Meta Analysis Bleeding and pneumonia in intensive care patients given ranitidine and sucralfate for prevention of stress ulcer:meta-analysis of randomised controlled trials
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Summary
Posted By:	Gordon S. Doig
E-Mail:	Gordon.Doig@EvidenceBased.net
Posted Date:	March 23, 2001
Title:	Bleeding and pneumonia in intensive care patients given ranitidine and sucralfate for prevention of stress ulcer:meta-analysis of randomised controlled trials
Authors:	Messori A, Trippoli S, Vaiani M, Gorini M and Corado A
Reference:	BMJ 2000;321:1103-6
Link:	Click here for a direct link to the paper. A password may be required for access to fulltext.
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.
Are the Results Valid?
1. Did the overview address a focused clinical question?
	Yes. The authors describe their intent to perform a meta-analysis to assess the impact of ranitidine or sucralfate, used for stress ulcer prophylaxis in critically ill patients, on the subsequent development of bleeding or pneumonia. Furthermore, the authors conducted individual meta-analyses to assess the effects of; A) ranitidine vs. placebo, B) sucralfate vs. placebo and C) ranitidine vs. sucralfate.
2. Were the criteria used to select articles for inclusion appropriate?
	Yes. The authors included all randomized studies conducted on patients who were either undergoing mechanical ventilation or were admitted to an ICU (or both).
3. Is it unlikely that important, relevant studies were missed?
	The authors report a Medline search combined with a search of the Iowa Drug Informaiton System. Unfortunatly they do not report whether they preformed a hand search of the reference lists from the papers obtained of whether they contacted experts in the field. The authors also do not mention whether they performed a search of any medical databases based in Europe (i.e. EMBASE etc) HOWEVER since they were likely to detect previous overviews that looked at this question and that did perform complete searches, it is unlikely that important papers were missed.
4. Was the validity of the included studies appraised?
	Although methodologic quality was appraised, we are uncertain of the validity of the tool used to conduct this appraisal.
5. Were assessments of studies reproducible?
	We are unable to tell if the appraisal of methdologic quality or the extraction of data from the studies was reproducible. It would have been better to have a duplication of work efforts (both methodological appraisal and data extraction) combined with a reporting of agreement between methdologists (kappa, error rate etc).
6. Were the results similar from study to study?
	The authors report non-signficant chi-square for heterogeneity for each meta-analysis. The authors also deal with the 'qualitative' aspects of heterogeneity by assessing and discussing the similarity between defintions of outcomes (i.e. pneumonia and bleeding events).
What are the Results?
1. What are the overall results of the overview?
	A) In five studies comparing ranitidine with placebo and reporting bleeding as an outcome, ranitidine was not found to reduce bleeding (OR 0.95, 95% CI 0.37 to 2.43 p=0.46) B) There was only one study comparing sucralfate to placebo that reported bleeding, so no meta-analysis was conducted. Results from the trial are OR 1.26, 95% CI 0.12 to 12.9, p=0.70. C) In three studies comparing ranitidine with placebo and reporting pneumonia as an outcome, ranitidine was no better than placebo at reducing pneumonia (OR 1.10, 95% CI 0.45 to 2.66, p=0.92). D) In two studes comparing sucrafate with placebo and reporting pneumonia as an outcome, sucralfate was not reported to be any better than placebo at reducing pneumonia (OR 2.11, 95% CI 0.79 to 5.64, p=0.14). E) In the eight trials comparing ranitidine to sucralfate and reporting pneumonia as an outcome, the use of ranitidine was associated with a significant increase in the rate of pneumonia (OR 1.51, 95% CI 1.00 to 2.29, p=0.05).
2. How precise were the results?
	The 95% confidence intervals are reported above.
Will the Results Help Me In Caring For My Patients?
1. Can the results be applied to my patient care
	The most recent large, well-done RCT comparing the effect of ranitidine vs. sucralfate reported that "Among critically ill patients requiring mechanical ventilation, those receiving ranitidine had a significantly lower rate of clinically important gastrointestinal bleeding than those treated with sucralfate. There were no significant differences in the rates of ventilator-associated pneumonia, the duration of the stay in the ICU, or mortality. (N Engl J Med 1998;338:791-7.)" Whether you accept the results of the recent RCT in preference to this meta-analysis should be driven by a comparison of the methodologic quality of the individual papers contributing to the meta-analysis combined with the quality of the meta-analysis itself.
2. Were all clinically important outcomes considered?
	No. Before we make a decision, it would be nice to understand the impact of these two therapies on mortality, length of stay, quality of life and costs.
3. Are the benefits worth the harms and costs?
	Unknown at this time. An evidence-based recommendation, which is the building block for an evidence-based guideline, that summarizes this topic can be found in the EBR section.
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