Vertical Pleural Pressure Gradient Research Articles

Pronation in acute respiratory distress syndrome (ARDS) secondary to COVID-19

: In March 2020, the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared a pandemic by the World Health Organization. Patients with SARS-CoV-2 infection can develop coronavirus disease 2019 (COVID-19), the most concerning complication of which is acute hypoxaemic respiratory failure requiring mechanical ventilation and intensive care unit (ICU) admission. In this context prone position ventilation is an established method to improve oxygenation in severe acute respiratory distress syndrome (ARDS), and its application was able to reduce mortality rate. Prone position has been used since the 1970s to treat severe hypoxemia in patients with ARDS because of its effectiveness at improving gas exchange. Compared with the supine position, placing patients in prone position effects a more even tidal volume distribution, in part, by reversing the vertical pleural pressure gradient, which becomes more negative in the dorsal regions. Prone position also improves resting lung volume in the dorsocaudal regions by reducing the superimposed pressure of both the heart and the abdomen. In contrast, pulmonary perfusion remains preferentially distributed to the dorsal lung regions, thus improving overall alveolar ventilation/perfusion relationships. Moreover, the larger tissue mass suspended from a wider dorsal chest wall effects a more homogeneous distribution of pleural pressures throughout the lung that reduces abnormal strain and stress development. This is believed to ameliorate the severity or development of ventilator-induced lung injury and may partly explain why prone position reduces mortality in severe ARDS. In this review we investigate the physiological aspects of the pronation.

Positive End-Expiratory Pressure, Pleural Pressure, and Regional Compliance during Pronation: An Experimental Study.

Rationale: The physiological basis of lung protection and the impact of positive end-expiratory pressure (PEEP) during pronation in acute respiratory distress syndrome are not fully elucidated. Objectives: To compare pleural pressure (Ppl) gradient, ventilation distribution, and regional compliance between dependent and nondependent lungs, and investigate the effect of PEEP during supination and pronation. Methods: We used a two-hit model of lung injury (saline lavage and high-volume ventilation) in 14 mechanically ventilated pigs and studied supine and prone positions. Global and regional lung mechanics including Ppl and distribution of ventilation (electrical impedance tomography) were analyzed across PEEP steps from 20 to 3 cm H2O. Two pigs underwent computed tomography scans: tidal recruitment and hyperinflation were calculated. Measurements and Main Results: Pronation improved oxygenation, increased Ppl, thus decreasing transpulmonary pressure for any PEEP, and reduced the dorsal-ventral pleural pressure gradient at PEEP < 10 cm H2O. The distribution of ventilation was homogenized between dependent and nondependent while prone and was less dependent on the PEEP level than while supine. The highest regional compliance was achieved at different PEEP levels in dependent and nondependent regions in supine position (15 and 8 cm H2O), but for similar values in prone position (13 and 12 cm H2O). Tidal recruitment was more evenly distributed (dependent and nondependent), hyperinflation lower, and lungs cephalocaudally longer in the prone position. Conclusions: In this lung injury model, pronation reduces the vertical pleural pressure gradient and homogenizes regional ventilation and compliance between the dependent and nondependent regions. Homogenization is much less dependent on the PEEP level in prone than in supine positon.

Gas Exchange in the Prone Posture.

The prone posture is known to have numerous effects on gas exchange, both under normal conditions and in patients with ARDS. Clinical studies have consistently demonstrated improvements in oxygenation, and a multi-center randomized trial found that, when implemented within 48 h of moderate-to-severe ARDS, placing subjects in the prone posture decreased mortality. Improvements in gas exchange occur via several mechanisms: alterations in the distribution of alveolar ventilation, redistribution of blood flow, improved matching of local ventilation and perfusion, and reduction in regions of low ventilation/perfusion ratios. Ventilation heterogeneity is reduced in the prone posture due to more uniform alveolar size secondary to a more uniform vertical pleural pressure gradient. The prone posture results in more uniform pulmonary blood flow when compared with the supine posture, due to an anatomical bias for greater blood flow to dorsal lung regions. Because both ventilation and perfusion heterogeneity decrease in the prone posture, gas exchange improves. Other benefits include a more uniform distribution of alveolar stress, relief of left-lower-lobe lung compression by the heart, enhanced secretion clearance, and favorable right-ventricular and systemic hemodynamics.

Pleural pressure theory revisited: a role for capillary equilibrium.

Theories elucidating pleural pressures should explain all observations including the equal and opposite recoil of the chest wall and lungs, the less than expected pleural hydrostatic gradient and its variation at lobar margins, why pleural pressures are negative and how pleural fluid circulation functions. A theoretical model describing equilibrium between buoyancy, hydrostatic forces, and capillary forces is proposed. The capillary equilibrium model described depends on control of pleural fluid volume and protein content, powered by an active pleural pump. The interaction between buoyancy forces, hydrostatic pressure and capillary pressure was calculated, and values for pleural thickness and pressure were determined using values for surface tension, contact angle, pleural fluid and lung densities found in the literature. Modelling can explain the issue of the differing hydrostatic vertical pleural pressure gradient at the lobar margins for buoyancy forces between the pleural fluid and the lung floating in the pleural fluid according to Archimedes' hydrostatic paradox. The capillary equilibrium model satisfies all salient requirements for a pleural pressure model, with negative pressures maximal at the apex, equal and opposite forces in the lung and chest wall, and circulatory pump action. This model predicts that pleural effusions cannot occur in emphysema unless concomitant heart failure increases lung density. This model also explains how the non-confluence of the lung with the chest wall (e.g., lobar margins) makes the pleural pressure more negative, and why pleural pressures would be higher after an upper lobectomy compared to a lower lobectomy. Pathological changes in pleural fluid composition and lung density alter the equilibrium between capillarity and buoyancy hydrostatic pressure to promote pleural effusion formation.

A Comprehensive Review of Prone Position in ARDS.

Prone position (PP) has been used since the 1970s to treat severe hypoxemia in patients with ARDS because of its effectiveness at improving gas exchange. Compared with the supine position (SP), placing patients in PP effects a more even tidal volume distribution, in part, by reversing the vertical pleural pressure gradient, which becomes more negative in the dorsal regions. PP also improves resting lung volume in the dorsocaudal regions by reducing the superimposed pressure of both the heart and the abdomen. In contrast, pulmonary perfusion remains preferentially distributed to the dorsal lung regions, thus improving overall alveolar ventilation/perfusion relationships. Moreover, the larger tissue mass suspended from a wider dorsal chest wall effects a more homogeneous distribution of pleural pressures throughout the lung that reduces abnormal strain and stress development. This is believed to ameliorate the severity or development of ventilator-induced lung injury and may partly explain why PP reduces mortality in severe ARDS. Over 40 years of clinical trials have consistently reported improved oxygenation in approximately 70% of subjects with ARDS. Early initiation of PP is more likely to improve oxygenation than initiation during the subacute phase. Maximal oxygenation improvement occurs over a wide time frame ranging from several hours to several days. Meta-analyses of randomized controlled trials suggest that PP provides a survival advantage only in patients with relatively severe ARDS (PaO2 /FIO2 < 150 mm Hg). Moreover, survival is enhanced when patients are managed with a smaller tidal volume (≤ 8 mL/kg), higher PEEP (10-13 cm H2O), and longer duration of PP sessions (> 10-12 h/session). Combining adjunctive therapies (high PEEP, recruitment maneuvers, and inhaled vasodilators) with PP has an additive effect in improving oxygenation and may be particularly helpful in stabilizing gas exchange in very severe ARDS.

Inhomogeneity during deflation of excised canine lungs. III. Single-breath O2 tests.

Both interregional and intraregional mechanisms may cause changes in N2 concentration of expired gas during the phases of the single-breath O2 test (SBO2) that follow dead-space washout. To evaluate the possible importance of each mechanism, we performed the SBO2 in excised canine lungs that were first suspended in air and then immersed in stable foams that simulated the vertical gradient of pleural pressure. The lungs were deflated at constant submaximal flows. The slope of phase III diminished with increasing expiratory flow and increased with foam immersion. The onset of phase IV depended on flow, and a terminal decrease in N2 concentration (phase V) was often observed. Simultaneously measured estimates of regional flows and volumes (J. Appl. Physiol. 65: 1764-1774, 1988) were used to further interpret these results. The onset of phase IV at flows greater than quasi-static signified the onset of flow limitation of dependent regions. The onset of phase V corresponded to flow limitation of nondependent regions.

Inhomogeneity during deflation of excised canine lungs. I. Alveolar pressures.

Factors both intrinsic and extrinsic to the lung may cause inhomogeneity of alveolar pressures during deflation. Wilson et al. (J. Appl. Physiol. 59: 1924-1928, 1985) predicted that any such inhomogeneity would be limited by interdependence of regional expiratory flows. To test this hypothesis and to explore how the pleural pressure gradient might affect inhomogeneity of alveolar pressures, we deflated at submaximal flows excised canine lobes that first were suspended in air and then were immersed in foams that simulated the vertical gradient of pleural pressure. Interregional inhomogeneity of regional transpulmonary pressures was measured with use of an alveolar capsule technique. Flow-dependent inhomogeneity of alveolar pressures was present, with differences in alveolar pressure quickly relaxing to a constant limiting value at each flow. Foam immersion increased inhomogeneity at a given flow. We conclude that factors intrinsic to the lung cause significant inhomogeneity of alveolar pressures at submaximal expiratory flows and that this inhomogeneity is enhanced by the extrinsic gradient of pleural pressure. These observations are consistent with the interdependence of flow proposed by Wilson et al.

Liquid thickness vs. vertical pressure gradient in a model of the pleural space.

In recent studies using relatively noninvasive techniques, the vertical gradient in pleural liquid pressure was 0.2-0.5 cmH2O/cm ht, depending on body position, and pleural liquid pressure closely approximated lung recoil (J. Appl. Physiol. 59: 597-602, 1985). We built a model to discover why the vertical gradient in pleural pressure is less than hydrostatic (1 cmH2O/cm). A long rubber balloon of cylindrical shape was inflated in a plastic cylinder. The "pleural" space between the balloon and cylinder was filled with blue-dyed water. With the cylinder vertical, we measured pleural pressure by a transducer through side taps at 2-cm intervals up the cylinder. The pressure was measured with different amounts of water in the pleural space. With a clear separation between the balloon and the container, the vertical gradient in pleural liquid pressure was hydrostatic. As water was withdrawn from the pleural space, the balloon approached the wall of the container. Over an 8-cm-long midregion of the model where the balloon diameter matched the cylinder diameter, the vertical gradient was not hydrostatic and was virtually absent. In this region, the pleural liquid pressure was uniform and equal to the recoil of the balloon. In this section we could not see any pleural space. By scintillation imaging using 99mTc-diethylenetriamine pentaacetic acid in the water, we estimated the thickness of this flat "costal" pleural space to be approximately 20 microns. Radioactive tracer injected at the top of the pleural space appeared by 24 h at the bottom, which indicated a slow drainage of liquid by gravity.(ABSTRACT TRUNCATED AT 250 WORDS)

Interstitial fluid pressure gradient measured by micropuncture in excised dog lung.

We have directly measured lung interstitial fluid pressure at sites of fluid filtration by micropuncturing excised left lower lobes of dog lung. We blood-perfused each lobe after cannulating its artery, vein, and bronchus to produce a desired amount of edema. Then, to stop further edema, we air-embolized the lobe. Holding the lobe at a constant airway pressure of 5 cmH2O, we measured interstitial fluid pressure using beveled glass micropipettes and the servo-null method. In 31 lobes, divided into 6 groups according to severity of edema, we micropunctured the subpleural interstitium in alveolar wall junctions, in adventitia around 50-micron venules, and in the hilum. In all groups an interstitial fluid pressure gradient existed from the junctions to the hilum. Junctional, adventitial, and hilar pressures, which were (relative to pleural pressure) 1.3 +/- 0.2, 0.3 +/- 0.5, and -1.8 +/- 0.2 cmH2O, respectively, in nonedematous lobes, rose with edema to plateau at 4.1 +/- 0.4, 2.0 +/- 0.2, and 0.4 +/- 0.3 cmH2O, respectively. We also measured junctional and adventitial pressures near the base and apex in each of 10 lobes. The pressures were identical, indicating no vertical interstitial fluid pressure gradient in uniformly expanded nonedematous lobes which lack a vertical pleural pressure gradient. In edematous lobes basal pressure exceeded apical but the pressure difference was entirely attributable to greater basal edema. We conclude that the presence of an alveolohilar gradient of lung interstitial fluid pressure, without a base-apex gradient, represents the mechanism for driving fluid flow from alveoli toward the hilum.

Effects of rib cage or abdominal restriction on lung mechanics.

The effects on lung mechanics of equal (37%) reduction in total lung capacity (TLC) by rib cage or abdominal restriction were studied in 10 healthy males. Lung recoil pressure (Pst) was simultaneously measured from three sites in the esophagus. This also provided an estimate of the vertical pleural pressure gradient (PPG). Deformation of the right hemithorax was quantified by roentgenograms in three subjects. At the same lung volume, abdominal restriction decreased lung height and increased anteroposterior diameter compared with the control case, whereas rib cage restriction had opposite effects. Maximum expiratory flow increased equally with both types of restriction, and average Pst increased equally with both types of restriction. There was a significant correlation between degree of TLC reduction and increase in Pst that was similar for both types of restriction. This study indicates that changes in lung mechanics depend primarily on the amount of volume reduction and not on the type of deformation producing the volume decrease.

Pressure-volume and airway closure relationships in each lung in anaesthetized man.

Airway closure, functional residual capacity (FRC) and transpulmonary pressure-volume curves were assessed for each lung separately in the anaesthetized subject by means of a double lumen tracheal catheter. In the supine position airway closure occurred synchronously in the two lungs and 0.2-0.31 above FRC. The pressure- volume curves in both lungs were rather similar and critical closing pressure (CP) was approximately 3 cmH2O in each lung. In the left lateral posture, FRC was increased in the non-dependent and reduced in the dependent lung, while closing capacity (CC) remained unaltered. Airway closure was asynchronous and discontinuous between the two lungs. This was caused by the non-linear transpulmonary pressure-volume curve in the lungs, in conjunction with the vertical pleural pressure gradient. An interpulmonary "pendelluft" phenomenon was observed in the left lateral posture, increasing inhomogeneity of ventilation. It may depend on regional differences in compliance.

Influence of diaphragmatic contraction and expiratory flow on the pattern of lung emptying

Transdiaphragmatic pressure (Pdi) and expiratory flow (V̇) were monitored during vital capacity single breath N 2 washouts in 7 seated subjects. Transient increases in V̇ were produced (1) actively, by subjects increasing mouth pressure while expiring through a constant resistance or (2) passively, by the operator transiently decreasing the resistance. Voluntary contraction of the diaphragm (increased Pdi) was achieved when abdominal muscles were tensed while maintaining V̇ constant. In 5 subjects a transient increase in Pdi of 25–150 cm H 20 consistently produced a transient increase in expired N 2 concentration of 1.80 ± 0.06 % (Mean ± 1 SE); in 1 subject N 2 concentration decreased by 0.8% to 2.7% N 2, and in one subject the alveolar plateau was uninfluenced by changes in Pdi. Passive increases in V̇ up to 21/sec had no effect on Fe N 2 in any of the subjects. Active increase in V̇ changed Fe N 2 only when associated with increases in Pdi. Qualitatively similar results were obtained during helium (He) bolus washouts. However, whereas diaphragmatic contraction, maintained throughout expiration, had no measurable influence on the N 2 washout, it changed the slope of the He alveolar plateau in 6 out of 7 subjects. We conclude that in normal subjects the alveolar N 2 plateau is relatively insensitive to flow variations up to 21/sec. The fluctuations in Fe N 2 observed when the expiratory flow is varied are due to concomittant changes in Pdi. We propose that diaphragmatic contraction changes the pattern of lung emptying by altering the vertical gradient of pleural pressure.

Simulation of regional lung emptying during slow and forced expirations.

Regional lung emptying was simulated by means of a bialveolar lung model. The influence of bronchial asymmetry and the vertical pleural pressure gradient was evaluated. The model suggests that 1) in vivo the influence of the pleural pressure gradient prevails over that of the bronchial asymmetry; 2) in the presence of this gradient, the shape of phases III and IV of the single-breath washout curves obtained following inspiration of a tracer gas bolus at residual volume is determined by the recoil pressure-volume curve of the lung, by the vertical displacements of the alveoli, and,, at higher flow rates, by the elastic characteristics of the airways; 3) if the pleural pressure gradient is independent of lung volume and of flow rate, the factors mentioned in 2 suffice to produce single-breath washout curves (phases III and IV) and regional vs. overall lung volume relationships corresponding to those observed in vivo; 4) the configuration of the maximal expiratory flow-volume curve is relatively insensitive to pulmonary and bronchial asymmetry, at least in healthy individuals.