Although neither there is no definitive quantitative criterion of EVLWI for pulmonary edema, we recently reported that the normal EVLWI value is approximately 7.4 �� 3.3 ml/kg for humans [25]. EVLWI �� 10 ml/kg was used for definition of pulmonary edema in the previously reported study [1,29].Measurement of EVLWI and PVPI using the transpulmonary thermodilution methodA 4-Fr or 5-Fr femoral arterial or 4-Fr brachial arterial thermistor-tipped catheter (PV2014L16N, PV2015L20N, or PV2014L22N; Pulsion Medical Systems, Munich, Germany) was inserted in all patients by the attending physicians’ discretion and connected to the PiCCO? plus or PiCCO? 2 monitor (Pulsion Medical Systems). The monitor uses a single-thermal indicator technique to calculate the cardiac output (CO), global end-diastolic volume (GEDV), EVLW, and other volumetric parameters.

A 15 ml bolus of 5% glucose at 5��C was injected through a central venous catheter, and the CO calculated using the Stewart-Hamilton method. A 15 ml bolus dose was selected as previously described [25] and the precision of measurements has been demonstrated [30,31]. The central venous catheters were accessed from the jugular or subclavian route in all patients. Concurrently, the mean transit time and exponential downslope time of the transpulmonary thermodilution curve were calculated. The product of CO and mean transit time represents the intrathoracic thermal volume [23]. The product of CO and exponential downslope time represents the pulmonary thermal volume [32].

GEDV is calculated as the difference between the intrathoracic thermal volume and the pulmonary thermal volume, and represents the combined end-diastolic volumes of the four cardiac chambers. The intrathoracic blood volume (ITBV) is calculated as the linear relationship with the GEDV [23]:ITBV = 1.25 �� GEDV – 28.4EVLW is the difference between the intrathoracic thermal volume and ITBV [23,32]. The detailed principles and calculations involved in deriving EVLW using the thermodilution technique are discussed elsewhere [7,33]. PVPI is calculated as the ratio of EVLW and pulmonary blood volume [7]. ITBV and GEDV are indexed to the body surface area.The median EVLW value was obtained after three bolus injections of 15 ml each [31]. The absolute EVLW value was indexed to predicted body weight, calculated as 50 + 0.91 (height (cm) – 152.4) for males and 45.

5 + 0.91 (height (cm) – 152.5) for females [34]. For indexing EVLW, the predicted body weight instead of the actual body weight was used because: lung volumes are dependent on gender and height, not on weight [35]; measurement of EVLW indexed to the actual body weight can be underestimated in GSK-3 obese patients [36,37]; and the EVLWI has been shown to be a better prognostic indicator than EVLW indexed to the actual body weight [38-40]. The results were analyzed using PiCCO-VoLEF Data Acquisition for Win32 Version 6.0 for PiCCO? plus or Version 2.0.0.