Objectives
We aim to assess patient-important benefits and harms of stress ulcer prophylaxis versus placebo or no prophylaxis in adult hospitalised acutely ill patients with high risk of gastrointestinal bleeding irrespective of hospital setting.
Research question: does stress ulcer prophylaxis improve patient-important outcomes in adult hospitalised acutely ill patients with high risk of gastrointestinal bleeding as compared with placebo or no prophylaxis?
Discussion
This systematic review will provide updated important knowledge on use of stress ulcer prophylaxis in adult hospitalised acutely ill patients irrespective of hospital setting. We will include recently published RCTs and include and assess adult hospitalised acutely ill patients with high risk of gastrointestinal bleeding both in- and outside the context of the ICU.
New RCTs may have provided important new data on the potential harm of stress ulcer prophylaxis, including the risk of cardiovascular events, hospital-acquired pneumonia and C. difficile infections, which is why an updated systematic review is warranted.
As critical illness is not restricted to ICU patients, we believe a wider scope is mandated in order to more accurately evaluate the attempted prevention of gastrointestinal bleedings due to stress ulcers. In a recent cohort study [
5], the incidence of gastrointestinal bleedings peaked on the first 1–2 days of ICU stay, suggesting that the risk of developing stress ulcerations and gastrointestinal bleeding in acutely ill patients is not limited to the ICU setting, but is a continuum not defined by the clinical setting. Consequently, an assessment of benefits and harms of stress ulcer prophylaxis in high-risk patients irrespective of clinical setting is needed.
Using TSA to assess the risk of random errors will increase the validity of the summary estimates calculated. The risk of type I errors (a false positive finding) are increased when multiple testing is done, e.g. when analysing multiple primary and secondary outcomes, during repeated testing of data, and, importantly, when meta-analyses are conducted and updated [
46]. Also, the risk of type II errors (a false negative finding) challenge the results of meta-analyses, due to sparse data. Statistically significant meta-analyses with few participants have low reliability, and the interventional effect is often overrated [
45,
53]. Furthermore, TSA allows to estimate if the required information size (sample size) has been reached and if additional trials are needed [
45,
46,
49,
50].
Finally, this systematic review may aid data monitoring and safety committees when assessing results of interim analyses of ongoing and upcoming trials on stress ulcer prophylaxis in acutely ill patients (SUP-ICU [
55], REVISE [
56], PEPTIC [
57]). A modern data monitoring and safety committee cannot allow themselves to conclude solely on the data provided from the interim-analysis within a specific single trial as evidence from the ‘outside’ may influence the overall decision of whether the trial shall continue or not. Therefore, to properly summarise the evidence provided before and during the trial, the data monitoring and safety committee must include the interim-part of the trial data in meta-analyses of all the evidence provided so far using e.g. TSA to reach realistic and firm results for the actual achieved evidence.
Today, stress ulcer prophylaxis with PPI or H2RA is recommended in international guidelines and regarded as standard of care in adult ICU patients [
16]. However, the quantity and quality of evidence supporting use of stress ulcer prophylaxis in ICU patients is low with no firm evidence for benefit or harm, and clinical equipoise exist [
1,
17‐
20]. The outlined systematic review will provide important data on the benefits and harms of stress ulcer prophylaxis in adult hospitalised acutely ill patients with high risk of gastrointestinal bleeding in and outside the context of the ICU.
Acknowledgements
Not applicable.
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