Intensive Care Medicine

, Volume 40, Issue 1, pp 11–22

Stress ulcer prophylaxis versus placebo or no prophylaxis in critically ill patients

A systematic review of randomised clinical trials with meta-analysis and trial sequential analysis
  • Mette Krag
  • Anders Perner
  • Jørn Wetterslev
  • Matt P. Wise
  • Morten Hylander Møller
Systematic Review

DOI: 10.1007/s00134-013-3125-3

Cite this article as:
Krag, M., Perner, A., Wetterslev, J. et al. Intensive Care Med (2014) 40: 11. doi:10.1007/s00134-013-3125-3



To assess the effects of stress ulcer prophylaxis (SUP) versus placebo or no prophylaxis on all-cause mortality, gastrointestinal (GI) bleeding and hospital-acquired pneumonia in adult critically ill patients in the intensive care unit (ICU).


We performed a systematic review using meta-analysis and trial sequential analysis (TSA). Eligible trials were randomised clinical trials comparing proton pump inhibitors or histamine 2 receptor antagonists with either placebo or no prophylaxis. Two reviewers independently assessed studies for inclusion and extracted data. The Cochrane Collaboration methodology was used. Risk ratios/relative risks (RR) with 95 % confidence intervals (CI) were estimated. The predefined outcome measures were all-cause mortality, GI bleeding, and hospital-acquired pneumonia.


Twenty trials (n = 1,971) were included; all were judged as having a high risk of bias. There was no statistically significant difference in mortality (fixed effect: RR 1.00, 95 % CI 0.84–1.20; P = 0.87; I2 = 0 %) or hospital-acquired pneumonia (random effects: RR 1.23, 95 % CI 0.86–1.78; P = 0.28; I2 = 19 %) between SUP patients and the no prophylaxis/placebo patients. These findings were confirmed in the TSA. With respect to GI bleeding, a statistically significant difference was found in the conventional meta-analysis (random effects: RR 0.44, 95 % CI 0.28–0.68; P = 0.01; I2 = 48 %); however, TSA (TSA adjusted 95 % CI 0.18–1.11) and subgroup analyses could not confirm this finding.


This systematic review using meta-analysis and TSA demonstrated that both the quality and the quantity of evidence supporting the use of SUP in adult ICU patients is low. Consequently, large randomised clinical trials are warranted.


Stress ulceration Gastrointestinal bleeding All-cause mortality Meta-analysis Trial sequential analysis Stress ulcer prophylaxis 

Supplementary material

134_2013_3125_MOESM1_ESM.doc (490 kb)
Supplementary material 1 (DOC 490 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2013

Authors and Affiliations

  • Mette Krag
    • 1
  • Anders Perner
    • 1
  • Jørn Wetterslev
    • 2
  • Matt P. Wise
    • 3
  • Morten Hylander Møller
    • 1
  1. 1.Department of Intensive CareCopenhagen University Hospital RigshospitaletCopenhagenDenmark
  2. 2.Copenhagen Trial Unit, Centre for Clinical Intervention ResearchCopenhagen University Hospital RigshospitaletCopenhagenDenmark
  3. 3.Department of Adult Critical CareUniversity Hospital of WalesCardiffUK

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