ABSTRACT
BACKGROUND: Critically ill patients are at risk of gastrointestinal bleeding, but clinically important gastrointestinal bleeding is rare. The majority of intensive care unit (ICU) patients receive stress ulcer prophylaxis (SUP), despite uncertainty concerning the balance between benefit and harm. For approximately half of ICU patients with gastrointestinal bleeding, onset is early, ie within the first two days of the ICU stay. The aetiology of gastrointestinal bleeding and consequently the balance between benefit and harm of SUP may differ between patients with early vs late gastrointestinal bleeding. METHODS: This is a protocol and statistical analysis plan for a preplanned exploratory substudy of the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) randomized clinical trial, comparing intravenous pantoprazole (40 mg once daily) with placebo in 3350 acutely ill adult ICU patients. We will describe baseline characteristics and assess the time to onset of the first clinically important episode of GI bleeding accounting for survival status and allocation to SUP or placebo. In addition, we will describe differences in therapeutic and diagnostic procedures used in patients with clinically important gastrointestinal bleeding according to early vs late bleeding and 90-day vital status. CONCLUSIONS: The study outlined in this protocol will provide detailed information on patient characteristics and the timing of onset of gastrointestinal bleeding in the patients enrolled in the SUP-ICU trial. This may provide additional knowledge and incentives for future studies on which patients benefit from SUP.
ABSTRACT
BACKGROUND: In the intensive care unit (ICU), stress ulcer prophylaxis with proton pump inhibitors or histamine-2-receptor antagonists is standard of care although gastrointestinal bleeding remains uncommon. It remains unknown whether its use is associated with benefits or harms and the quality of evidence supporting the use of stress ulcer prophylaxis has been questioned. Accordingly, the objective of this systematic review was to critically assess the evidence from randomized clinical trials on the benefits and harms of stress ulcer prophylaxis vs. placebo or no prophylaxis in adult ICU patients. METHODS: We will systematically search for randomized clinical trials in major international databases. Two authors will independently screen and select trials for inclusion, extract data and assess the methodological quality using the Cochrane risk of bias tool. Any disagreement will be resolved by consensus. We will perform conventional meta-analyses using Review Manager, and STATA 15, and we will assess the risk of random errors using Trial Sequential Analysis. Also, we will assess and report the overall quality of evidence for all outcomes according to GRADE. DISCUSSION: The evidence on the benefits and harms of stress ulcer prophylaxis in adult ICU patients is unclear and an updated systematic review is warranted as new trials have been published. To control risks of systematic and random errors, we will use Cochrane and GRADE methodology and Trial Sequential Analysis. Our ambition with this systematic review is to provide updated, reliable and precise data to better inform decision makers on the use of stress ulcer prophylaxis in adult ICU patients.
Subject(s)
Clinical Protocols , Peptic Ulcer/prevention & control , Stress, Psychological/complications , Adult , Humans , Intensive Care Units , Proton Pump Inhibitors/therapeutic use , Randomized Controlled Trials as TopicABSTRACT
BACKGROUND: The Scandinavian Starch for Severe Sepsis/Septic Shock (6S) trial showed increased 90-day mortality with hydroxyethyl starch (HES) 130/0.42 vs. Ringer's acetate. To explore the underlying pathophysiology, we compared early changes in plasma cytokine concentrations between patients resuscitated with HES vs. Ringer's acetate. METHODS: In a subgroup of 226 patients from the 6S trial, we calculated delta plasma concentrations of tumour necrosis factor alpha (TNF-α), interleukin (IL)-6 and IL-10 from randomization to day 2. We used multiple linear and logistic regression analyses to assess differences between the groups and associations between delta cytokine concentrations and 90-day mortality, respectively. RESULTS: Baseline characteristics and day 2 mortality were comparable between the groups. We observed similar delta cytokine concentrations in the HES vs. Ringer's group (mean difference in delta TNF-α: -1.5 pg/ml (95% CI, -4.9 to 1.9), P = 0.39; IL-6: 36.0 pg/ml (-24.1 to 96.1), P = 0.24; IL-10: -3.9 pg/ml (-21.1 to 28.9), P = 0.76). In all included patients, we observed a linear relationship between increases in TNF-α and 90-day mortality (P = 0.005). CONCLUSION: Resuscitation with HES 130/0.42 vs. Ringer's acetate did not appear to affect plasma concentrations of TNF-α, IL-6 or IL-10 differently during the first days after randomization into the 6S trial. In the overall cohort, increases in TNF-α were associated with increased 90-day mortality. Although interpretation should be done with caution, it seems unlikely that the increased mortality observed with the use HES in the 6S trial is signalled by early changes in three biomarkers of systemic inflammation.
