Pulmonary Vascular Permeability Index Research Articles

Deep Phenotyping of Pulmonary Edema and Pulmonary Vascular Permeability in COVID-19 ARDS.

Background Clinical monitoring of pulmonary edema due to vascular hyperpermeability in ARDS poses significant clinical challenges. Presently, no biological or radiological markers are available for quantifying pulmonary edema. Our aim was to phenotype pulmonary edema and pulmonary vascular permeability in patients with COVID-19 ARDS. Methods Transpulmonary thermodilution measurements were conducted in 65 COVID-19 ARDS patients on the day of intubation to determine extravascular lung water index (EVLWi) and pulmonary vascular permeability index (PVPi). In parallel, ventilatory parameters, clinical outcomes, the volume of lung opacity measured by chest CT, and plasma proteomics (358 unique proteins) were compared between tertiles based on the EVLWi and PVPi. Regression models were used to associate EVLWi and PVPi with plasma, radiological, and clinical parameters. Computational pathway analysis was performed on significant plasma proteins in the regression models. Results Patients with the highest EVLWi values at intubation exhibited poorer oxygenation parameters and more days on the ventilator. Extravascular lung water strongly correlated with the total volume of opacity observed on CT(r=0.72), while the PVPi had weaker associations with clinical and radiological parameters. Plasma protein concentrations demonstrated a stronger correlation with PVPi than with EVLWi. The highest tertile of PVPi was associated with proteins linked to the acute phase response (cytokine and chemokine signaling) and extracellular matrix turnover. Conclusions In the clinical setting of COVID-19 ARDS, pulmonary edema (EVLWi) can be accurately quantified through chest CT and parallels deterioration in ventilatory parameters and clinical outcomes. Vascular permeability (PVPi) is strongly reflected by inflammatory plasma proteins.

The influence of sex, age, and body height on the pulmonary vascular permeability index – a prospective observational study

The pulmonary vascular permeability index (PVPI) is a quotient of the extravascular lung water (EVLW) and the pulmonary blood volume (PBV). In acute respiratory distress syndrome (ARDS), the alveolar-capillary membrane integrity is disrupted. The result is a disproportionate increase of EVLW compared to the PBV and, hence, an increase in PVPI. Thus, PVPI has repetitively been discussed to extend the definition of ARDS. Besides sex, the influence of other anthropometric variables on PVPI has not been studied so far. However, since it is known that EVLW depends on body height and sex, we hypothesize that PVPI depends on anthropometric variables as well. This prospective single-center observational study included 1533 TPTD measurements of 251 non-critically ill patients (50.6% men) undergoing elective neuro-, thoracic, or abdominal surgery at the Munich Clinic Bogenhausen of the Technical University of Munich. Multivariate regressions were used to measure the influence of sex, age, and body height on PVPI. In all patients, PVPI was significantly higher in women (P < 0.001), with 34.4% having a PVPI > 2 compared to 15.9% of men. Mean PVPI significantly decreased with height (P < 0.001) and age (P < 0.001). Multivariate regressions allowed the calculation of mean reference surfaces. The 95th percentile surface for PVPI was > 3 for small and young women and well above 2 for all but tall and elderly men. In patients who underwent (lung reduction) thoracic surgery, the PVPI before and after surgery did not differ significantly (P = 0.531), and post-surgical PVPI did not correlate with the amount of lung resected (P = 0.536). Hence, we conclude that PVPI may be independent of the extent of lung volume reduction. However, PVPI is heavily dependent on sex, age, and body height. Anthropometric variables thus have a significant impact on the likelihood of misclassified abnormal PVPI. This warrants further studies since an increased PVPI, e.g. in the context of an ARDS, may be overlooked if anthropometric variables are not considered. We suggest reference surfaces based on the 95th-percentile corrected for sex, age, and height as a novel approach to normalize PVPI.

Study on the correlation between angiopoietin-2 and prognosis in patients with acute respiratory distress syndrome

To evaluate the predictive value of angiopoietin-2 (Ang-2) for the prognosis in patients with acute respiratory distress syndrome (ARDS). A retrospective study was conducted, and ARDS patients admitted to the department of emergency medicine of Tongde Hospital of Zhejiang Province from December 2020 to September 2022 were enrolled. General information including gender, age, causes of ARDS, disease severity scores, plasma Ang-2 levels before treatment and at 24, 48, and 72 hours after treatment, and record the 60-day prognosis were collected. Differences in clinical data between groups were compared. Multivariate Logistic regression analysis was used to identify the independent risk factors affecting the 60-day prognosis of ARDS patients, and the receiver operator characteristic curve (ROC curve) was plotted to assess the predictive value of these risk factors for patient outcomes. Pearson correlation analysis was used to assess the correlation between Ang-2 and pulmonary vascular permeability index (PVPI) and extravascular lung water index (EVLWI). A total of 132 ARDS patients were included, of which 49 patients died within 60 days and 83 patients survived. In the death group, plasma Ang-2 levels showed a gradually increasing trend, all significantly higher than before treatment (μg/L: 12.75±1.81, 12.74±1.48, 13.45±2.21 vs. 5.98±0.57, all P < 0.05), while the trend in the survival group was not significant. At 24, 48, and 72 hours after treatment, plasma Ang-2 levels in the death group were significantly higher than those in the survival group (μg/L: 12.75±1.81 vs. 7.48±1.22, 12.74±1.48 vs. 7.41±1.19, 13.45±1.41 vs. 6.88±1.41, all P < 0.05). After adjusting for confounding variables, increased plasma Ang-2 level was an independent risk factor for prognosis in ARDS patients within 60 days [odds ratio (OR) = 0.998, 95% confidence interval (95%CI) was 0.997-0.999, P < 0.01]. ROC curve analysis demonstrated that Ang-2 levels had predictive value for prognosis in ARDS patients [area under the ROC curve (AUC) = 0.985, 95%CI was 0.971-1.000, approximate maximum Youden's index 0.867, optimal cut-off value 8.43 μg/L]. Pearson correlation analysis showed that plasma Ang-2 levels were positively correlated with PVPI and EVLWI ( r values were 0.620 and 0.712 respectively, both P < 0.01). Elevated level of Ang-2 is an independent risk factor for increased mortality in patients with ARDS. Higher Ang-2 levels within 72 hours after treatment may indicate poorer prognosis.

The impact of positive end-expiratory pressure on right ventricular function in patients with moderate-to-severe ARDS: a prospective paired-design study.

To determine the effects of varying positive end-expiratory pressures (PEEPs) on right ventricular function, hemodynamics, oxygenation, and the incidence of acute cor pulmonale (ACP) in patients with moderate-to-severe acute respiratory distress syndrome (ARDS). This prospective paired-design study involved patients with moderate-to-severe ARDS in the ICU. Participants received lung-protective ventilation and hemodynamic monitoring. During the study, mechanical ventilation was administered with PEEPs of 5 cmH2O, 10 cmH2O, and 15 cmH2O, while maintaining an end-inspiratory plateau pressure ≤ 30 cmH2O. Various assessments, including transthoracic echocardiography, cardiac output measurement, and blood gas analysis, were conducted at baseline and after 1 h of ventilation at each PEEP. Subsequently, variations in ventilation oxygenation, echocardiographic parameters, and hemodynamic indicators under different PEEPs were analyzed to explore the potential effects of PEEP on right ventricular function and hemodynamics, as well as the incidence of ACP. A total of 317 ARDS patients were screened. Among them, 104 met the diagnostic criteria for moderate-to-severe ARDS, and 52 completed the study. The baseline PEEP of these 52 participants, acquired before commencement, was 11.5 ± 1.7 cmH2O, and the incidence of ACP was 25.0% (13/52). Intensive care unit mortality, overall hospital mortality, and 28-day mortality rates were 19.2% (10/52), 21.2% (11/52), and 32.7% (17/52), respectively. During the study, ACP incidences at PEEPs of 5 cmH2O, 10 cmH2O, and 15 cmH2O were 17.3% (9/52), 21.2% (11/52), and 38.5% (20/52), respectively. Meanwhile, the PaO2/FiO2 ratio improved with increasing PEEP, reaching 162.0 (140.9, 174.0), 171.0 (144.0, 182.0), and 176.5 (151.0, 196) mmHg at PEEPs of 5 cmH2O, 10 cmH2O, and 15 cmH2O, respectively. In addition, higher PEEPs were associated with a slight increase in PaCO2, showing statistically significant differences compared to moderate and low PEEPs. Compared to a PEEP of 5 cmH2O or 10 cmH2O, right ventricular function exhibited substantial changes at 15 cmH2O PEEP, manifested as increased pulmonary artery systolic pressure, enlarged right ventricular end-diastolic area, and decreased tricuspid annular plane systolic excursion, all with significant differences. Conversely, variations in left ventricular end-diastolic area and ejection fraction were not statistically significant. In terms of hemodynamics, increasing PEEP resulted in a decline in cardiac index (CI), with statistically significant differences between different PEEPs. Specifically, compared to the value at a PEEP of 5 cmH2O, the CI at a PEEP of 15 cmH2O decreased by 14.3% (2.63 [2.20, 2.95] vs. 3.07 [2.69, 3.67], p < 0.001). The decline in the stroke volume index with PEEP was more obvious (22.1 [18.4, 27.1] vs. 27.0 [24.2, 33.0], p < 0.001), reaching 18.1%. Additionally, both end-diastolic volume index and extravascular lung water index decreased significantly with increasing PEEP, while the pulmonary vascular permeability index remained unaffected. Different PEEPs can affect the incidence of ACP in patients with moderate-to-severe ARDS. High PEEP improves oxygenation and reduces extravascular lung water without significantly affecting the pulmonary vascular permeability index and left ventricular systolic function. Nevertheless, it can cause right ventricular dilation, as well as substantial declines in right ventricular systolic function and CI, thereby causing ACP.

Pulmonary Vascular Permeability and Extravascular Lung Water Index in Patients with Liver Cirrhosis and Septic Shock.

Backgrounds and Aims: Patients with cirrhosis are susceptible to sepsis and septic shock. Cirrhotic patients also have increased capillary permeability and are prone to developing volume overload. Patients with septic shock may have an enhanced pulmonary vascular permeability index (PVPI) and extravascular lung water index (EVLWI), both of which are associated with an unfavorable prognosis. It is plausible that pre-existing hyperpermeability may deteriorate when cirrhotic patients develop septic shock. However, it remains unknown whether PVPI and EVLWI can predict the prognosis of cirrhotic patients with septic shock. Pulse Indicator Continuous Cardiac Output (PiCCO) is an established tool to measure PVPI and EVLWI. Therefore, we conducted this retrospective study to investigate the prognostic significance of PVPI and EVLWI in cirrhotic patients with septic shock using PiCCO monitoring. Methods: We included 83 patients with liver cirrhosis and septic shock. EVLW indexed to actual body weight (aEVLWI), EVLW indexed to predicted body weight (pEVLWI), PVPI, disease severity scores, and other biomarkers were analyzed. We collected the PiCCO data on the first 2 days. Results: The overall 28-day mortality was 43.4%. The values of PVPI, aEVLWI, and pEVLWI on day 2 (PVPID2, aEVLWID2, EVLWID2) were significantly higher in non-survivors. The discriminating power of PVPID2 and EVLWID2 to predict 28-day mortality was tested using the area under a ROC curve. The areas under ROC curves (mean ± SEM) were 0.713 ± 0.061 and 0.650 ± 0.063 for PVPID2 and pEVLWID2. In the multivariate analysis, PVPID2, bilirubin, and lactate were independent factors which predicted 28-day mortality. Conclusions: Higher levels of PVPID2 and pEVLWID2 are associated with higher 28-day mortality rates in cirrhotic patients with septic shock. PVPI and pEVLWI may be useful to guide fluid management in this clinical setting.

Valproic Acid Treatment Improves Organ Function, Survival Rate, and Lipid Peroxidation in Fatally Scalded Rats

Background After hypovolemic shock caused by severe burns, lipid peroxidation is an important factor in tissue edema and multiorgan dysfunction syndrome (MODS). Many studies have shown that valproic acid (VPA) inhibits lipid peroxidation and reduces tissue and organ injury. Objectives This study investigated whether the VPA treatment of scalded rats reduced tissue edema by inhibiting lipid peroxidation, thereby improving organ function and survival rate. Materials and Methods A total of 60 male Sprague-Dawley rats (weighing: 280–300 g) with a 50% total body surface area (TBSA) full-thickness dermal burn were randomly assigned to the following 3 groups (with 20 rats per group): (I) the no infusion resuscitation (NR) group; (II) the sodium lactate Ringer’s solution (LR) group; and (III) the sodium valproate Ringer’s solution (VR) group. After scalding, the following hemodynamic parameters were measured: Copper2+-Zinc2+-superoxide dismutase (Cu2+-Zn2+-SOD) activity, thiobarbituric acid reactive substances (TBARSs), oxidized glutathione (GSSG), reduced glutathione (GSH), and antioxidant enzyme activities. Organ function parameters and water content were also measured. Another 60 male Sprague-Dawley rats were used to observe the 24-h survival rate of the rats using the same scald model and fluid resuscitation. Results VPA significantly increased the mean arterial pressure (MAP) and cardiac output (CO), and significantly decreased the pulmonary vascular permeability index (PVPI) and extravascular lung water index (ELWI). VPA also increased plasma Cu2+-Zn2+-SOD activity and decreased the plasma TBARS level. VPA reduced the TBARS level and GSSG in various tissues and increased the concentration of GSH. VPA decreased glutathione peroxidase (GPx) and catalase (CAT) activity, but significantly increased glutathione reductase (GR) activity in various tissues. VPA significantly improved organ functions and decreased water content. VPA significantly improved the survival rate, and the 24-h survival rate of the VR group was double that of the LR group. Conclusion Resuscitation with VPA reduced tissue edema, protected visceral functions, and improved the survival rate of rats with severe burn shock (BS) by alleviating lipid peroxidation.

Evaluation of extravascular lung water index in critically ill patients based on lung ultrasound radiomics analysis combined with machine learning

To explore lung ultrasound radiomics features which related to extravascular lung water index (EVLWI), and to predict EVLWI in critically ill patients based on lung ultrasound radiomics combined with machine learning and validate its effectiveness. A retrospective case-control study was conducted. The lung ultrasound videos and pulse indicated continuous cardiac output (PiCCO) monitoring results of critically ill patients admitted to the department of critical care medicine of the First Affiliated Hospital of Guangxi Medical University from November 2021 to October 2022 were collected, and randomly divided into training set and validation set at 8:2. The corresponding images from lung ultrasound videos were obtained to extract radiomics features. The EVLWI measured by PiCCO was regarded as the "gold standard", and the radiomics features of training set was filtered through statistical analysis and LASSO algorithm. Eight machine learning models were trained using filtered radiomics features including random forest (RF), extreme gradient boost (XGBoost), decision tree (DT), Naive Bayes (NB), multi-layer perceptron (MLP), K-nearest neighbor (KNN), support vector machine (SVM), and Logistic regression (LR). Receiver operator characteristic curve (ROC curve) was plotted to evaluate the predictive performance of models on EVLWI in the validation set. A total of 151 samples from 30 patients were enrolled (including 906 lung ultrasound videos and 151 PiCCO monitoring results), 120 in the training set, and 31 in the validation set. There were no statistically significant differences in main baseline data including gender, age, body mass index (BMI), mean arterial pressure (MAP), central venous pressure (CVP), heart rate (HR), cardiac index (CI), cardiac function index (CFI), stroke volume index (SVI), global end diastolic volume index (GEDVI), systemic vascular resistance index (SVRI), pulmonary vascular permeability index (PVPI) and EVLWI. The overall EVLWI range in 151 PiCCO monitoring results was 3.7-25.6 mL/kg. Layered analysis showed that both datasets had EVLWI in the 7-15 mL/kg interval, and there was no statistically significant difference in EVLWI distribution. Two radiomics features were selected by using LASSO algorithm, namely grayscale non-uniformity (weight was -0.006 464) and complexity (weight was -0.167 583), and they were used for modeling. ROC curve analysis showed that the MLP model had better predictive performance. The area under the ROC curve (AUC) of the prediction validation set EVLWI was higher than that of RF, XGBoost, DT, KNN, LR, SVM, NB models (0.682 vs. 0.658, 0.657, 0.614, 0.608, 0.596, 0.557, 0.472). The gray level non-uniformity and complexity of lung ultrasound were the most correlated radiomics features with EVLWI monitored by PiCCO. The MLP model based on gray level non-uniformity and complexity of lung ultrasound can be used for semi-quantitative prediction of EVLWI in critically ill patients.

Cardiac arrest related lung edema: examining the role of downtimes in transpulmonary thermodilution analysis.

Pulmonary edema and its association with low flow times has been observed in postcardiac arrest patients. However, diagnosis of distinct types of lung pathology is difficult.The aim of this study was to investigate pulmonary edema by transpulmonary thermodilution (TPTD) after out-of-hospital cardiac arrest (OHCA), and the correlation to downtimes. In this retrospective single-center study consecutive patients with return of spontaneous circulation (ROSC) following OHCA, age ≥ 18, and applied TPTD were enrolled. According to downtimes, patients were divided into a short and a long no-flow-time group, and data of TPTD were analysed. We identified 45 patients (n = 25 short no-flow time; n = 20 long no-flow time) who met the inclusion criteria. 24h after ROSC, the extra vascular lung water index (EVLWI) was found to be lower in the group with short no-flow time compared to the group with long no-flow time (10.7 ± 3.5ml/kg vs. 12.8 ± 3.9ml/kg; p = 0.08) and remained at a similar level 48h (10.9 ± 4.3ml/kg vs. 12.9 ± 4.9ml/kg; p = 0.25) and 72h (11.1 ± 5.0ml/kg vs. 13.9 ± 7.7ml/kg; p = 0.27) post-ROSC. We found a statistically significant and moderate correlation between no-flow duration and EVLWI 48h (r = 0.51; p = 0.002) and 72h (r = 0.54; p = 0.004) post-ROSC. Pulmonary vascular permeability index (PVPI) was not correlated with downtimes. Our observation underlines the presence of cardiac arrest-related lung edema by determination of EVLWI. The duration of no-flow times is a relevant factor for increased extravascular lung water index.

SULFORAPHANE ALLEVIATES POSTRESUSCITATION LUNG PYROPTOSIS POSSIBLY VIA ACTIVATING THE NRF2/HO-1 PATHWAY.

Introduction: Sulforaphane (SFN), known as the activator of the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway, has been proven to protect the lung against various pathological stimuli. The present study aimed to investigate the effect of SFN on lung injury induced by systemic ischemia reperfusion after cardiac arrest and resuscitation. Methods: After animal preparation, 24 pigs were randomly divided into sham group (n = 6), cardiopulmonary resuscitation group (CPR, n = 9), or CPR + SFN group (n = 9). The experimental model was then established by 10 min of cardiac arrest followed by 6 min of CPR. Once spontaneous circulation was achieved, a dose of 2 mg/kg of SFN diluted in 20 mL of saline was intravenously infused with a duration of 5 min. During 4 h of observation after resuscitation, extravascular lung water index (ELWI), pulmonary vascular permeability index (PVPI), and oxygenation index were regularly evaluated. At 24 h after resuscitation, lung tissues were harvested to evaluate the score of lung histopathological injury, the activity of superoxide dismutase, the contents of malondialdehyde, IL-1β, and IL-18, and the expression levels of NOD-like receptor pyrin domain 3, cleaved caspase 1, gasdermin D (GSDMD), GSDMD N-terminal, Nrf2, and HO-1. Results: During CPR, spontaneous circulation was achieved in six and seven pigs in the CPR and CPR + SFN groups, respectively. After resuscitation, the indicators of lung injury (ELWI, PVPI, and oxygenation index) were all better in the CPR + SFN group than in the CPR group, in which the differences in ELWI and PVPI at 2, and 4 h after resuscitation were significant between the two groups. In addition, SFN significantly reduced lung injury score, improved oxidative imbalance (superoxide dismutase, malondialdehyde), decreased pyroptosis-related proinflammatory cytokines (IL-1β, IL-18), downregulated pyroptosis-related proteins (NOD-like receptor pyrin domain 3, cleaved caspase 1, GSDMD, GSDMD N-terminal), and activated the Nrf2/HO-1 pathway when compared with the CPR group. Conclusion: SFN produced effective postresuscitation lung protection through alleviating lung pyroptosis possibly via activating the Nrf2/HO-1 pathway in pigs.

Relationship of Extravascular Lung Water and Pulmonary Vascular Permeability to Respiratory Mechanics in Patients with COVID-19-Induced ARDS

During acute respiratory distress syndrome (ARDS), the increase in pulmonary vascular permeability and lung water induced by pulmonary inflammation may be related to altered lung compliance. A better understanding of the interactions between respiratory mechanics variables and lung water or capillary permeability would allow a more personalized monitoring and adaptation of therapies for patients with ARDS. Therefore, our main objective was to investigate the relationship between extravascular lung water (EVLW) and/or pulmonary vascular permeability index (PVPI) and respiratory mechanic variables in patients with COVID-19-induced ARDS. This is a retrospective observational study from prospectively collected data in a cohort of 107 critically ill patients with COVID-19-induced ARDS from March 2020 to May 2021. We analyzed relationships between variables using repeated measurements correlations. We found no clinically relevant correlations between EVLW and the respiratory mechanics variables (driving pressure (correlation coefficient [CI 95%]: 0.017 [-0.064; 0.098]), plateau pressure (0.123 [0.043; 0.202]), respiratory system compliance (-0.003 [-0.084; 0.079]) or positive end-expiratory pressure (0.203 [0.126; 0.278])). Similarly, there were no relevant correlations between PVPI and these same respiratory mechanics variables (0.051 [-0.131; 0.035], 0.059 [-0.022; 0.140], 0.072 [-0.090; 0.153] and 0.22 [0.141; 0.293], respectively). In a cohort of patients with COVID-19-induced ARDS, EVLW and PVPI values are independent from respiratory system compliance and driving pressure. Optimal monitoring of these patients should combine both respiratory and TPTD variables.

The Clinical Significance of iNOS/NO Signaling Pathway in Traumatic Shock and the Mechanism under the Promotion on the Development of Traumatic Shock via Endoplasmic Reticulum Stress.

This study aims to clarify the clinical significance of the inducible nitric oxide synthase (iNOs)/nitric oxide (NO) signaling pathway and endoplasmic reticulum stress (ERS) in traumatic shock (TS) and the mechanism of action, so as to offer a novel direction for the emergency treatment of TS in the future. The clinical data of 90 patients with TS treated in our hospital between June 2019 and January 2021 were retrospectively analyzed. Patients were divided into mild (n = 30), moderate (n = 30), and severe group (n = 30) based on their disease severity. Furthermore, patients were assigned into Groups A and B for fluid resuscitation based on a pulse index continuous cardiac output (PICCO) monitor and fluid resuscitation based on monitoring results of central venous pressure (CVP) and mean arterial pressure (MAP), respectively. Additionally, the 18 purchased Sprague Dawley (SD) rats were randomized into model (TS model), control (normal rats) and intervention (TS model injected with iNOS inhibitor) groups, with 6 rats each. iNOs and NO levels were measured by colorimetry, and the concentrations of inflammatory factors were quantified using enzyme-linked immunosorbent assays (ELISAs). Polymerase chain reaction (PCR) and western blot were adopted for the quantification of ERS markers (glucose-related protein 78 (GRP78), GRP94 and C/EBP homologous protein (CHOP)), and hematoxylin-eosin (HE) staining of rat cardiac tissue was carried out to observe the pathological state of myocardial tissue. The moderate group showed higher levels of iNOS, NO, GRP78, GRP94 and CHOP than the mild group and lower levels of them than the severe group (all p < 0.05). MAP, extravascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI), and locus control region (LCR) increased in both Groups A and B after resuscitation, with more significant increases of these parameters in Group A. The application of PICCO technique lowered the levels of iNOS, NO, inflammatory factors, GRP78, GRP94 and CHOP in TS patients. In addition, the intervention group had lower levels of iNOS, NO, inflammatory factors, GRP78, GRP94, and CHOP than the model group and higher levels of them than the control group. According to the results of HE staining of myocardial tissue, the intervention group had significantly alleviated myocardial necrosis than the model group, with slightly stained cytoplasm, visible contraction bands in most myocardium, and significantly reduced neutrophil infiltration. iNOS/NO and ERS increase with the severity of TS, and PICCO can effectively lower their levels. The results of animal experiments suggest that the inhibition of iNOS/NO can relieve inflammation and ERS intensification, thus alleviating the progression of TS.

Diagnostic value of transpulmonary thermodilution measurements for acute respiratory distress syndrome in a pig model of septic shock

BackgroundNo direct approach assessing pulmonary vascular permeability exists in the current therapeutic strategy for patients with acute respiratory distress syndrome (ARDS). Transpulmonary thermodilution measures hemodynamic parameters such as pulmonary vascular permeability index and extravascular lung water, enabling clinicians to assess ARDS severity. The aim of this study is to explore a precise transpulmonary thermodilution-based criteria for quantifying the severity of lung injury using a clinically relevant septic-ARDS pig model.MethodsThirteen female pigs (weight: 31 ± 2 kg) were intubated, mechanically ventilated under anesthesia, and either assigned to septic shock-induced ARDS or control group. To confirm the development of ARDS, we performed computed tomography (CT) imaging in randomly selected animals. The pulmonary vascular permeability index, extravascular lung water, and other hemodynamic parameters were consecutively measured during the development of septic lung injury. Lung status was categorized as normal (partial pressure of oxygen/fraction of inspired oxygen ≥ 400), or injured at different degrees: pre-ARDS (300–400), mild-to-moderate ARDS (100–300), or severe ARDS (< 100). We also measured serum inflammatory cytokines and high mobility group box 1 levels during the experiment to explore the relationship of the pulmonary vascular permeability index with these inflammatory markers.ResultsUsing CT image, we verified that animals subjected to ARDS presented an extent of consolidation in bilateral gravitationally dependent gradient that expands over time, with diffuse ground-glass opacification. Further, the post-mortem histopathological analysis for lung tissue identified the key features of diffuse alveolar damage in all animals subjected to ARDS. Both pulmonary vascular permeability index and extravascular lung water increased significantly, according to disease severity. Receiver operating characteristic analysis demonstrated that a cut-off value of 3.9 for the permeability index provided optimal sensitivity and specificity for predicting severe ARDS (area under the curve: 0.99, 95% confidence interval, 0.98–1.00; sensitivity = 100%, and specificity = 92.5%). The pulmonary vascular permeability index was superior in its diagnostic value than extravascular lung water. Furthermore, the pulmonary vascular permeability index was significantly associated with multiple parameters reflecting clinicopathological changes in animals with ARDS.ConclusionThe pulmonary vascular permeability index is an effective indicator to measure septic ARDS severity.

Extravascular lung water index, pulmonary vascular permeability index, and global end-diastolic volume index in mechanically ventilated COVID-19 patients requiring prone position ventilation: a preliminary retrospective study.

There is a lack of data on extravascular lung water index (EVLWi), pulmonary vascular permeability index (PVPi), and global end-diastolic volume index (GEDVi) during prone position ventilation (PPV) in coronavirus disease 2019 (COVID-19) patients. The objectives of this study were to analyze trends in EVLWi, PVPi, and GEDVi during PPV and the relationships between these parameters and PaO2/FiO2. In this preliminary retrospective observational study, we performed transpulmonary thermodilution (TPTD) in seven mechanically ventilated COVID-19 patients without cardiac and pulmonary comorbidities requiring PPV for 18 hours, at specific times (30 minutes pre-PPV, 18 hours after PPV, and 3 hours after supination). EVLWi, PVPi and GEDVi were measured. The relationships between PaO2/FiO2 and EVLWi, and PVPi and GEDVi values, in the supine position were analyzed by linear regression. Correlation and determination coefficients were calculated. EVLWi was significantly different between three time points (analysis of variance, P=0.004). After 18 hours in PPV, EVLWi was lower compared with values before PPV (12.7±0.9 ml/kg vs. 15.3±1.5 ml/kg, P=0.002). Linear regression showed that only EVLWi was correlated with PaO2/FiO2 (β =-5.757; 95% confidence interval, -10.835 to -0.679; r=-0.58; R2 =0.34; F-test P=0.029). EVLWi was significantly reduced after 18 hours in PPV and values measured in supine positions were correlated with PaO2/FiO2. This relationship can help clinicians discriminate whether deterioration in gas exchange is related to fluid overload or disease progression. Further clinical research should evaluate the role of TPTD parameters as markers to stratify disease severity and guide clinical management.

ALDA-1 TREATMENT ALLEVIATES LUNG INJURY AFTER CARDIAC ARREST AND RESUSCITATION IN SWINE.

Introduction: Alda-1, an aldehyde dehydrogenase 2 (ALDH2) activator, has been shown to protect the lung against a variety of diseases including regional ischemia-reperfusion injury, severe hemorrhagic shock, hyperoxia, and so on. The present study was designed to investigate the effectiveness of Alda-1 treatment in alleviating lung injury after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) in swine. Methods: A total of 24 swine were randomized into three groups: sham (n = 6), CA/CPR (n = 10), and CA/CPR + Alda-1 (n = 8). The swine model was established by 8 min of electrically induced and untreated CA, and then 8 min of manual CPR. A dose of 0.88 mg/kg of Alda-1 was intravenously injected at 5 min after CA/CPR. After CA/CPR, extravascular lung water index (ELWI), pulmonary vascular permeability index (PVPI), and oxygenation index (OI) were regularly evaluated for 4 h. At 24 h after resuscitation, lung ALDH2 activity was detected, and its injury score, apoptosis, and ferroptosis were measured. Results: After experiencing the same procedure of CA and CPR, five swine in the CA/CPR group and six swine in the CA/CPR + Alda-1 group restored spontaneous circulation. Subsequently, significantly increased ELWI and PVPI, and markedly decreased OI were observed in these two groups compared with the sham group. However, all of them were gradually improved and significantly better in the swine treated with the Alda-1 compared with the CA/CPR group. Tissue analysis indicated that lung ALDH2 activity was significantly decreased in those swine experiencing the CA/CPR procedure compared with the sham group; nevertheless, its activity was significantly greater in the CA/CPR + Alda-1 group than in the CA/CPR group. In addition, lung injury score, and its apoptosis and ferroptosis were significantly increased in the CA/CPR and CA/CPR + Alda-1 groups compared with the sham group. Likewise, Alda-1 treatment significantly decreased these pathological damages in lung tissue when compared with the CA/CPR group. Conclusions: Alda-1 treatment was effective to alleviate lung injury after CA/CPR in a swine model, in which the protective role was possibly related to the inhibition of cell apoptosis and ferroptosis. It might provide a novel therapeutic target and a feasible therapeutic drug for lung protection after CA/CPR.

The Effects of Airway Pressure Release Ventilation on Pulmonary Permeability in Severe Acute Respiratory Distress Syndrome Pig Models.

Objective: The aim of the study was to compare the effects of APRV and LTV ventilation on pulmonary permeability in severe ARDS. Methods: Mini Bama adult pigs were randomized into the APRV group (n = 5) and LTV group (n = 5). A severe ARDS animal model was induced by the whole lung saline lavage. Pigs were ventilated and monitored continuously for 48 h. Results: Compared with the LTV group, CStat was significantly better (p < 0.05), and the PaO2/FiO2 ratio showed a trend to be higher throughout the period of the experiment in the APRV group. The extravascular lung water index and pulmonary vascular permeability index showed a trend to be lower in the APRV group. APRV also significantly mitigates lung histopathologic injury determined by the lung histopathological injury score (p < 0.05) and gross pathological changes of lung tissues. The protein contents of occludin (p < 0.05), claudin-5 (p < 0.05), E-cadherin (p < 0.05), and VE-cadherin (p < 0.05) in the middle lobe of the right lung were higher in the APRV group than in the LTV group; among them, the contents of occludin (p < 0.05) and E-cadherin (p < 0.05) of the whole lung were higher in the APRV group. Transmission electron microscopy showed that alveolar–capillary barrier damage was more severe in the middle lobe of lungs in the LTV group. Conclusion: In comparison with LTV, APRV could preserve the alveolar–capillary barrier architecture, mitigate lung histopathologic injury, increase the expression of cell junction protein, improve respiratory system compliance, and showed a trend to reduce extravascular lung water and improve oxygenation. These findings indicated that APRV might lead to more profound beneficial effects on the integrity of the alveolar–capillary barrier architecture and on the expression of biomarkers related to pulmonary permeability.

Comparative analysis of intraoperative lung protection technologies in patients having cardiorespiratory comorbidity during coronary bypass surgery with artificial circulation

Objective: Comparative analysis of the effect of budesonide and low-volume artificial lung ventilation (ALV) on pulmonary volemia, oxygen transport and respiratory biomechanics in patients having cardio-respiratory comorbidity during сoronary artery bypass graft (CABG) with artificial blood circulation (ABC).Methods: The clinical study included 50 patients having cardiorespiratory comorbidity with a median age of 66 years who were admitted to the clinic of the Far Eastern Federal University for planned CABG in conditions of ABC. The patients were divided into 2 groups by random sampling method. The first group consisted of 25 patients who underwent low-volume artificial lung ventilation (ALV) with inhalation of nebulized budesonide during ABC; the second – 25 patients underwent isolated low-volume ALV during ABC. The study was carried out in three stages: before the start of ABC, after its completion and a day after CABG. Extravascular lung water index (ELWI) and pulmonary vascular permeability index (PVPI) were registered using method of transpulmonary thermodilution. Oxygen transport indicators were determined: oxygen delivery index (DO2I) and oxygen consumption index (VO2I), pulmonary blood bypass fraction (Qs/Qt), oxygenation index (OI).Results: After turning off ABC in the first group, the ELWI decreased by 23%, in the second group it declined by 8%. Among patients treated with budesonide, PVPI significantly decreased after providing ABC. However among patients of the second group it remained unchanged. DO2I remained in the reference range among all patients. However VO2I was below it with a minimum value in the second group after ABC stopping. In this cohort the level of Qs/Qt was significantly higher, and OI was lower than in patients of the first group. The resistance of the lung tissue decreased on the background of an increase in its compliance among patients who received budesonide immediately after ABC and 2 hours after it. In the second group there was opposite dynamics of these indicators.Conclusions:The combination of low-volume ALV and inhalation of nebulized budesonide during ABC stabilizes the volemic status of the lungs, improves their oxygenating function and respiratory biomechanics in the postperfusion and early postoperative periods of CABG.

Autologous red blood cell transfusion does not result in a more profound increase in pulmonary capillary wedge pressure compared to saline in critically ill patients: A randomized crossover trial.

Background and ObjectivesTransfusion‐associated circulatory overload (TACO) is a major cause of severe transfusion‐related morbidity. Transfusion of red blood cells (RBCs) has been shown to induce hydrostatic pressure overload. It is unclear which product‐specific factors contribute. We set out to determine the effect of autologous RBC transfusion versus saline on pulmonary capillary wedge pressure (PCWP) change.Materials and MethodsIn a randomized crossover trial, patients who had undergone coronary bypass surgery were allocated to treatment post‐operatively in the intensive care unit with either an initial 300 ml autologous RBC transfusion (salvaged during surgery) or 300 ml saline infusion first, followed by the other. Primary outcome was the difference in PCWP change. Secondary outcome measures were the difference in extra‐vascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI).ResultsChange in PCWP was not higher after autologous RBC transfusion compared to saline (ΔPCWP 0.3 ± 0.4 vs. 0.1 ± 0.4 mmHg). ΔEVLWI and ΔPVPI were significantly decreased after autologous RBC transfusion compared to saline (ΔEVLWI −1.6 ± 0.6 vs. 0.2 ± 0.4, p = 0.02; ΔPVPI −0.3 ± 0.1 vs. 0.0 ± 0.1, p = 0.01). Haemodynamic variables and colloid osmotic pressure were not different for autologous RBC transfusion versus saline.ConclusionTransfusion of autologous RBCs did not result in a more profound increase in PCWP compared to saline. RBC transfusion resulted in a decrease of EVLWI and PVPI compared to saline. Our data suggest that transfusing autologous RBCs may lead to less pulmonary oedema compared to saline. Future studies with allogeneic RBCs are needed to investigate other factors that may mediate the increase of PCWP, resulting in TACO.

Protective effect of restrictive resuscitation on vascular endothelial glycocalyx in pigs with traumatic hemorrhagic shock.

BackgroundHemorrhagic shock is the leading cause of early traumatic death. Research and discussion on restrictive fluid resuscitation have been ongoing for many years. The purpose of this study was to explore whether restrictive resuscitation can inhibit the shedding of vascular endothelial glycocalyx in the prehospital treatment of traumatic hemorrhagic shock pigs.MethodsLandrace pigs were randomly divided into a restrictive resuscitation group (restrictive group) and a conventional resuscitation group (conventional group), with 6 pigs in each group. The gunshot caused a rupture of the pig’s receding right femoral artery, and the average arterial pressure was 40–45 mmHg stable for 30 minutes, which was defined as a successful shock model. The end point of resuscitation in the restrictive group was a mean arterial pressure (MAP) of 55–60 mmHg for 30 minutes, and the end point of resuscitation in the conventional group was a MAP of 70–75 mmHg for 30 minutes. The results of arterial blood gas analysis, hemodynamic indicators, endothelial glycocalyx damage and shedding marker Syndecan1 and soluble thrombomodulin (sTM) expression levels were compared between the two groups of experimental pigs after resuscitation.ResultsThe two groups of experimental pigs had the same baseline levels before injury in age, body weight, blood loss, cardiac output index, cardiac function index (CFI), extravascular lung water index (ELWI), and pulmonary vascular permeability index (PVPI). The arterial blood gas analysis of the two experimental pigs showed no significant difference in carbon dioxide partial pressure, oxygen partial pressure, blood oxygen saturation, or blood lactic acid after resuscitation. The difference in cardiac output index and CFI at the end of resuscitation between the two groups was not statistically significant; the absolute value and percentage of Syndecan1 level increase in the restrictive resuscitation group were lower than those in the conventional resuscitation group, and the difference was statistically significant.ConclusionsCompared with full resuscitation in a short period of prehospital treatment, restrictive resuscitation can achieve a similar effect in maintaining tissue oxygen supply and can reduce the loss of vascular endothelial glycocalyx to a certain extent.

Effects on extravascular lung water of lung protective ventilation strategy applied on piglets with acute respiratory distress syndrome induced by paraquat

Objective: To study the effects on extravascular lung water of lung protective ventilation strategy applying on piglets with acute respiratory distress syndrome (ARDS) induced by paraquat (PQ) under pulse indicating continuous cardiac output (PiCCO) monitoring. Methods: The piglets models with ARDS induced by PQ were established in June 2020 and all of them were received mechanical ventilation and divided into three groups according to tidal volume (V(T)) : small V(T) group (6 ml/kg) , middle V(T) group (10 ml/kg) and large V(T) group (15 ml/kg) , there were 5 piglets in each group. The positive end expiratory pressure (PEEP) were all setup on 10 cmH(2)O. The indexes such as arterial blood gas analysis, oxygenation index (OI) , extravascular lung water index (ELWI) and pulmonary vascular permeability index (PVPI) were monitored at time of before the model was established (baseline) , time of the model was established (t(0)) and 2 h (t(2)) , 4 h (t(4)) , 6 h (t(6)) after mechanical ventilation. Lung tissue were punctured at time of baseline, t(0) and t(6) to be stained by Hematoxylin-eosin (HE) staining and pulmonary pathology were observed under light microscopy. Results: The heart rate (HR) , mean arterial pressure (MAP) and partial pressure of carbon dioxide (PaCO(2)) of all groups were higher than the base value while the pH values, partial pressure of oxygen (PaO(2)) and OI were lower than the base value when the models were established (P<0.05) . After mechanical ventilation, the HR and MAP values of all groups at t(2), t(4) and t(6) were lower than t(0) while the PaCO(2) of t(4) and t(6) were all higher than t(0), the differences were statistically significant (P<0.05) . The PaO(2) and OI of all groups showed a trend of rising at first and then decreasing after mechanical ventilation. The MAP, PaO(2), PaCO(2) and OI of the middle V(T) group and large V(T) group were apparently lower than that of the small V(T) group at t(2), t(4) and t(6) (P<0.05) . The ELWI and PVPI at t(0) of all groups were higher than that of baseline (P<0.05) . The ELWI of the small V(T) group at t(6) were lower than t(0) of the same group and t(6) of the middle V(T) group and large V(T) group (P<0.05) . HE staining showed congestion and edema of alveolar tissue, swelling of capillaries, exudation of red blood cells and widening of alveolar septum in piglets after successful modeling. And further widening of alveolar septum and rupture of alveolar septum could be seen in the lung tissues of each group at t(6), and the injury was the slightest in the small V(T) group. Conclusion: The lung protective ventilation strategy can alleviate the extravascular lung water and ARDS induced by PQ and improve oxygenation.

Evaluation of volemic status during combined extracorporeal detoxification in patients with severe acute pancreatitis: a retrospective observational study

INTRODUCTION: The morbidity and mortality of severe acute pancreatitis (SAP) remains high. Intensive therapy aimed at stopping hypovolemia, systemic endotoxicosis is a debatable problem. OBJECTIVE: Improving treatment results in patients with SAP by assessing the dynamics of volumetric criteria and the degree of fluid therapy (FT). MATERIALS AND METHODS: The study included 25 patients. First, study group of 9 patient, used standard therapy in conjunction with selective hemoperfusion and continuous veno-venous hemofiltration. Second, control group of 16 patients, who received standard intensive care. FT in the groups was 2.5–3.5 ml/kg/h. Volemic parameters were measured by transpulmonary thermodilution. The central venous pressure and the diameter of the vena cava inferior were assessed. Comparative analysis was performed between two groups. RESULTS: FT in the amount of 58.7 (52.4–59.4) ml/kg/day in group 1, and 58.3 (54.2–61.4) ml/kg/day in group 2 in the first day, up to 83.9 (72.4–86.1) and 79.3 (72.4–84.1) ml/kg/day, was observed by day 3 (p &lt; 0.05), according to the results of transpulmonary thermodilution. From the 1st to the 3rd day, Global end-diastolic volume index increased from 345 (328–412) to 648 (590–690) ml/m2 in group 1, and from 375 (348–413) to 654 (599–701) ml/m2 in group 2 (p &lt; 0.05). Intrathoracic blood volume index increased from 440 (420–510) to 780 (750–40) ml/m2 in group 1 and 430 (417.5–465) to 750 (665–780) ml/m2 in group 2 (p &lt; 0.05). Extravascular lung water index and pulmonary vascular permeability index by 5 days in group 2 increased by 1.8 — 11 (10.5–11.8) and 2.2 times — 6.5 (5.75–7), respectively (p &lt; 0.05). CONCLUSIONS: FT 3.5 ml/kg/h, reaches isovolemia by the 3rd day of therapy. The use of extracorporeal detoxification methods in complex therapy is accompanied by an improvement in clinical and laboratory parameters.