Diarrhea in the ICU is usually multifactorial and may be a reflection of the severity of underlying illness and gut dysmotility (10). Several factors have been associated with a higher incidence, or risk, of developing diarrhea in the ICU (Table 98.1). Such factors include increased severity of illness, oxygen saturation levels, glucose control, albumin concentration, white blood cell count (5), and the need for mechanical ventilation (11). Other important factors relate to the acquisition of nosocomial infections, like Clostridium difficile, and of diarrhea associated with antibiotic use (8,12). In general terms, the causes of diarrhea in the ICU can be classified into one of two major categories: infectious and noninfectious.

Noninfectious causes include diarrhea that is induced by enteral feedings, fecal impaction, the side effects of medications, psychological stress, diagnostic test reagents, certain tumors, endocrine disorders, malabsorption, intestinal ischemia, exacerbation of inflammatory bowel disease, and hypoalbuminemia (9). Diarrhea is a frequently reported complication of enteral feedings, affecting up to 12%-78% of adult patients, even in the absence of GI dysfunction (5,8). Enteral feeding-related diarrhea might be associated with intolerance to enteral nutrients during illness (or after fasting), decreased absorptive capacity of the enteral mucosa, or the effect of osmolar load from the enteral formula. A short period of enteral fasting has been associated with the development of duodenal mucosal atrophy in critically ill patients (13). The role that formula osmolarity plays in the development of diarrhea is not clear. Even though findings are contradictory (11,14), the use of hyperosmolar formulas needs to be approached with caution as higher osmolality may result in excessive intraluminal volume and subsequent diarrhea (15). The delivery site of feedings should also be considered. A randomized controlled study conducted by Davies et al. showed no overall difference in diarrhea when feeds were delivered into the stomach as opposed to postpyloric (16,17). However, the jejunum is more reliant on isosmotic feeds, so hyperosmotic feeds and bolus feeds (bolus feeds cause dumping syndrome) into the jejunum have been associated with diarrhea. A decrease in the absorptive ability of the bowel can significantly interfere with nutrient uptake and lead to an osmotic diarrhea (fluid is drawn into the intestine by the increase in osmotically active contents).

Hypoalbuminemia has been implicated as a predisposing factor for diarrhea in the critically ill (18,19,20), and patients with chronic hypoalbuminemia seem to have a higher degree
of diarrhea than those with acute hypoalbuminemia suggesting that chronicity of malnutrition might be more important than disease severity when it comes to diarrhea (8).

Malabsorption of nonabsorbable solutes in the GI tract, such as carbohydrates, causes osmotic diarrhea. In addition, bacterial fermentation of a portion of the nonabsorbed carbohydrate reaching the colon results in the formation of short-chain fatty acids, which further contributes to the osmotic load presented to the colon and limits water reabsorption. In addition, short-chain fatty acids stimulate peristalsis. Bile acid malabsorption has also been associated with diarrhea in the critically ill (21).

Another factor is the use of antibiotics. They can act via direct effects on the GI tract as well as via their association with the development of C. difficile (8,12). Diarrhea associated with antibiotic use that is not due to development of C. difficile infections is likely due to a direct increase in intestinal motility or to a reduction in bacterial fermentation of carbohydrates. Either of these causes will cease shortly after the antibiotic is discontinued. The risk factors that put ICU patients at risk of C. difficile and other infections include antibiotic use, immune compromise, and acid blockade (22). Infectious diarrhea is troublesome due to the risk of spread of the infection from patient to patient. In adults, the most common cause of infectious diarrhea in the ICU is C. difficile, but Salmonella, rotavirus, and norovirus have also been associated with outbreaks (9). In children, while much of the focus is on C. difficile, it is estimated that 91%-94% of hospital-acquired infectious diarrhea is due to virus, especially rotavirus (9).

Recent years have witnessed an increase in the occurrence of C. difficile. The antibiotics most frequently implicated in C. difficile infection in children are ampicillin, penicillin, cephalosporins, amoxicillin, and clindamycin (23). Although diarrhea is considered the hallmark of C. difficile, it can also present with abdominal pain, and a lack of diarrhea could indicate severe ileus (9). Ang et al. (24) noted in his adult population that admission to the ICU carried a moderate risk of acquiring C. difficile. Its acquisition increased mortality from a baseline of 29%-34%. In another study, the 30-day mortality of patients with C. difficile infection in the ICU was demonstrated to be close to 40% and a 6% mortality rate was directly attributed to the infection (9). Others, however, have noted that if treated early, ICU-acquired C. difficile was not independently associated with increased mortality and only marginally impacted the length of stay in the ICU (6). C. difficile is diagnosed by testing the stool for specific toxins, or by new PCR methodologies. If toxin assays are used, it is important to remember that there are two toxins that can be associated with C. difficile infections (A and B) and that not all commercially available assays measure both. PCR detection is now being commonly used (25). Rarely, it may be necessary to perform emergency endoscopic procedures to establish the diagnosis. In those cases the typical pseudomembranes are seen (26).

Another type of diarrhea that can develop in the ICU patient is secretory diarrhea. This type of diarrhea is voluminous, and unlike osmotic diarrhea does not stop when the patient is fasted. It usually occurs from active intestinal secretion (e.g., secondary to cholera toxin), and it results in major shifts in fluid and electrolytes. It can occur in the setting of critical illness or systemic processes that affect the GI tract. It is often possible to differentiate osmotic from secretory diarrhea, which may help in the management. Osmotic diarrhea typically has less stool volume per day, a lower Na content, a pH of <5, tests positive for reducing/nonreducing sugars, and usually responds to fasting.

A thorough history will help determine if triggers are present, which could be discontinued (like medications) or treated (infections, malabsorption, and underlying inflammatory bowel disease) (2,27). Physical examination will help determine the presence of impaction. Gross stool examination can
detect blood, leukocytes, mucus, ova, and parasites. Presence of leukocytes suggests presence of invasive or toxin-producing microorganism in the gut. The pH and presence of reducing substances in the stool may indicate the presence of carbohydrate malabsorption.

The discontinuation of enteral feeds during diarrhea is not always justified (27). Feedings, however, may need to be adjusted to decrease osmolar load via the reduction of infusion rate, repositioning of feeding tube or dilution of nutrition formula (2). If there is evidence of carbohydrate malabsorption (low pH and reducing substances in stool), the formulas may need to be diluted or the infusion rate lowered. It is important to remember that formulas, which contain sucrose (a nonreducing substance), can produce an osmotic diarrhea and test negative for reducing substances. When there is severe osmotic diarrhea from malabsorption, it is likely that there is significant damage to the absorptive surface of the intestine, and it may be necessary to change to more predigested formulas.

The replacement of fluids and electrolytes and the establishment of hemodynamic stability are the major goals in diarrhea management. Fluid and electrolyte management in the ICU are reviewed in other sections.

The role of probiotics in the ICU is controversial. Some authors have demonstrated clinical improvement with their use (1,28,29), but others have not (30,31). Other therapies such as the addition of soluble fiber to feeds have also been suggested to prolong transit time and decrease diarrhea (2).

Specific treatment needs to be administered in the case of infections like C. difficile. The most commonly used treatments are oral metronidazole and vancomycin, although recent studies have shown the efficacy of rifaximin. The enteral route is preferred, but anecdotal experience suggests that parenteral metronidazole may also be effective (32).

In the cases of secretory diarrheas, it may be necessary to slow down intestinal secretions with the use of loperamide, or similar agents although they must be used with caution in the critically ill (33). Loperamide is not indicated in children <3 years old or who may suffer overgrowth of invasive infectious organisms associated with dysentery if motility is slowed.

Severe skin breakdown is another complication of significant diarrhea that should be anticipated, prevented when possible, and aggressively treated when it occurs.