Stress ulcer prophylaxis in the new millennium: A systematic review and meta-analysis

Background: Recent observational studies suggest that bleeding from stress ulceration is extremely uncommon in intensive care unit patients. Furthermore, the risk of bleeding may not be altered by the use of acid suppressive therapy. Early enteral tube feeding (initiated within 48 hrs of intensive care unit admission) may account for this observation. Stress ulcer prophylaxis may, however, increase the risk of hospital-acquired pneumonia and Clostridia difficile infection. Objective: A systematic review of the literature to determine the benefit and risks of stress ulcer prophylaxis and the moderating effect of enteral nutrition. Data Sources: MEDLINE, Embase, Cochrane Register of Controlled Trials, and citation review of relevant primary and review articles. Study Selection: Randomized, controlled studies that evaluated the association between stress ulcer prophylaxis and gastrointestinal bleeding. We included only those studies that compared a histamine-2 receptor blocker with a placebo. Data Extraction: Data were abstracted on study design, study size, study setting, patient population, the histamine-2 receptor blocker and dosage used, the incidence of clinically significant gastrointestinal bleeding, hospital-acquired pneumonia, mortality, and the use of enteral nutrition. Data Synthesis: Seventeen studies (which enrolled 1836 patients) met the inclusion criteria. Patients received adequate enteral nutrition in three of the studies. Overall, stress ulcer prophylaxis with a histamine-2 receptor blocker reduced the risk of gastrointestinal bleeding (odds ratio 0.47; 95% confidence interval, 0.29-0.76; p<.002; I-2 = 44%); however, the treatment effect was noted only in the subgroup of patients who did not receive enteral nutrition. In those patients who were fed enterally, stress ulcer prophylaxis did not alter the risk of gastrointestinal bleeding (odds ratio 1.26; 95% confidence interval, 0.43-3.7). Overall histamine-2 receptor blockers did not increase the risk of hospital-acquired pneumonia (odds ratio 1.53; 95% confidence interval, 0.89-2.61; p=.12; I-2 = 41%); however, this complication was increased in the subgroup of patients who were fed enterally (odds ratio 2.81; 95% confidence interval, 1.20-6.56; p=.02; I-2 = 0%). Overall, stress ulcer prophylaxis had no effect on hospital mortality (odds ratio 1.03; 95% confidence interval, 0.78-1.37; p=.82). The hospital mortality was, however, higher in those studies (n = 2) in which patients were fed enterally and received a histamine-2 receptor blocker (odds ratio 1.89; 95% confidence interval, 1.04-3.44; p=.04, I-2 = 0%). Sensitivity analysis and meta-regression demonstrated no relationship between the treatment effect (risk of gastrointestinal bleeding) and the classification used to define gastrointestinal bleeding, the Jadad quality score nor the year the study was reported. Conclusions: The results of this meta-analysis suggest that, in those patients receiving enteral nutrition, stress ulcer prophylaxis may not be required and, indeed, such therapy may increase the risk of pneumonia and death. However, because no clinical study has prospectively tested the influence of enteral nutrition on the risk of stress ulcer prophylaxis, our findings should be considered exploratory and interpreted with some caution. (Crit Care Med 2010; 38: 2222-2228)