Toxic Megacolon: Background, Pathophysiology, Management Challenges and Solutions

Figures & data

Table 1 Different Medication Use for the Treatment of Toxic Megacolon

Medication	Indications	Mechanism of Action/Dosages	Therapeutic Benefits/Risks/Complications
Sulfasalazine/5-ASA compounds	-In IBD related Toxic megacolon not as first line, after attack resolves	-Anti-inflammatory effects	-No enough data supporting beneficial use in IBD related toxic megacolon, it can be used after initial attack resolves
Glucocorticoids	-First-line therapy for all patients with IBD-related toxic megacolon	-Decreases diameter of colon by reducing nitrous oxide synthetase	-Not associated with risk of colonic perforation
	-Methylprednisolone due to its lower sodium retaining and potassium wasting properties, while other clinicians prefer prednisolone since the parenteral dose is equal to the oral dose	-Hydrocortisone 100 mg IV every 6 to 8 hours -Methylprednisone 60 mg daily for 5 days^Citation37,Citation38
Cyclosporine	If no response to Glucocorticoids within 3 days	-Inhibits T-lymphocyte function that is essential for the propagation of inflammation	-Cyclosporine should be reserved for those who cannot tolerate infliximab and there is only evidence for its effectiveness in ulcerative colitis, not Crohn’s disease
		-Rapid response 4 mg/kg per day; 82% with clinical improvement with possibility of avoiding colectomy^Citation39	-Cyclosporine better to be avoided in elderly patients with significant co-morbid conditions as well as patients in whom colectomy is likely to be necessary in near future
Infliximab	If no response to Glucocorticoids within 3 days	-Blocks the action of TNF-α by preventing it from binding to its receptor in the cell, but it also causes programmed cell death of TNF-α-expressing activated T lymphocytes that mediate inflammation -Infliximab 5 mg/kg (2 or 3 infusions)^Citation40	-Effective as rescue therapy for severe steroid refractory colitis in up to 70% of instancing -Clinical response usually occurs within 3 to 7 days of treatment - Infliximab also appears to induce a long-term remission comparable to that seen with cyclosporine

Table 2 Different Surgical Intervention for the Management of Toxic Megacolon

Surgical Intervention Indications
- Failure to respond to one of the second-line agents (infliximab or cyclosporine) for three days.
- Toxic megacolon while on either infliximab or cyclosporine should undergo surgery right away
- Patients with colonic perforation, abdominal compartment syndrome, full thickness colonic wall ischemia, worsening clinical status despite proper medical management, Leukocytosis >50,000 cell/mL and serum lactate level of >5 mmol/L are relative indications for surgery.
-Early surgical intervention before colonic perforation has a lower mortality rates compared to colectomy after perforation (8 versus 40 percent)^Citation9
Surgical Intervention	Description
Subtotal colectomy with end-ileostomy	Urgent surgery of choice for toxic megacolon secondary to either Crohn’s disease or Ulcerative colitis.^Citation6
	- Compared to single stage proctocolectomy, it has lower mortality (9%) with possibility of anastomosis subsequently in most patients
	- Common complications include small bowel obstruction (20%), wound infection (18%) and intraabdominal abscess (17%).
Total abdominal colectomy	Recommended procedure for patients with perforated colon, abdominal compartment syndrome or colonic necrosis.
Partial or segmental colectomy	No longer performed due to a higher mortality and reoperation rate.
Diverting loop ileostomy/colonic lavage	An alternative surgical intervention that has been associated low mortality in some studies.^Citation43

Table 3 Key Points to Keep in Mind when managing Toxic Megacolon

Key points of the Review Article:
1. Toxic megacolon (TM) was thought to be a complication for ulcerative colitis (UC) specifically. Later on, the Crohn’s disease (CD) was found to be a cause, and gradually it becomes evident that any inflammatory condition of the colon could predispose to TM.
2. Accurate history and physical examination, plain radiographs of the abdomen, sigmoidoscopy and, most important of all, awareness of the condition facilitate diagnosis in most cases.
3. The most common cause of hospital admission included Inflammatory bowel disease (IBD) (51.6%), followed by septicemia (10.2%) and intestinal infections (4.1%).
4. Computed tomography of the abdomen with contrast is usually performed to establish the diagnosis and also evaluating for complications that may require immediate surgery. Baseline and serial abdominal x rays are then performed to follow the progression of colonic dilatation.
5. Patients should be admitted and evaluated, preferably in the intensive care unit, with frequent examinations to assess for signs of toxicity.
6. Both medical and surgical teams should co-manage patients on admission with daily evaluation.
7. Female gender, age more than 40 years, hypoalbuminemia, acidosis, and high blood urea nitrogen levels are associated with high mortality in a previous study. This patient population requires a special attention from the admission.
8. It is important to examine the abdomen for hepatic dullness every day in patients who have severe colitis and are taking high-dose glucocorticoids because they might have a free perforation and not have classic signs of peritonitis.
9. The main goal for treatment for TM is to treat the underlying inflammation, restoring colonic motility, and preventing free colonic perforation.
10. In HIV infection patients with TM, an aggressive search for infectious and noninfectious causes is essential, including early limited endoscopy and imaging studies. Patients with cytomegalovirus (CMV) colitis or C. difficile infection respond poorly to medical therapy and often require emergent subtotal colectomy and ileostomy.
11. Women with known risk factors for toxic megacolon (most commonly ulcerative colitis) should plan conception during a state of remission.

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