Toxic megacolon is one of the most serious complications of severe colitis and, as such, is associated with high mortality and morbidity rates.[7]Autenrieth DM, Baumgart DC. Toxic megacolon. Inflamm Bowel Dis. 2012 Mar;18(3):584-91.
https://academic.oup.com/ibdjournal/article/18/3/584/4608027
http://www.ncbi.nlm.nih.gov/pubmed/22009735?tool=bestpractice.com
Mortality of toxic megacolon associated with pseudomembranous colitis was 31% to 35% between 1968 and 1992.[51]Trudel JL, Deschenes M, Mayrand S, et el. Toxic megacolon complicating pseudomembranous enterocolitis. Dis Colon Rectum. 1995 Oct;38(10):1033-8.
http://www.ncbi.nlm.nih.gov/pubmed/7555415?tool=bestpractice.com
Mortality rates associated with toxic colitis/toxic megacolon (TC/TM) have decreased in the last 30 years, likely secondary to improved intensive care management and a more aggressive surgical approach. While initial medical therapy of toxic megacolon is successful in up to 50% of patients, as many as 30% remain refractory to second-line medical management.[22]Sheth SG, LaMont JT. Toxic megacolon. Lancet. 1998 Feb 14;351(9101):509-13.
http://www.ncbi.nlm.nih.gov/pubmed/9482465?tool=bestpractice.com
[52]Grant CS, Dozois RR. Toxic megacolon: ultimate fate of patients after successful medical management. Am J Surg. 1984 Jan;147(1):106-10.
http://www.ncbi.nlm.nih.gov/pubmed/6691535?tool=bestpractice.com
At least half of the patients who initially respond to medical management will require colectomy within a few years.[52]Grant CS, Dozois RR. Toxic megacolon: ultimate fate of patients after successful medical management. Am J Surg. 1984 Jan;147(1):106-10.
http://www.ncbi.nlm.nih.gov/pubmed/6691535?tool=bestpractice.com
Mortality is higher in patients who require emergency surgery for complications of TC/TM: colectomy performed in patients with no colonic perforation carries a mortality rate of 2% to 13%, while colectomy in the face of perforation is associated with a mortality of over 40%.[22]Sheth SG, LaMont JT. Toxic megacolon. Lancet. 1998 Feb 14;351(9101):509-13.
http://www.ncbi.nlm.nih.gov/pubmed/9482465?tool=bestpractice.com
[53]D'Amico C, Vitale A, Angriman I, et al. Early surgery for the treatment of toxic megacolon. Digestion. 2005;72(2-3):146-9.
http://www.ncbi.nlm.nih.gov/pubmed/16172551?tool=bestpractice.com
Several studies have attempted to determine the variables associated with higher rates of morbidity and mortality. Most recent studies agree that the etiology of TC/TM most strongly affects the rates of morbidity and mortality, though other factors such as older age, presence of coagulopathy, renal failure, and comorbidities such as heart failure and chronic pulmonary disease are also associated with poor outcomes.[4]Ausch C, Madoff RD, Gnant M, et al. Aetiology and surgical management of toxic megacolon. Colorectal Dis. 2006 Mar;8(3):195-201.
http://www.ncbi.nlm.nih.gov/pubmed/16466559?tool=bestpractice.com
[8]Doshi R, Desai J, Shah Y, et al. Incidence, features, in-hospital outcomes and predictors of in-hospital mortality associated with toxic megacolon hospitalizations in the United States. Intern Emerg Med. 2018 Sep;13(6):881-7.
http://www.ncbi.nlm.nih.gov/pubmed/29948833?tool=bestpractice.com
[22]Sheth SG, LaMont JT. Toxic megacolon. Lancet. 1998 Feb 14;351(9101):509-13.
http://www.ncbi.nlm.nih.gov/pubmed/9482465?tool=bestpractice.com
Outcomes in pseudomembranous colitis
In the setting of Clostridium difficile, TC/TM has a reported mortality rate of 30% to 50%; surgical patients are at greatest risk of death.[51]Trudel JL, Deschenes M, Mayrand S, et el. Toxic megacolon complicating pseudomembranous enterocolitis. Dis Colon Rectum. 1995 Oct;38(10):1033-8.
http://www.ncbi.nlm.nih.gov/pubmed/7555415?tool=bestpractice.com
[54]Berman L, Carling T, Fitzgerald TN, et al. Defining surgical therapy for pseudomembranous colitis with toxic megacolon. J Clin Gastroenterol. 2008 May-Jun;42(5):476-80.
http://www.ncbi.nlm.nih.gov/pubmed/18277885?tool=bestpractice.com
[55]Perera AD, Akbari RP, Cowher MS, et al. Colectomy for fulminant Clostridium difficile colitis: predictors of mortality. Am Surg. 2010 Apr;76(4):418-21.
http://www.ncbi.nlm.nih.gov/pubmed/20420254?tool=bestpractice.com
Factors associated with severe disease and poor outcomes include the infecting strain of C difficile (the NAP/027/BI C difficile strain), the type of surgery performed, and the postoperative course (need for vasopressors, mechanical ventilation, and acute renal failure).[30]Kelly CR, Fischer M, Allegretti JR, et al. ACG clinical guidelines: prevention, diagnosis, and treatment of Clostridioides difficile infections. Am J Gastroenterol. 2021 Jun 1;116(6):1124-47.
https://journals.lww.com/ajg/Fulltext/2021/06000/ACG_Clinical_Guidelines__Prevention,_Diagnosis,.12.aspx
http://www.ncbi.nlm.nih.gov/pubmed/34003176?tool=bestpractice.com
Parameters associated with need for emergent colectomy or mortality in C difficile-associated TC/TM include: age >65 years, peritonitis on presentation, abdominal distention, end-organ failure, systolic blood pressure <90, heart rate >100, need for vasopressors, white blood cell count >16x10⁹/L, lactate >2.2 mmol/L, and radiologic evidence of pancolitis, ascites, megacolon, or perforation.[35]Klobuka AJ, Markelov A. Current status of surgical treatment for fulminant clostridium difficile colitis. World J Gastrointest Surg. 2013 Jun 27;5(6):167-72.
https://www.wjgnet.com/1948-9366/full/v5/i6/167.htm
http://www.ncbi.nlm.nih.gov/pubmed/23977418?tool=bestpractice.com
[56]Osman KA, Ahmed MH, Hamad MA, et al. Emergency colectomy for fulminant Clostridium difficile colitis: striking the right balance. Scand J Gastroenterol. 2011 Oct;46(10):1222-7.
http://www.ncbi.nlm.nih.gov/pubmed/21843039?tool=bestpractice.com
Outcomes in inflammatory bowel disease (IBD)
Mortality in IBD-associated TC/TM has fallen to about 2%, probably as a result of earlier recognition of toxic colitis, better intensive medical management options, earlier surgical intervention, and better postoperative care.[22]Sheth SG, LaMont JT. Toxic megacolon. Lancet. 1998 Feb 14;351(9101):509-13.
http://www.ncbi.nlm.nih.gov/pubmed/9482465?tool=bestpractice.com
However, emergency colectomy still has a 30-day postoperative mortality of 5%.[57]Bernstein CN, Ng SC, Lakatos PL, et al; Epidemiology and Natural History Task Force of the International Organization of the Study of Inflammatory Bowel Disease. A review of mortality and surgery in ulcerative colitis: milestones of the seriousness of the disease. Inflamm Bowel Dis. 2013 Aug;19(9):2001-10.
https://academic.oup.com/ibdjournal/article/19/9/2001/4608916
http://www.ncbi.nlm.nih.gov/pubmed/23624887?tool=bestpractice.com
There remains variation with respect to medical or surgical biases of treating physicians, which may contribute to geographic fluctuation in management algorithms or outcomes. Overall outcomes in this population have improved significantly. Compared to people with C difficile-related TC/TM, the IBD population is younger, and the incidence of medically significant comorbidities is less, so outcomes in general tend to be more favorable. However, coexisting IBD and C difficile infection is associated with a 4 times higher mortality rate than that for patients admitted with IBD alone.[30]Kelly CR, Fischer M, Allegretti JR, et al. ACG clinical guidelines: prevention, diagnosis, and treatment of Clostridioides difficile infections. Am J Gastroenterol. 2021 Jun 1;116(6):1124-47.
https://journals.lww.com/ajg/Fulltext/2021/06000/ACG_Clinical_Guidelines__Prevention,_Diagnosis,.12.aspx
http://www.ncbi.nlm.nih.gov/pubmed/34003176?tool=bestpractice.com
Medical management
Patients with IBD who survive an episode of toxic megacolon with medical management alone have a relatively poor long-term prognosis. While one study suggested prompt medical management could prevent the need for surgery in 50% of IBD patients, another study reported a 29% recurrence rate of either fulminant colitis or toxic megacolon over a 13-year follow-up period following initial medical management in an IBD population.[22]Sheth SG, LaMont JT. Toxic megacolon. Lancet. 1998 Feb 14;351(9101):509-13.
http://www.ncbi.nlm.nih.gov/pubmed/9482465?tool=bestpractice.com
[52]Grant CS, Dozois RR. Toxic megacolon: ultimate fate of patients after successful medical management. Am J Surg. 1984 Jan;147(1):106-10.
http://www.ncbi.nlm.nih.gov/pubmed/6691535?tool=bestpractice.com
Of patients who were initially managed medically, 47% eventually required a colectomy, 83% of which were performed urgently.[52]Grant CS, Dozois RR. Toxic megacolon: ultimate fate of patients after successful medical management. Am J Surg. 1984 Jan;147(1):106-10.
http://www.ncbi.nlm.nih.gov/pubmed/6691535?tool=bestpractice.com
The impact of newer treatment approaches (e.g., immunomodulators, biologic agents) on the long-term need for colectomy in this group of patients is unclear. While switching from one rescue therapy to another has been reported to achieve remission in 30% to 40% of treatment-refractory IBD patients, serious adverse events and infections occur in up to 20%.[42]Pola S, Patel D, Ramamoorthy S, et al. Strategies for the care of adults hospitalized for active ulcerative colitis. Clin Gastroenterol Hepatol. 2012 Dec;10(12):1315-25.
https://www.cghjournal.org/article/S1542-3565(12)00832-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/22835577?tool=bestpractice.com
These are related to excessive immunosuppression, and have led to the death of some patients.[42]Pola S, Patel D, Ramamoorthy S, et al. Strategies for the care of adults hospitalized for active ulcerative colitis. Clin Gastroenterol Hepatol. 2012 Dec;10(12):1315-25.
https://www.cghjournal.org/article/S1542-3565(12)00832-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/22835577?tool=bestpractice.com
The natural history of patients who survive an episode of C difficile-related TC/TM is not well described. However, the frequency with which patients are hospitalized for recurrence or persistence of disease may be a warning sign for a recurrent/relapsing type of disease. Fecal microbiota transfer (FMT) has been recommended as the therapy of choice for severe and fulminant C difficile infection, unresponsive to repeated antibiotic treatment, in patients who are unlikely to tolerate surgery.[34]van Prehn J, Reigadas E, Vogelzang EH, et al. European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults. Clin Microbiol Infect. 2021 Dec;27(2 suppl):S1-21.
https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(21)00568-1/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/34678515?tool=bestpractice.com
[58]Borgia G, Maraolo AE, Foggia M, et al. Fecal microbiota transplantation for Clostridium difficile infection: back to the future. Expert Opin Biol Ther. 2015 Jul;15(7):1001-14.
http://www.ncbi.nlm.nih.gov/pubmed/26063385?tool=bestpractice.com
The long-term outcome of this strategy remains to be seen.
Surgical management
Improved medical treatment and earlier surgical intervention have reduced the mortality associated with toxic megacolon. Outcomes of surgical management are dependent on etiology and the intervention used.
When a patient requires surgical management for TC/TM, the surgical procedure of choice is open abdominal colectomy with ileostomy regardless of the etiology of TC/TM. Preservation of the rectum is associated with lower morbidity and mortality from surgery, and retains the possibility of re-establishing intestinal continuity after recuperation. Additionally, as these patients are seriously ill, often hypoalbuminemic and anemic, and generally immunosuppressed by medications or severe illness, no anastomosis should be considered; ileostomy is the safe alternative. In the situation of severe TC/TM, removal of the rectum is reserved for rare cases of life-threatening rectal hemorrhage that cannot be managed by other means.
Toxic megacolon managed by abdominal colectomy with ileostomy is associated with a 6% mortality rate; the corresponding figure for total proctocolectomy (removal of the entire colon and rectum) is 21%.[4]Ausch C, Madoff RD, Gnant M, et al. Aetiology and surgical management of toxic megacolon. Colorectal Dis. 2006 Mar;8(3):195-201.
http://www.ncbi.nlm.nih.gov/pubmed/16466559?tool=bestpractice.com
Multi-organ failure accounts for two-thirds of deaths with either surgical approach.[4]Ausch C, Madoff RD, Gnant M, et al. Aetiology and surgical management of toxic megacolon. Colorectal Dis. 2006 Mar;8(3):195-201.
http://www.ncbi.nlm.nih.gov/pubmed/16466559?tool=bestpractice.com
The options of decompression and diversion alone had the poorest outcomes, with a mortality rate of 71%, all from multi-organ failure.[4]Ausch C, Madoff RD, Gnant M, et al. Aetiology and surgical management of toxic megacolon. Colorectal Dis. 2006 Mar;8(3):195-201.
http://www.ncbi.nlm.nih.gov/pubmed/16466559?tool=bestpractice.com