The main finding of this study was that TauE and its related TEI were able to assess physiologic responses to changes in PEEP, including recruitability in non-homogenously affected lungs. Secondly, when similar TEI is obtained at various PEEP levels (e.g. 5-10 cmH2O or 8-15 cmH2O), a range of PEEP values were identified that yielded similar lung mechanics.
Measuring TEI may be used to determine suitable PEEP for multiple reasons: First, a higher compliance produces higher TauE, resulting in a larger TEI. Also, studies have shown that Raw changes during PEEP titration, showing a decrease with increasing PEEP [12,13]. Because Cst and Raw vary with Vt, time constants differ between inspiration and exhalation and also within different lung regions [14]. Second, PEEP levels that increase Vt due to recruitment will create a larger TEI. Third, a Vt exhaled over longer TauE will result in a larger TEI (e.g. if 63% of 500 ml tidal volume is exhaled in 0.8 seconds at low-to-moderate PEEP, or 0.4 seconds is needed for the same amount of gas to be exhaled at higher PEEP levels, or vice-versa). Because of the aforementioned reasons, TauE and TEI may also prove superior for determining the suitable PEEP due to integrating changes of compliance, resistance and therefore also changes in Vt.
Larger values of TEI indicated greater product of Vte and TauE and greater time necessary to reach complete exhalation. This observation also led to the conclusion that maximum recruitment was usually associated with highest TauE and therefore TEI. Conversely, if Vte or TauE and therefore TEI were not changing significantly during ascending PEEP levels or were decreasing, the increased force of elastic recoil associated with higher PEEP was overshadowing any potential recruitment. This finding demonstrates that not only Vt, but also time through which particular Vt is exhaled, should be considered important when assessing optimal PEEP.
In the limited and existing evidence regarding TauE, no study has used TauE to assess changes in physiology associated with PEEP titration. The value of TEI lies in an integration of all aspects of lung emptying during passive exhalation, namely emptying of different areas of the non-homogenous lungs (short and long TauE compartments) and different regional compliances and resistances (laminar or turbulent flows in a different TauE areas of the ARDS lung).
It has been shown that aerated and ventilatable parenchyma in severe ARDS is markedly reduced [15,16]. Knowing the potential for recruitability may provide important information about the functional concept of ’baby lungs’. It can be assumed that the ‘hill’ pattern shows recruitment, the ‘flat’ pattern shows an almost equal trade off of recruitment and overdistension, and the ‘descending’ pattern shows lungs that cannot be recruited even at high PEEP values. Using these patterns, various degrees of baby lungs may be identified. With the ‘flat’ pattern where TEI does not change significantly across the PEEP range, higher PEEP levels might not be that harmful in terms of VILI (same Vte exhaled over the same TauE across the whole range of PEEPs). With the ‘descending’ pattern, we assume that higher PEEP levels will be harmful due to overdistention of relatively healthy areas of the ‘baby lung’ as there is no evidence of recruitability. Exposing non-homogenous lungs to diagnostic PEEP titration may therefore be well justified.
Studies have shown that using universally higher vs. lower PEEP for ventilating ARDS patients did not prove to be beneficial in terms of mortality [17,18]. On the other hand, it has been shown that utilization of higher PEEP has improved mortality in a subgroup of ARDS patients who responded to increased PEEP by improved oxygenation [19] or have been hypothesized to show recruitability [20]. Obtaining TEI maps and patterns that show recruitability might be beneficial in selecting those patients who may benefit from higher PEEPs.
The use of prone positioning has been well described in patients with COVID-19 ARDS [21,22]. Our measurements suggest that we may be able to identify more favorable pulmonary mechanics in terms of recruitment and PEEP levels in supine and prone position and therefore predicting those patients benefiting from either position (Figure 4).
From the TEI maps constructed in the sequential study of the same patients, pulmonary mechanics shifted as ARDS was changing over time. Therefore, ventilation and PEEP optimization may be required more frequently than previously thought, and TEI maps may be an efficient method of assessing these changes quickly.
Expiratory time constant and constructed TEI maps to find a suitable PEEP range can be performed at the bedside, it is fast, practical, repeatable, non-invasive, does not pose any radiation risk, nor does it require patient transport to other hospital locations (e.g. CT). Taking these findings into account, individual PEEP optimization settings based on assessing TauE and TEI may be easily performed, allowing for increasing PEEP where recruitment is found and avoiding higher PEEP levels where recruitment is not expected.
Our study suggests that if multiple PEEP levels would be beneficial in terms of lung recruitment and increased aeration, then using multiple alternating PEEP levels during mechanical ventilation warrants further clinical research. Using this approach to look at not only ARDS, but ALI or even healthy lungs may reveal additional useful information for clinicians.
LIMITATIONS
Our study includes a relatively small group of patients who present with moderate to severe COVID-19 related ARDS, and therefore further studies are required to validate TauE and TEI mapping usability with other etiologies causing ARDS.
Another possible limitation is that of equilibration time needed for proper recruitment at each PEEP level varies from patient to patient. Our study was designed to obtain results quickly at bedside due to critical illness connected with hypoxemia in ARDS patients. Thus, TauE at each PEEP level was evaluated during 15 breaths. Time spent at each PEEP could have therefore been relatively short for recruitment to manifest fully.