General observations
All subjects showed, to some degree, an increase in
E
drs
immediately following a PEEP step increase of 5 cmH
2O or 5 mbar. Each successive breath had a reduced peak
E
drs
indicating the time-dependent nature of recruitment and/or the lung’s viscoelastic properties, which cause hysteresis [
31,
32]. More specifically, there is a period of adaptation following an increase in PEEP that sees higher average
E
drs
, peak
E
drs
and PIP before the beneficial effect of lower
E
drs
is seen. Furthermore, the
E
drs
trajectory within a breath generally decreases during inspiration, suggesting in-breath recruitment. However, directly following a PEEP step increase, some subjects show a decreasing
E
drs
trajectory, followed by an increasing
E
drs
trajectory towards the end of inspiration. High elastance indicates serious potential for lung damage due to overstretching, and may not be captured by a single value of
E
rs
[
17,
18]. Thus, as a result of this study, PEEP increments during a RM might be reduced to 1 cmH
2O or 1 mbar, rather than increments of 5 cmH
2O or 5 mbar, to avoid any damage due to the raised elastance in the early breaths and adaptation period following a PEEP increase. During a RM, smaller PEEP increments, each followed by a short period of stabilisation, may substantially reduce the peak of the
E
drs
spikes at the end of inspiration. However, it is important to note that the occurrence of lower respiratory elastance after stabilisation may also be a direct consequence of the initial high overdistension immediately following an increase in PEEP. This finding warrants further investigation where staircase recruitment is performed using smaller PEEP increments. Changes in ventilator pattern or mode to modify the
E
drs
trajectory also have potential to guide therapy.
The
E
drs
trend is significantly different between increasing and decreasing PEEP (using a non-parametric Wilcoxon rank sum test, p < 0.05 for each subject) where decreasing PEEP titration generally results in lower overall
E
drs
. When PEEP increases, recruitment, as well as potential lung overstretching occurs. However, as PEEP is reduced, the lung remains compliant and
E
drs
drops to an overall minimum. Equally, this phenomenon is seen where the opening pressure of collapsed alveoli is higher than the closing pressure [
29,
33]. Considering increasing and decreasing PEEP separately, a local
E
drs
minimum generally occurs at the same PEEP level, suggesting that optimum PEEP can be selected either way. Recruitment is a function of PEEP and time [
28,
30], and, equally, the ARDS affected lung is prone to collapse due to the instability of affected lung units [
6,
29]. Assuming that the severity of ARDS does not change within a short period, respiratory elastance during increasing PEEP titration is expected to reduce as time progresses to achieve stability. In contrast, respiratory elastance will increase with time during decreased PEEP to achieve stability. Hence, the authors hypothesise that PEEP can be titrated to a minimum elastance either way, provided a stabilisation period is given at each PEEP level to obtain a true minimal elastance.
The time-varying
E
drs
map is a higher resolution metric of dynamic adaptation to PEEP than a single
E
rs
value. Selecting PEEP is a trade-off in minimising lung pressure and potential damage, versus maximising recruitment. Recruitment is a function of PEEP and time [
28,
30]. Therefore, true minimal
E
drs
can only be determined after a stabilisation period is provided at each PEEP level. Such a process could be readily automated and monitored in a ventilator. Setting PEEP at minimum elastance theoretically benefits ventilation by maximising recruitment, reducing work of breathing and minimising overdistension [
12,
14,
15,
34]. The PIP can be seen to follow the
E
drs
trend to some extent. However, it does not provide the same degree of resolution. In some cases PIP is seen to stabilise quickly or remain relatively constant following a change in PEEP, while
E
drs
continues to change significantly indicating the occurrence of significant lung dynamics not readily apparent from monitoring airway pressure alone. This result shows the greater sensitivity of using
E
drs
and that
E
drs
captures more relevant dynamics than airway pressure alone.
Limitations
The single compartment lung model used to derive
E
drs
does not capture some specific physiological aspects, such as cardiogenic oscillations or regional differences in mechanical properties [
21]. Furthermore, the effects of non-linear flow or variations in airway resistance during a breath are also neglected [
21]. The determination of
E
drs
accommodates whatever resistance value is chosen, such that the model perfectly fits the available pressure data. Hence, the assumption of constant resistance throughout a breath significantly impacts on the trends of
E
drs
. There is evidence to suggest that in some cases respiratory resistance can vary within a breath [
23]. However, the effect of the resistive term is mathematically limited in its impact [
17]. Since this analysis is predominantly based on the comparison of trends across PEEP values, where each subject is thus their own reference, the best validation is the ability to track clinically expected trends as shown here.
It is important to note that both ARDS animal models were different in many aspects and do not allow for a statistically significant comparison. More importantly, it was not able to fully justify PEEP optimisation based solely on minimal elastance. However, the main outcome of this research is that mapping of time-varying respiratory elastance of mechanically ventilated ARDS subjects can be monitored to provide a high resolution metric to describe disease state and physiological changes in response to PEEP. This outcome shows the robustness of both the model and the method of visualisation for application in the ICU. However, more inter-patient variability is present in patients admitted to the ICU. Thus, application of this monitoring technique warrants further investigation in both human and animal studies.
Selecting patient-specific optimal PEEP remains widely debatable with little consensus [
36,
37]. This study primarily provides a means to visualise respiratory system elastance continuously, thus allowing PEEP to be titrated to minimal elastance [
12,
14,
15], and it was suggested that it can be done using either incremental or decremental phase of a staircase RM. However, this suggestion is limited to the protocol and data available. If only the incremental phase of the RM is available, PEEP titration can be performed during incremental stage, or vice-versa. If both incremental and decremental phase of the staircase RM are available, PEEP should be titrated during decreasing PEEP, as the incremental PEEP functions to recruit the collapsed lung [
38,
39].
A further limitation is that the findings of this research are solely based on observation of the
E
drs
map. The findings require further investigation together with additional imaging and monitoring tools such as in-vivo microscopy, computer tomography and/or electrical impedance tomography for validation. However, high resolution imaging technology is currently limited to regional investigation and clinically impractical for full and continuous monitoring [
40‐
42]. Thus, the findings of this research are limited to comparisons with existing literature.