What is the term for the difference between the alveolar pressure and the pleural pressure?

Esophageal pressure

Transpulmonary pressure is defined as the pressure difference between the pleural space and the alveolar space.43 Conditions that decrease chest wall compliance, such as kyphoscoliosis, can increase airway pressure and lead to a false impression that lung stress is also increased. Measuring transpulmonary pressures can more accurately reflect the stress on lung parenchyma, as the measurement is independent of chest wall compliance. If transpulmonary pressure remains within normal limits, then it may be appropriate to ventilate above the accepted airway plateau pressures.

Esophageal pressure can be measured by positioning an air- or liquid-filled catheter (manometer) in the lower-third of the esophagus, and this can be used to estimate pleural pressure. Accuracy is variable due to patient positioning, the presence or absence of lung disease, and the position of the diaphragm.38 Talmor and colleagues have suggested correcting the esophageal pressure by –5 cm H2O mid-lung height, to estimate the true pleural pressure.44,45

In a single-center RCT (EPVent study), Talmor et al.46 compared mechanical ventilation guided by Pes measurements (experimental arm) with ventilation based on the ARMA trial protocol (control arm). Patients who had PEEP titrated to ensure a positive end-expiratory transpulmonary pressure experienced a higher PaO2/FiO2, better respiratory system compliance as a possible consequence of improved recruitment, but no difference in 28-day mortality. Limitations to the measurement include the fact that a single measurement of esophageal pressure is unlikely to accurately reflect pleural pressure throughout the lung. It is also a resource-intensive measurement requiring two to three operators.

Positive Pressure

High transpulmonary pressures (alveolar minus pleural pressure) and high tidal volumes can produce barotrauma, manifesting as pneumothorax, pneumomediastinum, or subcutaneous emphysema. Overdistension of the lung as well as repetitive opening and closing of alveoli can produce local lung injury, as well as systemic release of cytokines potentially resulting in multiorgan failure. PEEP may be beneficial by reducing the shear stresses associated with repeated opening and closing of alveoli. Positive pressure ventilation may reduce cardiac output and blood pressure by impairing venous return and right-ventricular filling, particularly in the volume-depleted patient.

Transpulmonary Pressure

The transpulmonary pressure, PL, represents the distending pressure across the lungs, which is the difference between the airway pressure and the pleural pressure. It is an essential concept because it represents the pressure that effectively promotes air flow and distends the lungs. At end-inspiration, if respiratory flow equals zero and there is a clear plateau of the airway pressure, end-inspiratory PL = Pplateau – end-inspiratory Ppleural represents the pressure acting across the alveolar units. At end exhalation, that pressure would be represented, in the absence of auto-PEEP, by end-expiratory PL = PEEP – end-expiratory Ppleural. The importance of the concept of PL becomes clear as the inspiratory PL is the pressure which provides tidal ventilation at the same time that could produce stretch lung injury; and the end-expiratory PL is that required to prevent lung collapse at end-exhalation by being kept positive.

Unfortunately, the assessment of PL is not usual in clinical practice because measurement of pleural pressure is not simple, in contrast to measurement of airway pressure. Yet, pleural pressure may be estimated using an esophageal balloon, which is either standalone or attached to an esophagogastric tube and positioned in the lowest third of the esophagus23–25 (Fig. 5.6). These esophagogastric tubes are generally 100 cm long, and the average depth for a correctly positioned balloon is approximately 35 to 45 cm. The catheter is connected to a pressure transducer via a three-way stopcock, and the balloon is inflated to a standard volume depending on the device, which is necessary to prevent artifact because of passive recoil of the balloon walls. Further, the balloon should be long enough to avoid regional variability, providing an average measurement of esophageal pressure to estimate pleural pressure. Although use of an esophageal balloon represents an improvement in the accuracy of pulmonary pressure monitoring, it is not without its limitations. Artifact may arise from mediastinal weight, gravitational gradients in pleural pressure, and airway closure at end exhalation.23 Furthermore, there is considerable controversy in the literature on whether the esophageal pressure measurements should be directly taken as absolute estimates of pleural pressures for PEEP adjustments,26 or whether changes in esophageal pressures should be used to compute chest wall and lung elastances, which are then used to set the level of the administered PEEP.27 Although a ventilator strategy guided by the transpulmonary pressure measured with esophageal balloons improved oxygenation and compliance in a small group of acute respiratory distress syndrome (ARDS) patients,28 a subsequent large trial on patients with moderate to severe ARDS resulted in no significant difference in death and days free from mechanical ventilation between patients receiving an esophageal balloon-guided PEEP and those receiving empirical high PEEP-FiO2 settings.29 Those findings did not support esophageal balloon-guided PEEP titration in ARDS. In critically ill patients with class 3 obesity (body mass index [BMI] ≥40 kg/m2) and ARDS, a retrospective analysis compared a standard protocol of ventilator settings determined by the ARDS net table for lower PEEP/higher FiO2 with a “lung rescue” management strategy with settings determined by an individualized protocol based on lung recruitment maneuvers, esophageal manometry, and hemodynamic monitoring.29 Patients receiving the standard protocol had almost double the 28-day mortality compared with the lung rescue cohort (31% vs. 16%, P = .012; hazard ratio [HR], 0.32; 95% confidence interval [CI] 95%, 0.13–0.78).

In robotic-assisted laparoscopic surgery, esophageal manometry can help delineate the portion of increased driving pressure, which is applied to the lungs versus that applied to the chest wall; the increase in elastance associated with pneumoperitoneum is substantially greater for the chest wall (ECW) than for the lungs (ELS).30 This may improve the ability to maintain open lung by appropriately titrating PEEP in this and other perioperative conditions with high susceptibility to lung derecruitment.

Force-Bearing Structure of Lung Parenchyma

The transpulmonary pressure is applied to the force-bearing structure of lung parenchyma, the extracellular matrix, which constitutes the lung skeleton.31 The lung skeleton is a complex and metabolically active structure that includes a network of several components—elastin, collagen, and proteoglycans. All these molecules are involved in determining the mechanical characteristics of the respiratory system. The elastin may be considered as an elastic spring, whereas the unextensible collagen, which is folded at end expiration and completely unfolded at a lung volume equal to total lung capacity, acts as a stop-length fiber.32,33 The proteoglycans stabilize the collagen-elastin network, contributing to lung elasticity and alveolar stability at low and medium lung volumes.34

The matrix of elastin, collagen, and proteoglycans is arranged in two main fiber systems: (1) the axial system, which originates from the pulmonary hilum and runs deeply into the lung parenchyma down to the alveolar level, where it joins (2) the peripheral system, which originates from the visceral pleura and runs centripetally within the lung parenchyma.31 The lung skeleton may be considered as a continuous elastic structure that reaches its extension limits at total lung capacity, a lung volume equal to about threefold the lung resting volume. At this level of alveolar distention, the collagen is completely unfolded, and further expansion is prevented. The epithelial and endothelial cells do not directly bear the applied forces because they are anchored to the extracellular matrix by a series of structural proteins (integrins), which are connected to the cytoskeleton. During lung expansion, the epithelial and the endothelial cells modify their shape.

It is well documented that mechanically induced cellular deformation activates a series of mechanosensors with the production of several inflammatory mediators, such as cytokines interleukin-6, tumor necrosis factor-α, and interferon-γ,27,35 metalloproteinases (enzymes involved in the remodeling of the matrix),36 leukotrienes,37 and interleukin-8,38–40 the most powerful attractor of neutrophils.41 Gross barotrauma (e.g., pneumothorax) is due to the stress at rupture of the lung skeleton, whereas intrapulmonary inflammation is primarily due to the excessive strain of the epithelial and endothelial cells.

Pathophysiology.

Under experimental conditions, transpulmonary pressures (i.e., the difference between intratracheal and intrapleural pressures) of 95 to 110 cm H2O are sufficient to disrupt the pulmonary parenchyma and force gas into the interstitium.10 Extra-alveolar gas will migrate through perivascular sheaths to cause mediastinal emphysema and pneumothorax.10 Gas can also dissect into the retroperitoneum and into the subcutaneous tissues of the neck. Extra-alveolar gas can pass into ruptured blood vessels, travel to the left side of the heart, and enter the arterial circulation as gaseous emboli. The dissemination of gas bubbles throughout the arterial circulation causes injury to other organ systems and to skeletal muscle, which is evident by a rise in serum creatine kinase level.11

Pulmonary barotrauma can be seen in divers who would not be considered at risk for lung overpressure. Occult lung disease may contribute to unexplained barotrauma and cerebral air embolism.12 Epidemiologic studies have not demonstrated a significant relationship between asthma and an increased risk for pulmonary barotrauma.13

Transmural pressure

The airspace opening pressure is the transpulmonary pressure (i.e., the difference between intraalveolar and pleural pressures). Transpulmonary pressure is a function of the pressure applied to the airways and of the elastances of the lung and chest wall, according to the following equation, in which Paw is the applied airway pressure, El is the elastance of the lung, and Ew is the elastance of the chest wall:

Transpulmonary pressure=Paw×[ EL/(EL+EW)]

Normally, El equals Ew, and the transmural pressure, as an average, would be approximately half of the pressure applied to the airways. However, as previously discussed, in ALI/ARDS caused by direct or indirect insult, the El/(El + Ew) value may be very different. For example, in ARDS that results from direct insult, the ratio is less than 1 for patients who have extrapulmonary disease. It follows that to achieve the same opening transmural pressure, a higher Paw is required in ARDS that arises from extrapulmonary problems than in ARDS that results from pulmonary conditions.

ROLE OF SURFACTANT IN ALVEOLAR STABILITY

Theoretical calculations based on measurements of transpulmonary pressure and morphologic considerations with normal and saline-filled lungs indicate that surface tension varies during lung inflation and deflation and falls to very low values during expiration.77,79,118–120 Studies in detergent-rinsed and fluorocarbon-filled lungs, in which surface tension is altered by the remaining detergent or fluorocarbon, support the view of low alveolar surface tension.

More direct evidence was obtained by Samuel Schÿrch and his co-workers119,122–125 by monitoring the spreading properties of fluorocarbon or silicone oil test droplets deposited on the lung's alveolar surfaces in situ.119,122–125 Such droplets spread to form a thin lens when surface tension of the droplet is similar to that of the underlying phase. When surface tension of the underlying substrate is lower than the test droplet, the droplet adopts a more nearly spherical shape (this is the reason water forms droplets on Teflon-coated materials). Calibration of the test droplets with DPPC monolayers on the Langmuir-Wilhelmy surface balance allowed precise estimation of the surface tension of the alveolar lining layer in situ. These microdroplet studies revealed that lung volume alterations corresponding to quiet breathing (e.g., between 40 and 50% total lung capacity) were associated with only modest increases in γ from 1 to 5 mN/m. Large inflations to total lung capacity resulted in alveolar surface tensions of approximately 30 mN/m, slightly higher than the equilibrium value of 23 mN/m. When lung volume was reduced to functional residual capacity, which is 40% of total lung capacity, γ fell to less than 1 mN/m. Furthermore, when the lung was held at this volume, surface tension remained at this low value for several minutes before increasing gradually. Even after 1 hour, γ at functional residual capacity remained at less than 10 mN/m. These measurements showed that the surface film covering the alveolar lining layer is very stable in the sense that it returns to equilibrium surface tension only very slowly. This property would minimize pressure differences between small and large alveoli and would prevent collapse of the smaller units. These observations reinforced the view that the endogenous surface monolayer must be highly enriched with DPPC and were considered consistent with the classical model of surfactant function.

The functional significance of the presence of a lipid-protein complex capable of generating low surface tensions within the lungs can be readily demonstrated through surfactant supplementation of surfactant-deficient lungs. Treatment of prematurely delivered rabbit fetuses of 27 days' gestation (term, 31 days) with natural or lipid extract surfactant increases survival. Surfactant administration results in a four- to fivefold increase in inflation during pressure-volume loops (Fig. 101-11)126–128 (see Chap. 106). Similar observations have been made with prematurely delivered fetuses of other species and with adult lungs made surfactant deficient through lavage. Administration of lipid mixtures similar to those present in surfactant has little immediate effect. This finding emphasizes the role of the SPs in surfactant function.1,49,51,129

Studies in which surfactant-deficient animals or prematurely delivered infants are treated with natural or lipid extract surfactants in vivo prove more difficult to interpret but clearly indicate increased compliance resulting in an increase in lung volume.1,126,130 Clinically, this can readily be monitored by a rapid increase in arterial oxygen tension, a finding indicating enhanced gaseous exchange.131 Studies by Bachofen and Schÿrch121 would indicate that, in addition to promoting lung expansion, surface tension reduction of the alveolar lining layer influences lung alveolar morphology. At low lung volumes, alveolar septa are elongated, thereby maximizing alveolar surface area. At high surface tensions of 20 to 30 mN/m, these septa are contracted through extensive folding, resulting in 30 to 50% decreases in alveolar surface area. The combined abilities of surfactant to increase compliance and optimize alveolar surface area would appear to explain the rapid (<30-minute) increases in gaseous exchange often noted on treatment of surfactant-deficient infants and would have important implications for ARDS.

Role of Surfactant in Alveolar Stability

Theoretical calculations based on measurements of transpulmonary pressure and morphologic considerations with normal and saline-filled lungs indicate that surface tension varies during lung inflation and deflation and falls to very low values during expiration.77,79,118-120 Studies in detergent-rinsed and fluorocarbon-filled lungs, in which surface tension is altered by the remaining detergent or fluorocarbon, support the view of low alveolar surface tension.

More direct evidence was obtained by Schürch and coworkers119,121-124 by monitoring the spreading properties of fluorocarbon or silicone oil test droplets deposited on the lung’s alveolar surfaces in situ.119,121-124 Such droplets spread to form a thin lens when surface tension of the droplet is similar to that of the underlying phase. When surface tension of the underlying substrate is lower than the test droplet, the droplet adopts a more nearly spherical shape (this is the reason water forms droplets on Teflon-coated materials). Calibration of the test droplets with DPPC monolayers on the Langmuir-Wilhelmy surface balance allowed precise estimation of the surface tension of the alveolar lining layer in situ. These microdroplet studies revealed that lung volume alterations corresponding to quiet breathing (e.g., between 40% and 50% total lung capacity) were associated with only modest increases in γ from 1 to 5 mN/m. Large inflations to total lung capacity resulted in alveolar surface tensions of approximately 30 mN/m, slightly higher than the equilibrium value of 23 mN/m. When lung volume was reduced to functional residual capacity, which is 40% of total lung capacity, γ fell to less than 1 mN/m. Furthermore, when the lung was held at this volume, surface tension remained at this low value for several minutes before increasing gradually. Even after 1 hour, γ at functional residual capacity remained at less than 10 mN/m. These measurements showed that the surface film covering the alveolar lining layer is very stable in the sense that it returns to equilibrium surface tension only very slowly. This property would minimize pressure differences between small and large alveoli and would prevent collapse of the smaller units. These observations reinforced the view that the endogenous surface monolayer must be highly enriched with DPPC and were considered consistent with the classical model of surfactant function.

The functional significance of the presence of a lipid-protein complex capable of generating low surface tensions within the lungs can be readily demonstrated through surfactant supplementation of surfactant-deficient lungs. Treatment of prematurely delivered rabbit fetuses of 27 days gestation (term, 31 days) with natural or lipid extract surfactant increases survival. Surfactant administration results in a four- to five-fold increase in inflation during pressure-volume loops125-127 (Figure 101-11) (see Chapter 106). Similar observations have been made with prematurely delivered fetuses of other species and with adult lungs made surfactant deficient through lavage. Administration of lipid mixtures similar to those present in surfactant has little immediate effect. This finding emphasizes the role of the SPs in surfactant function.1,49,51,128

Studies in which surfactant-deficient animals or prematurely delivered infants are treated with natural or lipid extract surfactants in vivo prove more difficult to interpret but clearly indicate increased compliance that results in an increase in lung volume.1,125,129 Clinically, this can readily be monitored by a rapid increase in arterial oxygen tension, a finding indicating enhanced gaseous exchange.130 Studies by Bachofen and Schürch131 indicate that, in addition to promoting lung expansion, surface tension reduction of the alveolar lining layer influences lung alveolar morphology. At low lung volumes, alveolar septa are elongated, thereby maximizing alveolar surface area. At high surface tensions of 20 to 30 mN/m, these septa are contracted through extensive folding, resulting in 30% to 50% decreases in alveolar surface area. The combined abilities of surfactant to increase compliance and optimize alveolar surface area would appear to explain the rapid increases (within 30 minutes) in gaseous exchange often noted on treatment of surfactant-deficient infants and would have important implications for acute RDS.

Measurement of Pulmonary Mechanics

Pulmonary mechanics are calculated by measurement of transpulmonary pressure (pressure at airway opening minus pleural pressure) and flow and volume changes throughout respiratory cycle.

Airflow and volume are measured by pneumotachography. Pleural pressure can be estimated by esophageal pressure56–60 measured by a pressure transducer connected to an air-filled balloon61,62 or a fluid-filled catheter,63,64 or by a microtransducer-tipped catheter. The accuracy of the esophageal pressure measurement can be evaluated by an occlusion test.59,61,65–67

The calculation of compliance and resistance are based on the assumption of a linear model.10 Thus, the driving pressure is always the sum of the elastic and resistive pressure. The calculations may be performed by the traditional “chord” analysis as shown in Figure 90-5.10,56–58 or by any of several computerized techniques, such as the least mean squares analysis method.11

Overstretch

The normal lung is fully inflated at a transpulmonary pressure of ∼25–30 cmH2O. Consequently, a maximum Pplat, an estimate of the elastic distending pressure, of 30 cmH2O has been recommended.48 However, overinflation may occur at much lower elastic distending pressures (18–26 cmH2O).52,56

The transpulmonary pressure may be lower than expected for a given Pplat in patients with a high chest wall elastance (e.g. obesity, abdominal compartment syndrome, after abdominal or thoracic surgery). While placement of an oesophageal balloon (see Ch. 38) allows measurement of the transpulmonary pressure and may allow better titration of PEEP,57 it must be correctly placed, have an adequate occlusion pressure ratio, and measurements are preferably performed in a semi-sitting position in order to lift the mediastinum off the oesophagus.

Finally, inspiratory muscle contraction through reduction of intrapleural pressure lowers Pplat, potentially avoiding simple detection of an excessive transpulmonary pressure. This is particularly common when pressure support ventilation is used as a primary mode of ventilatory support; VT that would produce an unacceptably high Pplat during mechanical ventilation will produce the same volutrauma during a spontaneous or supported mode of ventilation, and should be avoided. Provided the same VT is generated, spontaneous ventilation does not reduce VILI compared to controlled ventilation.58

Static or dynamic volume–pressure curves or quantitative chest CT can be used to infer overinflation, though chest CT cannot determine overstretch.5 Consequently, unless particular expertise is available, VT limitation is currently the most practical approach.