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Bleeding and pneumonia in intensive care patients given ranitidine and sucralfate for prevention of stress ulcer: meta-analysis of randomised controlled trials |
Messori A, Trippoli S, Vaiani M, Gorini M, Corrado A |
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Authors' 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.
Searching The authors searched MEDLINE from 1966 to June 2000 using the keywords 'stress', 'pneumonia', 'ranitidine' and 'sucralfate'. Randomised studies were identified using the keywords 'randomized controlled trial' or 'random'. The search was supplemented by examining the Iowa Drugs Information Service (IDIS) from 1966 to December 1999, and Drugdex (volume 104). The search was limited to English language publications.
Study selection Study designs of evaluations included in the reviewRandomised controlled trials (RCTs) were included.
Specific interventions included in the reviewRanitidine (50 mg intravenously, every 6 hours or three times daily; or 6.25 mg/hour by continuous infusion) and sucralfate (1 g by nasogastric tube every four hours) versus placebo.
Participants included in the reviewCritical patients diagnosed with stress ulcer who were either admitted to an intensive care unit or undergoing mechanical ventilation, or both.
Outcomes assessed in the reviewRates of clinically important gastrointestinal bleeding and nosocomial pneumonia. Studies were excluded where gastrointestinal bleeding did not meet the definition of 'clinically important bleeding'.
How were decisions on the relevance of primary studies made?The authors do not state how the papers were selected for the review, or how many of the reviewers performed the selection.
Assessment of study quality Methodological quality was assessed using a 5-item scale, based on a procedure similar to that of Cook et al. (see Other Publications of Related Interest), which evaluated patient selection, patient characteristics, randomisation, blinding, and definition of bleeding or pneumonia. Each of the five items was given a score of 0, 1 or 2, and the maximum score attainable was 10. Three reviewers independently performed the quality assessment, and any differences were resolved by consensus.
Data extraction The data were extracted by one reviewer using a structured form, and checked for accuracy by a second reviewer. Any differences were resolved by consensus.
Data were extracted for the following categories: study identification and year of publication; the meta-analysis in which they were included; the study setting; the mean age and number of participants, intervention and control; outcomes, which were reported in separate tables; and methodological quality scores.
Additional information and a more comprehensive version of this paper are available on the BMJ website. See Web Address at end of abstract.
Methods of synthesis How were the studies combined?The ranitidine trials were combined by calculating the pooled odds ratio (OR) with 95% confidence intervals (CIs).
A meta-analysis was not performed since there was only one trial for sucralfate versus placebo.
How were differences between studies investigated?Clinical heterogeneity was assessed by the reviewers. This included characteristics of participants, details of interventions and definition of outcomes. The assessment focused in particular on a comparison of the definitions of bleeding and pneumonia across the trials.
Statistical heterogeneity was assessed using the chi-squared statistic.
Results of the review Six RCTs were included in the review: 5 of ranitidine versus placebo with 398 participants (194 intervention and 204 control), and 1 of sucralfate versus placebo with 54 participants (24 intervention and 30 control).
The mean quality score for the five ranitidine trials was 6.6.
The quality score for the one sucralfate trial was 7.
Using a fixed-effect analysis, ranitidine (5 trials) was found to have the same effectiveness as placebo for bleeding (OR 0.72, 95% CI: 0.30, 1.70, p=0.46), which was not statistically significant. Using a random-effects analysis, the OR was 0.95 (95% CI: 0.37, 2.43, p=0.92). The chi-squared value for heterogeneity was 6.8 (d.f.=4, p=0.15.
The single trial of sucralfate showed no difference between sucralfate and placebo (OR 1.26, 95% CI: 0.12, 12.9, p=0.70).
Authors' conclusions The authors state that 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.
CRD commentary The authors stated a clear research question but descriptions of study design, participants, outcomes and intervention were very limited in the inclusion and exclusion criteria. The search strategy was not thorough and unpublished data was not sought. In addition, their search was limited to English language publications. It is possible that additional relevant studies may have been missed.
The authors did not describe the process for selecting papers for the review, but they did describe the process of quality assessment and data extraction. A quality scoring system was used for the quality assessment. The included studies were very small and the authors acknowledge that firm conclusions cannot be made at this time.
Statistical pooling was performed where possible, and heterogeneity was assessed and discussed in the review. The authors' results were not statistically significant. The only conclusion that does follow from the results is that there was insufficient data to form a definitive conclusion on the effectiveness of ranitidine. The authors also state that there were competing interests, in the form of indirect support from GlaxoWellcome (Italy), for some of the authors although there was no direct funding stated for this review.
Implications of the review for practice and research Practice: The authors did not state any implications for practice.
Research: The authors state that their results are an important argument for further RCTs, although they acknowledge that this may not be feasible because of ethical limitations.
Bibliographic details Messori A, Trippoli S, Vaiani M, Gorini M, Corrado A. Bleeding and pneumonia in intensive care patients given ranitidine and sucralfate for prevention of stress ulcer: meta-analysis of randomised controlled trials. BMJ 2000; 321: 1103-1107 Other publications of related interest Cook DJ, Reeve BK, Guyatt GH, Heyland DK, Griffith LE, Buckingham L, et al. Stress ulcer prophylaxis in critically ill patients: resolving discordant meta-analyses. JAMA 1996;275:308-14.
This additional published commentary may also be of interest. Ranitidine and gastrointestinal bleeding in intensive care. BMJ 2001;322:995.
Indexing Status Subject indexing assigned by NLM MeSH Anti-Ulcer Agents /adverse effects /therapeutic use; Cross Infection /chemically induced /etiology; Gastrointestinal Hemorrhage /chemically induced /prevention & Humans; Pneumonia /chemically induced /etiology; Randomized Controlled Trials as Topic; Ranitidine /adverse effects /therapeutic use; Risk Factors; Stomach Ulcer /prevention & Sucralfate /adverse effects /therapeutic use; control; control AccessionNumber 12000008611 Date bibliographic record published 31/01/2002 Date abstract record published 31/01/2002 Record Status This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn. |
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