The efficacy and safety of proton pump inhibitors vs histamine-2 receptor antagonists for stress ulcer bleeding prophylaxis among critical care patients: a meta-analysis

Crit Care Med. 2010 Apr;38(4):1197-205. doi: 10.1097/CCM.0b013e3181d69ccf.


Objective: To examine the efficacy and safety of proton pump inhibitors in comparison with histamine-2 receptor antagonists for stress-related upper gastrointestinal bleeding prophylaxis among critical care patients.

Data sources: PubMed, EMBASE, Cochrane Library, and

Study selection: Randomized, controlled trials that directly compare proton pump inhibitors with histamine-2 receptor antagonists in prevention of stress-related upper gastrointestinal bleeding in intensive care unit patients published before May 30, 2008.

Data extraction: Two reviewers independently applied selection criteria, performed quality assessment, and extracted data. The primary outcome was the incidence of stress-related upper gastrointestinal bleeding, and the secondary outcome measures were the incidence of pneumonia and intensive care unit mortality.

Data synthesis: The random effect model was used to estimate the pooled risk difference between two treatment arms irrespective of drug, dosage, and route of administration.

Results: We identified seven randomized, controlled trials with a total of 936 patients for planned comparison. The overall pooled risk difference (95% confidence interval; p value; I statistics) of stress-related upper gastrointestinal bleeding comparing proton pump inhibitors vs. histamine-2 receptor antagonists was -0.04 (95% confidence interval, -0.09-0.01; p = .08; I = 66%). In the sensitivity analysis, removing the Levy study significantly reduced the heterogeneity (from I = 66% to I = 26%) and shifted the overall risk difference closer to the null (pooled risk difference, -0.02; 95% confidence interval, -0.05-0.01; p = .19). There was no difference between proton pump inhibitors and histamine-2 receptor antagonists therapy in the risk of pneumonia and intensive care unit mortality, with pooled risk differences of 0.00 (95% confidence interval, -0.04-0.05; p = .86; I = 0%) and 0.02 (95% confidence interval, -0.04-0.08; p = .50; I = 0%), respectively.

Conclusions: This meta-analysis did not find strong evidence that proton pump inhibitors were different from histamine-2 receptor antagonists in terms of stress-related upper gastrointestinal bleeding prophylaxis, pneumonia, and mortality among patients admitted to intensive care units. Because of limited trial data, future well-designed and powerful randomized, clinical trials are warranted.

Publication types

  • Comparative Study
  • Meta-Analysis

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles / adverse effects
  • 2-Pyridinylmethylsulfinylbenzimidazoles / therapeutic use
  • Cimetidine / adverse effects
  • Cimetidine / therapeutic use
  • Critical Care / methods*
  • Histamine H2 Antagonists / adverse effects
  • Histamine H2 Antagonists / therapeutic use*
  • Humans
  • Odds Ratio
  • Omeprazole / adverse effects
  • Omeprazole / therapeutic use
  • Pantoprazole
  • Peptic Ulcer Hemorrhage / prevention & control*
  • Proton Pump Inhibitors / adverse effects
  • Proton Pump Inhibitors / therapeutic use*
  • Ranitidine / adverse effects
  • Ranitidine / therapeutic use
  • Risk
  • Stress, Psychological


  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Histamine H2 Antagonists
  • Proton Pump Inhibitors
  • Cimetidine
  • Ranitidine
  • Pantoprazole
  • Omeprazole