Toxic Secondary to Pseudomembranous

The Identification and TreatmentofToxic Megacolon Secondary to Pseudomembranous Colitis

Megan M. Earhart, MSN, RN

Toxic megacolon is an infrequently occurring, potentially life-threatening of pseudomembranous colitis. Although may be considered rare, incidence is expected to increase because of the rapidly increased prevalence of pseudomembranous colitis. This article discusses the pathophysiology, clinical manifestation, diagnosis, treatment, and prognosis for toxic megacolon secondary to pseudomembranous colitis. Critical care nurses should be aware of the disease to intervene early and increase the chance of the patient’s survival. Keywords: Inflammatory bowel disease, , Pseudomembranous colitis, Toxic megacolon

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CASE STUDY and was treated with Neosynephrine (Hospira, Inc., Lake A 49-year-old African American man with a history of Forest, IL) and Xigris (Eli Lilly and Co., Indianapolis, IN) hypertension, type 2 diabetes mellitus, and glaucoma was before seeking surgical treatment of toxic megacolon. The treated with chemotherapeutic agents for a new diagnosis patient underwent a subtotal and permanent of myelogenous leukemia. After he developed for an edematous, thickened, and hemorrhagic neutropenia from the chemotherapy, Ambisome (Astellas right colon up to the splenic flexure and sigmoid colon. Parm US, Inc., Deerfield, IL), Cefepime (Bristol-Myers Squibb Company, Princeton, NJ), Zyvox (Pfizer Inc., New INTRODUCTION York, NY), Valtrex (GlaxoSmithKline, Philadelphia, PA), Toxic megacolon is an infrequently occurring, potentially and Flagyl (Pfizer Inc., New York, NY) were administered life-threatening complication of pseudomembranous colitis. for repeated and , although all blood The first documented case of toxic megacolon secondary to cultures had been negative. The patient further developed pseudomembranous colitis was reported in 1968.1 Toxic renal failure, diarrhea with a positive Clostridium difficile megacolon is a disease characterized by segmental or total toxin, , and distention. A computed colonicdistentionofgreaterthan6cminthepresenceof tomography (CT) scan of the abdomen showed a acute colitis and signs of systemic toxicity.2 Toxic mega- thickened right colon. The patient developed hypotension colon is present when 3 of the 4 following criteria are

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Copyright @ 2008 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Toxic Megacolon Secondary to Pseudomembranous Colitis met: (1) temperature greater than 101.5-F, (2) heart rheal or anticholinergic drugs.2 Toxic megacolon has been rate more than 120 beats/min, (3) leukocyte count more seen in patients as a consequence of Crohn disease, Kaposi than 10,500/2L with a left shift, and (4) anemia with sarcoma, , human immunodeficiency virus a hemoglobin or hematocrit level of less than 60% of (HIV), acquired immunodeficiency syndrome (AIDS), is- normal.3 One of the following 4 signs must also exist: (1) chemic colitis, Cryptosporidium, Salmonella, , hypotension, (2) electrolyte imbalances, (3) mental status Yersinia, Campylobacter, Entameba,andC difficile.2 Che- changes, and/or (4) .3 Most cases of toxic motherapy and have been reported as pos- megacolon occur in individuals with inflammatory bowel sible risk factors, whereas graft-versus-host disease and disease, but there has been a significant increase in the radiation therapy have not been reported to induce toxic number of cases associated with pseudomembranous megacolon2 (see Table 1). colitis.2 Colonic distention is also seen in patients with Hirschsprung disease, idiopathic megacolon, and intestinal PATHOPHYSIOLOGY pseudo-obstruction () and is associated A variety of pathogenic mechanisms most likely contribute with postoperative complications, stroke, and spinal cord to the development of toxic megacolon. One of the most injury. Because these presentations lack systemic toxicity, important contributing factors in the development of toxic they are different from toxic megacolon.4 megacolon is the progression of the beyond the submucosa into the muscularis, and serosa.4 Severe in- Incidence flammation and damage to the colonic wall are necessary The incidence of toxic megacolon in pseudomembranous for the development of toxic megacolon.2 As acute inflam- colitis is reported at 0.4% to 3%, but it is challenging to mation progresses in the colon, neural injury occurs in the determine from the literature because it has not been bowel wall, resulting in both dysmotility and dilation.4 regularly reported. It affects all ages and both sexes, and Inflammation in the colon disrupts the normal absorptive the incidence is expected to increase in proportion owing function, leading to water, sodium, and potassium to be to the rapidly increasing prevalence of pseudomembra- trapped in the lumen of the colon. Hypokalemia and other nous colitis.2 The increase in use of broad-spectrum electrolyte abnormalities further decrease the bowel’s abil- may lead to a doubling of the overall inci- ity to contract.2 The barrier mechanism of the colon is lost, dence of pseudomembranous colitis.2 which allows for the absorption of toxins, microbes, and Critical care nurses must be aware of the signs and toxic wastes causing systemic toxicity.2 The systemic symptoms of toxic megacolon and be prepared to assess for symptoms associated with toxic megacolon are not directly potential complications. Acute colitis is often resistant to therapy, and the signs and symptoms can be present for a TABLE 1 Toxic Megacolon Risk Factors week before the onset of distention. Diarrhea, malaise, ab- dominal pain, and distention are the most common com- Pseudomembranous colitis plaints in patients presenting with infectious colitis and toxic Discontinuation of 5-aminosalicylate agents or steroids 5 megacolon. It is essential that the patient with toxic mega- Barium enemas colon secondary to pseudomembranous colitis be diagnosed Drugs that slow colonic motility, such as rapidly and correctly to decrease morbidity and mortality. Narcotics It is essential that the patient with Antidiarrheal drugs toxic megacolon secondary to Anticholinergic drugs pseudomembranous colitis be Crohn disease diagnosed rapidly and correctly to Kaposi sarcoma decrease morbidity and mortality. Cytomegalovirus Human immunodeficiency virus (HIV) Acquired immunodeficiency syndrome (AIDS) Risk Factors In addition to pseudomembranous colitis as an underlying Cryptosporidium, Salmonella, Shigella, Yersinia, Campylobacter, factor, additional risk factors for the occurrence of toxic Entameba, and Clostridium difficile megacolon include (1) discontinuation of 5-aminosalicylate Chemotherapy agents or steroids, (2) barium enemas, and (3) medications Colonoscopy that slow colonic motility, such as narcotics and antidiar-

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Copyright @ 2008 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Toxic Megacolon Secondary to Pseudomembranous Colitis related to bacteremia, colonic perforation, or ischemia films revealing a dilated colon (see Table 2). Toxic but to toxic-induced inflammatory mediators such as megacolon should be considered in all patients present- interleukin-8, macrophage-inflammatory protein-2, sub- ing with abdominal distention and acute or chronic stance P, and tumor necrosis factor !,releasedinthecolon.6 diarrhea.5 The best-accepted clinical criteria for diag- It has been postulated that nitric oxide, a known in- nosing toxic megacolon uses any 3 of the 4 following hibitor of tone, may also be involved in the criteria: (1) temperature greater than 101.5-F, (2) heart pathogenesis of toxic megacolon. Nitric oxide is generated rate greater than 120 beats/min, (3) in the macrophages and smooth muscle cells of the inflamed count greater than 10.5 Â 109/L, or (4) anemia. Patients colon.5 It is an important nonadrenergic, noncholinergic should also have one of the following: (1) dehydration, neurotransmitter in the intestines.2 One group of research- (2) mental changes, (3) electrolyte disturbances, or (4) ers found higher levels of nitric oxide synthase in colonic hypotension.3 muscles of patients with toxic megacolon than in those Abdominal radiographs should be obtained in the with uncomplicated colitis.7 Nitric oxide is a marker of left lateral decubitus and supine positions.4 The radio- increased inflammation, so it is uncertain if its production logical diagnosis is made when transverse colon or is directly involved in the pathogenesis of toxic megacolon. are greater than 6 cm dilated.2 Plain Medications that disrupt gastric motility act as films often show a loss of haustrations in patients with possible triggers for toxic megacolon.4 Antidiarrheal pseudomembranous colitis.1 It is recommended that medications including , with abdominal CT be obtained because it is useful in deter- atropine, and opiates, as well as anticholinergics and mining the etiology of toxic megacolon.2 Computed antidepressants all have the ability to slow and lead to dilation.4 Barium enemas and colonoscopy can cause further dilation, leading to impaired blood TABLE 2 Diagnosing Toxic Megacolon supply to the colon wall and an increase in absorption Clinical manifestation of bacterial products.5 All drugs that decrease gastric motility should be stopped in patients with severe colitis, Diarrhea 4 especially in patients with signs of systemic toxicity. Barium enemas and colonoscopy are contraindicated Chills because of the increased risk of colonic perforation.5 Altered mental status The pathological appearance of toxic megacolon secondary to pseudomembranous colitis includes diffuse ulcerations, raised mucosal nodules, yellowish white Malaise superficial plaques with a normal intervening mucosa, Abdominal cramping and extensive denudation.5 Locally or diffusely tender abdomen CLINICAL MANIFESTATIONS Reduced bowel sounds Toxic megacolon develops in patients of all ages and both Abdominal distention 2 sexes. The patient usually presents with signs and Clinical criteria symptoms of colitis before the onset of toxic megacolon.2 Any 3 of the 4 following: The symptoms of colitis include diarrhea, fever, chills, and abdominal cramping.2 Patients developing toxic megacolon Temperature 9101.5-F may exhibit (1) constipation, (2) malaise, (3) a white blood Heart rate 9120 beats/min 2 cell count greater than 10,500/ L, (4) anemia less than 12 White blood cell count 910.5 Â 109/L g, (5) albumin less than 3 g, (6) , (7) fever, (8) Anemia , and/or (9) hypotension.1 may reveal a locally or diffusely tender abdomen, reduced bowel At least 1 of the following: sounds, abdominal distention, and an altered mental Dehydration 5 status. Patients are often administered antibiotics, immu- Mental changes nosuppressants or chemotherapy, or antidiarrheals before Electrolyte disturbances developing toxic megacolon.1 Hypotension DIAGNOSIS Radiographic criteria The diagnosis of toxic megacolon is based on the clinical Transverse or ascending colon 96 cm dilated picture of severe systemic toxicity and plain abdominal

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Copyright @ 2008 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Toxic Megacolon Secondary to Pseudomembranous Colitis tomography has the ability to show diffuse colonic wall team. The goal of treatment of toxic megacolon is to thickening, submucosal edema, periodic stranding, sep- restore colonic motility and reduce the risk of perfo- tic emboli, and abscesses that may not appear on a ration.5 A surgeon and a gastroenterologist should be plain film.2 consulted early in the management of the patient, even Laboratory studies are nonspecific yet may be though medical management prevents in 50% helpful in the diagnosis of toxic megacolon.2 Leukocy- of the cases.8 Survival after a diagnosis with toxic mega- tosis is usually noted with a left shift indicating the colon may be improved with surgery before the develop- degree of inflammation and the leukocyte count may ment of multiple organ failure.9 Much of the literature reach as high as 40,000/2L.4 It is important to indicates a need for surgery if the condition of the remember that neutropenia, not leukocytosis, may be patient does not improve in the first 48 to 72 hours of seen in patients with AIDS or those receiving chemo- medical management.4 therapy.5 Metabolic acidosis and electrolyte imbalances such as low potassium, calcium, chloride, phosphate, Medical Management and magnesium may occur from prolonged diarrhea.4 Supportive care should occur in all patients with toxic Hypoalbuminemia is usually not present initially, but megacolon, as well as bowel rest and intravenous fluids.4 the albumin level often drops below 3 g/dL because of Crystalloids should be used aggressively, unless the chronic protein losses and decreased liver synthesis with patient is in a severe state of shock or hypoalbuminemia, malnutrition.4 A poor prognosis results when a patient in which case colloids are necessary.4 Fluid status, weight, develops metabolic alkalosis from volume depletion and and daily laboratories should be performed, including a potassium losses.4 Elevated erythrocyte sedimentation complete blood count with differential, electrolytes, rate and C-reactive protein levels are nonspecific blood chemistry, and serum albumin.4 Electrolytes inflammatory signs often useful when observing the should be replaced as necessary, and albumin should be progression of the disease.4 administered to maintain a level of 3.0 g/dL.4 The patient should be transferred to the intensive care unit for hemodynamic monitoring and signs of deterioration.2 A nasogastric tube or long intestinal tube should Leukocytosis is usually noted with a be placed for colonic decompression.2 A long intestinal left shift indicating the degree of tube is preferred but does require placement under inflammation, and the leukocyte count fluoroscopy.2 Patient repositioning can also be used as a may reach as high as 40,000/µL. technique for bowel decompression. Prone positioning for 10 to 15 minutes every 2 to 3 hours, allowing the patient to pass gas, is encouraged but often difficult in the uncooperative, intubated, or obtunded patient in the Stool samples should be sent for culture, sensitivity, intensive care unit.2 and C difficile toxin assay in patients with a history of Critical care nurses must closely monitor the number use or chemotherapy to help determine a of bowel movements, as a decreasing number is often diagnosis for pseudomembranous colitis.4 It is impor- indicative of a worsening condition and an increasing tant to consider an ova and parasite and number can indicate a response to therapy.4 Nursing cytomegalovirus in patients with HIV/AIDS.4 Blood staff should monitor for increasing abdominal ten- cultures should obtained to rule out bacteremia, consid- derness, guarding, hemodynamic instability, and a rise ering that occurs in up to 25% of patients with in temperature every 6 to 12 hours, which could all toxic megacolon.2 be signs of colonic perforation.4 Plain abdominal radio- A limited endoscopy, not full colonoscopy, without graph, looking for free air as a sign of perforation, bowel preparation may be useful to diagnose a should be performed every 12 to 24 hours and con- suspected infection in the colon. Only minimal amounts tinued until the bowel diameter returns to normal.4 of air should be used because of the risk of worsening All medications that impair gastric motility should distention, , or perforation.2 be stopped, including anticholinergic medications, antidiarrheal drugs, antidepressants, and narcotics4 (see TREATMENT Table 3). Patients should be administered an intravenous H2-blocker to prevent stress ulcers, and pneumatic General Management compression boots should be ordered to prevent deep The management of toxic megacolon requires an ag- vein thrombosis.5 Barium enemas and endoscopy beyond gressive effort from the medical, surgical, and nursing 20 cm should not be performed because of an increase in

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indicated. Patients older than 40 years with deep colonic TABLE 3 Medications Causing Impaired Gastric Motility ulcers, low albumin levels, and elevated erythrocyte sedimentation rates have been associated with a poor Antidiarrheal drugs response to medical treatment.4 When a patient does not Opiates respond to medical therapy in the first 48 to 72 hours or Loperamide when perforation, uncontrolled bleeding, or progressive dilation occurs, a subtotal colectomy with end-ileostomy Diphenoxylate with Atropine is the procedure of choice in emergent situations.5 A Anticholinergic agents temporary colostomy or colectomy may be possible if Atropine there is reversible damage in the colon.4 Much debate Hyoscyamine has taken place regarding the timing of surgery after a diagnosis of toxic megacolon. Studies have shown a low Propantheline mortality rate with medical management for up to 7 Dicyclomine days, as long as there is evidence of clinical improve- Levodopa ment.2 Elective surgery, with a mortality rate of 5%, is Sinemet preferred over emergent surgery, with a mortality rate of 30%.10 The fear when with delayed surgery is taking a Antidepressants critically ill patient with a friable colon to the operating Amitriptyline room.4 Mortality rate may increase from 30% in Nortriptyline emergent situations to 40% when surgery is prolonged for greater than 1 month.10 gastric distention and decrease in blood supply to the 4 PROGNOSIS colon wall. Total parenteral nutrition is controversial Toxic megacolon complicating pseudomembranous coli- and has shown no proven benefit in preventing surgery tis is a rare occurrence, but the mortality and morbidity or decreasing the length of hospital stay.5 rates are high, making early recognition and manage- In pseudomembranous colitis, it is necessary to ment crucial.2 The prognosis is guarded, even when discontinue the offending antibiotic and administer oral aggressive medical and surgical treatment is used.1 or intravenous metronidazole or oral .2 Immediate recognition and treatment of toxic mega- Intestinal absorption is often compromised or patients colon have decreased the number of deaths from this are too ill to tolerate oral antibiotics. At this point, it is diagnosis.4 The rate of colectomy and mortality from recommended to administer intravenous metronidazole pseudomembranous colitis has increased at an alarming and vancomycin plus oral vancomycin.1 Early surgical rate, mostly owing to patients developing toxic mega- intervention is often used in patients acutely ill from colon.2 There has been a reported mortality of 38% to toxic megacolon associated with pseudomembranous 80% in patients with toxic megacolon secondary to colitis.1 Antibiotics should be administered because of pseudomembranous colitis.2 A literature review of 36 the possibility for perforation until the patient is documented cases of toxic megacolon secondary to stabilized to cover gram-negative and anaerobic organ- pseudomembranous colitis since 1968 reveals a mortal- isms.4 Ampicillin or cephalosporin, plus gentamicin and ity rate of 42% for surgically treated patients and 18% metronidazole, is an appropriate regimen to cover the for medically managed patients.1 Often, surgically possible organisms.4 treated patients have failed medical treatment and have Surgical Management a more advanced disease, therefore increasing the mortality rate for surgical patients.1 Most patients acquiring toxic megacolon secondary to pseudomembranous colitis respond well to medical treatment, but in certain circumstances, surgery is CONCLUSION Toxic megacolon is a dire complication of pseudomem- branous colitis with a high morbidity and mortality. The Early surgical intervention is often rate of toxic megacolon is increasing because of the used in patients acutely ill from toxic increase in pseudomembranous colitis. Because surgical megacolon associated with treatment with a subtotal colectomy and end-ileostomy pseudomembranous colitis. can have a profound impact on quality of life, imme- diate recognition and medical management are essential. In addition to abdominal radiographs, critical care

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Copyright @ 2008 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Toxic Megacolon Secondary to Pseudomembranous Colitis nurses can identify the signs and symptoms and help 5. Sheth SG, LaMont JT. Toxic megacolon. Lancet. 1998; minimize the negative consequences. Rapid intervention 351(9101):509-513. 6. Dallal RM, Harbrecht BG, Boujoukas AJ, et al. Fulminant is necessary to decrease the number of deaths from a Clostridium difficile: an underappreciated and increasing cause rare yet life-threatening disease. of death and complications. Ann Surg. 2002;235(3):363-372. 7. Mourelle M, Casellas F, Guarner F, et al. Induction of nitric Acknowledgment oxide synthesis in colonic smooth muscle from patients with toxic megacolon. . 1995;109(5):1497-1502. The author would like to recognize the assistance and 8. Fazio VW. Toxic megacolon in and Crohn’s colitis. Clin Gastroenterol. 1980;9:389. support of Linda Baas, PhD, RN, CANP, CCNS, 9. Synnott K, Mealy K, Merry C, Kyne L, Keane C, Quill R. with the University of Cincinnati College of Nursing Timing of surgery for fulminating pseudomembranous colitis. in Cincinnati, Ohio. Br J Surg. 1998;85:229-231. 10. Greenstein AJ, Sachar DB, Gibas A, et al. Outcome of toxic dilatation in ulcerative and Crohn’s colitis. J Clin Gastro- References enterol. 1985;7:137-143. 1. Trudel JL, Deschenes M, Mayrand S, Barkun AN. Toxic megacolon complicating pseudomembranous . Dis Colon . 1005;38:1033-1038. ABOUT THE AUTHOR 2. Gan SI, Beck PL. A new look at toxic megacolon: update and review of incidence, etiology, pathogenesis, and management. Megan M. Earhart, MSN, RN, is currently employed by Jewish Am J Gastroenterol. 2003;98(11):2363-2371. Hospital in Cincinnati, Ohio, and works on the bone marrow 3. Jalan KN, Sircus W, Card WI, et al. An experience with transplant unit. ulcerative colitis: toxic dilation in 55 cases. Gastroenterology. Address correspondence and reprint requests to: Megan M. Earhart, 1969;57(1):68-82. 4. Levine CD. Toxic megacolon: diagnosis and treatment chal- MSN, RN, 5954 Beacraft Ave, No. 2, Cincinnati, OH 45213 lenges. AACN Clin Issues. 1999;10(4):492-499. ([email protected]).

Call for Student Abstracts

Dimensions of Critical Care Nursing would like to issue a call for abstracts from undergraduate and graduate nursing students for a new section called ‘‘Student Abstracts.’’ Both undergraduate and graduate nursing students in the area of critical care conduct much good research, and I would like to share the results of this research with our readers. So many times, the results of this research are presented in the classroom setting and not disseminated to others. Here is an opportunity for those students to publish their abstracts. If you would like to submit your research abstract, you must be either an undergraduate or graduate nursing student. Your research must be related to the area of critical care nursing. Please submit the following:

Title of the Abstract Your name and address School of Nursing No more than 2 paragraphs summarizing the research and its findings Please submit the abstract to DCCN at: Vickie Miracle, EdD, RN 424 Eastgate Village Wynde Louisville, KY 40223 You could also fax it to 502-253-5560. You could also e-mail it to [email protected]. Please submit your research and discover the pleasure of publishing.

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