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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.

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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.

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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.

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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.

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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.

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BACKGROUND: Within-breath oscillations in arterial oxygen tension (PaO2) can be detected using fast responding intra-arterial oxygen sensors in animal models. These PaO2 signals, which rise in inspiration and fall in expiration, may represent cyclical recruitment/derecruitment and, therefore, a potential clinical monitor to allow titration of ventilator settings in lung injury. However, in hypovolaemia models, these oscillations have the potential to become inverted, such that they decline, rather than rise, in inspiration. This inversion suggests multiple aetiologies may underlie these oscillations. A correct interpretation of the various PaO2 oscillation morphologies is essential to translate this signal into a monitoring tool for clinical practice. We present a pilot study to demonstrate the feasibility of a new analysis method to identify these morphologies. METHODS: Seven domestic pigs (average weight 31.1 kg) were studied under general anaesthesia with muscle relaxation and mechanical ventilation. Three underwent saline-lavage lung injury and four were uninjured. Variations in PEEP, tidal volume and presence/absence of lung injury were used to induce different morphologies of PaO2 oscillation. Functional principal component analysis and k-means clustering were employed to separate PaO2 oscillations into distinct morphologies, and the cardiorespiratory physiology associated with these PaO2 morphologies was compared. RESULTS: PaO2 oscillations from 73 ventilatory conditions were included. Five functional principal components were sufficient to explain ≥ 95% of the variance of the recorded PaO2 signals. From these, five unique morphologies of PaO2 oscillation were identified, ranging from those which increased in inspiration and decreased in expiration, through to those which decreased in inspiration and increased in expiration. This progression was associated with the estimates of the first functional principal component (P < 0.001, R2 = 0.88). Intermediate morphologies demonstrated waveforms with two peaks and troughs per breath. The progression towards inverted oscillations was associated with increased pulse pressure variation (P = 0.03). CONCLUSIONS: Functional principal component analysis and k-means clustering are appropriate to identify unique morphologies of PaO2 waveform associated with distinct cardiorespiratory physiology. We demonstrated novel intermediate morphologies of PaO2 waveform, which may represent a development of zone 2 physiologies within the lung. Future studies of PaO2 oscillations and modelling should aim to understand the aetiologies of these morphologies.

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Sepsis is a condition with high morbidity and mortality. Prompt recognition and initiation of treatment is essential. Despite forming an integral part of sepsis management, fluid resuscitation may also lead to volume overload, which in turn is associated with increased mortality. The optimal fluid strategy in sepsis resuscitation is yet to be defined. Hyaluronan, an endogenous glycosaminoglycan with high affinity to water is an important constituent of the endothelial glycocalyx. We hypothesized that exogenously administered hyaluronan would counteract intravascular volume depletion and contribute to endothelial glycocalyx integrity in a fluid restrictive model of peritonitis. In a prospective, blinded model of porcine peritonitis sepsis, we randomized animals to intervention with hyaluronan (n = 8) or 0.9% saline (n = 8). The animals received an infusion of 0.1% hyaluronan 6 ml/kg/h, or the same volume of saline, during the first 2 h of peritonitis. Stroke volume variation and hemoconcentration were comparable in the two groups throughout the experiment. Cardiac output was higher in the intervention group during the infusion of hyaluronan (3.2 ± 0.5 l/min in intervention group vs 2.7 ± 0.2 l/min in the control group) (p = 0.039). The increase in lactate was more pronounced in the intervention group (3.2 ± 1.0 mmol/l in the intervention group and 1.7 ± 0.7 mmol/l in the control group) at the end of the experiment (p < 0.001). Concentrations of surrogate markers of glycocalyx damage; syndecan 1 (0.6 ± 0.2 ng/ml vs 0.5 ± 0.2 ng/ml, p = 0.292), heparan sulphate (1.23 ± 0.2 vs 1.4 ± 0.3 ng/ml, p = 0.211) and vascular adhesion protein 1 (7.0 ± 4.1 vs 8.2 ± 2.3 ng/ml, p = 0.492) were comparable in the two groups at the end of the experiment. In conclusion, hyaluronan did not counteract intravascular volume depletion in early peritonitis sepsis. However, this finding is hampered by the short observation period and a beneficial effect of HMW-HA in peritonitis sepsis cannot be discarded based on the results of the present study.

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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.

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Today, there is a lack of clinically available imaging techniques to detect and quantify specific immune cell populations. Neutrophils are one of the first immune cells at the site of inflammation, and they secrete the serine protease neutrophil elastase (NE), which is crucial in the fight against pathogens. However, the prolonged lifespan of neutrophils increases the risk that patients will develop severe complications, such as acute respiratory distress syndrome (ARDS). Here, we evaluated the novel radiolabeled NE inhibitor 11C-GW457427 in a pig model of ARDS, for detection and quantification of neutrophil activity in the lungs. Methods: ARDS was induced by intravenous administration of oleic acid to 5 farm pigs, and 4 were considered healthy controls. The severity of ARDS was monitored by clinical parameters of lung function and plasma biomarkers. Each pig was studied with 11C-GW457427 and PET/CT, before and after pretreatment with the NE inhibitor GW311616 to determine in vivo binding specificity. PET image data were analyzed as SUVs and correlated with immunohistochemical staining for NE in biopsies. Results: The binding of 11C-GW457427 was increased in pig lungs with induced ARDS (median SUVmean, 1.91; interquartile range [IQR], 1.67-2.55) compared with healthy control pigs (P < 0.05 and P = 0.03, respectively; median SUVmean, 1.04; IQR, 0.66-1.47). The binding was especially strong in lung regions with high levels of NE and ongoing inflammation, as verified by immunohistochemistry. The binding was successfully blocked by pretreatment of an NE inhibitor drug, which demonstrated the in vivo specificity of 11C-GW457427 (P < 0.05 and P = 0.04, respectively; median SUVmean, 0.60; IQR, 0.58-0.77). The binding in neutrophil-rich tissues such as bone marrow (P < 0.05 and P = 0.04, respectively; baseline median SUVmean, 5.01; IQR, 4.48-5.49; block median SUVmean, 1.57; IQR, 0.95-1.85) and spleen (median SUVmean, 2.14; IQR, 1.19-2.36) was also high in all pigs. Conclusion: 11C-GW457427 binds to NE in a porcine model of oleic acid-induced lung inflammation in vivo, with a specific increase in regional lung, bone marrow, and spleen SUV. 11C-GW457427 is a promising tool for localizing, tracking, and quantifying neutrophil-facilitated inflammation in clinical diagnostics and drug development.

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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.

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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.

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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.

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PURPOSE: In the characterization of severe lung diseases, early detection of specific inflammatory cells could help to monitor patients' response to therapy and increase chances of survival. Macrophages contribute to regulating the resolution and termination of inflammation and have increasingly been of interest for targeted therapies. [68Ga]Ga-DOTA-TATE is an established clinical radiopharmaceutical targeting somatostatin receptor subtype 2 (SSTR 2). Since activated macrophages (M1) overexpress SSTR 2, the aim of this study was to investigate the applicability of [68Ga]Ga-DOTA-TATE for positron emission tomography (PET) imaging of M1 macrophages in pulmonary inflammation. METHODS: Inflammation in the pig lungs was induced by warm saline lavage followed by injurious ventilation in farm pigs (n = 7). Healthy pigs (n = 3) were used as control. A 60-min dynamic PET scan over the lungs was performed after [68Ga]Ga-DOTA-TATE injection and [18F]FDG scan was executed afterward for comparison. The uptake of both tracers was assessed as mean standardized uptake values (SUVmean) 30-60-min post-injection. The PET scans were followed by computed tomography (CT) scans, and the Hounsfield units (HU) were quantified of the coronal segments. Basal and apical segments of the lungs were harvested for histology staining. A rat lung inflammation model was also studied for tracer specificity using lipopolysaccharides (LPS) by oropharyngeal aspiration. Organ biodistribution, ex vivo autoradiography (ARG) and histology samples were conducted on LPS treated, octreotide induced blocking and control healthy rats. RESULTS: The accumulation of [68Ga]Ga-DOTA-TATE on pig lavage model was prominent in the more severely injured dorsal segments of the lungs (SUVmean = 0.91 ± 0.56), compared with control animals (SUVmean = 0.27 ± 0.16, p < 0.05). The tracer uptake corresponded to the damaged areas assessed by CT and histology and were in line with HU quantification. The [68Ga]Ga-DOTA-TATE uptake in LPS treated rat lungs could be blocked and was significantly higher compared with control group. CONCLUSION: The feasibility of the noninvasive assessment of tissue macrophages using [68Ga]Ga-DOTA-TATE/PET was demonstrated in both porcine and rat lung inflammation models. [68Ga]Ga-DOTA-TATE has a great potential to be used to study the role and presence of macrophages in humans in fight against severe lung diseases.

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The magnitude and distribution of strain imposed on the peripheral airspaces by mechanical ventilation at the microscopic level and the consequent deformations are unknown despite their importance for understanding the mechanisms occurring at the onset of ventilator-induced lung injury. Here a 4-Dimensional (3D + time) image acquisition and processing technique is developed to assess pulmonary acinar biomechanics at microscopic resolution. Synchrotron radiation phase contrast CT with an isotropic voxel size of 6 µm3 is applied in live anesthetized rats under controlled mechanical ventilation. Video animations of regional acinar and vascular strain are acquired in vivo. Maps of strain distribution due to positive-pressure breaths and cardiovascular activity in lung acini and blood vessels are derived based on CT images. Regional strain within the lung peripheral airspaces takes average values of 0.09 ± 0.02. Fitting the expression S = kVn, to the changes in peripheral airspace area (S) and volume (V) during a positive pressure breath yields an exponent n = 0.82 ± 0.03, suggesting predominant alveolar expansion rather than ductal expansion or alveolar recruitment. We conclude that this methodology can be used to assess acinar conformational changes during positive pressure breaths in intact peripheral lung airspaces.

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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.

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Synchrotron radiation offers unique properties of coherence, utilized in phase-contrast imaging, and high flux as well as a wide energy spectrum which allow the selection of very narrow energy bands of radiation, used in K-edge subtraction imaging (KES) imaging. These properties extend X-ray computed tomography (CT) capabilities to quantitatively assess lung morphology, and to map regional lung ventilation, perfusion, inflammation, aerosol particle distribution and biomechanical properties, with microscopic spatial resolution. Four-dimensional imaging, allows the investigation of the dynamics of regional lung functional parameters simultaneously with structural deformation of the lung as a function of time. These techniques have proven to be very useful for revealing the regional differences in both lung structure and function which is crucial for better understanding of disease mechanisms as well as for evaluating treatment in small animal models of lung diseases. Here, synchrotron radiation imaging methods are described and examples of their application to the study of disease mechanisms in preclinical animal models are presented.

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OBJECTIVE: To develop a method based on CT angiography and the maximum slope model (MSM) to measure regional lung perfusion in anesthetized ponies. ANIMALS: 6 ponies. PROCEDURES: Anesthetized ponies were positioned in dorsal recumbency in the CT gantry. Contrast was injected, and the lungs were imaged while ponies were breathing spontaneously and while they were mechanically ventilated. Two observers delineated regions of interest in aerated and atelectatic lung, and perfusion in those regions was calculated with the MSM. Measurements obtained with a computerized method were compared with manual measurements, and computerized measurements were compared with previously reported measurements obtained with microspheres. RESULTS: Perfusion measurements obtained with the MSM were similar to previously reported values obtained with the microsphere method. While ponies were spontaneously breathing, mean ± SD perfusion for aerated and atelectatic lung regions were 4.0 ± 1.9 and 5.0 ± 1.2 mL/min/g of lung tissue, respectively. During mechanical ventilation, values were 4.6 ± 1.2 and 2.7 ± 0.7 mL/min/g of lung tissue at end expiration and 4.1 ± 0.5 and 2.7 ± 0.6 mL/min/g of lung tissue at peak inspiration. Intraobserver agreement was acceptable, but interobserver agreement was lower. Computerized measurements compared well with manual measurements. CLINICAL RELEVANCE: Findings showed that CT angiography and the MSM could be used to measure regional lung perfusion in dorsally recumbent anesthetized ponies. Measurements are repeatable, suggesting that the method could be used to determine efficacy of therapeutic interventions to improve ventilation-perfusion matching and for other studies for which measurement of regional lung perfusion is necessary.

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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.

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Pig experiments often require anaesthesia, and a rapid stress-free induction is desired. Induction drugs may alter the subsequent anaesthesia. Therefore, the aim of the present study was to compare, in pigs, the effects of two different injectable anaesthetic techniques on the induction and on the physiological variables in a subsequent eight hours of total intravenous anaesthesia (TIVA). Twelve domestic castrates (Swedish Landrace/Yorkshire) 27‒31 kg were used. The pigs were randomly assigned to different induction drug combinations of zolazepam-tiletamine and medetomidine intramuscularly (ZTMe) or midazolam, ketamine intramuscularly and fentanyl intravenously (MiKF). Time from injection to unconsciousness was recorded and the ease of endotracheal intubation assessed. The TIVA infusion rate was adjusted according to the response exhibited from the nociceptive stimulus delivered by mechanically clamping the dewclaw. The time from injection to unconsciousness was briefer and intubation was easier in the ZTMe group. Results from the recorded heart rate, cardiac index and arterial blood pressure variables were satisfactorily preserved and cardiovascular function was maintained in both groups. Shivering was not observed in the ZTMe group, but was observed in four of the pigs in the MiKF group. The requirement of TIVA was lower in the ZTMe group. In conclusion, ZTMe had better results than MiKF in areas such as shorter induction time, better intubation scoring results and less adjustment and amount of TIVA required up to six hours of anaesthesia. The results may have been due to a greater depth of anaesthesia achieved with the ZTMe combination at the dose used.

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