Stress ulcer prophylaxis in the intensive care unit
- Gerald L Weinhouse, MD
Gerald L Weinhouse, MD
- Assistant Professor of Medicine
- Harvard Medical School
Stress ulcerations usually occur in the fundus and body of the stomach, but sometimes develop in the antrum, duodenum, or distal esophagus. They tend to be shallow and cause oozing of blood from superficial capillary beds. Deeper lesions may also occur, which can erode into the submucosa and cause massive hemorrhage or perforation .
The epidemiology, pathophysiology, risk factors, and prognosis of stress ulceration in the intensive care unit (ICU) are discussed in this topic review. In addition, stress ulcer prophylaxis is reviewed. Diagnosis and treatment of bleeding peptic ulcers are discussed separately. (See "Approach to acute upper gastrointestinal bleeding in adults" and "Overview of the treatment of bleeding peptic ulcers".)
Epidemiology — Estimates of the incidence of overt gastrointestinal (GI) bleeding range from 1.5 to 8.5 percent among all intensive care unit (ICU) patients, but may be as high as 15 percent among patients who do not receive stress ulcer prophylaxis [2-5]. Most episodes of overt GI bleeding in critically ill patients are due to gastric or esophageal ulceration, as determined by endoscopic studies [2,5]. Stress ulceration can also cause perforation. However, this complication is rare, occurring in fewer than 1 percent of surgical ICU patients .
Pathophysiology — Stress ulceration generally begins in the proximal regions of the stomach within hours of major trauma or serious illness. Endoscopy performed within 72 hours of a major burn or cranial trauma reveals acute mucosal abnormalities in greater than 75 percent of patients . Up to 50 percent of such lesions have endoscopic evidence of recent or ongoing bleeding, although only a small percentage of patients experience hemodynamic compromise due to acute blood loss .
Stress ulcerations that develop after the first several days of hospitalization tend to be deeper and more distal . In a study of 67 patients with GI bleeding that occurred an average of 14 days after admission, duodenal ulceration was the most common source of bleeding .
- Cook DJ. Stress ulcer prophylaxis: gastrointestinal bleeding and nosocomial pneumonia. Best evidence synthesis. Scand J Gastroenterol Suppl 1995; 210:48.
- Cook DJ, Fuller HD, Guyatt GH, et al. Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group. N Engl J Med 1994; 330:377.
- Ben-Menachem T, Fogel R, Patel RV, et al. Prophylaxis for stress-related gastric hemorrhage in the medical intensive care unit. A randomized, controlled, single-blind study. Ann Intern Med 1994; 121:568.
- Shuman RB, Schuster DP, Zuckerman GR. Prophylactic therapy for stress ulcer bleeding: a reappraisal. Ann Intern Med 1987; 106:562.
- Cook DJ, Griffith LE, Walter SD, et al. The attributable mortality and length of intensive care unit stay of clinically important gastrointestinal bleeding in critically ill patients. Crit Care 2001; 5:368.
- Tsiotos GG, Mullany CJ, Zietlow S, van Heerden JA. Abdominal complications following cardiac surgery. Am J Surg 1994; 167:553.
- DePriest JL. Stress ulcer prophylaxis. Do critically ill patients need it? Postgrad Med 1995; 98:159.
- Czaja AJ, McAlhany JC, Pruitt BA Jr. Acute gastroduodenal disease after thermal injury. An endoscopic evaluation of incidence and natural history. N Engl J Med 1974; 291:925.
- Terdiman JP, Ostroff JW. Gastrointestinal bleeding in the hospitalized patient: a case-control study to assess risk factors, causes, and outcome. Am J Med 1998; 104:349.
- Ritchie WP Jr. Role of bile acid reflux in acute hemorrhagic gastritis. World J Surg 1981; 5:189.
- Schindlbeck NE, Lippert M, Heinrich C, Müller-Lissner SA. Intragastric bile acid concentrations in critically ill, artificially ventilated patients. Am J Gastroenterol 1989; 84:624.
- Navab F, Steingrub J. Stress ulcer: is routine prophylaxis necessary? Am J Gastroenterol 1995; 90:708.
- Geus WP, Lamers CB. Prevention of stress ulcer bleeding: a review. Scand J Gastroenterol Suppl 1990; 178:32.
- Bowen JC, Fleming WH, Thompson JC. Increased gastrin release following penetrating central nervous system injury. Surgery 1974; 75:720.
- Stremple JF, Molot MD, McNamara JJ, et al. Posttraumatic gastric bleeding: prospective gastric secretion composition. Arch Surg 1972; 105:177.
- Watts CC, Clark K. Gastric acidity in the comatose patient. J Neurosurg 1969; 30:107.
- Maury E, Tankovic J, Ebel A, et al. An observational study of upper gastrointestinal bleeding in intensive care units: is Helicobacter pylori the culprit? Crit Care Med 2005; 33:1513.
- Robertson MS, Cade JF, Clancy RL. Helicobacter pylori infection in intensive care: increased prevalence and a new nosocomial infection. Crit Care Med 1999; 27:1276.
- Martin LF, Booth FV, Reines HD, et al. Stress ulcers and organ failure in intubated patients in surgical intensive care units. Ann Surg 1992; 215:332.
- Hatton J, Lu WY, Rhoney DH, et al. A step-wise protocol for stress ulcer prophylaxis in the neurosurgical intensive care unit. Surg Neurol 1996; 46:493.
- McBride DQ, Rodts GE. Intensive care of patients with spinal trauma. Neurosurg Clin N Am 1994; 5:755.
- Daley RJ, Rebuck JA, Welage LS, Rogers FB. Prevention of stress ulceration: current trends in critical care. Crit Care Med 2004; 32:2008.
- ASHP Therapeutic Guidelines on Stress Ulcer Prophylaxis. ASHP Commission on Therapeutics and approved by the ASHP Board of Directors on November 14, 1998. Am J Health Syst Pharm 1999; 56:347.
- Spirt MJ, Stanley S. Update on stress ulcer prophylaxis in critically ill patients. Crit Care Nurse 2006; 26:18.
- Guillamondegui, OD, Gunter OL, et al. Practice management guidelines for stress ulcer prophylaxis, Eastern Association for the Surgery of Trauma (EAST), Chicago 2008. p.24.
- Pingleton SK, Hadzima SK. Enteral alimentation and gastrointestinal bleeding in mechanically ventilated patients. Crit Care Med 1983; 11:13.
- Raff T, Germann G, Hartmann B. The value of early enteral nutrition in the prophylaxis of stress ulceration in the severely burned patient. Burns 1997; 23:313.
- Cook D, Heyland D, Griffith L, et al. Risk factors for clinically important upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. Crit Care Med 1999; 27:2812.
- Marik PE, Vasu T, Hirani A, Pachinburavan M. Stress ulcer prophylaxis in the new millennium: a systematic review and meta-analysis. Crit Care Med 2010; 38:2222.
- Schupp KN, Schrand LM, Mutnick AH. A cost-effectiveness analysis of stress ulcer prophylaxis. Ann Pharmacother 2003; 37:631.
- Cash BD. Evidence-based medicine as it applies to acid suppression in the hospitalized patient. Crit Care Med 2002; 30:S373.
- Herzig SJ, Vaughn BP, Howell MD, et al. Acid-suppressive medication use and the risk for nosocomial gastrointestinal tract bleeding. Arch Intern Med 2011; 171:991.
- Grube RR, May DB. Stress ulcer prophylaxis in hospitalized patients not in intensive care units. Am J Health Syst Pharm 2007; 64:1396.
- Wohlt PD, Hansen LA, Fish JT. Inappropriate continuation of stress ulcer prophylactic therapy after discharge. Ann Pharmacother 2007; 41:1611.
- Pemberton LB, Schaefer N, Goehring L, et al. Oral ranitidine as prophylaxis for gastric stress ulcers in intensive care unit patients: serum concentrations and cost comparisons. Crit Care Med 1993; 21:339.
- Baghaie AA, Mojtahedzadeh M, Levine RL, et al. Comparison of the effect of intermittent administration and continuous infusion of famotidine on gastric pH in critically ill patients: results of a prospective, randomized, crossover study. Crit Care Med 1995; 23:687.
- Ballesteros MA, Hogan DL, Koss MA, Isenberg JI. Bolus or intravenous infusion of ranitidine: effects on gastric pH and acid secretion. A comparison of relative efficacy and cost. Ann Intern Med 1990; 112:334.
- McCarthy DM. Sucralfate. N Engl J Med 1991; 325:1017.
- Rees WD. Mechanisms of gastroduodenal protection by sucralfate. Am J Med 1991; 91:58S.
- Tryba M, Kurz-Müller K, Donner B. Plasma aluminum concentrations in long-term mechanically ventilated patients receiving stress ulcer prophylaxis with sucralfate. Crit Care Med 1994; 22:1769.
- Wilson DE. Antisecretory and mucosal protective actions of misoprostol. Potential role in the treatment of peptic ulcer disease. Am J Med 1987; 83:2.
- Dajani EZ. Overview of the mucosal protective effects of misoprostol in man. Prostaglandins 1987; 33 Suppl:117.
- Cook DJ, Reeve BK, Guyatt GH, et al. Stress ulcer prophylaxis in critically ill patients. Resolving discordant meta-analyses. JAMA 1996; 275:308.
- Cook DJ, Witt LG, Cook RJ, Guyatt GH. Stress ulcer prophylaxis in the critically ill: a meta-analysis. Am J Med 1991; 91:519.
- Phillips JO, Metzler MH, Palmieri MT, et al. A prospective study of simplified omeprazole suspension for the prophylaxis of stress-related mucosal damage. Crit Care Med 1996; 24:1793.
- Lasky MR, Metzler MH, Phillips JO. A prospective study of omeprazole suspension to prevent clinically significant gastrointestinal bleeding from stress ulcers in mechanically ventilated trauma patients. J Trauma 1998; 44:527.
- Tryba M. Prophylaxis of stress ulcer bleeding. A meta-analysis. J Clin Gastroenterol 1991; 13 Suppl 2:S44.
- Barkun AN, Bardou M, Pham CQ, Martel M. Proton pump inhibitors vs. histamine 2 receptor antagonists for stress-related mucosal bleeding prophylaxis in critically ill patients: a meta-analysis. Am J Gastroenterol 2012; 107:507.
- MacLaren R, Reynolds PM, Allen RR. Histamine-2 receptor antagonists vs proton pump inhibitors on gastrointestinal tract hemorrhage and infectious complications in the intensive care unit. JAMA Intern Med 2014; 174:564.
- Cook D, Guyatt G, Marshall J, et al. A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. N Engl J Med 1998; 338:791.
- Messori A, Trippoli S, Vaiani M, et al. Bleeding and pneumonia in intensive care patients given ranitidine and sucralfate for prevention of stress ulcer: meta-analysis of randomised controlled trials. BMJ 2000; 321:1103.
- Prod'hom G, Leuenberger P, Koerfer J, et al. Nosocomial pneumonia in mechanically ventilated patients receiving antacid, ranitidine, or sucralfate as prophylaxis for stress ulcer. A randomized controlled trial. Ann Intern Med 1994; 120:653.
- Driks MR, Craven DE, Celli BR, et al. Nosocomial pneumonia in intubated patients given sucralfate as compared with antacids or histamine type 2 blockers. The role of gastric colonization. N Engl J Med 1987; 317:1376.
- Bateman BT, Bykov K, Choudhry NK, et al. Type of stress ulcer prophylaxis and risk of nosocomial pneumonia in cardiac surgical patients: cohort study. BMJ 2013; 347:f5416.
- Eom CS, Jeon CY, Lim JW, et al. Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis. CMAJ 2011; 183:310.
- Torres A, El-Ebiary M, Soler N, et al. Stomach as a source of colonization of the respiratory tract during mechanical ventilation: association with ventilator-associated pneumonia. Eur Respir J 1996; 9:1729.
- Ryan P, Dawson J, Teres D, et al. Nosocomial pneumonia during stress ulcer prophylaxis with cimetidine and sucralfate. Arch Surg 1993; 128:1353.
- Bonten MJ, Gaillard CA, de Leeuw PW, Stobberingh EE. Role of colonization of the upper intestinal tract in the pathogenesis of ventilator-associated pneumonia. Clin Infect Dis 1997; 24:309.
- Maier RV, Mitchell D, Gentilello L. Optimal therapy for stress gastritis. Ann Surg 1994; 220:353.
- Dial S, Delaney JA, Barkun AN, Suissa S. Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease. JAMA 2005; 294:2989.
- Dial S, Delaney JA, Schneider V, Suissa S. Proton pump inhibitor use and risk of community-acquired Clostridium difficile-associated disease defined by prescription for oral vancomycin therapy. CMAJ 2006; 175:745.
- Linsky A, Gupta K, Lawler EV, et al. Proton pump inhibitors and risk for recurrent Clostridium difficile infection. Arch Intern Med 2010; 170:772.
- Howell MD, Novack V, Grgurich P, et al. Iatrogenic gastric acid suppression and the risk of nosocomial Clostridium difficile infection. Arch Intern Med 2010; 170:784.
- Morrison RH, Hall NS, Said M, et al. Risk factors associated with complications and mortality in patients with Clostridium difficile infection. Clin Infect Dis 2011; 53:1173.
- Kwok CS, Arthur AK, Anibueze CI, et al. Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis. Am J Gastroenterol 2012; 107:1011.
- Tleyjeh IM, Abdulhak AB, Riaz M, et al. The association between histamine 2 receptor antagonist use and Clostridium difficile infection: a systematic review and meta-analysis. PLoS One 2013; 8:e56498.