Accumulation Of Extravascular Lung Water Research Articles

The potential of the ultrasound method in diagnosing pulmonary edema in critically ill patients with liver failure

Background. Pulmonary edema is a common complication in critically ill patients. The liberal tactics of fluid therapy and pathological accumulation of extravascular lung water increase the risks of mortality in Intensive Care Unit patients. Timely and non-invasive diagnosis of pulmonary edema is a primary goal in the intensive care of patients in the Critical Care Unit. We prefer to use lung ultrasound with the registration of B-lines to diagnose lung edema. However, in our country, this method is not validated due to the lack of a sufficient number of clinical studies and necessary regulatory framework.Objective. To assess the potential of diagnostic ultrasonography for pulmonary edema in critically ill patients.Material and methods. A retrospective study was conducted on 27 patients, including 15 males and 12 females aged from 43 to 67 years old (mean age 45.05±17.2 years). All patients were in critical condition due either to acute liver failure, or acute-on-chronic liver failure, or early post-transplant liver graft failure, or posthepatectomy liver failure. Some patients had a systemic inflammatory response syndrome with the development of multiple organ failure and clinical signs of redistribution shock. All patients underwent ultrasound examination of the lungs, and had hemodynamic parameters measured using the transpulmonary thermodilution technique. The data obtained by the two diagnostic modalities were compared.Results. A significant correlation (p<0.05) was found between the extravascular lung water index and the presence of lung edema. We identified a significant correlation (p<0.05) between the number of B-lines and the presence of pulmonary edema. In assessing the relationship between the "B-line" parameter and the "EVLWI" parameter, a strong positive correlation was identified. The area under the ROC curve (AUC) was 0.9±0.06 with a 95% CI [0.77–1.00].Conclusions. Ultrasound data in diagnosing pulmonary edema have a significant correlation with the level of extravascular pulmonary water. Lung ultrasound is an accurate, non-invasive method for assessing extravascular lung water. It can be used for the rapid and accurate diagnosis of pulmonary edema.

Lung "Comet Tails" in Healthy Individuals: Accumulation or Clearance of Extravascular Lung Water?

Parks, Jordan K, Courtney M. Wheatley-Guy, Glenn M. Stewart, Caitlin C. Fermoyle, Bryan J. Taylor, Jesse Schwartz, Briana Ziegler, Kay Johnson, Alice Gavet, Loïc Chabridon, Paul Robach, and Bruce D. Johnson. Lung "Comet Tails" in healthy individuals: accumulation or clearance of extravascular lung water? High Alt Med Biol. 24:230-233, 2023-Ultrasound lung comet tails (or B-lines) tend to be limited in number (<5) or absent under ultrasound examination, and the appearance of diffuse B-lines with lung sliding has been suggested to identify pulmonary edema. Clinical evaluation of B-lines has been utilized as a bedside test to assess pulmonary congestion in patients with heart failure. Exposure to altitude or prolonged exercise can alter fluid regulation and can lead to pulmonary congestion or edema. As such, B-lines have been utilized in the field to monitor for pathological lung fluid accumulation. However, ultrasound lung comet lines might not be as reliable for identifying extravascular lung water (EVLW) as previously thought in healthy individuals exercising at altitude where an increase in the number of ultrasound lung comets would reflect fluid buildup in the interstitial space of the alveoli and pulmonary capillaries. This report will focus on reviewing the literature and our data from a group of ultraendurance runners that completed the Ultra Trail Mont Blanc race that demonstrates that lung comet tails may not always be evidence of pathological fluid accumulation in healthy individuals and as such should be used to assess EVLW in concert with other diagnostic testing.

Dynamic lung water MRI during exercise stress.

Exercise-induced dyspnea caused by lung water is an early heart failure symptom. Dynamic lung water quantification during exercise is therefore of interest to detect early stage disease. This study developed a time-resolved 3D MRI method to quantify transient lung water dynamics during rest and exercise stress. The method was evaluated in 15 healthy subjects and 2 patients with heart failure imaged in transitions between rest and exercise, and in a porcine model of dynamic extravascular lung water accumulation through mitral regurgitation (n = 5). Time-resolved images were acquired at 0.55T using a continuous 3D stack-of-spirals proton density weighted sequence with 3.5 mm isotropic resolution, and derived using a motion corrected sliding-window reconstruction with 90-s temporal resolution in 20-s increments. A supine MRI-compatible pedal ergometer was used for exercise. Global and regional lung water density (LWD) and percent change in LWD (ΔLWD) were automatically quantified. A ΔLWD increase of 3.3 ± 1.5% was achieved in the animals. Healthy subjects developed a ΔLWD of 7.8 ± 5.0% during moderate exercise, peaked at 16 ± 6.8% during vigorous exercise, and remained unchanged over 10 min at rest (-1.4 ± 3.5%, p = 0.18). Regional LWD were higher posteriorly compared the anterior lungs (rest: 33 ± 3.7% vs 20 ± 3.1%, p < 0.0001; peak exercise: 36 ± 5.5% vs 25 ± 4.6%, p < 0.0001). Accumulation rates were slower in patients than healthy subjects (2.0 ± 0.1%/min vs 2.6 ± 0.9%/min, respectively), whereas LWD were similar at rest (28 ± 10% and 28 ± 2.9%) and peak exercise (ΔLWD 17 ± 10% vs 16 ± 6.8%). Lung water dynamics can be quantified during exercise using continuous 3D MRI and a sliding-window image reconstruction.

MONITORING OF PULMONARY EDEMA USING ULTRASOUND RADIOFREQUENCY SIGNAL.

Objectives: Excessive accumulation of extravascular lung water impairs respiratory gas exchange and results in respiratory distress. Real-time radiofrequency signals of ultrasound can continuously and quantitatively monitor excessive lung water. This study aims to evaluate the availability of continuous real-time quantitative pulmonary edema monitoring using ultrasound radiofrequency signals and compare it with Pa o2 (partial pressure of arterial oxygen)/F io2 (fraction of inspired oxygen) (PF) ratio, conventional lung ultrasound, and the Hounsfield unit of chest computed tomography. Methods: Male Yorkshire pigs (40.5 ± 0.5 kg) were anesthetized and mechanically ventilated. A balanced crystalloid was administered to induce hydrostatic pulmonary edema. Three different infusion rates of 2, 4, and 6 mL/kg per minute were tested to determine the infusion rate for the appropriate swine model. The chest computed tomography and ultrasonography with radiofrequency signals were taken every 5 min during the full inspiration. The ultrasonography scans with radiofrequency signals were measured at the intercostal space where the line crossing the two armpits and the right anterior axillary line intersected. Results: The infusion rate of fluid for the pulmonary edema model was determined to be 6 mL/kg per minute, and a total of four pigs were tested at an injection rate of 6 mL/kg. The adjusted R2 values of regression analysis between the radiofrequency signal and computer tomography Hounsfield score were 0.990, 0.993, 0.988, and 0.993 (all P values <0.05). All radiofrequency signal changes preceded changes in PF ratio or lung ultrasound changes. The area under the receiver operating characteristic curve of the radiofrequency signal for predicting PF ratio <300 was 0.88 (95% confidence interval, 0.82-0.93). Conclusion: We evaluated ultrasound radiofrequency signals to assess pulmonary edema in a swine model that can worsen gradually and showed that quantitative ultrasound radiofrequency signal analysis could assess pulmonary edema and its progression before PF ratio or lung ultrasound changes.

MEDEX 2015: Prophylactic Effects of Positive Expiratory Pressure in Trekkers at Very High Altitude.

Purpose: Positive expiratory pressure (PEP) breathing has been shown to increase arterial oxygenation during acute hypoxic exposure but the underlying mechanisms and consequences on symptoms during prolonged high-altitude exposure remain to be elucidated.Methods: Twenty-four males (41 ± 16 years) were investigated, at sea level and at 5,085 m after 18 days of trekking from 570 m. Participants breathed through a face-mask with PEP = 0 cmH2O (PEP0, 0–45th min) and with PEP = 10 cmH2O (PEP10, 46–90th min). Arterial (SpO2), quadriceps and prefrontal (near infrared spectroscopy) oxygenation was measured continuously. Middle cerebral artery blood velocity (MCAv, transcranial Doppler), cardiac function (2D-echocardiography), extravascular lung water accumulation (UsLC, thoracic ultrasound lung comets) and acute mountain sickness (Lake Louise score, LLS) were assessed during PEP0 and PEP10.Results: At 5,085 m with PEP0, SpO2 was 78 ± 4%, UsLC was 8 ± 5 (a.u.) and the LLS was 2.3 ± 1.7 (all P < 0.05 versus sea level). At 5,085 m, PEP10 increased significantly SpO2 (+9 ± 5%), quadriceps (+2 ± 2%) and prefrontal cortex (+2 ± 2%) oxygenation (P < 0.05), and decreased significantly MCAv (−16 ± 14 cm.s–1) and cardiac output (−0.7 ± 1.2 L.min–1) together with a reduced stroke volume (−9 ± 15 mL, all P < 0.05) and no systemic hypotension. PEP10 decreased slightly the number of UsLC (−1.4 ± 2.7, P = 0.04) while the incidence of acute mountain sickness (LLS ≥ 3) fell from 42% with PEP0 to 25% after PEP10 (P = 0.043).Conclusion: PEP10 breathing improved arterial and tissue oxygenation and symptoms of acute mountain sickness after trekking to very high altitude, despite reduced cerebral perfusion and cardiac output. Further studies are required to establish whether PEP-breathing prophylactic mechanisms also occur in participants with more severe acute mountain sickness.

P1506Pulmonary decongestion pattern during stress lung ultrasound

Abstract Background B-profile detected by lung ultrasound (LUS) during stress echocardiography (SE) consists in B-lines with lung sliding and mirrors extra-vascular lung water accumulation (“wet lung”), more often found with ischemic regional wall motion abnormalities (RWMA) and/or diastolic dysfunction. B-lines present at rest may also decrease during stress. Aim To assess the frequency and functional correlates of decreasing B-profile (“drying lung” pattern) during SE. Methods We prospectively performed transthoracic echocardiography (TTE) and LUS evaluation at rest and peak stress in 780 patients with B-lines at rest referred for exercise (n=387), vasodilator (n=324) or dobutamine (n=69) SE for known/suspected coronary artery disease (CAD) and/or heart failure (HF). Recruitment occurred in 17 certified labs of 8 countries with the ABCD protocol, including regional wall motion abnormalities with wall motion score index (WMSI), B-lines, left ventricular contractile reserve (LVCR based on force, systolic blood pressure/end-systolic volume) and Doppler-based coronary flow velocity reserve (CFVR, available in 473 patients). By LUS, we adopted the 4-site simplified scan, each site scored from 0=normal A-lines, to 10=coalescing B-lines. By selection, all patients had resting B-lines score ≥2. Invasive or noninvasive coronary angiography was available in 208 patients. Results Two B-lines stress patterns were identified: Group 1, increase or unchanged pattern (B-line stress score ≥ rest, n=698, 89%); Group 2, decrease-disappearance pattern (B-line stress score &lt; rest for ≤2 points, n=82, 11%). Group 1 showed higher prevalence of inducible ischemia (Group 1 = 74/698 vs. Group 2 = 5/82, 11% vs. 6%, p&lt;0.001), abnormal LVCR (Group 1 = 403/698 vs. Group 2 = 36/82, 58% vs. 42%, p=0.012) and impaired CFVR (Group 1 = 173/433 vs. Group 2 = 5/40, 40 vs. 12%, p&lt;0.001): see figure. Two- or three-vessel coronary artery disease was also more frequent in fixed-worsening pattern (Group 1 = 88/191 vs. Group 2 = 3/17, 46 vs. 17%, p=0.024). Multivariate logistic regression analysis identified peak Force (Odds Ratio, OR, 1.039, 95% Confidence Intervals, CI: 1.006–1.074, P=0.022), stress-rest Δ-WMSI (OR 0.190, 95% CI 0.086–0.419, P&lt;0.001) and normal CFVR (OR=1.754, 95% CI: 1.147–2.682, P=0.010) as significant predictors of drying lung pattern. Disappearing BLines Conclusion About one out of 10 patients with resting B-lines exhibit a decrease-disappearance pattern during stress. They show a more benign coronary anatomic, myocardial functional and coronary physiological profile compared to patients with the fixed-worsening pattern. The drying lung pattern is more often accompanied by a strong (higher peak force), non-ischemic and warm heart (with normal CFVR).

Extravascular lung water monitoring for thoracic and lung transplant surgeries

Excessive accumulation of extravascular lung water (EVLW) resulting in pulmonary edema is the most feared complication following thoracic surgery and lung transplant. ICUs have long relied on chest radiography to monitor pulmonary status postoperatively but the increasing recognition of the limitations of bedside plain films has fueled development of newer technologies, which offer earlier detection, quantitative assessments, and can aide in preoperative screening of surgical candidates. In this review, we focus on the emergence of transpulmonary thermodilution (TPTD) and lung ultrasound with a focus on the clinical integration of these modalities into current intraoperative and critical care practices. Recent studies demonstrate transpulmonary thermodilution and lung ultrasound provide greater sensitivity and earlier detection of lung water accumulation and are useful to guide clinical management. Assessments from these techniques have predictive value of postoperative outcome. Further, EVLW assessment shows promise as a preoperative screening tool in lung transplant patients. Monitoring EVLW in the perioperative period offers clinicians a powerful tool to guide fluid therapy and manage pulmonary edema. Both TPTD and lung ultrasound have unique attributes in the care of thoracic surgery and lung transplant patients.

Phosgene-induced lung edema: Comparison of clinical criteria for increased extravascular lung water content with postmortem lung gravimetry and lavage-protein in rats and dogs

Phosgene-induced acute lung injury (ALI) is characterized by a concentration x time (Cxt)-dependent increased pulmonary vascular permeability, phenotypically manifested as potentially life-threatening acute lung edema. In contemporary animal bioassays, the quantification of protein in bronchoalveolar lavage fluid (BAL) is taken as an unequivocal endpoint suggestive of disruption of alveolar barrier function. However, extravasated protein can only be a surrogate endpoint for assessing the extravascular fluid dynamics of the lung. This pathophysiological hallmark of ALI is diagnosed and quantified in vivo in humans by assessing the accumulation of excess extravascular lung water (EVLW). The Point of Departure (POD) of the Cxt relationship of this adverse outcome pathway should also constitute the basis for setting safe occupational and emergency response values. Unlike the EVLW approach, toxicology-based animal models utilize postmortem analyses of total protein in BAL and lung weights as the basis for human risk assessment. With either approach, it remains difficult to unequivocally evaluate pulmonary edema in terms of etiopathology and specificity, i.e., cardiogenic and hydrostatic versus increased permeability edema. The objective of this paper is to retrospectively analyze the clinical scoring of the severity grades of in vivo EVLWs from humans with the respective postmortem biomarkers BAL protein and collagen versus wet lung weights in rats and dogs exposed by inhalation to phosgene gas. Despite the different methodological approaches taken in humans and animals, the EVLW-based predicted thresholds for the onset of pulmonary edema and potentially life-threatening severe pulmonary edema were in remarkable agreement. Data from dogs appear to more aptly reflect the human etiopathology and should be given preference over data from rodents. Especially in rats, elevations in BAL protein may lead to a marked overestimation of the edematous potency of phosgene due to secreted protein into airways. In summary, increased lung weight in rats and dogs scaled favorably with the human-EVLW and was shown to be the biomarker of choice for the scaling lung edema. Caution is advised when using BAL protein in isolation as a surrogate endpoint of pulmonary edema.

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

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. 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). 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 reviewIncrease 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 findingsAlthough 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).SummaryEVLW 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.

Effects of 6% Tetrastarch and Lactated Ringer's Solution on Extravascular Lung Water and Markers of Acute Renal Injury in Hemorrhaged, Isoflurane-Anesthetized Healthy Dogs.

BackgroundTetrastarch can cause acute kidney injury (AKI) in humans with sepsis, but less likely to result in tissue edema than lactated Ringer's solution (LRS).ObjectivesCompare effects of volume replacement (VR) with LRS and 6% tetrastarch solution (TS) on extravascular lung water (EVLW) and markers of AKI in hemorrhaged dogs.AnimalsSix healthy English Pointer dogs (19.7–35.3 kg).MethodsProspective crossover study. Animals underwent anesthesia without hemorrhage (Control). Two weeks later, dogs hemorrhaged under anesthesia on 2 occasions (8‐week washout intervals) and randomly received VR with LRS or TS at 3 : 1 or 1 : 1 of shed blood, respectively. Anesthesia was maintained until 4 hour after VR for EVLW measurements derived from transpulmonary thermodilution cardiac output. Neutrophil gelatinase‐associated lipocalin (NGAL) and creatinine concentrations in plasma and urine were measured until 72 hour after VR.ResultsThe EVLW index (mL/kg) was lower at 1 hour after TS (10.0 ± 1.9) in comparison with controls (11.9 ± 3.4, P = 0.04), and at 4 hour after TS (9.7 ± 1.9) in comparison with LRS (11.8 ± 2.7, P = 0.03). Arterial oxygen partial pressure‐to‐inspired oxygen fraction ratio did not differ among treatments from 0.5 to 4 hour after VR. Urine NGAL/creatinine ratio did not differ among treatments and remained below threshold for AKI (120,000 pg/mg).Conclusions and Clinical ImportanceAlthough TS causes less EVLW accumulation than LRS, neither fluid produced evidence of lung edema (impaired oxygenation). Both fluids appear not to cause AKI when used for VR after hemorrhage in healthy nonseptic dogs.

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

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. Investigate how fluid balance influences clinical outcomes in children hospitalized for asthma exacerbation. 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. 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). Excess volume administration leading to fluid overload in children with acute asthma exacerbation is associated with increased extravascular lung water and worse clinical outcomes.

Cardiovascular Mechanisms of Extravascular Lung Water Accumulation in Divers

This study assessed the relation between altered cardiac function and the development of interstitial pulmonary edema in scuba divers. Fifteen healthy men performed a 30-minute scuba dive in open sea. They were instructed to fin for 30minutes and were wearing wet suits. Before and immediately after immersion, cardiac indexes and extravascular lung water were measured using echocardiography and lung ultrasound, respectively. The mean ultrasound lung comet score increased from 0 to 4.6 ± 3.4. The diameter of the inferior caval vein increased by 47 ± 5.2%, systolic pulmonary artery pressure by 105 ± 8.6%, left atrial volume by 18.0 ± 3.3%, and left ventricle end-diastolic volume by 10 ± 2.4% suggesting that both right and left ventricular (LV) filling pressures were elevated. Doppler studies showed an increased mitral E peak (+2.5 ± 0.3%) and E/A ratio (+22.5 ± 3.4%) with a decreased mitral A peak (-16.4 ± 2.7%), E peak deceleration time (-14.5 ± 2.4%) consistent with rapid early LV filling but without a change in LV stroke volume. There was an increase in right/left ventricle diameter ratio (+33.6 ± 4.8%) suggesting a relative increase in right-sided heart output compared with the left. Furthermore, the lung comet score correlated significantly with inferior caval vein diameter, systolic pulmonary artery pressure, right/left ventricle diameter ratio, and E-wave deceleration time. In conclusion, the altered right/left heart stroke volume balance could play an essential role in the development of immersion pulmonary edema. Our findings have important implications for the pathogenesis of cardiogenic pulmonary edema.

Ultrasound of extravascular lung water: a new standard for pulmonary congestion.

Extravascular lung water (EVLW) is a key variable in heart failure management and prognosis, but its objective assessment remains elusive. Lung imaging has been traditionally considered off-limits for ultrasound techniques due to the acoustic barrier of high-impedance air wall. In pulmonary congestion however, the presence of both air and water creates a peculiar echo fingerprint. Lung ultrasound shows B-lines, comet-like signals arising from a hyper-echoic pleural line with a to-and-fro movement synchronized with respiration. Increasing EVLW accumulation changes the normal, no-echo signal (black lung, no EVLW) into a black-and-white pattern (interstitial sub-pleural oedema with multiple B-lines) or a white lung pattern (alveolar pulmonary oedema) with coalescing B-lines. The number and spatial extent of B-lines on the antero-lateral chest allows a semi-quantitative estimation of EVLW (from absent, ≤5, to severe pulmonary oedema, >30 B-lines). Wet B-lines are made by water and decreased by diuretics, which cannot modify dry B-lines made by connective tissue. B-lines can be evaluated anywhere (including extreme environmental conditions with pocket size instruments to detect high-altitude pulmonary oedema), anytime (during dialysis to titrate intervention), by anyone (even a novice sonographer after 1 h training), and on anybody (since the chest acoustic window usually remains patent when echocardiography is not feasible). Cardiologists can achieve much diagnostic gain with little investment of technology, training, and time. B-lines represent ‘the shape of lung water’. They allow non-invasive detection, in real time, of even sub-clinical forms of pulmonary oedema with a low cost, radiation-free approach.

The Apelin-APJ Axis Is an Endogenous Counterinjury Mechanism in Experimental Acute Lung Injury

Although the mechanisms and pathways mediating ARDS have been studied extensively, less attention has been given to the mechanisms and pathways that counteract injury responses. This study found that the apelin-APJ pathway is an endogenous counterinjury mechanism that protects against ARDS. Using a rat model of oleic acid (OA)-induced ARDS, the effects of ARDS on apelin and APJ receptor expressions and on APJ receptor binding capacity were examined. The protective effect of activating the apelin-APJ pathway against OA- or lipopolysaccharide (LPS)-induced ARDS was evaluated. ARDS was coupled to upregulations of the apelin and APJ receptor. Rats with OA-induced ARDS had higher lung tissue levels of apelin proprotein and APJ receptor expressions; elevated plasma, BAL fluid (BALF), and lung tissue levels of apelin-36 and apelin-12/13; and an increased apelin-APJ receptor binding capacity. Upregulation of the apelin-APJ system has important pathophysiologic function. Stimulation of the apelin-APJ signaling using receptor agonist apelin-13 alleviated, whereas inhibition of the apelin-APJ signaling using receptor antagonist [Ala]-apelin-13 exacerbated, OA-induced lung pathologies, extravascular lung water accumulation, capillary-alveolar leakage, and hypoxemia. The APJ receptor agonist inhibited, and the APJ receptor antagonist augmented, OA-induced lung tissue and BALF levels of tumor necrosis factor-α and monocyte chemoattractant protein-1, and plasma and lung tissue levels of malondialdehyde. Postinjury treatment with apelin-13 alleviated lung inflammation and injury and improved oxygenation in OA- and LPS-induced lung injury. The apelin-APJ signaling pathway is an endogenous anti-injury and organ-protective mechanism that is activated during ARDS to counteract the injury response and to prevent uncontrolled lung injury.

Extravascular Lung Water and Tissue Perfusion Biomarkers After Lung Resection Surgery Under a Normovolemic Fluid Protocol.

The optimal fluid management for lung resection surgery remains undefined. Concern related to postoperative pulmonary edema has led to the practice of fluid restriction. This practice risks hypovolemia and tissue hypoperfusion. The authors examined the extravascular lung water accumulation and tissue perfusion biomarkers under protective lung ventilation and normovolemia. A prospective observational study. A single-center study. Forty patients aged 18 years or older undergoing lung resection surgery. Patients were maintained on protective lung ventilation and a normovolemic fluid protocol. Hemodynamic variables, including global end-diastolic volume index, cardiac index, and extravascular lung water index, together with tissue perfusion biomarkers, including serum creatinine, lactic acid, central venous oxygen saturation, and brain natriuretic peptide, were measured perioperatively. Parametric or nonparametric techniques were used to assess changes of these parameters over 72 hours postoperatively. The global end-diastolic volume index was maintained; cardiac index was increased, without a significant change in extravascular lung water index. Acute kidney injury based on AKIN criteria occurred in 3 patients (7.5%), and in 1 patient (2.5 %) based on RIFLE criteria. Lactic acid and central venous oxygen saturation remained within normal limits, and brain natriuretic peptide showed an insignificant increase. In patients undergoing lesser lung resections, a fluid protocol targeting normovolemia together with protective lung ventilation did not increase extravascular lung water. These results suggest further study to identify the optimal fluid regimen to mitigate pulmonic and extrapulmonic complications after lung resection.

Lung injury related to extreme environments.

As extreme sports become more popular, related respiratory injury may compromise the athlete’s performance and result in morbidity and even mortality. In this article we will discuss different lung injuries in relation to performing different activities in an extreme environment. The evolution of fish to amphibians, reptiles to endothermic birds and mammals has been accompanied by a progressively thinner pulmonary blood gas barrier, to accommodate the constraint of increased oxygen uptake and carbon dioxide output [1]. Accordingly, pulmonary circulation has evolved as a separate high flow–low pressure system. In humans, mean pulmonary artery pressures (PAP) are 8–20 mmHg, pulmonary wedge pressures are 5–14 mmHg and pulmonary capillary pressures are 8–12 mmHg [2]. A low-pressure regimen preserves the integrity of an alveolar capillary membrane only 0.3 μm thick. However, this structure is vulnerable to increased pressures during strenuous exercise or environmental hypoxic exposure as a cause of stress failure of the pulmonary capillaries and accumulation of extravascular lung water [3]. Reports of lung injury related to extremes of exercise and variations in ambient pressure and altitude confirm this vulnerability. The resulting lung injury takes the form of noncardiogenic pulmonary oedema. The occurrence of noncardiogenic pulmonary oedema and pulmonary haemorrhage has been described in relation to a variety of disorders related to auto- and exogenous immunological reactions, infections and certain inhalants. However, numerous reports of lung injury manifesting as pulmonary oedema with associated haemorrhage have been described more recently in relation to immersion underwater, swimming, extreme exercise and exposure to altitude. In addition, pulmonary oedema resulting from negative intra-alveolar pressure has been described in the anaesthesia literature and may play a role in exercise- and immersion-induced pulmonary oedema. A single mechanism responsible for production of noncardiogenic pulmonary oedema related to immersion, altitude and exercise has not …

Study of perioperative extravascular lung water and intrathoracic blood volume in patients undergoing CABG surgery with or without cardiopulmonary bypass

BackgroundWhether off-pump coronary artery bypass graft (OPCAB) surgery is superior to traditional on-pump coronary artery bypass graft (CABG) surgery still one of the most controversial areas of cardiac surgery and anesthesia. We hypothesized that OPCAB surgery may result in less accumulation of extra-vascular lung water (EVLW) and intra-thoracic blood volume (ITBV) in the peri-operative period.Patients and MethodsThirty patients underwent elective CABG surgery were randomized for this study, 15 OPCAB (group 1) and 15 on Pump (group 2). We measured EVLW and ITBV by PiCCO monitor in 8 times; before induction of anesthesia, after induction of anesthesia and before skin incision, before starting revascularization in group 1 or before cardiopulmonary bypass in group 2, at the end of revascularization in group 1 or at the end of CBP in group 2, at the end of surgery (after skin closure), two hours after the end of surgery, six hours after the end of surgery, twelve hours after the end of surgery and finally in the morning of first postoperative period.ResultsDemographic data and the preoperative characteristics were comparable in both patient groups. The intra-operative course was uneventful, and the intra-operative and postoperative characteristics were comparable in both patient groups. In all patients, complete revascularization was achieved. Extra-vascular lung water and intra-thoracic blood volume did not differ between groups in all times of measurements.Discussion and ConclusionThe clinical advantage of off-pump CABG surgery over standard extracorporeal circulation in regard to lung water content was not found in our study. In conclusion, the presumed superiority of off pump surgery for coronary artery bypass grafting could not be confirmed in our group of patients.

Early-phase changes of extravascular lung water index as a prognostic indicator in acute respiratory distress syndrome patients.

BackgroundThe features of early-phase acute respiratory distress syndrome (ARDS) are leakage of fluid into the extravascular space and impairment of its reabsorption, resulting in extravascular lung water (EVLW) accumulation. The current study aimed to identify how the initial EVLW values and their change were associated with mortality.MethodsThis was a post hoc analysis of the PiCCO Pulmonary Edema Study, a multicenter prospective cohort study that included 23 institutions. Single-indicator transpulmonary thermodilution-derived EVLW index (EVLWi) and conventional prognostic factors were prospectively collected over 48 h after enrollment. Associations between 28-day mortality and each variable including initial (on day 0), mean, maximum, and Δ (subtracting day 2 from day 0) EVLWi were evaluated.ResultsWe evaluated 192 ARDS patients (median age, 69 years (quartile, 24 years); Sequential Organ Failure Assessment (SOFA) score on admission, 10 (5); all-cause 28-day mortality, 31%). Although no significant differences were found in initial, mean, or maximum EVLWi, Δ-EVLWi was significantly higher (i.e., more reduction in EVLWi) in survivors than in non-survivors (3.0 vs. −0.3 mL/kg, p = 0.006). Age, maximum, and Δ-SOFA scores and Δ-EVLW were the independent predictors for survival according to the Cox proportional hazard model. Patients with Δ-EVLWi > 2.8 had a significantly higher incidence of survival than those with Δ-EVLWi ≤ 2.8 (log-rank test, χ2 = 7.08, p = 0.008).ConclusionsDecrease in EVLWi during the first 48 h of ARDS may be associated with 28-day survival. Serial EVLWi measurements may be useful for understanding the pathophysiologic conditions in ARDS patients. A large multination confirmative trial is required.

The potential value of integrated natriuretic peptide and echo-guided heart failure management.

There is increasing interest in guiding Heart Failure (HF) therapy with Brain Natriuretic Peptide (BNP) or N-terminal prohormone of Brain Natriuretic Peptide (NT-proBNP), with the goal of lowering concentrations of these markers (and maintaining their suppression) as part of the therapeutic approach in HF. However, recent European Society of Cardiology (ESC) and American Heart Association/ American College of Cardiology (AHA/ACC) guidelines did not recommend biomarker-guided therapy in the management of HF patients. This has likely to do with the conceptual, methodological, and practical limitations of the Natriuretic Peptides (NP)-based approach, including biological variability, slow time-course, poor specificity, cost and venipuncture, as well as to the lack of conclusive scientific evidence after 15 years of intensive scientific work and industry investment in the field. An increase in NP can be associated with accumulation of extra-vascular lung water, which is a sign of impending acute heart failure. If this is the case, an higher dose of loop diuretics will improve symptoms. However, if no lung congestion is present, diuretics will show no benefit and even harm. It is only a combined clinical, bio-humoral (for instance with evaluation of renal function) and echocardiographic assessment which may unmask the pathophysiological (and possibly therapeutic) heterogeneity underlying the same clinical and NP picture. Increase in B-lines will trigger increase of loop diuretics (or dialysis); the marked increase in mitral insufficiency (at baseline or during exercise) will lead to increase in vasodilators and to consider mitral valve repair; the presence of substantial inotropic reserve during stress will give a substantially higher chance of benefit to beta-blocker or Cardiac Resynchronization Therapy (CRT). To each patient its own therapy, not with a "blind date" with symptoms and NP and carpet bombing with drugs, but with an open-eye targeted approach on the mechanism predominant in that individual patient. A monocular, specialistic, unidimensional approach to HF can miss its pathogenetic and clinical complexity, which only can be overcome with an integrated, versatile and tailored approach.