Could stress ulcer prophylaxis increase mortality in high-acuity patients?

Background In previous studies of predictors of gastrointestinal (GI) bleeding in the intensive care unit (ICU), most patients received pharmacological stress ulcer prophylaxis (SUP). We aimed to assess associations between potential predictors of clinically important GI bleeding (CIB) and overt GI bleeding in adult ICU patients, while considering the effect and potential interaction with use of SUP. Methods We included 3291 acutely admitted adult ICU patients with risk factors for GI bleeding randomized to SUP (pantoprazole) or placebo in the SUP‐ICU trial. We used logistic regression models adjusted for allocation to SUP to estimate associations between 23 potential predictors and CIB (primary outcome) and overt GI bleeding (secondary outcome). Furthermore, we assessed associations between potential predictors and both outcomes in each allocation group and assessed potential interaction with allocation to SUP. Results Increasing SAPS II and SOFA scores, use of circulatory support and renal replacement therapy were associated with increased risk of CIB and overt GI bleeding; chronic lung disease was associated with increased risk of overt GI bleeding. Results for the remaining potential predictors were compatible with both no difference or increased and decreased risks. We found no strong evidence for any interaction between treatment allocation and any potential predictors. Conclusion In adult ICU patients at risk of GI bleeding, severity of illness, use of circulatory support and renal replacement therapy were associated with higher odds of CIB, with no strong evidence of interaction with SUP.

Section: Introductionmentioning

confidence: 99%

“…On the contrary, subgroup analyses from recent randomized clinical trials have suggested increased risk of death with SUP using PPIs in the most severely ill patients, who are usually those at highest risk of GI bleeding 4,10,12,17,18 . This may affect patient and clinician preferences with regard to use of SUP 11 …”

Section: Introductionmentioning

confidence: 99%

Predictors of gastrointestinal bleeding in adult ICU patients in the SUP‐ICU trial

Granholm

Krag

Marker

et al. 2021

“…However, as corticosteroids are generally considered safe and are widely used in critically ill patients, the clinical threshold for using a higher dose of corticosteroids in COVID‐19 may be different from thresholds for introducing new, potentially expensive and potentially invasive treatments 42 . Given the current pandemic, it may be considered reasonable to act on probabilities in spite of uncertainty, as has recently been argued for other treatment decisions in the critically ill 42,43 …”

Section: Discussionmentioning

confidence: 99%

Higher vs Lower Doses of Dexamethasone in Patients with COVID‐19 and Severe Hypoxia (COVID STEROID 2) trial: Protocol for a secondary Bayesian analysis

Granholm

Munch

Myatra

et al. 2021

Background Coronavirus disease 2019 (COVID‐19) can lead to severe hypoxic respiratory failure and death. Corticosteroids decrease mortality in severely or critically ill patients with COVID‐19. However, the optimal dose remains unresolved. The ongoing randomised COVID STEROID 2 trial investigates the effects of higher vs lower doses of dexamethasone (12 vs 6 mg intravenously daily for up to 10 days) in 1,000 adult patients with COVID‐19 and severe hypoxia. Methods This protocol outlines the rationale and statistical methods for a secondary, pre‐planned Bayesian analysis of the primary outcome (days alive without life support at day 28) and all secondary outcomes registered up to day 90. We will use hurdle‐negative binomial models to estimate the mean number of days alive without life support in each group and present results as mean differences and incidence rate ratios with 95% credibility intervals (CrIs). Additional count outcomes will be analysed similarly and binary outcomes will be analysed using logistic regression models with results presented as probabilities, relative risks and risk differences with 95% CrIs. We will present probabilities of any benefit/harm, clinically important benefit/harm and probabilities of effects smaller than pre‐defined clinically minimally important differences for all outcomes analysed. Analyses will be adjusted for stratification variables and conducted using weakly informative priors supplemented by sensitivity analyses using sceptic priors. Discussion This secondary, pre‐planned Bayesian analysis will supplement the primary, conventional analysis and may help clinicians, researchers and policymakers interpret the results of the COVID STEROID 2 trial while avoiding arbitrarily dichotomised interpretations of the results. Trial registration ClinicalTrials.gov: NCT04509973; EudraCT: 2020‐003363‐25.

“…However, there were some concerns about how the guideline should be used bedside, as it may be somewhat difficult to decide whether the risk of gastrointestinal bleeding is low, moderate, or high based on the presence of one or more risk factors. Also, the available evidence does not uniformly rule out clinically important harm from acid suppressants 6 …”

Section: Discussionmentioning

confidence: 99%

“…Also, the available evidence does not uniformly rule out clinically important harm from acid suppressants. 6 Nevertheless, the clinical practice guideline serves as a useful decision aid for clinicians caring for critically ill patients and can be used together with clinical experience to decide whether a specific critically ill patient may benefit from gastrointestinal bleeding prophylaxis.…”

Section: Discussionmentioning

confidence: 99%

Clinical practice guideline on gastrointestinal bleeding prophylaxis for critically ill patients: Endorsement by the Scandinavian Society of Anaesthesiology and Intensive Care Medicine

Sverrisson

Chew

Olkkola

et al. 2021

The Scandinavian Society of Anaesthesiology and Intensive Care Medicine Clinical practice Committee endorses the BMJ Rapid Recommendation Gastrointestinal bleeding prophylaxis for critically ill patients—a clinical practice guideline. The guideline serves as a useful decision aid for clinicians caring for critically ill patients, and can be used together with clinical experience to decide whether a specific critically ill patient may benefit from gastrointestinal bleeding prophylaxis.