In this study, we compared the physiological response of prone positioning between patients with COVID-19 ARDS and non-COVID ARDS, focusing on changes in oxygenation and static Crs. Most patients with COVID-19 ARDS showed improvement in PaO2/FiO2 ratio and static Crs after the first session of prone positioning. The extent of improvement in these parameters appeared to be higher in patients with COVID-19 ARDS when compared crudely with the entire group of patients with non-COVID ARDS. However, when 1:1 matched samples (PaO2/FiO2-matched and compliance-matched) were analyzed, the physiological response to prone positioning was not different between patients with COVID-19 ARDS and those with non-COVID ARDS.
Whether patients with COVID-19 ARDS have a clinically different phenotype compared with those with typical non-COVID ARDS continues to be a controversial issue (5, 21). One of the issues related to this controversy is regarding static Crs. Since the COVID-19 pandemic started, some patients with COVID-19 ARDS have been reported to have preserved static Crs despite impaired oxygenation, which is referred to as “type L (low elastance) phenotype” compared with “type H (high elastance) phenotype” (21, 22). A multicenter study in Italy reported that patients with COVID-19 ARDS had higher median static Crs than those with non-COVID ARDS (41 vs. 32 mL/cmH2O), although there was a substantial overlap between the two groups (11). However, in several other studies, patients with COVID-19 ARDS presented with static Crs of approximately 30–35 mL/cmH2O, which is similar to that in previous reports of typical non-COVID ARDS (6, 10, 23-26).
In our study, patients in both groups showed substantially reduced static Crs (median 27.2 and 21.9 mL/cmH2O in COVID-19 and non-COVID group, respectively). Especially, patients with non-COVID ARDS in this study had extremely poor static Crs considering that a recent secondary analysis of the LUNG SAFE study, which included a large multinational cohort of patients, reported the median static Crs of 30 mL/cmH2O (27). This may be due to the selection bias that occurs in single-center studies. In fact, we could not identify any patient in either group (COVID-19 or non-COVID) who can be classified as having type L phenotype (static Crs ≥ 50 mL/cmH2O). Therefore, our findings may not be applicable to patients with type L phenotype.
Almost every patient with COVID-19 ARDS in this study showed improvement in PaO2/FiO2 ratio after prone positioning. Such improvement was rapid and most noticeable after 10 hours of prone positioning. This finding is consistent with that of another single-center study of intubated patients with COVID-19 treated using prone positioning, which reported that PaO2/FiO2 ratio improved within 2 hours after initiation of prone positioning (28). In a prospective study of prone positioning in nonintubated patients, improvement in oxygenation was observed even 10 minutes after initiation of prone positioning (29). In contrast, a previous study on non-COVID ARDS showed that the oxygenation status was not always improved immediately after initiation of prone positioning (30). In other studies, including the PROSEVA trial, PaO2/FiO2 ratio was higher at the end of the prone positioning session than at 1 hour after initiation of prone positioning, which is similar to our findings for patients with non-COVID ARDS (7, 31). Based on these findings, it can be suggested that the speed of the oxygenation response after prone positioning may differ between patients with COVID-19 ARDS and those with non-COVID ARDS. Because PaO2/FiO2 ratio cannot be monitored on real-time basis, monitoring oxygenation based on SpO2/FiO2 ratio might provide more information on this issue.
The change in static Crs after prone positioning has not been studied as much as the change in oxygenation. In one study, static Crs was improved with prone positioning when it was accompanied only with application of high PEEP, but not with low PEEP (32). Crs is determined by compliance of the chest wall and lung. Because chest wall compliance usually decreases during prone positioning, the overall change in Crs after prone positioning depends on how much the compliance of the lung improves, which may be related to lung recruitability (8). In our study, the extent of improvement in static Crs after prone positioning appeared to be higher in patients with COVID-19 ARDS than in patients with non-COVID ARDS in a crude analysis. However, the difference was not significant when the analysis was performed using the matched samples. In addition to static Crs, it may be useful to monitor the lung recruitability while implementing prone positioning (33-36).
The major finding of our study was that oxygenation and Crs responses after prone positioning were not different between patients with COVID-19 ARDS and those with non-COVID ARDS after careful matching and adjusting for baseline between-group differences. Because non-COVID ARDS comprises lung injuries from very heterogeneous causes, it is not easy to make a proper comparison between the two groups. Furthermore, although COVID-19 ARDS occurs by infection caused by a common single pathogen, results of several studies indicated that respiratory mechanics of patients with COVID-19 ARDS show a substantial interindividual variability, highlighting the importance of individualization in ventilator management (37). As in our study, it may be because of this interindividual variability that other studies also failed to identify significant differences between COVID-19 ARDS and non-COVID ARDS (38, 39). However, our finding suggests prone positioning in patients with COVID-19 ARDS is at least as effective in improving respiratory physiology as in patients with typical non-COVID ARDS.
We have recently reported that the extent of improvement in oxygenation after the first session of prone positioning could be predictive of clinical outcome for patients with non-COVID ARDS (9). In this study, we confirmed this finding in patients with COVID-19 ARDS. In addition, we found that the improvement in static Crs after prone positioning was also associated with clinical outcome. Therefore, if the physiological effect of prone positioning is not substantial at the end of first session, intensivists may have to consider another therapeutic options.
Our study has several limitations. First, our study was conducted at a single center and the number of patients studied was limited, although we enrolled every consecutive patient treated using prone positioning until December 2020. Second, despite our efforts to adjust for between-group differences including 1:1 matched analysis, we cannot exclude the possibility that uncontrolled individual factors affected our study findings. Third, we could not evaluate the effect of prone positioning in patients with preserved static Crs (type L phenotype), because there were no such patients in our cohort.