To the best of our knowledge, this is the first cohort of C-ARDS patients in which the effect of chest wall loading was assessed both in the supine and prone position. The main findings of the current investigation are that: (1) chest wall loading did not change respiratory system compliance, gas exchange or alveolar dead space in an unselected cohort of critically ill patients with C-ARDS; (2) the effect of chest wall loading was modulated by the respiratory system compliance at enrolment in the study, so that patients with a lower compliance experienced an improvement in gas exchange, dead space and the mechanical characteristics of their respiratory system; (3) the lower the respiratory system compliance at enrolment, the greater was the improvement, while the phase of disease is not associated with the response. Even a 6-h period of chest wall loading was safe, as no signs of discomfort or distress were recorded.
In general, respiratory system mechanics depend on the elastic properties of lung and chest wall. The regional distensibility of the chest wall, which is composed by the rib cage and abdomen, varies markedly from site to site, with dorsal regions being more rigid than ventral ones, and the rib cage being less flexible than the abdomen [27]. Prone positioning is a manoeuver used in patients with moderate-severe ARDS to improve oxygenation and reduce mortality [3]. The change to prone position reversibly stiffens the relatively compliant anterior portions of the chest wall and ventral abdomen, relieves the superimposed pressure of both the heart and the abdomen on the lungs and induces a more uniform distribution of tidal volume by reversing the vertical pleural pressure gradient [2, 28]. Since pulmonary perfusion remains preferentially distributed to the dorsal regions, an overall improved alveolar ventilation/perfusion matching also occurs.
If the restricting effect on the anterior chest wall is considered the main pathophysiologic correlate of prone positioning, then at least some of its effects should be replicated by stiffening the chest surface. Chest wall restriction has long been used as a model for studying the physiology of restrictive diseases, respiratory muscle weakness, and the effects of general anesthesia and muscle relaxants [29,30,31]. Indeed, external chest wall compression uniformly reduces chest wall compliance; if tidal volume and PEEP do not change, an increased driving pressure and a reduced respiratory system compliance are expected [9]. However, this can only occur provided that lung compliance does not simultaneously improve by the imposed stiffening of the chest wall.
Before the COVID-19 era, only few papers investigated the effects of chest wall loading in critically-ill patients. In 11 supine, mechanically ventilated patients with acute lung injury, loading of the anterior chest wall with a 10 kg sand bag led to a 25% decrease in EELV and an increase in compliance. While oxygenation did not change in the whole cohort, patients who improved their oxygenation were the same who reduced their chest wall compliance [10]. Samanta et al. report two cases of trauma where prone position could not be performed, chest wall compression with 2-kg weight on each side of the chest wall bilaterally while the patients were in the supine position led to significant improvements in oxygenation [32]. Notably, several recent reports of C-ARDS patients, mainly enrolled in a late phase of their illness, described a paradox, unexpected improvement in respiratory system compliance and gas exchange in response to anterior chest wall loading [11,12,13,14,15,16].
In an unselected sample of C-ARDS patients, we were unable to find any effect of chest wall loading on respiratory system compliance, gas exchange or dead space during either supine or prone position. In fact, previous reports [11,12,13,14,15,16] found that the paradoxical increase in respiratory system compliance with anterior chest compression was mostly due to the decrease in overdistension because of the decrease in end-expiratory lung volume. In the present study, indeed, patients who increased Crs during chest wall compression had higher baseline PEEP, plateau and driving pressure. It is interesting to note that a positive effect of chest wall loading on respiratory mechanics and oxygenation was only seen in patients with signs of overdistension. To test this hypothesis, we analyzed the effects of chest wall compression depending on the basal driving pressure, considered a surrogate for lung strain [25]. We found a statistically significant, linear effect of baseline airway driving pressure and the response to chest wall loading, so that the higher the strain, the higher was the improvement in compliance and oxygenation, and the higher was the reduction in alveolar dead-space.
The apparent inconsistency between our results and the improvements seen in previous reports might lie in the fact that all the patients included in those reports had a severely reduced respiratory system compliance, ranging from 13 to 35 ml/cmH2O [11,12,13,14,15,16]. Similar to those findings, we also noticed a positive effect of chest wall loading in terms of gas exchange, mechanical characteristics and a reduction in alveolar dead space when considering only patients with a reduced supine respiratory system compliance, whereas in patients with a higher respiratory system compliance oxygenation improved only with prone positioning with no effects of chest wall loading.
On the other side, prone positioning led to an improvement in oxygenation, respiratory system compliance and alveolar dead space in the whole cohort, irrespective of the baseline degree of distention or the value of respiratory system compliance. This is in line with the available literature of both COVID-19 and non-COVID-19 patients [3, 33, 34] and confirms how prone positioning is the standard of care in patients with moderate-severe forms of ARDS [35, 36]. Notably, the response to chest wall loading in the supine position was not able to predict the physiologic response to prone positioning: such manoeuver should better be used as a way to assess whether the patient is overdistended at end-inspiration than as a proxy of the response to prone positioning, and be used to optimize PEEP, tidal volume or both, rather than to decide whether to proceed with prone positioning.
That prone positioning led to improved respiratory system compliance while anterior chest wall loading did not is a finding that deserves some discussion. Chest wall loading increases intrapleural pressure, and this should normally lead to a proportional rise in airway plateau pressure and hence to an increased driving pressure and a reduced compliance. However, if the aerated lung volume is reduced to a very low extent, the remaining lung units operate closer to their non-compliant upper range [8]. In such cases, chest wall loading leads to reduction in the distension of previously overstretched lung units [13], allowing them to operate on a more linear portion of their pressure–volume curves [12]. As a consequence, respiratory system compliance can only improve if a significant amount of lung units were overdistended right before chest wall loading. On the other side, prone positioning does more than selectively stiffening the relatively compliant anterior chest wall: it relieves the lungs from the weight of the heart and reduced the cephalad push of abdominal pressure on dorsal lung areas [2].
Based on the generally reduced respiratory system compliance of the reports available in the literature on chest wall loading, we hypothesized that the effect of such manoeuver could in fact depend upon the baseline level of respiratory system compliance. In our case-mix, 16 out of 40 patients (40%) had a low respiratory system compliance at enrolment in the study, which is in line with other studies [23]. Patients in the lower compliance group were on average older, had a lower absolute body weight and a similar pattern of comorbidities as compared with patients with higher compliance; the two groups had a similar severity at ICU admission, despite those with reduced compliance had a higher mortality. Upon enrolment, patients in the reduced compliance group were ventilated with a lower tidal volume, a higher respiratory rate and a higher PEEP. With chest wall loading, respiratory system compliance increased in this group by 30.5%, while it decreased by 26% in the higher compliance group. This finding suggests that in those patients with reduced baseline compliance, some degree of end-tidal overinflation occurred within the aerated part of the diseased lung; chest wall loading then leads to a reduction in the end-expiratory lung volume, while at the same time easing the end-inspiratory lung overdistension sufficiently to offset the reduction in chest wall compliance, causing a downward shift of the pressure volume curve, with reduction in tidal hyper-inflation and possibly increase in tidal recruitment [15, 16]. Since tidal volume was unchanged, such improvement in compliance in patients with lower respiratory system compliance implies recruitment to a higher lung volume. This is notable, as both groups of patients had PEEP titrated to the best respiratory system compliance. Indeed, the main limitation to the titration of PEEP to respiratory system mechanics is that, given the high degree of inhomogeneity in the lungs of ARDS patients, any change in PEEP introduces regional lung overdistension and recruitment at the same time, making assumptions on the effect of PEEP on the lung volume recruited unreliable. As a matter of fact, it has been shown how PEEP selection with lung mechanics-based methods is unrelated to the lung recruitability and may lead to higher values applied to patients with lower recruitability [37]. Because of the heterogeneity of the disease, the effects of PEEP in COVID-19 patients have been shown to be highly variable and cannot be easily predicted by respiratory system characteristics [38]. This implies caution in mechanic-based methods for the selection of PEEP in COVID-19 patients.
Moreover, a further 20% improvement in compliance was found when chest wall loading was applied in patients in the prone position, suggesting a reduction in hyperinflation in the dorsal lung region despite the already compressed anterior chest wall of prone positioning [14].
The effects of chest wall loading on the mechanical characteristics of the respiratory system and gas exchange are considered to depend on a reduction in lung overinflation. Indeed, we cannot exclude that patients with a reduced respiratory system compliance are the same patients in which an inadequate setting of the mechanical ventilator leads to some degree of overinflation; notably, patients in the low compliance group also had a statistically significant higher PEEP, which was shown to be associated with a larger extent of tidal and maximal hyperinflation in patients with pulmonary ARDS [39].
Another finding consistently reported with a positive response to chest wall loading in the available literature is the association with a late phase of the disease [11, 12, 14, 16]. This has been interpreted as patients in the late phase are more overdistended, as unresolving C-ARDS may be characterized by impressive loss of aeratable lung units, in part due to fibroblastic proliferation and organization within the parenchyma [8]. We enrolled patients across a wide range of days from ICU admission and classified patients into early (within the first week) and late phase. We were unable to find any association between the effect of chest wall loading and the early and late phase of C-ARDS. Indeed, studies from non-COVID-19 ARDS have shown that the persistent phase of ARDS for 7-days was not associated with any change in respiratory mechanics or oxygenation [40].
Several limitations need to be considered when interpreting our findings. The results are not sufficient to clearly identify the underlying mechanisms, as we did not assess lung volumes, regional ventilation distribution or partitioned the mechanical characteristics of the chest wall and the lung. The lack of esophageal pressure monitoring significantly lessens the interpretation of our findings. Moreover, a single weight was used for all patients, rather than individualizing the effect of chest wall loading; in particular, we arbitrarily chose 10 kg because we previously noted that the pressure exerted by this weight seemed to induce significant changes to the respiratory system [14]. However, we acknowledge that it is unclear, from the available literature, which is the most appropriate weight to be applied. Rezoagli et al. applied a 5 kg weight [13] while Carteaux et al. [11] applied a saline bag which generated a pressure of 80 cmH2O over the chest. Kummer et al. [12] performed a manual compression without quantifying the weight in terms of kilograms. We think that this issue still needs further explorations, and ideally the weight might be patient-tailored.
Similarly, the duration of chest wall loading sessions was standardized and arbitrarily defined. Again, the literature lacks information as to the ideal duration of any such session. We aimed to assess the effect of chest wall loading in the setting of the need for prone positioning, which is known to be associated with improvements in the clinical outcome. Since international guidelines recommend that patients with moderate–severe ARDS receive prone positioning for at least 12 h per day [36], we designed a study in which a 12-h session of prone positioning was combined with chest wall loading, hence the 6-h periods. The small sample size does not allow generalizability to patients with different body morphologies, positions, or illnesses. Eventually, any benefit of long-term chest wall loading is not proved, and its impact on gas exchange remains unclear.