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Are we ready to think differently about setting PEEP?
Critical Care ( IF 8.8 ) Pub Date : 2022-07-19 , DOI: 10.1186/s13054-022-04058-1
Matthew E Cove 1 , Michael R Pinsky 2 , John J Marini 3
Affiliation  

In stark contrast to the undisputed mortality benefit of lower tidal volume ventilation in patients with acute respiratory distress syndrome (ARDS) [1], the best strategy to determine optimal positive end expiratory pressure (PEEP) remains an unresolved question [2,3,4,5,6]. It is an important question because conventional understanding predicts the right PEEP will maintain recruitment of mechanically unstable alveoli, improving both oxygenation and lung compliance. Improved compliance, combined with lower ventilation volumes, maximizes lung protection by limiting tidal airway pressure changes.

Oxygenation is a convenient target for determining PEEP, and protocols directing clinicians to increase PEEP in a stepwise fashion, based on the fraction of inspirated oxygen (FiO2) required to maintain arterial oxygen levels within a specified range, have been used in several studies and guidelines [1,2,3]. Increasing PEEP to “chase” FiO2 requirements in this manner is simple, reproducible, and in the absence of a superior strategy [2,3,4,5,6], commonly practiced. However, it assumes the dominant mechanism of hypoxemia is alveolar collapse and an associated reduction in compliance, where increasing PEEP increases recruitment of functional lung units. These assumptions fail when patients meet ARDS criteria and the dominant mechanism of hypoxemia is not alveolar collapse, because hypoxemia may coexist with minimally impaired lung compliance. While such patients may only represent one end of the compliance spectrum in ARDS [7], increasing PEEP to “chase” FiO2 requirements in this setting leads to the use of ever higher PEEP, even though relatively few functional lung units are re-opened.

This mechanistic distinction is important. When increasing PEEP does not recruit functional lung units and improve pulmonary compliance, it will increase lung distention and energy transfer to the pulmonary-parenchymal matrix [8]. This raises the risk of lung injury, dead-space formation, pneumothorax, and detrimental hemodynamic consequences. Oxygenation measures are not sensitive to this; increasing PEEP elevates mean airway pressure, and Henry’s law predicts this also increases the partial pressure of oxygen (PaO2) to FiO2 (P:F) ratio regardless of whether functional lung units are recruited, at least until cardiac output becomes impaired. This would be of no consequence if the coexistence of hypoxemia and minimally impaired compliance was exceedingly rare in ARDS. However, this is not the case because the ARDS definition only accounts for P:F ratio, a measure of oxygenation, not compliance. Therefore, although mean lung compliance in ARDS cohorts is usually low, the range is wide and some patients may experience only mild compliance reductions [7].

Patients with COVID-19 are an example of this phenomenon. The mechanisms of hypoxemia in the early phases of disease appear to be driven more by pulmonary endothelial dysfunction than by collapse of functional alveoli. This is because the virus gains cellular entry via the angiotensin-converting enzyme II receptor, which is not only present in the lung epithelium, but also abundantly present in vascular endothelium and arterial smooth muscle cells [9]. Therefore, as well as causing pneumonia, the virus incites inflammation of the pulmonary vasculature leading to a ‘VA/Q’ mismatch and P:F ratio that is out of proportion to the change in pulmonary mechanics [9]. Under these circumstances, “chasing” FiO2 with PEEP might lead to continued upward titration of PEEP even though few functional lung units are re-opened, potentially causing harm.

That different ARDS patients might respond differently to PEEP was documented well before COVID-19. In 2014 Calfee and colleagues identified two ARDS sub-phenotypes based on inflammatory biomarkers [10]. They demonstrated that higher PEEP reduced mortality in patients with a hyper-inflammatory sub-phenotype and increased mortality in those with a hypo-inflammatory sub-phenotype. Although the effect of PEEP on different ARDS sub-phenotypes of lung compliance has not been described [7], it is harmful in other settings where hypoxemia leads to the use of high PEEP levels despite relatively conserved compliance [11]. Given the inherent pitfalls of an oxygenation-based PEEP strategy, perhaps a more physiologic approach is required.

Setting PEEP to target optimal compliance can overcome these pitfalls. When an increase in PEEP benefits any patient, functional lung units are recruited and compliance increases. If an increase in PEEP is unhelpful, few functional units will be recruited and compliance will remain unchanged or decrease, even though the P:F ratio may still increase. In the modern ICU, compliance is easily determined. The least-squares fit procedure determines breath-to-breath dynamic respiratory compliance from the monitored airway pressure, volume and flow [12], without an end inspiratory breath hold. In the absence of real-time dynamic compliance, using PEEP to optimize driving pressure may be a suitable surrogate. In spontaneously breathing patients, reliable compliance measurements can be provided with modes like proportional assist ventilation [13].

Using these real-time compliance measures, PEEP can be titrated upward or downward, and the effect on compliance observed [14]. If compliance increases, the new PEEP is more optimal, and if compliance decreases, the new PEEP is either too high or too low. When compliance is unchanged after titrating PEEP upward, a clinical judgment on the likelihood of recruiting functional lung units with higher PEEP is required. The clinician’s goal should be achieving the highest possible compliance with the lowest possible PEEP, rather than a specific compliance target, since this will vary from patient-to-patient and is sensitive to other commonly used ventilator settings. Optimizing PEEP in this manner also reduces dead-space ventilation, and while this is a more complex bedside measurement, the ventilatory ratio closely corresponds and can be simply tracked [15], helping confirm whether the new PEEP is more optimal.

Prescribing PEEP based on oxygen requirements is a “one-size-fits-all” approach, destined to help some patients, while exposing others to harm. Alternatively, using modern monitoring tools to optimize PEEP based on measures of pulmonary physiology, such as compliance, allows clinicians to better personalize ventilator settings to help all patients. Although we still lack high-quality clinical trials demonstrating that setting PEEP based on respiratory compliance measures is superior to using measures of oxygenation, we hypothesize that future ARDS management strategies which optimize PEEP based on patient physiology, while observing threshold limits for variables like plateau pressure and driving pressure, will further improve outcomes for all ARDS patients.

Not applicable.

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Nil to note.

MEC has received consulting fees from Medtronic and Baxter and is supported by a National Medical Research Council Grants (CIA18nov-0010 and CSAINV20nov-0014). MRP has received consulting fees from Baxter, LiDCO and Exostat Medical.

Authors and Affiliations

  1. Department of Medicine, National University Singapore, NUHS Tower Block Level 10, 1E Kent Ridge Road, Singapore, 119228, Singapore

    Matthew E. Cove

  2. Department of Critical Care Medicine, 638 Scaife Hall, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA, 15261, USA

    Michael R. Pinsky

  3. Pulmonary and Critical Care Medicine, Regions Hospital and University of Minnesota, Minneapolis/Saint Paul, MN, USA

    John J. Marini

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  2. Michael R. PinskyView author publications

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Contributions

MEC, MRP and JJM conceived the idea and edited the manuscript. MEC wrote the first draft. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Matthew E. Cove.

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Cove, M.E., Pinsky, M.R. & Marini, J.J. Are we ready to think differently about setting PEEP?. Crit Care 26, 222 (2022). https://doi.org/10.1186/s13054-022-04058-1

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中文翻译：
我们准备好以不同的方式考虑设置 PEEP 了吗？

与低潮气量通气对急性呼吸窘迫综合征 (ARDS) 患者的无可争议的死亡率益处形成鲜明对比 [1]，确定最佳呼气末正压 (PEEP) 的最佳策略仍然是一个悬而未决的问题 [2,3,4 ,5,6]。这是一个重要的问题，因为传统的理解预测正确的 PEEP 将维持机械不稳定肺泡的募集，改善氧合和肺顺应性。提高顺应性，结合较低的通气量，通过限制潮气道压力变化最大限度地保护肺。

氧合是确定 PEEP 的一个方便目标，指导临床医生逐步增加 PEEP 的方案基于将动脉氧水平维持在特定范围内所需的吸入氧 (FiO 2 ) 分数，已用于多项研究和指南 [1,2,3]。以这种方式增加 PEEP 以“追逐” FiO 2要求是简单的、可重复的，并且在没有更好的策略 [2,3,4,5,6] 的情况下是常用的。然而，它假设低氧血症的主要机制是肺泡塌陷和相关的顺应性降低，其中增加 PEEP 会增加功能性肺泡的募集。肺单位。当患者符合 ARDS 标准并且低氧血症的主要机制不是肺泡塌陷时，这些假设就失效了，因为低氧血症可能与最小程度的肺顺应性受损并存。虽然此类患者可能仅代表 ARDS [7] 顺应性范围的一端，但在这种情况下增加 PEEP 以“追逐” FiO 2要求会导致使用更高的 PEEP，即使重新开放的功能性肺单位相对较少.

这种机械区别很重要。当增加 PEEP 不会募集功能性肺单位并改善肺顺应性时，它会增加肺膨胀和向肺实质基质的能量转移 [8]。这会增加肺损伤、死腔形成、气胸和有害血流动力学后果的风险。氧合措施对此不敏感；增加 PEEP 会提高平均气道压力，亨利定律预测这也会增加氧气分压 (PaO 2 ) 与 FiO 2 (P:F) 的比值，而不管功能是否正常。肺单位被募集，至少在心输出量受损之前。如果在 ARDS 中同时存在低氧血症和轻微的依从性受损是极其罕见的，那么这将没有任何意义。然而，情况并非如此，因为 ARDS 的定义只考虑了 P:F 比，一种氧合量度，而不是依从性。因此，虽然 ARDS 队列中的平均肺顺应性通常较低，但范围很广，一些患者可能只会出现轻微的顺应性降低 [7]。

COVID-19 患者就是这种现象的一个例子。疾病早期低氧血症的机制似乎更多是由肺内皮功能障碍而非功能性肺泡塌陷所致。这是因为病毒通过血管紧张素转换酶 II 受体进入细胞，该受体不仅存在于肺上皮，而且大量存在于血管内皮和动脉平滑肌细胞中 [9]。因此，除了引起肺炎外，该病毒还会引发肺血管炎症，导致“ V A/ Q ”不匹配和与肺力学变化不成比例的 P:F 比 [9]。在这种情况下，“追逐”FiO 2使用 PEEP 可能会导致 PEEP 持续向上滴定，即使很少有功能性肺单位重新打开，可能会造成伤害。

早在 COVID-19 之前就已经记录了不同的 ARDS 患者对 PEEP 的反应可能不同。2014 年，Calfee 及其同事根据炎症生物标志物确定了两种 ARDS 亚表型 [10]。他们证明，较高的 PEEP 降低了高炎症亚表型患者的死亡率，并增加了低炎症亚表型患者的死亡率。尽管尚未描述 PEEP 对不同 ARDS 肺顺应性亚表型的影响 [7]，但在低氧血症导致使用高 PEEP 水平的其他环境中，尽管顺应性相对保守[11]，但它是有害的。鉴于基于氧合的 PEEP 策略的固有缺陷，也许需要一种更符合生理学的方法。

将 PEEP 设置为最佳顺应性目标可以克服这些缺陷。当 PEEP 的增加使任何患者受益时，功能性肺单位就会被募集，顺应性也会增加。如果 PEEP 的增加没有帮助，那么很少有功能单位将被招募，合规性将保持不变或下降，即使 P:F 比率可能仍会增加。在现代 ICU 中，合规性很容易确定。最小二乘拟合程序根据监测的气道压力、容量和流量 [12] 确定呼吸对呼吸的动态呼吸顺应性，而无需吸气末屏气。在没有实时动态顺应性的情况下，使用 PEEP 来优化驱动压力可能是一个合适的替代方法。在自主呼吸患者中，可以通过比例辅助通气等模式提供可靠的顺应性测量 [13]。

使用这些实时依从性测量，PEEP 可以向上或向下滴定，并观察对依从性的影响 [14]。如果顺应性增加，则新的 PEEP 更佳，如果顺应性降低，则新的 PEEP 要么太高要么太低。当向上滴定 PEEP 后依从性没有变化时，临床判断招募功能性复张的可能性需要具有较高 PEEP 的肺单元。临床医生的目标应该是在尽可能低的 PEEP 下达到尽可能高的顺应性，而不是特定的顺应性目标，因为这会因患者而异，并且对其他常用的呼吸机设置很敏感。以这种方式优化 PEEP 还可以减少死腔通气，虽然这是一种更复杂的床边测量，但通气比率密切相关并且可以简单地跟踪 [15]，有助于确认新的 PEEP 是否更优化。

根据氧气需求开出 PEEP 是一种“一刀切”的方法，旨在帮助一些患者，同时使其他患者受到伤害。或者，使用现代监测工具根据肺部生理指标（如依从性）优化 PEEP，使临床医生能够更好地个性化呼吸机设置，以帮助所有患者。尽管我们仍然缺乏高质量的临床试验，证明基于呼吸顺应性测量设置 PEEP 优于使用氧合测量，但我们假设未来的 ARDS 管理策略会根据患者生理学优化 PEEP，同时观察平台压等变量的阈值限制和驱动压力，将进一步改善所有 ARDS 患者的预后。

不适用。

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MEC 已收到 Medtronic 和 Baxter 的咨询费，并得到国家医学研究委员会资助（CIA18nov-0010 和 CSAINV20nov-0014）的支持。MRP 已收到 Baxter、LiDCO 和 Exostat Medical 的咨询费。

作者和附属机构

  1. 新加坡国立大学医学系, NUHS Tower Block Level 10, 1E Kent Ridge Road, Singapore, 119228, Singapore

    马修·E·科夫

  2. 美国宾夕法尼亚州匹兹堡 3550 露台街 3550 号匹兹堡大学 Scaife Hall 638 号重症监护医学系，美国 15261

    迈克尔·平斯基

  3. 美国明尼阿波利斯/明尼苏达州圣保罗地区医院和明尼苏达大学肺和重症监护医学

    约翰·J·马里尼

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MEC、MRP 和 JJM 构思并编辑了手稿。MEC 编写了初稿。所有作者阅读并认可的终稿。

通讯作者

与 Matthew E. Cove 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

作者声明他们没有相互竞争的利益。

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Cove, ME, Pinsky, MR & Marini, JJ 我们准备好以不同的方式思考设置 PEEP 了吗？重症监护 26, 222 (2022)。https://doi.org/10.1186/s13054-022-04058-1

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  • DOI ：https ://doi.org/10.1186/s13054-022-04058-1

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更新日期：2022-07-19
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