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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

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Abstract

Purpose

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).

Methods

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.

Results

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; I 2 = 0 %) or hospital-acquired pneumonia (random effects: RR 1.23, 95 % CI 0.86–1.78; P = 0.28; I 2 = 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; I 2 = 48 %); however, TSA (TSA adjusted 95 % CI 0.18–1.11) and subgroup analyses could not confirm this finding.

Conclusions

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.

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Authors and Affiliations

  1. Department of Intensive Care, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark

    Mette Krag, Anders Perner & Morten Hylander Møller

  2. Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

    Jørn Wetterslev

  3. Department of Adult Critical Care, University Hospital of Wales, Cardiff, UK

    Matt P. Wise

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  1. Mette Krag
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  2. Anders Perner
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Correspondence to Morten Hylander Møller.

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The International Prospective Register of Systematic Reviews (PROSPERO), No. CRD42013004142.

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Krag, M., Perner, A., Wetterslev, J. et al. Stress ulcer prophylaxis versus placebo or no prophylaxis in critically ill patients. Intensive Care Med 40, 11–22 (2014). https://doi.org/10.1007/s00134-013-3125-3

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