Pavone Lucio A, Albert Scott, Carney David, Gatto Louis A, Halter Jeffrey M, Nieman Gary F
Department of Surgery, SUNY Upstate Medical University, 750 East Adams St Syracuse, NY 13210, USA.
Crit Care. 2007;11(3):R64. doi: 10.1186/cc5940.
Acute respiratory distress syndrome causes a heterogeneous lung injury, and without protective mechanical ventilation a secondary ventilator-induced lung injury can occur. To ventilate noncompliant lung regions, high inflation pressures are required to 'pop open' the injured alveoli. The temporal impact, however, of these elevated pressures on normal alveolar mechanics (that is, the dynamic change in alveolar size and shape during ventilation) is unknown. In the present study we found that ventilating the normal lung with high peak pressure (45 cmH(2)0) and low positive end-expiratory pressure (PEEP of 3 cmH(2)O) did not initially result in altered alveolar mechanics, but alveolar instability developed over time.
Anesthetized rats underwent tracheostomy, were placed on pressure control ventilation, and underwent sternotomy. Rats were then assigned to one of three ventilation strategies: control group (n = 3, P control = 14 cmH(2)O, PEEP = 3 cmH(2)O), high pressure/low PEEP group (n = 6, P control = 45 cmH(2)O, PEEP = 3 cmH(2)O), and high pressure/high PEEP group (n = 5, P control = 45 cmH(2)O, PEEP = 10 cmH(2)O). In vivo microscopic footage of subpleural alveolar stability (that is, recruitment/derecruitment) was taken at baseline and than every 15 minutes for 90 minutes following ventilator adjustments. Alveolar recruitment/derecruitment was determined by measuring the area of individual alveoli at peak inspiration (I) and end expiration (E) by computer image analysis. Alveolar recruitment/derecruitment was quantified by the percentage change in alveolar area during tidal ventilation (%I - E Delta).
Alveoli were stable in the control group for the entire experiment (low %I - E Delta). Alveoli in the high pressure/low PEEP group were initially stable (low %I - E Delta), but with time alveolar recruitment/derecruitment developed. The development of alveolar instability in the high pressure/low PEEP group was associated with histologic lung injury.
A large change in lung volume with each breath will, in time, lead to unstable alveoli and pulmonary damage. Reducing the change in lung volume by increasing the PEEP, even with high inflation pressure, prevents alveolar instability and reduces injury. We speculate that ventilation with large changes in lung volume over time results in surfactant deactivation, which leads to alveolar instability.
急性呼吸窘迫综合征会导致肺部出现异质性损伤,若不采用保护性机械通气,可能会引发继发性呼吸机所致肺损伤。为使顺应性差的肺区域通气,需要较高的充气压力来“撑开”受损的肺泡。然而,这些升高的压力对正常肺泡力学(即通气过程中肺泡大小和形状的动态变化)的时间影响尚不清楚。在本研究中,我们发现用高峰压(45 cmH₂O)和低呼气末正压(3 cmH₂O的呼气末正压)对正常肺进行通气,最初并不会导致肺泡力学改变,但随着时间推移会出现肺泡不稳定。
对麻醉的大鼠进行气管切开术,置于压力控制通气,并进行胸骨切开术。然后将大鼠分配到三种通气策略之一:对照组(n = 3,控制压力 = 14 cmH₂O,呼气末正压 = 3 cmH₂O)、高压/低呼气末正压组(n = 6,控制压力 = 45 cmH₂O,呼气末正压 = 3 cmH₂O)和高压/高呼气末正压组(n = 5,控制压力 = 45 cmH₂O,呼气末正压 = 10 cmH₂O)。在基线时以及呼吸机调整后的90分钟内,每隔15分钟拍摄胸膜下肺泡稳定性(即募集/解募集)的体内显微镜图像。通过计算机图像分析测量吸气峰值(I)和呼气末(E)时单个肺泡的面积,以确定肺泡募集/解募集情况。肺泡募集/解募集通过潮气量通气期间肺泡面积的百分比变化(%I - E Δ)进行量化。
在整个实验过程中,对照组的肺泡保持稳定(%I - E Δ较低)。高压/低呼气末正压组的肺泡最初是稳定的(%I - E Δ较低),但随着时间推移出现了肺泡募集/解募集。高压/低呼气末正压组肺泡不稳定的发展与肺部组织学损伤有关。
每次呼吸时肺容积的大幅变化最终会导致肺泡不稳定和肺部损伤。通过增加呼气末正压来减少肺容积变化,即使在高充气压力下,也能防止肺泡不稳定并减少损伤。我们推测,随着时间推移,肺容积大幅变化的通气会导致表面活性剂失活,从而导致肺泡不稳定。