**3. The hole of extravascular lung water and pulmonary vascular index in the evaluation of severe ARDS**

The extravascular lung water index (EVLWi) is calculated as the intra-thoracic total volume minus the intra-thoracic blood volume indexed by predicted body weight measured using a transpulmonary thermodilution method. The pulmonary vascular permeability index (PVPI) was calculated as extravascular lung water divided by the pulmonary blood volume [5]. Theoretically, the greater the EVLWi and PVPi, the greater the severity of ARDS. Recently, Kushimoto and colleagues [5] evaluated the relationship among the severity categories of ARDS as defined by the Berlin definition, EVLWi and PVPi to confirm their predictive validity for severity of ARDS. They measured EVLWi and PVPi in 195 patients with an EVLWi of ≥10 mL/kg, which fulfilled the Berlin definition of ARDS in 23 intensive care units for three consecutive days. Patients with moderate and severe ARDS had higher acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment scores (SOFA) on the day of enrollment compared to patients with mild ARDS. Patients with severe ARDS had higher EVLWi (severe, 19.1; moderate, 17.2; mild, 16.1; *P* < 0.05) and PVPI (3.2; 3.0; 2.7; *P* < 0.05). When the authors evaluated 495 independent measurements over three consecutive days, they observed a moderative and negative correlation between PaO<sup>2</sup> /FIO<sup>2</sup> ratio and EVLWi (r = −0.355, *P* < 0.001) and PaO<sup>2</sup> /FIO<sup>2</sup> and PVPi (r = −0.345, *P* < 0.001 The authors observed an association between ARDS severity according to Berlin definition and 28-day mortality rate: severe, the odds ratio 4.167 relative to mild.

**1. Diagnosing and evaluating the severe acute respiratory distress** 

Acute respiratory distress syndrome is characterized by an increase of the permeability of the lungs alveolar-capillary membranes leading to the extravasation of the intravascular plasma of the lungs capillary network surrounding the alveoli to the alveolar spaces that were previously filled by air. This accumulation of liquid rich in proteins inside the alveolar spaces turns an air-filled lungs into a heavy high-osmotic pressure liquid-filled lungs and the consequent collapse of the lowermost lung regions, shunt, refractory hypoxemia, decrease in lungs compliance and increase in dead space that are more pronounced the more severe the permeability changes of the pulmonary alveoli-capillary membrane. Regarding the physiopathology of ARDS, the hallmark mechanism of injury is inflammation leading to increased endothelial and epithelial permeability and liberation of receptors for angiopoietin-2 and advanced glyca-

According to the recent Berlin definition, severe acute respiratory distress syndrome is defined by bilateral pulmonary infiltrates of recent onset (less than 1 week) in a patient that have a PaO<sup>2</sup>

no evidence of cardiac failure or hypervolemia. The patient also needs to present a risk factor for ARDS development as respiratory infection, gastric content aspiration, lungs contusion, blood products transfusion, sepsis, high-risk trauma, high-risk surgery, shock, and pancreatitis [1–4].

The extravascular lung water index (EVLWi) is calculated as the intra-thoracic total volume minus the intra-thoracic blood volume indexed by predicted body weight measured using a transpulmonary thermodilution method. The pulmonary vascular permeability index (PVPI) was calculated as extravascular lung water divided by the pulmonary blood volume [5]. Theoretically, the greater the EVLWi and PVPi, the greater the severity of ARDS. Recently, Kushimoto and colleagues [5] evaluated the relationship among the severity categories of ARDS as defined by the Berlin definition, EVLWi and PVPi to confirm their predictive validity for severity of ARDS. They measured EVLWi and PVPi in 195 patients with an EVLWi of ≥10 mL/kg, which fulfilled the Berlin definition of ARDS in 23 intensive care units for three consecutive days. Patients with moderate and severe ARDS had higher acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment scores (SOFA) on the day of enrollment compared to patients with mild ARDS. Patients with severe

equal or less than 100 with a positive end-expiratory pressure equal or more 5 cm H<sup>2</sup>

**3. The hole of extravascular lung water and pulmonary vascular** 

/

O with

**syndrome**

FIO<sup>2</sup>

tion end products (RAGE) [1–4].

50 Advances in Extra-corporeal Perfusion Therapies

**2. Severe ARDS according to Berlin definition**

**index in the evaluation of severe ARDS**
