These criteria are also not sensitive predictors of disease sever

These criteria are also not sensitive predictors of disease severity and outcomes [4,5,15-17] because: the P/F ratio varies considerably across different FiO2 levels, particularly when FiO2 < 0.5, PaO2 > 100 mmHg, or when the shunt fraction is low; many patients who initially fulfill the ARDS criteria might improve the P/F ratio > 200 mmHg after application of positive end-expiratory pressure several for a short time or the use of higher FiO2; and hypoxemia in ARDS may also be related to atelectasis or a low cardiac output [14]. Based on these limitations, a novel definition has been proposed that takes into account the clinical and physiologic characteristics of ALI/ARDS [18]. The Berlin definition for ARDS was published recently and was demonstrated to have better predictive validity for mortality than the AECC definition [10].

Although ARDS has been described as a type of acute, diffuse inflammatory lung injury leading to increased pulmonary vascular permeability, increased lung weight, and loss of aerated lung tissue, as the panel agreed in their conceptual model, none of the suggested criteria evaluates the increase in pulmonary microvascular permeability, a hallmark of ARDS [10]. Not only the AECC definition but also the Berlin definition may include an extensive range of respiratory insufficiencies without an increase in pulmonary microvascular permeability.Previous studies have reported on methods of quantifying pulmonary edema [19,20]. The double-indicator thermodilution technique allows the measurement of EVLW, and excellent correlation between in vivo and postmortem gravimetric EVLW values was obtained in both animal and human studies using this method [21,22].

However, this method is cumbersome and technically challenging for routine clinical application. The single-indicator technique is therefore used in clinical settings; this method is as sensitive as the double-indicator technique [23,24]. We previously validated the accuracy of EVLW measurements obtained using the single-indicator GSK-3 technique in the postmortem lung samples and defined the statistically normal EVLW values in a human autopsy study [25]. The close relationship between EVLW and outcome has been also demonstrated [26].The transpulmonary thermodilution technique provides an estimation of both EVLW and the pulmonary blood volume, and the ratio of these two parameters – the pulmonary vascular permeability index (PVPI) – has been shown to reflect the pulmonary microvascular permeability [7,27].Increased pulmonary vascular permeability is the crucial pathophysiological feature of ALI/ARDS and has been considered a quantitative diagnostic criterion for ALI/ARDS [28]. PVPI has been evaluated to enable one to differentiate ALI/ARDS from hydrostatic edema [7].

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