Lung ultrasound as tool to evaluate fluid accumulation in dialysis patients

Background: Volume overload is the main mechanism of BP elevation in end-stage kidney disease (ESKD) patients undergoing hemodialysis or peritoneal dialysis and has been linked to adverse outcomes and increased mortality in this population. Summary: This review discusses current knowledge on lung ultrasound as a tool for detection of extracellular volume overload through evaluation of extravascular lung water content. We describe the principles of lung US, the main protocols to apply it in clinical practice, and accumulated data evidence regarding its associations with cardiovascular events and mortality. We also summarize available evidence on the effect of lung-ultrasound guided volume management strategies on BP control, echocardiographic parameters and major outcomes in patients undergoing dialysis. Key Messages: Among interventions attempting to reduce the burden of cardiovascular disease in ESKD, effective management of volume overload represents an unmet clinical need. Assessment of hydration status by lung-ultrasound is a cheap, easy to employ and real-time technique that can offer accurate dry weight assessment leading to several clinical benefits.

Pulmonary Interstitial Matrix and Lung Fluid Balance From Normal to the Acutely Injured Lung

This review analyses the mechanisms by which lung fluid balance is strictly controlled in the air-blood barrier (ABB). Relatively large trans-endothelial and trans-epithelial Starling pressure gradients result in a minimal flow across the ABB thanks to low microvascular permeability aided by the macromolecular structure of the interstitial matrix. These edema safety factors are lost when the integrity of the interstitial matrix is damaged. The result is that small Starling pressure gradients, acting on a progressively expanding alveolar barrier with high permeability, generate a high transvascular flow that causes alveolar flooding in minutes. We modeled the trans-endothelial and trans-epithelial Starling pressure gradients under control conditions, as well as under increasing alveolar pressure (Palv) conditions of up to 25 cmH2O. We referred to the wet-to-dry weight (W/D) ratio, a specific index of lung water balance, to be correlated with the functional state of the interstitial structure. W/D averages ∼5 in control and might increase by up to ∼9 in severe edema, corresponding to ∼70% loss in the integrity of the native matrix. Factors buffering edemagenic conditions include: (i) an interstitial capacity for fluid accumulation located in the thick portion of ABB, (ii) the increase in interstitial pressure due to water binding by hyaluronan (the “safety factor” opposing the filtration gradient), and (iii) increased lymphatic flow. Inflammatory factors causing lung tissue damage include those of bacterial/viral and those of sterile nature. Production of reactive oxygen species (ROS) during hypoxia or hyperoxia, or excessive parenchymal stress/strain [lung overdistension caused by patient self-induced lung injury (P-SILI)] can all cause excessive inflammation. We discuss the heterogeneity of intrapulmonary distribution of W/D ratios. A W/D ∼6.5 has been identified as being critical for the transition to severe edema formation. Increasing Palv for W/D > 6.5, both trans-endothelial and trans-epithelial gradients favor filtration leading to alveolar flooding. Neither CT scan nor ultrasound can identify this initial level of lung fluid balance perturbation. A suggestion is put forward to identify a non-invasive tool to detect the earliest stages of perturbation of lung fluid balance before the condition becomes life-threatening.

Quantitative Lung Ultrasonography for the Nephrologist: Applications in Dialysis and Heart Failure

Volume overload and its attendant increase in acute care utilization and cardiovascular morbidity and mortality represents a critical challenge for the practicing nephrologist. This is particularly true among patients with ESKD on HD where pre-dialysis volume overload and intradialytic and postdialytic hypovolemia account for almost a third of all cost for the Medicare dialysis benefit. Quantitative lung ultrasound is a tool for assessing the extent of extravascular lung water which outperforms physical exam and plain chest radiography. B-lines are vertical hyperechoic artifacts present in patients with increased extravascular lung water. B-lines have been shown to decrease dynamically during the hemodialysis treatment in proportion to ultrafiltration volume. Among patients with chronic heart failure, titration of diuretics based on the extent of pulmonary congestion noted on lung ultrasonography has been shown to decrease recurrent acute care utilization. Early data from randomized-controlled trials of lung ultrasound-guided ultrafiltration therapy among patients with ESKD on HD have shown promise for potential reduction in recurrent episodes of decompensated heart failure and cardiovascular events. Ultimately lung ultrasound may predict those who are ultrafiltration tolerant and could be used to decreased acute care utilization and thus cost in this population.

Anesthetic management during whole-lung lavage using lung ultrasound in a patient with pulmonary alveolar proteinosis: a case report

Pulmonary alveolar proteinosis (PAP) is an uncommon disease characterized by progressive accumulation of lipoprotein material in the lungs due to impaired surfactant clearance. Whole-lung lavage (WLL) is the current standard treatment and consists of sequential lavage of each lung to mechanically remove the residual material from the alveoli. Although WLL is considered safe, unexpected complications can occur. Moreover, due to the rarity of the disease itself, this procedure is unknown to many physicians, and management of intraoperative complications can be challenging for anesthesiologists. Lung ultrasound (LUS) provides reliable and valuable information for detecting perioperative pulmonary complications and, in particular, quantitation of lung water content. There have been reports on monitoring the different stages of controlled deaeration of the non-ventilated lung during WLL using LUS. However, it has been limited to non-ventilated lungs. Therefore, we report the use of LUS in WLL to proactively detect pulmonary edema in the ventilated lung and implement a safe and effective anesthesia strategy. Given the limited diagnostic tools available to anesthesiologists in the operating room, LUS is a reliable, fast, and noninvasive method for identifying perioperative pulmonary complications in patients with PAP undergoing WLL.

Measuring lung water adds prognostic value in heart failure patients undergoing cardiac magnetic resonance

To assess whether a simplified cardiac magnetic resonance (CMR)–derived lung water density (LWD) quantification predicted major events in Heart Failure (HF). Single-centre retrospective study of consecutive HF patients with left ventricular ejection fraction (LVEF) < 50% who underwent CMR. All measurements were performed on HASTE sequences in a parasagittal plane at the right midclavicular line. LWD was determined by the lung-to-liver signal ratio multiplied by 0.7. A cohort of 102 controls was used to derive the LWD upper limit of normal (21.2%). The primary endpoint was a composite of time to all-cause death or HF hospitalization. Overall, 290 patients (mean age 64 ± 12 years) were included. LWD measurements took on average 35 ± 4 s, with good inter-observer reproducibility. LWD was increased in 65 (22.4%) patients, who were more symptomatic (NYHA ≥ III 29.2 vs. 1.8%; p = 0.017) and had higher NT-proBNP levels [1973 (IQR: 809–3766) vs. 802 (IQR: 355–2157 pg/mL); p < 0.001]. During a median follow-up of 21 months, 20 patients died and 40 had ≥ 1 HF hospitalization. In multivariate analysis, NYHA (III–IV vs. I–II; HR: 2.40; 95%-CI: 1.30–4.43; p = 0.005), LVEF (HR per 1%: 0.97; 95%-CI: 0.94–0.99; p = 0.031), serum creatinine (HR per 1 mg/dL: 2.51; 95%-CI: 1.36–4.61; p = 0.003) and LWD (HR per 1%: 1.07; 95%-CI: 1.02–1.12; p = 0.007) were independent predictors of the primary endpoint. These findings were mainly driven by an association between LWD and HF hospitalization (p = 0.026). A CMR-derived LWD quantification was independently associated with an increased HF hospitalization risk in HF patients with LVEF < 50%. LWD is a simple, reproducible and straightforward measurement, with prognostic value in HF.

Nintedanib reduces corticosteroid resistance pulmonary fibrosis induced by bleomycin in mice by increasing the expression of β3 & β6 integrins

Background: Corticosteroid resistance pulmonary fibrosis is a major health problem. This study aimed to determine the effectiveness of nintedanib on corticosteroid resistance pulmonary fibrosis induced by bleomycin in mice. Methods: The mice were divided into five groups 12 mice each. control group, BLM group received single dose of bleomycin (BLM), BLM+MP group received BLM and methylprednisolone (MP), BLM+NIN group received BLM and nintedanib(NIN) and BLM + NIN + MP group. The lung tissues were obtained for biochemical analysis, gene expression and histopathological examination on day 7 and day 28. Results: after 7 days, both NIN groups showed a significant decrease in the levels of interleukin-2, interleukin-4, interferon-gamma, lung tumor necrosis factor-alpha, Malondialdehyde and lung water content with a significant increase in the Glutathione level in lung tissues compared to MP group. After 28 days, both NIN groups showed a significant reduction in hydroxyproline, and Trans-forming Growth Factor beta lung tissues contents compared to MP group, and they showed a positive effect on the expression of β 3 &β6 integrins compared to the negative effect of MP group. Histopathologically, both NIN groups showed significant improvement compared to MP group by H&E and Masson’s trichrome stains. Immunohistochemical staining revealed negative BCL-2 expression in the cytoplasm of bronchiolar epithelium in both NIN groups after 7 and 28 days of treatment. Lung tissue morphometric studies showed significant improvement of pathological changes induced by BLM in both NIN groups. Conclusions: Altogether, our data indicates that nintedanib overcame corticosteroid resistance pulmonary fibrosis induced by bleomycin.

Nintedanib reduces corticosteroid resistance pulmonary fibrosis induced by bleomycin in mice by increasing the expression of β3 & β6 integrins

Background:Corticosteroid resistance pulmonary fibrosis is a major health problem. This study aimed to determine the effectiveness of nintedanib on corticosteroid resistance pulmonary fibrosis induced by bleomycin in mice.Methods:The mice were divided into five groups 12 mice each. control group, BLM group received single dose of bleomycin (BLM), BLM+MP group received BLM and methylprednisolone (MP), BLM+NIN group received BLM and nintedanib(NIN) and BLM + NIN + MP group. The lung tissues were obtained for biochemical analysis, gene expression and histopathological examination on day 7 and day 28.Results:After 7 days, both NIN groups showed a significant decrease in the levels of interleukin-2, interleukin-4, interferon-gamma, lung tumor necrosis factor-alpha, Malondialdehyde and lung water content with a significant increase in the Glutathione level in lung tissues compared to MP group. After 28 days, both NIN groups showed a significant reduction in hydroxyproline, and Trans-forming Growth Factor beta lung tissues contents compared to MP group, and they showed a positive effect on the expression of β 3 &β6 integrins compared to the negative effect of MP group. Histopathologically, both NIN groups showed significant improvement compared to MP group by H&E and Masson’s trichrome stains. Immunohistochemical staining revealed negative BCL-2 expression in the cytoplasm of bronchiolar epithelium in both NIN groups after 7 and 28 days of treatment. Lung tissue morphometric studies showed significant improvement of pathological changes induced by BLM in both NIN groups.Conclusion:Altogether, our data indicates that nintedanib overcame corticosteroid resistance pulmonary fibrosis induced by bleomycin.

Nintedanib reduces corticosteroid resistance pulmonary fibrosis induced by bleomycin in mice by increasing the expression of β3 & β6 integrins

Background: Corticosteroid resistance pulmonary fibrosis is a major health problem. This study aimed to determine the effectiveness of nintedanib on corticosteroid resistance pulmonary fibrosis induced by bleomycin in mice. Methods: The mice were divided into five groups 12 mice each. control group, BLM group received single dose of bleomycin (BLM), BLM+MP group received BLM and methylprednisolone (MP), BLM+NIN group received BLM and nintedanib(NIN) and BLM + NIN + MP group. The lung tissues were obtained for biochemical analysis, gene expression and histopathological examination on day 7 and day 28. Results: after 7 days, both NIN groups showed a significant decrease in the levels of interleukin-2, interleukin-4, interferon-gamma, lung tumor necrosis factor-alpha, Malondialdehyde and lung water content with a significant increase in the Glutathione level in lung tissues compared to MP group. After 28 days, both NIN groups showed a significant reduction in hydroxyproline, and Trans-forming Growth Factor beta lung tissues contents compared to MP group, and they showed a positive effect on the expression of β 3 &β6 integrins compared to the negative effect of MP group. Histopathologically, both NIN groups showed significant improvement compared to MP group by H&E and Masson’s trichrome stains. Immunohistochemical staining revealed negative BCL-2 expression in the cytoplasm of bronchiolar epithelium in both NIN groups after 7 and 28 days of treatment. Lung tissue morphometric studies showed significant improvement of pathological changes induced by BLM in both NIN groups. Conclusion: Altogether, our data indicates that nintedanib overcame corticosteroid resistance pulmonary fibrosis induced by bleomycin.

Association Between Arterial Oxygen Saturation and Lung Ultrasound B-Lines After Competitive Deep Breath-Hold Diving

Breath-hold diving (freediving) is an underwater sport that is associated with elevated hydrostatic pressure, which has a compressive effect on the lungs that can lead to the development of pulmonary edema. Pulmonary edema reduces oxygen uptake and thereby the recovery from the hypoxia developed during freediving, and increases the risk of hypoxic syncope. We aimed to examine the efficacy of SpO2, via pulse-oximetry, as a tool to detect pulmonary edema by comparing it to lung ultrasound B-line measurements after deep diving. SpO2 and B-lines were collected in 40 freedivers participating in an international deep freediving competition. SpO2 was measured within 17 ± 6 min and lung B-lines using ultrasound within 44 ± 15 min after surfacing. A specific symptoms questionnaire was used during SpO2 measurements. We found a negative correlation between B-line score and minimum SpO2 (rs = −0.491; p = 0.002) and mean SpO2 (rs = −0.335; p = 0.046). B-line scores were positively correlated with depth (rs = 0.408; p = 0.013), confirming that extra-vascular lung water is increased with deeper dives. Compared to dives that were asymptomatic, symptomatic dives had a 27% greater B-line score, and both a lower mean and minimum SpO2 (all p &lt; 0.05). Indeed, a minimum SpO2 ≤ 95% after a deep dive has a positive predictive value of 29% and a negative predictive value of 100% regarding symptoms. We concluded that elevated B-line scores are associated with reduced SpO2 after dives, suggesting that SpO2 via pulse oximetry could be a useful screening tool to detect increased extra-vascular lung water. The practical application is not to diagnose pulmonary edema based on SpO2 – as pulse oximetry is inexact – rather, to utilize it as a tool to determine which divers require further evaluation before returning to deep freediving.