Spontaneous breathing promotes lung injury in an experimental model of alveolar collapse

Abstract

Vigorous spontaneous breathing has emerged as a promotor of lung damage in acute lung injury, an entity known as "patient self-inflicted lung injury". Mechanical ventilation may prevent this second injury by decreasing intrathoracic pressure swings and improving regional air distribution. Therefore, we aimed to determine the effects of spontaneous breathing during the early stage of acute respiratory failure on lung injury and determine whether early and late controlled mechanical ventilation may avoid or revert these harmful effects. A model of partial surfactant depletion and lung collapse was induced in eighteen intubated pigs of 32 ±4 kg. Then, animals were randomized to (1) SB-group: spontaneous breathing with very low levels of pressure support for the whole experiment (eight hours), (2) Early MV-group: controlled mechanical ventilation for eight hours, or (3) Late MV-group: first half of the experiment on spontaneous breathing (four hours) and the second half on controlled mechanical ventilation (four hours). Respiratory, hemodynamic, and electric impedance tomography data were collected. After the protocol, animals were euthanized, and lungs were extracted for histologic tissue analysis and cytokines quantification. SB-group presented larger esophageal pressure swings, progressive hypoxemia, lung injury, and more dorsal and inhomogeneous ventilation compared to the early MV-group. In the late MV-group switch to controlled mechanical ventilation improved the lung inhomogeneity and esophageal pressure swings but failed to prevent hypoxemia and lung injury. In a lung collapse model, spontaneous breathing is associated to large esophageal pressure swings and lung inhomogeneity, resulting in progressive hypoxemia and lung injury. Mechanical ventilation prevents these mechanisms of patient self-inflicted lung injury if applied early, before spontaneous breathing occurs, but not when applied late.

Figure 1

Study design and timeline. Preparation corresponds to anesthesia and invasive monitoring, which took around 2 h, baseline was measured at the end of this period. Alveolar collapse model corresponds to partial surfactant depletion and lung collapse model. After induction of the model, animals were randomized for spontaneous breathing, early controlled MV and late controlled MV by a period of 8 h. Arrows: data record points.

Figure 2

Changes in esophageal pressure swings over time in the three ventilatory groups. MV corresponds to mechanical ventilation, SB corresponds to spontaneous breathing, Pes corresponds to esophageal pressure. *p < 0.05.

Figure 3

Representative tracing of Volume, Airflow (Flow), Airway pressure (Paw) and Esophageal pressure (Pes) from two animals from the Early MV and SB group. The scale of Paw in the SB animal was adjusted to improve visualization.

Figure 4

Changes in PaO₂/FIO₂ over time in SB-group, Early MV group, and Late MV group. *p < 0.05, using GLMM for the SB-group, and the Friedman test for the Late VM group.

Figure 5

Representative images of an animal from the SB-group (right) and another from the Early MV group (left). The pulmonary ventilation distribution assessed by electric impedance tomography showed that SB presented dorsal predominant ventilation, as is shown by the impedance ratio = 0.8; in contrast, Early MV ventilation was predominantly ventral, as is shown by the impedance ratio = 1.3. IR impedance ratio.

Figure 6

Regional ventilation delay values from SB and Early MV and Late MV groups. MV mechanical ventilation, SB spontaneous breathing, RVD regional ventilation delay, AU arbitrary units. *p < 0.05, using GLMM for the SB-group, and the Friedman test for the Late VM group.

Figure 7

Regional and global histological lung injury score. MV mechanical ventilation, SB spontaneous breathing, AU arbitrary units. *p < 0.05.

Figure 8

Global inhomogeneity index values from SB and Early MV and Late MV groups. MV mechanical ventilation, SB spontaneous breathing, RVD regional ventilation delay, AU arbitrary units. *p < 0.05, using the Friedman test for the Late VM group.