Personalised mechanical ventilation tailored to lung morphology versus low positive end-expiratory pressure for patients with acute respiratory distress syndrome in France (the LIVE study): a multicentre, single-blind, randomised controlled trial
Personalised mechanical ventilation tailored to lung morphology versus low positive end-expiratory pressure for patients with acute respiratory distress syndrome in France (the LIVE study): a multicentre, single-blind, randomised controlled trial
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DOI：
10.1016/s2213-2600(19)30138-9
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发表时间：
2019-10-01
影响因子：
76.2
通讯作者：
Futier, Emmanuel
中科院分区：
文献类型：
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作者：
Constantin, Jean-Michel;Jabaudon, Matthieu;Futier, Emmanuel
个体化机械通气对急性呼吸窘迫综合征（ARDS）患者临床结局的影响尚不确定，需要进行评估。我们的目的是测试是否是个性化的个别患者的肺形态的机械通气策略将提高生存率的患者与ARDS相比，与standard of care.Methods我们设计了一个多中心，单盲，分层，平行组，随机对照试验中，中度至重度ARDS患者在20所大学或非大学重症监护病房在法国。年龄大于18岁的早期ARDS持续时间小于12小时的患者使用最小化算法随机分配（1：1）至对照组或个性化组，并根据研究部位、肺形态和机械通气持续时间分层。仅患者对分配设盲。对照组患者接受每预测体重6 mL/kg的潮气量，根据低PEEP和吸入氧表分数选择呼气末正压（PEEP），并鼓励早期俯卧位。在个性化组中，治疗方法基于肺形态学;局灶性ARDS患者接受8 mL/kg潮气量、低PEEP和俯卧位。非局灶性ARDS患者接受6 mL/kg潮气量，沿着肺复张和高PEEP。主要结局是通过意向治疗分析确定的90天死亡率。本研究在ClinicalTrials在线注册。结果从2014年6月12日至2017年2月2日，420名患者被随机分配到治疗组。个性化组排除了11例患者，对照组排除了9例患者;个性化组196例患者和对照组204例患者纳入分析。在多变量分析中，在意向治疗分析中，个体化通气治疗组和对照组的90天死亡率无差异（风险比[HR] 1.01; 95% CI 0.61-1.66; p=0.98）。然而，在400例患者中，有85例（21%）观察到研究者将患者错误分类为局灶性或非局灶性ARDS。我们发现错误分类和随机分组在主要结果方面存在显著的相互作用（p< 0.001）。在亚组分析中，个性化组中错误分类患者的90天死亡率较高（40例患者中的26例[65%]）比对照组（57例患者中的18例[32%]; HR 2.8; 95% CI 1.5-5.1; P= 0.012。解释个性化机械通气并没有降低ARDS患者的死亡率，可能是因为21%的患者分类错误。与肺形态不一致的呼吸机策略大大增加了死亡率。ARDS表型的改善是否可以降低死亡率，应该在未来的临床试验中进行评估。
Background The effect of personalised mechanical ventilation on clinical outcomes in patients with acute respiratory distress syndrome (ARDS) remains uncertain and needs to be evaluated. We aimed to test whether a mechanical ventilation strategy that was personalised to individual patients' lung morphology would improve the survival of patients with ARDS when compared with standard of care.Methods We designed a multicentre, single-blind, stratified, parallel-group, randomised controlled trial enrolling patients with moderate-to-severe ARDS in 20 university or non-university intensive care units in France. Patients older than 18 years with early ARDS for less than 12 h were randomly assigned (1: 1) to either the control group or the personalised group using a minimisation algorithm and stratified according to the study site, lung morphology, and duration of mechanical ventilation. Only the patients were masked to allocation. In the control group, patients received a tidal volume of 6 mL/kg per predicted bodyweight and positive end-expiratory pressure (PEEP) was selected according to a low PEEP and fraction of inspired oxygen table, and early prone position was encouraged. In the personalised group, the treatment approach was based on lung morphology; patients with focal ARDS received a tidal volume of 8 mL/kg, low PEEP, and prone position. Patients with non-focal ARDS received a tidal volume of 6 mL/kg, along with recruitment manoeuvres and high PEEP. The primary outcome was 90-day mortality as established by intention-totreat analysis. This study is registered online with ClinicalTrials. gov, NCT02149589.Findings From June 12, 2014, to Feb 2, 2017, 420 patients were randomly assigned to treatment. 11 patients were excluded in the personalised group and nine patients were excluded in the control group; 196 patients in the personalised group and 204 in the control group were included in the analysis. In a multivariate analysis, there was no difference in 90-day mortality between the group treated with personalised ventilation and the control group in the intention-to-treat analysis (hazard ratio [HR] 1.01; 95% CI 0.61-1.66; p=0.98). However, misclassification of patients as having focal or non-focal ARDS by the investigators was observed in 85 (21%) of 400 patients. We found a significant interaction between misclassification and randomised group allocation with respect to the primary outcome (p< 0.001). In the subgroup analysis, the 90-day mortality of the misclassified patients was higher in the personalised group (26 [65%] of 40 patients) than in the control group (18 [32%] of 57 patients; HR 2.8; 95% CI 1.5-5.1; p=0.012.Interpretation Personalisation of mechanical ventilation did not decrease mortality in patients with ARDS, possibly because of the misclassification of 21% of patients. A ventilator strategy misaligned with lung morphology substantially increases mortality. Whether improvement in ARDS phenotyping can decrease mortality should be assessed in a future clinical trial.