Critical Care Medicine

Diarrhea in the ICU

Diagnosis and management of diarrhea in the intensive care unit

Related conditions

Diarrhea in the critical care setting

Hospital-acquired diarrhea

Nosocomial diarrhea

1. Description of the problem

What every clinician needs to know

Diarrhea is defined as more than 3 bowel movements per day and stool weight greater than 200-300 grams per day or volume greater than 250 mL per day.

  • Acute diarrhea is defined as a duration less than 4 weeks.

  • Chronic diarrhea is defined as a duration greater than 4 weeks.

  • Hospital-associated diarrhea is defined as diarrhea developing in a patient hospitalized for more than 3 days.

  • Identifying the cause of diarrhea is vital for appropriate treatment.

Epidemiology

Hospital-acquired diarrhea is quite common, with diarrhea reported occurring in the range of 40-90% in ICU patients. Certain patient populations are at highest risk, such as extensive burn patients.

  • Clostridium difficile is the leading cause of hospital-acquired diarrhea. Lack of previous colonization with Clostridium difficile is the highest risk for developing symptomatic infection.

  • Reported risk factors for diarrhea in the ICU include fever, hypothermia, malnutrition, hypoalbuminemia, cessation of oral feeding, and the presence of an infection site.

Pathophysiology

Diarrheal illnesses may be divided into categories by pathophysiologic mechanism, although some diseases may cause diarrhea by more than once mechanism:

Inflammatory diarrhea

  • May be a result of invasive infections.

  • Immune-mediated (i.e. inflammatory bowel disease, graft-versus-host disease).

  • May lead to bloody stools and stool with mucus/pus.

Secretory diarrhea

  • A result of mucosal secretion of electrolytes and fluid into intestinal lumen and may also be associated with decreased absorption.

  • Production of "secretagogues" by neuroendocrine tumors such as gastrin, vasoactive intestinal polypeptide.

  • Leads to watery and voluminous diarrhea.

Osmotic diarrhea

  • A result of an osmotically active agent in the intestinal tract that cannot be absorbed.

  • Common culprits: medications such as magnesium hydroxide/phosphate or sulfate; antacids containing magnesium; lactose in lactase-deficient individuals, sorbitol-containing products; enteral feeds.

  • Leads to watery and intermittent diarrhea.

Malabsorption

  • Reduction in mucosal surface area available for absorption (i.e. surgical resection or extensive mucosal ulceration), ileal resection leading to bile salt malabsorption, or lack of pancreatic enzymes.

  • Stool may appear oily, foul-smelling.

Motility

  • Gut hypermotility leading to decreased contact of solutes to mucosal surface.

  • Associated with vagotomy, hyperthyroidism, diabetic autonomic neuropathy.

Hospital-associated diarrhea (by categories)

  • Non-infectious causes

    • Enteral feeding

    • Osmotic

    • Malabsorption

    • Medications

    • Intestinal ischemia

    • Bacterial overgrowth

    • Fecal impaction

    • Endocrine disorder

    • Exacerbation of underlying disease such as inflammatory bowel disease

  • Infections

    • Clostridium difficile

    • Rotavirus

    • Norovirus

    • Salmonella

    • Cryptosporidium

    • Microorganisms not typically associated with diarrhea: Candida albicans, Klebsiella oxytoca, Staphylococcus aureus

Hospital-associated non-infectious diarrhea (in more detail)

  • Enteral feeding

    • Most common cause of ICU related diarrhea.

    • Enteral nutrition > 60% of energy target

    • Mode of feeding (continuous vs. gravity vs. intermittent) plays more of a factor than site of feeding (gastric vs. jejunal) for risk of diarrhea. Continuous feeding is associated with the least risk for diarrhea.

    • The composition of enteral feeds may also play a factor in causing diarrhea:

      • Carbohydrate load

      • Fat

      • High osmolarity (acquired lactose intolerance may contribute to this)

      • Bacterial contamination

      • Lack of non-absorbable fiber

  • Medications may lead to diarrhea

    • Antibiotics

    • Gastric acid suppressants (histamine-2 receptor antagonists and proton pump inhibitors)

    • Magnesium-containing oral medications

    • Sorbitol-containing compounds/products

    • Laxatives (inadvertent)

    • Oral hypoglycemic (metformin)

    • Anti-arrhythmics (quinidine)

    • Theophylline

    • Prokinetic agents (metoclopramide)

  • Steatorrhea

    • Associated with the following in the ICU: shock, sepsis, diabetes, cardiac arrest, hyperlactacidemia, mechanical ventilation and hemodialysis

    • Caused by pancreatic insufficiency from septic shock

    • Caused by bile salt malabsorption

  • Endocrine disorders

    • Adrenal insufficiency

    • Hyperthyroidism

    • Diabetes

  • Intestinal ischemia (colon, small intestine)

    • At-risk patients age >65 years

    • Etiology

      • Hypotension, shock (colon affected > small intestine)

      • Thromboembolic (colon, small intestine), hospital-associated infectious diarrhea

Hospital-associated infectious diarrhea

  • Clostridium difficile (a bacteria classified as an anaerobic gram-positive bacillus that produces spores and toxin)

    • Most common cause of health care associated diarrhea

    • Incidence of 2% in the hospitalized setting and 4% in the intensive care unit

    • Risk factors for developing Clostridium difficile infection

      • Exposure to antibiotics

      • Exposure to Clostridium difficile

      • Comorbid conditions (such as gastrointestinal surgery, Inflammatory bowel disease)

      • Medications that reduced gastric acid

      • Elderly (age >60 years)

    • Transmission: fecal-oral

    • Common source: person-person, contact with contaminated surface or item

    • Incubation/duration: unknown, possibly 7 days/requires treatment

  • Salmonella (a bacteria classified as a facultative intracellular gram-negative bacillus) (non-typhoid)

    • 35% of cases in the United States occur in the health care setting.

    • Reportable to public health department

    • Risk factors for developing Salmonella infection

      • Age <20 years and >70 years

      • Immunocompromised (such as HIV, chemotherapy)

      • Aplastic anemia

    • Transmission: fecal-oral

    • Common source: classically contaminated food-poultry, eggs; person-person; contaminated equipment (i.e. endoscopes)

    • Incubation/duration: 12-72 hours/4-7 days

  • Rotavirus (a non-enveloped segmented double-stranded RNA virus)

    • Risk factors

      • Children between the ages of 2-3 years

      • Elderly

    • Transmission: fecal-oral

    • Common source: contact with infected individual

    • Incubation/duration: 2 days/3-8 days

  • Norovirus (a single-stranded RNA virus)

    • 17-46% hospital-acquired in children

    • Risk factors

      • Lack of immunity to norovirus

    • Transmission: fecal-oral, emesis-oral

    • Common source: contact with infected individual

    • Incubation/duration: 12-48 hours/24-60 hours

  • Cryptosporidium (a parasite in the class Protozoa)

    • Risk factors

      • Immune suppression

    • Transmission: fecal-oral

    • Common source: contaminated water

    • Incubation/duration: 2-10 days /1-2 weeks (may be chronic in immune-suppressed patients)

2. Clinical features

Clinical features of non-infectious/noninflammatory diarrhea

  • Non-bloody

  • Absence of fever

  • Osmotic diarrhea: stool output predominately occurs with feeding

  • Malabsorptive diarrhea: increased stool fat, foul smelling

Clinical features of infectious or inflammatory diarrhea

  • Symptoms and signs of possible infection or inflammatory diarrhea

    • stool with blood or mucus

    • fever

    • severe abdominal pain

    • vomiting

    • toxic megacolon: fever and abdominal pain associated with abdominal distention and tenderness, see below for diagnostic testing

    • intestinal ischemia: potential symptoms: bloody diarrhea, abdominal pain

    • hemolytic uremic syndrome (occurs 5-10 days after onset of diarrhea): microangiopathic hemolytic anemia, thrombocytopenia, and renal failure

  • Clostridium difficile

    • potential symptoms: foul-smelling stool, watery diarrhea, abdominal cramps, fever, nausea

    • severe disease: abdominal pain, lack of diarrhea, fever

  • Salmonella

    • potential symptoms: fever, extra-intestinal symptoms (i.e. arthralgia, arthritis), sepsis

  • Rotavirus

    • potential symptoms: profuse watery diarrhea, vomiting

  • Norovirus

    • potential symptoms: fever, diarrhea, nausea, abdominal pain, vomiting

  • Cryptosporidium

    • potential symptoms: watery diarrhea, fever, abdominal pain, nausea and vomiting

    • chronic: bulky/foul-smelling stool, weight loss

3. Diagnosis

Establishing the diagnosis

Obtain a detailed history and physical exam to help focus evaluation.

  • duration of diarrhea

  • onset in relation to hospitalization

  • characteristics of diarrhea: Is it bloody, watery/voluminous, postprandial?

  • weight loss

  • travel history

  • dietary history

  • medications

  • sick contacts

General diagnostic tests

  • Stool studies

  • Serum electrolytes, albumin, and complete blood cell count and serum albumin

  • Blood cultures if febrile

Specific diagnostic tests

Acute diarrhea hospitalized for <3 days, admitted to the ICU (diagnostic tests to include community-acquired infections)

  • stool culture (Salmonella, Shigella, Campylobacter; may also include Aeromonas and Plesiomonas)

  • stool ova and parasites

  • stool Clostridium difficile

  • stool E. coli 0157 (if bloody)

  • stool Yersinia (if bloody)

  • serum: electrolytes, complete blood cell count

  • stool Rotavirus (if watery): reverse transcriptase PCR (most sensitive) or enzyme-linked immunoassays VP2/VP6

Acute diarrhea evaluation hospitalized for 3 days or more

  • similar to acute diarrhea evaluation <3 days hospitalization

  • routine stool cultures may be rejected due to low yield. exceptions: neutropenia <0.5 x 106 cells/mL, HIV, extraintestinal manifestation (i.e. salmonella: erythema nodosum, polyarthritis, fever of undetermined origin), patient > 65 years with comorbidities and end-organ deterioration, possible hospital outbreak

  • bloody diarrhea with or without abdominal pain after shock or hypotension: to consider CT scan for ischemia evaluation

Chronic diarrhea hospitalized for less than 3 days, admitted to the ICU

  • stool ova and parasites

  • stool Clostridium difficile

  • serum electrolytes (to include magnesium, calcium, zinc), albumin

  • complete blood cell count

  • serum thyroid-stimulating hormone

  • celiac antibodies (tissue transglutaminase IgA, anti-endomysial antibody igA, serum IgA level)

  • stool electrolytes (sodium, potassium)

    • calculate stool osmotic gap (290 mOsm/kg - 2 x (sodium + potassium)

    • stool pH <6 indicates carbohydrate malabsorption

  • alpha-1 antitrypsin (A1A) level (stool and serum

    • calculate A1A clearance = [fecal A1A concentration x stool volume/24hrs]/A1A serum concentration

    • A1A clearance >50 mL/24 hours suggests protein-losing enteropathy.

  • colonoscopy if preliminary test unrevealing; to exclude inflammatory bowel disease; microscopic colitis; CMV in immune-suppressed

  • additional testing, see American Gastroenterological Association guidelines for diarrhea evaluation

Chronic diarrhea evaluation hospitalized for 3 days or more

  • evaluation similar to those hospitalized less than 3 days

  • to also consider serum AM cortisol to assess for adrenal insufficiency

4. Management

General complications of diarrhea

  • Dehydration (manifested as tachycardia and/or hypotension)

  • Serum electrolyte imbalances

  • Metabolic acidosis

  • Malnutrition

  • Skin breakdown

General Management

  • avoidance of malnutrition

  • fluid resuscitation

  • electrolyte resuscitation (potassium, magnesium, zinc)

  • treating underlying source for diarrhea

  • anti-diarrheal in the absence of bloody diarrhea, abdominal pain and fever

Emergency Management

Emergent complications of diarrhea

  • Toxic megacolon is a surgical emergency due to the high risk of perforation.

  • Hemolytic uremic syndrome (complication of E. coli 0157)

  • Intestinal ischemia

  • Sepsis

Management

  • Toxic megacolon

    • NPO

    • NGT

    • fluid and electrolyte repletion

    • discontinue antimotility medications: i.e. narcotics, anti-diarrheals, anti-cholinergics.

    • surgery consultation

    • consideration for systemic antibiotics

  • Hemolytic uremic syndrome

    • volume expansion with isotonic saline or Ringer's lactate

    • transfuse for symptomatic anemia

    • transfuse platelets if clinically significant bleeding or invasive procedure needed

    • close monitoring: urine output, weight, volume status, cardiovascular function, respiratory function, and early signs of CNS compromise

    • nephrology consultation; indication for dialysis the same as for acute renal failure; to consider plasmapheresis but unclear benefit

  • Intestinal ischemia

    • imaging (i.e. CT) to assess location (i.e. small intestine, colon)

    • follow abdominal exam for signs of worsening tenderness, peritoneal signs

    • follow labs for metabolic acidosis, rise in serum lactate

    • consultation: surgery to follow, may need gastroenterology to aid/verify diagnosis (i.e. flexible sigmoidoscopy)

  • Sepsis

    • see other chapters for general management of sepsis in the ICU

    • blood cultures

    • antibiotics, best if specific to organism suspected

    • aggressive volume repletion

    • may need vasopressors

Treatment and prevention

Empiric therapy with loperamide or diphenoxylate may help minimize volume loss. Adsorbents (bismuth subsalicylate [Pepto-Bismol], dioctahedral smectite, attapulgite [Kaopectate]), tincture of opium, and codeine can also be used in refractory cases. Antidiarrheal medications are not recommended in the setting of fever or bloody diarrhea. Absorbents should be avoided if oral antibiotics are given, since absorbents may interfere with antibiotic absorption.

Special considerations:

  • Noninfectious causes

    • Enteral feeding : if bolus or gravity feeding, consider changing to continuous, and if other causes have been excluded, consider changing enteral feed composition, rate, consider adding fiber

    • Intestinal ischemia: if related to hypotension may be able to be managed conservatively, consult surgery and gastroenterology services

    • Bacterial overgrowth: once diagnosed; treatment with antibiotics (i.e. rifaximin, metronidazole)

  • Infections

    • Clostridium difficile: 1) Vancomycin 125 mg PO or per enteral tube every 6 hours x 10 days or metronidazole 250 mg PO or per enteral tube every 6 hours x 10 days. 2) Severe cases (serum albumin <3 g/dl and WBC ≥ 15,000 cells/mm3 or abdominal tenderness): vancomycin 125 mg PO or per enteral tube is preferred over metronidazole and 250 mg PO or per enteral tube may be used if concern for ileus. In severe cases vancomycin may also be combined with metronidazole IV or PO/per enteral tube. 3) Severe and complicated cases (any of the following due to Clostridium difficile infection: admission to the ICU, hypotension, fever ≥38.5°C, ileus or significant abdominal distention, mental status changes, WBC ≥ 35,000 cells/mm3 or <2,000 cells/mm3, serum lactate ≥2.2 mmol/l, end organ failure (mechanical ventilation, renal failure, etc.): vancomycin 500 mg PO or per enteral tube, metronidazole 500 mg IV every 8 hours and vancomycin 500 mg per rectal tube four times a day. Surgery consultation also recommended. 4) Surgery should be considered if any of the following caused by Clostridium difficile infection: hypotension requiring vasopressor therapy, clinical signs of sepsis or organ dysfunction; mental status changes; WBC ≥50,000 cells/mm3, lactate ≥5 mmol/l; or complicated CDI with failure to improve on medical therapy after 5 days. 5) Recurrent Clostridium difficile (within 8 weeks)- with 3rd episode consider Vancomycin pulsed regimen, if recurrence after pulsed regimen consider FMT. 6)Avoid antibiotics that lead to Clostridium difficile diarrhea. If antibiotics are absolutely necessary then consider switching to antibiotics associated with less risk (i.e. avoiding fluoroquinolones, ampicillin, clindamycin and cephalosporins). 7) Contact precautions. 8) Probiotics are not yet recommended to prevent Clostridium difficile infection in the ICU.

    • Norovirus : 1) General management of diarrhea. 2) Contact precautions. 3) Resistance to alcohol and environment may need to be cleaned with bleach. 4) Employees involved in cleaning may benefit by wearing a mask because heavily soiled surfaces may lead to aerosolization.

    • Salmonella : usually self-limited; antibiotic therapy recommended for moderate to severe disease, bacteremia, signs of extraintestinal disease, patients with sickle cell disease or prosthetic grafts, and immune-suppressed patients. Levofloxacin 500 mg once a day for 7-10 days or azithromycin 500 mg once a day for 7 days.

    • Cryptosporidium : usually self-limited in immune-competent individuals; may use nitazoxanide 500 mg PO twice a day for 3days; HIV patients: unclear benefit of nitazoxanide, need to improve CD4 count

Special considerations for nursing and allied health professionals.

N/A

What's the evidence?

"AGA Technical Review on the Evaluation and Management of Chronic Diarrhea". Gastroenterology. vol. 116. 1999. pp. 1464-86.

(An extensive review on the diagnostic evaluation of chronic diarrhea released by the American Gastroenterological Association.)

Bitzan, M. "Treatment options for HUS secondary to Escherichia coli O157:H7". Kidney international Supplement. vol. 112. 2009. pp. S62-6.

(Current management recommendations for hemolytic uremic syndrome due to Escherichia coli O157:H7.)

Bobo, LD. "Recognition and prevention of hospital-associated enteric infection in the intensive care unit". Crit Care Med. vol. 38. 2010. pp. S324-34.

(An excellent overview of infectious diarrhea in the intensive care unit.)

Blaser, A. "Diarrhoea in the critically ill". Cur Opin Crit Care. vol. 21. 2015. pp. 142-153.

(Review focused on the evaluation of diarrhea in the intensive care unit.)

Pawlowski, SW. "Diagnosis and treatment of acute or persistent diarrhea". Gastroenterology. vol. 136. 2009. pp. 1874-86.

(An excellent review of infectious causes of acute and chronic diarrhea.)

Riddle, D. "Clostridium difficile infection in the intensive care unit". Infectious Disease Clinics of North America. vol. 23. 2009. pp. 727-43.

(A comprehensive review of the epidemiology, pathophysiology, diagnostic evaluation and management of Clostridium difficile infection in the intensive care setting.)

Suracicz, C. "Guidelines for Diagnosis. Treatment and Prevention of Clostridium difficile Infections". Am J Gastroenterol. vol. 108. 2013. pp. 478-498.

(Guidelines from the American College of Gastroenterology for evaluation and management of Clostridium difficile infection.)

Zilberberg, M. "Preventing Clostridium Difficile Infection in the Intensive Care Unit". Crit Care Clin. vol. 29. 2013. pp. 11-18.

(Review of the methods and supporting evidence for preventing Clostridium difficile infection in the Intensive Care Unit.)
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