Stress Ulcer Prophylaxis in Critically Ill Patients

Clinical Question

Does stress ulcer prophylaxis decrease clinically important gastrointestinal bleeding and mortality in critically ill patients?

Clinical Bottom Line

  1. Clinically important gastrointestinal bleeding is reduced with the use of H-2 receptor antagonists in critically ill patients, but not with sucralfate or antacids.
  2. H-2 blockers show the greatest reduction in overt bleeding, but sucralfate also shows a reduction, when these are compared to placebo or antacids.
  3. Sucralfate was the only drug that, when compared to antacids, reduced mortality.
  4. There are TRENDS toward decreased incidence of nosocomial pneumonia and mortality when sucralfate is compared to H-2 blockers and increased incidence of pneumonia when H-2 blockers or sucralfate are compared to placebo.

The Evidence

H-2 blocker/placebo (95% CI)[NNT] H-2 blocker/Antacid (95% CI)[NNT] Sucralfate/placebo (95% CI)[NNT] Antacid/placebo (95% CI)[NNT] Sucralfate/H-2 blocker (95% CI)[NNT] Sucralfate/Antacid (95% CI)[NNT]
Clinically important bleeding 0.44 (0.22-0.88) [11] 0.86 (0.46-1.59) 1.26 (0.12-12.87) 0.35 (0.09-1.41) 1.28 (0.27-6.11) 1.49 (0.42-5.27)
Overt bleeding 0.58 (0.42-0.79) [27] 0.56 (0.37-0.84) [24] 0.58 (0.34-0.99) [27] 0.66 (0.37-1.17) 0.89 (0.63-1.27) 0.97 (0.62-1.51)
Pneumonia 1.25 (0.78-2.00) 1.01 (0.65-1.57) 2.11 (0.82-5.44) NA 0.77 (0.60-1.01) [54] 0.80 (0.56-1.15)
Mortality 1.15(0.86-1.53) 0.89 (0.66-1.21) 1.06 (0.67-1.67) 1.42(0.82-2.47) 0.83 (0.63-1.09) [73] 0.73 (0.54-0.97) [43]

Comments

  1. This was a rigorous meta-analysis, and is valid according to all the JAMA User's guidelines for appraising a meta-analysis.
  2. Of note is that this meta-analysis did appraise the validity of each included study in the analysis, and this was taken into account during the statistical manipulations.
  3. Despite not showing any differences in mortality or pneumonia when they were compared to placebo or antacids, there was a trend towards pneumonia and mortality reduction when sucralfate was compared to H-2 blockers, and a definite reduction in mortality when sucralfate was compared to antacids.
  4. NNT's were calculated according to a standard table of Odds Ratios and expected event rates. A review of the literature resulted in a wide range of patient expected event rates [PEER] (5% - 100%). Based on the reviews which included similar patient demographics to our institution, the PEER for clinically significant bleeding was close to 15%, and overt bleeding probably around 10% (likewise with pneumonia and mortality).
  5. For patients at greater risk for GI bleeding, H-2 blockers may be preferable. For those more at risk for pneumonia, sucralfate may be preferable.
  6. More studies need to be done evaluating the effect on mortality.

APPRAISED BY: Mark Hainer, D.O.

DATE: November 2, 1996

REVIEWED BY: Patrick J. Sousa, MD

Cook DJ, et al. Stress Ulcer Prophylaxis in Critically Ill Patients: Resolving Discordant Meta-analyses. NEJM, 1996;275:308-314.