Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants in acutely ill adult intensive care patients

Krag, Mette; Perner, Anders; Wetterslev, Jørn; Wise, Matthew Peter; Borthwick, Mark; Bendel, Stepani; McArthur, Colin; Cook, Deborah J.; Nielsen, Niklas; Pelosi, Paolo; Keus, Frederik; Guttormsen, Anne Berit; Möller, Alma D.; Møller, Morten Hylander

doi:10.1007/s00134-015-3725-1

Cited by 223 publications

(247 citation statements)

References 39 publications

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“…These results suggest that bleeding simply identifies patients at greater risk of dying and, when treated, bleeding per se does not cause death [3]. Data from Krag and colleagues [1] support this hypothesis: when the investigators conducted an adjusted analysis accounting for possible confounders, bleeding was not associated with mortality.…”

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confidence: 92%

“…Every clinician involved in the administration of acidsuppressive drugs to critically ill patients should read the observations presented in a recent article in this journal [1]. Krag and colleagues [1] have conducted an international, multi-centre, observational study and provide a modern and relatively precise estimate of the incidence of, and risk factors for, gastrointestinal (GI) bleeding in critically ill patients.…”

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confidence: 99%

“…Krag and colleagues [1] have conducted an international, multi-centre, observational study and provide a modern and relatively precise estimate of the incidence of, and risk factors for, gastrointestinal (GI) bleeding in critically ill patients. Notwithstanding the methodological limitations that the authors acknowledge, these are very important data directly pertaining to clinical practice.…”

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confidence: 99%

“…This may explain the widespread use of these drugs [1,13]. In addition to the considerations outlined regarding the potential adverse effects of these medications, the costs incurred with these frequently prescribed drugs demand that further data are available to inform and guide clinical practice [14].…”

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confidence: 99%

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Primum non nocere and challenging conventional treatment

Deane

Guyatt

2015

Intensive Care Med

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confidence: 92%

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confidence: 99%

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confidence: 99%

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Primum non nocere and challenging conventional treatment

Deane

Guyatt

2015

Intensive Care Med

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“…Given the routine acid suppression in many ICUs [2,3], and incorporation of this approach in practice guidelines [4], it appears that the critical care community shares our assessment of the existing evidence. We therefore suggest that the key issue is whether the magnitude of effect on clinically important upper gastrointestinal bleeding from stress ulcer prophylaxis is sufficient that it warrants continued use, particularly given risks and costs [5].…”

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confidence: 99%

Trials on stress ulcer prophylaxis: finding the balance between benefit and harm. Response to Krag et al.

Deane

Guyatt

2015

Intensive Care Med

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Effect of Stress Ulcer Prophylaxis With Proton Pump Inhibitors vs Histamine-2 Receptor Blockers on In-Hospital Mortality Among ICU Patients Receiving Invasive Mechanical Ventilation

Young

Bagshaw

Forbes

et al. 2020

JAMA

160

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IMPORTANCE Proton pump inhibitors (PPIs) or histamine-2 receptor blockers (H 2 RBs) are often prescribed for patients as stress ulcer prophylaxis drugs in the intensive care unit (ICU). The comparative effect of these drugs on mortality is unknown. OBJECTIVE To compare in-hospital mortality rates using PPIs vs H 2 RBs for stress ulcer prophylaxis.DESIGN, SETTING, AND PARTICIPANTS Cluster crossover randomized clinical trial conducted at 50 ICUs in 5 countries between August 2016 and January 2019. Patients requiring invasive mechanical ventilation within 24 hours of ICU admission were followed up for 90 days at the hospital.INTERVENTIONS Two stress ulcer prophylaxis strategies were compared (preferential use with PPIs vs preferential use with H 2 RBs). Each ICU used each strategy sequentially for 6 months in random order; 25 ICUs were randomized to the sequence with use of PPIs and then use of H 2 RBs and 25 ICUs were randomized to the sequence with use of H 2 RBs and then use of PPIs (13 436 patients randomized by site to PPIs and 13 392 randomized by site to H 2 RBs). MAIN OUTCOMES AND MEASURESThe primary outcome was all-cause mortality within 90 days during index hospitalization. Secondary outcomes were clinically important upper gastrointestinal bleeding, Clostridioides difficile infection, and ICU and hospital lengths of stay. RESULTS Among 26 982 patients who were randomized, 154 opted out, and 26 828 were analyzed (mean [SD] age, 58 [17.0] years; 9691 [36.1%] were women). There were 26 771 patients (99.2%) included in the mortality analysis; 2459 of 13 415 patients (18.3%) in the PPI group died at the hospital by day 90 and 2333 of 13 356 patients (17.5%) in the H 2 RB group died at the hospital by day 90 (risk ratio, 1.05 [95% CI, 1.00 to 1.10]; absolute risk difference, 0.93 percentage points [95% CI, −0.01 to 1.88] percentage points; P = .054). An estimated 4.1% of patients randomized by ICU site to PPIs actually received H 2 RBs and an estimated 20.1% of patients randomized by ICU site to H 2 RBs actually received PPIs. Clinically important upper gastrointestinal bleeding occurred in 1.3% of the PPI group and 1.8% of the H 2 RB group (risk ratio, 0.73 [95% CI, 0.57 to 0.92]; absolute risk difference, −0.51 percentage points [95% CI, −0.90 to −0.12 percentage points]; P = .009). Rates of Clostridioides difficile infection and ICU and hospital lengths of stay were not significantly different by treatment group. One adverse event (an allergic reaction) was reported in 1 patient in the PPI group.CONCLUSIONS AND RELEVANCE Among ICU patients requiring mechanical ventilation, a strategy of stress ulcer prophylaxis with use of proton pump inhibitors vs histamine-2 receptor blockers resulted in hospital mortality rates of 18.3% vs 17.5%, respectively, a difference that did not reach the significance threshold. However, study interpretation may be limited by crossover in the use of the assigned medication.

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Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants in acutely ill adult intensive care patients

Cited by 223 publications

References 39 publications

Primum non nocere and challenging conventional treatment

Primum non nocere and challenging conventional treatment

Trials on stress ulcer prophylaxis: finding the balance between benefit and harm. Response to Krag et al.

Effect of Stress Ulcer Prophylaxis With Proton Pump Inhibitors vs Histamine-2 Receptor Blockers on In-Hospital Mortality Among ICU Patients Receiving Invasive Mechanical Ventilation

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