involved in toxic megacolon pathogenesis. Neutrophils invade the muscle layer in toxic megacolon and directly damage the myocytes by the release of proteolytic enzymes, cytokines, and leukotriene B4. Systemic uptake of cytokines and other inflammatory mediators leads to fever, tachycardia, hypotension, and other signs of systemic toxicity. NO is generated by macrophages and smooth muscles cells in the inflamed portions of the colon, inhibiting smooth muscle tone and leading to colonic dilatation.[1]

These findings were supported by the idea that, in animal models, giving dexamethasone and/or decontaminating the bowel with broad-spectrum antibiotics led to decreased NO levels and improvement in colonic dilatation.[8] According to a study by Schworer et al, patients with toxic megacolon were successfully treated with NO synthase inhibitor.[10]

A number of other precipitating factors have been identified, including antimotility agents, opiates, anticholinergics, antidepressants, barium enemas, colonoscopies/bowel preparations, and immunotherapies.[5, 11, 12]

Myenteric plexus involvement is not consistent and likely does not contribute to colonic dilatation.

Inflammatory causes of toxic megacolon include the following:

• Ulcerative colitis[4, 13]

• Crohn colitis[14]

Infectious causes of toxic megacolon include the following:

• Salmonella species[15]

• Shigella species[16]

• Campylobacter species[17]

• Yersinia species

• Clostridium difficile[18, 19, 20]

• Entamoeba histolytica: About 3% of patients with amoebic infections develop severe colitis and a small percentage of these will have toxic megacolon; use of loperamide in this setting increases the risk of developing toxic megacolon[21]

• Cryptosporidium[22]

• Cytomegalovirus[23]

• Rotavirus[24]

• Invasive aspergillosis[25]

Other etiologies of toxic megacolon include the following:

• Radiation colitis

• Ischemic colitis

• Nonspecific colitis secondary to chemotherapy[11, 26, 27]

• (Rarely) As a complication of collagenous colitis[28, 29]

• Behçet syndrome: Rarely, affected patients can develop toxic megacolon as a complication[30, 31]

• Kaposi sarcoma[1]

• Methotrexate therapy[32]

Often, triggering or predisposing factors can be identified. Signs and symptoms of acute colitis may be present for as long as 1 week before dilatation develops. Although the risk of toxic megacolon increases with the severity of the 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 are also implicated in the development of toxic megacolon. These include, but are not limited to, anticholinergics, antidepressants, loperamide, atropine,[5] and opioids. Procedures such as barium enema or colonoscopy may cause distention, impair blood supply, or exacerbate a microperforation and cause subsequent toxemia.[12]

A retrospective study by Tschudin-Sutter et al indicated that the incidence of toxic megacolon is higher in pediatric patients with community–associated, rather than healthcare facility–associated, C difficile infection.[33] The study involved 202 pediatric patients with C difficile infection, including 38 with community–associated infection, 144 with healthcare facility–associated infection, and 20 with an indeterminate source of infection. Compared with the healthcare facility–associated group, children with a community–associated infection had a higher rate not only of toxic megacolon but also of toxic shock and recurrence. (They were less likely, however, to have comorbidities than were children with healthcare facility–associated infection.)[33]

There is a lack in literature regarding accurate reporting of toxic megacolon prevalence. The incidence rates can change based on the main etiology. The risk of developing toxic megacolon can increase with older age and/or the presence of other risk factors such as hypertension, neurologic disorders, coagulopathy, anemia, chronic pulmonary disease, congestive heart failure, and renal failure.[34, 35]

Doshi et al reported the results of an analysis of data collected from the Nationwide Inpatient Sample database from January 2010 through December 2014: The most common cause of hospital admissions was inflammatory bowel disease (IBD) (51.6%), followed by septicemia (10.2%) and intestinal infections (4.1%).[34, 36]

Three decades ago, the incidence of toxic megacolon in IBD patients was approximately 1-5%.[14] However, this rate has diminished due to early recognition and intensive medical management of severe colitis. Unfortunately, the data on the incidence of toxic megacolon in ulcerative colitis versus Crohn disease are contradicting; some studies show a higher incidence in patients with Crohn disease compared to those with ulcerative colitis (1-2.5% ulcerative colitis; 4.4-6.3% Crohn disease),[14] whereas others report the opposite.[4, 37]

The incidence of toxic megacolon in patients with C difficile colitis rapidly increased from 0.4% to 3% before 1990 to 4.3% after 1990, due to the rising use of broad spectrum antibiotics and the development of a hypervirulent Crohn disease strain.[4, 35, 37]

Toxic megacolon mortality is variable depending on the treatment modality. One study revealed that before 1976, there was a 27% mortality of toxic megacolon among patients treated medically and a 19% mortality in patients treated surgically.[38] In-hospital mortality for patients with toxic megacolon fell from 9.2% to 6.5%, according to an observational study for the period between 2010 and 2014.[35] Older age, hypertension, neurologic disorders, coagulopathy, anemia, chronic lung disease, heart failure, and renal failure were the main predictors of increased mortality.[35]

Colon perforation is associated with higher surgical mortality relative to undergoing surgery before colonic perforation.[34, 38]  Similarly, postoperative mortality in patients with C difficile infection and toxicity is lower when they undergo surgery before the development of septic shock compared to septic patients who have surgery.[39]

Fecal microbiota transplantation has shown promise as a salvage therapy for critically ill patients with C difficile infection and toxic megacolon in whom maximum medical therapy failed and who are not a surgical candidates.[40]

Mortality in patients with inflammatory bowel disease (IBD) and toxic megacolon have fallen in the last 3 decades due to multiple factors, including early recognition of toxic megacolon, early escalation from steroid treatment to biologics such as infliximab or cyclosporine, improved care in the intensive care unit (ICU), earlier surgical intervention, and optimal postoperative care.[41]

Note that C difficile infection in patients with IBD are associated with higher rates of colectomy and longer hospital stays compared to IBD patients without C difficile infection.[42]

Educating patients about toxic megacolon, is crucial. First, educate the patient about the causes of the disease, of which the most common is inflammatory bowel disease (IBD). However, with the rising incidence of C difficile infections, pseudomembranous colitis must always be considered, even in patients with IBD. Educate patients about ulcerative colitis, Crohn disease, and indeterminate colitis.

Also discuss with patients that medications such as corticosteroids, immunosuppressants, and/or immunomodulators may be administered to control the disease severity and that antibiotics may be used to prevent or treat infection. Inform patients of the potential risks and benefits of these agents as well as those that can exacerbate their condition (eg, opioids, antidepressants, nonsteroidal anti-inflammatories, antidiarrheals, anticholinergics.)

Secondly, clearly inform patients that if an operation is required for this acute problem, an ostomy likely will be the necessary procedure, regardless of the cause. Patients require at least a temporary and, possibly, a permanent ostomy. Provide a thoughtful, compassionate discussion regarding this aspect of their treatment: The psychological aspects of dealing with an ostomy can be extremely difficult.

Finally, educate patients so that they understand that this disease may require several months to overcome if an operation is needed and that a two- or three-stage procedure is usually required.

Patients with inflammatory bowel disease (IBD) are at a higher risk of developing toxic megacolon during the early stages of their disease; in some cases, it can be the first manifestation of the disease.[43, 44] Patients with Crohn colitis are more vulnerable than those with ulcerative colitis for developing toxic megacolon.[14]

Findings of ileus may indicate the severity of colitis in patients with C difficile infection.[45]

Patients with toxic megacolon 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. In a paper that studied the clinical presentation of pseudomembranous enterocolitis complicated with toxic megacolon, the presenting symptoms and signs included diarrhea (100%), malaise (91%), abdominal pain (82%), abdominal distention (82%), and abdominal tenderness (72%).[46] However, another study revealed that absence of diarrhea does not rule out the severity of the C difficile infections and the risk of developing toxic megacolon.[47]

A careful history may reveal recent travel, antibiotic use, chemotherapy, occupational exposure, or immunosuppression. Patients are usually very ill, and they can present with signs of fever, tachycardia, hypotension, and/or abdominal distention and tenderness.

The vital signs in a patient with toxic megacolon generally reveal tachycardia and fever. If the condition is severe, the patient may be hypotensive or tachypneic; patients may be obtunded.

In inflammatory colitides (ie, ulcerative colitis, Crohn colitis), physical findings may be minimal, because high-dose steroids are routinely administered; however, the abdomen may be distended, and the bowel sounds are usually hypoactive. Signs of perforation may also be masked by high-dose steroids.

Peritoneal signs may indicate perforation. They include the following:

• Rebound

• Rigidity

• Peritoneal irritation

In general, toxic megacolon should be suspected in patients presenting with abdominal pain with distention and acute-onset chronic diarrhea. The diagnosis is made based on the clinical picture of systemic toxicity along with evidence of colon dilatation more than 6 cm.[4]

The most common criteria used to diagnose toxic megacolon are the ones proposed by Jalan et al in 1969,[43] as follows:

• Radiographic evidence of colonic dilatation: The classic finding is a more than 6-cm dilatation in the transverse colon

• Any three of the following: Fever (>101.5°F [>38°C]), tachycardia (>120 beats/min), neutrophilic leukocytosis (>10.5 x 103/µL), or anemia

• Any of the following: Dehydration, altered mental status, electrolyte abnormality, or hypotension

Complete blood cell (CBC) count 

Patients with toxic megacolon may develop leukocytosis with a left shift. Patients can also present with leukemoid reaction. Additionally, bloody diarrhea results in anemia.

Although the presence of an increased white blood cell (WBC) count contributes to the diagnosis of toxic megacolon—and most investigators believe that the absence of a high WBC count makes defining a disease as toxic megacolon difficult—an abnormally low count, or even a WBC count that is within normal limits, does not rule out toxic megacolon. This is because in immunosuppressed or extremely toxic patients, the WBC count actually may be normal or low.

Chemistry panel

Electrolyte disturbances are very common in toxic megacolon secondary to inflammatory diarrhea, steroid use, and ongoing gastrointestinal losses. The inflamed colon is unable to reabsorb salt and water. Acid-base disorders have been described (eg, metabolic alkalosis) with the large volume loss.[48] Metabolic acidosis can occur with advanced disease and the development of bowel ischemia.

Nutrition and coagulation panels

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 in assessing the patient's nutritional status. Hypoalbuminemia is common at the later stages of the disease due to protein wasting, decreased hepatic production, and severe inflammation.

ESR and CRP

Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels are usually elevated. Although these findings are not specific to toxic megacolon, they may support the diagnosis.

Histology

Pathology in cases of toxic megacolon 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 plexuses are usually preserved.

Stool studies

Stool cultures, examination for ova and parasites (O&P), and as well as testing for C difficile toxin should be obtained.

Plain abdominal radiographs are essential for the diagnosis and management of toxic megacolon. Repeated serial abdominal plain films are necessary to monitor the progress of the disease and the efficacy of treatment.

Radiographic findings include the following:

• Air-fluid levels in the colon with an absent or abnormal haustral pattern

• Deep mucosal ulcerations and possible pseudopolyp projections into the colon lumen

• The presence of air in the small bowel on x-ray: Can be predictive of toxic megacolon[49]

• Segmental parietal thinning: Pathognomic for toxic megacolon[3]

Comparison with old baseline films, if available, is helpful. Avoid barium enema studies in a patient who is severely toxic; the potential for perforation is considerable.

The following image depicts a dilated (>6 cm) transverse colon.

Loss of colonic haustrations, possible "thumbprinting," is shown below

Severe dilatation and a featureless transverse and sigmoid colon are demonstrated in the following image.

Ultrasonography of the intestines appears to be a potential diagnostic test for toxic megacolon.[50]  In one study, investigators demonstrated similar findings in four cases, including the following:

• Complete loss of haustra coli of the colon

• Hypoechoic and thickened bowel walls with irregular internal margins in the sigmoid and descending colon

• Marked dilatation of the transverse colon (>6 cm), a finding that correlated well with the plain radiograph of the abdomen

• Hypoechoic and thin (< 2 mm) bowel walls without haustra coli in the dilated colon; in patients who underwent surgery, the postoperative pathohistologic findings of the bowel walls correlated with the ultrasonographic features observed before surgery

• Slight dilatation of ileal bowel loops (diameter >18 mm) with increased intraluminal gas and fluid

Computed tomography (CT) scanning should be obtained in patients in whom the diagnosis of toxic megacolon is being considered. This imaging modality may identify a local or contained perforation.[4] If the diagnosis remains unclear or the cause of toxicity is thought to be an abscess, CT scanning may be helpful.

Imbriaco and Balthazar found that CT scanning was more accurate than plain radiography in detecting severe colitis.[51] CT scans may show diffuse colonic wall thickening, thickened haustra with alternating bands of high and low density (‘‘accordion sign’’), a multilayered appearance caused by different densities of edematous submucosa, or hyperemic mucosa (‘‘target sign") and peri colic stranding. CT scanning was superior in showing the severity and length of colitis as well as the presence of dilatation.[51]

Endoscopy can provide a further advantage for evaluating the etiology of toxic megacolon such as identifying cytomegalovirus (CMV) or pseudomembranous colitis, especially when clinical suspicion exists despite negative stool studies for C difficile.

Endoscopy may take the form of flexible sigmoidoscopy or colonoscopy. However, if clinical concern for toxic megacolon exists, the examination should not progress beyond the sigmoid colon, if at all. The scope should be advanced only as far as necessary for diagnosis. Air insufflation should be minimal. Sigmoidoscopy can miss the diagnosis of CMV infection because the lesions can be localized in the cecum or ascending colon.[52]

According to some experts, colonoscopy is generally justified only if the patient has no or minimal inflammation of the sigmoid colon or rectum. Perforation is an obvious potential complication of this approach.[12]

The main goal of treatment for toxic megacolon is to control the severity of the colitis and to restore the colon function as soon as possible to avoid further complications, including colon perforation, dehydration, and electrolyte derangements. The initial plan and management should be coordinated between the medical and surgical teams.

Electrolyte abnormalities, especially hypokalemia as well as dehydration and anemia, must be addressed aggressively as they may exacerbate the colon dilatation. Cessation of medications that impact colonic motility, including opioids, anticholinergics, and antidiarrheals, is important.[4]

Bowel rest is recommended. Total parenteral nutrition (TPN) has not been shown to improve outcomes regarding reducing the need for surgery or decreasing hospital stay in patients with severe colitis secondary to ulcerative colitis.[53]  Placement of a nasogastric tube (NGT) is recommended to relieve upper gastrointestinaI distention, but it will not help with the colon dilatation. Some authors suggest repositioning the patient to decompress the colon by moving the air to the descending colon and rectum; these techniques include rolling maneuvers[54] and a prone knee-elbow position.[55]

Patients with severe colitis, especially those with a history of inflammatory bowel disease (IBD), carry higher risk for deep vein thrombosis (DVT); thus, DVT prophylaxis is recommended.

Broad-spectrum antibiotics are also recommended to decrease the risk of septic complications.

Enteral feeding should be started as soon as the patient shows clinical improvement to expedite mucosal healing and improve motility.

Inflammatory bowel disease (IBD)

Acute severe ulcerative colitis is defined as the presence of six or more bowel movements daily with at least one sign of systemic toxicity, including tachycardia, fever, anemia with hemoglobin less than 10.5 g/dL, or elevated inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Admission to the hospital for inpatient management is recommended for patients with acute severe ulcerative colitis.

Diagnostics

Stool studies are recommended, including testing for C difficile, for every patient admitted with acute severe ulcerative colitis. In one case series, up to 47% of hospitalized patients with ulcerative colitis were diagnosed with C difficile infection.[42]

Endoscopic evaluation can identify the severity of inflammation as well as establish the diagnosis at the patient's initial presentation; it can be used to obtain biopsies; and it can rule out cytomegalovirus (CMV) colitis.[56]

Complete colonoscopy can increase the risk of complications, especially perforation; therefore, limited sigmoidoscopy with minimal insufflation is appropriate for most patients. It has been found that patients with worse endoscopic scores have an increased likelihood of need for rescue therapy as well as increased need for colectomy compared to those who have a more favorable endoscopic scoring.[56]

CMV colitis can be found in up to one third of patients with acute severe ulcerative colitis refractory to steroid treatment.[57, 58] Risk factors for CMV colitis include severe medically refractory disease as well as receipt of steroid treatment and the presence of endoscopic ulceration (as CMV has preference for actively inflamed tissues).[59] Predictors of nonresponse to steroids are frequent bowel movements as well as elevated CRP and ESR, hypoalbuminemia, and colon dilatation.[56]

Pharmacotherapy

Sulfasalazine and 5-ASA have no role in treating acute severe ulcerative colitis or IBD-related toxic megacolon; these medications can only be started after the control of the severe acute disease.

Systemic intravenous (IV) steroids remain the mainstay of treatment for acute severe ulcerative colitis; treatment response to steroids should occur within 1 to 3 days. Dexamethasone had been shown to be effective in decreasing the expression of nitric oxide synthase.[8]  Either hydrocortisone 100 mg IV piggyback (IVPB) every 6 hours or methylprednisolone 60 mg IVPB every 24 hours is acceptable. Methylprednisolone is preferred due to its lower incidence of side effects (eg, sodium retention, potassium wasting) and its greater relative anti-inflammatory potency.

If a response to steroids is not seen, consider other rescue medical therapies, including infliximab or cyclosporine. In a study of 20 patients with severe ulcerative colitis without response to IV steroids, cyclosporine was superior to placebo in controlling the disease.[60]

The use of cyclosporine should be limited to patients not responding to steroids or are intolerant of these agents. Observational studies have confirmed the efficacy of infliximab in managing acute severe ulcerative colitis.[61, 62] In a randomized control trial that compared cyclosporine with infliximab in patients with acute severe ulcerative colitis resistant to intravenous steroids, the median time to response was similar between both groups, and there was no difference in the rate of mucosal healing or the need for surgery.[63] Therefore, the choice between cyclosporine and infliximab should be based on the provider's comfort level with using either drug. Patients whose condition fail to respond to immune modulators may not show improvement with cyclosporine; therefore infliximab may be a better option for these patients.[56]

Tacrolimus, a calcineurin inhibitor, has been also evaluated for the treatment of severe ulcerative colitis refractory to steroids. In one study, the clinical response was 50% with tacrolimus compared to 13% in the placebo group.[64]

Supportive care

While the patient is on medical therapy, daily assessment of their fluid balance and electrolytes as well as serial abdominal examinations should be pursued to rule out worsening of the disease and to monitor for complications such as perforation or an abscess.

Clostridium difficile colitis

Medical management is the initial recommended step in treating patients with severe fulminant C difficile colitis.

Initial medical management for severe C difficile infection is defined by a white blood cell (WBC) count above 15,000 cells/mL and/or a serum creatinine of at least 1.5 mg/dL; in this setting, vancomycin 125 mg orally 4 times a day for 10 days or fidaxomicin 200 mg orally twice a day for 10 days is recommended.[65]

Fulminant disease is defined by severe C difficile infection plus supportive data of hypotension, shock, ileus, or megacolon. It should be treated with vancomycin 500 mg orally or through a nasogastric (NG) tube and metronidazole 500 mg IV every 8 hours. If ileus is present, rectal vancomycin is recommended.[65]

Patients who have fulminant colitis that fails to respond to initial medical treatment should be considered as candidates for fecal transplantation. Studies have revealed that fecal transplantation is an effective treatment for critically ill patients with C difficile infection refractory to maximum medical therapy and who are not deemed to be surgical candidates.[40]

Additional therapies

Leukocytapheresis (LCAP) has been reported to be effective against toxic megacolon. In a series of six patients whose conditions failed to improve after treatment with antibiotics and high-dose steroids, toxic megacolon resolved in four patients by the morning after initiation of treatment with LCAP.[66] In the remaining two patients, toxic megacolon resolved approximately 40 hours later. Improvement continued in four of the six patients.[66]

Hyperbaric oxygen therapy has also been reported to be of use in the treatment of toxic,[67] but further studies are needed to confirm these results.

Shetler et al demonstrated that colonoscopic decompression and intracolonic vancomycin administration in the management of severe, acute, pseudomembranous colitis associated with ileus and toxic megacolon is feasible, safe, and effective in approximately 57-71% of these cases.[68]

IV immune globulin (IG) may potentially be a last-line adjunct therapy in patients with severe, complicated, refractory C difficile infection (eg, shock, ileus, megacolon), taking into account the possibility of adverse effects.[69]

Special patient populations

Patients infected with human immunodeficiency virus (HIV)

Careful management of HIV patients is recommended, with extensive work-up to rule out an infectious or inflammatory etiology for toxic megacolon. Early treatment for infections in HIV patients helps to lower mortality and morbidity in this subgroup of patients because the need for emergency laparotomy with subtotal colectomy and ileostomy is higher if treatment is delayed.[70, 71]

Pregnant women

It is always recommended that IBD be under remission before proceeding with pregnancy. If pregnant patients with ulcerative colitis develop severe fulminant colitis with toxic megacolon, high doses of IV steroids are recommended, and they are successful in 75% of the cases. Infliximab or urgent colectomy will be the solution for the remainder of gravid patients.[72, 73]

Inflammatory bowel disease (IBD)

The procedure of choice for urgent colectomy is subtotal colectomy with end ileostomy for both ulcerative colitis and Crohn disease.[37]

Absolute indications for surgery in patients with acute, severe ulcerative colitis include the development of the following[74] :

• Toxic megacolon
• Perforation
• Uncontrolled hematochezia
• Multiorgan failure

Surgery should be considered in cases of acute severe colitis that fail to respond to steroid therapy within 3 to 5 days of treatment initiation. Delays in surgery can be associated with increased postoperative morbidity.[75]

If possible, optimize the patient's nutrition status before colectomy because poor nutritional status is associated with increased mortality and morbidity. Indications of poor nutritional status include the following[76, 77] :

• Weight loss of more than 10-15% within 6 months
• Body mass index (BMI) below 18.5 kg/m²
• Albumin level less than 30 g/L

Clostridium difficile colitis

Indications for surgical intervention in patients with severe C difficile colitis include the following:

• Colon perforation
• Colon-wall full-thickness ischemia
• Necrosis
• Increased intra-abdominal pressure or abdominal compartment syndrome
• Signs of peritonitis
• End-organ failure

Relative indications for surgery are severe leukocytosis with a white blood cell (WBC) count over 50,000 cells/mL and serum lactate levels above 5 mmol/L.

If surgical management is necessary for severely ill patients, perform subtotal colectomy with preservation of the rectum. Another option is a diverting loop ileostomy with colonic lavage, which has been associated with lower morbidity and mortality.

Medications that may aid in controlling or treating toxic megacolon include corticosteroids, immunosuppressants, and/or immunomodulators. Antibiotics may be administered to prevent or treat infection.

Note that certain agents may exacerbate toxic megacolon, such as opioids, antidepressants, nonsteroidal anti-inflammatories, antidiarrheals, and anticholinergics.

Class Summary

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

Hydrocortisone (Solu-Cortef, Cortef)

Hydrocortisone decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

Methylprednisolone (A-Methapred, Depo-Medrol, Medrol, Solu-Medrol)

Methylprednisolone decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

Class Summary

Immunosuppressant agents inhibit immune reactions resulting from diverse stimuli.

Cyclosporine (Neoral, Gengraf, Sandimmune)

Cyclosporine is used in acute, severe ulcerative colitis that is refractory to IV corticosteroids. An 11-amino acid cyclic peptide and a natural product of fungi, it acts on T-cell replication and activity.

Cyclosporine is a specific modulator of T-cell function and an agent that depresses cell-mediated immune responses by inhibiting helper T-cell function. Preferential and reversible inhibition of T lymphocytes in the G0 or G1 phase of the cell cycle is suggested.

Cyclosporine binds to cyclophilin, an intracellular protein, which, in turn, prevents formation of interleukin-2 and the subsequent recruitment of activated T cells.

Cyclosporine has about 30% bioavailability, but there is marked interindividual variability. This agent specifically inhibits T-lymphocyte function, with minimal activity against B cells. Maximum suppression of T-lymphocyte proliferation requires that the drug be present during the first 24 hours of antigenic exposure.

Cyclosporine suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions (eg, delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, graft-vs-host disease) for a variety of organs.

Class Summary

Immunomodulatory agents regulate immune reactions that are responsible for inflammation.

Infliximab (Remicade)

Infliximab neutralizes the cytokine TNF-alpha and inhibits its binding to the TNF-alpha receptor. Mix in 250 mL normal saline for infusion over 2 hours. It must be used with a low-protein-binding filter (1.2 µm or less).