Do All Hospitalized Patients Need Stress Ulcer Prophylaxis?
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1-MINUTE CONSULT CME EDUCATIONAL OBJECTIVE: Readers will recognize which critically ill patients need stress ulcer prophylaxis CREDIT BRIEF ANSWERS TO SPECIFIC CLINICAL Q: Do all hospitalized patients QUESTIONS need stress ulcer prophylaxis? NASEEM EISA, MD Department of Hospital Medicine, Cleveland Clinic, Cleveland, OH and increased stomach acidity through gastrin stimulation of parietal cells. FATEH BAZERBACHI, MD Department of Medicine, University of Minnesota, Minneapolis, MN More than 75% of patients with major burns or cranial trauma develop endoscopic mucosal ABDUL HAMID ALRAIYES, MD 1 Department of Pulmonary Diseases, Critical Care, and Environmental Medi- abnormalities within 72 hours of injury. In cine, Tulane University Health Sciences Center, New Orleans, LA critically ill patients, the risk of ulcer-related M. CHADI ALRAIES, MD overt bleeding is estimated to be 5% to 25%. Division of Cardiology, University of Minnesota, Minneapolis Furthermore, 1% to 5% of stress ulcers can be deep enough to erode into the submucosa, caus- ing clinically significant GI bleeding, defined as No. Based on current evidence and bleeding complicated by hemodynamic com- A: guidelines, routine acid-suppressive promise or a drop in hemoglobin that requires therapy to prevent stress ulcers has no ben- a blood transfusion.2 In contrast, in inpatients efit in hospitalized patients outside the crit- who are not critically ill, the risk of overt bleed- ical-care setting. Only critically ill patients ing from stress ulcers is less than 1%.3 who meet specific criteria, as described in the In the guidelines of the American Society of Health ■ ADDRESSING RISK United States, System Pharmacists, should receive acid-sup- pressive therapy. A multicenter prospective cohort study of stress ulcer Unfortunately, routine stress ulcer prophy- 2,252 intensive care patients2 reported two prophylaxis laxis is common in US hospitals, unnecessar- main risk factors for significant bleeding is overused ily putting patients at risk of complications caused by stress ulcers: mechanical ventila- and adding costs. tion for more than 48 hours and coagulopathy, in general-care defined as a platelet count below 50× 109/L, hospital floors ■ STRESS ULCER AND CRITICAL ILLNESS an international normalized ratio greater than 1.5, or a partial thromboplastin time more despite the lack Stress ulcers—ulcerations of the upper part than twice the control value.4 In hemody- of supporting of the gastrointestinal (GI) mucosa in the namically stable patients receiving anticoagu- setting of acute disease—usually involve the lation in a general medical or surgical ward, evidence fundus and body of the stomach. The stomach the risk of GI bleeding was low, and acid sup- is lined with a glycoprotein mucous layer rich pression failed to lower the rate of stress ulcer in bicarbonates, forming a physiologic barrier occurrence.3 to protect the gastric wall from acid insult by Other risk factors include severe sepsis, neutralizing hydrogen ions. Disruption of this shock, liver failure, kidney failure, burns over protective layer can occur in critically ill pa- 35% of the total body surface, organ trans- tients (eg, those with shock or sepsis) through plantation, cranial trauma, spinal cord trau- overproduction of uremic toxins, increased ma, history of peptic ulcer disease, and history reflux of bile salts, compromised blood flow, of upper GI bleeding.3,5,6 Steroid therapy is not considered a risk factor for stress ulcers unless doi:10.3949/ccjm.81a.13070 it is used in the presence of another risk fac- CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 81 • NUMBER 1 JANUARY 2014 23 Downloaded from www.ccjm.org on September 24, 2021. For personal use only. All other uses require permission. STRESS ULCER PROPHYLAXIS tor such as use of aspirin or nonsteroidal anti- anism is not clear. (Small-bowel bacterial inflammatory drugs (NSAIDs).2 overgrowth is the hypothesized cause.) ■ INDICATIONS FOR PROPHYLAXIS Bone fracture PPIs lower gastric acidity, and this can inhibit Prophylaxis with a proton pump inhibitor intestinal calcium absorption. Furthermore, (PPI) is indicated in specific conditions—ie, PPIs may directly inhibit bone resorption by peptic ulcer disease, gastroesophageal re- osteoclasts.14 flux disease, chronic NSAID therapy, and Zollinger-Ellison syndrome—and to eradicate Reduction in clopidogrel efficacy Helicobacter pylori infection.7 But in the Unit- PPIs may reduce the efficacy of clopidogrel as a ed States, stress ulcer prophylaxis is overused result of competitive inhibition of cytochrome in general-care floors despite the lack of sup- CYP2C19, which is necessary to metabolize porting evidence. clopidogrel to its active forms. Therefore, con- The American Society of Health System comitant use of clopidogrel with omeprazole, Pharmacists guidelines recommend it in the esomeprazole, or other CYP2C19 inhibitors is intensive care unit for patients with any of the not recommended.15 following: coagulopathy, prolonged mechani- cal ventilation (more than 48 hours), GI ulcer Nutritional deficiencies or bleeding within the past year, sepsis, a stay The overgrown microorganisms consume co- longer than 1 week in the intensive care unit, balamin in the stomach, resulting in vitamin occult GI bleeding for 6 or more days, and B12 deficiency. Acid-suppressive therapy can steroid therapy with more than 250 mg of hy- also reduce the absorption of magnesium and drocortisone daily.8 Hemodynamically stable iron.12 patients admitted to general-care floors should not receive stress ulcer prophylaxis, as it only Unnecessary cost negligibly decreases the rate of GI bleeding, Heidelbaugh and Inadomi16 reviewed the Only critically from 0.33% to 0.22%.9 non-evidence-based use of stress ulcer prophy- ill patients laxis in patients admitted to a large university ■ WHY ROUTINE ULCER PROPHYLAXIS hospital and estimated that it entailed a cost who meet IS NOT FOR ALL HOSPITALIZED PATIENTS to the hospital of $111,791 over the course of specific criteria a year. should receive Although stress ulcer prophylaxis is often considered benign, its lack of proven benefit, ■ WHICH ULCER PROPHYLAXIS SHOULD BE stress ulcer additional cost, and risk of adverse effects, USED IN CRITICALLY ILL PATIENTS? prophylaxis including interactions with foods and other drugs, preclude using it routinely for all hos- Studies have shown histamine-2 blockers to pitalized patients.10,11 Chronic use of PPIs has be superior to antacids and sucralfate in pre- been associated with complications, as dis- venting stress ulcer and GI bleeding,8,15 but no cussed below. study has compared PPIs with sucralfate and antacids. Infection When indicated, an oral PPI is preferred Acid suppression may impair the destruction over an oral histamine-2 blocker for GI pro- of ingested microorganisms, resulting in over- phylaxis.17 This practice is considered cost- growth of bacteria.12 Overuse of PPIs may in- effective and is associated with lower rates of crease the risk of several infections: stress ulcer and GI bleeding. In intubated pa- • Diarrhea due to Clostridium difficile12 tients, however, an intravenous histamine-2 • Community-acquired pneumonia, from in- blocker is preferable to an intravenous PPI.3,8,11 creased microaspiration of overgrown micro- Interestingly, no difference was reported be- organisms into the lung.12 tween PPIs and histamine-2 blockers in terms • Spontaneous bacterial peritonitis in pa- of mortality rate or reduction in the incidence tients with cirrhosis,13 although the mech- of nosocomial pneumonia.17 24 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 81 • NUMBER 1 JANUARY 2014 Downloaded from www.ccjm.org on September 24, 2021. For personal use only. All other uses require permission. EISA AND COLLEAGUES ■ OUR RECOMMENDATION and pharmacists about current guidelines. Computerized ordering templates and re- Only critically ill patients who meet the minders to discontinue prophylaxis at dis- specific criteria described here should re- charge or step-down may decrease overall ceive stress ulcer prophylaxis. More effort is use, reduce costs, and limit potential side needed to educate residents, medical staff, effects.18 ■ terol Suppl 1995; 210:48–52. ■ REFERENCES 11. Messori A, Trippoli S, Vaiani M, Gorini M, Corrado A. Bleeding and 1. DePriest JL. Stress ulcer prophylaxis. Do critically ill patients need it? pneumonia in intensive care patients given ranitidine and sucralfate Postgrad Med 1995; 98:159–168. for prevention of stress ulcer: meta-analysis of randomised con- 2. Cook DJ, Fuller HD, Guyatt GH, et al. Risk factors for gastrointestinal trolled trials. BMJ 2000; 321:1103–1106. bleeding in critically ill patients. Canadian Critical Care Trials Group. 12. Heidelbaugh JJ, Kim AH, Chang R, Walker PC. Overutilization of N Engl J Med 1994; 330:377–381. proton-pump inhibitors: what the clinician needs to know. Therap 3. Qadeer MA, Richter JE, Brotman DJ. Hospital-acquired gastrointes- Adv Gastroenterol 2012; 5:219–232. tinal bleeding outside the critical care unit: risk factors, role of acid 13. Deshpande A, Pasupuleti V, Thota P, et al. Acid-suppressive therapy suppression, and endoscopy findings. J Hosp Med 2006; 1:13–20. 4. Shuman RB, Schuster DP, Zuckerman GR. Prophylactic therapy for stress is associated with spontaneous bacterial peritonitis in cirrhotic ulcer bleeding: a reappraisal. Ann Intern Med 1987; 106:562–567. patients: a meta-analysis. J Gastroenterol Hepatol 2013; 28:235–242. 5. Dellinger RP, Levy MM, Rhodes A, et al; Surviving Sepsis Campaign 14. Farina C, Gagliardi S. Selective inhibition of osteoclast vacuolar H(+)- Guidelines Committee including the Pediatric Subgroup. Surviving ATPase. Curr Pharm Des 2002; 8:2033–2048. sepsis campaign: international guidelines for management of severe 15. ASHP Therapeutic Guidelines on Stress Ulcer Prophylaxis. ASHP sepsis and septic shock: 2012. Crit Care Med 2013; 41:580–637. Commission on Therapeutics and approved by the ASHP Board of 6. Cook DJ, Reeve BK, Guyatt GH, et al. Stress ulcer prophylaxis in criti- Directors on November 14, 1998. Am J Health Syst Pharm 1999; cally ill patients. Resolving discordant meta-analyses. JAMA 1996; 56:347–379. 275:308–314. 16. Heidelbaugh JJ, Inadomi JM.