Stress ulcer prophylaxis: Is mortality a useful endpoint?
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EDITORIAL
Stress ulcer prophylaxis: Is mortality a useful endpoint? Armin Finkenstedt1, Mette M. Berger2 and Michael Joannidis1* © 2020 Springer-Verlag GmbH Germany, part of Springer Nature
The risk of stress ulceration and related bleeding has long been a concern in critically ill patients. Since the first description of an association between major burns and the occurrence of gastric ulceration by J. Swan in 1823, several further risk factors for stress ulcerations have been identified. The two most common are mechanical ventilation for more than 48 h and coagulopathy [1], and others are listed in Table 1. Although gastric erosions have been found in up to 90% of patients on the third ICU day in endoscopic studies [2], overt gastrointestinal bleeding is much less frequent and occurs in 1.5% to 8% of patients. Nevertheless, overt bleeding from ulcerations is associated with an increased ICU mortality [3], and most guidelines recommend stress ulcer prophylaxis for ICU patients who are at risk for the development of ulceration and bleeding [4, 5]. After decades of randomized trials, stress ulcer prophylaxis remains debated. Although the efficacy of pharmacological prophylaxis has been confirmed for patients at high bleeding risk in numerous trials and meta-analyses enabling clear guidelines [5], the choice of the agent [H2 receptor antagonist (H2RA), proton pump inhibitors (PPI), or sucralfate] and its possible influence on mortality remains controversial. The major concerns are eventual association between stress ulcer prophylaxis and an increased risk of nosocomial pneumonia, Clostridium difficile infection, and mortality. In this issue of Intensive Care Medicine, Wang and coworkers present the results from an update [6] of their previous systematic review and network meta-analysis
*Correspondence: michael.joannidis@i‑med.ac.at 1 Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria Full author information is available at the end of the article
[7]. In addition to another very small trial, the authors included the PEPTIC trial, a multi-centre cluster randomized trial including over 26.000 patients [8] and thus increasing the number of analysed patients from 12 660 to 39 569. This massive augmentation in numbers should have increased certainty, which is not the case. The present meta-analysis was motivated by an apparently increased mortality for PPIs over H2RAs in the PEPTIC trial [8], and compared potential benefits and harms of stress ulcer prophylaxis with PPIs, H2RAs, and sucralfate in critically ill patients. The main finding of this latest meta-analysis of 74 individual trials [6] is that neither PPIs nor H2RAs compared to no prophylaxis are likely to have a significant influence on mortality, without any difference between PPIs and H2RAs. This meta-analysis is the latest of over 60 studies found on PubMed (access 3rd SEP20) since 1991 using the words “stress ulcer AND prophylaxis AND metaanalysis”. The
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