STRESS-ULCER PROPHYLAXIS IN CRITICALLY ILL PATIENTS - RESOLVING DISCORDANT METAANALYSES

Purpose. - To resolve discrepancies in previous systematic overviews a nd provide estimates of the effect of stress ulcer prophylaxis on gast rointestinal bleeding, pneumonia, and mortality in critically ill pati ents. Data Identification. - Computerized search of published and unpu blished research, bibliographies, pharmaceutical and personal files, a nd conference abstract reports. Study Selection. - Independent review of 269 articles identified 63 relevant randomized trials for inclusion . Data Abstraction. - We made independent, duplicate assessment of the methodologic quality, population, intervention, and outcomes of each trial. Results. - The source of discrepancies between prior meta-analy ses included incomplete identification of relevant studies, differenti al inclusion of non-English language and nonrandomized trials, differe nt definitions of bleeding, provision of additional information throug h direct correspondence with authors, and different statistical method s. The current overview demonstrates that prophylaxis with histamine(2 )-receptor antagonists decreases the incidence of overt gastrointestin al bleeding (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.42 to 0.79) and clinically important bleeding (OR, 0.44; 95% CI, 0.22 to 0.88). There is a trend toward decreased overt bleeding when antacids are compared with no therapy (OR, 0.66; 95% CI, 0.37 to 1.17). Histam ine(2)-receptor antagonists and antacids are associated with a trend t oward lower clinically important bleeding rates than sucralfate is. Th ere is a trend toward an increased risk of pneumonia associated with h istamine(2)-receptor antagonists as compared with no prophylaxis (OR, 1.25; 95% CI, 0.78 to 2.00). Sucralfate is associated with a lower inc idence of nosocomial pneumonia when compared with antacids (OR, 0.80; 95% CI, 0.56 to 1.15) and histamine(2)-receptor antagonists (OR, 0.77; 95% CI, 0.60 to 1.01). Sucralfate is also associated with a reduced m ortality rate (OR, 0.73; 95% CI, 0.54 to 0.97) relative to antacids an d to histamine(2)-receptor antagonists (OR, 0.83; 95% CI, 0.63 to 1.09 ). Conclusions. - Our results emphasize the need for registries to inc lude all randomized trials and demonstrate the importance of explicit methodology for systematic reviews. There is strong evidence of reduce d clinically important gastrointestinal bleeding with histamine(2)-rec eptor antagonists, Sucralfate may be as effective in reducing bleeding as gastric pH-altering drugs and is associated with lower rates of pn eumonia and mortality. However, the data are insufficient to determine the net effect of sucralfate compared with no prophylaxis.