Diarrhea, the principal manifestation of intestinal infection among the critically ill, affects approximately one third of all patients admitted to the ICU.10 Patients in the ICU with diarrhea are especially vulnerable to the clinical sequelae of infection. For the critically ill patient, the dehydration that frequently accompanies severe diarrhea strains a circulatory capacity already limited by impaired cardiac contractility and septic hemodynamics. Such individuals are at high risk for further systemic deterioration, often culminating in multisystem organ failure. In addition to life-threatening volume loss, diarrhea in the critically ill patient can precipitate metabolic derangements including electrolyte imbalances and acidosis, further exacerbating the potential for cardiac rhythm irritability. Finally, uncontrolled diarrhea in a severely ill immobile patient can predispose to compromise of the protective barrier of the skin. As such, the patient is rendered vulnerable to further infectious complications. Considering these dire clinical consequences, the prompt detection, microbiologic diagnosis, and therapy of diarrhea must be a high priority for clinicians in the ICU.
The epidemiology of diarrheal illness among patients in the ICU is substantially different from that seen among less severely ill patients in the community. Such differences render most of the schemes used to classify diarrhea in other settings less applicable to the evaluation of the critically ill patient. Infectious diarrhea acquired in the outpatient setting is rarely sufficiently severe to warrant admission to the ICU. Therefore, infectious diarrhea among patients in the ICU is most often acquired in the hospital. As a result, the spectrum of clinical disease and associated pathogens for the patient in the ICU tends to be less diverse than that encountered in the community. In fact, the majority of all cases of infectious diarrhea diagnosed in the ICU can be attributed to a single pathogen, Clostridium difficile. For many of these patients, the differential diagnosis consists largely of noninfectious entities, such as diarrhea induced by hyperosmolar enteral feeding solutions.11 Norwalk-like viruses, one of the most common causes of endemic and epidemic diarrhea in the outpatient setting, are rarely identified as the cause of diarrhea in critically ill patients. Similarly, while outbreaks of food-borne gastroenteritis have been reported among hospitalized patients,12 in the absence of an identified cluster, the work-up of the ICU patient with diarrhea usually need not include consideration of these pathogens.
It is in recognition of the rarity with which the clinician in the ICU will encounter diarrhea that is not hospital-acquired that a review of these less familiar presentations is warranted. While the distinctions between these syndromes are somewhat arbitrary, and there is considerable overlap between them, it is imperative that the clinician caring for critically ill patients at least be able to recognize these syndromes. In the sections that follow, inflammatory, noninflammatory, and hemorrhagic diarrheas are considered separately. Each is discussed with respect to the most common clinical presentations and pathogens that could be expected in the ICU (Table 57-2). A general approach to the diagnosis and treatment of diarrhea among patients in the ICU follows. The chapter concludes with an in-depth discussion of diarrhea caused by C. difficile—an organism whose central role as a cause of diarrhea among patients in the ICU has already been discussed.
In general, the noninflammatory diarrheal syndromes are characterized by the production of large volumes of watery stool devoid of gross blood or inflammatory cells. By definition, stool examination for fecal leukocytes in such patients will be negative. The typical presentation and pathophysiology of noninflammatory diarrhea is best exemplified by infection with Vibrio cholerae. While this gram-negative bacillus is the most prevalent cause of dehydrating diarrhea throughout the world, it is rarely encountered as a pathogen causing serious disease in the developed world. That said, the metabolic sequelae of cholera are capable of generating systemic illness sufficiently severe as to require ICU admission in a returning traveler.
While the diarrhea experienced by the patient infected with V. cholerae is characteristic of the other noninflammatory diarrheal infections, the severity of disease is unique to cholera. Diarrhea is voluminous, and patients can lose more than 1 liter of fluid everyhour. Affected patients are at high risk for life-threatening dehydration. Vital signs will reveal tachycardia and hypotension. The metabolic abnormalities can precipitate severe acidosis. To compensate, the patient may become tachypneic. Skin evaluation in these individuals reveals decreased turgor. The mucous membranes, including conjunctivae, appear dry. In extreme cases, the patient's eyes will appear sunken, producing a characteristic facies. If fluids are not replaced promptly and in sufficient quantity, the infection will be fatal.
The diarrhea of cholera is secretory in nature. Having established itself in the lumen of the bowel, V. cholerae releases an extracellular protein that binds to the membrane of intestinal epithelial cells. The enterotoxin induces an increase in intracellular cyclic adenosine monophosphate (cAMP). The high concentration of cAMP induces an increase in chloride secretion and a decrease in sodium absorption, producing the massive fluid and electrolyte loss characteristic of cholera.13
While V. cholerae is the prototypical pathogen associated with noninflammatory diarrhea, an array of other organisms can produce the same syndrome. While the diarrhea induced by these other pathogens tends to be less severe than that of cholera, the greater frequency with which these organisms cause infection in the developed world makes them more likely to be encountered as a cause of diarrhea in this setting. Most important among these are the so-called enterotoxigenic strains of Escherichiacoli. These isolates produce an extracellular toxin, a component of which is similar to that produced by V. cholerae. The end result is comparable—profuse watery diarrhea that challenges patient and clinician to maintain adequate hydration.
Spanning a broad spectrum of clinical severity, inflammatory diarrhea is strictly defined by the presence of fecal leukocytes when the stool from affected patients is examined microscopically. In terms of pathophysiology, these infections are characterized by compromise of the integrity of the intestinal epithelium. Depending on the causative organism, there may be varying degrees of bacterial invasion. As a result of this process, inflammatory cells, including both neutrophils and lymphocytes, are recruited to the affected area, where some are shed into the intestinal lumen.
In the most extreme cases, inflammatory diarrhea causes the clinical syndrome commonly referred to as dysentery. The patient with dysentery presents with semisolid or liquid bowel movements that are not as voluminous as those seen with noninflammatory diarrhea. In fact, some patients report very scant production of fecal matter. For them, bowel movements are characterized by small quantities of gross blood and mucus. Fever is often present, but is usually not exceedingly high. Patients with dysentery may experience severe cramping abdominal pain or tenesmus—pain with the passage of bowel movements. Because of the limited ability of critically ill patients to report such complaints, clinicians should be alert for the presence of the unique stool characteristics that identify the patient with dysentery and inflammatory diarrhea.
A number of pathogens have been described in association with the clinical manifestations of inflammatory diarrhea, but the classical description of the syndrome is associated with infection with Shigella species, particularly S. dysenteriae. As was true for cholera and other noninflammatory diarrheas, this association once again points to a shared pathophysiology. Pathogenic Shigella species elaborate an exotoxin (Shiga toxin) that acts by inhibiting protein synthesis, damaging the intestinal mucosa. Analogous shiga-like toxins have been detected in association with other bacterial species linked to inflammatory diarrhea, including both enteroinvasive and enterohemorrhagic strains of E. coli.
Like Shigella, the other bacterial species commonly identified in cases of inflammatory diarrhea are generally acquired through fecal oral transmission, often in the setting of food-borne outbreaks. In the United States, the most common such pathogens are members of the Salmonella species. Outbreaks of food-borne salmonellosis, while most commonly linked to undercooked poultry and dairy products, have even been reported in the context of a deliberate release associated with an episode of domestic bioterrorism.14 Other important pathogens identified in association with inflammatory diarrhea include E. coli and Campylobacter jejuni.
Patients with hemorrhagic diarrhea, characterized by the presence of frank blood, are increasingly being seen in the setting of the ICU. In addition to the hemodynamic and metabolic complications that characterize other inflammatory diarrheas, patients with hemorrhagic diarrhea have been found to be predisposed to systemic illness that can warrant admission to critical care. Strains of E. coli belonging to serogroup O157:H7 have been epidemiologically linked to the development of the hemolytic uremic syndrome.15 While the mechanism linking infection and this syndrome is not yet well understood, the resultant deposition of fibrin thrombi in the renal glomeruli can induce sufficient anemia, thrombocytopenia, and azotemia as to be life threatening. The hemolytic uremic syndrome typically follows the onset of diarrhea by about 1 week. While many of these patients will require intensive supportive therapy, including blood transfusion and hemodialysis, for most the condition is reversible. Of particular concern to clinicians caring for these patients is the observation that antimicrobial treatment may contribute to the emergence of this syndrome.16
Evaluation of the Critically Ill Patient with Diarrhea
The foremost consideration in the evaluation of the critically ill patient with diarrhea is the prompt recognition of infection with C. difficile. In the setting of prior exposure to antimicrobials or antineoplastic therapy, diarrhea can be presumptively attributed to C. difficile infection until proven otherwise. Identification of these patients is critical not only for the initiation of directed therapy, but to ensure that adequate infection control procedures are followed to limit the spread of infection to other vulnerable patients in the ICU. A comprehensive approach to the diagnosis of C. difficile is provided at the end of this chapter.
Whether or not C. difficile infection can be excluded, the evaluation of diarrhea in the ICU must progress in a systematic fashion with respect to the microbiology of the most likely infecting organism (Table 57-3). The initial assessment of these patients should include an accurate history of both the course of diarrhea and the presence of any precipitating factors that might suggest a causative organism. The patient, or for the uncommunicative patient a family member or friend, should be queried about the timing of onset of diarrhea, the progression of symptoms, associated systemic complaints such as fever or chills, and the nature and quantity of bowel movements (with particular emphasis on the presence or absence of bloody stools). Additional essential data includes information about recent travel, unusual dietary intake, and the presence of similar symptoms among companions with whom the patient has shared a meal. Of course, a history of prior antibiotic therapy or cancer chemotherapy will be needed to distinguish individuals at risk for C. difficile colitis. By the end of this process, the clinician should be able to characterize the diarrhea as acute or chronic, community- or hospital-acquired, and severe or mild. The last finding is of particular importance in that supportive therapy to alleviate severe dehydration should not be withheld pending further laboratory and microbiologic evaluation.
Table 57–3. Diagnostic Approach to the Patient with Infectious Diarrhea ||Download (.pdf)
Table 57–3. Diagnostic Approach to the Patient with Infectious Diarrhea
| Timing and rapidity of onset|
| Associated signs and symptoms (fever)|
| Nature and quantity of bowel movements|
| Prior antibiotics or chemotherapy|
| Hemodynamic compromise (tachycardia or hypotension)|
| Signs of dehydration (orthostasis, skin tenting)|
| Rectal examination for gross or occult bleeding|
| Stool for fecal leukocytes|
| Immunoassay for C. difficile toxins A and B|
| Stool culture (especially in the setting of outbreak or community acquisition)|
| Stool for ova and parasites (if travel-related)|
| Endoscopy (reserve for persistent cases in which other tests are not revealing)|
Given the emphasis placed on distinguishing inflammatory from noninflammatory diarrhea, it will come as no surprise that the initial laboratory work-up of the critically ill patient with diarrhea should include an objective measure of inflammation. Testing for fecal leukocytes offers a reliable means by which to do so. The test is performed by mixing a drop of stool with methylene blue on a slide, followed by examination under a microscope. Testing for stool occult blood has been suggested as another useful tool to identify patients in the ICU with inflammatory diarrhea. Unfortunately, testing for occult blood, even in the presence of a new fever in a critically ill patient, may be of little use in discriminating inflammatory infectious diarrhea from other common, noninfectious causes of bloody bowel movements among such patients, including stress-induced gastric ulceration and ischemic colitis.
In the setting of noninflammatory diarrhea, epidemiologic data must be interpreted to assess the likelihood of infection with V. cholerae. For a traveler returning from an endemic area presenting with signs and symptoms consistent with cholera, direct stool examination under darkfield or phase contrast microscopy can reveal the linear motility characteristic of V. cholerae. The organism will also grow on nonselective bacteriologic media, but the preferred method is culture on thiosulfate-citrate-bile salts-sucrose agar. If infection with enterotoxigenic E. coli is suspected, an assay to detect toxin is available from reference laboratories.
Especially in a patient with community-acquired diarrhea, the identification of fecal leukocytes on direct observation should warrant a search for bacterial pathogens that cause inflammatory diarrhea, including E. coli, C. jejuni, Salmonella, and Shigella species.17 Stool culture can be particularly useful in distinguishing the bacterial pathogens that are commonly associated with these food-borne gastroenteritides. Selective media, such as MacConkey, desoxycholate, and salmonella-shigella agars, are employed in the microbiology lab to enhance the ability to detect these pathogens. It is useful to identify particular epidemiologic concerns to the microbiology lab so that the appropriate media can be employed.
The examination of stool for the presence of ova and parasites is of limited utility among patients in the ICU. First and foremost, the clinical syndromes caused by infection with these organisms tend not to be so serious as to require admission to the ICU. Moreover, the incidence of parasitic infections in ICU patients is so low as to make the positive predictive value of the stool ova and parasite examination vanishingly small. In this context, even a positive finding on stool ova and parasite exam is more likely to represent a false-positive than it is to represent actual infection. Many clinical laboratories have gone so far as to not accept stool ova and parasite specimens from patients who have been hospitalized for 48 to 72 hours.
The role of endoscopy in the evaluation of infectious diarrhea is limited. While biopsy may detect the presence of specific pathogens such as Entamoeba histolytica, the relatively low incidence of these infections in this population makes this the diagnostic procedure of last resort. Lower GI endoscopy will not help to discriminate or diagnose infection with common bacterial pathogens such as E. coli or C. jejuni. As discussed later, sigmoidoscopy and colonoscopy can be helpful in the detection and diagnosis of colitis caused by C. difficile infection.
The foremost objective in the care of the patient with infectious diarrhea is to restore the patient to a normal fluid and electrolyte balance as rapidly as possible. While oral rehydration solutions, such as that recommended by the World Health Organization, have proven safe and effective in settings in which intravenous therapy is either impractical or unavailable, most patients with diarrhea in the ICU will require parenteral replenishment. Effective regimens include lactated Ringer solution and normal saline with electrolyte supplementation. The use of large volumes of 5% dextrose and water for these patients may precipitate dangerous hyponatremia. No matter the regimen selected, serum chemistry analyses should be performed frequently to ensure adequacy of electrolyte replacement.
In general, empirical antimicrobial therapy for infectious diarrhea not associated with C. difficile should be avoided. Indiscriminant antibiotic use for this indication exposes the patient to needless toxicity, may precipitate the emergence of resistant organisms as a cause of systemic infection, can worsen the course of some infection (as in the case of E. coli serotype O157:H7), and might predispose the patient to prolonged carriage with the offending pathogen.18 However, once a specific pathogen has been identified, therapy can be directed by documented susceptibility information—or at least trends among known or suspected pathogens. Pathogen-specific recommendations are listed in Table 57-4.
Table 57–4. Recommended Antimicrobial Regimens for Patients Hospitalized with Bacterial Diarrhea ||Download (.pdf)
Table 57–4. Recommended Antimicrobial Regimens for Patients Hospitalized with Bacterial Diarrhea
|Pathogen||Recommended Treatment Regimen||Notes|
|Campylobacter jejuni||Azithromycin or ciprofloxacin||Fluoroquinolone resistance increasing in some regions|
|Clostridium difficile||Metronidazole||Vancomycin is not preferred because of risk of precipitating resistance; avoid antimotility agents|
|Escherichia coli O157:H7||No antimicrobial therapy advised||Antimicobials may increase the risk of hemolytic uremic syndrome|
|Salmonella species||Ciprofloxacin||Treat only if symptoms are severe or patient is immunocompromised|
|Traveler's diarrhea||Fluoroquinolone||Use of antimotility agents is appropriate|
|Vibrio cholerae||Ciprofloxacin||Rehydration is cornerstone of therapy|