As a relatively new technique available for clinical use, EIT has provided an opportunity to dug into the physiological fundamentals of ARDS. In use of EIT, this study has provided some proof-of-concept evidences regarding the ventilation-perfusion matching effect of PP during mechanical ventilation in ARDS patients. First, the increased ventilation was mainly distributed in the dorsal region while ventral ventilation was hardly changed, suggesting the aeration increment in dorsal lung regions was not offset by loss of aeration in ventral regions. Changes in ventilation were observed early in the prone position. Second, the redistribution effect of PP on lung perfusion was relatively mild compared to ventilation, with the dorsal lung perfusion increased and the trend of the ventral decreased, while global perfusion remained constant. Changes in blood flow were observed during prolonged prone positions. Third, ventilation-perfusion matched region was increased and correlated with the increased PaO2/FiO2 by PP, which was specifically attributed to reduced functional shunt and increased dorsal ventilation and perfusion matching by the procedure.
During PP, patients exhibited a shift of the tidal volume distribution from the ventral to dorsal ROIs, and the inhomogeneity of tidal ventilation distribution (GI) was reduced. In ARDS, with the lung weight usually increases by 2–3 times, the potentially open alveoli at the dorsal region tend to collapse in the supine position. In the prone position, these alveoli may open up as the superimposed pressure of the dorsal regions is released [21]. Previous study reported that the inflation of pulmonary units was far more homogeneous at pronation than supination, which was interpreted as the lung-distending force (i.e. the gravitational gradient of pleural pressure, trans-pulmonary pressure or lung stress) was more homogeneously distributed [21, 22]. The primary reason was considered to be improved shape matching between the chest wall and the lung [23]. The gravitational gradient of pleural pressure, regional end-expiratory and end-inspiratory lung volumes, regional ventilation were all more uniform at prone position than at supine position [24].
Theoretically, the gravitational distribution of pulmonary blood flow is only minimally altered by pronation [25, 26], which is consistent with our findings. The increased perfusion in dorsal region and roughly maintained perfusion in ventral region could be attributed to less lung/heart geometry, fewer airspace compression of vessels (with more end-expiratory volume), and reduction of hypoxic vasoconstriction in dorsal region [5]. Similarly, Perier et al. recently reported that improvement of lung aeration and unmodified dorsal of pulmonary perfusion after three hours of the prone positioning in COVID-19-associated ARDS [27]. Unlike these studies we repeated EIT assessment at PP initiation, 3 hours after PP initiation and the end of PP within the first PP session. Based on theses evidences, we hypothesized that during prone ventilation, pulmonary blood flow remains unmodified at the early stage and then gradually increases in dorsal regions over time.
In the present study, we found that Matched Region% improved before the end of the prone position with the significant decrease in Shunt-EIT%. Dead Space-EIT% showed no significant difference but did show a mild reduction. The matching between lung ventilation and perfusion is fundamental to effective gas exchange, and both shunt and dead space are the determinants of ventilation-perfusion matching. In the present study, ventilation-perfusion matched region was increased by PP, and increased PaO2/FiO2 was significantly correlated with increased matched region and reduced shunt, which was in accordance with previous studies [24, 28].
By recruiting the lungs, prone position has the potential to increase ventilation-perfusion matching, decrease hypoxemia, reduce hypoxic vasoconstriction, and thereby improve right ventricular function, hemodynamics and pulmonary perfusion. It is interesting to note that placing patients in prone position had a large impact on dose of vasopressors (norepinephrine was decreased from 0.17 to 0.02 ug/Kg/min at the end of PP).
Although this study has provided notable evidences regarding physiological effects of prone ventilation in ARDS patients, its limitation should be noticed. First, this study was carried out within a small number of patients in a single center, which reduces the statistical power. Second, EIT measures only a portion of the lung, projecting the 3 dimensional distribution of ventilation/perfusion to the 2 dimensional image, which is not enough for assessment of the entire spectrum of ventilation-perfusion matching in the lung [29]. Third, the EIT assessment was only performed at the 3 indicated time points during PP instead of throughout the process, which failed to fully uncover the longitudinal effect of PP. The present study missed the changes in ventilation and perfusion after resupination as well. Forth, cardiac output of the patients were not measured. The potential effect of PPV on CO might influence the oxygenation and V-Q matching.