Carafate :: Multiple pharmacies comparison.

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 ill 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.

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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.
Introduction
Ranitidine and sucralfate are widely used to prevent stress ulcers in patients admitted to intensive care units.[1] A meta-analysis published by Cook et al in 1996 showed that [H.sub.2] receptor antagonists (such as cimetidine and ranitidine together) are more effective than placebo for this clinical indication.[2] With regard to sucralfate, this meta-analysis found a small but significant reduction in overt bleeding but no effect on clinically important events. The meta-analysis did not resolve the question of an increased risk of nosocomial pneumonia related to the use of [H.sub.2] receptor antagonists.
Several arguments emphasise the need for up to date information on this issue. Firstly, ranitidine has become the main [H.sub.2] receptor antagonist used for prophylaxis for stress ulcers, and cimetidine has generally been abandoned[1]; secondly, new findings have been published on effectiveness and complications of ranitidine; and, thirdly, a meta-analytic comparison of ranitidine versus placebo has never been carried out, and, as the comparison of sucralfate and placebo made by Cook et al gave no proof of the effectiveness of this drug, ranitidine and sucralfate might both be ineffective. Another problem is that the most recent randomised studies on this topic did not include a group with no prophylaxis and compared supposedly active treatments with one another.[3 4]
We conducted a literature search to identify randomised trials, and we carried out a meta-analysis to update the results of Cook’s study with regard to effectiveness and infectious complications.
Methods
Searching
Our Medline search covered the period from 1966 to 20 June 2000 and was based on four key words (stress, pneumonia, ranitidine, sucralfate) and on the extraction of studies published in English. Randomised studies were identified by using the key words “randomized controlled trial” or “random” according to a validated literature search.[5]
This search was supplemented by examining the Iowa-IDIS system (Iowa Drug Information, Iowa University, United States) from 1966 to December 1999 and Drugdex (CD Rom Drugdex, vol 104, Micromedex, Englewood, Colorado, United States).
Selection
We carried out five meta-analyses that evaluated data on effectiveness in terms of rates of bleeding (meta-analysis A: ranitidine v placebo; meta-analysis B: sucralfate v placebo) and incidence of nosocomial pneumonia (meta-analysis C: ranitidine v placebo; meta-analysis D: sucralfate v placebo; meta-analysis E: ranitidine v sucralfate). Eligible studies were included in meta-analysis A or B if they met the following criteria: patients were admitted to an intensive care unit or were undergoing mechanical ventilation, or both; randomised design; assessment of gastrointestinal bleeding. In meta-analyses C, D, and E the inclusion criterion gastrointestinal bleeding was replaced by the assessment of pneumonia.