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Abstract & Commentary
Synopsis: Meta-analysis of randomized controlled trials of the use of ranitidine and sucralfate to prevent stress ulcer bleeding in ICU patients failed to show conclusive efficacy of either drug in preventing bleeding and suggested that ranitidine might increase the incidence of nosocomial pneumonia.
Source: Messori A, et al. Bleeding and pneumonia in intensive care patients given ranitidine and sucralfate for prevention of stress ulcer: Meta-analysis of randomised controlled trials. BMJ. 2000;321:1103-1106.
Messori and colleagues in florence, italy, performed a series of meta-analyses of available randomized controlled trials of the use of ranitidine and sucralfate for the prevention of stress ulcer bleeding in ICU patients. They searched Medline and other databases for English-language studies with placebo controls.
Five separate meta-analyses were performed. The first of these examined the effectiveness of ranitidine vs. placebo in five trials including a total of 398 patients, and found that ranitidine had the same effectiveness as placebo (odds ratio of bleeding, 0.72, 95% CI 0.30-1.70, P = .46). The planned second meta-analysis of sucralfate vs. placebo could not be performed, as only one clinical trial met Messori et al’s entry criteria. Three studies comprised 311 patients in the third meta-analysis of ranitidine vs. placebo with respect to nosocomial pneumonia. In this and the fourth meta-analysis, of sucralfate vs. placebo in two studies totalling 226 patients, no difference in the incidence of pneumonia with respect to placebo vs. either drug could be found. However, in the fifth meta-analysis, directly comparing ranitidine to sucralfate in a total of 1825 patients in eight studies, there was a significantly higher incidence of nosocomial pneumonia in patients receiving ranitidine (odds ratio, 1.35; 95% CI, 1.07-1.70; P = .012).
The mean quality score in the four meta-analyses that could be completed ranged from 5.6-6.6 on a 10-point scale. Messori et al conclude that ranitidine is ineffective in preventing gastrointestinal bleeding in ICU patients and may increase the risk of pneumonia. Because of small numbers of published studies and total reported patients, Messori et al were unable to make any definitive statements about the clinical effects of sucralfate. They recommend that current recommendations on prophylaxis of stress ulcers be revised.
COMMENT BY DAVID J. PIERSON, MD, FACP, FCCP
Most published studies of drugs for prophylaxis against stress ulcer bleeding in the ICU compare one supposedly active agent with another. According to Messori et al, this is the first ever meta-analysis of the effects of ranitidine vs. placebo on the incidence of gastrointestinal bleeding in ICU patients. A previous meta-analysis on H2 blockers and gastrointestinal bleeding1 included five trials using cimetidine, the use of which in the ICU has now largely been abandoned, which generally favored the therapy, plus three trials with negative results using ranitidine. As Messori et al point out, there is only a single placebo-controlled, randomized clinical trial using sucralfate;2 they believe that no conclusions as to the efficacy of that drug can be made from that study.
Both ranitidine and sucralfate are widely used to prevent gastrointestinal bleeding in ICU patients. According to the British Medical Journal, although a number of groups have recommended the prophylactic use of these agents, the FDA has not approved either drug for this purpose. This study casts considerable doubt on the clinical use of our current practice, and Messori et al emphasize that presently "there are insufficient data on effectiveness to conclude anything one way or another." Once again, further trials are needed. (Dr. Pierson is Professor of Medicine, University of Washington, Medical Director, Respiratory Care, Harborview Medical Center, Seattle, Wash.)
1. Cook DJ, et al. Stress ulcer prophylaxis in critically ill patients. JAMA. 1996;275:308-314.
2. Ruiz-Santana S, et al. Stress-induced gastroduodenal lesions and total parenteral nutrition in critically ill patients: frequency, complications, and the value of prophylactic treatment. Crit Care Med. 1991;19:887-891.