Alveolar Pressure Research Articles

PNEUMOMEDIASTINUM AND PNEUMOTHORAX DUE TO NONINVASIVE POSITIVE PRESSURE VENTILATION IN COVID-19 PNEUMONIA

SESSION TITLE: Medical Student/Resident Disorders of the Pleura Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Barotrauma as a consequence of high alveolar pressures is well described in invasive mechanically ventilated (IMV) patients with pneumonia or pneumonitis. Limited data exists on the incidence of barotrauma in patients with Coronavirus Disease 19 pneumonia (COVID-19). We present a case of barotrauma occurring in a non-intubated patient with COVID-19 receiving noninvasive positive pressure ventilation (NPPV). CASE PRESENTATION: A 43-year-old male with obesity presented with 2 days of cough and dyspnea. Polymerase chain reaction (PCR) testing confirmed COVID-19. He initially required 5L of oxygen (O2) per minute by nasal cannula. Due to worsening hypoxemic respiratory failure (HRF) on day 3, the patient was placed on high-flow nasal cannula (HFNC) at 90% FiO2 at a flow rate of 30 L/min . By day 7, the patient had worsening HRF and increased work of breathing. He was transitioned to continuous positive airway pressure (CPAP) at 100% FiO2 with continuous pressure set at 12 cm H2O. On day 13, he developed tachycardia and desaturation. Chest CT found gas dissecting along the axial interstitium resulting in pneumomediastinum, bilateral pneumothoraces, and extensive subcutaneous emphysema. The lung parenchyma exhibited coarse ground glass opacities and early evidence of fibrotic changes. Chest tubes were placed in each hemithorax with resolution of his pnemothoraces after 5 days. His O2 requirements decreased, and he was transferred to a rehabilitation hospital on 10 L/min O2 by facemask on day 25. DISCUSSION: Barotrauma leading to pneumomediastinum and pneumothoraces are a well-documented complication of mechanical ventilation.1 In an effort to mitigate the morbidity and mortality associated with mechanical ventilation, many clinicians have shifted toward using NPPV in HRF in COVID-19, however NPPV may not necessarily protect patients against a complication more commonly associated with IMV.2,3 Progressive and cumulative alveolar injury may predispose COVID-19 patients to barotrauma regardless of mode of ventilation.3 CONCLUSIONS: Due to the mortality associated with IMV in COVID-19, many clinicians have shifted toward using NPPV to manage HRF. However, patients receiving NPPV may still be subject to complications such as barotrauma. Additionally, given our evolving understanding of COVID-19 and the pulmonary parenchymal distortion seen in many patients, a deterioration in respiratory status should prompt clinicians to search for evidence of barotrauma, even in patients receiving NPPV. Reference #1: Mentzer SJ, Tsuda A, Loring SH. Pleural mechanics and the pathophysiology of air leaks. J Thorac Cardiovasc Surg. 2018;155(5):2182-2189. Reference #2: Xu XP, Zhang XC, Hu SL, et al. Noninvasive Ventilation in Acute Hypoxemic Nonhypercapnic Respiratory Failure: A Systematic Review and Meta-Analysis. Crit Care Med. 2017;45(7):e727-e733. Reference #3: Sun R, Liu H, Wang X. Mediastinal Emphysema, Giant Bulla, and Pneumothorax Developed during the Course of COVID-19 Pneumonia. Korean J Radiol. 2020;21(5):541-544. DISCLOSURES: no disclosure on file for Nikhil Barot; No relevant relationships by Michael Kahn, source=Web Response No relevant relationships by Nader Kamangar, source=Web Response No relevant relationships by Jay Thetford, source=Web Response

A CASE OF HAMMAN SYNDROME AND EPIDURAL PNEUMORRHACHIS IN THE SETTING OF METHAMPHETAMINE ABUSE

SESSION TITLE: Late-breaking Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Hamman’s syndrome can rarely coexist with pneumorrhachis when spontaneous collection of air in the mediastinum traverses through the fascial planes into the spinal canal. We report an unusual circumstance of Hamman’s syndrome developing into a pneumorrhachis in a patient after inhaled methamphetamine abuse. METHODS: A 20-year-old male presented after inhaling methamphetamine and developed severe bouts of cough and dyspnea. He also complained of neck pain that was sudden in onset and worsened with flexion and subsequent chest pain. Vitals on presentation were stable and swelling of his neck with subcutaneous crepitations in the jaw and chest were found on examination. Heart sounds were distant, but audible. Urine toxicology was positive for amphetamines. A chest x-ray revealed air around the upper mediastinum as well as periclavicular regions. A computer tomography (CT) scan showed the presence of subcutaneous emphysema and pneumomediastinum along with air column noted in the spinal canal, establishing a diagnosis of Hamman’s syndrome with pneumorrhachis. A gastrograffin study did not reveal esophageal tears or ruptures. During his admission, he was conservatively managed with serial chest x-rays showing gradual improvement in his subcutaneous emphysema. RESULTS: Hamman’s syndrome includes both subcutaneous emphysema and spontaneous pneumomediastinum (SPM). Risk factors such as coughing, vomiting and scuba diving, as well as systemic conditions such as asthma and cystic fibrosis can lead to an increase in intrathoracic pressure and alveolar rupture with dissection of air in the interstitial space, bronchovascular sheaths and subsequently to the mediastinum, also known as Macklin effect. Methamphetamine use can increase inflammatory markers such as tumor necrosis factor (TNF) alpha and IL-6, potentiating alveolar damage and risk of SPM. The combination of Hamman’s syndrome with pneumorrhachis is uncommon and occurs due to the passage of air between fascial planes from the posterior mediastinum into the neural foramina and epidural space. Examination of the patient includes auscultatory findings of pulmonary crackles synchronized with the heart sounds, known as Hamman’s sign. CT scan is considered as the gold standard imaging modality for diagnosis and anatomic localization. Treatment for uncomplicated SPM is supportive including analgesia, rest, treatment of underlying lung disease and avoidance of maneuvers that increase alveolar pressure. Surgical management is reserved for those who develop pneumorrhachis that is iatrogenic in nature or in the presence of complications such as hemodynamic instability and esophageal ruptures. CONCLUSIONS: We describe a unique case of symptomatic Hamman's syndrome and epidural pneumorrhachis secondary to methamphetamine use. CLINICAL IMPLICATIONS: Although uncommon, both these entities can be life-threatening and requires prompt evaluation and treatment. DISCLOSURES: No relevant relationships by Adhiraj Bhattacharya, source=Web Response No relevant relationships by Gahyun Gim, source=Web Response no disclosure on file for David Lee; No relevant relationships by Gemini Yesodharan, source=Web Response

Upscaling the poroelastic behavior of the lung parenchyma: A finite-deformation micromechanical model

The lungs are among the most deformable body organs, a mechanical feature that is key to the vital process of breathing. Current micromechanical constitutive models of the lung parenchyma construct the tissue response function either as strain-driven or pressure-driven. However, the lung parenchyma resembles an open-cell foam material consisting of a solid phase and a fluid phase that closely interact with each other. In this work, we introduce a novel finite-deformation micromechanical poroelastic model of the lung parenchyma. Using a two-scale homogenization framework for poroelasticity, we construct the effective coarse-scale response of the tissue by solving a poroelastic fine-scale problem. To this end, we develop a non-linear structural model based on a tetrakaidecahedron (TKD) unit cell that only depends on four microstructural parameters. We validate the TKD model showing that it predicts the effective response of representative volume elements (RVE) constructed from micro-computed-tomography images of the lung under several combinations of deformation and alveolar pressure. Further, we show that the estimation of the effective stress using the TKD model delivers a speed-up in computation time of more than 284,000 × when compared to RVE simulations, at the same time that it delivers higher numerical stability. In addition, we demonstrate through a sensitivity analysis that the model response predominantly depends on the alveolar-wall elasticity and initial tissue porosity, which are parameter values that are inherently connected to measurable microstructural features of the lung tissue. The present TKD model opens the door to large-scale poroelastic simulations of the lung by providing a predictive yet efficient constitutive model of the lung parenchyma. Codes are available for download at https://github.com/dehurtado/PoroelasticTKDModel.

End-tidal to Arterial Gradients and Alveolar Deadspace for Anesthetic Agents.

According to the "three-compartment" model of ventilation-perfusion ((Equation is included in full-text article.)) inequality, increased (Equation is included in full-text article.)scatter in the lung under general anesthesia is reflected in increased alveolar deadspace fraction (VDA/VA) customarily measured using end-tidal to arterial (A-a) partial pressure gradients for carbon dioxide. A-a gradients for anesthetic agents such as isoflurane are also significant but have been shown to be inconsistent with those for carbon dioxide under the three-compartment theory. The authors hypothesized that three-compartment VDA/VA calculated using partial pressures of four inhalational agents (VDA/VAG) is different from that calculated using carbon dioxide (VDA/VACO2) measurements, but similar to predictions from multicompartment models of physiologically realistic "log-normal" (Equation is included in full-text article.)distributions. In an observational study, inspired, end-tidal, arterial, and mixed venous partial pressures of halothane, isoflurane, sevoflurane, or desflurane were measured simultaneously with carbon dioxide in 52 cardiac surgery patients at two centers. VDA/VA was calculated from three-compartment model theory and compared for all gases. Ideal alveolar (PAG) and end-capillary partial pressure (Pc'G) of each agent, theoretically identical, were also calculated from end-tidal and arterial partial pressures adjusted for deadspace and venous admixture. Calculated VDA/VAG was larger (mean ± SD) for halothane (0.47 ± 0.08), isoflurane (0.55 ± 0.09), sevoflurane (0.61 ± 0.10), and desflurane (0.65 ± 0.07) than VDA/VACO2 (0.23 ± 0.07 overall), increasing with lower blood solubility (slope [Cis], -0.096 [-0.133 to -0.059], P < 0.001). There was a significant difference between calculated ideal PAG and Pc'G median [interquartile range], PAG 5.1 [3.7, 8.9] versus Pc'G 4.0[2.5, 6.2], P = 0.011, for all agents combined. The slope of the relationship to solubility was predicted by the log-normal lung model, but with a lower magnitude relative to calculated VDA/VAG. Alveolar deadspace for anesthetic agents is much larger than for carbon dioxide and related to blood solubility. Unlike the three-compartment model, multicompartment (Equation is included in full-text article.)scatter models explain this from physiologically realistic gas uptake distributions, but suggest a residual factor other than solubility, potentially diffusion limitation, contributes to deadspace.

Effect of Intravenous Injection of Vitamin C on Postoperative Pulmonary Complications in Patients Undergoing Cardiac Surgery: A Double-Blind, Randomized Trial.

PurposeIn this study, the effect of intravenous vitamin C during surgery on the incidence of postoperative pulmonary complications (PPCs) in patients undergoing cardiopulmonary bypass and cardiac surgery was observed, and its protective effect on the lungs was evaluated to provide a reference for clinical medication.Patients and MethodsPatients undergoing cardiac surgery under cardiopulmonary bypass (CPB) were selected. The patients were divided into group A and group C by random sequence. Patients in group A received intravenous vitamin C 1 g 10 minutes after induction of anesthesia, 10 minutes before cardiac reanimation and at the moment of sternal closure. Patients in group C were intravenously injected with the same volume of saline at the same time. The primary outcome was the postoperative pulmonary complication severity score. Other outcomes were the incidence of PPCs, awakening time, extubation time, length of ICU stay, length of hospital stay, adverse events, oxygenation index (PaO2/FiO2), alveolar arterial oxygen partial pressure difference (A-aDO2), dynamic lung compliance (Cd) and static lung compliance (Cs).ResultsSeventy patients completed the study. Compared to group C, the postoperative pulmonary complication score [2(2–3) vs 2(1–2); P=0.009] and the incidence of postoperative pulmonary complications (32.43% vs 12.12%; P =0.043) were lower in group A. There were no significant differences in awakening time, extubation time, length of ICU stay, length of hospital stay, adverse events, PaO2/FiO2, A-aDO2, Cs, and Cd between the two groups (P>0.05).ConclusionIn summary, this small randomized trial including low-risk cardiac surgery patients shows that intravenous vitamin C may safely be administered and may be helpful to prevent PPCs after cardiac surgery.

Novel coronavirus SARS-CoV-2 (Covid-19) dynamics inside the human body.

SummaryA knowledge‐based cybernetic framework model representing the dynamics of SARS‐CoV‐2 inside the human body has been studied analytically and in silico to explore the pathophysiologic regulations. The following modeling methodology was developed as a platform to introduce a predictive tool supporting a therapeutic approach to Covid‐19 disease. A time‐dependent nonlinear system of ordinary differential equations model was constructed involving type‐I cells, type‐II cells, SARS‐CoV‐2 virus, inflammatory mediators, interleukins along with host pulmonary gas exchange rate, thermostat control, and mean pressure difference. This formalism introduced about 17 unknown parameters. Estimating these unknown parameters requires a mathematical association with the in vivo sparse data and the dynamic sensitivities of the model. The cybernetic model can simulate a dynamic response to the reduced pulmonary alveolar gas exchange rate, thermostat control, and mean pressure difference under a very critical condition based on equilibrium (steady state) values of the inflammatory mediators and system parameters. In silico analysis of the current cybernetical approach with system dynamical modeling can provide an intellectual framework to help experimentalists identify more active therapeutic approaches.

Prevalence of Complete Airway Closure According to Body Mass Index in Acute Respiratory Distress Syndrome.

Complete airway closure during expiration may underestimate alveolar pressure. It has been reported in cases of acute respiratory distress syndrome (ARDS), as well as in morbidly obese patients with healthy lungs. The authors hypothesized that complete airway closure was highly prevalent in obese ARDS and influenced the calculation of respiratory mechanics. In a post hoc pooled analysis of two cohorts, ARDS patients were classified according to body mass index (BMI) terciles. Low-flow inflation pressure-volume curve and partitioned respiratory mechanics using esophageal manometry were recorded. The authors' primary aim was to compare the prevalence of complete airway closure according to BMI terciles. Secondary aims were to compare (1) respiratory system mechanics considering or not considering complete airway closure in their calculation, and (2) and partitioned respiratory mechanics according to BMI. Among the 51 patients analyzed, BMI was less than 30 kg/m2 in 18, from 30 to less than 40 in 16, and greater than or equal to 40 in 17. Prevalence of complete airway closure was 41% overall (95% CI, 28 to 55; 21 of 51 patients), and was lower in the lowest (22% [3 to 41]; 4 of 18 patients) than in the highest BMI tercile (65% [42 to 87]; 11 of 17 patients). Driving pressure and elastances of the respiratory system and of the lung were higher when complete airway closure was not taken into account in their calculation. End-expiratory esophageal pressure (ρ = 0.69 [95% CI, 0.48 to 0.82]; P < 0.001), but not chest wall elastance, was associated with BMI, whereas elastance of the lung was negatively correlated with BMI (ρ = -0.27 [95% CI, -0.56 to -0.10]; P = 0.014). Prevalence of complete airway closure was high in ARDS and should be taken into account when calculating respiratory mechanics, especially in the most morbidly obese patients.

Expiratory Pressure Generation In Adult Survivors Of Preterm Birth

Adult survivors of preterm birth (PRE) have arrested lung development resulting in lower pulmonary function compared to their counterparts born at full term (CON). PRE have normal lung volumes, but lower expiratory airflow, which could be caused, in part, by a lesser driving (alveolar) pressure. During forced expiration alveolar pressure is the sum of pleural pressure, a function of respiratory muscle effort/strength, and lung recoil pressure. Whether or not PRE have normal respiratory muscle strength and/or lung compliance (CL) has not yet been explored. PURPOSE: The purpose of this study was to quantify respiratory muscle strength and CL in PRE and CON. Based upon the existing literature, we hypothesized that PRE and CON will have equivalent respiratory muscle strength and CL. METHODS: To date, n = 8 PRE and n = 5 CON, visited the lab on two occasions. First, subjects performed standard spirometry (e.g. fast and slow vital capacity maneuvers). Next, to assess respiratory muscle strength, subjects performed maximal inspiratory and maximal expiratory pressure maneuvers (MIP and MEP, respectively). For MIP, subjects inhaled maximally against an occluded mouthpiece at residual volume. For MEP, subjects exhaled exhale maximally against an occluded mouthpiece at total lung capacity. Each maneuver was performed 3-5 times. On the second visit, CL was measured. To do so, subjects were instrumented with an esophageal balloon catheter and performed quasi-static expiratory deflation curves (i.e., very slow exhalations from total lung capacity to residual volume). To test for differences in MIP, MEP, and CL between groups we computed multiple independent samples t-tests with significance set to p<0.05. RESULTS: We found no difference in MIP (-130.6 ± 29.3 vs. -106.5 ± 36.1 cm H2O; p = 0.24) or MEP (165.7 ± 42.9 vs.121.0 ± 51.6 cm H2O; p = 0.14) between CON and PRE, respectively. Likewise, CL was comparable between CON (0.29 ± 0.11 L/cm H2O) and PRE (0.33 ± 0.10 L/cm H2O; p = 0.53). CONCLUSION: Our data suggests no effect of birth status on the ability to generate expiratory pressure during forced expiration. Likewise, results suggest that the lower pulmonary function in PRE is not the result of a lesser driving pressure, but instead may be the result of excessive airflow resistance. Support: Hooper Undergraduate Research Award from NAU.

Estimating the Damaging Power of High-Stress Ventilation.

Redirection of our clinical attention from the pressures and volumes of the individual cycle to the broader and more inclusive considerations of energy load and power has untapped potential to reduce iatrogenic risk from ventilation (ie, ventilator-induced lung injury). Power is the product of breathing frequency and inflation energy per breath. Yet, while feasible to calculate at the bedside, measuring total power may not prove to be precise enough for accurate prediction of ventilator-induced lung injury, even if normalized to lung capacity (ie, specific power). The same power value can be reached by a multitude of frequency and tidal volume combinations, not all of which carry equal risk of damage. If some arbitrary level of alveolar pressure were accepted as a sharply defined hazard boundary, a rather straightforward geometric analysis theoretically would allow partitioning of overall tidal energy into components above and below a damage threshold. In this discussion, we introduce the concept of quantitative power partitioning and illustrate how tidal energy and power might be deconstructed into their key parts.

In silico study of airway/lung mechanics in normal human breathing

The airway/lung mechanics is usually represented with nonlinear 0-D models based on a pneumatic-electrical analogy.The aim of this work is to provide a detailed description of the human respiratory mechanics in healthy and diseased conditions. The model used for this purpose employs some known constitutive functions of the main components of the respiratory system. We give a detailed mathematical description of these functions and subsequently derive additional key ones. We are interested not only in the main output such as airflow at the mouth or alveolar pressure and volume, but also in other quantities such as resistance and pressure drop across each element of the system and even recoil and compliance of the chest wall.Pathological conditions are simulated by altering the parameters of the constitutive functions. Results show that increased upper airway resistance induces airflow reduction with concomitant narrowing of volume and pressure ranges without affecting lung compliance. Instead, increased elastic recoil leads to low volumes and decreased lung compliance.The model could be used in the study of the interaction between respiratory and cardiovascular systems in pathophysiological conditions.

The equal pressure point is greater in men than women near total lung capacity

The equal pressure point (EPP) states that expiratory flow limitation occurs at the precise location along the tracheobronchial tree where intraluminal and peribronchial pressures are equal (i.e., where the local transmural pressure is 0 cmH2O). The EPP may be determined numerically via the expiratory isovolume pressure flow (IVPF) curve. For instance, using data from a given isovolume curve, the EPP is determined as the point along the x‐axis at which pressure‐flow data fails to conform to Rohrer’s equation: driving pressure = k1(flow) + k2(flow2). The probability of incurring expiratory flow‐limitation can be greatly determined by the EPP such that a lower EPP at a given lung volume requires only minimal pressure development to create a flow‐limiting segment during expiration. The EPP is affected by two principal factors: lung elastic recoil (PLUNG) &amp; airway geometry. Given recent evidence suggesting that airway geometry is different between men &amp; women, we sought to determine whether the EPP is likewise affected by sex in healthy adults.PurposeDetermine whether or not there is an effect of sex on the magnitude of the EPP.MethodsTo address this question, 11 men (23.1 ± 4.8 years) and 12 women (21.2 ± 1.0 years) completed a study requiring two visits to the laboratory. On the initial visit, we obtained written informed consent and conducted spirometry to ensure subjects met the inclusion criteria of normal (&gt;85% of predicted) lung function. During the second visit, a balloon catheter was passed intranasally to the lower one‐third of the esophagus and remained there for the duration of the visit to measure esophageal pressure (PES). Subjects then performed a minimum of 10–15 graded vital capacity maneuvers from 100‐5% of maximal effort. Data were imported into Matlab and, using custom‐written code, multiple calculations were performed. First, the lowest effort vital capacity efforts were taken as quasi‐static expiratory deflations of the lung and the negative sign of PES was taken to equal PLUNG. Second, alveolar pressure (PALV) was taken to equal PES + PLUNG. Finally, the EPP was determined by iteratively fitting Rohrer’s equation to pressure‐flow data at a given iso‐volume. The pressure at which Rohrer’s equation no longer adequately fit the data (&gt;5% error) was termed the EPP. To test for an effect of sex and lung volume, a two‐way ANOVA was computed. Pairwise comparisons were adjusted for multiple comparisons using the Tukey‐Sidak post hoc test.ResultsThere was no effect of sex on PLUNG, but PALV was greater in men than women throughout the entire VC range. EPP was significantly greater in men than women during the initial half of VC (95‐55% of VC) (p &lt; 0.05), but not the remaining half (p &gt; 0.05).ConclusionBecause PLUNG did not differ between men and women, the differing location of EPP was the result of a greater PES in men. This suggests that the larger airways present in men are more resistant to compression than those of women.

Optical Determination of Age‐Related Changes in Subpleural Collagen of Live Human Lungs

The impact of age on lung physiology is not known. Collagen is an important determinant of lung structure and function. Therefore, age‐related changes in collagen quantity, geometry and structure can lead to changes in lung function. CT scans of asymptomatic patients reveal age‐dependent increase of subpleural radiologic densities, called interstitial lung abnormalities (ILAs) that predispose to pulmonary fibrosis. However it is not known whether ILAs are collagen deposits that impair alveolar function. Since real‐time fluorescence microscopy (RFI) of the human lung has not been done, we carried out two‐photon and confocal microscopy (2P‐CF) of live, transplant‐reject lungs to determine the age‐related profile of subpleural collagen density (SCD) and whether this affects surfactant secretion. For RFI, we cannulated the bronchus and the artery of the lingular lobe to enable inflation and perfusion. Then, we held the lobe at constant alveolar pressure of 5 cmH2O. To stain alveolar epithelial cells, we subpleurally injected fluorescent dyes by means of a 31‐gauge needle. We detected subpleural collagen as the fluorescence of second harmonics generation (SHG). We quantified subpleural collagen density (SCD) as the integrated collagen fluorescence occurring in the space between the visceral pleura and the alveolar epithelium. To determine surfactant secretion, we quantified the timed appearance of lipid‐sensitive fluorescence in the alveolar space following a transient hyperinflation of the lingular lobe. Our data show that subpleural collagen was evident as well‐defined and evenly spaced cables in young lungs (median age 37 years). By contrast, subpleural collagen in aged lungs (median age 63 years) was marked by poorly formed cables surrounded by diffuse SHG fluorescence. We show that SCDs varied in different regions in all lungs and that SCD was significantly higher in aged than young lungs. Further, in high SCD regions, hyperinflation‐induced alveolar expansion and surfactant secretion were abrogated (p&lt;0.05). Thus, SCDs increase with age and negatively regulate surfactant secretion from adjacent alveoli. SCDs may correspond to ILAs. Our findings raise the novel possibility that a risk‐factor in development of pulmonary fibrosis might be the disruption of alveolar homeostasis caused by age‐related changes in subpleural collagen (HL145547, HL36024).Support or Funding InformationHL145547, HL36024

Thoracic gas compression during forced expiration is greater in men than women.

Intrapleural pressure during a forced vital capacity (VC) maneuver is often in excess of that required to generate maximal expiratory airflow. This excess pressure compresses alveolar gas (i.e., thoracic gas compression [TGC]), resulting in underestimated forced expiratory flows (FEFs) at a given lung volume. It is unknown if TGC is influenced by sex; however, because men have larger lungs and stronger respiratory muscles, we hypothesized that men would have greater TGC. We examined TGC across the “effort‐dependent” region of VC in healthy young men (n = 11) and women (n = 12). Subjects performed VC maneuvers at varying efforts while airflow, volume, and esophageal pressure (POES) were measured. Quasistatic expiratory deflation curves were used to obtain lung recoil (PLUNG) and alveolar pressures (i.e., PALV = POES–PLUNG). The raw maximal expiratory flow–volume (MEFVraw) curve was obtained from the “maximum effort” VC maneuver. The TGC‐corrected curve was obtained by constructing a “maximal perimeter” curve from all VC efforts (MEFVcorr). TGC was examined via differences between curves in FEFs (∆FEF), area under the expiratory curves (∆AEX), and estimated compressed gas volume (∆VGC) across the VC range. Men displayed greater total ∆AEX (5.4 ± 2.0 vs. 2.0 ± 1.5 L2·s−1; p < .001). ∆FEF was greater in men at 25% of exhaled volume only (p < .05), whereas ∆VGC was systematically greater in men across the entire VC (main effect; p < .05). PALV was also greater in men throughout forced expiration (p < .01). Taken together, these findings demonstrate that men display more TGC, occurring early in forced expiration, likely due to greater expiratory pressures throughout the forced VC maneuver.

CrossTalk opposing view: Barometric pressure, independent of , is not the forgotten parameter in altitude physiology and mountain medicine.

CrossTalk opposing view: Barometric pressure, independent of , is not the forgotten parameter in altitude physiology and mountain medicine.

Oxygen therapy in chronic obstructive pulmonary disease: insight from convex optimisation

Application of additional oxygen for managing acute exacerbation of Chronic Obstructive Pulmonary Disease (COPD) has an associated risk of oxygen toxicity. The aim of this work is to determine the appropriate level of oxygen for managing such conditions using a mathematical model. In this approach, a noted respiratory regulation model is modified to simulate COPD condition. Using the proposed model, it is established that higher inspired oxygen increases alveolar oxygen, as well as alveolar carbon dioxide. It is also shown that higher inspired oxygen increases oxygen saturation and lowers the ventilation-perfusion ratio mismatch. Using quadratic combination of alveolar oxygen and carbon dioxide pressure, an objective function is proposed to calculate the optimal level of inspired oxygen. Results obtained from this analysis methodology are in agreement with clinical data.

Venous return and pulmonary hemodynamics under the positive end-expiratory pressure mechanical ventilation

In the review we have discussed the mechanisms of the changes of the venous return and pulmonary hemodynamics which take place in clinical cases of the mechanical lung ventilation with positive end-expiratory pressure. In these conditions the elevating of right atrial pressure does not cause the decreasing of the venous return, because the mean circulatory filling pressure also increases. Thus, the gradient for venous return remains relatively constant. In case of the mechanical lung ventilation with positive end-expiratory pressure the decreasing of the venous return is the result of the elevation of the venous resistance as consequence of the direct increasing of the intrathoracic and transdiaphragmatic pressures and activation of the reflectory neurogenic mechanisms. In the conditions, indicated above, the increased alveolar pressure leads to the improvement of the diffused lung capacity for oxygen, which decreases the manifestations of the hypoxic pulmonary vasoconstriction and thus diminishes pulmonary vascular resistance. The character of changes of the last one is determined by the reactions of the two types (alveolar and extraalveolar) intraparenchimal pulmonary vessels. This leads to the changes of the resistive and capacitive functions of the pulmonary vessels. In case of the high levels of the positive end-expiratory pressure (more than 30 cm of water column) the value of alveolar pressure is comparable or even more excessive than pulmonary artery pressure (1216 mm Hg), which can be the reason of the decreasing of the right ventricular contractility and the venous return. The increasing of the capillary filtration coefficient of pulmonary vessels in the conditions of the mechanical lung ventilation with positive end-expiratory pressure can be the result of the activation of the mechanosensitive transient receptor potential vanilloid-4 (TRPV4) channels and the increasing endothelial calcium entry.

Association between hydrogen sulfide and OSA-associated hypertension: a clinical study.

We sought to unravel the role of hydrogen sulfide (H2S) in the development of hypertension in patients with obstructive sleep apnea (OSA). The study sample included 80 patients with OSA and 45 healthy controls. All subjects underwent measurement of blood pressure (BP) and serum H2S level in the morning. Twentynine of the 39 patients with OSA and concomitant hypertension and 23 of the 41 patients with OSA but no concomitant hypertension received continuous positive alveolar pressure (CPAP) therapy for 4 weeks. Twenty-four-hour ambulatory BP and serum H2S were determined before and after CPAP. Respiratory indices including apnea hypopnea index (AHI), lowest oxygen saturation (SaO2), and length of time < 90% saturated (T90) were determined by polysomnography. Associations between H2S, BP, respiratory indices, and changes with CPAP were analyzed. OSA patients had significantly higher systolic BP (p = 0.003) and diastolic BP (p = 0.009) and lower H2S levels (p = 0.02) compared to healthy controls. H2S negatively correlated with AHI (p = 0.005), T90 (p = 0.009), morning systolic BP (p = 0.02), and morning diastolic BP (p = 0.03). All respiratory indices were significantly improved (p < 0.05) after CPAP in OSA patients with or without hypertension. BP was significantly reduced and H2S significantly increased after CPAP in OSA patients with hypertension (p < 0.05) but not in OSA patients without hypertension (p > 0.05). Multivariate linear regression analysis demonstrated that 24h systolic BP and 24h diastolic BP correlated with H2S as well as their changes after CPAP treatment. Reduction in H2S may play a role in the pathogenesis of hypertension in patients with OSA.

Analysis of pressure-time and flow-time curve in ventilator

To better understand the significance of the pressure-time curve and flow-time curve from the perspective of PB840 ventilator working principle. (1) Mechanical principle: flow supply valves (air valve and oxygen valve) and exhalation valve in PB840 ventilator were controlled to achieve the ventilation target (volume or pressure) by the central processing unit according to the monitoring data from pressure sensors (P1 at the supply side, P2 at the exhalation side) and flow sensors (Q1 at the air side, Q2 at the oxygen side, Q3 at the exhalation side). (2) The essence of curve: each point means a value of pressure or flow at a certain time measured by the sensors or calculated by the system. (3) The respiratory process could be divided into inspiratory part, expiratory part, and the connection part from expiratory to inspiratory. The air running state and the respiratory mechanics relationship at the three parts could be inferred according to the form of curves. (1) Inspiratory process: at volume-controlled and constant flow ventilation: there should be a relationship "Pc-Pa = XR" between alveolar pressure (Pa) and circuit pressure (Pc) according to Ohm law. So, the Pc curve (pressure-time curve) could indirectly reflect the Pa curve with the flow (X) and resistance (R) being constant. At pressure-set ventilation: it is the goal of ventilator to maintain the Pc at the target level. So, the stability of the target pressure line in pressure-time curve reflects the matching ability of the flow supply valves and the exhalation valve. (2) Expiratory process: it could be divided into pre-expiratory [without basic flow (Ba) or bias flow (Bi)] and post-expiratory (with Ba or Bi), where Ba or Bi is equal to "Q1+Q2". So, the mathematical function are "X(t) = Q3t" in pre-part, and "X(t) = Q3t-(Q1t+Q2t)" in post-part. The relationship between pressure and flow at peak expiratory flow point: it could be found that there is an obvious time span and area formation under the curve from 0 to peak point (Fpeak) after stretching the abscissa axis of flow-time curve. It means that some gas have been discharged from the lung when it arrives at the peak point. So, the alveolar pressure should be lower than the platform pressure at the point (Pplat). The circuit pressure is significantly higher than positive end expiratory pressure (PEEP) at the point in the stretching axis diagram. So, it means that the formula "RE = (Pplat-PEEP)/Fpeak" to calculate the expiratory resistance (E) is unreasonable in the angle of Ohm law. (3) The process from exhalation to inspiratory: according to the difference of the starting point of the conversion, it could be divided into two cases: one is that the inspiratory started from the ending of exhalation. Here, the inhaling starting point is lying in the abscissa axis. The other is that the inspiratory started before the ending of exhalation (with endogenous positive end expiratory pressure). Here, the starting point is lying below the abscissa axis, and the slope of the following curve is obviously larger than the slope of natural expiratory curve. According to the difference of results from the starting point to the end of the inhalation triggering effort, it could be divided into two cases: one is that it reach the trigger point. Here, the expiratory curve extends upward from or below the horizontal axis until an effective air supply is triggered. The other is that it could not reach the trigger point. Here, the expiratory curve extends upward from or below the horizontal axis, but then runs downward (meaning exhaling). It is helpful to analyze the ventilation state, ventilation failure, and the causes of man-machine confrontation with understanding the ventilation principle and the air route map of the ventilator.

Trans Alveolar Pressure Measurement as an Index for Lung Recruitment.

Trans Alveolar Pressure Measurement as an Index for Lung Recruitment.

Differences in alveolo-capillary equilibration in healthy subjects on facing O2 demand

Oxygen diffusion across the air-blood barrier in the lung is commensurate with metabolic needs and ideally allows full equilibration between alveolar and blood partial oxygen pressures. We estimated the alveolo-capillary O2 equilibration in 18 healthy subjects at sea level at rest and after exposure to increased O2 demand, including work at sea level and on hypobaric hypoxia exposure at 3840 m (PA ~ 50 mmHg). For each subject we estimated O2 diffusion capacity (DO2), pulmonary capillary blood volume (Vc) and cardiac output (dot{Q}). We derived blood capillary transit time {boldsymbol{(}}{boldsymbol{T}}{boldsymbol{t}}{boldsymbol{=}}frac{{boldsymbol{V}}{boldsymbol{c}}}{dot{{boldsymbol{Q}}}}{boldsymbol{)}} and the time constant of the equilibration process ({boldsymbol{tau }}{boldsymbol{=}}frac{{boldsymbol{beta }}{boldsymbol{V}}{boldsymbol{c}}}{{boldsymbol{D}}{{boldsymbol{O}}}_{{boldsymbol{2}}}}, β being the slope of the hemoglobin dissociation curve). O2 equilibration at the arterial end of the pulmonary capillary was defined as {{bf{L}}}_{{bf{e}}{bf{q}}}{boldsymbol{=}}{{bf{e}}}^{{boldsymbol{-}}frac{{bf{T}}t}{{boldsymbol{tau }}}}. Leq greately differed among subjects in the most demanding O2 condition (work in hypoxia): lack of full equilibration was found to range from 5 to 42% of the alveolo-capillary PO2 gradient at the venous end. The present analysis proves to be sensible enough to highlight inter-individual differences in alveolo-capillary equilibration among healthy subjects.