Radiologic Assessment of Lung Edema Score as a Predictor of Clinical Outcome in Children with Acute Respiratory Distress Syndrome.

PURPOSE: The radiographic assessment of lung edema (RALE) score enables objective quantification of lung edema and is a valuable prognostic marker of adult acute respiratory distress syndrome (ARDS). We aimed to evaluate the validity of RALE score in children with ARDS. MATERIALS AND METHODS: The RALE score was measured for its reliability and correlation to other ARDS severity indices. ARDS-specific mortality was defined as death from severe pulmonary dysfunction or the need for extracorporeal membrane oxygenation therapy. The C-index of the RALE score and other ARDS severity indices were compared via survival analyses. RESULTS: Among 296 children with ARDS, 88 did not survive, and there were 70 ARDS-specific non-survivors. The RALE score showed good reliability with an intraclass correlation coefficient of 0.809 [95% confidence interval (CI), 0.760-0.848]. In univariable analysis, the RALE score had a hazard ratio (HR) of 1.19 (95% CI, 1.18-3.11), and the significance was maintained in multivariable analysis adjusting with age, ARDS etiology, and comorbidity, with an HR of 1.77 (95% CI, 1.05-2.91). The RALE score was a good predictor of ARDS-specific mortality, with a C-index of 0.607 (95% CI, 0.519-0.695). CONCLUSION: The RALE score is a reliable measure for ARDS severity and a useful prognostic marker of mortality in children, especially for ARDS-specific mortality. This score provides information that clinicians can use to decide the proper time of aggressive therapy targeting severe lung injury and to appropriately manage the fluid balance of children with ARDS.

Relationship between lung ultrasound and electrical impedance tomography as regional assessment tools during PEEP titration in acute respiratory distress syndrome caused by multi-lobar pneumonia: a pilot study.

Acute respiratory distress syndrome (ARDS) caused by multilobar pneumonia (MLP) is markedly different from typical ARDS in pathology, imaging characteristics, and lung mechanics. Regional lung assessment is required. We aimed to analyze the relationship between two regional assessment tools, lung ultrasound (LUS) and electrical impedance tomography (EIT) during positive end-expiratory pressure (PEEP) titration, and determine an appropriate PEEP level. We conducted a prospective study of patients with ARDS caused by MLP with PaO2/FiO2 < 150 mmHg. All subjects were equipped with two EIT belts connected with a single EIT machine to measure upper and lower hemithorax impedance change alternatingly at each PEEP level. LUS score was simultaneously determined in chest wall regions corresponding to the EIT regions during PEEP titration. We acquired EIT and LUS data in eight regions of interest at seven PEEP levels in 12 subjects. Therefore, 672 pairs of data were obtained for analysis. There were significant relationships between LUS score and tidal impedance variation and pixel compliance (Cpix). The Spearman's rho between LUS score vs. tidal impedance variation and LUS score vs. the Cpix were - 0.142, P < 0.001, and - 0.195, P < 0.001, respectively. The relationship between the LUS score and Cpix remained the same at every PEEP level but did not reach statistical significance. The individual's mean expected PEEP by LUS was similar to the EIT [10.33(± 1.67) vs. 10.33(± 1.44) cm H2O, P = 0.15]. Regarding the MLP, the LUS scores were associated with EIT parameters, and LUS scores might proof helpful for finding individual PEEP settings in MLP.

Use of radiolabeled hyaluronic acid for preclinical assessment of inflammatory injury and acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is accompanied by a dramatic increase in lung hyaluronic acid (HA), leading to a dose-dependent reduction of pulmonary oxygenation. This pattern is associated with severe infections, such as COVID-19, and other important lung injury etiologies. HA actively participates in molecular pathways involved in the cytokine storm of COVID-19-induced ARDS. The objective of this study was to evaluate an imaging approach of radiolabeled HA for assessment of dysregulated HA deposition in mouse models with skin inflammation and lipopolysaccharide (LPS)-induced ARDS using a novel portable intensified Quantum Imaging Detector (iQID) gamma camera system. METHODS: HA of 10 kDa molecular weight (HA10) was radiolabeled with 125I and 99mTc respectively to produce [125I]I-HA10 and [99mTc]Tc-HA10, followed by comparative studies on stability, in vivo biodistribution, and uptake at inflammatory skin sites in mice with 12-O-tetradecanoylphorbol-13-acetate (TPA)-inflamed ears. [99mTc]Tc-HA10 was used for iQID in vivo dynamic imaging of mice with ARDS induced by intratracheal instillation of LPS. RESULTS: [99mTc]Tc-HA10 and [125I]I-HA10 had similar biodistribution and localization at inflammatory sites. [99mTc]Tc-HA10 was shown to be feasible in measuring skin injury and monitoring skin wound healing. [99mTc]Tc-HA10 dynamic pulmonary images yielded good visualization of radioactive uptake in the lungs. There was significantly increased lung uptake and slower lung washout in mice with LPS-induced ARDS than in control mice. Postmortem biodistribution measurement of [99mTc]TcHA10 (%ID/g) was 11.0 ± 3.9 vs. 1.3 ± 0.3 in the ARDS mice (n = 6) and controls (n = 6) (P < 0.001), consistent with upregulated HA expression as determined by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) staining. CONCLUSIONS: [99mTc]Tc-HA10 is promising as a biomarker for evaluating HA dysregulation that contributes to pulmonary injury in ARDS. Rapid iQID imaging of [99mTc]Tc-HA10 clearance from injured lungs may provide a functional template for timely assessment and quantitative monitoring of pulmonary pathophysiology and intervention in ARDS.

Development of an Image-Based HCS-Compatible Method for Endothelial Barrier Function Assessment.

The recent renascence of phenotypic drug discovery (PDD) is catalyzed by its ability to identify first-in-class drugs and deliver results when the exact molecular mechanism is partially obscure. Acute respiratory distress syndrome (ARDS) is a severe, life-threatening condition with a high mortality rate that has increased in frequency due to the COVID-19 pandemic. Despite decades of laboratory and clinical study, no efficient pharmacological therapy for ARDS has been found. An increase in endothelial permeability is the primary event in ARDS onset, causing the development of pulmonary edema that leads to respiratory failure. Currently, the detailed molecular mechanisms regulating endothelial permeability are poorly understood. Therefore, the use of the PDD approach in the search for efficient ARDS treatment can be more productive than classic target-based drug discovery (TDD), but its use requires a new cell-based assay compatible with high-throughput (HTS) and high-content (HCS) screening. Here we report the development of a new plate-based image cytometry method to measure endothelial barrier function. The incorporation of image cytometry in combination with digital image analysis substantially decreases assay variability and increases the signal window. This new method simultaneously allows for rapid measurement of cell monolayer permeability and cytological analysis. The time-course of permeability increase in human pulmonary artery endothelial cells (HPAECs) in response to the thrombin and tumor necrosis factor α treatment correlates with previously published data obtained by transendothelial resistance (TER) measurements. Furthermore, the proposed image cytometry method can be easily adapted for HTS/HCS applications.

[Value of radiographic assessment of lung edema score in evaluating the severity and prognosis of patients with acute respiratory distress syndrome].

OBJECTIVE: To explore the value of radiographic assessment of lung edema (RALE) score in evaluating the severity and prognosis of patients with acute respiratory distress syndrome (ARDS). METHODS: A retrospective study was conducted. Patients with ARDS admitted to the department of intensive care unit (ICU) of Affiliated Nantong Third Hospital of Nantong University from January 2016 to November 2020 were enrolled. Clinical data of those patients were collected, and two senior radiologists who did not know the outcome of the patients independently scored each chest radiograph, the mean value of which was taken as the RALE score. The patients were divided into death group and survival group according to the 28-day prognosis. The differences of the basic data, PaO2/FiO2, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation II (APACHE II) score and RALE score between groups were analyzed. ARDS patients were classified according to the Berlin standard and RALE scores were compared between groups. Then, the correlations between RALE score and PaO2/FiO2, SOFA score, APACHE II score were analyzed. The prognostic capacity of RALE score for 28-day prognosis of ARDS patients were analyzed by Kaplan-Meier survival curve. RESULTS: Of the 98 ARDS patients, 62 were included in the final analysis, 39 patients survived and 23 patients died. The 28-day mortality was 37.1%. Compared with the survival group, patients in the death group were older (years old: 72.83±12.21 vs. 64.44±14.68), had lower PaO2/FiO2 [mmHg (1 mmHg = 0.133 kPa): 122.66±48.32 vs. 150.26±50.40], and higher SOFA score and greater difference of RALE score between the third day and the first day after admission (D3-D1 RALE score) (SOFA score: 11.26±3.91 vs. 9.04±3.72, D3-D1 RALE score: 1.35±6.42 vs. -2.74±7.35), with statistically significant differences (all P < 0.05). However, there were no significant differences in gender, cause of ARDS, APACHE II score, and RALE scores on the first and the third day of admission (D1 RALE, D3 RALE) between the two groups. Among the 62 patients, there were 11 mild cases (17.7%), 36 moderate cases (58.1%), and 15 severe cases (24.2%). The D1 RALE score of patients with mild and moderate ARDS were lower than those of patients with severe ARDS (19.09±3.65, 22.58±6.79 vs. 27.07±5.23, both P < 0.05). Correlation analysis showed that D1 RALE score was negatively correlated with PaO2/FiO2 (r = -0.385, P = 0.002), and positively correlated with SOFA score and APACHE II score (r1 = 0.433, r2 = 0.442, both P < 0.001). Kaplan-Meier survival curve analysis showed that the 28-day survival rate of ARDS patients in D3-D1 RALE score ≥ -1 group was significantly higher than that in D3-D1 RALE score < -1 group (73.08% vs. 55.56%; log-rank test: χ2 = 3.979, P = 0.046). CONCLUSIONS: The RALE score is a simple and reliable non-invasive evaluation index, which can be used to evaluate the severity of ARDS patients. The difference of RALE score in early stage is helpful to identify ARDS patients with poor prognosis.

Assessment of Lung Reaeration at 2 Levels of Positive End-expiratory Pressure in Patients With Early and Late COVID-19-related Acute Respiratory Distress Syndrome.

PURPOSE: Patients with novel coronavirus disease (COVID-19) frequently develop acute respiratory distress syndrome (ARDS) and need invasive ventilation. The potential to reaerate consolidated lung tissue in COVID-19-related ARDS is heavily debated. This study assessed the potential to reaerate lung consolidations in patients with COVID-19-related ARDS under invasive ventilation. MATERIALS AND METHODS: This was a retrospective analysis of patients with COVID-19-related ARDS who underwent chest computed tomography (CT) at low positive end-expiratory pressure (PEEP) and after a recruitment maneuver at high PEEP of 20 cm H2O. Lung reaeration, volume, and weight were calculated using both CT scans. CT scans were performed after intubation and start of ventilation (early CT), or after several days of intensive care unit admission (late CT). RESULTS: Twenty-eight patients were analyzed. The median percentages of reaerated and nonaerated lung tissue were 19% [interquartile range, IQR: 10 to 33] and 11% [IQR: 4 to 15] for patients with early and late CT scans, respectively (P=0.049). End-expiratory lung volume showed a median increase of 663 mL [IQR: 483 to 865] and 574 mL [IQR: 292 to 670] after recruitment for patients with early and late CT scans, respectively (P=0.43). The median decrease in lung weight attributed to nonaerated lung tissue was 229 g [IQR: 165 to 376] and 171 g [IQR: 81 to 229] after recruitment for patients with early and late CT scans, respectively (P=0.16). CONCLUSIONS: The majority of patients with COVID-19-related ARDS undergoing invasive ventilation had substantial reaeration of lung consolidations after recruitment and ventilation at high PEEP. Higher PEEP can be considered in patients with reaerated lung consolidations when accompanied by improvement in compliance and gas exchange.

Quantitative Assessment of Chest CT Patterns in COVID-19 and Bacterial Pneumonia Patients: a Deep Learning Perspective.

BACKGROUND: It is difficult to distinguish subtle differences shown in computed tomography (CT) images of coronavirus disease 2019 (COVID-19) and bacterial pneumonia patients, which often leads to an inaccurate diagnosis. It is desirable to design and evaluate interpretable feature extraction techniques to describe the patient's condition. METHODS: This is a retrospective cohort study of 170 confirmed patients with COVID-19 or bacterial pneumonia acquired at Yeungnam University Hospital in Daegu, Korea. The Lung and lesion regions were segmented to crop the lesion into 2D patches to train a classifier model that could differentiate between COVID-19 and bacterial pneumonia. The K-means algorithm was used to cluster deep features extracted by the trained model into 20 groups. Each lesion patch cluster was described by a characteristic imaging term for comparison. For each CT image containing multiple lesions, a histogram of lesion types was constructed using the cluster information. Finally, a Support Vector Machine classifier was trained with the histogram and radiomics features to distinguish diseases and severity. RESULTS: The 20 clusters constructed from 170 patients were reviewed based on common radiographic appearance types. Two clusters showed typical findings of COVID-19, with two other clusters showing typical findings related to bacterial pneumonia. Notably, there is one cluster that showed bilateral diffuse ground-glass opacities (GGOs) in the central and peripheral lungs and was considered to be a key factor for severity classification. The proposed method achieved an accuracy of 91.2% for classifying COVID-19 and bacterial pneumonia patients with 95% reported for severity classification. The CT quantitative parameters represented by the values of cluster 8 were correlated with existing laboratory data and clinical parameters. CONCLUSION: Deep chest CT analysis with constructed lesion clusters revealed well-known COVID-19 CT manifestations comparable to manual CT analysis. The constructed histogram features improved accuracy for both diseases and severity classification, and showed correlations with laboratory data and clinical parameters. The constructed histogram features can provide guidance for improved analysis and treatment of COVID-19.

Lung Ultrasound for Detection of Pulmonary Complications in Critically Ill Obstetric Patients in a Resource-Limited Setting.

Critically ill parturients have an increased risk of developing pulmonary complications. Lung ultrasound (LUS) could be effective in addressing the cause of respiratory distress in resource-limited settings with high maternal mortality. We aimed to determine the frequency, timing of appearance, and type of pulmonary complications in critically ill parturients in an obstetric unit in Sierra Leone. In this prospective observational study, LUS examinations were performed on admission, after 24 and 48 hours, and in case of respiratory deterioration. Primary endpoint was the proportion of parturients with one or more pulmonary complications, stratified for the presence of respiratory distress. Secondary endpoints included timing and types of complications, and their association with "poor outcome," defined as a composite of transfer for escalation of care or death. Of 166 patients enrolled, 35 patients (21% [95% CI: 15-28]) had one or more pulmonary complications, the majority diagnosed on admission. Acute respiratory distress syndrome (period prevalence 4%) and hydrostatic pulmonary edema (4%) were only observed in patients with respiratory distress. Pneumonia (2%), atelectasis (10%), and pleural effusion (7%) were present, irrespective of respiratory distress. When ultrasound excluded pulmonary complications, respiratory distress was related to anemia or metabolic acidosis. Pulmonary complications were associated with an increased risk of poor outcome (odds ratio: 5.0; 95% CI: 1.7-14.6; P = 0.003). In critically ill parturients in a resource-limited obstetric unit, LUS contributed to address the cause of respiratory distress by identifying or excluding pulmonary complications. These were associated with a poor outcome.

CT fatty muscle fraction as a new parameter for muscle quality assessment predicts outcome in venovenous extracorporeal membrane oxygenation.

Impaired skeletal muscle quality is a major risk factor for adverse outcomes in acute respiratory failure. However, conventional methods for skeletal muscle assessment are inapplicable in the critical care setting. This study aimed to determine the prognostic value of computed tomography (CT) fatty muscle fraction (FMF) as a biomarker of muscle quality in patients undergoing extracorporeal membrane oxygenation (ECMO). To calculate FMF, paraspinal skeletal muscle area was obtained from clinical CT and separated into areas of fatty and lean muscle based on densitometric thresholds. The cohort was binarized according to median FMF. Patients with high FMF displayed significantly increased 1-year mortality (72.7% versus 55.8%, P = 0.036) on Kaplan-Meier analysis. A multivariable logistic regression model was built to test the impact of FMF on outcome. FMF was identified as a significant predictor of 1-year mortality (hazard ratio per percent FMF, 1.017 [95% confidence interval, 1.002-1.033]; P = 0.031), independent of anthropometric characteristics, Charlson Comorbidity Index, Simplified Acute Physiology Score, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction Score, and duration of ECMO support. To conclude, FMF predicted 1-year mortality independently of established clinical prognosticators in ECMO patients and may have the potential to become a new muscle quality imaging biomarker, which is available from clinical CT.

Echocardiographic assessment of the right ventricle and its correlation with patient outcome in acute respiratory distress syndrome.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is a life-threatening chest disease associated with a poor outcome and increased mortality. It may lead to pulmonary hypertension and, eventually, right ventricular failure. These changes can be investigated by transthoracic echocardiography (TTE) which is considered a non-invasive and cost-effective modality. We studied the role of right ventricular function in the prediction of the severity and mortality in ARDS. MATERIAL AND METHODS: In this observational study, 94 patients suffering from ARDS were subjected to TTE to evaluate the parameters of right ventricular function by measuring tricuspid annular plane systolic excursion (TAPSE), right ventricular fractional area change (RV-FAC), myocardial performance index (Tei index), and systolic pulmonary artery pressure (SPAP) to assess their relation to the severity and mortality in ARDS. RESULTS: TAPSE, SPAP, Tei index, and RV-FAC showed significant differences between survivors and non-survivors after 30 days (all p < 0.001). An increased length of intensive care unit stay was significantly correlated with TAPSE, Tei index, and RV-FAC (p = 0.002' 0.007' and 0.013, respectively). Meanwhile, the length of mechanical ventilation days was significantly correlated with the Tei index only (p < 0.001). Multivariate regression analysis found that TAPSE and the Tei index were independent factors affecting mortality (p = 0.004' and 0.006, respectively). RV-FAC, with a cut-off point ≤ 57%, had the highest sensitivity' while TAPSE, with a cut-off point ≤ 17 mm, had the highest specificity to predict mortality. CONCLUSIONS: Transthoracic echocardiographic parameters of the right ventricle could be used to predict severity and mortality in patients with ARDS with high sensitivity and specificity.

Assessment of electrical impedance tomography to set optimal positive end-expiratory pressure for veno-venous ECMO-treated severe ARDS patients.

PURPOSE: Ultra-protective ventilation with low tidal volume is used in severe acute respiratory distress syndrome (ARDS) patients under extracorporeal membrane oxygenation (ECMO). However, the optimal positive end-expiratory pressure (PEEP) is unknown. The aim of our study was to assess electrical impedance tomography's (EIT) ability to choose the best PEEP for these patients. MATERIALS AND METHODS: A recruitment maneuver and after a decremental PEEP trial from 20 to 5 cmH20 were monitored by EIT, with lung images divided into four ventral-to-dorsal horizontal regions of interest. For each patient, three EIT-based PEEP were defined: PEEP ODCLmin (lowest pressure with the least EIT-based collapse lung [CL] and overdistension [OD]), PEEP ODCL15 (lowest pressure able to limit EIT-based collapse to less than or equal to 15% with the least overdistension) and PEEP Comp (PEEP with the highest EIT-based compliance). RESULTS: High PEEP levels were significantly associated with more overdistension while decreasing PEEP led to more collapsed zones. PEEP ODCL15 and PEEP Comp were in complete agreement with the reference Pulmonary PEEP (chosen according to usual respiratory clinical and ultrasound criteria), PEEP ODCLmin was in average agreement with the Pulmonary PEEP. CONCLUSION: EIT may be a useful real-time monitoring technique to optimize the PEEP level in severe ARDS patients under ECMO. TAKE-HOME MESSAGE: Ultra-protective ventilation with low tidal volume is used in severe acute respiratory distress syndrome patients under extracorporeal membrane oxygenation (ECMO), but the optimal positive end-expiratory pressure is unknown. This trial shows that electrical impedance tomography may be an interesting non-invasive bedside tool to provide real-time monitoring of PEEP impact in severe ARDS patients under ECMO. The Pulmovista® electrical impedance tomography was provided by Dräger (Lübeck, Germany) during the study period. Dräger had no role in the study design, collection, analysis and interpretation of the data, writing the article, or the decision to submit the article for publication.

Lung ultrasound for early diagnosis and severity assessment of pneumonia in patients with coronavirus disease 2019.

BACKGROUND/AIMS: Current evidence supports lung ultrasound as a point-ofcare alternative diagnostic tool for various respiratory diseases. We sought to determine the utility of lung ultrasound for early detection of pneumonia and for assessment of respiratory failure among patients with coronavirus disease 2019 (COVID-19). METHODS: Six patients with confirmed COVID-19 by reverse transcription-polymerase chain reaction were enrolled. All had undergone chest X-ray and chest computed tomography (CT) on the day of admission and underwent multiple point-of-care lung ultrasound scans over the course of their hospitalization. RESULTS: Lung ultrasound detected early abnormal findings of representative B-lines in a patient with a normal chest X-ray, corresponding to ground-glass opacities on the chest CT scan. The ultrasound findings improved as her clinical condition improved and her viral load decreased. In another minimally symptomatic patient without significant chest X-ray findings, the ultrasound showed B-lines, an early sign of pneumonia before abnormalities were detected on the chest CT scan. In two critically ill patients, ultrasound was performed to assess for evaluation of disease severity. In both patients, the clinicians conducted emergency rapid sequence intubation based on the ultrasound findings without awaiting the laboratory results and radiological reports. In two children, ultrasound was used to assess the improvement in their pneumonia, thus avoiding further imaging tests such as chest CT. CONCLUSION: Lung ultrasound is feasible and useful as a rapid, sensitive, and affordable point-of-care screening tool to detect pneumonia and assess the severity of respiratory failure in patients hospitalized with COVID-19.

Dynamic bedside assessment of the physiologic effects of prone position in acute respiratory distress syndrome patients by electrical impedance tomography.

BACKGROUND: Prone position (PP) improves acute respiratory distress syndrome (ARDS) survival by reducing the risk of ventilation-induced lung injury. However, inter-individual variability is a hallmark of ARDS and lung protection by PP might not be optimal in all patients. In the present study, we dynamically assessed physiologic effects of PP by electrical impedance tomography (EIT) and identified predictors of improved lung protection by PP in ARDS patients. METHODS: Prospective physiologic study on 16 intubated, sedated and paralyzed patients with ARDS undergoing PP as per clinical decision. EIT data were recorded during two consecutive steps: 1) baseline supine position before and after a recruitment maneuver (RM); 2) prone position before and after a RM. "Improved lung protection" by PP was defined in the presence of simultaneous improvement of ventilation homogeneity (Hom), alveolar overdistension and collapse (ODCL) and amount of recruitable lung volume by RM in comparison to supine. RESULTS: PP versus supine increased the tidal volume distending the dependent regions (Vtdep), resulting in improved Hom (1.1±0.9 vs. 1.7±0.9, P=0.021). PP also reduced ODCL (19±9% vs. 28±8%, P=0.005) and increased the recruitable lung volume (80 [71-157] vs. 59 [1-110] mL, P=0.025). "Improved lung protection" by PP was predicted by lower Vtdep, higher Vtndep and poorer Hom measured during baseline supine position (P<0.05). CONCLUSIONS: EIT enables dynamic bedside assessment of the physiologic effects of PP and might support early recognition of ARDS patients more likely to benefit from PP.

Ultrasound Assessment of Diaphragmatic Motion in Subjects With ARDS During Transpulmonary Pressure-Guided PEEP Titration.

BACKGROUND: We aimed to investigate the effects of incremental PEEP titration in patients with ARDS on regional diaphragmatic motion with bedside ultrasound. METHODS: Dorsal diaphragmatic excursion (DDE) and ventral diaphragmatic excursion (VDE) were measured using anatomic M-mode ultrasonography of the right hemidiaphragm as PEEP was randomized to -6, -3, +3, and +6 cm H2O from baseline to achieve a positive transpulmonary pressure. Inter-operator variability of DDE was assessed in 10 separate subjects. RESULTS: A total of 14 subjects ventilated for ARDS were enrolled. Subjects had a mean age of 54 ± 12 y, mean PaO2 /FIO2 = 137 ± 54 mm Hg, and mean sequential organ failure assessment (SOFA) score = 14 ± 1). Transpulmonary pressure, DDE, and DDE/VDE ratio increased with incremental PEEP titration (-1.15 cm H2O vs 3.63 cm H2O, P < .001; 4.9 mm vs 8.2 mm, P < .001; and 62% vs 93%, P < .001, respectively). When transpulmonary pressure became positive, a visual increase in DDE and DDE/VDE ratio 0.60 to 0.93 was observed (from 0.48 cm to 0.82 cm, R2 = 0.87, P = .02; and R2 = 0.93, P = .006, respectively). There was high agreement in DDE measurements between 2 ultrasonographers (intra-class correlation 0.987, P < .001). CONCLUSIONS: DDE was affected by incremental PEEP titration toward a positive transpulmonary pressure. The ultrasound assessment using anatomic M-mode allowed for specific measurement of regional diaphragmatic excursion. This pattern of motion in the dependent regions of the diaphragm during PEEP titration in subjects with ARDS achieving a positive transpulmonary pressure may reflect a potential target for future studies in the bedside assessment for lung recruitment. (Clinical Trials.gov registration NCT02463773.).

Semi-quantitative visual assessment of chest radiography is associated with clinical outcomes in critically ill patients.

BACKGROUND: Respiratory pathology is a major driver of mortality in the intensive care unit (ICU), even in the absence of a primary respiratory diagnosis. Prior work has demonstrated that a visual scoring system applied to chest radiographs (CXR) is associated with adverse outcomes in ICU patients with Acute Respiratory Distress Syndrome (ARDS). We hypothesized that a simple, semi-quantitative CXR score would be associated with clinical outcomes for the general ICU population, regardless of underlying diagnosis. METHODS: All individuals enrolled in the Registry of Critical Illness at Brigham and Women's Hospital between June 2008 and August 2018 who had a CXR within 24 h of admission were included. Each patient's CXR was assigned an opacification score of 0-4 in each of four quadrants with the total score being the sum of all four quadrants. Multivariable negative binomial, logistic, and Cox regression, adjusted for age, sex, race, immunosuppression, a history of chronic obstructive pulmonary disease, a history of congestive heart failure, and APACHE II scores, were used to assess the total score's association with ICU length of stay (LOS), duration of mechanical ventilation, in-hospital mortality, 60-day mortality, and overall mortality, respectively. RESULTS: A total of 560 patients were included. Higher CXR scores were associated with increased mortality; for every one-point increase in score, in-hospital mortality increased 10% (OR 1.10, CI 1.05-1.16, p < 0.001) and 60-day mortality increased by 12% (OR 1.12, CI 1.07-1.17, p < 0.001). CXR scores were also independently associated with both ICU length of stay (rate ratio 1.06, CI 1.04-1.07, p < 0.001) and duration of mechanical ventilation (rate ratio 1.05, CI 1.02-1.07, p < 0.001). CONCLUSIONS: Higher values on a simple visual score of a patient's CXR on admission to the medical ICU are associated with increased in-hospital mortality, 60-day mortality, overall mortality, length of ICU stay, and duration of mechanical ventilation.

Ultrasound Assessment of Lung Aeration in Subjects Supported by Venovenous Extracorporeal Membrane Oxygenation.

BACKGROUND: The value of ultrasound in assessing lung aeration of patients with ARDS who require venovenous extracorporeal membrane oxygenation (ECMO) has, to our knowledge, never been studied. The objective of the study was to evaluate by using ultrasound lung aeration at ECMO initiation and withdrawal in subjects with severe ARDS supported by venovenous ECMO. METHODS: Fifty subjects were included in this pilot retrospective study. The lung ultrasound aeration score (LUS) and respiratory variables were collected at ECMO initiation (T0) and ECMO withdrawal (T1). The LUS at T0 between the subjects who survived to ICU discharge and those who died in ICU was compared. The relationship between changes in LUS and changes in PaO2 /FIO2 from T0 to T1 was assessed. RESULTS: The ICU mortality was 34%. The LUS at T0 did not differ between survivors and non-survivors (median 22 [interquartile range] {IQR} 19-26 vs median 24 [IQR, 19-28]; P = .60). From T0 to T1, the LUS decreased significantly in survivors (median 22 [IQR, 19-26] vs median 16 [IQR, 13-19]; P < .001), it decreased moderately in non-survivors who were weaned off ECMO (median 26 [24-29]) vs median 22 (IQR, 17-24), P = .031), and remained stable in those who died during ECMO (median 25 [IQR, 19-29] vs median 25 [IQR, 23-31]; P = .22). Changes in PaO2 /FIO2 were not related to changes in the LUS between T0 and T1. CONCLUSIONS: At the time of ECMO placement, the subjects who survived ARDS had aeration loss close to that observed in the subjects who did not survive. At the time of ECMO withdrawal, there was a significant improvement in lung aeration in the survivors, whereas a severe loss of lung aeration persisted in the non-survivors, although some were weaned off ECMO. Lung ultrasound provided a valuable tool for bedside assessment of lung aeration in subjects supported by ECMO.

Automatic proximal airway volume segmentation using optical coherence tomography for assessment of inhalation injury.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury with a mortality rate of up to 40%. Early management of ARDS has been difficult due to the lack of sensitive imaging tools and robust analysis software. We previously designed an optical coherence tomography (OCT) system to evaluate mucosa thickness (MT) after smoke inhalation, but the analysis relied on manual segmentation. The aim of this study is to assess in vivo proximal airway volume (PAV) after inhalation injury using automated OCT segmentation and correlate the PAV to lung function for rapid indication of ARDS. METHODS: Anesthetized female Yorkshire pigs (n = 14) received smoke inhalation injury (SII) and 40% total body surface area thermal burns. Measurements of PaO2-to-FiO2 ratio (PFR), peak inspiratory pressure (PIP), dynamic compliance, airway resistance, and OCT bronchoscopy were performed at baseline, postinjury, 24 hours, 48 hours, 72 hours after injury. A tissue segmentation algorithm based on graph theory was used to reconstruct a three-dimensional (3D) model of lower respiratory tract and estimate PAV. Proximal airway volume was correlated with PFR, PIP, compliance, resistance, and MT measurement using a linear regression model. RESULTS: Proximal airway volume decreased after the SII: the group mean of proximal airway volume at baseline, postinjury, 24 hours, 48 hours, 72 hours were 20.86 cm (±1.39 cm), 17.61 cm (±0.99 cm), 14.83 cm (±1.20 cm), 14.88 cm (±1.21 cm), and 13.11 cm (±1.59 cm), respectively. The decrease in the PAV was more prominent in the animals that developed ARDS after 24 hours after the injury. PAV was significantly correlated with PIP (r = 0.48, p < 0.001), compliance (r = 0.55, p < 0.001), resistance (r = 0.35, p < 0.01), MT (r = 0.60, p < 0.001), and PFR (r = 0.34, p < 0.01). CONCLUSION: Optical coherence tomography is a useful tool to quantify changes in MT and PAV after SII and burns, which can be used as predictors of developing ARDS at an early stage. LEVEL OF EVIDENCE: Prognostic, level III.

Trans-Esophageal Doppler Assessment of Acute Hemodynamic Changes Due to Prone Positioning in Acute Respiratory Distress Syndrome Patients.

BACKGROUND: Effect of prone positioning on acute hemodynamic changes (within 10 min) in acute respiratory distress syndrome (ARDS) has not been studied. METHODS: In this prospective observational study, hemodynamic assessment by trans-esophageal Doppler (TED) was done with the primary aim of measuring early changes in cardiac index (CI), if any, after prone positioning in moderate to severe ARDS patients. A subgroup analysis was also done based on the response to passive leg raise (PLR). RESULTS: The baseline hemodynamic variables of 26 included patients were: CI 3.5 (3.1-4.3) L/min/m, peak velocity (PV) 83.2 (60.9-99.3) cm/s, flow time corrected (FTc) 341 (283-377) ms, mean acceleration (MA) 9.0 (7.04-11.7) m/s. After prone position, there were no statistically significant changes in CI, 3.5 (P=0.83), 3.75 (P = 0.96), 3.7 (P = 0.34), and 3.9 (P = 0.95) at 5, 10, 20, and 30 min respectively. FTc, mainly indicator of preload, showed decreasing trend to 315 (275-367) ms at 30 min post prone (P = 0.06). On the basis of PLR test also, CI did not change significantly in both PLR+ and PLR- groups. In PLR+ group, PV increased from 72.4 to 83 (P = 0.01), 74.9 (P = 0.03), 82 (P = 0.02), and 82 (P = 0.03) cm/s; while in PLR- group, MA increased from 8.8 to 9.7 (P = 0.03), 10.1 (P = 0.03), 9.3 (P = 0.04), and 10.6 (P = 0.01) m/s at 5, 10, 20, and 30 min respectively. CONCLUSIONS: In moderate to severe ARDS patients, there were no significant changes in CI during first 30 min after prone positioning, even in the subgroups on the basis of PLR response.

Diagnostic Bedside Ultrasonography for Acute Respiratory Failure and Severe Hypoxemia in the Medical Intensive Care Unit: Basics and Comprehensive Approaches.

Bedside goal-directed ultrasound is a powerful tool for rapid differential diagnosis and monitoring of cardiopulmonary disease in the critically ill patient population. The bedside intensivist is in a unique position to integrate ultrasound findings with the overall clinical situation. Medically critically ill patients who require urgent bedside diagnostic assessment fall into 2 categories: (1) acute respiratory failure and (2) hemodynamic derangements. The first portion of this review outlines the diagnostic role of bedside ultrasound in the medically critically ill patient population for the diagnosis and treatment of acute respiratory failure, acute respiratory distress, and severe hypoxemia. The second portion will focus on the diagnostic role of ultrasound for the evaluation and treatment of shock states, as well as describe protocolized approaches for evaluation of shock during cardiopulmonary resuscitation. Different respiratory system pathologies that result in acute respiratory failure (such as increased interstitial fluid, alveolar consolidation, pleural effusion) cause characteristic ultrasonographic findings; diaphragmatic assessment may also add information. Intracardiac shunting can cause severe hypoxemia. Protocolized approaches for the evaluation of patients with acute respiratory failure or distress are discussed.