Sucralfate vs. Ranitidine to Prevent GI Bleeding
ABSTRACT & COMMENTARY
Synopsis: A large, randomized, placebo-controlled study demonstrates the superiority of ranitidine over sucralfate in preventing significant GI bleeding in patients receiving mechanical ventilation. Sucralfate also demonstrated a non-significant trend toward a lower rate of pneumonia (P = 0.19).
Source: Cook D, et al. N Engl J Med 1998(12);338: 791-797.
Gastrointestinal bleeding remains a significant source of morbidity and increased cost in critically ill patients. H2-blockers, antacids, early enteral feedings, and the cytoprotective agent sucralfate have all been advocated to reduce the incidence of this complication. Sucralfate has been proposed as offering the additional benefit of reducing the incidence of bacterial pneumonia by preventing colonization of the stomach and upper GI tract by preserving an acid environment. Direct comparison of various prophylactic methods has been difficult due to the need to study large groups of patients, varying definitions of hemorrhage and pneumonia, and blinding difficulties. This large Canadian study solves several of these problems.
One thousand two hundred patients requiring mechanical ventilation for more than 48 hours were randomly assigned to receive either ranitidine or sucralfate and an identical appearing placebo of the other agent. Study pharmacists delivered all study agents in the 16 participating ICUs. Active ranitidine was given as a bolus 50 mg dose every eight hours with corrections in schedule for renal failure. One gram of sucralfate was given by gastric tube or by mouth every six hours. Gastric pH was not monitored, since this would have unblinded the study. Randomization resulted in similar patient populations, with nearly identical age (59 years), sex (40% females), APACHE II Score (24), ICU length-of-stay (9 days), and mortality (23%).
The rate of significant GI bleeding, defined by hemodynamic or hematologic changes, need for transfusion, hematemesis, hematochezia, or endoscopic confirmation, was 1.7% in the ranitidine group and 3.8% in the sucralfate group (P = 0.02). The incidence of ventilator-associated pneumonia (VAP) tended to be less in the sucralfate group, but this difference failed to reach statistical significance. The difficulty in diagnosing VAP was handled in this study by using several accepted as well as unique definitions of VAP and by analyzing the data using each definition. All patients were classified without knowledge of the treatment group. If a definite new pneumonia was the criterion, statistical reduction with sucralfate was reached (0 vs 5; P = 0.03). With all of the VAP definitions evaluated, a definite trend to lower rate with sucralfate was seen.
COMMENT BY CHARLES G. DURBIN, Jr., MD, FCCM
This is an impressive study in design and size, which demonstrates a halving of significant GI bleeding rate using ranitidine compared to sucralfate. The hemorrhage rate in the sucralfate group is similar to that in untreated patients reported in older studies. The trend to low VAP rate in the sucralfate group may also be important. The touted preventive effects of sucralfate on the development of VAP may be underestimated in this study because the majority of patients were also receiving gastric feedings, which may have preventive effects as well. The study had a power to detect 25% change in rates. It is likely that sucralfate is preventive for VAP but that the effect is less than 25% under these study conditions.
This study confirms less efficacy of sucralfate as compared to ranitidine in preventing GI hemorrhage. Cost-effective analysis is needed to recommend abandoning sucralfate altogether.
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