February 20, 2019

EJRC - Is the use of stress ulcer prophylaxis still relevant?

Updated, exhaustive review on the efficacity of PPI or H2RA to prevent stress ulcers and gastro-intestinal bleeding in adult ICUs


Gastro -intestinal bleeding (GI) is a severe but rare event in adult ICUs, and although recommendations remain ambiguous on this issue, three out of four units use stress ulcer prophylaxis.

M. Barbateskovic and her team performed a systematic, updated analysis of all trials proposing stress ulcer prophylaxis with PPI or H2RA versus placebo or no prophylaxis in adult ICU patients; the aim was to clarify the impact of stress ulcer prophylaxis on overall mortality and, more specifically, on GI bleeding, and if it could have an effect on other serious adverse events.

Pre-defined, co-primary outcomes were all-cause mortality and the proportion of participants with any GI bleeding. Other outcomes were the occurrence of one or more serious adverse events (SAE): health related quality of life (HRQoL) described through validated scales, myocardial ischemia, hospital-acquired pneumonia and Clostridium Difficile enteritis.

After identifying 10,054 references, the authors included 41 RCTs covering 44 trial comparisons, published between 1977 and 2018 and representing 6790 participants. 32 trials assessed the use of H2RA and 12 the use of PPI. Only three trials were considered as having overall low risk of bias.

Results showed no effect on mortality (RR 1.03, 95% CI 0.94-1.14; TSA-adjusted 0.94-1.14) and a reduction of overall GI bleeding (0.60, 95% CI 0.47-0.77; TSA-adjusted 0.36-1.00).



This review benefits from a rigorous and validated methodology, including a pre-planned statistical analysis plan on a published protocol, the application of the Cochrane Collaboration and PRISMA methodologies, exhaustive sub-group and sensitivity analysis, and a trial sequential analysis (TSA).

Main limitations were the risk of clinical heterogeneity among trials, of bias resulting from missing data and losses to follow-up, and the sparse data on SAE. Therefore, the final balance between benefits and risks on the use of ulcer prophylaxis on SAE remains inconclusive.



Stress ulcer prophylaxis compared to placebo or no prophylaxis does not impact mortality rates in adult ICU patients.

An absolute reduction of overall GI bleeding could be found, but firm evidence for a reduction in clinically significant GI bleeding is still lacking.


This article review was prepared and submitted by Silvia Calvino Gunther, from the N&AHP section, on behalf of the ESICM Journal Review Club.


1)  Barbateskovic M et al. Stress ulcer prophylaxis with proton pump inhibitors or histamin-receptor antagonists in adult intensive care patients: a systematic review with meta-analysis and trial sequential analysis. Intensive Care Med. 2019 Feb;45(2):143-158.

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