ORIGINAL ARTICLE

Pantoprazole in Patients at Risk for Gastrointestinal Bleeding in the ICU

Mette Krag, Søren Marker, Anders Perner, et al

N Engl J Med October 24, 2018

DOI: 10.1056/NEJMoa1714919

Abstract

BACKGROUND 背景

Prophylaxis for gastrointestinal stress ulceration is frequently given to patients in the intensive care unit (ICU), but its risks and benefits are unclear.

ICU患者常常接受胃肠道应激性溃疡的预防，但其风险及获益并不清楚。

METHODS 方法

In this European, multicenter, parallel-group, blinded trial, we randomly assigned 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 to receive 40 mg of intravenous pantoprazole (a proton-pump inhibitor) or placebo daily during the ICU stay. The primary outcome was death by 90 days after randomization.

在欧洲进行的这项多中心、平行对照、设盲临床试验中，将因急性病入住ICU（即非计划收入）且胃肠道出血高危的成年患者随机分组，在ICU住院期间接受静脉泮托拉唑（质子泵抑制剂）40 mg/d或安慰剂治疗。主要预后指标为随机分组后90天病死率。

RESULTS 结果

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.

共有3298名患者入选；1645名随机分至泮托拉唑组，1653名分至安慰剂组。3282名患者(99.5%)有主要预后终点指标。90天时，泮托拉唑组510名(31.1%)患者，安慰剂组499名(30.4%)患者死亡（相对危险度1.02；95% 可信区间 [CI]，0.91 to 1.13; P=0.76）。在ICU住院期间，泮托拉唑组和安慰剂组分别有21.9%和22.6%的患者至少发生一次临床重要事件（包括临床重要的胃肠道出血，肺炎，难辨梭状芽孢杆菌感染，或心肌缺血）（相对危险度0.96；95% CI, 0.83 to 1.11）。在泮托拉唑组，2.5%的患者发生临床重要的胃肠道出血，安慰剂组则为4.2%。两组患者中感染或严重不良反应发生率以及90天内无生命支持的存活天数相似。

CONCLUSIONS 结论

Among adult patients in the ICU who were at risk for gastrointestinal bleeding, mortality at 90 days and the number of clinically important events were similar in those assigned to pantoprazole and those assigned to placebo.

对于具有胃肠道出血风险的成年ICU患者，泮托拉唑组及安慰剂组90天病死率及临床重要事件发生率相似。

(Funded by Innovation Fund Denmark and others; SUP-ICU ClinicalTrials.gov number, NCT02467621.)