在危重症患者中停用泮托拉唑进行应激性溃疡预防：一项初步随机临床试验和荟萃分析。

Withholding Pantoprazole for Stress Ulcer Prophylaxis in Critically Ill Patients: A Pilot Randomized Clinical Trial and Meta-Analysis.

作者信息

Alhazzani Waleed, Guyatt Gordon, Alshahrani Mohammed, Deane Adam M, Marshall John C, Hall Richard, Muscedere John, English Shane W, Lauzier François, Thabane Lehana, Arabi Yaseen M, Karachi Tim, Rochwerg Bram, Finfer Simon, Daneman Nick, Alshamsi Fayez, Zytaruk Nicole, Heel-Ansdell Diane, Cook Deborah

机构信息

1Department of Medicine, McMaster University, Hamilton, ON, Canada.2Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.3Department of Critical Care, University of Dammam, Dammam, Saudi Arabia.4Discipline of Acute Care Medicine, University of Adelaide, Adelaide, SA, Australia.5Department of Surgery and Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.6Departments of Anesthesia, Pain Management and Perioperative Medicine and Critical Care Medicine, Dalhousie University, Halifax, NS, Canada.7Department of Critical Care, Queens University, Kingston, ON, Canada.8Department of Medicine (Critical Care), University of Ottawa, Ottawa, ON, Canada.9Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.10Departments of Medicine, Anesthesiology and Critical Care, Université Laval, Quebec City, QC, Canada.11Biostatistics Unit, St Joseph's Healthcare Hamilton, Hamilton, ON, Canada.12Intensive Care Department, King Saud Bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.13The George Institute for Global Health and Royal North Shore Hospital, University of Sydney, Sydney, NSW, Australia.14Department of Medicine, University of Toronto, Toronto, ON, Canada.15Department of Internal Medicine, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.

出版信息

Crit Care Med. 2017 Jul;45(7):1121-1129. doi: 10.1097/CCM.0000000000002461.

DOI:10.1097/CCM.0000000000002461

PMID:28459708

Abstract

INTRODUCTION

A decreased frequency of upper gastrointestinal bleeding and a possible association of proton pump inhibitor use with Clostridium difficile and ventilator-associated pneumonia have raised concerns recently. The Reevaluating the Inhibition of Stress Erosions Pilot Trial determined the feasibility of undertaking a larger trial investigating the efficacy and safety of withholding proton pump inhibitors in critically ill patients.

METHODS

In 10 ICUs, we randomized adult ICU patients anticipated to be mechanically ventilated for greater than or equal to 48 hours to receive 40 mg of IV pantoprazole daily or placebo. We excluded patients who had acute or recent gastrointestinal bleed, used dual antiplatelet agents, had a medical condition requiring proton pump inhibitor treatment, or had already received more than one dose of acid suppression daily. Patients, families, clinicians, and research staff were blinded. We conducted a systematic review and meta-analysis of similar trials.

MAIN RESULTS

Ninety-one patients (49 pantoprazole and 42 placebo) from 10 centers in Canada, Saudi Arabia, and Australia were enrolled. All feasibility goals were met: 1) recruitment rate was 2.6 patients per month; 2) consent rate was 77.8%; and 3) protocol adherence was 97.7%. Upper gastrointestinal bleeding developed in 6.1% of patients in the pantoprazole group and 4.8% in the placebo group (p = 1.0). Ventilator-associated pneumonia developed in 20.4% of patients in the pantoprazole group and 14.3% in the placebo group (p = 0.58). C. difficile was identified in 4.1% pantoprazole patients and in 2.4% placebo patients (p = 1.0). We meta-analyzed five trials (604 patients) of proton pump inhibitors versus placebo; there was no statistically significant difference in the risk of upper gastrointestinal bleeding, infections, or mortality.

CONCLUSIONS

Our results support the feasibility of a larger trial to evaluate the safety of withholding stress ulcer prophylaxis. Although the results are imprecise, there was no alarming increase in the risk of upper gastrointestinal bleeding; the effect of proton pump inhibitors on ventilator-associated pneumonia and C. difficile remain unclear.

摘要

引言

近期，上消化道出血发生率降低以及质子泵抑制剂的使用可能与艰难梭菌感染及呼吸机相关性肺炎有关，这引发了人们的关注。“应激性溃疡抑制再评估试点试验”确定了开展一项更大规模试验的可行性，该试验旨在研究在重症患者中停用质子泵抑制剂的疗效和安全性。

方法

在10个重症监护病房中，我们将预期接受机械通气≥48小时的成年重症监护病房患者随机分组，分别每日静脉注射40毫克泮托拉唑或接受安慰剂治疗。我们排除了患有急性或近期胃肠道出血、使用双联抗血小板药物、患有需要质子泵抑制剂治疗的疾病或已经每日接受超过一剂抑酸治疗的患者。患者、家属、临床医生和研究人员均处于盲态。我们对类似试验进行了系统评价和荟萃分析。

主要结果

来自加拿大、沙特阿拉伯和澳大利亚10个中心的91名患者（49名接受泮托拉唑治疗，42名接受安慰剂治疗）入组。所有可行性目标均实现：1）招募率为每月2.6名患者；2）同意率为77.8%；3）方案依从率为97.7%。泮托拉唑组6.1%的患者发生上消化道出血，安慰剂组为4.8%（p = 1.0）。泮托拉唑组20.4%的患者发生呼吸机相关性肺炎，安慰剂组为14.3%（p = 0.58）。4.1%接受泮托拉唑治疗的患者和2.4%接受安慰剂治疗的患者检测出艰难梭菌（p = 1.0）。我们对五项比较质子泵抑制剂与安慰剂的试验（604名患者）进行了荟萃分析；在上消化道出血、感染或死亡率风险方面，未发现统计学上的显著差异。