Bleeding and pneumonia in intensive care patients given ranitidine and sucralfate for prevention of stress ulcer: meta-analysis of randomised controlled

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Abstract
Objectives: To determine the effectiveness of ranitidine and sucralfate in the prevention of stress ulcer in critical patients and to assess if these treatments affect the risk of nosocomial pneumonia. Design: Published studies retrieved through Medline and other databases. Five meta-analyses evaluated effectiveness in terms of bleeding rates (A: ranitidine v placebo; B: sucralfate v placebo) and infectious complications in terms of incidence of nosocomial pneumonia (C: ranitidine v placebo; D: sucralfate v placebo; E: ranitidine v sucralfate). Trial quality was determined with an empirical ad hoc procedure. Main outcome measures: Rates of clinically important gastrointestinal bleeding and nosocomial pneumonia (compared between the two study arms and expressed with odds ratios specific for individual studies and meta-analytic summary odds ratios). Results: Meta-analysis A (five studies) comprised 398 patients; meta-analysis C (three studies) comprised 311 patients; meta-analysis D (two studies) comprised 226 patients: and meta-analysis E (eight studies) comprised 1825 patients. Meta-analysis B was not carried out as the literature search selected only one clinical trial. In meta-analysis A ranitidine was found to have the same effectiveness as placebo (odds ratio of bleeding 0.72, 95% confidence interval 0.30 to 1.70, P=0.46). In placebo controlled studies (meta-analyses C and D) ranitidine and sucralfate had no influence on the incidence of nosocomial pneumonia. In comparison with sucralfate, ranitidine significantly increased the incidence of nosocomial pneumonia (meta-analysis E: 1.35, 1.07 to 1.70, P=0.012). The mean quality score in the four analyses (on a 0 to 10 scale) ranged from 5.6 in meta-analysis E to 6.6 in meta-analysis A. Conclusions: Ranitidine is ineffective in the prevention of gastrointestinal bleeding in patients in intensive care and might increase the risk of pneumonia. Studies on sucralfate do not provide conclusive results. These findings are based on small numbers of patients, and firm conclusions cannot presently be proposed.