Extravascular Lung Water Research Articles

Diagnosis of pulmonary contusions with point-of-care lung ultrasonography and thoracic radiography compared to thoracic computed tomography in dogs with motor vehicle trauma: 29 cases (2017-2018).

To determine the accuracy of lung ultrasound (LUS) using the Veterinary Bedside Lung Ultrasound Examination (VetBLUE) protocol and 3-view thoracic radiographs (TXR) compared to thoracic computed tomography (TCT) for diagnosing the presence and quantification of pulmonary contusions (PC). Prospective cohort study conducted from February 2017 to June 2018. Private emergency and referral center. Thirty-two dogs having sustained motor vehicle trauma were consecutively enrolled. Three dogs were excluded from statistical analysis. All dogs survived to hospital discharge. Within 24hours of sustaining trauma, dogs had LUS, TXR, and TCT performed. Using the VetBLUE protocol, LUS PC were scored according to the presence and number of B-lines and C-lines, indicating extravascular lung water. Thoracic radiographs and TCT were scored for PC in a similar topographical pattern to the VetBLUE protocol. Lung ultrasound and TXR were compared to "gold standard" TCT for the presence and quantification of PC. On TCT, 21 of 29 (72.4%) dogs were positive and 8 of 29 (27.6%) dogs were negative for PC. When LUS was compared to TCT, 19 of 21 dogs were positive for PC (90.5% sensitivity) and 7 of 8 dogs were negative (87.5% specificity) for PC. LUS PC score correlated strongly with TCT PC score (R=0.8, P<0.001). When TXR was compared to TCT, 14 of 21 dogs were positive for PC (66.7% sensitivity) and 7 of 8 dogs were negative (87.5% specificity) for PC. TXR PC score correlated strongly with TCT PC score (R=0.74, P<0.001). In this population of dogs with motor vehicle trauma, LUS had high sensitivity for diagnosis of PC when compared to "gold standard" TCT. LUS provides reliable diagnosis of PC after trauma. More patients with PC were identified with LUS than with TXR, and additional studies are warranted to determine whether this increased sensitivity is statistically significant.

Prognostic value of the extravascular lung water and pulmonary vascular permeability indices in severe adult respiratory distress syndrome managed with extracorporeal membrane oxygenation

Prognostic value of the extravascular lung water and pulmonary vascular permeability indices in severe adult respiratory distress syndrome managed with extracorporeal membrane oxygenation

The value of growth differentiation factor-15 and extravascular lung water index in severity grading of acute respiratory distress syndrome patients and their prognosis prediction

To investigate the value of growth differentiation factor-15 (GDF-15) and extravascular lung water index (EVLWI) in severity grading and prognosis prediction of patients with acute respiratory distress syndrome (ARDS). Patients with ARDS aged 18-75 years admitted to the department of respiratory intensive care unit (RICU) of Zhengzhou Central Hospital Affiliated to Zhengzhou University from January 2019 to February 2020 were enrolled. All patients were treated with conventional therapies such as mechanical ventilation, anti-infection, stabilization of water, electrolytes and acid-base environment, blood purification and nutritional support according to their conditions. Besides, the pulse-indicated continuous cardiac output (PiCCO) was performed after admission to the department, and EVLWI before treatment and at 24, 48 and 72 hours of treatment were recorded. Serum GDF-15 level was measured by enzyme linked immunosorbent assay (ELISA) during the same period. Patients were classified as mild, moderate, and severe degree according to the 2012 Berlin Definition of ARDS, and EVLWI and GDF-15 levels in patients with different disease levels before and after treatment were compared. In addition, the length of intensive care unit (ICU) stay, ICU mortality, and 28-day mortality of patients with different GDF-15 or EVLWI levels were analyzed comparatively, with the GDF-15 3 458 ng/L and EVLWI 15 mL/kg as the cut point. A total of 82 patients with ARDS were enrolled, including 22 patients with mild ARDS, 28 patients with moderate ARDS, and 32 patients with severe ARDS. The GDF-15 and EVLWI levels in patients with moderate and severe ARDS at each time point before and after treatment were higher than those in patients with mild ARDS. Both GDF-15 and EVLWI levels in patients with severe ARDS were higher than those in the patients with moderate ARDS. The differences were statistically significant at all the time points except for the difference of GDF-15 levels at 24 hours after treatment (ng/L: 3 900.41±546.43 vs. 3 695.66±604.73, P > 0.05). [GDF-15 (ng/L): 3 786.11±441.45 vs. 3 106.83±605.09 before treatment, 3 895.48±558.96 vs. 3 333.29±559.66 at 48 hours, 3 397.33±539.56 vs. 3 047.53±499.57 at 72 hours; EVLWI (mL/kg): 19.06±1.91 vs. 14.31±1.50 before treatment, 18.56±2.23 vs. 13.26±1.69 at 24 hours, 17.23±1.76 vs. 12.45±1.36 at 48 hours, 15.47±1.81 vs. 11.13±2.19 at 72 hours, all P < 0.05]. According to the cut-off value, there were 23 patients with GDF-15 ≥ 3 458 ng/L and GDF-15 < 3 458 ng/L respectively and there were 23 patients with EVLWI ≥ 15 mL/kg and EVLWI < 15 mL/kg respectively. The length of ICU stay and 28-day mortality in patients with high GDF-15 were significantly higher than those in patients with low GDF-15 [length of ICU stay (days): 21.22±2.69 vs. 15.37±3.14, 28-day mortality: 56.5% vs. 21.7%, both P < 0.05]. The length of ICU stay and 28-day mortality in patients with high EVLWI were also significantly higher than those in patients with low EVLWI [length of ICU stay (days): 18.45±2.61 vs. 14.98±2.75, 28-day mortality: 47.8% vs. 17.4%, both P < 0.05]. To some extent, GDF-15 and EVLWI levels reflect the severity of patients with ARDS, and high GDF-15 and EVLWI levels are significantly associated with poor prognosis in patients with ARDS.

Lung ultrasound to quantitatively evaluate extravascular lung water content and its clinical significance

Background As we all know, pulmonary edema can be diagnosed by lung ultrasound (LUS), but how to accurately and quantitatively evaluate lung water content by ultrasound is a difficult problem that needs to be solved urgently. B-line assessment with LUS has recently been proposed as a reliable, noninvasive semiquantitative tool for evaluating extravascular lung water (EVLW). To date, however, there has been no easy quantitative method to evaluate EVLW by LUS. Objective (1) To explore the feasibility of establishing a rabbit model with increased EVLW by injecting warm normal saline (NS) into the lungs via the endotracheal tube. (2) To establish a simple, accurate and clinically operable method for quantitative assessment of EVLW using LUS. (3) To develop LUS into a resource for guiding the clinical treatment of patients with increased EVLW. Methods Forty-five New Zealand rabbits were randomized into nine groups (n = 5). After anesthesia, each group of rabbits was injected with different amounts of warm sterile NS (0 ml/kg, 2 ml/kg, 4 ml/kg, 6 ml/kg, 8 ml/kg, 10 ml/kg, 15 ml/kg, 20 ml/kg, 30 ml/kg) via the endotracheal tube. Each rabbit was examined by LUS before and after NS injection. At the same time, the spontaneous respiratory rate (RR, breaths per minute), heart rate (HR, bpm) and arterial blood gas (ABG) of the rabbits were recorded. Then, both lungs were dissected to obtain the wet and dry weight and conduct a complete histological examination. Results Injecting NS into the lungs through a tracheal tube can successfully establish a rabbit model with increased EVLW. The extent of EVLW increase is related to the volume of NS injected into the lungs. As the EVLW increases, three different types of B-lines can be seen in the LUS. When the NS injection volume is 2–6 ml/kg, comet-tail artifacts and B-lines are the main patterns found on LUS; as additional NS is injected into the lungs, the rabbits' RR gradually increases, while their HR gradually decreases, ABG remains normal or shows mild metabolic acidosis (MA). Confluent B-lines grow gradually but significantly, reaching a dominant position when the NS injection volume reaches 6–8 ml/kg and predominating almost entirely when the NS injection volume is 8–15 ml/kg; at that time, rabbits' RRs and HRs decrease sharply, and the ABG indicated type I respiratory failure (RF).Compact B-lines occur and predominate almost entirely when the NS injection volume reaches 10 ml/kg and 15–20 ml/kg, respectively. At that time, rabbits begin to enter cardiac and respiratory arrest, and ABG shows type II RF and MA. Conclusion In this study, the establishment of an animal model with increased EVLW confirmed that different lung water content had corresponding manifestations in ultrasound and was associated with different degrees of clinical symptoms, and the study results can be used to guide clinical practice.

Fluid Administration in Emergency Room Limited by Lung Ultrasound in Patients with Sepsis: Protocol for a Prospective Phase II Multicenter Randomized Controlled Trial.

BackgroundSepsis remains a major health challenge with high mortality. Adequate volume administration is fundamental for a successful outcome. However, individual fluid needs differ between patients due to varying degrees of systemic vasodilation, circulatory flow maldistribution, and increased vascular permeability. The current fluid resuscitation practice has been questioned. Fluid overload is associated with higher mortality in sepsis. A sign of fluid overload is extravascular lung water, seen as B lines in lung ultrasound. B lines correlate inversely with oxygenation (measured by a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen ie, PaO2/FiO2). Thus, B lines seen by bedside ultrasound may have a role in guiding fluid therapy.ObjectiveWe aim to evaluate if fluid administration guided by lung ultrasound in patients with sepsis in emergency departments will lead to better oxygenation and patient outcomes than those in the standard therapy.MethodsA phase II, multicenter, randomized, open-label, parallel-group, superiority trial will be performed. Patients will be recruited at emergency departments of the participating centers. A total of 340 patients will be randomly allocated to the intervention or standard-of-care group (30mL/kg). The intervention group will receive ultrasound-guided intravenous fluid until 3 B lines appear. The primary outcome will be oxygenation (measured as PaO2/FiO2 ratio) at 48 hours after starting intravenous fluid administration. Secondary outcomes will be patients’ outcome parameters, including oxygenation after 15 mL/kg fluid at 6, 12, 24, and 48 hours; sepsis progress through Sequential Organ Failure Assessment (SOFA) scores; pulmonary edema evaluation; and 30-day mortality.ResultsThe trial will be conducted in accordance with the Declaration of Helsinki. Institutional review board approval will be sought after the participating sites are selected. The protocol will be registered once the institutional review board approval is granted. The trial duration is expected to be 1.5-2.5 years. The study is planned to be performed from 2021 to 2022, with enrollment starting in 2021. First results are expected in 2022. Informed written consent will be obtained before the patient’s enrollment in the study. An interim analysis and data monitoring will ensure the patient safety. The results will be published in a peer-reviewed journal and discussed at international conferences.ConclusionsThis is a protocol for a randomized control trial that aims to evaluate the role of bedside ultrasound in guiding fluid therapy in patients with sepsis via B lines evaluation.International Registered Report Identifier (IRRID)PRR1-10.2196/15997

Extravascular Lung Water and Effect on Oxygenation Assessed by Lung Ultrasound in Adult Cardiac Surgery.

IntroductionThe extravascular lung water content is determined by the use of lung ultrasound (LUS) which is represented as B-lines. The aim of this study was to investigate whether the LUS measurement of extravascular lung water was correlated to changes in oxygenation.MethodsThis prospective cohort study was comprised of 73 patients with an average age of 56 (range: 18 to 87 years) who underwent elective cardiac surgery using cardiopulmonary bypass. The LUS score was performed preoperatively, time zero (T0), at one hour (T1), and at 24 hours (T2) post-surgery. Additionally, arterial oxygen partial pressure and fraction of inspired oxygen (PaO2/FiO2) ratio were measured at each time and the time-to-extubation.ResultsA negative correlation was found between the LUS score and PaO2/FiO2 at T1 (p < 0.004). Extubation time and changes in the lung ultrasound score at T0 - T2 were positively correlated (p < 0.03). Plus, there was a positive correlation between fluid balance and lung ultrasound score at T2 (p < 0.03).ConclusionWe found three significant correlations that support the use of LUS in cardiac surgery: 1) the more B-lines, the lower the oxygenation; 2) the more B-lines, the longer the period of ventilation; 3) the more B-lines, the more positive the fluid balance. LUS is a non-invasive bedside investigation that can be used to judge extravascular lung water, providing useful information in the management of patient oxygenation, fluid balance, and extubation.

Unexpected increase in extravascular lung water after acute lunginjury

We report on a 27-year-old female patient presenting with pneumonia and developing acute respiratory distress syndrome. Using transpulmonary thermodilution, an elevated extravascular lung water was detected (17 ml/kg). Patient required lung-protective mechanical ventilation and received antibiotic therapy. Negative fluid balance was targeted. Under this treatment, respiratory function improved, inflammation parameters declined, and extravascular lung water was recurrent (10 ml/kg). Subsequently, extravascular lung water increased to 29 ml/kg. In a chest x-ray, the central venous catheter tip was dislocated into the right internal jugular vein. 7 days before, the catheter was shown to be in projection of the Vena cava superior in a previous chest x-ray. After insertion of a new central venous catheter, extravascular lung water was quantified at 10 ml/kg again. After 10 days of mechanical ventilation the patient was successfully extubated. As mechanism for this catheter dislocation, we propose a Valsalva maneuver or spontaneous movements of the upper body of the patient. Sudden increase in extravascular lung water may reflect central venous catheter tip dislocation and chest x-ray should be considered to verify catheter tip position.

A CLUE for better assessment of donor lungs: Novel technique in clinical ex vivo lung perfusion

The direCt Lung Ultrasound Evaluation (CLUE) technique was proven to be an accurate method for monitoring extravascular lung water in donor lungs during ex vivo lung perfusion (EVLP) in an experimental model. The aim of this study was to examine the application of CLUE in the clinical setting. Lungs were evaluated using acellular EVLP protocol. Ultrasound images were obtained directly from the lung surface. Images were graded according to the percentage of B-lines seen on ultrasound. CLUE scores were calculated at the beginning and end of EVLP for the whole lung, each side, and lobe based on the number (No.) of images in each grade and the total No. of images taken and evaluated retrospectively. A total of 23 EVLP cases were performed resulting in 13 lung transplants (LTxs) with no hospital mortality. Primary graft dysfunction (PGD) occurred in only 1 recipient (PGD3, no PGD2). Significant differences were found between suitable and non-suitable lungs in CLUE scores (1.03 vs 1.85, p < 0.001), unlike the partial pressure of oxygen/fraction of inspired oxygen ratio. CLUE had the highest area under the receiver operating characteristic curve (0.98) compared with other evaluation parameters. The initial CLUE score of standard donor lungs was significantly better than marginal lungs. The final CLUE score in proned lungs showed improvement when compared with initial CLUE score, especially in the upper lobes. The CLUE technique shows the highest accuracy in evaluating donor lungs for LTx suitability compared with other parameters used in EVLP. CLUE can optimize the outcomes of LTx by guiding the decision making through the whole process of clinical EVLP.

Use of perfusion index to detect hemodynamic changes in endotoxemic pigs.

The perfusion index (PI) derived from plethysmographic signals provides a noninvasive indication of peripheral perfusion. This study aimed to investigate changes in PI and other hemodynamic variables in pigs subjected to endotoxemia. Prospective experimental study. University teaching hospital. Twelve healthy pigs weighing a mean (± standard deviation [SD]) of 31.7 ± 2.0kg. Pigs were divided into control and endotoxin groups (n=6 each). Endotoxemia was induced by IV infusion of lipopolysaccharide. Heart rate, mean arterial pressure, cardiac index (CI), central venous pressure, systemic vascular resistance index (SVRI), extravascular lung water index (ELWI), Global end-diastolic volume (GEDV) index, and pulmonary permeability index were measured using a transpulmonary thermodilution monitor in all pigs. PI was measured using a pulse oximeter probe attached to the tail. Pao2 , Paco2 , and plasma lactate concentration were measured by blood gas analysis. Measurements were taken at baseline (T0 ). Saline or lipopolysaccharide was then administered for 30min to all pigs (control or endotoxemia group, respectively), and each parameter was measured every 30min up to 270min. Data were analyzed by analysis of variance and Student's t-tests. There were no significant changes in any variables in the control group, but CI, SVRI, PI, ELWI, blood lactate concentration, and Pao2 changed significantly from baseline in the endotoxin group (P< 0.001, P= 0.0048, P< 0.001, P= 0.0064, P< 0.001, and P= 0.0220, respectively). In the endotoxin group, mean (± SD) %PI increased from T0 to 154 ± 34% at T60 (P=.001) and 135 ± 50% at T90 (P=0.004), which mirrored significant changes in %CI and %SVRI. The PI may be useful to detect changes in CI and SVRI.

Extravascular Lung Water And Lung Diffusing Capacity In Response To Ultra-endurance Exercise Performed At Moderate Altitude

PURPOSE: Strenuous exercise performed at altitude increases cardiac output and pulmonary arterial and capillary pressures to levels that may exceed a tolerable alveolar-capillary load, thereby evoking fluid leakage into the interstitial space. Accordingly, this study aimed to determine whether running an ultramarathon at moderate altitude increases extravascular lung water (EVLW) and whether this inhibits the transfer of gas across the alveolar-capillary membrane. METHODS: Cardiac biomarkers (cTnI & BNP), exhaled nitric oxide (ExNO), echocardiographic signs of EVLW, and lung (DLco) and alveolar-capillary membrane (Dm) diffusing capacity for carbon monoxide (determined via a single-breath DLco/DLno method) were assessed in 53 runners (10 Females; Age:41±10y BMI:23±2kg/m2) before, 1-4h and 24h after a 100km (CCC: 6,100m of ascent, altitude range of 1,035-2,584m) or 170km (UTMB: 10,000m of ascent, altitude range of 1,035-2,565m) mountain ultramarathon. RESULTS: Participants finished the ultramarathon in 27±12h with an average heart rate of 124±13bpm. Cardiac biomarkers were increased acutely after the race (cTnI: 0.01±0.00 vs. 0.04±0.01ng/ml, p<0.01; BNP: 21±2 vs. 123±12pg/ml, p<0.01), while ExNO decreased (25.6±2.0 vs. 14.5±1.3 ppb, p<0.01). Signs of EVLW increased after the race (average comet tails count: 2±1 vs. 7±1, p<0.01) while DLco decreased (31.6±1.0 vs. 28.6±0.9 ml/min/mmHg, p<0.01) but Dm remained unchanged (171.4±7.6 vs. 167.2±8.8 ml/min/mmHg, p>0.05). Cardiac biomarkers, ExNO, EVLW and Dm were similar to baseline values after 24h of recovery, while DLco remained mildly reduced (30.6±1.6 ml/min/mmHg, p<0.05). CONCLUSIONS: These data suggest a mild and transient increase in cardiac biomarkers and extravascular lung water occur after completing an ultramarathon at moderate altitude, but this has minimal impact on the transfer of gas across the alveolar-capillary membrane, despite an overall reduction in lung diffusion. In some subjects an exaggerated increase in extravascular lung water and decrease in alveolar-capillary membrane diffusion was observed, suggesting that some individuals may have an increased propensity for developing mild exercise-induced pulmonary edema at altitude.

Management of primary blast lung injury: a comparison of airway pressure release versus low tidal volume ventilation

BackgroundPrimary blast lung injury (PBLI) presents as a syndrome of respiratory distress and haemoptysis resulting from explosive shock wave exposure and is a frequent cause of mortality and morbidity in both military conflicts and terrorist attacks. The optimal mode of mechanical ventilation for managing PBLI is not currently known, and clinical trials in humans are impossible due to the sporadic and violent nature of the disease.MethodsA high-fidelity multi-organ computational simulator of PBLI pathophysiology was configured to replicate data from 14 PBLI casualties from the conflict in Afghanistan. Adaptive and responsive ventilatory protocols implementing low tidal volume (LTV) ventilation and airway pressure release ventilation (APRV) were applied to each simulated patient for 24 h, allowing direct quantitative comparison of their effects on gas exchange, ventilatory parameters, haemodynamics, extravascular lung water and indices of ventilator-induced lung injury.ResultsThe simulated patients responded well to both ventilation strategies. Post 24-h investigation period, the APRV arm had similar PF ratios (137 mmHg vs 157 mmHg), lower sub-injury threshold levels of mechanical power (11.9 J/min vs 20.7 J/min) and lower levels of extravascular lung water (501 ml vs 600 ml) compared to conventional LTV. Driving pressure was higher in the APRV group (11.9 cmH2O vs 8.6 cmH2O), but still significantly less than levels associated with increased mortality.ConclusionsAppropriate use of APRV may offer casualties with PBLI important mortality-related benefits and should be considered for management of this challenging patient group.

P0190POINT-OF-CARE ULTRASONOGRAPHY FOR VOLUME ASSESSMENT IS EASY TO LEARN AND HAS GOOD REPRODUCIBILITY IN NEW USERS

Abstract Background and Aims In recent years, point-of-care ultrasonography (POCUS) with lung ultrasonography (LUS) and inferior vena cava diameter (IVCD) measurements have attracted growing attention due to their capacity to estimate volume status in end-stage kidney disease (ESKD). There have been concerns about inter-operator reproducibility in POCUS, particularly the new user’s ability to distinguish varying lung pathologies on LUS accurately. For instance, lung diseases with thickening of subpleural structures, such as pulmonary fibrosis, can mimic LUS B-lines. B-lines are artefacts produced by extravascular lung water, which is summated into a B-line score (BLS). This study aims to investigate the ease of learning, and the inter-operator reproducibility of LUS and IVCD in an Asian haemodialysis (HD) cohort, in users with no prior ultrasound experience. Method A subgroup of 14 HD patients from the observational study by Teng et al comparing LUS and IVCD with other fluid assessment methods in a HD cohort, underwent LUS and IVCD pre- and post-HD with 2 operators in separate settings. LUS was performed via a 28-point protocol, while IVCD was measured in both inspiration (IVCDmin) and expiration (IVCDmax). IVCDi was calculated by indexing IVCD to body surface area. Study details are available elsewhere. One operator was a Nephrologist experienced in ultrasonography who had done 150 previous studies, whilst the second operator was a Resident who had no prior exposure to POCUS. The Resident underwent 4 hours of instructional teaching including theory sessions, simulation and image interpretation. Images acquired by the Resident during the study were audited for interpretative accuracy, such as the ability to diagnose lung pathology accurately. The Resident was required to review the clinical presentations of all patients before making ultrasound diagnoses. Results 392 lung images and 56 IVC images were acquired for 14 HD patients. 100% of patients’ clinical notes were reviewed prior to making ultrasound diagnosis. &amp;gt;98% of the diagnoses were correctly made, and only in 1 patient (7 lung images; case of bronchiectasis), was the ultrasonographic diagnosis incorrectly made of B-lines, although B-lines were seen in other lung fields in the same patient. There was excellent inter-operator variability for BLS (r = 0.983, p &amp;lt; 0.001). There was moderate agreement between both operators in terms of BLS and by BLS categories (k = 0.586, p = 0.015 and k = 0.521, p = 0.010). In 14 independent LUS studies, only 1 reading demonstrated interobserver difference exceeding 1.96 standard deviation (SD). There was also excellent inter-operator variability for IVCDimax (r = 0.994, p &amp;lt; 0.001) and IVCDimin. In 14 independent IVCDimax readings, 2 readings demonstrated interobserver difference exceeding 1.96 SD. Conclusion Point-of-care ultrasonography for volume assessment is able to demonstrate good inter-operator reproducibility and is easy for new users to learn. There is hence potential for more widespread incorporation of these volume assessment tools into community dialysis centres. POCUS has traditionally been performed by medical professionals, but in light of the relative ease of learning curve, it may be possible for allied healthcare professionals to acquire skills in POCUS.

P1068LUNG ULTRASONOGRAPHY IS MORE EFFECTIVE THAN BIOIMPEDENCE OR NT-PRO BNP AT ASSESSING POST-DIALYSIS VOLUME CHANGES

Abstract Background and Aims At present, there are no precise and quantitative clinical indices for assessing fluid status in haemodialysis (HD). Existing modalities such as plasma B-type natriuretic peptide (NT-pro BNP), measurement of inferior vena cava diameter (IVCD) by ultrasound or bioimpedance spectroscopy (BIS) have limitations and do not always give quantitative measurements to guide dry weight titration. Lung ultrasonography (LUS) has emerged as a novel real-time technique to assess extravascular lung water (EVLW) on HD. Current studies comparing the above techniques often lack standardized dialysis days and timepoints for sampling volume assessment methods. This study aims to compare the performance of LUS against existing methods (NT-pro BNP, IVCD, BIS) of volume assessment in an Asian HD cohort, using a standardised protocol for sampling. The secondary aim was to measure the turnover time required for performing each volume assessment method. Method This was a prospective study of 50 chronic HD patients in a single dialysis unit. In this cohort, 34 (68%) had diabetes, and 43 (86%) were on at least 1 antihypertensive. Patients aged more than 21 years, on thrice weekly dialysis with a high flux dialyser for more than 3 months with residual urine output less then 500 ml per day were recruited. NT-pro BNP, IVCD and BIS were sampled immediately pre- and post- midweek dialysis. 28-intercostal space LUS was performed by a Nephrologist with appropriate certification immediately pre- and 30 minutes after midweek dialysis. EVLW produces lung artefacts (B-lines), which is summated into a B-line score (BLS). We also measured the time required, from performing each volume assessment methodology, to the point of result acquisition. Results Pre-HD, lung congestion was classified as mild (BLS ≤ 15) in 6 patients (12%), moderate (BLS 15 – 30) in 12 patients (24%) and severe (BLS &amp;gt; 30) in 32 patients (64%). Median BLS reduced from 46.5 (22.5 – 77.0) pre-HD to 15.5 (9.9 – 21.5) post-HD. There was a linear correlation between changes in BLS and ultrafiltration on HD, with UF 500ml approximately equal to 8.2 B-lines. There were significant but weak to moderate correlations between pre-HD LUS and BIS (r = 0.457, p = 0.004), IVCD indexed to body surface area during expiration (IVCDimax) (r = 0.371, p = 0.026) and NT-pro BNP (r = 0.406, p = 0.004). Post-HD, correlations between LUS and IVCDimax remained similar (r = 0.353, p = 0.02), but weakened with BIS (r = 0.329, p = 0.021) and became non-significant with NT-pro BNP. This was related to a paradoxical increment in NT-pro BNP and BIS overhydration values post-HD, in up to 40% of the cohort. Separately, the mean execution time for the various volume measurements were LUS: 6 ± 0.2 minutes, BIS: 5.9 ± 0.4 minutes, IVCD: 4.1 ± 0.3 minutes and the laboratory turnaround time to obtain a NT-pro BNP result was 125 ± 10.6 minutes. Conclusion LUS was able to demonstrate a linear correlation with UF volume, and may be more effective then NT-pro BNP or BIS at real-time assessment of fluid changes post-HD. The execution of LUS was no more time-consuming then BIS. LUS is hence likely to be a useful clinical tool for dry weight titration in HD patients.

Prognostic Value of Dynamic Changes in Pulmonary Congestion During Exercise Stress Echocardiography in Heart Failure With Preserved Ejection Fraction.

Patients with heart failure (HF) with preserved ejection fraction (HFpEF) typically develop dyspnea and pulmonary congestion upon exercise. Lung ultrasound is a simple diagnostic tool, providing semiquantitative assessment of extravascular lung water through B-lines. It has been shown that patients with HFpEF develop B-lines upon submaximal exercise stress echocardiography; however, whether exercise-induced pulmonary congestion carries prognostic implications is unknown. This study aimed at evaluating the prognostic value of B-line assessment during exercise in patients with HFpEF. Sixty-one New York Heart Association class I to II patients with HFpEF underwent standard echocardiography, lung ultrasound (28-scanning point method), and BNP (B-type natriuretic peptide) assessment during supine exercise echocardiography (baseline and peak exercise). The primary end point was a composite of cardiovascular death or HF hospitalization at 1 year. B-lines, E/e', and BNP significantly increased during exercise (P<0.001 for all). By multivariable analysis, both peak (hazard ratio, 1.50 [95% CI, 1.21-1.85], P<0.001), and change (hazard ratio 1.34 [95% CI, 1.12-1.62], P=0.002) B-lines were retained as independent predictors of outcome (hazard ratios per 1 B-line increment), along with BNP and E/e' ratio. Importantly, adding peak B-line on top of a clinical model significantly improved prognostic accuracy (C-index increase, 0.157 [0.056-0.258], P=0.002) and net reclassification (continuous net reclassification improvement, 0.51 [0.09-0.74], P=0.016), with similar results for B-line change. Detection of exercise-induced pulmonary congestion by lung ultrasound is an independent predictor of outcome in patients with HFpEF; its use may help refining the routine risk stratification of these patients on top of well-established clinical variables.

P1185LUNG COMETS AND EVALUATION OF HYDRATION STATUS IN PERITONEAL DIALYSIS PATIENTS

Abstract Background and Aims Assessment of optimal hydration status in patients with end-stage renal disease (ESRD) on peritoneal dialysis (PD) is a challenge. Multiple diagnostic options to determine hydration status in PD patients are available. Multifrequency bioimpedance spectroscopy (MBIS) is a cheap, simple and non-invasive method of estimating body composition, including estimates of total body water (TBW), extracellular water (ECW), intracellular water (ICW) and the ratio between both spaces (ECW/ICW). Lung ultrasonography (LUS) and lung B-lines (lung comets) can be used for the evaluation of extravascular lung water. Ultrasound evaluation of inferior vena cava (UIVC) provides rapid, non-invasive assessment of a patient's hemodynamic and volume status. N-terminal pro-brain natriuretic peptide (NT-proBNP) is related to fluid status and fluid distribution. The aim of our study was to assess fluid status in PD patients comparing four different methods: MBIS, LUS, UIVC and NT-proBNP. Method We performed a single-centre cohort study in 19 PD patients. The body composition was measured using the portable whole-body MBIS device, Body Composition Monitor-BCM(®) (Fresenius Medical Care, Bad Homburg, Germany), LUS with portable US device (VScan, General Electrics Corporate), UIVC index with SonoSite US device. NT-proBNP was measured in a one-step sandwich chemiluminescent immunoassay (Dimension Vista® System 1500, Siemens Healthcare Diagnostics Inc., Newark, NJ, USA). Results The mean age of patients was 54 ± 10 years, mean dialysis vintage 53 (10-194) months, 63% were men. Thirteen (68.4%) patients had fluid overload (FO) &amp;gt; 1.1 L. Data of patients are presented in table 1. We found a statistically significant correlation between the number of lung comets and ECW/ICW ratio (r = 0.496, P = 0.031) and NT-proBNP (r = 0.759, P &amp;lt; 0.0001). In contrast, there was no significant correlation between the number of lung comets and UIVC (r = 0.221, P &amp;lt; 0.364). Conclusion According to our results, LUS with lung comets, MBIS with ECW/ICW ratio and NT-proBNP are useful and complementary methods for evaluation of fluid status in PD patients.

P1085EFFECT OF INTRAVASCULAR FLUID REMOVAL ON THE RATE OF CHANGE OF THE INFERIOR VENA CAVA DIAMETER, EARLY DIASTOLIC MITRAL VALUE INFLOW AND NUMBER OF LUNG ECHO B-LINES IN HEMODIALYSIS PATIENTS

Abstract Background and Aims In hemodialysis therapy, intravascular fluid is removed first. As intravascular water is removed, the circulating serum protein concentrations increase, resulting in a marked increase in the driving force which pulls water from the extravascular space into the blood vessels, by a process called plasma refilling. We examined the effect of total fluid removal and intravascular fluid removal as estimated by the change of the hematocrit value during dialysis on the rate of change of the inferior vena cava (IVC) diameter, early diastolic mitral valve inflow (E wave), and lung echo B-lines. Method We enrolled 59 patients under maintenance hemodialysis for this study. Lung ultrasound was performed at the first session of the week. Bilateral scanning of the anterior and lateral chest walls was performed with the patient in a supine position. The chest wall was divided into 8 areas (2 anterior and 2 lateral areas per side), and 1 scan was obtained for each area. The total number of B-lines was estimated. Echocardiographic measurements were obtained at the same time and the IVC dimensions and E wave were estimated. We performed each ultrasound examinations at two time-points (just after the start and just before the end of the hemodialysis therapy). We then investigated the rate of change ((post-pre)/post) of the IVC diameter, E wave, and number of B-lines. A peripheral blood sample was obtained before and after the hemodialysis session and the hematocrit was measured. We estimated the intravascular fluid volume as pre body weight /13, and estimated intravascular fluid removal as (post hematocrit – pre hematocrit)/post hematocrit x estimated intravascular fluid. We also defined estimated extravascular fluid removal as total fluid removal – estimated intravascular fluid removal. We investigated the relationship between the total, intravascular and extravascular fluid removals and the rate of change of the IVC diameter, E wave, and number of B-lines. Results The rate of change of the IVC diameter was negatively related to the estimated intravascular fluid volume (r=-0.285, P=0.033), but not to the estimated extravascular fluid or total fluid removal. The rate of change of the E wave was negatively related to the estimated intravascular fluid volume (r=-0.422, P=0.001), and the estimated extravascular fluid (r=-0.369, P=0.006) and total fluid removal (r=-0.419, P=0.002). Among these, the rate of change of the E wave was most closely related to the estimated intravascular fluid volume. The rate of change of the number of B-lines was not associated with the estimated intravascular fluid volume, but was negatively correlated with the estimated extravascular fluid (r=-0.368, P=0.005) and total fluid removal (r=-0.353, P=0.008). The estimated extravascular fluid removal was the most closely related to the rate of change of the number of B-lines. Conclusion The rates of changes of the IVC diameter and E wave were strongly associated with the estimated intravascular fluid removal, whereas the rate of change of the number of B-lines was correlated with estimated extravascular fluid removal. The E wave represents the flow to the left ventricle, which occurs after left ventricular diastole, reflecting the preload status. The IVC dimensions are strongly associated with the right atrial pressure and blood volume and therefore reflect the intravascular volume. Therefore, both the E wave and the IVC diameter may represent the intravascular fluid volume. On the other hand, the number of B-lines has been reported to be correlated with the amount of extravascular lung water. Our results were consistent with these reports.

A nebulised antitumour necrosis factor receptor-1 domain antibody in patients at risk of postoperative lung injury: A randomised, placebo-controlled pilot study.

BACKGROUNDTumour necrosis factor receptor 1 (TNFR1) signalling mediates the cell death and inflammatory effects of TNF-α.OBJECTIVEThe current clinical trial investigated the effects of a nebulised TNFR1 antagonist (GSK2862277) on signs of lung injury in patients undergoing oesophagectomy.DESIGNRandomised double-blind (sponsor unblind), placebo-controlled, parallel group study.SETTINGEight secondary care centres, the United Kingdom between April 2015 and June 2017.PATIENTSThirty-three patients undergoing elective transthoracic oesophagectomy.INTERVENTIONSPatients randomly received a single nebulised dose (26 mg) of GSK2862277 (n = 17) or placebo (n = 16), given 1 to 5 h before surgery; 14 and 16, respectively competed the study.MAIN OUTCOME MEASUREMENTSPhysiological and biochemical markers of lung injury, pharmacokinetic and safety endpoints were measured. The primary endpoint was the change from baseline in pulmonary vascular permeability index (PVPI) at completion of surgery, measured using single-indicator transpulmonary thermodilution. Adjusted point estimates and 95% credible intervals (analogous to conventional confidence intervals) were constructed for each treatment using Bayesian statistical models.RESULTSThe mean change (with 95% credible intervals) from baseline in PVPI on completion of surgery was 0.00 (−0.23, 0.39) in the placebo and 0.00 (−0.24, 0.37) in the GSK2862277 treatment groups. There were no significant treatment-related differences in PaO2/FiO2 or Sequential Organ Failure Assessment score. Levels of free soluble TNFR1, Macrophage Inflammatory Protein-1 alpha and total protein were significantly reduced in the bronchoalveolar lavage fluid of patients treated with GSK2862277 (posterior probability of decrease with GSK2862277 vs. placebo:≥0.977; equivalent to P < 0.05). The frequency of adverse events and serious adverse events were distributed evenly across the two treatment arms.CONCLUSIONPre-operative treatment with a single 26 mg inhaled dose of GSK2862277 did not result in significantly lower postoperative alveolar capillary leak or extra vascular lung water. Unexpectedly small increases in transpulmonary thermodilution-measured PVPI and extra vascular lung water index at completion of surgery suggest less postoperative lung injury than historically reported, which may have also compromised a clear assessment of efficacy in this trial. GSK2862277 was well tolerated, resulted in expected lung exposure and reduced biomarkers of lung permeability and inflammation.TRIAL REGISTRATIONclinicaltrials.gov: NCT02221037.

Prediction of outcome in patients with ARDS: A prospective cohort study comparing ARDS-definitions and other ARDS-associated parameters, ratios and scores at intubation and over time.

BackgroundEarly recognition of high-risk-patients with acute respiratory distress syndrome (ARDS) might improve their outcome by less protracted allocation to intensified therapy including extracorporeal membrane oxygenation (ECMO). Among numerous predictors and classifications, the American European Consensus Conferenece (AECC)- and Berlin-definitions as well as the oxygenation index (OI) and the Murray-/Lung Injury Score are the most common. Most studies compared the prediction of mortality by these parameters on the day of intubation and/or diagnosis of ARDS. However, only few studies investigated prediction over time, in particular for more than three days.ObjectiveTherefore, our study aimed at characterization of the best predictor and the best day(s) to predict 28-days-mortality within four days after intubation of patients with ARDS.MethodsIn 100 consecutive patients with ARDS severity according to OI (mean airway pressure*FiO2/paO2), modified Murray-score without radiological points (Murray_mod), AECC- and Berlin-definition, were daily documented for four days after intubation. In the subgroup of 49 patients with transpulmonary thermodilution (TPTD) monitoring (PiCCO), extravascular lung water index (EVLWI) was measured daily.Primary endpointPrediction of 28-days-mortality (Area under the receiver-operating-characteristic curve (ROC-AUC)); IBM SPSS 26.ResultsIn the totality of patients the best prediction of 28-days-mortality was found on day-1 and day-2 (mean ROC-AUCs for all predictors/scores: 0.632 and 0.620). OI was the best predictor among the ARDS-scores (AUC=0.689 on day-1; 4-day-mean AUC = 0.625). AECC and Murray_mod had 4-day-means AUCs below 0.6. Among the 49 patients with TPTD, EVLWI (4-day-mean AUC=0.696) and OI (4-day-mean AUC=0.695) were the best predictors. AUCs were 0.789 for OI on day-1, and 0.786 for EVLWI on day-2. In binary regression analysis of patients with TPTD, EVLWI (B=-0.105; Wald=7.294; p=0.007) and OI (B=0.124; Wald=7.435; p=0.006) were independently associated with 28-days-mortality. Combining of EVLWI and OI provided ROC-AUCs of 0.801 (day-1) and 0.824 (day-2). Among the totality of patients, the use of TPTD-monitoring „per se“ and a lower SOFA-score were independently associated with a lower 28-days-mortality.ConclusionsPrognosis of ARDS-patients can be estblished within two days after intubation. The best predictors were EVLWI and OI and their combination. TPTD-monitoring „per se“ was independently associated with reduced mortality.

Application of lung ultrasonography on evaluating extravascular lung water and prognosis in patients with acute respiratory distress syndrome

To evaluate the value of lung ultrasonography score (LUS) on assessing extravascular lung water (EVLW) and prognosis in patients with acute respiratory distress syndrome (ARDS). The clinical data of 46 patients meeting ARDS Berlin definition admitted to intensive care unit (ICU) of Ningbo Yinzhou People's Hospital from July 2016 to December 2019 were retrospectively collected. The general data, vital signs, blood lactic acid (Lac), oxygenation index (OI), LUS, extravascular lung water index (EVLWI), sequential organ failure assessment (SOFA) score, clinical pulmonary infection score (CPIS) and the length of ICU stay were collected. According to the prognosis of patients during ICU treatment, the patients were divided into survival group and non-survival group, and the clinical characteristics between the two groups were compared. The correlation between LUS and OI, EVLWI, SOFA, and CPIS were analyzed by Pearson correlation analysis. Receiver operator characteristic (ROC) curve was plotted to determine the prognostic value of LUS for ARDS patients during ICU treatment. Forty-six patients were enrolled in the analysis, of whom 32 patients survived (69.6%), and 14 patients died (30.4%) during ICU treatment. There was no significant difference in gender, age, left ventricular ejection fraction (LVEF) or heart rate (HR) between the two groups. Compared with the survival group, the mean arterial pressure (MAP) and OI in the non-survival group were significantly lowered [MAP (mmHg, 1 mmHg = 0.133 kPa): 57.48±33.34 vs. 85.45±19.56, OI (mmHg): 74.50±18.40 vs. 233.06±28.28, both P < 0.05], while Lac, LUS, EVLWI, SOFA and CPIS were significantly increased [Lac (mmol/L): 6.78±2.56 vs. 2.21±1.42, LUS score: 23.57±2.03 vs. 15.58±2.24, EVLWI (mL/kg): 22.93±2.56 vs. 12.96±2.18, SOFA score: 20.21±3.35 vs. 12.43±2.97, CPIS score: 8.07±1.38 vs. 4.59±1.04, all P < 0.01], and the length of ICU stay was significantly shortened (days: 9.33±3.28 vs. 16.89±4.12, P < 0.05]. Pearson correlation analysis showed that a significant negative linear correlation was found between LUS and OI (r = -0.823, P < 0.01), and positive linear correlations were found between LUS and EVLWI, SOFA, CPIS (r values were 0.745, 0.614, 0.757, respectively, all P < 0.01). ROC curve analysis showed that both LUS and EVLWI could predict the prognosis of ARDS patients during ICU treatment, and the areas under ROC curve (AUC) of LUS and EVLWI were 0.936 and 0.991, respectively. When the cut-off of LUS score was 20.5, the sensitivity and specificity were 85.7% and 81.2% respectively. LUS score has a good correlation with EVLWI monitored by pulse index continuous cardiac output (PiCCO), which can reflect lung water content. LUS score can be used as an early prognostic indicator for ARDS patients.

Prognostic value of plasma microRNA-30b-5p combined with extravascular lung water index in patients with acute respiratory distress syndrome

To evaluate the prognostic value of plasma microRNA-30b-5p (miR-30b-5p) combined with extravascular lung water index (EVLWI) in patients with acute respiratory distress syndrome (ARDS). 120 ARDS patients admitted to Danzhou People's Hospital from January 2016 to June 2019 were enrolled. The gender, age, body mass index (BMI), underlying diseases, etiology and baseline values of heart rate (HR), respiratory rate (RR), oxygenation index (OI), arterial partial pressure of carbon dioxide (PaCO2) and acute physiology and chronic health evaluation II (APACHE II) score were collected. According to the survival outcome during hospitalization, the patients were divided into survival group and death group. According to OI, the patients were divided into mild-moderate group (OI > 100 mmHg, 1 mmHg = 0.133 kPa) and severe group (OI ≤ 100 mmHg). The expression of plasma miR-30b-5p was detected by real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR), and EVLWI was measured. The receiver operating characteristic (ROC) curve was drawn to analyze the value of plasma miR-30b-5p and EVLWI in predicting the death of patients with ARDS. Pearson correlation method was used to analyze the correlation between miR-30b-5p and EVLWI in ARDS patients with different prognosis during hospitalization. 120 patients with ARDS were enrolled in the analysis, with 42 patients in the death group, and 78 in the survival group; with 67 patients in the mild-moderate group, and 53 in the severe group. APACHE II score in the death group was higher than that in the survival group, but there was no significant difference in gender, age, BMI, underlying diseases, etiology or baseline values of HR, RR, OI, or PaCO2 between the two groups. The expression of plasma miR-30b-5p and EVLWI level in the death group were significantly higher than those in the survival group [miR-30b-5p (2-ΔΔCt): 2.28±0.74 vs. 0.52±0.06, EVLWI (mL/kg): 15.38±4.60 vs. 10.24±2.15,both P < 0.01]. The expression of plasma miR-30b-5p, EVLWI and mortality during hospitalization in the severe group were significantly higher than those in the mild-moderate group [miR-30b-5p (2-ΔΔCt): 2.05±0.65 vs. 0.93±0.17, EVLWI (mL/kg): 14.65±4.20 vs. 11.36±2.28, mortality during hospitalization: 58.5% (31/53) vs. 16.4% (11/67), all P < 0.01]. ROC curve analysis showed that the best cut-off value of plasma miR-30b-5p and EVLWI in predicting the death during hospitalization of ARDS patients were 1.62 and 13.28 mL/kg, respectively. Moreover, the area under ROC curve (AUC) of the combination of two parameters was significantly higher than that of the two alone (0.897 vs. 0.827, 0.785), with high sensitivity and specificity, 90.5% and 84.2%, respectively. Pearson correlation analysis showed that plasma miR-30b-5p in dead ARDS patients was significantly positively correlated with EVLWI (r = 0.768, P < 0.01), but the correlation was not found in surviving patients (r = 0.118, P > 0.05). The expression of plasma miR-30b-5p and EVLWI are related to the severity and prognosis of patients with ARDS, and the combination of the two has certain evaluation value for the prognosis of ARDS patients.