驱动压与急性呼吸窘迫综合征患者的生存。

Driving pressure and survival in the acute respiratory distress syndrome.

机构信息

From the Cardio-Pulmonary Department, Pulmonary Division, Heart Institute (Incor), University of São Paulo (M.B.P.A., E.L.V.C., C.R.R.C.), and the Research and Education Institute, Hospital Sirio-Libanês (E.L.V.C.) - both in São Paulo; the Departments of Clinical Epidemiology and Biostatistics and Medicine, McMaster University, Hamilton, ON (M.O.M., T.E.S., M.B.), and the Keenan Research Centre for Biomedical Science, St. Michael's Hospital (A.S.S., L.B.), and the Interdepartmental Division of Critical Care Medicine and Department of Medicine, University of Toronto (A.S.S., L.B.), Toronto - all in Canada; the Massachusetts General Hospital Biostatistics Center, Harvard Medical School (D.A.S.), and Department of Anesthesia, Critical Care, and Pain Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School (D.T.) - both in Boston; the Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland (M.B.); the Department of Intensive Care and Hyperbaric Medicine, Angers University Hospital, Angers (A.M.), the Emergency Department, General Hospital of Annecy, Annecy (J.-C.M.R.), and INSERM UMR 955, Creteil (J.-C.M.R.) - all in France; and the Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore (R.G.B.).

出版信息

N Engl J Med. 2015 Feb 19;372(8):747-55. doi: 10.1056/NEJMsa1410639.

DOI:10.1056/NEJMsa1410639

PMID:25693014

Abstract

BACKGROUND

Mechanical-ventilation strategies that use lower end-inspiratory (plateau) airway pressures, lower tidal volumes (VT), and higher positive end-expiratory pressures (PEEPs) can improve survival in patients with the acute respiratory distress syndrome (ARDS), but the relative importance of each of these components is uncertain. Because respiratory-system compliance (CRS) is strongly related to the volume of aerated remaining functional lung during disease (termed functional lung size), we hypothesized that driving pressure (ΔP=VT/CRS), in which VT is intrinsically normalized to functional lung size (instead of predicted lung size in healthy persons), would be an index more strongly associated with survival than VT or PEEP in patients who are not actively breathing.

METHODS

Using a statistical tool known as multilevel mediation analysis to analyze individual data from 3562 patients with ARDS enrolled in nine previously reported randomized trials, we examined ΔP as an independent variable associated with survival. In the mediation analysis, we estimated the isolated effects of changes in ΔP resulting from randomized ventilator settings while minimizing confounding due to the baseline severity of lung disease.

RESULTS

Among ventilation variables, ΔP was most strongly associated with survival. A 1-SD increment in ΔP (approximately 7 cm of water) was associated with increased mortality (relative risk, 1.41; 95% confidence interval [CI], 1.31 to 1.51; P<0.001), even in patients receiving "protective" plateau pressures and VT (relative risk, 1.36; 95% CI, 1.17 to 1.58; P<0.001). Individual changes in VT or PEEP after randomization were not independently associated with survival; they were associated only if they were among the changes that led to reductions in ΔP (mediation effects of ΔP, P=0.004 and P=0.001, respectively).

CONCLUSIONS

We found that ΔP was the ventilation variable that best stratified risk. Decreases in ΔP owing to changes in ventilator settings were strongly associated with increased survival. (Funded by Fundação de Amparo e Pesquisa do Estado de São Paulo and others.).

摘要

背景

在急性呼吸窘迫综合征（ARDS）患者中，使用较低的吸气末（平台）气道压力、较低的潮气量（VT）和较高的呼气末正压（PEEP）的机械通气策略可以提高生存率，但这些因素的相对重要性尚不确定。由于呼吸系统顺应性（CRS）与疾病期间充气剩余功能肺的体积（称为功能肺大小）密切相关，我们假设驱动压（ΔP=VT/CRS），其中 VT 本质上与功能肺大小（而不是健康人预测的肺大小）成正比，将是一个比 VT 或 PEEP 更能与非主动呼吸患者的生存率相关的指标。

方法

使用一种称为多级中介分析的统计工具，对 9 项先前报道的随机试验中纳入的 3562 名 ARDS 患者的个体数据进行分析，我们将 ΔP 作为与生存相关的独立变量进行研究。在中介分析中，我们在最小化基线肺疾病严重程度造成的混杂因素的同时，估计了由于随机呼吸机设置引起的 ΔP 变化的单独影响。

结果

在通气变量中，ΔP 与生存率的相关性最强。ΔP 增加 1 个标准差（约 7cmH2O）与死亡率增加相关（相对风险，1.41；95%置信区间[CI]，1.31 至 1.51；P<0.001），即使在接受“保护性”平台压力和 VT 的患者中也是如此（相对风险，1.36；95%CI，1.17 至 1.58；P<0.001）。随机分组后 VT 或 PEEP 的个体变化与生存率无关；只有当它们是导致 ΔP 降低的变化之一时，它们才与生存率相关（ΔP 的中介效应，P=0.004 和 P=0.001）。