Imitating the respiratory activity of the brain stem by using artificial neural networks: exploratory study on an animal model of lactic acidosis and proof of concept.

Artificial neural networks (ANNs) are versatile tools capable of learning without prior knowledge. This study aims to evaluate whether ANN can calculate minute volume during spontaneous breathing after being trained using data from an animal model of metabolic acidosis. Data was collected from ten anesthetized, spontaneously breathing pigs divided randomly into two groups, one without dead space and the other with dead space at the beginning of the experiment. Each group underwent two equal sequences of pH lowering with pre-defined targets by continuous infusion of lactic acid. The inputs to ANNs were pH, ΔPaCO2 (variation of the arterial partial pressure of CO2), PaO2, and blood temperature which were sampled from the animal model. The output was the delta minute volume (ΔVM), (the change of minute volume as compared to the minute volume the animal had at the beginning of the experiment). The ANN performance was analyzed using mean squared error (MSE), linear regression, and the Bland-Altman (B-A) method. The animal experiment provided the necessary data to train the ANN. The best architecture of ANN had 17 intermediate neurons; the best performance of the finally trained ANN had a linear regression with R2 of 0.99, an MSE of 0.001 [L/min], a B-A analysis with bias ± standard deviation of 0.006 ± 0.039 [L/min]. ANNs can accurately estimate ΔVM using the same information that arrives at the respiratory centers. This performance makes them a promising component for the future development of closed-loop artificial ventilators.

Homogenizing effect of PEEP on tidal volume distribution during neurally adjusted ventilatory assist: study of an animal model of acute respiratory distress syndrome.

BACKGROUND: The physiological response and the potentially beneficial effects of positive end-expiratory pressure (PEEP) for lung protection and optimization of ventilation during spontaneous breathing in patients with acute respiratory distress syndrome (ARDS) are not fully understood. The aim of the study was to compare the effect of different PEEP levels on tidal volume distribution and on the ventilation of dependent lung region during neurally adjusted ventilatory assist (NAVA). METHODS: ARDS-like lung injury was induced by using saline lavage in 10 anesthetized and spontaneously breathing farm-bred pigs. The animals were ventilated in NAVA modality and tidal volume distribution as well as dependent lung ventilation were assessed using electric impedance tomography during the application of PEEP levels from 0 to 15 cmH20, in steps of 3 cmH20. Tidal volume distribution and dependent fraction of ventilation were analysed using Wilcoxon signed rank test. Furthermore, airway, esophageal and transpulmonary pressure, as well as airway flow and delivered volume, were continuously measured during the assisted spontaneous breathing. RESULTS: Increasing PEEP improved oxygenation and re-distributed tidal volume. Specifically, ventilation distribution changed from a predominant non-dependent to a more even distribution between non-dependent and dependent areas of the lung. Dependent fraction of ventilation reached 47 ± 9% at PEEP 9 cmH20. Further increasing PEEP led to a predominant dependent ventilation. CONCLUSION: During assisted spontaneous breathing in this model of induced ARDS, PEEP modifies the distribution of ventilation and can achieve a homogenizing effect on its spatial arrangement. The study indicates that PEEP is an important factor during assisted spontaneous breathing and that EIT can be of valuable interest when titrating PEEP level during spontaneous breathing, by indicating the most homogeneous distribution of gas volumes throughout the PEEP spectrum.

Chest dual-energy CT to assess the effects of steroids on lung function in severe COVID-19 patients.

BACKGROUND: Steroids have been shown to reduce inflammation, hypoxic pulmonary vasoconstriction (HPV) and lung edema. Based on evidence from clinical trials, steroids are widely used in severe COVID-19. However, the effects of steroids on pulmonary gas volume and blood volume in this group of patients are unexplored. OBJECTIVE: Profiting by dual-energy computed tomography (DECT), we investigated the relationship between the use of steroids in COVID-19 and distribution of blood volume as an index of impaired HPV. We also investigated whether the use of steroids influences lung weight, as index of lung edema, and how it affects gas distribution. METHODS: Severe COVID-19 patients included in a single-center prospective observational study at the intensive care unit at Uppsala University Hospital who had undergone DECT were enrolled in the current study. Patients' cohort was divided into two groups depending on the administration of steroids. From each patient's DECT, 20 gas volume maps and the corresponding 20 blood volume maps, evenly distributed along the cranial-caudal axis, were analyzed. As a proxy for HPV, pulmonary blood volume distribution was analyzed in both the whole lung and the hypoinflated areas. Total lung weight, index of lung edema, was estimated. RESULTS: Sixty patients were analyzed, whereof 43 received steroids. Patients not exposed to steroids showed a more extensive non-perfused area (19% vs 13%, p < 0.01) and less homogeneous pulmonary blood volume of hypoinflated areas (kurtosis: 1.91 vs 2.69, p < 0.01), suggesting a preserved HPV compared to patients treated with steroids. Moreover, patients exposed to steroids showed a significantly lower lung weight (953 gr vs 1140 gr, p = 0.01). A reduction in alveolar-arterial difference of oxygen followed the treatment with steroids (322 ± 106 mmHg at admission vs 267 ± 99 mmHg at DECT, p = 0.04). CONCLUSIONS: The use of steroids might cause impaired HPV and might reduce lung edema in severe COVID-19. This is consistent with previous findings in other diseases. Moreover, a reduced lung weight, as index of decreased lung edema, and a more homogeneous distribution of gas within the lung were shown in patients treated with steroids. TRIAL REGISTRATION: Clinical Trials ID: NCT04316884, Registered March 13, 2020.

Limitations of the ARDS criteria during high-flow oxygen or non-invasive ventilation: evidence from critically ill COVID-19 patients.

BACKGROUND: The ratio of partial pressure of arterial oxygen to inspired oxygen fraction (PaO2/FIO2) during invasive mechanical ventilation (MV) is used as criteria to grade the severity of respiratory failure in acute respiratory distress syndrome (ARDS). During the SARS-CoV2 pandemic, the use of PaO2/FIO2 ratio has been increasingly used in non-invasive respiratory support such as high-flow nasal cannula (HFNC) and non-invasive ventilation (NIV). The grading of hypoxemia in non-invasively ventilated patients is uncertain. The main hypothesis, investigated in this study, was that the PaO2/FIO2 ratio does not change when switching between MV, NIV and HFNC. METHODS: We investigated respiratory function in critically ill patients with COVID-19 included in a single-center prospective observational study of patients admitted to the intensive care unit (ICU) at Uppsala University Hospital in Sweden. In a steady state condition, the PaO2/FIO2 ratio was recorded before and after any change between two of the studied respiratory support techniques (i.e., HFNC, NIV and MV). RESULTS: A total of 148 patients were included in the present analysis. We find that any change in respiratory support from or to HFNC caused a significant change in PaO2/FIO2 ratio. Changes in respiratory support between NIV and MV did not show consistent change in PaO2/FIO2 ratio. In patients classified as mild to moderate ARDS during MV, the change from HFNC to MV showed a variable increase in PaO2/FIO2 ratio ranging between 52 and 140 mmHg (median of 127 mmHg). This made prediction of ARDS severity during MV from the apparent ARDS grade during HFNC impossible. CONCLUSIONS: HFNC is associated with lower PaO2/FIO2 ratio than either NIV or MV in the same patient, while NIV and MV provided similar PaO2/FIO2 and thus ARDS grade by Berlin definition. The large variation of PaO2/FIO2 ratio indicates that great caution should be used when estimating ARDS grade as a measure of pulmonary damage during HFNC.

What is new in respiratory monitoring?

This paper provides a review of a selection of papers published in the Journal of Clinical Monitoring and Computing in 2020 and 2021 highlighting what is new within the field of respiratory monitoring. Selected papers cover work in pulse oximetry monitoring, acoustic monitoring, respiratory system mechanics, monitoring during surgery, electrical impedance tomography, respiratory rate monitoring, lung ultrasound and detection of patient-ventilator asynchrony.

A quantitative analysis of extension and distribution of lung injury in COVID-19: a prospective study based on chest computed tomography.

BACKGROUND: Typical features differentiate COVID-19-associated lung injury from acute respiratory distress syndrome. The clinical role of chest computed tomography (CT) in describing the progression of COVID-19-associated lung injury remains to be clarified. We investigated in COVID-19 patients the regional distribution of lung injury and the influence of clinical and laboratory features on its progression. METHODS: This was a prospective study. For each CT, twenty images, evenly spaced along the cranio-caudal axis, were selected. For regional analysis, each CT image was divided into three concentric subpleural regions of interest and four quadrants. Hyper-, normally, hypo- and non-inflated lung compartments were defined. Nonparametric tests were used for hypothesis testing (α = 0.05). Spearman correlation test was used to detect correlations between lung compartments and clinical features. RESULTS: Twenty-three out of 111 recruited patients were eligible for further analysis. Five hundred-sixty CT images were analyzed. Lung injury, composed by hypo- and non-inflated areas, was significantly more represented in subpleural than in core lung regions. A secondary, centripetal spread of lung injury was associated with exposure to mechanical ventilation (p < 0.04), longer spontaneous breathing (more than 14 days, p < 0.05) and non-protective tidal volume (p < 0.04). Positive fluid balance (p < 0.01), high plasma D-dimers (p < 0.01) and ferritin (p < 0.04) were associated with increased lung injury. CONCLUSIONS: In a cohort of COVID-19 patients with severe respiratory failure, a predominant subpleural distribution of lung injury is observed. Prolonged spontaneous breathing and high tidal volumes, both causes of patient self-induced lung injury, are associated to an extensive involvement of more central regions. Positive fluid balance, inflammation and thrombosis are associated with lung injury. Trial registration Study registered a priori the 20th of March, 2020. Clinical Trials ID NCT04316884.

Expiratory Resistances Prevent Expiratory Diaphragm Contraction, Flow Limitation, and Lung Collapse.

Rationale: Tidal expiratory flow limitation (tidal-EFL) is not completely avoidable by applying positive end-expiratory pressure and may cause respiratory and hemodynamic complications in ventilated patients with lungs prone to collapse. During spontaneous breathing, expiratory diaphragmatic contraction counteracts tidal-EFL. We hypothesized that during both spontaneous breathing and controlled mechanical ventilation, external expiratory resistances reduce tidal-EFL.Objectives: To assess whether external expiratory resistances 1) affect expiratory diaphragmatic contraction during spontaneous breathing, 2) reduce expiratory flow and make lung compartments more homogeneous with more similar expiratory time constants, and 3) reduce tidal atelectasis, preventing hyperinflation.Methods: Three positive end-expiratory pressure levels and four external expiratory resistances were tested in 10 pigs after lung lavage. We analyzed expiratory diaphragmatic electric activity and respiratory mechanics. On the basis of computed tomography scans, four lung compartments-not inflated (atelectasis), poorly inflated, normally inflated, and hyperinflated-were defined.Measurements and Main Results: Consequently to additional external expiratory resistances, and mainly in lungs prone to collapse (at low positive end-expiratory pressure), 1) the expiratory transdiaphragmatic pressure decreased during spontaneous breathing by >10%, 2) expiratory flow was reduced and the expiratory time constants became more homogeneous, and 3) the amount of atelectasis at end-expiration decreased from 24% to 16% during spontaneous breathing and from 32% to 18% during controlled mechanical ventilation, without increasing hyperinflation.Conclusions: The expiratory modulation induced by external expiratory resistances preserves the positive effects of the expiratory brake while minimizing expiratory diaphragmatic contraction. External expiratory resistances optimize lung mechanics and limit tidal-EFL and tidal atelectasis, without increasing hyperinflation.

Transpulmonary driving pressure during mechanical ventilation-validation of a non-invasive measurement method.

BACKGROUND: Transpulmonary driving pressure plays an important role in today's understanding of ventilator induced lung injury. We have previously validated a novel non-invasive method based on stepwise increments of PEEP to assess transpulmonary driving pressure in anaesthetised patients with healthy lungs. The aim of this study was to validate the method in patients who were mechanically ventilated for different diagnoses requiring intensive care. METHODS: We measured transpulmonary pressure (Ptp) and calculated transpulmonary driving pressure (ΔPtp) in 31 patients undergoing mechanical ventilation in an intensive care unit. Parallel triplicate measurements were performed with the PEEP step method (PtpPSM) and the conventional oesophageal balloon method (Ptpconv). Their agreement was compared using the intraclass correlation coefficient (ICC) and the Bland Altman plot. RESULT: The coefficient of variation for the repeated measurements was 4,3 for ΔPtpPSM and 9,2 for ΔPtpconv. The ICC of 0,864 and the Bland Altman plot indicate good agreement between the two methods. CONCLUSION: The non-invasive method can be applied in mechanically ventilated patients to measure transpulmonary driving pressure with good repeatability and accuracy comparable to the traditional oesophageal balloon method.

Individual Airway Closure Characterized In Vivo by Phase-Contrast CT Imaging in Injured Rabbit Lung.

OBJECTIVES: Airway closure is involved in adverse effects of mechanical ventilation under both general anesthesia and in acute respiratory distress syndrome patients. However, direct evidence and characterization of individual airway closure is lacking. Here, we studied the same individual peripheral airways in intact lungs of anesthetized and mechanically ventilated rabbits, at baseline and following lung injury, using high-resolution synchrotron phase-contrast CT. DESIGN: Laboratory animal investigation. SETTING: European synchrotron radiation facility. SUBJECTS: Six New-Zealand White rabbits. INTERVENTIONS: The animals were anesthetized, paralyzed, and mechanically ventilated in pressure-controlled mode (tidal volume, 6 mL/kg; respiratory rate, 40; FIO2, 0.6; inspiratory:expiratory, 1:2; and positive end-expiratory pressure, 3 cm H2O) at baseline. Imaging was performed with a 47.5 × 47.5 × 47.5 µm voxel size, at positive end-expiratory pressure 12, 9, 6, 3, and 0 cm H2O. The imaging sequence was repeated after lung injury induced by whole-lung lavage and injurious ventilation in four rabbits. Cross-sections of the same individual airways were measured. MEASUREMENTS AND MAIN RESULTS: The airways were measured at baseline (n = 48; radius, 1.7 to 0.21 mm) and after injury (n = 32). Closure was observed at 0 cm H2O in three of 48 airways (6.3%; radius, 0.35 ± 0.08 mm at positive end-expiratory pressure 12) at baseline and five of 32 (15.6%; radius, 0.28 ± 0.09 mm) airways after injury. Cross-section was significantly reduced at 3 and 0 cm H2O, after injury, with a significant relation between the relative change in cross-section and airway radius at 12 cm H2O in injured, but not in normal lung (R = 0.60; p < 0.001). CONCLUSIONS: Airway collapsibility increases in the injured lung with a significant dependence on airway caliber. We identify "compliant collapse" as the main mechanism of airway closure in initially patent airways, which can occur at more than one site in individual airways.

Imaging the Injured Lung: Mechanisms of Action and Clinical Use.

Acute respiratory distress syndrome (ARDS) consists of acute hypoxemic respiratory failure characterized by massive and heterogeneously distributed loss of lung aeration caused by diffuse inflammation and edema present in interstitial and alveolar spaces. It is defined by consensus criteria, which include diffuse infiltrates on chest imaging-either plain radiography or computed tomography. This review will summarize how imaging sciences can inform modern respiratory management of ARDS and continue to increase the understanding of the acutely injured lung. This review also describes newer imaging methodologies that are likely to inform future clinical decision-making and potentially improve outcome. For each imaging modality, this review systematically describes the underlying principles, technology involved, measurements obtained, insights gained by the technique, emerging approaches, limitations, and future developments. Finally, integrated approaches are considered whereby multimodal imaging may impact management of ARDS.

The Diaphragm Acts as a Brake during Expiration to Prevent Lung Collapse.

RATIONALE: The diaphragm is the major inspiratory muscle and is assumed to relax during expiration. However, electrical postinspiratory activity has been observed. Whether there is an expiratory diaphragmatic contraction that preserves lung patency has yet to be explored. OBJECTIVES: We hypothesized the occurrence of an expiratory diaphragmatic contraction directed at stabilizing peripheral airways and preventing or reducing cyclic expiratory lung collapse. METHODS: Mild acute respiratory distress syndrome was induced in 10 anesthetized, spontaneously breathing pigs. Lung volume was decreased by lowering end-expiratory airway pressure in a stepwise manner. We recorded the diaphragmatic electric activity during expiration, dynamic computed tomographic scans, and respiratory mechanics. In five pigs, the same protocol was repeated during mechanical ventilation after muscle paralysis. MEASUREMENTS AND MAIN RESULTS: Diaphragmatic electric activity during expiration increased by decreasing end-expiratory lung volume during spontaneous breathing. This enhanced the diaphragm muscle force, to a greater extent with lower lung volume, indicating a diaphragmatic electromechanical coupling during spontaneous expiration. In turn, the resulting diaphragmatic contraction delayed and reduced the expiratory collapse and increased lung aeration compared with mechanical ventilation with muscle paralysis and absence of diaphragmatic activity. CONCLUSIONS: The diaphragm is an important regulator of expiration. Its expiratory activity seems to preserve lung volume and to protect against lung collapse. The loss of diaphragmatic expiratory contraction during mechanical ventilation and muscle paralysis may be a contributing factor to unsuccessful respiratory support.

Dynamic Mechanical Interactions Between Neighboring Airspaces Determine Cyclic Opening and Closure in Injured Lung.

OBJECTIVES: Positive pressure ventilation exposes the lung to mechanical stresses that can exacerbate injury. The exact mechanism of this pathologic process remains elusive. The goal of this study was to describe recruitment/derecruitment at acinar length scales over short-time frames and test the hypothesis that mechanical interdependence between neighboring lung units determines the spatial and temporal distributions of recruitment/derecruitment, using a computational model. DESIGN: Experimental animal study. SETTING: International synchrotron radiation laboratory. SUBJECTS: Four anesthetized rabbits, ventilated in pressure controlled mode. INTERVENTIONS: The lung was consecutively imaged at ~ 1.5-minute intervals using phase-contrast synchrotron imaging, at positive end-expiratory pressures of 12, 9, 6, 3, and 0 cm H2O before and after lavage and mechanical ventilation induced injury. The extent and spatial distribution of recruitment/derecruitment was analyzed by subtracting subsequent images. In a realistic lung structure, we implemented a mechanistic model in which each unit has individual pressures and speeds of opening and closing. Derecruited and recruited lung fractions (Fderecruited, Frecruited) were computed based on the comparison of the aerated volumes at successive time points. MEASUREMENTS AND MAIN RESULTS: Alternative recruitment/derecruitment occurred in neighboring alveoli over short-time scales in all tested positive end-expiratory pressure levels and despite stable pressure controlled mode. The computational model reproduced this behavior only when parenchymal interdependence between neighboring acini was accounted for. Simulations closely mimicked the experimental magnitude of Fderecruited and Frecruited when mechanical interdependence was included, while its exclusion gave Frecruited values of zero at positive end-expiratory pressure greater than or equal to 3 cm H2O. CONCLUSIONS: These findings give further insight into the microscopic behavior of the injured lung and provide a means of testing protective-ventilation strategies to prevent recruitment/derecruitment and subsequent lung damage.

Monitoring of total positive end-expiratory pressure during mechanical ventilation by artificial neural networks.

Ventilation treatment of acute lung injury (ALI) requires the application of positive airway pressure at the end of expiration (PEEPapp) to avoid lung collapse. However, the total pressure exerted on the alveolar walls (PEEPtot) is the sum of PEEPapp and intrinsic PEEP (PEEPi), a hidden component. To measure PEEPtot, ventilation must be discontinued with an end-expiratory hold maneuver (EEHM). We hypothesized that artificial neural networks (ANN) could estimate the PEEPtot from flow and pressure tracings during ongoing mechanical ventilation. Ten pigs were mechanically ventilated, and the time constant of their respiratory system (τRS) was measured. We shortened their expiratory time (TE) according to multiples of τRS, obtaining different respiratory patterns (Rpat). Pressure (PAW) and flow (V'AW) at the airway opening during ongoing mechanical ventilation were simultaneously recorded, with and without the addition of external resistance. The last breath of each Rpat included an EEHM, which was used to compute the reference PEEPtot. The entire protocol was repeated after the induction of ALI with i.v. injection of oleic acid, and 382 tracings were obtained. The ANN had to extract the PEEPtot, from the tracings without an EEHM. ANN agreement with reference PEEPtot was assessed with the Bland-Altman method. Bland Altman analysis of estimation error by ANN showed -0.40 ± 2.84 (expressed as bias ± precision) and ±5.58 as limits of agreement (data expressed as cmH2O). The ANNs estimated the PEEPtot well at different levels of PEEPapp under dynamic conditions, opening up new possibilities in monitoring PEEPi in critically ill patients who require ventilator treatment.

Positive end-expiratory pressure limits inspiratory effort through modulation of the effort-to-drive ratio: an experimental crossover study.

BACKGROUND: How assisted spontaneous breathing should be used during acute respiratory distress syndrome is questioned. Recent evidence suggests that high positive end-expiratory pressure (PEEP) may limit the risk of patient self-inflicted lung injury (P-SILI). The aim of this study was to assess the effects of PEEP on esophageal pressure swings, inspiratory drive, and the neuromuscular efficiency of ventilation. We hypothesized that high PEEP would reduce esophageal pressure swings, regardless of inspiratory drive changes, by modulating the effort-to-drive ratio (EDR). This was tested retrospectively in an experimental animal crossover study. Anesthetized pigs (n = 15) were subjected to mild to moderate lung injury and different PEEP levels were applied, changing PEEP from 0 to 15 cmH2O and back to 0 cmH2O in steps of 3 cmH2O. Airway pressure, esophageal pressure (Pes), and electric activity of the diaphragm (Edi) were collected. The EDR was calculated as the tidal change in Pes divided by the tidal change in Edi. Statistical differences were tested using the Wilcoxon signed-rank test. RESULTS: Inspiratory esophageal pressure swings decreased from - 4.2 ± 3.1 cmH2O to - 1.9 ± 1.5 cmH2O (p < 0.01), and the mean EDR fell from - 1.12 ± 1.05 cmH2O/µV to - 0.24 ± 0.20 (p < 0.01) as PEEP was increased from 0 to 15 cmH2O. The EDR was significantly correlated to the PEEP level (rs = 0.35, p < 0.01). CONCLUSIONS: Higher PEEP limits inspiratory effort by modulating the EDR of the respiratory system. These findings indicate that PEEP may be used in titration of the spontaneous impact on ventilation and in P-SILI risk reduction, potentially facilitating safe assisted spontaneous breathing. Similarly, ventilation may be shifted from highly spontaneous to predominantly controlled ventilation using PEEP. These findings need to be confirmed in clinical settings.

Quantifying heterogeneity in an animal model of acute respiratory distress syndrome, a comparison of inspired sinewave technique to computed tomography.

The inspired sinewave technique (IST) is a non-invasive method to measure lung heterogeneity indices (including both uneven ventilation and perfusion or heterogeneity), which reveal multiple conditions of the lung and lung injury. To evaluate the reproducibility and predicted clinical outcomes of IST heterogeneity values, a comparison with a quantitative lung computed tomography (CT) scan is performed. Six anaesthetised pigs were studied after surfactant depletion by saline-lavage. Paired measurements of lung heterogeneity were then taken with both the IST and CT. Lung heterogeneity measured by the IST was calculated by (a) the ratio of tracer gas outputs measured at oscillation periods of 180 s and 60 s, and (b) by the standard deviation of the modelled log-normal distribution of ventilations and perfusions in the simulation lung. In the CT images, lungs were manually segmented and divided into different regions according to voxel density. A quantitative CT method to calculate the heterogeneity (the Cressoni method) was applied. The IST and CT show good Pearson correlation coefficients in lung heterogeneity measurements (ventilation: 0.71, and perfusion, 0.60, p < 0.001). Within individual animals, the coefficients of determination average ventilation (R2 = 0.53) and perfusion (R2 = 0.68) heterogeneity. Strong concordance rates of 98% in ventilation and 89% when the heterogeneity changes were reported in pairs measured by CT scanning and IST methods. This quantitative method to identify heterogeneity has the potential to replicate CT lung heterogeneity, and to aid individualised care in ARDS.

Body mass index is associated with pulmonary gas and blood distribution mismatch in COVID-19 acute respiratory failure. A physiological study.

Background: The effects of obesity on pulmonary gas and blood distribution in patients with acute respiratory failure remain unknown. Dual-energy computed tomography (DECT) is a X-ray-based method used to study regional distribution of gas and blood within the lung. We hypothesized that 1) regional gas/blood mismatch can be quantified by DECT; 2) obesity influences the global and regional distribution of pulmonary gas and blood; 3) regardless of ventilation modality (invasive vs. non-invasive ventilation), patients' body mass index (BMI) has an impact on pulmonary gas/blood mismatch. Methods: This single-centre prospective observational study enrolled 118 hypoxic COVID-19 patients (92 male) in need of respiratory support and intensive care who underwent DECT. The cohort was divided into three groups according to BMI: 1. BMI<25 kg/m2 (non-obese), 2. BMI = 25-40 kg/m2 (overweight to obese), and 3. BMI>40 kg/m2 (morbidly obese). Gravitational analysis of Hounsfield unit distribution of gas and blood was derived from DECT and used to calculate regional gas/blood mismatch. A sensitivity analysis was performed to investigate the influence of the chosen ventilatory modality and BMI on gas/blood mismatch and adjust for other possible confounders (i.e., age and sex). Results: 1) Regional pulmonary distribution of gas and blood and their mismatch were quantified using DECT imaging. 2) The BMI>40 kg/m2 group had less hyperinflation in the non-dependent regions and more lung collapse in the dependent regions compared to the other BMI groups. In morbidly obese patients, gas and blood were more evenly distributed; therefore, the mismatch was lower than in other patients (30% vs. 36%, p < 0.05). 3) An increase in BMI of 5 kg/m2 was associated with a decrease in mismatch of 3.3% (CI: 3.67% to -2.93%, p < 0.05). Neither the ventilatory modality nor age and sex affected the gas/blood mismatch (p > 0.05). Conclusion: 1) In a hypoxic COVID-19 population needing intensive care, pulmonary gas/blood mismatch can be quantified at a global and regional level using DECT. 2) Obesity influences the global and regional distribution of gas and blood within the lung, and BMI>40 kg/m2 improves pulmonary gas/blood mismatch. 3) This is true regardless of the ventilatory mode and other possible confounders, i.e., age and sex. Trial Registration: Clinicaltrials.gov, identifier NCT04316884, NCT04474249.

Regional distribution of mechanical strain and macrophage-associated lung inflammation after ventilator-induced lung injury: an experimental study.

BACKGROUND: Alveolar macrophages activation to the pro-inflammatory phenotype M1 is pivotal in the pathophysiology of Ventilator-Induced Lung Injury (VILI). Increased lung strain is a known determinant of VILI, but a direct correspondence between regional lung strain and macrophagic activation remains unestablished. [68Ga]Ga-DOTA-TATE is a Positron Emission Tomography (PET) radiopharmaceutical with a high affinity for somatostatin receptor subtype 2 (SSTR2), which is overexpressed by pro-inflammatory-activated macrophages. Aim of the study was to determine, in a porcine model of VILI, whether mechanical strain correlates topographically with distribution of activated macrophages detected by [68Ga]Ga-DOTA-TATE uptake. METHODS: Seven anesthetized pigs underwent VILI, while three served as control. Lung CT scans were acquired at incremental tidal volumes, simultaneously recording lung mechanics. [68Ga]Ga-DOTA-TATE was administered, followed by dynamic PET scans. Custom MatLab scripts generated voxel-by-voxel gas volume and strain maps from CT slices at para-diaphragmatic (Para-D) and mid-thoracic (Mid-T) levels. Analysis of regional Voxel-associated Normal Strain (VoStrain) and [68Ga]Ga-DOTA-TATE uptake was performed and a measure of the statistical correlation between these two variables was quantified using the linear mutual information (LMI) method. RESULTS: Compared to controls, the VILI group exhibited statistically significant higher VoStrain and Standardized Uptake Value Ratios (SUVR) both at Para-D and Mid-T levels. Both VoStrain and SUVR increased along the gravitational axis with an increment described by statistically different regression lines between VILI and healthy controls and reaching the peak in the dependent regions of the lung (for strain in VILI vs. control was at Para-D: 760 ± 210 vs. 449 ± 106; at Mid-T level 497 ± 373 vs. 193 ± 160; for SUVR, in VILI vs. control was at Para-D: 2.2 ± 1.3 vs. 1.3 ± 0.1; at Mid-T level 1.3 ± 1.0 vs. 0.6 ± 0.03). LMI in both Para-D and Mid-T was statistically significantly higher in VILI than in controls. CONCLUSIONS: In this porcine model of VILI, we found a topographical correlation between lung strain and [68Ga]Ga-DOTA-TATE uptake at voxel level, suggesting that mechanical alteration and specific activation of inflammatory cells are strongly linked in VILI. This study represents the first voxel-by-voxel examination of this relationship in a multi-modal imaging analysis.

Quantitative assessment of atelectasis formation under high frequency jet ventilation during liver tumour ablation-A computer tomography study.

BACKGROUND: High frequency jet ventilation (HFJV) can be used to minimise sub-diaphragmal organ displacements. Treated patients are in a supine position, under general anaesthesia and fully muscle relaxed. These are factors that are known to contribute to the formation of atelectasis. The HFJV-catheter is inserted freely inside the endotracheal tube and the system is therefore open to atmospheric pressure. AIM: The aim of this study was to assess the formation of atelectasis over time during HFJV in patients undergoing liver tumour ablation under general anaesthesia. METHOD: In this observational study twenty-five patients were studied. Repeated computed tomography (CT) scans were taken at the start of HFJV and every 15 minutes thereafter up until 45 minutes. From the CT images, four lung compartments were defined: hyperinflated, normoinflated, poorly inflated and atelectatic areas. The extension of each lung compartment was expressed as a percentage of the total lung area. RESULT: Atelectasis at 30 minutes, 7.9% (SD 3.5, p = 0.002) and at 45 minutes 8,1% (SD 5.2, p = 0.024), was significantly higher compared to baseline 5.6% (SD 2.5). The amount of normoinflated lung volumes were unchanged over the period studied. Only a few minor perioperative respiratory adverse events were noted. CONCLUSION: Atelectasis during HFJV in stereotactic liver tumour ablation increased over the first 45 minutes but tended to stabilise with no impact on normoinflated lung volume. Using HFJV during stereotactic liver ablation is safe regarding formation of atelectasis.