Increased extravascular lung water index (EVLWI) reflects rapid non-cardiogenic oedema and mortality in COVID-19 associated ARDS

Nearly 5% of patients suffering from COVID-19 develop acute respiratory distress syndrome (ARDS). Extravascular lung water index (EVLWI) is a marker of pulmonary oedema which is associated with mortality in ARDS. In this study, we evaluate whether EVLWI is higher in patients with COVID-19 associated ARDS as compared to COVID-19 negative, ventilated patients with ARDS and whether EVLWI has the potential to monitor disease progression. EVLWI and cardiac function were monitored by transpulmonary thermodilution in 25 patients with COVID-19 ARDS subsequent to intubation and compared to a control group of 49 non-COVID-19 ARDS patients. At intubation, EVLWI was noticeably elevated and significantly higher in COVID-19 patients than in the control group (17 (11–38) vs. 11 (6–26) mL/kg; p < 0.001). High pulmonary vascular permeability index values (2.9 (1.0–5.2) versus 1.9 (1.0–5.2); p = 0.003) suggested a non-cardiogenic pulmonary oedema. By contrast, the cardiac parameters SVI, GEF and GEDVI were comparable in both cohorts. High EVLWI values were associated with viral persistence, prolonged intensive care treatment and in-hospital mortality (23.2 ± 6.7% vs. 30.3 ± 6.0%, p = 0.025). Also, EVLWI showed a significant between-subjects (r = − 0.60; p = 0.001) and within-subjects correlation (r = − 0.27; p = 0.028) to Horowitz index. Compared to non COVID-19 ARDS, COVID-19 results in markedly elevated EVLWI-values in patients with ARDS. High EVLWI reflects a non-cardiogenic pulmonary oedema in COVID-19 ARDS and could serve as parameter to monitor ARDS progression on ICU.

B-Lines Scores Derived From Lung Ultrasound Provide Accurate Prediction of Extravascular Lung Water Index: An Observational Study in Critically Ill Patients

Introduction: Visualization of B-lines via lung ultrasound provides a non-invasive estimation of pulmonary hydration. Extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) assessed by transpulmonary thermodilution (TPTD) represent the most validated parameters of lung water and alveolocapillary permeability, but measurement is invasive and expensive. This study aimed to compare the correlations of B-lines scores from extensive 28-sector and simplified 4-sector chest scan with EVLWI and PVPI derived from TPTD in the setting of intensive care unit (primary endpoint). Methods: We performed scoring of 28-sector and 4-sector B-Lines in 50 critically ill patients. TPTD was carried out with the PiCCO-2-device (Pulsion Medical Systems SE, Maquet Getinge Group). Median time exposure for ultrasound procedure was 12 minutes for 28-sector and 4 minutes for 4-sector scan. Results: Primarily, we found close correlations of 28-sector as well as 4-sector B-Lines scores with EVLWI (R2 = 0.895 vs. R2 = 0.880) and PVPI (R2 = 0.760 vs. R2 = 0.742). Both B-lines scores showed high accuracy to identify patients with specific levels of EVLWI and PVPI. The extensive 28-sector B-lines score revealed a moderate advantage compared to simplified 4-sector scan in detecting a normal EVLWI ≤ 7 (28-sector scan: sensitivity = 81.8%, specificity = 94.9%, AUC = 0.939 versus 4-sector scan: sensitivity = 81.8%, specificity = 82.1%, AUC = 0.902). Both protocols were approximately equivalent in prediction of lung edema with EVLWI ≥ 10 (28-sector scan: sensitivity = 88.9%, specificity = 95.7%, AUC = 0.977 versus 4-sector scan: sensitivity = 81.5%, specificity = 91.3%, AUC = 0.958) or severe pulmonary edema with EVLWI ≥ 15 (28-sector scan: sensitivity = 91.7%, specificity = 97.4%, AUC = 0.995 versus 4-sector scan: sensitivity = 91.7%, specificity = 92.1%, AUC = 0.978). As secondary endpoints, our evaluations resulted in significant associations of 28-sector as well as simplified 4-sector B-Lines score with parameters of respiratory function. Conclusion: Both B-line protocols provide accurate non-invasive evaluation of lung water in critically ill patients. The 28-sector scan offers a marginal advantage in prediction of pulmonary edema, but needs substantially more time than 4-sector scan.

Increased extravascular lung water index (EVLWI) reflects rapid inflammatory oedema and mortality in COVID-19 associated ARDS

OBJECTIVE: Nearly 5 % of the patients with COVID-19 develop an acute respiratory distress syndrome (ARDS). Extravascular lung water index (EVLWI) is a marker of pulmonary oedema which is associated with mortality in ARDS. In this study we evaluate whether EVLWI is higher in patients with COVID-19 associated ARDS as compared to controls and whether EVLWI has the potential to monitor disease progression. METHODS: From the day of intubation, EVLWI, cardiac function were monitored by transpulmonary thermodilution in n=25 patients with COVID-19 and compared to a control group of 49 non-COVID-19 ARDS-patients. RESULTS: EVLWI in COVID-19-patients was noticeably elevated and significantly higher than in the control group (17 (11-38) vs. 11 (6-26) mL/kg; p<0.001). High pulmonary vascular permeability index values (2.9 (1.0-5.2) versus 1.9 (1.0-5.2); p=0.003) suggest inflammatory oedema. By contrast, the cardiac parameters SVI, GEF and GEDVI were comparable. High EVLWI values were associated with viral persistence, prolonged intensive care treatment and mortality (23.2±6.7% vs. 30.3±6.0%, p=0.025). CONCLUSIONS: Compared to the control group, COVID-19 results in markedly elevated EVLWI-values in patients with ARDS. EVLWI reflects a non-cardiogenic pulmonary oedema in COVID-19 associated ARDS and could serve as parameter to monitor ARDS progression.

Management of Phosgene-Induced Acute Lung Injury (ALI) by Personalized Protective PEEP-ECMO: What Can We Learn from Animal Bioassays?

Background: Phosgene (carbonyl dichloride) gas is an indispensable chemical intermediate used in numerous industrial processes. Acute lung injury (ALI) caused by accidental inhalation exposure to phosgene is characterized pulmonary edema being phenotypically manifested after an asymptomatic or more precisely phrased “clinical occult” period. Opposite to common clinical practice, protective treatment should be given preference to curative treatment. Treatment initiated already during the asymptomatic phase shortly after exposure requires prognostic endpoints preceding the lung edema for triage and re-triage. Treatment strategies need to be personalized and exposure-dose related. The objective of this post-hoc analysis of published data is to assess prognostic value of ventilation dead-space (Vd/Vt) and extravascular lung water index (EVLWI) to guide treatment by protective PEEP supplemented by venovenous (vv) ECMO. Methods: This paper aims to compare the overarching published framework from systematic toxicological research of phosgene in animal bioassays with the clinical evidence from four accidentally phosgenepoisoned workers admitted to hospital with life-threatening lung edema. Treatment focused on a combination of protective PEEP and ECMO to reverse phosgene-induced deterioration in lung mechanics by personalized mechanical ventilation. Endpoints selected for titration PEEP focused on endpoints indicative of decoupling cardiopulmonary and vascular functions. To better understand any cardiogenic and vascular disturbances, titration endpoints included calculated ventilation dead-space (Vd/Vt), measured extravascular lung water index (EVLWI), arterial blood gases and acid-base status, systemic vascular resistance index (SVRI), and cardiac index (CI). EVLWI and APACHE II criteria guided the course of treatment in adjusting plateau pressure (Pplat), positive end-expiratory pressure (PEEP), and driving pressure (ΔP). Results: Remarkable equivalence of human data and those from controlled inhalation studies with phosgene on rats and dogs was found. The endpoint of choice guiding PEEP ventilation and implementation of ECMO was EVLWI. This maker of lung edema precisely reflects the increased wet lung weights in animals. Conclusions: ECMO-supplemented PEEP not only mitigates hypoxemia at conditions of severe ARDS and it also provides a means to reduce driving and plateau pressures minimizing ventilatorassociated lung injury.