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Extravascular lung water index and pulmonary vascular permeability index/intrathoracic blood volume correlation in non-ALI/ARDS patients. Correlation between extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) and that between EVLWI and intrathoracic blood volume (ITBV) in patients with non-acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). For this analysis, cardiogenic edema and pleural effusion with atelectasis patients were combined as non-ALI/ARDS. EVLWI had a moderate correlation with PVPI (r = 0.464, P < 0.01) (A) and with ITBV (r = 0.493, P < 0.01) (B). EVLWI-0, extravascular lung water index on the day of enrollment; PVPI-0, pulmonary vascular permeability index on the day of enrollment; ITBV-0, intrathoracic blood volume on the day of enrollment.
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Introduction:
Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by features other than increased pulmonary vascular permeability. Pulmonary vascular permeability combined with increased extravascular lung water content has been considered a quantitative diagnostic criterion of ALI/ARDS. This prospective, multi-ins...
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Haemodynamic monitoring before extra-corporeal membrane oxygenation (ECMO) might help to optimize the effectiveness of ECMO. However, there are concerns that pulmonary arterial and trans-pulmonary thermodilution (TPTD) might be confounded by a loss of indicator into the ECMO-circuit, resulting in an overestimation of volumetric parameters. Since th...
Citations
... It has been reported that pulmonary vascular permeability index may be a useful diagnostic tool in differentiating ARDS and cardiogenic pulmonary edema. 31 A previous study by our team showed that high cardiac output can increase extravascular lung water and pulmonary edema while tissue perfusion-aimed lower CO could decrease pulmonary edema and achieve a better prognosis. 32 The disruption of glycocalyx of pulmonary capillaries plays an important role in lung water leakage and pulmonary edema. ...
The high respiratory and cardiac drive is essential to the host-organ unregulated response. When a primary disease and an unregulated secondary response are uncontrolled, the patient may present in a high respiratory and cardiac drive state. High respiratory drive can cause damage to the lungs, pulmonary circulation, and diaphragm, while high cardiac drive can lead to fluid leakage and infiltration as well as pulmonary interstitial edema. A “respiratory and cardiac dual high drive” state may be a sign of an unregulated response and can lead to secondary lung injury through the increase of transvascular pressure and pulmonary microcirculation injury. Ultrasound examination of the lung, heart, and diaphragm is important when evaluating the phenotype of high respiratory drive in critically ill patients. Ultrasound assessment can guide sedation, analgesia, and antistress treatment and reduce the risk of high respiratory and cardiac drive-induced lung injury in these patients.
... PiCCO-derived EVLWi is a validated, quantitative measure of pulmonary edema in ARDS [11,[17][18][19]. Recent years have seen an effort to quantify pulmonary edema using LUS [7,14,15] using B-lines, ultrasonographic artifacts thought to arise from the change in acoustic impedance between aerated and non-aerated tissue [20]. ...
Background
Lung ultrasound (LUS) can detect pulmonary edema and it is under consideration to be added to updated acute respiratory distress syndrome (ARDS) criteria. However, it remains uncertain whether different LUS scores can be used to quantify pulmonary edema in patient with ARDS.
Objectives
This study examined the diagnostic accuracy of four LUS scores with the extravascular lung water index (EVLWi) assessed by transpulmonary thermodilution in patients with moderate-to-severe COVID-19 ARDS.
Methods
In this predefined secondary analysis of a multicenter randomized-controlled trial (InventCOVID), patients were enrolled within 48 hours after intubation and underwent LUS and EVLWi measurement on the first and fourth day after enrolment. EVLWi and ∆EVLWi were used as reference standards. Two 12-region scores (global LUS and LUS–ARDS), an 8-region anterior–lateral score and a 4-region B-line score were used as index tests. Pearson correlation was performed and the area under the receiver operating characteristics curve (AUROCC) for severe pulmonary edema (EVLWi > 15 mL/kg) was calculated.
Results
26 out of 30 patients (87%) had complete LUS and EVLWi measurements at time point 1 and 24 out of 29 patients (83%) at time point 2. The global LUS ( r = 0.54), LUS–ARDS ( r = 0.58) and anterior–lateral score ( r = 0.54) correlated significantly with EVLWi, while the B-line score did not ( r = 0.32). ∆global LUS ( r = 0.49) and ∆anterior–lateral LUS ( r = 0.52) correlated significantly with ∆EVLWi. AUROCC for EVLWi > 15 ml/kg was 0.73 for the global LUS, 0.79 for the anterior–lateral and 0.85 for the LUS–ARDS score.
Conclusions
Overall, LUS demonstrated an acceptable diagnostic accuracy for detection of pulmonary edema in moderate–to–severe COVID-19 ARDS when compared with PICCO. For identifying patients at risk of severe pulmonary edema, an extended score considering pleural morphology may be of added value.
Trial registration : ClinicalTrials.gov identifier NCT04794088, registered on 11 March 2021. European Clinical Trials Database number 2020–005447-23.
... Kushimoto et al. measured extravascular lung water and pulmonary vascular permeability in 266 patients with a PaO 2 /FiO 2 ratio less than 300 mmHg and bilateral infiltrates on chest radiographs [56,57]. Three expert clinicians retrospectively reviewed clinical information to determine if the patients had ARDS, cardiogenic pulmonary edema, or atelectasis with pleural effusion. ...
At present, the management of patients with acute respiratory distress syndrome (ARDS) largely focuses on ventilator settings to limit intrathoracic pressures by using low tidal volumes and on FiO2/PEEP relationships to maintain optimal gas exchange. Acute respiratory distress syndrome is a complex medical disorder that can develop in several primary acute disorders, has a rapid time course, and has several classifications that can reflect either the degree of hypoxemia, the extent of radiographic involvement, or the underlying pathogenesis. The identification of subtypes of patients with ARDS would potentially make precision medicine possible in these patients. This is a very difficult challenge given the heterogeneity in the clinical presentation, pathogenesis, and treatment responses in these patients. The analysis of large databases of patients with acute respiratory failure using statistical methods such as cluster analysis could identify phenotypes that have different outcomes or treatment strategies. However, clinical information available on presentation is unlikely to separate patients into groups that allow for secure treatment decisions or outcome predictions. In some patients, non-invasive positive pressure ventilation provides adequate support through episodes of acute respiratory failure, and the development of specialized units to manage patients with this support might lead to the better use of hospital resources. Patients with ARDS have capillary leak, which results in interstitial and alveolar edema. Early attention to fluid balance in these patients might improve gas exchange and alter the pathophysiology underlying the development of severe ARDS. Finally, more attention to the interaction of patients with ventilators through complex monitoring systems has the potential to identify ventilator dyssynchrony, leading to ventilator adjustments and potentially better outcomes. Recent studies with COVID-19 patients provide tentative answers to some of these questions. In addition, expert clinical investigators have analyzed the promise and difficulties associated with the development of precision medicine in patients with ARDS.
... In the early stage, occurring from the first few hours to several days, histopathological changes in the lungs include alveolar epithelial and capillary endothelial cell damage, increased microvascular permeability, exudation of inflammatory cells and cytokines, and tiny alveolar consolidation and edema. The late stage, occurring several days later, is characterized by lung tissue fibrosis [10][11][12]. Despite the numerous scientific and technological advancements, ALI still poses a significant threat to human life and health, given its rapid clinical development, high pathogenic rate, lack of effective treatment, poor prognosis, and high mortality rate. ...
Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a critical and life-threatening illness that causes severe dyspnea, and respiratory distress and is often caused by a variety of direct or indirect factors that damage the alveolar epithelium and capillary endothelial cells, leading to inflammation factors and macrophage infiltration. Macrophages play a crucial role in the progression of ALI/ARDS, exhibiting different polarized forms at different stages of the disease that control the disease outcome. MicroRNAs (miRNA) are conserved, endogenous, short non-coding RNAs composed of 18-25 nucleotides that serve as potential markers for many diseases and are involved in various biological processes, including cell proliferation, apoptosis, and differentiation. In this review, we provide a brief overview of miRNA expression in ALI/ARDS and summarize recent research on the mechanism and pathways by which miRNAs respond to macrophage polarization, inflammation, and apoptosis. The characteristics of each pathway are also summarized to provide a comprehensive understanding of the role of miRNAs in regulating macrophage polarization during ALI/ARDS.
... The calculation was based on an anticipated baseline EVLWi of 17 ml/kg with a standard deviation (SD) of 7 ml/kg. This was based on previously performed EVLW measurements in patients with moderate to severe ARDS [32][33][34]. The expected EVLWi reduction of 25% was based on preclinical data [11]. ...
Purpose
A hallmark of acute respiratory distress syndrome (ARDS) is hypoxaemic respiratory failure due to pulmonary vascular hyperpermeability. The tyrosine kinase inhibitor imatinib reversed pulmonary capillary leak in preclinical studies and improved clinical outcomes in hospitalized COVID-19 patients. We investigated the effect of intravenous (IV) imatinib on pulmonary edema in COVID-19 ARDS.
Methods
This was a multicenter, randomized, double-blind, placebo-controlled trial. Invasively ventilated patients with moderate-to-severe COVID-19 ARDS were randomized to 200 mg IV imatinib or placebo twice daily for a maximum of seven days. The primary outcome was the change in extravascular lung water index (∆EVLWi) between days 1 and 4. Secondary outcomes included safety, duration of invasive ventilation, ventilator-free days (VFD) and 28-day mortality. Posthoc analyses were performed in previously identified biological subphenotypes.
Results
66 patients were randomized to imatinib (n = 33) or placebo (n = 33). There was no difference in ∆EVLWi between the groups (0.19 ml/kg, 95% CI − 3.16 to 2.77, p = 0.89). Imatinib treatment did not affect duration of invasive ventilation ( p = 0.29), VFD ( p = 0.29) or 28-day mortality ( p = 0.79). IV imatinib was well-tolerated and appeared safe. In a subgroup of patients characterized by high IL-6, TNFR1 and SP-D levels (n = 20), imatinib significantly decreased EVLWi per treatment day (− 1.17 ml/kg, 95% CI − 1.87 to − 0.44).
Conclusions
IV imatinib did not reduce pulmonary edema or improve clinical outcomes in invasively ventilated COVID-19 patients. While this trial does not support the use of imatinib in the general COVID-19 ARDS population, imatinib reduced pulmonary edema in a subgroup of patients, underscoring the potential value of predictive enrichment in ARDS trials.
Trial registration NCT04794088 , registered 11 March 2021. European Clinical Trials Database (EudraCT number: 2020-005447-23).
... As the gold standard for the diagnosis of ARDS, chest CT/X-ray is not suitable for the continuous and rapid pulmonary assessment of patients supported with VA-ECMO due to its transport difficulties and high cost.Hydrostatic pulmonary oedema is one of the serious complications of VA-ECMO support therapy, and increased pulmonary oedema leads to impaired gas exchange, contributing to respiratory failure in ARDS. Systematic prospective multi-institutional studies showed that pulmonary oedema is directly correlated with PaO 2 /FiO 2 [19]. A strong negative association between the LUS score and Cdyn at 48 h, Day 5 and Day 10 after the commencement of VV-ECMO was observed in adult patients with ARDS [20]. ...
Purpose
The aim of the study was to evaluate the value of lung ultrasound (LUS) in patients with cardiogenic shock treated by venoarterial extracorporeal membrane oxygenation (VA-ECMO).
Methods
A retrospective study was conducted in Xuzhou Central Hospital from September 2015 to April 2022. Patients with cardiogenic shock who received VA-ECMO treatment were enrolled in this study. The LUS score was obtained at the different time points of ECMO.
Results
Twenty-two patients were divided into a survival group (n = 16) and a nonsurvival group (n = 6). The intensive care unit (ICU) mortality was 27.3% (6/22). The LUS scores in the nonsurvival group were significantly higher than those in the survival group after 72 h (P < 0.05). There was a significant negative correlation between LUS scores and PaO2/FiO2 and LUS scores and pulmonary dynamic compliance(Cdyn) after 72 h of ECMO treatment (P < 0.001). ROC curve analysis showed that the area under the ROC curve (AUC) of T72-LUS was 0.964 (95% CI 0.887 ~ 1.000, P < 0.01).
Conclusion
LUS is a promising tool for evaluating pulmonary changes in patients with cardiogenic shock undergoing VA-ECMO.
Trial registration
The study had been registered in the Chinese Clinical Trial Registry(NO.ChiCTR2200062130 and 24/07/2022).
... Presumably, in ARDS patients, taking into account pleural morphology increases diagnostic accuracy for EVLW because pleural abnormalities are highly speci c for noncardiogenic interstitial syndromes such as ARDS 21 . Moreover, they may represent a surrogate of ARDS severity, which is associated with the degree of pulmonary edema 37 . In combination with its recently reported high accuracy for ARDS diagnosis 22 , our ndings provide further support that the LUS-ARDS score may be a useful adjunct to improve assessment of ARDS patients. ...
Background: Lung ultrasound (LUS) is a non-invasive method to detect and quantify pulmonary edema. However, it remains uncertain how components of the LUS examination should be aggregated into a score for quantifying pulmonary edema. We examined the diagnostic accuracy of various LUS scores with the extravascular lung water index (EVLWi) assessed with PiCCO in patients with moderate-to-severe COVID-19 ARDS.
Methods: In this predefined secondary analysis of a multicenter randomized-controlled trial (InventCOVID), patients were included within 48h after intubation and underwent LUS and EVLWi measurement at two time points (first and fourth study day). EVLWi and ∆EVLWi were used as reference standard. Two 12-region scores (global LUS and LUS-ARDS), an 8-region anterior-lateral score and a 4-region B-line score were used as index tests. Pearson correlation was performed and the area under the receiver operating characteristics curve (AUROCC) for severe pulmonary edema (EVLWi>15mL/kg) was calculated.
Results: 26 of 30 patients (87%) had complete LUS and EVLWi measurements at time point 1 and 24 of 29 patients (83%) at time point 2. The global LUS (r=0.54), LUS-ARDS (r=0.58) and anterior-lateral score (r=0.54) were significantly correlated with EVLWi, while the B-line score was not (r=0.32). ∆global LUS (r=0.49) and ∆anterior-lateral LUS (r=0.52) were significantly correlated with ∆EVLWi, while correlation of ∆LUS-ARDS (r=0.43) and ∆B-lines (r=0.32) did not reach statistical significance. AUROCC for EVLWi>15ml/kg was 0.73 for the global LUS, 0.79 for the anterior-lateral and 0.85 for the LUS-ARDS score.
Conclusions: The global LUS, LUS-ARDS and antero-lateral score can quantify PiCCO-derived pulmonary edema measurements in COVID-19 ARDS. The LUS-ARDS score showed the highest diagnostic accuracy for severe pulmonary edema.
Trial registration: ClinicalTrials.gov identifier NCT04794088, registered on 11 March 2021. European Clinical Trials Database number 2020-005447-23.
... [70,71] An increase in EVLW is a readout of hydrostatic pulmonary edema and acute respiratory distress syndrome, which was seen in many EVALI patients. [72] A concentration-dependent surface pressure was also observed in serum albumin, which can surpass the respreading pressures of collapsed monolayer in vitro and ultimately play into the pathophysiology of EVALI. ...
In the summer of 2019, a cluster of cases were observed with users of battery-operated or superheating devices presenting with multiple symptoms, such as dyspnea, cough, fever, constitutional symptoms, gastrointestinal upset, and hemoptysis, that is now termed e-cigarette, or vaping, product use-associated lung injury (EVALI). The Centers for Disease Control and Prevention reported 2807 cases within the USA leading to at least 68 deaths as of February 18, 2020. The heterogeneous presentations of EVALI make diagnosis and treatment difficult; however, treatment focused on identifying and removal of the noxious substance and providing supportive care. Vitamin E acetate (VEA) is a likely cause of this lung injury, and others have reported other components to play a possible role, such as nicotine and vegetable glycerin/propylene glycol. EVALI is usually observed in adolescents, with a history of vaping product usage within 90 days typically containing tetrahydrocannabinol, and presenting on chest radiograph with pulmonary infiltrates or computed tomography scan with ground-glass opacities. Diagnosis requires a high degree of suspicion to diagnose and exclusion of other possible causes of lung disease. Here, we review the current literature to detail the major factors contributing to EVALI and primarily discuss the potential role of VEA in EVALI. We will also briefly discuss other constituents other than just VEA, as a small number of EVALI cases are reported without the detection of VEA, but with the same clinical diagnosis.
... Transpulmonary thermodilution (TPTD) is an established technique for comprehensively measuring the hemodynamic parameters, extravascular lung volume, and lung permeability at the bedside [8,[11][12][13]. A body of evidence have shown the clinical usefulness of the TPTD technique for quantitative measurement of EVLW and pulmonary vascular permeability in previous decades [14][15][16][17][18][19][20]. The normal range of the EVLW indexed to the actual body weight (i.e., extravascular lung water index: ELWI) is < 10 mL/kg, according to early human observational studies [14,15]. ...
... A body of evidence have shown the clinical usefulness of the TPTD technique for quantitative measurement of EVLW and pulmonary vascular permeability in previous decades [14][15][16][17][18][19][20]. The normal range of the EVLW indexed to the actual body weight (i.e., extravascular lung water index: ELWI) is < 10 mL/kg, according to early human observational studies [14,15]. Higher pulmonary vascular permeability is another hallmark of ARDS and can be assessed by calculating the pulmonary vascular permeability index (PVPI), which refers to the ratio between the ELWI and pulmonary blood volume [11,14,18,21]. ...
... The normal range of the EVLW indexed to the actual body weight (i.e., extravascular lung water index: ELWI) is < 10 mL/kg, according to early human observational studies [14,15]. Higher pulmonary vascular permeability is another hallmark of ARDS and can be assessed by calculating the pulmonary vascular permeability index (PVPI), which refers to the ratio between the ELWI and pulmonary blood volume [11,14,18,21]. PVPI obtained using a TPTD is the only procedure to estimate the degree of lung permeability at the bedside. ...
Background:
No 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.
Methods:
Thirteen 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.
Results:
Using 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.
Conclusion:
The pulmonary vascular permeability index is an effective indicator to measure septic ARDS severity.
... 77 However, EVLWI may also be increased in patients with pneumonia and pleural effusion. 74,78 The presence of pneumonia or pleural effusion is clinically evident. In the absence of these clinical conditions, GEDVI and EVLWI can be used to differentiate between cardiogenic and noncardiogenic pulmonary edema and fluid therapy can be implemented appropriately. ...
Unlabelled:
Hemodynamic assessment along with continuous monitoring and appropriate therapy forms an integral part of management of critically ill patients with acute circulatory failure. In India, the infrastructure in ICUs varies from very basic facilities in smaller towns and semi-urban areas, to world-class, cutting-edge technology in corporate hospitals, in metropolitan cities. Surveys and studies from India suggest a wide variation in clinical practices due to possible lack of awareness, expertise, high costs, and lack of availability of advanced hemodynamic monitoring devices. We, therefore, on behalf of the Indian Society of Critical Care Medicine (ISCCM), formulated these evidence-based guidelines for optimal use of various hemodynamic monitoring modalities keeping in mind the resource-limited settings and the specific needs of our patients. When enough evidence was not forthcoming, we have made recommendations after achieving consensus amongst members. Careful integration of clinical assessment and critical information obtained from laboratory data and monitoring devices should help in improving outcomes of our patients.
How to cite this article:
Kulkarni AP, Govil D, Samavedam S, Srinivasan S, Ramasubban S, Venkataraman R, et al. ISCCM Guidelines for Hemodynamic Monitoring in the Critically Ill. Indian J Crit Care Med 2022;26(S2):S66-S76.
