Secretory Diarrhea

Active chloride secretion is the basic mechanism leading to secretory diarrhea. There are many known stimuli, including toxins, peptides, amines, and derivatives of arachidonic acid. The majority of these substances exert their action through intracellular mediators that stimulate active chloride secretion. The secreted chloride drives the retention of water in the gastrointestinal lumen leading to more liquid stools. Secretory diarrhea occurs even when the patient fasts because the secretory process is independent of enteral intake or the absorptive process (see Table 38.1). Active secretion of chloride anion creates an osmotic gradient in favor of moving water passively from plasma and interstitial space into the intestinal lumen. The osmolality of secretory diarrhea should be nearly iso-osmolar to plasma. This is reflected in the calculation of a fecal osmotic gap, which should be < 50 mOsm/kg in patients who have secretory diarrhea (Figure 38.2).

Osmotic Diarrhea

An osmotic agent causing diarrhea is (1) soluble in water, (2) cannot be absorbed by the small intestine, or (3) may be metabolized by bacteria and converted to substances with smaller molecular weight in the distal intestine. On a per gram basis, a smaller molecular weight substance is a more effective osmotic agent than is a larger molecular weight substance. Osmotic diarrhea is the result of consuming nonabsorbable solutes by mouth or by nasogastric or nasoenteral tube. Thus, this type of diarrhea resolves once the osmotic load is eliminated—that is, after the patient is fasting (see Table 38.1). Because nonelectrolytes cause water retention in cases of osmotic diarrhea, the measured osmolality of the stool will differ (be higher than) from the osmolality of plasma. This will be reflected in the calculation of a fecal osmotic gap, which is typically > 125 mOsm/kg in osmotic diarrhea (Figure 38.2).

Inflammatory Diarrhea

Inflammatory (leaky membrane) diarrhea is usually associated with a damaged intestinal lining. Exudation via the damaged mucosa plus a decrease in absorption is the underlying mechanism. There are several clinical characteristics of leaky membrane diarrhea, including (1) mucosal damage that can be detected by endoscopy, (2) the presence of fecal leukocytes, (3) diarrhea that persists after fasting, and (4) diarrhea that often worsens after feeding (see Table 38.1).

Motility-Related Diarrhea

Antibiotic-Associated Diarrhea

Antibiotic-associated diarrhea is frequently seen in patients in the ICU. Diarrhea may occur in up to 25% of patients receiving antibiotics. Antibiotic therapy predisposes the patient to the development of at least two separate types of diarrhea: (1) osmotic diarrhea caused by altered colonic salvage of carbohydrates and (2) secretory diarrhea caused by Clostridium (C.) difficile toxin. Administration of oral or systemic antibiotics reduces the normal competitive flora, impairs colonic fermentation of carbohydrates, and increases the risk for the development of C. difficile strains. In patients with antibiotic-associated diarrhea (without C. difficile toxin), ingested carbohydrate that is unabsorbed in the small intestine enters the colon. There, it is not metabolized as normally occurs and can induce an osmotic diarrhea. Stool studies are typically normal in these individuals, and diarrhea resolves once the offending antibiotics are discontinued.

However, when an individual patient acquires diarrhea after the antibiotics are discontinued, one should suspect the development of C. difficile–related diarrhea. One third of the cases of C. difficile–related diarrhea occur after the antibiotics have been discontinued. It may be several weeks or longer between discontinuing antibiotics and the onset of the diarrhea. C. difficile is the pathogen in one third of cases of antibiotic-induced diarrhea. However, it is also present in many hospitalized patients with diarrhea unrelated to C. difficile toxin. Those who harbor the organism without the demonstration of symptoms are not at increased risk for the development of subsequent clinical illness, for example, pseudomembranous colitis or colonic perforation. However, they are capable of transmitting the organism to other patients through person-to-person contact and environmental contamination. In addition to antibiotic use, there are other risk factors for the development of C. difficile–related diarrhea including treatment in the ICU setting, proton-pump inhibitor therapy, and enteral feeding.

Intestinal Ischemia

Intestinal ischemia is another cause of diarrhea in patients in the ICU. Risk factors include hypotension, hypoxemia, or sepsis. Ischemic colitis often presents with an abrupt onset of lower abdominal cramping, rectal bleeding, vomiting, and fever. The finding of fecal leukocytes indicates colonic involvement. Individuals with underlying atherosclerotic disease are especially vulnerable, as are those who have undergone an abdominal aortic aneurysm repair (during which the inferior mesenteric artery may be compromised) (see Chapter 92). Ischemic colitis may also result from vasculitis, a ruptured abdominal aneurysm, collagen vascular disease (e.g., systemic lupus erythematosus, rheumatoid arthritis, polyarteritis nodosa, scleroderma), or colorectal cancer. The clinical presentation may vary from mild to severe diarrhea, with or without substantial abdominal discomfort. Ischemia involving the small bowel—that is, mesenteric ischemia—is a more serious problem than is ischemic colitis because of its higher associated mortality.

Diarrhea-Related to Enteral Feeding

Another cause of diarrhea occurring in the ICU is enteral feeding because of poor tolerance to the constituents of enteral feeding formulas. A number of causes have been proposed, including a high osmolality of the solution (e.g., up to 690 mOsm/kg in some preparations), high rate of delivery, bacterial contamination of the feeding solution, malabsorption caused by partial villous atrophy of small bowel mucosa from prolonged fasting, previous malabsorption, and motility alterations with rapid intestinal transit.