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Why compliance and driving pressure may be inappropriate targets for PEEP setting during ARDS
Critical Care ( IF 8.8 ) Pub Date : 2022-08-02 , DOI: 10.1186/s13054-022-04109-7
Domenico Luca Grieco 1, 2 , Filippo Bongiovanni 1, 2 , Antonio M Dell'Anna 1, 2 , Massimo Antonelli 1, 2
Affiliation  

We read with great interest the viewpoint by Cove and coworkers entitled “Are we ready to think differently about setting PEEP?”, recently published in the journal [1]. The authors provide an insightful explanation of the unresolved issue of positive end-expiratory (PEEP) setting in acute respiratory distress syndrome (ARDS) patients, addressing the pitfalls of the protocols foreseeing stepwise increases in PEEP proportional to the fraction of inspirated oxygen (FiO2) required to maintain arterial oxygen levels within a physiological range (the so-called PEEP-FiO2 tables) [2]. These PEEP-FiO2 tables are based on the concept that there is a substantial correlation between ARDS severity and lung recruitability [3]; due to their simplicity to use, they are often applied at the bedside and used as control strategy in randomized studies, especially as no other approach has been proven superior in terms of clinical outcome in randomized trials.

Indeed, lung recruitability as a response to PEEP has wide inter-subject variability. High PEEP in patients with poor recruitability increases static stress and strain and may induce right ventricular dysfunction, finally contributing to ventilator-induced lung injury and multi-organ dysfunction. Low PEEP in recruitable patients does not fully exert its potential benefits, which include avoidance of atelectrauma and reduction in the mechanical distortion provided by tidal volume in the aerated lung (i.e., the dynamic strain) [4]. Cove and coworkers propose that a PEEP-setting approach to target the highest respiratory system compliance (and lowest driving pressure), which can be easily measured on every mechanical ventilator, can identify the PEEP level that best benefits the patient. From authors’ perspective, if PEEP generates recruitment of functional lung units, compliance increases; conversely, if few or no functional units are recruited, compliance remains unchanged or decreases due to overdistension of already open lung tissue. This hypothesis comes from the classical physiological concept of proportionality between respiratory system compliance and aerated lung size [5].

The idea of personalizing PEEP based on the amount of individual recruitment is physiologically sound [6]. Unfortunately, raising evidence indicates that PEEP-induced changes in compliance and driving pressure are inaccurate measures of the amount of recruitment. This happens both in COVID-19 and non-COVID-19 ARDS.

Alveolar recruitment can be measured with different tools: Computed tomography scan provides information about the so-termed tissue recruitment; electrical impedance tomography, pressure–volume curves and their derived indices (as the recruitment-to-inflation ratio) measure gas recruitment in the lungs [7, 8].

In a recent computed tomography scan study, significant tissue recruitment was not systematically accompanied by increases in compliance, nor absence of recruitment could be identified by unchanged or reduced compliance [9]. Regarding gas recruitment, we re-analyzed data from a previously published study on 30 COVID-19 suffering from moderate-to-severe ARDS early after intubation [10]: Respiratory mechanics were measured at PEEP 15 and 5 cmH2O, and alveolar recruitment was measured through a simplified derecruitment maneuver. With constant tidal volume, change in PEEP from 5 to 15 cmH2O was associated with increased (> 5 ml/cmH2O) compliance in 6 patients (20%), unchanged compliance in 11 patients (37%) and reduced (< 5 ml/cmH2O) compliance in 13 patients (43%). Average alveolar recruitment was 32 ml per cmH2O of applied PEEP, and mean recruitment-to-inflation ratio was 0.81. As shown in Fig. 1, neither alveolar recruitment nor the recruitment-to-inflation ratio could be predicted by changes in respiratory system compliance (p = 0.58 and p = 0.14, respectively).

Fig. 1
figure 1

Potential for lung recruitment and changes in respiratory system compliance induced by PEEP in 30 ARDS patients. Re-analysis of data from [10]. Lung recruitability (assessed as absolute recruited volume normalized to the change in PEEP—left, and the recruitment-to-inflation ratio—right) in patients who showed increased, unchanged (defined as a clinically relevant modification of < 5 ml/cmH2O) or diminished respiratory system compliance as a response to 10-cmH2O PEEP increase. Changes in respiratory system compliance are ineffective measure of the recruitment induced by PEEP. Data from individual patients, medians and interquartile ranges are displayed. The dotted horizontal lines represent the mean values of recruitment and recruitment-to-inflation ratio in the study cohort. Data were analyzed with the Kruskal Wallis test. CRS = respiratory system compliance

Full size image

These data indicate that compliance and driving pressure are ineffective estimates of PEEP-induced lung recruitment, both if recruitment is assessed as tissue recruitment with computed tomography scan or as gas recruitment with pressure–volume curves-derived indices. Using compliance and driving pressure to assess the response to PEEP may seriously mislead clinicians.

There are several mechanisms that explain why the “physiologically sound” model foreseeing that changes in compliance reflect presence or absence of recruitment fails to work in clinical practice. First, compliance and driving pressure are global measures and do not account for the regional behavior of lung tissue; alveolar recruitment and overdistension are regional and heterogeneous phenomena. Second, tidal recruitment is a common phenomenon in ARDS patients, especially at low PEEP. Tidal recruitment is the cyclic opening and closing of alveolar units during tidal ventilation. When this occurs, alveolar units that are collapsed at end-expiration reopen due to the increase in airway pressure produced by tidal volume inflation. Respiratory system compliance is the sum of the compliance of each alveolar unit that is open at end-inspiration. When a collapsed alveolar unit reopens during inspiration, as it is in case of tidal recruitment, its individual compliance tends toward infinity. This finally increases static respiratory system compliance. This is why tidal recruitment makes static compliance very high at low PEEP and explains why increases in PEEP, which limits tidal recruitment, may generate worsening compliance also in case of significant recruitment. In our study [10], 80% of patients showed unchanged or decreased compliance in spite of alveolar recruitment within average values. Reduced compliance and increased driving pressure despite significant recruitment have been reported also in patients with ARDS of non-COVID-19 etiology [11].

Importantly, one large randomized trial on more than 1,000 patients showed that PEEP set to maximize respiratory system compliance (and limit driving pressure) may worsen patients’ survival, as compared to the low-PEEP-FiO2 table [12].

We fully agree with Cove and coworkers that the search for a personalized PEEP-setting strategy for moderate-to-severe ARDS patients is of utmost importance and represents a research priority. Assessment of respiratory system compliance and limiting driving pressure are essential to guide tidal volume setting [13]. Differently, clinical and physiological data do not support the use of a PEEP-setting strategy to target maximal respiratory system compliance (or minimal driving pressure) during ARDS.

From a clinical standpoint, setting PEEP with the aim of achieving a transpulmonary pressure close to 0 cmH2O seems promising in obese patients [14, 15]. Other physiology-based protocols providing individualized PEEP driven by lung recruitability assessment through electrical impedance tomography, recruitment-to-inflation ratio (NCT03963622) or bedside lung volume measurement (NCT04012073) are being tested in randomized trials and will hopefully illuminate the important aspect of PEEP individualization during ARDS.

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

ARDS:

Acute respiratory distress syndrome

PEEP:

Positive end-expiratory pressure

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This study was funded solely by institutional/departmental resources.

Authors and Affiliations

  1. Department of Emergency, Intensive Care Medicine and Anesthesia, Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go F. Vito, 00168, Rome, Italy

    Domenico Luca Grieco, Filippo Bongiovanni, Antonio M. Dell’Anna & Massimo Antonelli

  2. Istituto di Anestesiologia e Rianimazione, Università Cattolica del Sacro Cuore, Rome, Italy

    Domenico Luca Grieco, Filippo Bongiovanni, Antonio M. Dell’Anna & Massimo Antonelli

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  1. Domenico Luca GriecoView author publications

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Contributions

DLG and FB drafted the letter. AMDA and MA critically revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Domenico Luca Grieco.

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Competing interests

DLG has received payments for travel expenses by Getinge and Air Liquide, speaking fees by Intersurgical, GE, Fisher and Paykel and Gilead. MA has received payments for Board participation from Maquet, Air Liquide and Chiesi. DLG and MA disclose a research grant by General Electric Healthcare. DLG is supported by grants by ESICM and SIAARTI.

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Grieco, D.L., Bongiovanni, F., Dell’Anna, A.M. et al. Why compliance and driving pressure may be inappropriate targets for PEEP setting during ARDS. Crit Care 26, 234 (2022). https://doi.org/10.1186/s13054-022-04109-7

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中文翻译：
为什么顺应性和驱动压力可能不是 ARDS 期间设置 PEEP 的不合适目标

我们怀着极大的兴趣阅读了 Cove 及其同事最近发表在期刊 [1] 上的题为“我们准备好以不同方式思考设置 PEEP 了吗？”的观点。作者对急性呼吸窘迫综合征 (ARDS) 患者呼气末正向 (PEEP) 设置的未解决问题提供了深刻的解释，解决了预期 PEEP 逐步增加与吸入氧气比例 (FiO 2 ) 需要将动脉血氧水平维持在生理范围内（所谓的 PEEP-FiO 2表）[2]。这些 PEEP-FiO 2表格基于 ARDS 严重程度与肺复张性之间存在显着相关性的概念 [3]；由于它们使用简单，它们经常在床边应用并用作随机研究中的控制策略，特别是因为在随机试验的临床结果方面没有其他方法被证明是更好的。

事实上，肺复张性作为对 PEEP 的反应具有广泛的受试者间变异性。肺复张性差的患者的高 PEEP 会增加静态应力和应变，并可能导致右心室功能障碍，最终导致呼吸机引起的肺损伤和多器官功能障碍。可复张患者的低 PEEP 并未充分发挥其潜在益处，包括避免肺不张和减少充气肺中潮气量提供的机械变形（即动态应变）[4]。Cove 和他的同事提出，一种 PEEP 设置方法可以针对最高的呼吸系统顺应性（和最低的驱动压力），这可以在每台机械呼吸机上轻松测量，可以确定最有利于患者的 PEEP 水平。从作者的角度来看，如果 PEEP 产生功能性肺单位的募集，则顺应性增加；相反，如果很少或没有功能单位被招募，顺应性保持不变或由于已经开放的肺组织过度扩张而降低。这一假设来自于呼吸系统顺应性与充气肺大小之间比例的经典生理概念 [5]。

基于个体招募量个性化 PEEP 的想法在生理上是合理的 [6]。不幸的是，越来越多的证据表明，PEEP 引起的顺应性和驱动压力变化是对招募量的不准确衡量。这发生在 COVID-19 和非 COVID-19 急性呼吸窘迫综合征中。

肺泡复张可以使用不同的工具进行测量：计算机断层扫描提供有关所谓的组织复张的信息；电阻抗断层扫描、压力-容积曲线及其衍生指数（作为募集与充气比率）测量肺部的气体募集 [7, 8]。

在最近的一项计算机断层扫描研究中，显着的组织募集并没有系统地伴随依从性的增加，也不能通过改变或降低依从性来识别缺乏募集 [9]。关于气体募集，我们重新分析了先前发表的一项关于 30 例在插管后早期患有中度至重度 ARDS 的 COVID-19 研究的数据 [10]：在 PEEP 15 和 5 cmH 2 O 和肺泡募集时测量呼吸力学是通过简化的招募操作来衡量的。在潮气量恒定的情况下，PEEP 从 5 到 15 cmH 2 O 的变化与 6 名患者 (20%) 的顺应性增加 (> 5 ml/cmH 2 O)、11 名患者 (37%) 的顺应性保持不变和降低 (< 5毫升/厘米H 2O) 13 名患者 (43%) 的依从性。平均肺泡复张为每 cmH 2 O 应用 PEEP 32 ml，平均复张与充气比率为 0.81。如图 1 所示，呼吸系统顺应性的变化既不能预测肺泡复张，也不能预测肺泡复张（分别为p  = 0.58 和p  = 0.14）。

图。1
图1

在 30 名 ARDS 患者中，PEEP 引起的肺复张和呼吸系统顺应性变化的可能性。重新分析[10]中的数据。肺复张性（评估为根据 PEEP 变化标准化的绝对复张量—左，复张与充气比率—右）显示增加、未改变（定义为临床相关的修正 < 5 ml/cmH 2 O ）的患者) 或呼吸系统顺应性降低作为对 10-cmH 2的反应O PEEP 增加。呼吸系统顺应性的变化是 PEEP 诱导的募集的无效测量。显示来自个体患者、中位数和四分位间距的数据。水平虚线代表研究队列中招募和招募与通货膨胀比率的平均值。使用 Kruskal Wallis 检验分析数据。C RS  = 呼吸系统顺应性

全尺寸图片

这些数据表明，顺应性和驱动压力对于 PEEP 诱导的肺复张是无效的估计，无论是通过计算机断层扫描将肺复张评估为组织复张，还是通过压力-体积曲线衍生指数评估为气体复张。使用依从性和驱动压力来评估对 PEEP 的反应可能会严重误导临床医生。

有几种机制可以解释为什么“生理健全”模型预见到依从性的变化反映了招募的存在或不存在，但在临床实践中却失败了。首先，顺应性和驱动压力是全局测量，不考虑肺组织的区域行为；肺泡复张和过度扩张是区域性和异质性现象。其次，潮汐肺复张是 ARDS 患者的常见现象，尤其是在低 PEEP 时。潮气复张是潮气通气期间肺泡单位的循环打开和关闭。当这种情况发生时，由于潮气量膨胀产生的气道压力增加，在呼气末塌陷的肺泡单位会重新打开。呼吸系统顺应性是在吸气末打开的每个肺泡单位顺应性的总和。当一个塌陷的肺泡单位在吸气时重新打开时，就像潮汐募集的情况一样，它的个体顺从性趋于无穷大。这最终增加了静态呼吸系统的顺应性。这就是为什么潮汐肺复张在低 PEEP 时静态顺应性非常高，并解释了为什么限制潮汐肺复张的 PEEP 增加可能会在显着招募的情况下导致顺应性恶化。在我们的研究 [10] 中，尽管肺泡复张在平均值范围内，但 80% 的患者的依从性没有改变或降低。在非 COVID-19 病因的 ARDS 患者中也有报道称，尽管有大量招募，但依从性降低和驱动压力增加 [11]。这最终增加了静态呼吸系统的顺应性。这就是为什么潮汐肺复张在低 PEEP 时静态顺应性非常高，并解释了为什么限制潮汐肺复张的 PEEP 增加可能会在显着招募的情况下导致顺应性恶化。在我们的研究 [10] 中，尽管肺泡复张在平均值范围内，但 80% 的患者的依从性没有改变或降低。在非 COVID-19 病因的 ARDS 患者中也有报道称，尽管有大量招募，但依从性降低和驱动压力增加 [11]。这最终增加了静态呼吸系统的顺应性。这就是为什么潮汐肺复张在低 PEEP 时静态顺应性非常高，并解释了为什么限制潮汐肺复张的 PEEP 增加可能会在显着招募的情况下导致顺应性恶化。在我们的研究 [10] 中，尽管肺泡复张在平均值范围内，但 80% 的患者的依从性没有改变或降低。在非 COVID-19 病因的 ARDS 患者中也有报道称，尽管有大量招募，但依从性降低和驱动压力增加 [11]。在我们的研究 [10] 中，尽管肺泡复张在平均值范围内，但 80% 的患者的依从性没有改变或降低。在非 COVID-19 病因的 ARDS 患者中也有报道称，尽管有大量招募，但依从性降低和驱动压力增加 [11]。在我们的研究 [10] 中，尽管肺泡复张在平均值范围内，但 80% 的患者的依从性没有改变或降低。在非 COVID-19 病因的 ARDS 患者中也有报道称，尽管有大量招募，但依从性降低和驱动压力增加 [11]。

重要的是，一项针对 1,000 多名患者的大型随机试验表明，与低 PEEP-FiO 2表相比，PEEP 设置为最大限度地提高呼吸系统顺应性（并限制驱动压力）可能会恶化患者的生存率[12]。

我们完全同意 Cove 和同事的观点，即为中重度 ARDS 患者寻找个性化的 PEEP 设置策略至关重要，并且代表了研究重点。评估呼吸系统顺应性和限制驱动压力对于指导潮气量设置至关重要 [13]。不同的是，临床和生理数据不支持使用 PEEP 设置策略来针对 ARDS 期间的最大呼吸系统顺应性（或最小驱动压力）。

从临床的角度来看，设定 PEEP 以实现接近 0 cmH 2 O 的跨肺压对肥胖患者来说似乎是有希望的 [14, 15]。其他基于生理学的协议通过电阻抗断层扫描、肺复张率 (NCT03963622) 或床边肺容积测量 (NCT04012073) 评估肺复张性来提供个性化 PEEP，这些协议正在随机试验中进行测试，并有望阐明 PEEP 的重要方面ARDS期间的个体化。

当前研究期间使用和/或分析的数据集可根据合理要求从相应的作者处获得。

ARDS：

急性呼吸窘迫综合征

窥视：

呼气末正压

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    文章谷歌学术

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    文章谷歌学术

  3. Gattinoni L、Caironi P、Cressoni M、Chiumello D、Ranieri VM、Quintel M 等。急性呼吸窘迫综合征患者的肺复张。N Engl J Med。2006；354:1775–86。

    CAS 文章 谷歌学术

  4. Jonkman AH、Ranieri VM、Brochard L. Lung 招募。重症监护医学。2022；48:936–8。

    文章谷歌学术

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  6. Spinelli E、Grieco DL、Mauri T. 急性呼吸窘迫综合征的个性化方法：最新进展和未来挑战。J胸椎病。2019；11：5619-25。

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  8. Spinelli E、Mauri T、Fogagnolo A、Scaramuzzo G、Rundo A、Grieco DL 等。围手术期医学中的电阻抗断层扫描：为量身定制的干预措施进行仔细的呼吸监测。BMC 麻醉剂。2019；19:140。

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  9. Protti A、Santini A、Pennati F、Chiurazzi C、Cressoni M、法拉利 M 等。机械通气 COVID-19 患者肺对较高呼气末正压的反应。胸部。2022；161:979–88。

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  10. Grieco DL、Bongiovanni F、Chen L、Menga LS、Cutuli SL、Pintaudi G 等。与其他病因的 ARDS 相比，COVID-19 引起的呼吸衰竭的呼吸生理学。暴击护理。2020；24:529。

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  11. Chen L、Del Sorbo L、Grieco DL、Junhasavasdikul D、Rittyamai N、Soliman I 等。通过急性呼吸窘迫综合征中的肺复张与充气比率估计肺复张的潜力。一项临床试验。Am J Respir Crit Care Med。2020；201：178-87。

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  12. 急性呼吸窘迫综合征试验 (ART) 调查员的肺泡招募写作小组，Cavalcanti AB，Suzumura ÉA，Laranjeira LN，Paisani D de M，Damiani LP 等。肺复张和滴定呼气末正压 (PEEP) 与低 PEEP 对急性呼吸窘迫综合征患者死亡率的影响：一项随机临床试验。贾马。2017；318：1335–45。

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这项研究完全由机构/部门资源资助。

作者和附属机构

  1. 急诊、重症监护医学和麻醉科，Fondazione Policlinico Universitario A. Gemelli IRCCS, L.go F. Vito, 00168, Rome, Italy

    Domenico Luca Grieco、Filippo Bongiovanni、Antonio M. Dell'Anna 和 Massimo Antonelli

  2. Istituto di Anestesiologia e Rianimazione, Università Cattolica del Sacro Cuore, 罗马, 意大利

    Domenico Luca Grieco、Filippo Bongiovanni、Antonio M. Dell'Anna 和 Massimo Antonelli

作者
  1. Domenico Luca Grieco查看作者的出版物

    您也可以在PubMed  Google Scholar中搜索该作者

  2. Filippo Bongiovanni查看作者的出版物

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  3. Antonio M. Dell'Anna查看作者的出版物

    您也可以在PubMed  Google Scholar中搜索该作者

  4. Massimo Antonelli查看作者的出版物

    您也可以在PubMed  Google Scholar中搜索该作者

贡献

DLG 和 FB 起草了这封信。AMDA 和 MA 严格修改了手稿。所有作者阅读并认可的终稿。

通讯作者

与多梅尼科·卢卡·格里科的通信。

伦理批准和同意参与

不适用。

同意发表

不适用。

利益争夺

DLG 已收到 Getinge 和 Air Liquide 的差旅费，Intersurgical、GE、Fisher and Paykel 和 Gilead 的演讲费。MA 已收到来自 Maquet、Air Liquide 和 Chiesi 的董事会参与付款。DLG 和 MA 披露了通用电气医疗保健公司的一项研究资助。DLG 得到 ESICM 和 SIAARTI 的资助。

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引用这篇文章

Grieco，DL，Bongiovanni，F.，Dell'Anna，AM等。为什么顺应性和驱动压力可能不是 ARDS 期间设置 PEEP 的合适目标。重症监护 26, 234 (2022)。https://doi.org/10.1186/s13054-022-04109-7

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  • DOI ：https ://doi.org/10.1186/s13054-022-04109-7

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更新日期：2022-08-03
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