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Stress ulcer, also referred to as stress-related erosive syndrome or stress-related mucosal disease, was initially recognized by Skillman and Silen in the 1970s.1 If not addressed, it can result in minimal to severe gastrointestinal blood loss and may lead to the need for blood transfusion. Several drugs have been tested in randomized trials to prevent the occurrence of stress ulcer in critically ill patients. The two most common classes used in clinical practice include proton pump inhibitors (PPIs) and histamine 2 receptor antagonists (H2RAs). 

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A meta-analysis in 1996 found that H2RAs reduced the risk of clinically important bleeding compared with placebo (odds ratio [OR] 0.44; 95% confidence interval [CI] 0.22–0.88).2 A recent meta-analysis comparing H2RAs to placebo included 1,836 patients from 17 trials and showed similar results (OR 0.47; 95% CI 0.29–0.76).3 Neither meta-analysis showed a statistically significant increase in the risk of nosocomial pneumonia with H2RA administration.2,3 The use of PPIs have also been addressed in the literature but with mixed results. The most recent meta-analysis published4 included 1,587 patients from 13 trials and reported less clinically important bleeding with PPIs compared to H2RAs (OR 0.30; 95% CI 0.17–0.54). Currently, in the United States, it was reported that H2RAs were used as first line by 64% of 500 random intensivists, while PPIs were used by 23%.5

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A recent meta-analysis6 was just published in critical care medicine to determine the safety and efficacy of PPIs vs. H2RAs for the prevention of upper gastrointestinal bleeding in critically ill patients. The authors in this study searched multiple databases including the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, ACPJC, CINHAL, online trials registries (clinicaltrials.gov, ISRCTN Register, WHO ICTRP), conference proceedings databases, and reference lists of relevant articles and included only randomized controlled parallel group trials published before March 2012. The meta-analysis included fourteen trials enrolling a total of 1,720 patients.

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The authors showed that PPIs were more effective than H2RAs at reducing clinically important upper gastrointestinal bleeding (relative risk 0.36; 95% confidence interval 0.19–0.68; p = 0.002) and overt upper gastrointestinal bleeding (RR 0.35; 95% CI 0.21–0.59; p < 0.0001). There were no differences in the risk of nosocomial pneumonia (RR 1.06; 95% CI 0.73–1.52; p = 0.76), ICU mortality (RR 1.01; 95% CI 0.83–1.24; p = 0.91), or ICU length of stay (mean difference −0.54 days; 95% CI −2.20 to 1.13; p = 0.53).  There were no reports related to C. difficile infection in any trial. The authors concluded that PPIs compared to H2RAs seem to be more effective in preventing both clinically important and overt upper gastrointestinal bleeding.

1. Skillman JJ, Silen W. Acute gastroduodenal “stress” ulceration: Barrier disruption of varied pathogenesis? Gastroenterology 1970;59:478–482.   [PubMed: 5458292]
2. Cook DJ, Reeve BK, Guyatt GH, et al. Stress ulcer prophylaxis in critically ill patients. Resolving discordant meta-analyses. JAMA 1996;275:308–314.   [PubMed: 8544272]
3. Marik PE, Vasu T, Hirani A, et al. Stress ulcer prophylaxis in the new millennium: A systematic ...

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