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A bedside definition of acute respiratory distress syndrome based on a conceptual model

We would like to thank Perel for his discerning comments [1], published in the previous issue of Critical Care, about our study [2]. We agree with his pathophysiology-based view of the diagnosis of acute respiratory distress syndrome (ARDS).

In regard to his first concern, we excluded 14 patients, who were judged to have respiratory failure secondary to sepsis-induced increased pulmonary vascular permeability, because owing to hypovolemia their values of extravascular lung water indexed to predicted body weight (extravascular lung water index, or EVLWI) were less than 10 mL/kg. Because EVLWI in patients with ARDS correlated not only with pulmonary vascular permeability but also with cardiac preload [2], we interpreted that their low levels of EVLWI could be secondary to inappropriate preload. Although the mechanisms of hypoxemia were unclear, ventilation/perfusion mismatch may occur because of lung perfusion failure. The pathophysiology of the condition of these patients must be clarified in the future.

In regard to the concern that the experts may have had some idea of the pulmonary vascular permeability index (PVPI) value during the exclusion and allocation processes, the value of EVLWI was provided only to determine whether the patients had pulmonary edema (EVLWI of at least 10 mL/kg), and the value itself was not discussed during the review process. Therefore, estimating the PVPI value must be impractical.

We believe that the direct measurement of PVPI and EVLW will provide an important advance over current methods of assessing the presence and origin of lung edema and the precise condition of ARDS [3] and could be incorporated into the future definition of ARDS.

Authors' response

Azriel Perel

I thank Kushimoto for addressing my commentary [1] on his group's study on the clinical usefulness of EVLWI and PVPI in defining ARDS [2]. Kushimoto points out that the reason for excluding 14 patients from the final analysis was that, although they were judged to have sepsis-induced increased pulmonary vascular permeability, they had normal EVLW values due to inappropriate preload (hypovolemia). Furthermore, he believes that the weak correlation between EVLWI and the indexed intrathoracic blood volume (ITBVI) supports this physiologic explanation.

Fluid loading indeed may increase EVLW [4] whereas the institution of negative fluid balance therapy may decrease elevated EVLW values [5]. However, in the presence of sepsis-induced increased pulmonary vascular permeability, which is associated with severe hypoxemia (as, presumably, in the case of this excluded group of patients), pulmonary edema cannot be prevented or completely resolved by hypovolemia per se. The presence of such a theoretical extreme hypovolemia can also be ruled out in these patients because patients with a cardiac index of less than 1.5 L/minute per m2 were excluded from the study [2]. Furthermore, Figure 4 in the article by Kushimoto and colleagues [2] shows that ARDS patients with normal ITBVI values (850 to 1,000 mL/m2) may have very high EVLWI values. Indeed, the combination of hypovolemia and pulmonary edema is not rare and may present a challenging 'therapeutic conflict' [6]. I agree with Kushimoto that the pathophysiology of these patients needs further clarification.



acute respiratory distress syndrome


extravascular lung water


indexed extravascular lung water


indexed intrathoracic blood volume


pulmonary vascular permeability index.


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SK thanks the members of the PiCCO Pulmonary Edema Study Group for their cooperation.

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Correspondence to Shigeki Kushimoto.

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Competing interests

SK declares that he has no competing interests. AP is a member of the Medical Advisory Board of Pulsion Medical Systems, Munich, Germany.

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Kushimoto, S. A bedside definition of acute respiratory distress syndrome based on a conceptual model. Crit Care 17, 418 (2013).

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  • Pulmonary Edema
  • Acute Respiratory Distress Syndrome
  • Acute Respiratory Distress Syndrome Patient
  • Extravascular Lung Water
  • Cardiac Preload