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Toxic dilatation of the colon
GI EMERGENCIES
Toxic dilatation of the colon Victoria Blackwell Simon Travis
Abstract Toxic megacolon (TM) is defined as total or non-segmental obstructive dilatation of the colon to an external diameter of 6.0 cm or greater, associated with systemic toxicity. It is a potentially fatal condition that represents the end of a spectrum of severe colitis. Typically a complication of ulcerative colitis, it is increasingly seen as a consequence of infective colitis. This reflects the increasing prevalence and severity of pseudomembranous colitis. TM associated with Clostridium difficile infection proves fatal in as many as two out of every three patients.
Keywords Clostridium difficile; colectomy; pseudomembranous colitis; toxic dilatation; ulcerative colitis
Patients with TM present with diarrhoea (often bloody), abdominal pain and pyrexia. Diagnosis requires radiographic evidence of a dilated colon and tachycardia or fever in a patient with severe colitis. CT is more sensitive than plain films for detecting perforation. Flexible sigmoidoscopy should be performed to confirm colitis and exclude complications such as cytomegalovirus infection. Joint surgical and medical management are critical. Medical therapy includes corticosteroids, antibiotics, and fluid and electrolyte management as well as nutrition. Approximately half of those with TM resulting from ulcerative colitis will respond to medical treatment. Colectomy is indicated if the dilatation persists beyond the first 24 h of admission in association with pyrexia and tachycardia. Delayed decision-making increases the likelihood of perforation, with a rise in morbidity and mortality.
Figure 1 Toxic megacolon: plain abdominal radiograph showing gross dilatation (double head arrow) and mucosal oedema, with effaced haustral folds in the transverse and descending colon.
antibiotics, but developed diarrhoea, distension and abdominal pain. This progressed to severe pain, with guarding and rebound tenderness in the right iliac fossa with a distended abdomen. A plain abdominal radiograph showed a grossly dilated colon (Figure 2). Flexible sigmoidoscopy showed a macroscopically normal mucosa and a CT scan excluded perforation. A diagnosis of pseudo-obstruction rather than toxic megacolon was made.
Illustrative case reports A 48-year-old woman was admitted with profuse watery diarrhoea and vomiting. Stool cultures were positive for Campylobacter jejuni. Her abdomen was diffusely tender with no rebound tenderness or guarding. An abdominal radiograph revealed a dilated colon (Figure 1). She was treated with azithromycin and a flexible sigmoidoscopy demonstrated deep, punched-out ulcers. Review of a chest radiograph prior to sigmoidoscopy revealed gas under the hemidiaphragms and a subsequent CT scan showed free gas with thickening of the colonic wall. She underwent emergency subtotal colectomy and end-ileostomy. An 83-year-old man was admitted to hospital with breathlessness. Imaging revealed bilateral pulmonary emboli and a lower respiratory tract infection. He was anticoagulated and treated with
Incidence and aetiology Toxic megacolon (TM) is defined as total or segmental nonobstructive dilatation of the colon to an external diameter 6.0 cm associated with systemic toxicity.1 It is a potential complication of any form of colitis and the differential diagnosis includes both inflammatory and infectious causes. It is classically a complication of ulcerative colitis, but is today most commonly associated with Clostridium difficile-associated (‘pseudomembranous’) colitis. Crohn’s disease, infection (Salmonella enteritidis, Campylobacter sp., amoebic colitis, Shigella sp., cytomegalovirus) and ischaemic colitis are all recognized causes. Toxic megacolon represents the end of a spectrum of severe colitis that has been unrecognized or undertreated. For ulcerative colitis, around 25% of all patients are admitted to hospital with a severe attack and about 5% of these will have toxic dilatation,2,3 consistent with a lifetime risk of TM in ulcerative colitis of 1e2%.4 The risk may be highest early on in the disease, since 16/55 (30%) of an early case series developed TM within three months of diagnosis.5 Earlier diagnosis, more intensive medical management
Victoria Blackwell MRCP is a Registrar in Gastroenterology at the John Radcliffe Hospital, Oxford, UK. Competing interests: none declared. Simon Travis DPhil FRCP is a Consultant Gastroenterologist at the John Radcliffe Hospital, Oxford, UK. Competing interests: none declared.
MEDICINE 39:2
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Ó 2010 Elsevier Ltd. All rights reserved.
GI EMERGENCIES
patients receiving corticosteroids. Distension is not prominent, although the alert clinician may detect the abdominal asymmetry of a dilated transverse colon. The abdomen is usually tender in the line of the colon. If peritonism is present, perforation (which may initially be localized) is likely. Diagnosis of TM is simple: it requires radiographic evidence of dilated colon (6.0 cm) and a tachycardia or temperature in a patient with severe colitis of any cause. This requires that a plain abdominal radiograph is performed on any patient presenting with severe colitis.9 While some have suggested multiple criteria for diagnosis,4 these serve little purpose since the condition must be recognized at an early, rather than a terminal stage. Laboratory findings in TM are those of a systemic inflammatory response, including leukocytosis, raised ESR or CRP and hypoalbuminaemia. Hypokalaemia and hypomagnesaemia are common and exacerbate the condition. The plain abdominal radiograph is pivotal for diagnosis. The external diameter is measured at the widest point of the colon, which is usually the transverse colon because it is the least dependent part of the bowel. Mucosal islands (oedematous remnants of mucosa projecting into the lumen, or seen en face) or an associated ileus with three or more small bowel loops have been associated with the need for colectomy in severe colitis independent of dilatation.10,11 CT scanning is unnecessary for diagnosis, but is more sensitive than plain films for detecting localized perforation.12 In a series of 18 patients, 12 with pseudomembranous colitis, two colonic perforations and two septic portal thromboses were identified.12 Gentle flexible sigmoidoscopy without preparation and with minimal air insufflation is necessary on admission to confirm the diagnosis of colitis and take biopsies to exclude complications such as cytomegalovirus (CMV) infection. Urgent histology is appropriate if CMV colitis is suspected, because a decision about colectomy is needed within 24 h of admission.
Figure 2 Colonic pseudo-obstruction: plain abdominal radiograph showing gross dilatation, but sharply defined mucosal folds in the transverse and descending colon.
and earlier surgery have reduced the incidence of TM complicating ulcerative colitis.3 In contrast, TM complicating infective colitis is rising, reflecting the increasing prevalence and severity of pseudomembranous colitis.6 Among patients with C. difficile-associated colitis (CDAD), 3e8% will develop TM that will often require surgical intervention.7
Management The key aspects of management are aggressive medical therapy and early surgical decision-making. Fluid and electrolyte resuscitation, with intravenous hydrocortisone 100 mg 6-hourly, should be commenced immediately, together with antibiotics (vancomycin 125 mg and azithromycin 500 mg four times daily) if an infective aetiology is suspected. Vancomycin is the first choice of antibiotic for CDAD and quinolone resistance in Campylobacter sp. colitis is now so common that a macrolide is preferred. The combination of corticosteroids and antibiotics is appropriate pending stool culture and C. difficile toxin assay, in case a new diagnosis of ulcerative colitis is missed. Corticosteroids reduce inflammation in pseudomembranous colitis.13 Large amounts of potassium may be needed to correct hypokalaemia. All anti-motility agents, opioids and anticholinergics should be stopped. Thromboprophylaxis with subcutaneous low-molecular-weight heparin should be started. Nasogastric suction cannot be expected to decompress the colon and is unnecessary. A senior surgical opinion is best sought on the day of admission. It should be made clear to all that there is a 24-h window of opportunity for medical treatment to work and that if there is no improvement early colectomy will be necessary.
Pathology and pathogenesis The pathogenesis of TM is unclear, but chemical mediators such as nitric oxide may play a pivotal role. Acute mucosal inflammation becomes transmural and is associated with neurogenic loss of motor tone in the smooth muscle layer that leads to dilatation of the colon. Nitric oxide inhibits smooth muscle tone. The amount and activity of inducible nitric oxide synthase are significantly increased in those with TM.8 The potential for TM is enhanced by any factor that adversely affects colonic motility; this includes hypokalaemia, hypomagnesaemia, and anticholinergic or antidiarrhoeal drugs. This is as relevant in pseudomembranous colitis as it is in ulcerative colitis. Histopathology demonstrates acute inflammation in all layers of the colon, with muscle necrosis and replacement by granulation tissue infiltrated by leukocytes and plasma cells that leads to perforation in about 20%.
Clinical features and investigations Typical features of acute severe colitis (diarrhoea, usually bloody, with anorexia, tachycardia and fever),9 predate the onset of acute dilatation by a week or more. Symptoms are masked in
MEDICINE 39:2
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Ó 2010 Elsevier Ltd. All rights reserved.
GI EMERGENCIES
REFERENCES 1 Sheth SG, LaMont JT. Toxic megacolon. Lancet 1998; 351: 509e13. 2 Dinesen L, Walsh A, Cummings JRF, et al. The pattern and outcome of acute severe colitis. J Crohn’s Colitis, in press. 3 Gan SI, Beck PL. A new look at toxic megacolon: an update and review of incidence, etiology, pathogenesis, and management. Am J Gastroenterol 2003; 98: 2363e71. 4 Jalan KN, Sircus W, Card WI, et al. An experience of ulcerative colitis: toxic dilatation in 55 cases. Gastroenterology 1969; 57: 68e82. 5 Dudukgian H, Sie E, Gonzalez-Ruiz C, et al. C. difficile colitis e predictors of fatal outcomes. J Gastrointest Surg 2010; 14: 315e22. 6 Oldfield 3rd EC. Clostridium difficile-associated diarrhea: resurgence with a vengeance. Rev Gastroenterol Disord 2006; 6: 79e96. 7 Hookman P, Barkin JS. Clostridium difficile associated infection, diarrhoea and colitis. World J Gastroenterol 2009; 15: 1554e80. 8 Mourelle M, Casellas F, Guarner F, et al. Induction of nitric oxide synthase in colonic smooth muscle from patients with toxic megacolon. Gastroenterology 1995; 109: 1497e502. 9 Travis SPL, Stange EF, Lemann M, et al. for the European Crohn’s and Colitis Organisation (ECCO). European consensus on the diagnosis and management of ulcerative colitis: current management. J Crohn’s Colitis 2008; 2: 24e62. 10 Loftus E. Imaging in inflammatory bowel disease. In: Targan SR, Shanahan F, Karp LC, eds. Inflammatory bowel disease: translating basic science into clinical practice. Oxford: Wiley-Blackwell, 2010: 266e78 [update Targan]. 11 Travis SPL, Satsangi J, Lemann M. Predicting the need for colectomy in severe UC: a critical appraisal of clinical parameters and currently available biomarkers. Gut, in press. 12 Imbriaco M, Balthazar EJ. Toxic megacolon: role of CT in evaluation and detection of complications. Clin Imaging 2001; 25: 349e54. 13 Goodman MJ, Truelove SC. Intensive intravenous regimen for membranous colitis. Br Med J 1976; 2: 354. 14 Koss K, Clark MA, Sanders DSA, et al. The outcome of surgery in fulminant Clostridium difficile colitis. Colorectal Dis 2005; 8: 149e54. 15 Kaur N, Gupta MK, Minocha VR. Early enteral feeding by nasoenteric tubes in patients with perforation peritonitis. World J Surg 2005; 29: 1023e8. 16 Moskovitz DN, Van Assche G, Maenhout B, et al. Incidence of colectomy during long-term follow-up after cyclosporine-induced remission of severe ulcerative colitis. Clin Gastroenterol Hepatol 2006; 4: 760e5. 17 Ausch C, Madoff R, Gnant M, et al. Aetiology and surgical management of toxic megacolon. Colorectal Dis 2006; 8: 195e201. 18 Lamontagne F, Labbe AC, Haeck O, et al. Impact of emergency colectomy on survival of patients with fulminant Clostridium difficile colitis during an epidemic caused by a hypervirulent strain. Ann Surg 2007; 245: 267e72. 19 Faris B, Blackmore A, Haboubi N. Review of medical and surgical management of Clostridium difficile infection. Tech Coloproctol 2010; 14: 97e105.
On the day after admission, the plain abdominal radiograph should be repeated. If the diameter has decreased then medical treatment can be continued and the radiograph repeated the following day. If the diameter has increased, or if it remains unchanged with an accompanying tachycardia or temperature, then urgent colectomy is indicated. If there is doubt, or if there is focal tenderness, a CT scan to look for localized perforation is appropriate. Management decisions should be made jointly between an experienced gastroenterologist and colorectal surgeon. There are few objective criteria to guide surgical decision-making in TM associated with CDAD. In a small retrospective study, indications for surgery included radiological or clinical evidence of progressive toxic dilatation and systemic toxicity, peritonitis, or perforation.14 Nutritional support is vital, especially with TM complicating pseudomembranous colitis. If there has been an extended period of poor nutrition, intravenous vitamins, phosphate (if serum phosphate <0.4 mmol/L) and magnesium (if serum magnesium <0.5 mmol/L) replacement should be given along with potassium in the first 24 h. This will reduce the risk of re-feeding syndrome. On the day after admission, if a decision is made to continue medical therapy then fine-bore nasogastric feeding is best considered under the supervision of a dietitian. If a decision is made to proceed to colectomy, parenteral nutrition may be appropriate. Enteral feeding promotes intestinal epithelial restitution and repair and can be given safely to patients with an ileus.15
Prognosis There are no randomized trials and it should be understood that the condition is potentially fatal. The mortality increases if perforation occurs, while inappropriate persistence with medical treatment ‘because the patient is too sick for surgery’ is a selffulfilling prophecy. That said, around 50% of patients with toxic megacolon resulting from ulcerative colitis respond to medical therapy,3 even if a high proportion with refractory colitis (up to 88%) ultimately require colectomy.9,16 In a series of 70 patients with surgically managed TM (half of whom had ulcerative colitis and half some other aetiology) over 20 years, the total mortality rate was 16%.17 The mortality of TM associated with ulcerative colitis is now <5% if early colectomy is performed. TM associated with C. difficile has a higher mortality (up to 67%3,7) reflecting serious comorbidity with more difficult (and thereby delayed) decision-making. Emergency colectomy has been shown to reduce mortality in these patients, particularly those who were aged 65 years or older, immunocompetent, or had a leukocytosis or a raised plasma lactate.5 Mortality rates following colectomy for TM associated with CDAD still remain high,18 but adverse outcomes in severe colitis seem to reflect the impact of delayed surgery, allowing development of shock and organ failure, rather than the risk of surgery itself.19 A
MEDICINE 39:2
107
Ó 2010 Elsevier Ltd. All rights reserved.
Toxic dilatation of the colon Victoria Blackwell Simon Travis
Abstract Toxic megacolon (TM) is defined as total or non-segmental obstructive dilatation of the colon to an external diameter of 6.0 cm or greater, associated with systemic toxicity. It is a potentially fatal condition that represents the end of a spectrum of severe colitis. Typically a complication of ulcerative colitis, it is increasingly seen as a consequence of infective colitis. This reflects the increasing prevalence and severity of pseudomembranous colitis. TM associated with Clostridium difficile infection proves fatal in as many as two out of every three patients.
Keywords Clostridium difficile; colectomy; pseudomembranous colitis; toxic dilatation; ulcerative colitis
Patients with TM present with diarrhoea (often bloody), abdominal pain and pyrexia. Diagnosis requires radiographic evidence of a dilated colon and tachycardia or fever in a patient with severe colitis. CT is more sensitive than plain films for detecting perforation. Flexible sigmoidoscopy should be performed to confirm colitis and exclude complications such as cytomegalovirus infection. Joint surgical and medical management are critical. Medical therapy includes corticosteroids, antibiotics, and fluid and electrolyte management as well as nutrition. Approximately half of those with TM resulting from ulcerative colitis will respond to medical treatment. Colectomy is indicated if the dilatation persists beyond the first 24 h of admission in association with pyrexia and tachycardia. Delayed decision-making increases the likelihood of perforation, with a rise in morbidity and mortality.
Figure 1 Toxic megacolon: plain abdominal radiograph showing gross dilatation (double head arrow) and mucosal oedema, with effaced haustral folds in the transverse and descending colon.
antibiotics, but developed diarrhoea, distension and abdominal pain. This progressed to severe pain, with guarding and rebound tenderness in the right iliac fossa with a distended abdomen. A plain abdominal radiograph showed a grossly dilated colon (Figure 2). Flexible sigmoidoscopy showed a macroscopically normal mucosa and a CT scan excluded perforation. A diagnosis of pseudo-obstruction rather than toxic megacolon was made.
Illustrative case reports A 48-year-old woman was admitted with profuse watery diarrhoea and vomiting. Stool cultures were positive for Campylobacter jejuni. Her abdomen was diffusely tender with no rebound tenderness or guarding. An abdominal radiograph revealed a dilated colon (Figure 1). She was treated with azithromycin and a flexible sigmoidoscopy demonstrated deep, punched-out ulcers. Review of a chest radiograph prior to sigmoidoscopy revealed gas under the hemidiaphragms and a subsequent CT scan showed free gas with thickening of the colonic wall. She underwent emergency subtotal colectomy and end-ileostomy. An 83-year-old man was admitted to hospital with breathlessness. Imaging revealed bilateral pulmonary emboli and a lower respiratory tract infection. He was anticoagulated and treated with
Incidence and aetiology Toxic megacolon (TM) is defined as total or segmental nonobstructive dilatation of the colon to an external diameter 6.0 cm associated with systemic toxicity.1 It is a potential complication of any form of colitis and the differential diagnosis includes both inflammatory and infectious causes. It is classically a complication of ulcerative colitis, but is today most commonly associated with Clostridium difficile-associated (‘pseudomembranous’) colitis. Crohn’s disease, infection (Salmonella enteritidis, Campylobacter sp., amoebic colitis, Shigella sp., cytomegalovirus) and ischaemic colitis are all recognized causes. Toxic megacolon represents the end of a spectrum of severe colitis that has been unrecognized or undertreated. For ulcerative colitis, around 25% of all patients are admitted to hospital with a severe attack and about 5% of these will have toxic dilatation,2,3 consistent with a lifetime risk of TM in ulcerative colitis of 1e2%.4 The risk may be highest early on in the disease, since 16/55 (30%) of an early case series developed TM within three months of diagnosis.5 Earlier diagnosis, more intensive medical management
Victoria Blackwell MRCP is a Registrar in Gastroenterology at the John Radcliffe Hospital, Oxford, UK. Competing interests: none declared. Simon Travis DPhil FRCP is a Consultant Gastroenterologist at the John Radcliffe Hospital, Oxford, UK. Competing interests: none declared.
MEDICINE 39:2
105
Ó 2010 Elsevier Ltd. All rights reserved.
GI EMERGENCIES
patients receiving corticosteroids. Distension is not prominent, although the alert clinician may detect the abdominal asymmetry of a dilated transverse colon. The abdomen is usually tender in the line of the colon. If peritonism is present, perforation (which may initially be localized) is likely. Diagnosis of TM is simple: it requires radiographic evidence of dilated colon (6.0 cm) and a tachycardia or temperature in a patient with severe colitis of any cause. This requires that a plain abdominal radiograph is performed on any patient presenting with severe colitis.9 While some have suggested multiple criteria for diagnosis,4 these serve little purpose since the condition must be recognized at an early, rather than a terminal stage. Laboratory findings in TM are those of a systemic inflammatory response, including leukocytosis, raised ESR or CRP and hypoalbuminaemia. Hypokalaemia and hypomagnesaemia are common and exacerbate the condition. The plain abdominal radiograph is pivotal for diagnosis. The external diameter is measured at the widest point of the colon, which is usually the transverse colon because it is the least dependent part of the bowel. Mucosal islands (oedematous remnants of mucosa projecting into the lumen, or seen en face) or an associated ileus with three or more small bowel loops have been associated with the need for colectomy in severe colitis independent of dilatation.10,11 CT scanning is unnecessary for diagnosis, but is more sensitive than plain films for detecting localized perforation.12 In a series of 18 patients, 12 with pseudomembranous colitis, two colonic perforations and two septic portal thromboses were identified.12 Gentle flexible sigmoidoscopy without preparation and with minimal air insufflation is necessary on admission to confirm the diagnosis of colitis and take biopsies to exclude complications such as cytomegalovirus (CMV) infection. Urgent histology is appropriate if CMV colitis is suspected, because a decision about colectomy is needed within 24 h of admission.
Figure 2 Colonic pseudo-obstruction: plain abdominal radiograph showing gross dilatation, but sharply defined mucosal folds in the transverse and descending colon.
and earlier surgery have reduced the incidence of TM complicating ulcerative colitis.3 In contrast, TM complicating infective colitis is rising, reflecting the increasing prevalence and severity of pseudomembranous colitis.6 Among patients with C. difficile-associated colitis (CDAD), 3e8% will develop TM that will often require surgical intervention.7
Management The key aspects of management are aggressive medical therapy and early surgical decision-making. Fluid and electrolyte resuscitation, with intravenous hydrocortisone 100 mg 6-hourly, should be commenced immediately, together with antibiotics (vancomycin 125 mg and azithromycin 500 mg four times daily) if an infective aetiology is suspected. Vancomycin is the first choice of antibiotic for CDAD and quinolone resistance in Campylobacter sp. colitis is now so common that a macrolide is preferred. The combination of corticosteroids and antibiotics is appropriate pending stool culture and C. difficile toxin assay, in case a new diagnosis of ulcerative colitis is missed. Corticosteroids reduce inflammation in pseudomembranous colitis.13 Large amounts of potassium may be needed to correct hypokalaemia. All anti-motility agents, opioids and anticholinergics should be stopped. Thromboprophylaxis with subcutaneous low-molecular-weight heparin should be started. Nasogastric suction cannot be expected to decompress the colon and is unnecessary. A senior surgical opinion is best sought on the day of admission. It should be made clear to all that there is a 24-h window of opportunity for medical treatment to work and that if there is no improvement early colectomy will be necessary.
Pathology and pathogenesis The pathogenesis of TM is unclear, but chemical mediators such as nitric oxide may play a pivotal role. Acute mucosal inflammation becomes transmural and is associated with neurogenic loss of motor tone in the smooth muscle layer that leads to dilatation of the colon. Nitric oxide inhibits smooth muscle tone. The amount and activity of inducible nitric oxide synthase are significantly increased in those with TM.8 The potential for TM is enhanced by any factor that adversely affects colonic motility; this includes hypokalaemia, hypomagnesaemia, and anticholinergic or antidiarrhoeal drugs. This is as relevant in pseudomembranous colitis as it is in ulcerative colitis. Histopathology demonstrates acute inflammation in all layers of the colon, with muscle necrosis and replacement by granulation tissue infiltrated by leukocytes and plasma cells that leads to perforation in about 20%.
Clinical features and investigations Typical features of acute severe colitis (diarrhoea, usually bloody, with anorexia, tachycardia and fever),9 predate the onset of acute dilatation by a week or more. Symptoms are masked in
MEDICINE 39:2
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Ó 2010 Elsevier Ltd. All rights reserved.
GI EMERGENCIES
REFERENCES 1 Sheth SG, LaMont JT. Toxic megacolon. Lancet 1998; 351: 509e13. 2 Dinesen L, Walsh A, Cummings JRF, et al. The pattern and outcome of acute severe colitis. J Crohn’s Colitis, in press. 3 Gan SI, Beck PL. A new look at toxic megacolon: an update and review of incidence, etiology, pathogenesis, and management. Am J Gastroenterol 2003; 98: 2363e71. 4 Jalan KN, Sircus W, Card WI, et al. An experience of ulcerative colitis: toxic dilatation in 55 cases. Gastroenterology 1969; 57: 68e82. 5 Dudukgian H, Sie E, Gonzalez-Ruiz C, et al. C. difficile colitis e predictors of fatal outcomes. J Gastrointest Surg 2010; 14: 315e22. 6 Oldfield 3rd EC. Clostridium difficile-associated diarrhea: resurgence with a vengeance. Rev Gastroenterol Disord 2006; 6: 79e96. 7 Hookman P, Barkin JS. Clostridium difficile associated infection, diarrhoea and colitis. World J Gastroenterol 2009; 15: 1554e80. 8 Mourelle M, Casellas F, Guarner F, et al. Induction of nitric oxide synthase in colonic smooth muscle from patients with toxic megacolon. Gastroenterology 1995; 109: 1497e502. 9 Travis SPL, Stange EF, Lemann M, et al. for the European Crohn’s and Colitis Organisation (ECCO). European consensus on the diagnosis and management of ulcerative colitis: current management. J Crohn’s Colitis 2008; 2: 24e62. 10 Loftus E. Imaging in inflammatory bowel disease. In: Targan SR, Shanahan F, Karp LC, eds. Inflammatory bowel disease: translating basic science into clinical practice. Oxford: Wiley-Blackwell, 2010: 266e78 [update Targan]. 11 Travis SPL, Satsangi J, Lemann M. Predicting the need for colectomy in severe UC: a critical appraisal of clinical parameters and currently available biomarkers. Gut, in press. 12 Imbriaco M, Balthazar EJ. Toxic megacolon: role of CT in evaluation and detection of complications. Clin Imaging 2001; 25: 349e54. 13 Goodman MJ, Truelove SC. Intensive intravenous regimen for membranous colitis. Br Med J 1976; 2: 354. 14 Koss K, Clark MA, Sanders DSA, et al. The outcome of surgery in fulminant Clostridium difficile colitis. Colorectal Dis 2005; 8: 149e54. 15 Kaur N, Gupta MK, Minocha VR. Early enteral feeding by nasoenteric tubes in patients with perforation peritonitis. World J Surg 2005; 29: 1023e8. 16 Moskovitz DN, Van Assche G, Maenhout B, et al. Incidence of colectomy during long-term follow-up after cyclosporine-induced remission of severe ulcerative colitis. Clin Gastroenterol Hepatol 2006; 4: 760e5. 17 Ausch C, Madoff R, Gnant M, et al. Aetiology and surgical management of toxic megacolon. Colorectal Dis 2006; 8: 195e201. 18 Lamontagne F, Labbe AC, Haeck O, et al. Impact of emergency colectomy on survival of patients with fulminant Clostridium difficile colitis during an epidemic caused by a hypervirulent strain. Ann Surg 2007; 245: 267e72. 19 Faris B, Blackmore A, Haboubi N. Review of medical and surgical management of Clostridium difficile infection. Tech Coloproctol 2010; 14: 97e105.
On the day after admission, the plain abdominal radiograph should be repeated. If the diameter has decreased then medical treatment can be continued and the radiograph repeated the following day. If the diameter has increased, or if it remains unchanged with an accompanying tachycardia or temperature, then urgent colectomy is indicated. If there is doubt, or if there is focal tenderness, a CT scan to look for localized perforation is appropriate. Management decisions should be made jointly between an experienced gastroenterologist and colorectal surgeon. There are few objective criteria to guide surgical decision-making in TM associated with CDAD. In a small retrospective study, indications for surgery included radiological or clinical evidence of progressive toxic dilatation and systemic toxicity, peritonitis, or perforation.14 Nutritional support is vital, especially with TM complicating pseudomembranous colitis. If there has been an extended period of poor nutrition, intravenous vitamins, phosphate (if serum phosphate <0.4 mmol/L) and magnesium (if serum magnesium <0.5 mmol/L) replacement should be given along with potassium in the first 24 h. This will reduce the risk of re-feeding syndrome. On the day after admission, if a decision is made to continue medical therapy then fine-bore nasogastric feeding is best considered under the supervision of a dietitian. If a decision is made to proceed to colectomy, parenteral nutrition may be appropriate. Enteral feeding promotes intestinal epithelial restitution and repair and can be given safely to patients with an ileus.15
Prognosis There are no randomized trials and it should be understood that the condition is potentially fatal. The mortality increases if perforation occurs, while inappropriate persistence with medical treatment ‘because the patient is too sick for surgery’ is a selffulfilling prophecy. That said, around 50% of patients with toxic megacolon resulting from ulcerative colitis respond to medical therapy,3 even if a high proportion with refractory colitis (up to 88%) ultimately require colectomy.9,16 In a series of 70 patients with surgically managed TM (half of whom had ulcerative colitis and half some other aetiology) over 20 years, the total mortality rate was 16%.17 The mortality of TM associated with ulcerative colitis is now <5% if early colectomy is performed. TM associated with C. difficile has a higher mortality (up to 67%3,7) reflecting serious comorbidity with more difficult (and thereby delayed) decision-making. Emergency colectomy has been shown to reduce mortality in these patients, particularly those who were aged 65 years or older, immunocompetent, or had a leukocytosis or a raised plasma lactate.5 Mortality rates following colectomy for TM associated with CDAD still remain high,18 but adverse outcomes in severe colitis seem to reflect the impact of delayed surgery, allowing development of shock and organ failure, rather than the risk of surgery itself.19 A
MEDICINE 39:2
107
Ó 2010 Elsevier Ltd. All rights reserved.