Approach Considerations
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.
Medical Care
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]
Surgical Care
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] :
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Toxic megacolon
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Perforation
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Uncontrolled hematochezia
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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] :
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Weight loss of more than 10-15% within 6 months
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Body mass index (BMI) below 18.5 kg/m²
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Albumin level less than 30 g/L
Clostridium difficile colitis
Indications for surgical intervention in patients with severe C difficile colitis include the following:
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Colon perforation
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Colon-wall full-thickness ischemia
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Necrosis
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Increased intra-abdominal pressure or abdominal compartment syndrome
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Signs of peritonitis
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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.
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Toxic Megacolon. A 22-year-old man presented with abdominal pain, passage of blood and mucus per rectum, abdominal distention, fever, and disorientation. Findings from sigmoidoscopy confirmed ulcerative colitis. Abdominal radiographs obtained 2 days apart show mucosal edema and worsening of the distention in the transverse colon. The patient's clinical condition deteriorated over the next 36 hours despite steroid and antibiotic therapy, and the patient had to undergo a total colectomy and ileostomy.
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Toxic Megacolon. A 72-year-old woman presented with vomiting and abdominal distention. The supine (right) and erect (left) plain abdominal radiographs show gross dilatation of the colon with multiple air-fluid levels. On further questioning, the patient revealed that she was taking diuretics for hypertension. Blood biochemical tests revealed markedly lowered potassium levels. After potassium replacement therapy, the patient's pseudo-obstruction completely resolved.
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Toxic Megacolon. Gross pathology specimen from a case of pseudomembranous colitis demonstrating characteristic yellowish plaques.
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Toxic Megacolon. Computed tomography scan from a patient with pseudomembranous colitis demonstrating the classic accordion sign.
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Toxic Megacolon. Plain abdominal radiograph from a patient with known ulcerative colitis who presented with an acute exacerbation of his symptoms. This image shows thumbprinting in the region of the splenic flexure of the colon.
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Toxic Megacolon. Increased postrectal space is a known feature of ulcerative colitis.
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Toxic Megacolon. A 45-year-old woman presented with acute pain and colitis of uncertain etiology. The radiograph shows an increase in gaseous distention of the distal transverse colon, now measuring up to 80 mm in diameter (it was 60 mm 2 days previous). The transverse colon and sigmoid colon are both featureless, consistent with severe colitis. There is fecal loading in the right side of colon. No evidence of free gas or pneumatosis intestinalis is noted. The appearance is concerning for toxic megacolon. Courtesy of Craig Hacking, MBBS, Associate Professor, Royal Brisbane and Women’s Hospital (Radiopaedia.org, rID: 79194).
