We have constructed a model of the respiratory system with a recoiling lung and an expanding chest wall, where tidal airway (total respiratory system) pressure/volume curves are seemingly left-shifted when increasing PEEP in accordance with what is seen in patients [21, 22, 24, 25, 27]. A change in end-expiratory airway pressure, PEEP with an ensuing inflation of the lung, causes a negligible increase in end-expiratory “pleural” pressure, indicating that end-expiratory elastance of the chest wall is close to zero, i.e., the end-expiratory chest wall compliance is extremely high. As a consequence, the end-expiratory transpulmonary pressure increases as much as PEEP is increased. The increase in end-expiratory lung volume following a PEEP step is determined by the size of the change in PEEP and lung elastance. If the change in volume is measured, lung elastance can be determined as the change in PEEP divided by the change in end-expiratory lung volume, ΔPEEP/ΔEELV. Thus, we do not need to know pleural or esophageal pressure to estimate lung elastance and changes in transpulmonary pressure.
Tidal and end-expiratory chest wall elastance
The expanding chest wall has a fundamental physiological role in counteracting the recoil of the lung at end-expiration, i.e., functional residual capacity (FRC). This has previously been described in a number of classical studies and in textbooks of physiology [10, 13, 28–31] but have only recently been introduced in studies of mechanical ventilation [8, 9, 11].
The outward directed force of the chest wall has a pulling effect on the lung, which in itself strives to recoil to a lower volume, the minimal volume, slightly below the residual volume. The net effect of these contra-directional forces is that a negative pleural pressure and an equally large positive transpulmonary pressure are created, 5–10 cmH2O [29–32]. Thus, instead of compressing, squeezing, or leaning at the lung at end-expiration, the chest wall tends to expand the lung at end-expiration as long as the end-expiratory lung volume, irrespective of the reason for the increased volume, emphysema or PEEP inflation, is below the resting volume of the chest wall at 70–90 % of total lung capacity (TLC) [10, 30, 31, 33–36]. The resilience of the chest wall originates in the ribs, ligaments, and cartilages of the rib cage, which are unaffected in severe acute lung injury (ARDS) [11]. This means that the resting volume of the chest wall, i.e., the volume where the chest wall does not strive outwards any more, is around 3 l above FRC, also in respiratory failure patients. As the mean pleural pressure at FRC is around −5 and 0 cmH2O at the chest wall resting volume, the end-expiratory chest wall compliance is 3000/5 ≈ 600 ml/cmH2O estimated from the chest wall relaxation P/V curve as described by Rahn and coworkers in 1946 [10]. In emphysema patients, who were subjected to lung reduction surgery, end-expiratory chest wall compliance is estimated to be 700 ml/cmH2O [37]. In the present lung/chest wall/abdomen model, the end-expiratory chest wall compliance was also very high, i.e., around 600 ml/cmH2O, confirming that the geometry of the model reflects chest wall mechanics in humans. Between FRC and the resting volume of the chest wall pleural pressure is negative, and the chest wall strives outwards at end-expiration, irrespective of the pressure inside the lung, of which there are no receptors in the chest wall [10, 31, 37, 38]. This indicates that the chest wall has a negligible influence on the lung during end-expiration as a result of the rib cage spring-out force.
Tidal pleural pressure variations, the chest wall-driving pressure, reflect the force needed to displace a weight, the chest wall, and the abdominal content during inspiration, rather than inflating a recoiling structure. As the weight of the chest wall and the abdomen does not change with changing PEEP, tidal chest wall elastance is almost constant during increasing PEEP levels in the respiratory system model, as also reported for patients in several studies [8, 9, 25, 39, 40] (Fig. 7). During an inspiration from ZEEP/FRC pressure/volume equilibrium, pleural pressure increases from a negative pressure level to a less negative pressure level, or if the chest wall is very stiff, to a positive end-inspiratory pleural pressure (Figs. 3 and 7). But, during the expiration, the lung will recoil back to the baseline, and from a volume point of view, the interior volume of the chest wall is always essentially equal to the lung exterior volume; the lung will pull the chest wall back to baseline volume. In doing so, pleural pressure will return to a negative level because of the rib cage spring-out force opposing the recoil of the lung.
When PEEP is stepwise increased, the ventilator expiratory valve is closing at the selected, new PEEP level during the first expiration after increasing PEEP, and a volume corresponding to total respiratory system compliance times the change in PEEP is retained in the lung (Fig. 3). As long as this first expiration lung volume increase does not cause the end-expiratory lung volume to exceed the chest wall resting volume at 70–80 % of TLC, the end-expiratory pleural pressure will be negative when the expiratory valve closes (Figs. 3 and 7), indicating that the rib cage spring-out force is active. During the ensuing breaths, the end-expiratory lung volume increases breath by breath and the end-expiratory pleural pressure subsides back to or close to the baseline negative pleural pressure level and a new P/V equilibrium is reached. PEEP inflation of the lung is a pressure control inflation of the lung with constant airway pressure, and end-expiratory airway pressure is the sum of end-expiratory transpulmonary and end-expiratory pleural pressure. As end-expiratory transpulmonary pressure increases breath by breath, when the end-expiratory lung volume increases breath by breath, end-expiratory pleural pressure must decrease after the initial first expiration increase, as much as the transpulmonary pressure increases (Fig. 3). If the chest wall behaved as an elastic entity recoiling to a lower volume like the lung, end-expiratory chest wall elastance, ΔPPLEE/ΔEELV, would be equal to tidal chest wall elastance, ΔPPL/VT, like end-expiratory lung elastance, ΔPTPEE/ΔEELV, is equal to tidal lung elastance ΔPTP/VT. Consequently, total end-expiratory elastance would be the sum of tidal chest wall and tidal lung elastance, total respiratory system elastance (ETOT) = ΔPPL/VT + ΔPTP/VT and the change in end-expiratory lung volume change following a PEEP increase could not exceed the change in PEEP (=ΔPAWEE) divided by the total respiratory system elastance, ΔPEEP/ETOT. However, such a low change in end-expiratory lung volume is only present in isolated lung, where total respiratory system elastance is the same as lung elastance, as seen when ventilating isolated test lungs in the model (Fig. 2). In patients, the change in end-expiratory lung volume is always larger than ΔPEEP/ETOT, except in isolated lung, as reported in multiple studies [20, 21, 22, 27] and determined by the size of the PEEP step and lung elastance, ΔEELV = P ΔPEEP/EL, as seen in the model and in accordance with findings in previous studies in pigs and acute lung injury (ALI) patients [8, 9].
Transpulmonary pressure
The consequence of the mean end-expiratory pleural pressure remaining at a baseline negative level when PEEP is increased is that the end-expiratory transpulmonary pressure increases as much as PEEP is increased. This is in accordance with findings in a porcine and in an ALI patient study, where the transpulmonary pressure variations of a tidal volume equal to the change in end-expiratory lung volume was closely related to the change in PEEP [8, 9]. As the transpulmonary pressure increases as much as the end-expiratory airway pressure changes, the static end-expiratory and end-inspiratory transpulmonary pressure at a certain lung volume level is independent of whether this volume is reached by tidal or PEEP inflation (Fig. 8). Consequently, end-expiratory and end-inspiratory transpulmonary pressure/volume points are aligned on a common, single transpulmonary (lung) P/V curve, as seen in the model, irrespective of whether one, two, or three test lungs are used, or the chest wall is normal or stiff (Figs. 2, 4, 5, 6, and 7).
An indication that the model is physiologically adequate would be if it could be shown, also in patients, that the increase in end-expiratory transpulmonary pressure following a PEEP increase is equal to the ΔPEEP. To confirm this, we calculated the increase in end-expiratory transpulmonary pressure of an end-expiratory lung volume increase following a PEEP increase as ΔEELV × EL from the reported mean values in 8 patients representative of patients with healthy lungs, 8 patients representative of moderate acute lung injury (ALI), and 8 patients representative of severe acute lung injury (ARDS) of a study by Pesenti and coworkers [39], and in 9 patients with pulmonary and 12 patients with extrapulmonary ARDS from a study by Gattinoni and coworkers [25]. In these representative “patients,” PEEP was increased from ZEEP to 5, 10, and 15 cmH2O in random order and the increase in lung volume was determined during a prolonged expiration to ZEEP from the different PEEP levels. In addition, the same calculation was performed in a group of 26 patients, representative of patients with mixed ALI, during incremental PEEP steps of 5 cmH2O, from 5 to 40 and back to 5 cmH2O [41]. In all three studies, lung elastance was determined as the tidal difference in airway pressure minus the tidal difference in esophageal pressure divided by the tidal volume, EL = (ΔPAWLP − ΔPPLLP)/VT, avoiding uncertainties of the validity of absolute end-expiratory esophageal pressure in relation to absolute pleural pressure [6, 15, 42, 43, 44]. Twenty-eight PEEP steps in six mean “patients” representative of the most extreme lung conditions, from healthy lungs to the most severe pulmonary and extrapulmonary ARDS, were included and showed that the transpulmonary pressure increased 5.1 ± 0.7 cmH2O, when the PEEP was increased by 5 cmH2O and that end-expiratory pleural pressure, as a consequence did not increase, −0.1 ± 0.7 cmH2O. This is a strong indication that the model performs in accordance with human physiology as the increase in end-expiratory “pleural” pressure in the model also was negligible, 0.2 ± 0.1 cmH2O.
Clinical implications
At end-expiration at any PEEP/EELV level below the resting volume of the chest wall, which is more than 3 l above FRC [30, 33], the spring-out force of the resilient rib cage makes the chest wall strive to a higher volume, while the end-expiratory airway pressure keeps the lung distended. The end-expiratory transpulmonary pressure and the end-expiratory pleural pressure at supine at FRC is zero at the most dorsal region of the open lung due to the gravitational pleural pressure gradient [11]. Thus, at end-expiratory pressure/volume equilibrium at increased PEEP, the end-expiratory transpulmonary pressure of most dorsal region of the open lung is equal to the end-expiratory airway pressure, as the chest wall is “lifted” from the lung, i.e., the chest wall does not squeeze or lean on the lung at end-expiration. It has been shown in a porcine study that the static transpulmonary pressure, PTPEE, is less damaging than the dynamic, transpulmonary driving pressure during tidal inspiration, ΔPTP [2, 45]. In humans, the key factor in ventilator-induced lung injury is the airway driving pressure [1], but in an accompanying editorial, it was pointed out that the culprit was not the total respiratory system (airway) but rather the transpulmonary driving pressure [3]. As the transpulmonary (lung) driving pressure can constitute anything between 50 % in mainly extrapulmonary ARDS and 90 % of the total respiratory system (airway) driving pressure in mainly direct, pulmonary ARDS, it is of great importance to be able to determine the lung driving pressure, both to know when there is a possibility to use higher airway driving pressure without harming the lung and when the tidal volume should be reduced to prevent harmful lung driving pressures. The present model shows that the ΔPTP can be calculated by a simple PEEP step procedure, where the change in end-expiratory lung volume is determined following a PEEP change. Then, lung elastance for the lung volume range between the two PEEP levels can be calculated as the change in PEEP divided by the change in end-expiratory lung volume, EL = ΔPEEP/ΔEELV. Tidal chest wall elastance can be determined as the difference between total respiratory system elastance (ΔPAW/VT) and lung elastance, chest wall elastance (ECW) = ETOT − ΔPEEP/ΔEELV. As tidal chest wall elastance is essentially constant when increasing PEEP, transpulmonary driving pressure at any PEEP level can be calculated as total respiratory system driving pressure minus tidal chest wall elastance times the tidal volume, ΔPAW − ECW × VT.