Imaging the pulmonary vasculature in acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is characterized by a redistribution of regional lung perfusion that impairs gas exchange. While speculative, experimental evidence suggests that perfusion redistribution may contribute to regional inflammation and modify disease progression. Unfortunately, tools to visualize and quantify lung perfusion in patients with ARDS are lacking. This review explores recent advances in perfusion imaging techniques that aim to understand the pulmonary circulation in ARDS. Dynamic contrast-enhanced computed tomography captures first-pass kinetics of intravenously injected dye during continuous scan acquisitions. Different contrast characteristics and kinetic modeling have improved its topographic measurement of pulmonary perfusion with high spatial and temporal resolution. Dual-energy computed tomography can map the pulmonary blood volume of the whole lung with limited radiation exposure, enabling its application in clinical research. Electrical impedance tomography can obtain serial topographic assessments of perfusion at the bedside in response to treatments such as inhaled nitric oxide and prone position. Ongoing technological improvements and emerging techniques will enhance lung perfusion imaging and aid its incorporation into the care of patients with ARDS.

Esophageal balloon catheter system identification to improve respiratory effort time features and amplitude determination.

Objective. Understanding a patient's respiratory effort and mechanics is essential for the provision of individualized care during mechanical ventilation. However, measurement of transpulmonary pressure (the difference between airway and pleural pressures) is not easily performed in practice. While airway pressures are available on most mechanical ventilators, pleural pressures are measured indirectly by an esophageal balloon catheter. In many cases, esophageal pressure readings take other phenomena into account and are not a reliable measure of pleural pressure.Approach.A system identification approach was applied to provide accurate pleural measures from esophageal pressure readings. First, we used a closed pressurized chamber to stimulate an esophageal balloon and model its dynamics. Second, we created a simplified version of an artificial lung and tried the model with different ventilation configurations. For validation, data from 11 patients (five male and six female) were used to estimate respiratory effort profile and patient mechanics.Main results.After correcting the dynamic response of the balloon catheter, the estimates of resistance and compliance and the corresponding respiratory effort waveform were improved when compared with the adjusted quantities in the test bench. The performance of the estimated model was evaluated using the respiratory pause/occlusion maneuver, demonstrating improved agreement between the airway and esophageal pressure waveforms when using the normalized mean squared error metric. Using the corrected muscle pressure waveform, we detected start and peak times 130 ± 50 ms earlier and a peak amplitude 2.04 ± 1.46 cmH2O higher than the corresponding estimates from esophageal catheter readings.Significance.Compensating the acquired measurements with system identification techniques makes the readings more accurate, possibly better portraying the patient's situation for individualization of ventilation therapy.

Electrical Impedance Tomography Identifies Evolution of Regional Perfusion in a Porcine Model of Acute Respiratory Distress Syndrome.

BACKGROUND: Bedside electrical impedance tomography could be useful to visualize evolving pulmonary perfusion distributions when acute respiratory distress syndrome worsens or in response to ventilatory and positional therapies. In experimental acute respiratory distress syndrome, this study evaluated the agreement of electrical impedance tomography and dynamic contrast-enhanced computed tomography perfusion distributions at two injury time points and in response to increased positive end-expiratory pressure (PEEP) and prone position. METHODS: Eleven mechanically ventilated (VT 8 ml · kg-1) Yorkshire pigs (five male, six female) received bronchial hydrochloric acid (3.5 ml · kg-1) to invoke lung injury. Electrical impedance tomography and computed tomography perfusion images were obtained at 2 h (early injury) and 24 h (late injury) after injury in supine position with PEEP 5 and 10 cm H2O. In eight animals, electrical impedance tomography and computed tomography perfusion imaging were also conducted in the prone position. Electrical impedance tomography perfusion (QEIT) and computed tomography perfusion (QCT) values (as percentages of image total) were compared in eight vertical regions across injury stages, levels of PEEP, and body positions using mixed-effects linear regression. The primary outcome was agreement between QEIT and QCT, defined using limits of agreement and Pearson correlation coefficient. RESULTS: Pao2/Fio2 decreased over the course of the experiment (healthy to early injury, -253 [95% CI, -317 to -189]; early to late injury, -88 [95% CI, -151 to -24]). The limits of agreement between QEIT and QCT were -4.66% and 4.73% for the middle 50% quantile of average regional perfusion, and the correlation coefficient was 0.88 (95% CI, 0.86 to 0.90]; P < 0.001). Electrical impedance tomography and computed tomography showed similar perfusion redistributions over injury stages and in response to increased PEEP. QEIT redistributions after positional therapy underestimated QCT in ventral regions and overestimated QCT in dorsal regions. CONCLUSIONS: Electrical impedance tomography closely approximated computed tomography perfusion measures in experimental acute respiratory distress syndrome, in the supine position, over injury progression and with increased PEEP. Further validation is needed to determine the accuracy of electrical impedance tomography in measuring perfusion redistributions after positional changes.

Regional lung perfusion using different indicators in electrical impedance tomography.

Management of acute respiratory distress syndrome (ARDS) is classically guided by protecting the injured lung and mitigating damage from mechanical ventilation. Yet the natural history of ARDS is also dictated by disruption in lung perfusion. Unfortunately, diagnosis and treatment are hampered by the lack of bedside perfusion monitoring. Electrical impedance tomography is a portable imaging technique that can estimate regional lung perfusion in experimental settings from the kinetic analysis of a bolus of an indicator with high conductivity. Hypertonic sodium chloride has been the standard indicator. However, hypertonic sodium chloride is often inaccessible in the hospital, limiting practical adoption. We investigated whether regional lung perfusion measured using electrical impedance tomography is comparable between indicators. Using a swine lung injury model, we determined regional lung perfusion (% of total perfusion) in five pigs, comparing 12% sodium chloride to 8.4% sodium bicarbonate across stages of lung injury and experimental conditions (body position, positive end-expiratory pressure). Regional lung perfusion for four lung regions was determined from maximum slope analysis of the indicator-based impedance signal. Estimates of regional lung perfusion between indicators were compared in the lung overall and within four lung regions. Regional lung perfusion estimated with a sodium bicarbonate indicator agreed with a hypertonic sodium chloride indicator overall (mean bias 0%, limits of agreement -8.43%, 8.43%) and within lung quadrants. The difference in regional lung perfusion between indicators did not change across experimental conditions. Sodium bicarbonate may be a comparable indicator to estimate regional lung perfusion using electrical impedance tomography.NEW & NOTEWORTHY Electrical impedance tomography is an emerging tool to measure regional lung perfusion using kinetic analysis of a conductive indicator. Hypertonic sodium chloride is the standard agent used. We measured regional lung perfusion using another indicator, comparing hypertonic sodium chloride to sodium bicarbonate in an experimental swine lung injury model. We found strong agreement between the two indicators. Sodium bicarbonate may be a comparable indicator to measure regional lung perfusion with electrical impedance tomography.

Improving pulmonary perfusion assessment by dynamic contrast-enhanced computed tomography in an experimental lung injury model.

Pulmonary perfusion has been poorly characterized in acute respiratory distress syndrome (ARDS). Optimizing protocols to measure pulmonary blood flow (PBF) via dynamic contrast-enhanced (DCE) computed tomography (CT) could improve understanding of how ARDS alters pulmonary perfusion. In this study, comparative evaluations of injection protocols and tracer-kinetic analysis models were performed based on DCE-CT data measured in ventilated pigs with and without lung injury. Ten Yorkshire pigs (five with lung injury, five healthy) were anesthetized, intubated, and mechanically ventilated; lung injury was induced by bronchial hydrochloric acid instillation. Each DCE-CT scan was obtained during a 30-s end-expiratory breath-hold. Reproducibility of PBF measurements was evaluated in three pigs. In eight pigs, undiluted and diluted Isovue-370 were separately injected to evaluate the effect of contrast viscosity on estimated PBF values. PBF was estimated with the peak-enhancement and the steepest-slope approach. Total-lung PBF was estimated in two healthy pigs to compare with cardiac output measured invasively by thermodilution in the pulmonary artery. Repeated measurements in the same animals yielded a good reproducibility of computed PBF maps. Injecting diluted isovue-370 resulted in smaller contrast-time curves in the pulmonary artery (P < 0.01) and vein (P < 0.01) without substantially diminishing peak signal intensity (P = 0.46 in the pulmonary artery) compared with the pure contrast agent since its viscosity is closer to that of blood. As compared with the peak-enhancement model, PBF values estimated by the steepest-slope model with diluted contrast were much closer to the cardiac output (R2 = 0.82) as compared with the peak-enhancement model. DCE-CT using the steepest-slope model and diluted contrast agent provided reliable quantitative estimates of PBF.NEW & NOTEWORTHY Dynamic contrast-enhanced CT using a lower-viscosity contrast agent in combination with tracer-kinetic analysis by the steepest-slope model improves pulmonary blood flow measurements and assessment of regional distributions of lung perfusion.

Modulation of pulmonary blood flow in patients with acute respiratory failure.

BACKGROUND: Impairment of ventilation and perfusion (V/Q) matching is a common mechanism leading to hypoxemia in patients with acute respiratory failure requiring intensive care unit (ICU) admission. While ventilation has been thoroughly investigated, little progress has been made to monitor pulmonary perfusion at the bedside and treat impaired blood distribution. The study aimed to assess real-time changes in regional pulmonary perfusion in response to a therapeutic intervention. METHODS: Single-center prospective study that enrolled adult patients with ARDS caused by SARS-Cov-2 who were sedated, paralyzed, and mechanically ventilated. The distribution of pulmonary perfusion was assessed through electrical impedance tomography (EIT) after the injection of a 10-ml bolus of hypertonic saline. The therapeutic intervention consisted in the administration of inhaled nitric oxide (iNO), as rescue therapy for refractory hypoxemia. Each patient underwent two 15-min steps at 0 and 20 ppm iNO, respectively. At each step, respiratory, gas exchange, and hemodynamic parameters were recorded, and V/Q distribution was measured, with unchanged ventilatory settings. RESULTS: Ten 65 [56-75] years old patients with moderate (40%) and severe (60%) ARDS were studied 10 [4-20] days after intubation. Gas exchange improved at 20 ppm iNO (PaO2/FiO2 from 86 ± 16 to 110 ± 30 mmHg, p = 0.001; venous admixture from 51 ± 8 to 45 ± 7%, p = 0.0045; dead space from 29 ± 8 to 25 ± 6%, p = 0.008). The respiratory system's elastic properties and ventilation distribution were unaltered by iNO. Hemodynamics did not change after gas initiation (cardiac output 7.6 ± 1.9 vs. 7.7 ± 1.9 L/min, p = 0.66). The EIT pixel perfusion maps showed a variety of patterns of changes in pulmonary blood flow, whose increase positively correlated with PaO2/FiO2 increase (R2 = 0.50, p = 0.049). CONCLUSIONS: The assessment of lung perfusion is feasible at the bedside and blood distribution can be modulated with effects that are visualized in vivo. These findings might lay the foundations for testing new therapies aimed at optimizing the regional perfusion in the lungs.

Mixed-integer quadratic programming approach for noninvasive estimation of respiratory effort profile during pressure support ventilation.

Information about respiratory mechanics such as resistance, elastance, and muscular pressure is important to mitigate ventilator-induced lung injury. Particularly during pressure support ventilation, the available options to quantify breathing effort and calculate respiratory system mechanics are often invasive or complex. We herein propose a robust and flexible estimation of respiratory effort better than current methods. We developed a method for non-invasively estimating breathing effort using only flow and pressure signals. Mixed-integer quadratic programming (MIQP) was employed, and the binary variables were the switching moments of the respiratory effort waveform. Mathematical constraints, based on ventilation physiology, were set for some variables to restrict feasible solutions. Simulated and patient data were used to verify our method, and the results were compared to an established estimation methodology. Our algorithm successfully estimated the respiratory effort, resistance, and elastance of the respiratory system, resulting in more robust performance and faster solver times than a previously proposed algorithm that used quadratic programming (QP) techniques. In a numerical simulation benchmark, the worst-case errors for resistance and elastance were 25% and 23% for QP versus <0.1% and <0.1% for MIQP, whose solver times were 4.7 s and 0.5 s, respectively. This approach can estimate several breathing effort profiles and identify the respiratory system's mechanical properties in invasively ventilated critically ill patients.

Amorphization and modified release of ibuprofen by post-synthetic and solvent-free loading into tailored silica aerogels.

Promising active pharmaceutical ingredients (APIs) often exhibit poor aqueous solubility and thus a low bioavailability that substantially limits their pharmaceutical application. Hence, efficient formulations are required for an effective translation into highly efficient drug products. One strategy is the preservation of an amorphous state of the API within a carrier matrix, which leads to enhanced dissolution. In this work, mesoporous silica aerogels (SA) were utilized as a carrier matrix for the amorphization of the poorly water-soluble model drug ibuprofen. Loading of tailored SA was performed post-synthetically and solvent-free, either by co-milling or via the melting method. Thorough analyses of these processes demonstrated the influence of macrostructural changes during the drying and grinding process on the microstructural properties of the SA. Furthermore, interfacial SA-drug interaction properties were selectively tuned by attaching terminal hydrophilic amino- or hydrophobic methyl groups to the surface of the gel. We demonstrate that not only the chemical surface properties of the SA, but also formulation-related parameters, such as the carrier-to-drug ratio, as well as process-related parameters, such as the drug loading method, decisively influence the ibuprofen adsorption efficiency. In addition, the drug-loaded SA formulations exhibited a remarkable physical stability over a period of 6 months. Furthermore, the release behavior is shown to change considerably with different surface properties of the SA matrix. Hence, the reported results demonstrate that utilizing specifically processed and modified SA offers a compelling technique for enhancement of the bioavailability of poorly-water soluble APIs and a versatile adjustment of their release profile.

Sequential lateral positioning as a new lung recruitment maneuver: an exploratory study in early mechanically ventilated Covid-19 ARDS patients.

BACKGROUND: A sequential change in body position from supine-to-both lateral positions under constant ventilatory settings could be used as a postural recruitment maneuver in case of acute respiratory distress syndrome (ARDS), provided that sufficient positive end-expiratory pressure (PEEP) prevents derecruitment. This study aims to evaluate the feasibility and physiological effects of a sequential postural recruitment maneuver in early mechanically ventilated COVID-19 ARDS patients. METHODS: A cohort of 15 patients receiving lung-protective mechanical ventilation in volume-controlled with PEEP based on recruitability were prospectively enrolled and evaluated in five sequentially applied positions for 30 min each: Supine-baseline; Lateral-1st side; 2nd Supine; Lateral-2nd side; Supine-final. PEEP level was selected using the recruitment-to-inflation ratio (R/I ratio) based on which patients received PEEP 12 cmH2O for R/I ratio ≤ 0.5 or PEEP 15 cmH2O for R/I ratio > 0.5. At the end of each period, we measured respiratory mechanics, arterial blood gases, lung ultrasound aeration, end-expiratory lung impedance (EELI), and regional distribution of ventilation and perfusion using electric impedance tomography (EIT). RESULTS: Comparing supine baseline and final, respiratory compliance (29 ± 9 vs 32 ± 8 mL/cmH2O; p < 0.01) and PaO2/FIO2 ratio (138 ± 36 vs 164 ± 46 mmHg; p < 0.01) increased, while driving pressure (13 ± 2 vs 11 ± 2 cmH2O; p < 0.01) and lung ultrasound consolidation score decreased [5 (4-5) vs 2 (1-4); p < 0.01]. EELI decreased ventrally (218 ± 205 mL; p < 0.01) and increased dorsally (192 ± 475 mL; p = 0.02), while regional compliance increased in both ventral (11.5 ± 0.7 vs 12.9 ± 0.8 mL/cmH2O; p < 0.01) and dorsal regions (17.1 ± 1.8 vs 18.8 ± 1.8 mL/cmH2O; p < 0.01). Dorsal distribution of perfusion increased (64.8 ± 7.3% vs 66.3 ± 7.2%; p = 0.01). CONCLUSIONS: Without increasing airway pressure, a sequential postural recruitment maneuver improves global and regional respiratory mechanics and gas exchange along with a redistribution of EELI from ventral to dorsal lung areas and less consolidation. Trial registration ClinicalTrials.gov, NCT04475068. Registered 17 July 2020, https://clinicaltrials.gov/ct2/show/NCT04475068.

Electrical impedance tomography to titrate positive end-expiratory pressure in COVID-19 acute respiratory distress syndrome.

RATIONALE: Patients with coronavirus disease-19-related acute respiratory distress syndrome (C-ARDS) could have a specific physiological phenotype as compared with those affected by ARDS from other causes (NC-ARDS). OBJECTIVES: To describe the effect of positive end-expiratory pressure (PEEP) on respiratory mechanics in C-ARDS patients in supine and prone position, and as compared to NC-ARDS. The primary endpoint was the best PEEP defined as the smallest sum of hyperdistension and collapse. METHODS: Seventeen patients with moderate-to-severe C-ARDS were monitored by electrical impedance tomography (EIT) and evaluated during PEEP titration in supine (n = 17) and prone (n = 14) position and compared with 13 NC-ARDS patients investigated by EIT in our department before the COVID-19 pandemic. RESULTS: As compared with NC-ARDS, C-ARDS exhibited a higher median best PEEP (defined using EIT as the smallest sum of hyperdistension and collapse, 12 [9, 12] vs. 9 [6, 9] cmH2O, p < 0.01), more collapse at low PEEP, and less hyperdistension at high PEEP. The median value of the best PEEP was similar in C-ARDS in supine and prone position: 12 [9, 12] vs. 12 [10, 15] cmH2O, p = 0.59. The response to PEEP was also similar in C-ARDS patients with higher vs. lower respiratory system compliance. CONCLUSION: An intermediate PEEP level seems appropriate in half of our C-ARDS patients. There is no solid evidence that compliance at low PEEP could predict the response to PEEP.