Pantoprazole in Patients at Risk for Gastrointestinal Bleeding in the ICU

Krag M, Marker S, Perner A, et al. N Engl J Med. 2018 Dec 6;379(23):2199-2208. [CrossRef] [PubMed]

Prophylaxis for gastrointestinal stress ulceration is frequently given to patients in the intensive care unit (ICU), but its risks and benefits are unclear. A recent meta-analysis suggested that proton-pump inhibitors result in a decrease in gastrointestinal bleeding but an increase in pneumonia. In this European, multicenter, parallel-group, blinded trial, adults who had been admitted to the ICU for an acute condition (i.e., an unplanned admission) and who were at risk for gastrointestinal bleeding were randomly assigned to receive 40 mg of intravenous pantoprazole (a proton-pump inhibitor) or placebo. The primary outcome was death by 90 days after randomization. A total of 3298 patients were enrolled; 1645 were randomly assigned to the pantoprazole group and 1653 to the placebo group. Data on the primary outcome were available for 3282 patients (99.5%). At 90 days, 510 patients (31.1%) in the pantoprazole group and 499 (30.4%) in the placebo group had died (relative risk, 1.02; 95% confidence interval [CI], 0.91 to 1.13; P=0.76). During the ICU stay, at least one clinically important event (a composite of clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection, or myocardial ischemia) had occurred in 21.9% of patients assigned to pantoprazole and 22.6% of those assigned to placebo (relative risk, 0.96; 95% CI, 0.83 to 1.11). In the pantoprazole group, 2.5% of patients had clinically important gastrointestinal bleeding, as compared with 4.2% in the placebo group. The number of patients with infections or serious adverse reactions and the percentage of days alive without life support within 90 days were similar in the two groups. The authors conclude that the number of clinically important events were similar in those assigned to pantoprazole and those assigned to placebo.