Thrombin worsens extravascular lung water and outcomes of septic patients with acute respiratory distress syndrome: A case control study.

Endothelial cell (EC) activation may increase systemic vascular permeability, causing extravascular lung water (EVLW) in sepsis with acute respiratory distress syndrome (ARDS). However, the correlation between thrombin and EVLW in sepsis and ARDS has not yet been addressed. Patients with sepsis and ARDS were prospectively enrolled between 2014 and 2016, and EVLW and serum thrombin levels on days 1 and 3 were measured and compared between surviving and non-surviving patients. Additionally, morphological changes in human umbilical vein endothelial cells (HUVECs) in the serum of patients with high and low EVLW were evaluated. The levels of EVLW, endothelial cells, and thrombin may positively correlate with the survival of patients with severe sepsis and ARDS. Twenty-seven patients were enrolled, and baseline characteristics, including age, sex, Acute Physiology and Chronic Health Evaluation (APACHE) II, prior 24-h fluid balance, body mass index, and shock status, were similar between survivors and non-survivors; however, day 1 EVLW was higher in non-survivors (27.5 ±â€…8.4 vs 22 ±â€…6.5 mL/kg, P = .047). EVLW of survivors improved from day 1 to day 3 (22 ±â€…6.5 vs 11 ±â€…3.8 mL/kg, P < .001), but did not improve in non-survivors (27.5 ±â€…8.4 vs 28 ±â€…6.7 mL/kg, P = .086), which means that patients had significantly lower EVLW on day 3 than on day 1. Thrombin levels of survivors significantly improved (1.03 ±â€…0.55 vs 0.87 ±â€…0.25 U/mL, P = .04) but did not improve in non-survivors (1.97 ±â€…0.75 vs 2.2 ±â€…0.75 U/mL, P = .08) from day 1 to day 3. EVLW and thrombin levels were positively correlated (r2 = 0.71, P < .0001). In vitro, the morphology and junctions of HUVECs changed when the serum from patients with high EVLW was added. The intercellular distances among the control, high EVLW, and low EVLW groups were 5.25 ± 1.22, 21.33 ± 2.15, and 11.17 ± 1.64 µm, respectively (P < .05).

A century of exercise physiology: lung fluid balance during and following exercise.

PURPOSE: This review recalls the principles developed over a century to describe trans-capillary fluid exchanges concerning in particular the lung during exercise, a specific condition where dyspnea is a leading symptom, the question being whether this symptom simply relates to fatigue or also implies some degree of lung edema. METHOD: Data from experimental models of lung edema are recalled aiming to: (1) describe how extravascular lung water is strictly controlled by "safety factors" in physiological conditions, (2) consider how waning of "safety factors" inevitably leads to development of lung edema, (3) correlate data from experimental models with data from exercising humans. RESULTS: Exercise is a strong edemagenic condition as the increase in cardiac output leads to lung capillary recruitment, increase in capillary surface for fluid exchange and potential increase in capillary pressure. The physiological low microvascular permeability may be impaired by conditions causing damage to the interstitial matrix macromolecular assembly leading to alveolar edema and haemorrhage. These conditions include hypoxia, cyclic alveolar unfolding/folding during hyperventilation putting a tensile stress on septa, intensity and duration of exercise as well as inter-individual proneness to develop lung edema. CONCLUSION: Data from exercising humans showed inter-individual differences in the dispersion of the lung ventilation/perfusion ratio and increase in oxygen alveolar-capillary gradient. More recent data in humans support the hypothesis that greater vasoconstriction, pulmonary hypertension and slower kinetics of alveolar-capillary O2 equilibration relate with greater proneness to develop lung edema due higher inborn microvascular permeability possibly reflecting the morpho-functional features of the air-blood barrier.

Early restrictive fluid resuscitation has no clinical advantage in experimental severe pediatric acute respiratory distress syndrome.

Intravenous fluids are widely used to treat circulatory deterioration in pediatric acute respiratory distress syndrome (PARDS). However, the accumulation of fluids in the first days of PARDS is associated with adverse outcome. As such, early fluid restriction may prove beneficial, yet the effects of such a fluid strategy on the cardiopulmonary physiology in PARDS are unclear. In this study, we compared the effect of a restrictive with a liberal fluid strategy on a hemodynamic response and the formation of pulmonary edema in an animal model of PARDS. Sixteen mechanically ventilated lambs (2-6 wk) received oleic acid infusion to induce PARDS and were randomized to a restrictive or liberal fluid strategy during a 6-h period of mechanical ventilation. Transpulmonary thermodilution determined extravascular lung water (EVLW) and cardiac output (CO). Postmortem lung wet-to-dry weight ratios were obtained by gravimetry. Restricting fluids significantly reduced fluid intake but increased the use of vasopressors among animals with PARDS. Arterial blood pressure was similar between groups, yet CO declined significantly in animals receiving restrictive fluids (P = 0.005). There was no difference in EVLW over time (P = 0.111) and lung wet-to-dry weight ratio [6.1, interquartile range (IQR) = 6.0-7.3 vs. 7.1, IQR = 6.6-9.4, restrictive vs. liberal, P = 0.725] between fluid strategies. Both fluid strategies stabilized blood pressure in this model, yet early fluid restriction abated CO. Early fluid restriction did not limit the formation of pulmonary edema; therefore, this study suggests that in the early phase of PARDS, a restrictive fluid strategy is not beneficial in terms of immediate cardiopulmonary effects.

Assessment of extravascular lung water by measuring the number of pulmonary ultrasound B-lines before and after CBP in patients with MODS.

ABSTRACT: To determine whether the change in the number of pulmonary ultrasound B-line can accurately assess the extravascular lung water (EVLW) before and after continuous bedside blood purification (CBP) in patients with multiple organ dysfunction syndrome (MODS).Seventy-six patients with MODS who underwent CBP were examined within 24 hours before and after CBP using pulmonary ultrasound to detect the number of ultrasound B-line or using pulse indicator continuous cardiac output method to examine extravascular lung water, blood oxygenation index, and B-type natriuretic peptide (BNP) content. The correlation of the change in the number of B lines before and after CBP treatment with the negative balance of 24 hours liquid, the change of oxygenation index, and BNP content were analyzed.In the 76 patients, CBP treatment significantly decreased EVLW, the number of B-line, and BNP (P < .05 for all), while it significantly increased the oxygenation index (P < .05). Correlation analysis showed that the decrease in B-line number after CBP treatment was positively correlated with the 24 hours negative lung fluid balance, decrease of EVLW, oxygenation index improvement, and decreased BNP content. The change in the numbers of pulmonary ultrasound B-line can accurately assess the change of EVLW before and after CBP treatment and reflect the efficiency of ventilation in the lungs and the risk of heart failure.Thus, it can replace pulse indicator continuous cardiac output as an indicator for evaluating EVLW in patients with MODS treated with CBP.

Effect of ultrafiltration on extravascular lung water assessed by lung ultrasound in children undergoing cardiac surgery: a randomized prospective study.

BACKGROUND: Increased lung water and the resultant atelectasis are significant pulmonary complications after cardiopulmonary bypass (CPB) in children undergoing cardiac surgery; these complications are observed after CPB than after anaesthesia alone. Ultrafiltration has been shown to decrease total body water and postoperative blood loss and improve the alveolar to arterial oxygen gradient and pulmonary compliance. This study investigated whether conventional ultrafiltration during CPB in paediatric heart surgeries influences post-bypass extravascular lung water (EVLW) assessed by lung ultrasound (LUS). METHODS: This randomized controlled study included 60 patients with congenital heart disease (ASA II-III), aged 1 to 48 months, with a body weight > 3 kg. Conventional ultrafiltration targeting a haematocrit (HCT) level of 28% was performed on the ultrafiltration group, while the control group did not receive ultrafiltration. LUS scores were recorded at baseline and at the end of surgery. The PaO2/FiO2 ratio (arterial oxygen tension divided by the fraction of inspired oxygen), urine output, and haemodynamic parameters were also recorded. RESULTS: LUS scores were comparable between the two groups both at baseline (p = 0.92) and at the end of surgery (p = 0.95); however, within the same group, the scores at the end of surgery significantly differed from their baseline values in both the ultrafiltration (p = 0.01) and non-ultrafiltration groups (p = 0.02). The baseline PaO2/FiO2 ratio was comparable between both groups. at the end of surgery, The PaO2/FiO2 ratio increased in the ultrafiltration group compared to that in the non-ultrafiltration group, albeit insignificant (p = 0.16). no correlation between the PaO2/FiO2 ratio and LUS score was found at baseline (r = - 0.21, p = 0.31). On the other hand, post-surgical measurements were negatively correlated (r = - 0.41, p = 0.045). CONCLUSION: Conventional ultrafiltration did not alter the EVLW when assessed by LUS and oxygenation state. Similarly, ultrafiltration did not affect the urea and creatinine levels, intensive care unit (ICU) stays, ventilation days, or mortality. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT03146143 registered on 29-April-2017.

Critical hemodynamic therapy oriented resuscitation helping reduce lung water production and improve survival.

BACKGROUND: Increased extravascular lung water (EVLW) in shock is common in the critically ill patients. This study aimed to explore the effect of cardiac output (CO) on EVLW and its relevant influence on prognosis. METHODS: The hemodynamic data of 428 patients with pulse-indicated continuous CO catheterization from Department of Critical Care Medicine, Peking Union Medical College Hospital were retrospectively collected and analyzed. The patients were assigned to acute respiratory distress syndrome group, cardiogenic shock group, septic shock group, and combined shock (cardiogenic and septic) group according to their symptoms. Information on 28-day mortality and renal function was also collected. RESULTS: The CO and EVLW index (EVLWI) in the cardiogenic and combined shock groups were lower than those in the other groups (acute respiratory distress syndrome group vs. cardiogenic shock group vs. septic shock group vs. combined shock group: CO, 5.1 [4.0, 6.2] vs. 4.7 [4.0, 5.7] vs. 5.5 [4.3, 6.7] vs. 4.6 [3.5, 5.7] at 0 to 24 h, P = 0.009; 4.6 [3.8, 5.6] vs. 4.8 [4.1, 5.7] vs. 5.3 [4.4, 6.5] vs. 4.5 [3.8, 5.3] at 24 to 48 h, P = 0.048; 4.5 [4.1, 5.4] vs. 4.8 [3.8, 5.5] vs. 5.3 [4.0, 6.4] vs. 4.0 [3.2, 5.4] at 48 to 72 h, P = 0.006; EVLWI, 11.4 [8.7, 19.1] vs. 7.9 [6.6, 10.0] vs. 8.8 [7.4, 11.0] vs. 8.2 [6.7, 11.3] at 0 to 24 h, P < 0.001; 11.8 [7.7, 17.2] vs. 7.8 [6.3, 10.2] vs. 8.7 [6.6, 12.2] vs. 8.0 [6.6, 11.1] at 24 to 48 h, P < 0.001; and 11.3 [7.7, 18.7] vs. 7.5 [6.3, 10.0] vs. 8.8 [6.3, 12.2] vs. 8.4 [6.4, 11.2] at 48 to 72 h, P < 0.001. The trend of the EVLWI in the septic shock group was higher than that in the cardiogenic shock group (P < 0.05). Moreover, there existed some difference in the pulmonary vascular permeability index among the cardiogenic shock group, the septic shock group, and the combined shock group, without statistical significance (P > 0.05). In addition, there was no significant difference in tissue perfusion or renal function among the four groups during the observation period (P > 0.05). However, the cardiogenic shock group had a higher 28-day survival rate than the other three groups [log rank (Mantel-Cox) = 31.169, P < 0.001]. CONCLUSION: Tissue-aimed lower CO could reduce the EVLWI and achieve a better prognosis.

Lung Ultrasound B-lines Occurrence in Relation to Left Ventricular Function and Hydration Status in Hemodialysis Patients.

BACKGROUND AND OBJECTIVE: Reliable assessment of the fluid status in hemodialysis (HD) patients is often difficult. A lung ultrasound with an assessment of the B-lines ("lung comets" (LCs)) number is a novel hydration status measure. However, the occurrence of left ventricular dysfunction may have a significant effect on pulmonary congestion and further modulate the LC number. The aim of this study was to analyze to what extent left ventricular dysfunction, pulmonary hypertension, and hypervolemia affect the occurrence of LC in a cohort of prevalent HD patients. MATERIAL AND METHODS: This cross-sectional study included 108 assessments performed in 54 patients who attended thrice weekly outpatient HD. Each patient's fluid status was evaluated twice, prior to HD sessions, using echocardiography, LC number assessment, measurement of inferior vena cava (IVC) diameters, and bioelectric impedance analysis (BIA). Patients were stratified into three subgroups according to their LC number. RESULTS: There were 76 separate assessments with mild (<14), 16 with moderate (14⁻30), and 16 with severe (>30) LC occurrence. There was a negative correlation between the LC number and left ventricular ejection fraction (LVEF), and positive correlations between the LC number and mitral gradient, and the left and right atrium area and volume, but not with the BIA-derived relative fluid overload. Multivariate linear regression analysis revealed that the LC number was proportionally related to the mitral gradient (ß = 0.407 (0.247⁻0.567), p < 0.001) and IVC max diameter (ß = 0.219 (0.060⁻0.378), p < 0.01), and was inversely related to LVEF (ß = -0.431 (-0.580 to -0.282), p < 0.001). CONCLUSIONS: The number of LCs appears to reflect both overhydration and left ventricular dysfunction in our HD patients cohort. Therefore, heart failure must be considered as an important factor limiting the usefulness of LCs number assessment in this population.

Reducing lung liquid volume increases biventricular outputs and systemic arterial blood flows despite decreased cardiac filling pressures in fetal lambs.

As prior work has shown that reducing lung liquid volume 1) increases pulmonary arterial (PA) blood flow, 2) augments right ventricular (RV) output/power, and 3) decreases left atrial (LA) pressure, we tested the hypothesis that this perturbation has global cardiovascular effects. Ten anesthetized, open-chest fetal lambs (128 ± 2 days gestation, full term = 147 days) were acutely instrumented with 1) LA and right atrial (RA) catheters, 2) aortic and pulmonary trunk catheters, 3) brachiocephalic trunk, aortic isthmus, ductal, and left PA flow probes to obtain left ventricular (LV) and RV outputs and hydraulic power and flow in the descending thoracic aorta, and 4) an endotracheal tube to remove lung liquid. A 17 ± 7 ml/kg reduction of lung liquid volume 1) decreased LA and RA pressures similarly (1.5-1.6 mmHg, P < 0.001), 2) augmented LV and RV outputs (21-24%, P < 0.001) and total power (27-28%, P < 0.005), 3) increased systolic flows in the brachiocephalic trunk (18%, P < 0.001), aortic isthmus (29%, P < 0.005), ductus (12%, P < 0.005), and descending thoracic aorta (16%, P < 0.001), 4) increased mean PA flow via a higher systolic inflow (37%, P < 0.001) and lower diastolic backflow (-16%, P < 0.05), and 5) did not change systemic vascular conductance or arterial compliance but increased both pulmonary vascular conductance and arterial compliance (1.8-fold, P < 0.001). These data suggest that hemodynamic effects of lung liquid volume reduction are not confined to the lungs but extend to all cardiac chambers via rises in LV and RV outputs and power, despite falls in cardiac filling pressures, as well as the systemic circulation, via downstream increases in systolic flows of major central arteries.

Effect of age on the presence of comet tails at high altitude.

Extravascular lung water (EVLW) increases in healthy adults upon exposure to high altitude, likely due to increased pulmonary vascular resistance (PVR). Older individuals experience increased PVR during exercise, which may be exacerbated by trekking at high altitude. This study aimed to determine whether EVLW development is greater in older versus younger adults during graded altitude exposure. Fourteen younger (32 ± 6y) and 12 older (58 ± 5y) healthy adults completed an 11-day trek of Mount Kilimanjaro. EVLW was assessed at rest via comet tails prior to the trek in Moshi (950 m), at Shira Camp (3505 m), at Barafu Camp (4837 m), and post-descent. An increase in altitude from Baseline to Barafu tended to increase the proportion of participants with mild EVLW (p = 0.06). A higher proportion of older versus younger individuals tended to show mild EVLW at Barafu (56 vs. 14%, p = 0.06). In conclusion, EVLW formation may be more common in older adults trekking at high altitude. However, the presence of EVLW in older adults was subclinical.

Effect of Fluid Bolus Therapy on Extravascular Lung Water Measured by Lung Ultrasound in Children With a Presumptive Clinical Diagnosis of Sepsis.

OBJECTIVES: Fluid bolus therapy for the treatment of sepsis may lead to the accumulation of extravascular lung water (EVLW) and result in respiratory dysfunction. We aimed to assess changes in EVLW using lung ultrasound (US) in children with a presumptive clinical diagnosis of sepsis after fluid bolus therapy and correlate these changes with respiratory signs. METHODS: This work was a prospective observational study set in the emergency department of the Royal Children's Hospital. Children meeting international consensus criteria for sepsis receiving fluid bolus therapy were included. Respiratory signs were recorded, and lung US examinations were performed immediately before, 5 minutes after, and 60 minutes after fluid bolus therapy. A pediatric emergency physician blinded to the participants' identities and timing of US calculated an EVLW score from lung US. Results-Fifty fluid boluses were recorded in 41 children. The lung US score (range, 0-8) increased over the study period: median, 1 (interquartile range, 0-2) before fluid bolus therapy, 1 (interquartile range, 0-3) 5 minutes after fluid bolus therapy, and 3 (interquartile range, 1-4) 60 minutes after fluid bolus therapy. Respiratory effort, but not the respiratory rate or the presence of rales, increased over the study period and was correlated with the lung US score (ρ = 0.33; P = .02). CONCLUSIONS: Extravascular lung water as measured by lung US increased after fluid bolus therapy in septic children and was correlated with an increase in the respiratory distress score. The respiratory rate and the presence of rales did not change over the study period. The role of lung US for titrating fluid bolus therapy in sepsis warrants further investigation.

Extravascular lung water measurements in acute respiratory distress syndrome: why, how, and when?

PURPOSE OF REVIEW: Increase in pulmonary vascular permeability accompanied with accumulation of excess extravascular lung water (EVLW) is the hallmark of acute respiratory distress syndrome (ARDS). Currently, EVLW and pulmonary vascular permeability index (PVPI) can be quantitatively measured using the transpulmonary thermodilution (TPTD) technique. We will clarify why, how, and when EVLW and PVPI measurements should be performed. RECENT FINDINGS: Although the Berlin criteria of ARDS are simple and widely used, several criticisms of them have been published. The last 2 decades have witnessed the introduction and evolution of the TPTD technique for measuring EVLW and PVPI. Several publications have recommended to evaluate EVLW and the PVPI during the treatment of critically ill patients. Accurate and objective diagnoses can be made for ARDS patients using EVLW and PVPI. EVLW more than 10 ml/kg is a reasonable criterion for pulmonary edema, and EVLW more than 15 ml/kg for a severe condition. In addition to EVLW more than 10 mL/kg, PVPI more than three suggests increased vascular permeability (i.e., ARDS), and PVPI less than 2 represent normal vascular permeability (i.e., cardiogenic pulmonary edema). SUMMARY: EVLW and PVPI measurement will open the door to future ARDS clinical practice and research, and have potential to be included in the future ARDS definition.

A Simplified Ultrasound Comet Tail Grading Scoring to Assess Pulmonary Congestion in Patients with Heart Failure.

Ultrasound lung comets (ULCs) are a nonionizing bedside approach to assess extravascular lung water. We evaluated a protocol for grading ULC score to estimate pulmonary congestion in heart failure patients and investigated clinical and echocardiographic correlates of the ULC score. Ninety-three patients with congestive heart failure, admitted to the emergency department, underwent pulmonary ultrasound and echocardiography. A ULC score was obtained by summing the ULC scores of 7 zones of anterolateral chest scans. The results of ULC score were compared with echocardiographic results, the New York Heart Association (NYHA) functional classification, radiologic score, and N-terminal pro-b-type natriuretic peptide (NT-proBNP). Positive linear correlations were found between the 7-zone ULC score and the following: E/e', systolic pulmonary artery pressure, severity of mitral regurgitation, left ventricular global longitudinal strain, NYHA functional classification, radiologic score, and NT-proBNP. However, there was no significant correlation between ULC score and left ventricular ejection fraction, left ventricle diameter, left ventricular volume, or left atrial volume. A multivariate analysis identified the E/e', systolic pulmonary artery pressure, and radiologic score as the only independent variables associated with ULC score increase. The simplified 7-zone ULC score is a rapid and noninvasive method to assess lung congestion. Diastolic rather than systolic performance may be the most important determinant of the degree of lung congestion in patients with heart failure.

Fluid Balance Is Associated with Clinical Outcomes and Extravascular Lung Water in Children with Acute Asthma Exacerbation.

RATIONALE: The effects of fluid administration during acute asthma exacerbation are likely unique in this patient population: highly negative inspiratory intrapleural pressure resulting from increased airway resistance may interact with excess fluid administration to favor the accumulation of extravascular lung water, leading to worse clinical outcomes. OBJECTIVES: Investigate how fluid balance influences clinical outcomes in children hospitalized for asthma exacerbation. METHODS: We analyzed the association between fluid overload and clinical outcomes in a retrospective cohort of children admitted to an urban children's hospital with acute asthma exacerbation. These findings were validated in two cohorts: a matched retrospective and a prospective observational cohort. Finally, ultrasound imaging was used to identify extravascular lung water and investigate the physiological basis for the inferential findings. MEASUREMENTS AND MAIN RESULTS: In the retrospective cohort, peak fluid overload [(fluid input - output)/weight] is associated with longer hospital length of stay, longer treatment duration, and increased risk of supplemental oxygen use (P values < 0.001). Similar results were obtained in the validation cohorts. There was a strong interaction between fluid balance and intrapleural pressure: the combination of positive fluid balance and highly negative inspiratory intrapleural pressures is associated with signs of increased extravascular lung water (P < 0.001), longer length of stay (P = 0.01), longer treatment duration (P = 0.03), and increased risk of supplemental oxygen use (P = 0.02). CONCLUSIONS: Excess volume administration leading to fluid overload in children with acute asthma exacerbation is associated with increased extravascular lung water and worse clinical outcomes.

The effect of diuresis on extravascular lung water and pulmonary function in acute decompensated heart failure.

AIMS: The effect of extravascular lung water (EVLW) and relationship to functional status as a result of acute decompensated heart failure (ADHF) are not well understood. We sought to quantify changes in clinical variables, EVLW, airway anatomy, spirometry, and diffusing capacity for carbon monoxide before and after treatment for ADHF. METHODS AND RESULTS: Fifteen patients were recruited within 24 h of hospital admission. Spirometry, diffusing capacity for carbon monoxide, and surrogates of EVLW by computed tomography were measured and were then repeated within 24 h of discharge. From the computed tomography (CT) scan, surrogates of EVLW were calculated from the distribution of CT attenuation of the lung tissue. Airways were segmented using the VIDA Apollo software. Patients were hospitalized for 4.6 ± 2.1 days, had 10 ± 4.8 L of fluid removed (7.0 ± 4.2 L between study visits), and lost 7.1 ± 4.9 kg. Patients had significant clearance of fluid from the lungs (per cent change: mean, 4.2 ± 6.1%; skew, 17.5 ± 27.0%; kurtosis, 37.6 ± 56.7%; full-width half-maximum, 10.2 ± 13.5%). Static lung volumes and maximal flows improved significantly (per cent change: forced vital capacity, 14.5 ± 13.6%; forced expiratory volume in 1 s, 15.9 ± 14.0%; forced expiratory flow at 25-75% of forced vital capacity, 27.2 ± 42.9%). The ratio of membrane conductance to capillary blood volume improved significantly (per cent change: alveolar-capillary membrane conductance/capillary blood volume, 23.4 ± 22.8%). Weight loss during hospitalization was significantly correlated with improved spirometry and diffusing capacity. CONCLUSIONS: Extravascular lung water contributes to the pulmonary congestive syndrome in ADHF patients, and its clearance is an important component of the improvement in pulmonary function as a result of inpatient treatment.

Assessment of Pulmonary Edema: Principles and Practice.

Pulmonary edema increasingly is recognized as a perioperative complication affecting outcome. Several risk factors have been identified, including those of cardiogenic origin, such as heart failure or excessive fluid administration, and those related to increased pulmonary capillary permeability secondary to inflammatory mediators. Effective treatment requires prompt diagnosis and early intervention. Consequently, over the past 2 centuries a concentrated effort to develop clinical tools to rapidly diagnose pulmonary edema and track response to treatment has occurred. The ideal properties of such a tool would include high sensitivity and specificity, easy availability, and the ability to diagnose early accumulation of lung water before the development of the full clinical presentation. In addition, clinicians highly value the ability to precisely quantify extravascular lung water accumulation and differentiate hydrostatic from high permeability etiologies of pulmonary edema. In this review, advances in understanding the physiology of extravascular lung water accumulation in health and in disease and the various mechanisms that protect against the development of pulmonary edema under physiologic conditions are discussed. In addition, the various bedside modalities available to diagnose early accumulation of extravascular lung water and pulmonary edema, including chest auscultation, chest roentgenography, lung ultrasonography, and transpulmonary thermodilution, are examined. Furthermore, advantages and limitations of these methods for the operating room and intensive care unit that are critical for proper modality selection in each individual case are explored.

Evaluation of Cardiac Index and Extravascular Lung Water After Single-Lung Transplantation Using the Transpulmonary Thermodilution Technique by the PiCCO2 Device.

OBJECTIVES: First evaluation of the transpulmonary thermodilution technique by the PiCCO2 device to assess cardiac index and pulmonary edema during the postoperative course after single-lung transplantation. DESIGN: Prospective observational study. SETTINGS: Intensive care unit, university hospital (single center). PARTICIPANTS: Single-lung transplant patients. INTERVENTIONS: The authors compared cardiac index measured by PiCCO2 and pulmonary artery catheter and assessed pulmonary edema using extravascular lung water index and pulmonary vascular permeability index measured by PiCCO2. MEASUREMENTS AND MAIN RESULTS: A Bland-Altman method was used to compare cardiac index measured by PiCCO2 and pulmonary artery catheter. Extravascular lung water index and pulmonary vascular permeability index were compared according to the PaO2/FiO2 ratio with a threshold value of 150 mmHg. Ten single-lung transplant patients were included. Cardiac index measured by PiCCO2 and pulmonary artery catheter were 3.3 L/min/m2 (2.9-3.6) and 2.5 L/min/m2 (2.2-3.0). Bias for cardiac index was 0.71 L/min/m2 (-0.03; 1.44) and limit of agreements were -0.03 and 1.44 L/min/m2. Extravascular lung water index was 12 mL/kg (11-16) and pulmonary vascular permeability index was 2.3 (2.0-3.1), consistent with pulmonary edema. Extravascular lung water index was higher in the group of PaO2/FiO2 ratio ≤150 mmHg compared with the group of PaO2/FiO2 ratio >150 mmHg (17 v 12 mL/kg, p = 0.04), whereas pulmonary vascular permeability index only tended to be higher (3.1 v 2.1, p = 0.06). CONCLUSION: PiCCO2 device systematically overestimated cardiac index compared with pulmonary artery catheter. However, it might be useful to assess pulmonary edema in acute respiratory failure after single-lung transplantation.

B-lines with Lung Ultrasound: The Optimal Scan Technique at Rest and During Stress.

Various lung ultrasound (LUS) scanning modalities have been proposed for the detection of B-lines, also referred to as ultrasound lung comets, which are an important indication of extravascular lung water at rest and after exercise stress echo (ESE). The aim of our study was to assess the lung water spatial distribution (comet map) at rest and after ESE. We performed LUS at rest and immediately after semi-supine ESE in 135 patients (45 women, 90 men; age 62 ± 12 y, resting left ventricular ejection fraction = 41 ± 13%) with known or suspected heart failure or coronary artery disease. B-lines were measured by scanning 28 intercostal spaces (ISs) on the antero-lateral chest, 2nd-5th IS, along with the midaxillary (MA), anterior axillary (AA), mid-clavicular (MC) and parasternal (PS) lines. Complete 28-region, 16-region (3rd and 4th IS), 8-region (3rd IS), 4-region (3rd IS, only AA and MA) and 1-region (left 3rd IS, MA) scans were analyzed. In each space, the B-lines were counted from 0 = black lung to 10 = white lung. Interpretable images were obtained in all spaces (feasibility = 100 %). B-lines (>0 in at least 1 space) were present at ESE in 93 patients (69%) and absent in 42. More B-lines were found in the 3rd IS and along AA and MA lines. The B-line cumulative distribution was symmetric at rest (right/left = 1.10) and asymmetric with left lung predominance during stress (right/left = 0.67). The correlation of per-patient B-line number between 28-S and 16-S (R2 = 0.9478), 8-S (R2 = 0.9478) and 4-S scan (R2 = 0.9146) was excellent, but only good with 1-S (R2 = 0.8101). The average imaging and online analysis time were 5 s per space. In conclusion, during ESE, the comet map of lung water accumulation follows a predictable spatial pattern with wet spots preferentially aligned with the third IS and along the AA and MA lines. The time-saving 4-region scan is especially convenient during stress, simply dismissing dry regions and focusing on wet regions alone.

Effect of rhubarb on extravascular lung water in patients with acute respiratory distress syndrome.

OBJECTIVE:: The aim of this study was to evaluate the effect of rhubarb on extravascular lung water (EVLW) in patients with acute respiratory distress syndrome (ARDS). METHOD:: A total of 80 patients with ARDS were randomly divided into a treatment group (40 cases) and control group (40 cases). Patients in the treatment group received rhubarb (30.0 g/d) and patients in the control group received conventional therapy for seven consecutive days. Extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) were determined using pulse contour cardiac output (PiCCO) technology, and the oxygenation index was measured by blood gas analysis at baseline and on days 3, 5 and 7 after treatment. RESULTS:: The oxygenation index was higher and the levels of EVLWI and PVPI were lower after treatment in the two groups; however, these indexes showed significant differences on the 5th and 7th days after rhubarb treatment compared with the results in the control group (p<0.05). CONCLUSION:: Rhubarb can decrease EVLWI and PVPI, and improve oxygenation in patients with ARDS.

Influence of Thoracic Fluid Compartments on Pulmonary Congestion in Chronic Heart Failure.

INTRODUCTION: Pulmonary congestion is a common finding of heart failure (HF), but it remains unclear how pulmonary and heart blood volumes (Vp and Vh, respectively) and extravascular lung water (EVLW) change in stable HF and affect lung function. METHODS: Fourteen patients with HF (age 68 ± 11 y, LVEF 33 ± 8%) and 12 control subjects (age 65 ± 9 y) were recruited. A pulmonary function test, thoracic computerized tomographic (CT) scan, and contrast perfusion scan were performed. From the thoracic scan, a histogram of CT attenuation of lung tissue was generated and skew, kurtosis, and full-width half-max (FWHM) calculated as surrogates of EVLW. Blood volumes were calculated from the transit time of the contrast through the great vessels of the heart. RESULTS: Patients with HF had greater Vp and Vh (Vp 0.55 ± 0.21 L vs 0.41 ± 0.13 L; Vh 0.53 ± 0.33 L vs 0.40 ± 0.15 L) and EVLW (skew 3.2 ± 0.5 vs 3.7 ± 0.7; kurtosis 19.4 ± 6.6 vs 25.9 ± 9.4; FWHM 73 ± 13 HU vs 59 ± 9 HU). Spirometric measures were decreased in HF (percentage of predicted: forced vital capacity 86 ± 17% vs 104 ± 9%; forced expiratory volume in 1 second 83 ± 20% vs 105 ± 11%; maximal mid-expiratory flow 82 ± 42% vs 115 ± 43%). Vp was associated with decreased expiratory flows, and EVLW was associated with decreased lung volumes. CONCLUSIONS: Congestion in stable patients with HF includes expanded Vp and Vh and increased EVLW associated with reductions in lung volumes and expiratory flows.