Department of Anesthesiology, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Amsterdam Cardiovascular Sciences Research Institute, Amsterdam, The Netherlands.
J Appl Physiol (1985). 2021 Oct 1;131(4):1328-1339. doi: 10.1152/japplphysiol.00184.2021. Epub 2021 Sep 2.
Positive end-expiratory pressure (PEEP) is routinely applied in mechanically ventilated patients to improve gas exchange and respiratory mechanics by increasing end-expiratory lung volume (EELV). In a recent experimental study in rats, we demonstrated that prolonged application of PEEP causes diaphragm remodeling, especially longitudinal muscle fiber atrophy. This is of potential clinical importance, as the acute withdrawal of PEEP during ventilator weaning decreases EELV and thereby stretches the adapted, longitudinally atrophied diaphragm fibers to excessive sarcomere lengths, having a detrimental effect on force generation. Whether this series of events occurs in the human diaphragm is unknown. In the current study, we investigated if short-term application of PEEP affects diaphragm geometry and function, which are prerequisites for the development of longitudinal atrophy with prolonged PEEP application. Nineteen healthy volunteers were noninvasively ventilated with PEEP levels of 2, 5, 10, and 15 cmHO. Magnetic resonance imaging was performed to investigate PEEP-induced changes in diaphragm geometry. Subjects were instrumented with nasogastric catheters to measure diaphragm neuromechanical efficiency (i.e., diaphragm pressure normalized to its electrical activity) during tidal breathing with different PEEP levels. We found that increasing PEEP from 2 to 15 cmHO resulted in a caudal diaphragm displacement (19 [14-26] mm, < 0.001), muscle shortening in the zones of apposition (20.6% anterior and 32.7% posterior, < 0.001), increase in diaphragm thickness (36.4% [0.9%-44.1%], < 0.001) and reduction in neuromechanical efficiency (48% [37.6%-56.6%], < 0.001). These findings demonstrate that conditions required to develop longitudinal atrophy in the human diaphragm are present with the application of PEEP. We demonstrate that PEEP causes changes in diaphragm geometry, especially muscle shortening, and decreases in vivo diaphragm contractile function. Thus, prerequisites for the development of diaphragm longitudinal muscle atrophy are present with the acute application of PEEP. Once confirmed in ventilated critically ill patients, this could provide a new mechanism for ventilator-induced diaphragm dysfunction and ventilator weaning failure in the intensive care unit (ICU).
呼气末正压（PEEP）在机械通气患者中常规应用，通过增加呼气末肺容积（EELV）来改善气体交换和呼吸力学。在最近的一项大鼠实验研究中，我们证明了长时间应用 PEEP 会导致膈肌重塑，特别是纵向肌纤维萎缩。这具有潜在的临床重要性，因为在呼吸机脱机过程中急性撤去 PEEP 会降低 EELV，从而使适应的、纵向萎缩的膈肌纤维过度拉伸到肌节长度，对肌力产生不利影响。这种系列事件是否发生在人类膈肌中尚不清楚。在目前的研究中，我们研究了短期应用 PEEP 是否会影响膈肌的几何形状和功能，这是长时间应用 PEEP 导致纵向萎缩的前提条件。19 名健康志愿者接受 PEEP 水平为 2、5、10 和 15 cmHO 的无创通气。进行磁共振成像（MRI）以研究 PEEP 引起的膈肌几何形状变化。通过鼻胃管测量不同 PEEP 水平下的膈肌神经机械效率（即膈肌压力与电活动的比值），为受试者配备仪器。我们发现，PEEP 从 2 增加到 15 cmHO 会导致膈的尾部位移（19 [14-26]mm，<0.001）、附着区的肌肉缩短（前部 20.6%和后部 32.7%，<0.001）、膈肌厚度增加（36.4% [0.9%-44.1%]，<0.001）和神经机械效率降低（48% [37.6%-56.6%]，<0.001）。这些发现表明，在应用 PEEP 时，人类膈肌发生纵向萎缩所需的条件已经存在。我们证明 PEEP 会引起膈肌几何形状的变化，特别是肌肉缩短，并降低膈肌的体内收缩功能。因此，在急性应用 PEEP 时，出现了膈肌纵向肌肉萎缩的发展的先决条件。一旦在机械通气的危重病患者中得到证实，这可能为 ICU 中呼吸机引起的膈肌功能障碍和呼吸机脱机失败提供新的机制。
