患者水平的中介分析?

The use of lung-protective strategies for patients with ARDS is supported by clinical trials and has been widely accepted; however, the precise tidal volume for an individual ARDS patient requires adjustment for factors such as the plateau pressure, the selected positive end-expiratory pressure (PEEP), thoracoabdominal compliance, and the patient’s breathing effort. Patients with profound metabolic acidosis, high minute ventilation, or short stature may require additional manipulation of tidal volumes. Some clinicians believe it may be safe to ventilate with tidal volumes > 6 mL/kg PBW as long as plateau pressure can be maintained ≤ 30 cm H2O [429, 430]. The plateau pressure is only truly valuable if the patient is passive during the inspiratory hold. Conversely, patients with very stiff chest/ abdominal walls and high pleural pressures may tolerate plateau pressures > 30 cm H2O because transpulmonary pressures will be lower. A retrospective study suggested that tidal volumes should be lowered even with plateau pressures ≤ 30 cm H2O [431] because lower plateau pressures were associated with reduced hospital mortality [432]. A recent patient-level mediation analysis suggested that a tidal volume that results in a driving pressure (plateau pressure minus set PEEP) below 12–15 cm H2O may be advantageous in patients without spontaneous breathing efforts [433]. Prospective validation of tidal volume titration by driving pressure is needed before this approach can be recommended. Tidal volumes > 6 cc/kg coupled with plateau pressures > 30 cm H2O should be avoided in ARDS. Clinicians should use as a starting point the objective of reducing tidal volume over 1–2 h from its initial value toward the goal of a “low” tidal volume (≈ 6 mL/kg PBW) achieved in conjunction with an end-inspiratory plateau pressure ≤ 30 cm H2O. If plateau pressure remains > 30 cm H2O after reduction of tidal volume to 6 mL/kg PBW, tidal volume may be further reduced to as low as 4 mL/kg PBW. The clinician should keep in mind that very low tidal volumes may result in significant patient-ventilatory dyssynchrony and patient discomfort. Respiratory rate should be increased to a maximum of 35 breaths/min during tidal volume reduction to maintain minute ventilation. Volume- and pressure-limited ventilation may lead to hypercapnia even with these maximum-tolerated set respiratory rates; this appears to be tolerated and safe in the absence of contraindications (e.g., high intracranial pressure, sickle cell crisis). No single mode of ventilation (pressure control, volume control) has consistently been shown to be advantageous when compared with any other that respects the same principles of lung protection.

ARDS 患者肺保护策略的使用得到了临床研究的支持，已被广泛接受；然而，需要根据诸如平台压、选择的呼气末正压(PEEP)、胸腹顺应性和患者的吸气努力 等因素进行个体 ARDS 患者潮气量的精确调整。严重代谢性酸中毒、高分钟通气量或身材矮小患者可能需要频繁地调节潮气量。某些临床医生认为，只要能维持 平台压≤30cmH2O，潮气量>6mL/kgPBW 通气可能是安全的。只有当被动呼吸的 吸气暂停期间，平台压才是真正有价值的。相反，因为跨肺压较低，胸/腹壁顺应 性非常差和胸膜腔压较高的患者可能耐受平台压>30cmH2O。一项回顾性研究表明，即使平台压≤30cmH2O，也应降低潮气量，因为较低的平台压与住院死亡率降低相关。最近的一项患者水平的中介分析表明，导致驱动压（平台压减去设定 的 PEEP）低于 12-15cmH2O 的潮气量可能对无自主呼吸努力的患者有利。在推荐这种方法之前，需要通过驱动压对潮气量的滴定进行前瞻性验证。ARDS 患者应避免潮气量>6ml/kg 以及避免平台压>30cmH2O。临床医生应在 1-2h 内将潮气量从初始值为起点进行降低，以达到“低”潮气量(≈6mL/kgPBW)同时吸气末平台 压≤30cmH2O 的目标。如果潮气量降至 6mL/kgPBW 后平台压仍>30cmH2O，则 潮气量可进一步降至4mL/kgPBW。应注意潮气量过低可能导致明显的人-机不同步和患者不适。潮气量减少时呼吸速率可增至最大 35bpm，以维持分钟通气量。即使设置了最大耐受的呼吸频率，通气的容积和压力限制也可能导致高碳酸血症，在无禁忌证(如高颅压、镰状细胞危象)时，高碳酸血症似乎是可以耐受和安全的。与其他其他任何遵守肺保护原则的模式相比，无单独的通气模式（压力控制、容量控制）始终显示出优势。

patient-level mediation analysis?是不是就是患者为导向的中期分析？谢谢