Clinical Hemodynamics And Plasma Endothelin-1 In Patients With Acute Lung Injury

Objective: To assess clinical value of extravascular lung water index (EVLWI) determined by the single transpulmonary thermodilution technique and to observe the plasma concentration of endothelin-1(ET-1) in patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS)Methods: 16 patients with ALI/ARDS were enrolled according to the American-European Consensus Conference (AECC)definition, which was published in 1994. Hemodynamic measurements were obtained by the PiCCO (Pulse indicator Continous Cardiac Output) catheter system which uses the single indicator transpulmonary thermodilution technique to determine EVLW, Cardiac Output (CO) and volumetric parameters. CO calibrations and determination of EVLW were performed immediately after catheter insertion and at least every 24 hours for at least 72 hours. The measurements included EVLWI, cardiac index (CI), systemic vascular resistance index (SVRI), global end-diastolic volume index (GEDVI), pulmonary vascular permeability index (PVPI), central venous pressure (CVP). Oxygenation ratio (PaO₂/FiO₂ ratio), MODS score, lung injury score (LIS), and the plasma concentration of ET-1 were also determined. And 28-day mortality was followed. 20 healthy volunteers were assigned as health control for the plasma concentration of ET-1. Based on PaO₂/FiO₂ ratio at enrollment (baseline PaO₂/FiO₂ ratio) according to AECC definition, patients were divided into ARDS group (PaO₂/FiO₂<200mmHg) and ALI group (200mmHg< PaO₂/FiO₂<300mmHg). While based on EVLWI (10ml/kg), patients were divided into EVLWI>10 group and EVLWI<10 group. Difference between ARDS group and ALI group or between EVLWI>10 group and EVLWI<10 group was compared respectively. Correlativity between EVLWI and its related parameters was analyzed.Results:1 Baseline PaO₂/FiO₂ ratio at enrollment was lower in ARDS group than in ALI group (p<0.05), but there was no significant difference between ARDS group and ALI group in cumulative mean PaO₂/FiO₂ ratio, MODS score, LIS, EVLWI and other hemodynamic measurements over 72 hours after enrollment, and in 28-day mortality (p>0.05). It is shown that baseline PaO₂/FiO₂ ratio do not estimate severity and predict outcomes in patients with ALI/ARDS.2 There was no significant difference between EVLWI>10 group and EVLWI<10 group in PaO₂/FiO₂ ratio, CI, GEDVI, and SVRI (P>0.05). PVPI, MODS score, and LIS was higher in EVLWI>10 group than in EVLWI<10 group (p<0.0001). 28-day mortality was higher in EVLWI>10 group than in EVLWI<10 group (67% vs 0%, p=0.0082). It is shown that EVLWI may reflect the severity of lung injury and predict outcomes. Concerning the difference between EVLWI>10 group and EVLWI<10 group in the value of EVLWI, there was no significant difference between the two groups in baseline EVLWI at the time of enrollment (P>0.05). While the value of EVLWI was higher in EVLWI>10 group than in EVLWI<10 group at the time of 24-hour, 48-hour, and 72-hour after enrollment (p<0.05). Cumulative mean EVLWI over 72 hours after enrollment was higher in EVLWI>10 group than in EVLWI<10 group (median 11.0 ml/kg [IQR 10.1-12.4 ml/kg] versus median 5.1 ml/kg [IQR 3.9-6.0 ml/kg],p<0.0001). It is shown that EVLWI should not be used at a single point in time and its changes should be followed to evaluate severity and the degree of lung edema in patients with ALI/ARDS.3 Correlates with EVLWI: There was no statistically significant correlation between EVLWI and PaO₂/FiO₂ ratio for all patients (p>0.05), while a statistically significant but moderate negative correlation between EVLWI and PaO₂/FiO₂ ratio (r2=0.29,p=0.0039) was found in non-survivors. There was a poor positive correlation between elevated EVLWI (EVLWI>7ml/kg) and LIS (r2=0.10,p=0.0341). Among CI, SI, SVRI, GEDVI, and CVP, no relationship with EVLWI was found (p>0.05). It is shown that PaO₂/FiO₂ ratio and LIS could not directly indicate the degree of lung edema and that EVLWI as a method assessing severity in ALI/ARDS is independent on the state of circulation.4 PVPI: There was a significant positive correlation between PVPI and EVLWI (r²=0.61,p<0.0001). And PVPI is higher in EVLWI>10 group than in EVLWI<10 group (1.9 [IQR 1.5-2.5] versus 1.1 [IQR 0.9-1.2],p<0.0001). PVPI showed some degree of agreement with EVLWI on judging severity and outcomes. It is shown that PVPI may also reflect the characteristic of lung edema and severity in patients with ALI/ARDS.5 ET-1 concentration: The plasma concentration of ET-1 for all patients was higher than that of health control (43.9 pg/ml [IQR 34.8-52.6 pg/ml] versus 15.0 pg/ml [IQR 13.5-16.0 pg/ml], p<0.0001). The plasma concentration of ET-1 was higher in both of ARDS group and ALI group than in the health control group, but there was no significant difference between the two groups. While the plasma concentration of ET-1 was higher in EVLWI>10 group than in the EVLWI<10 group (48.5 pg/ml [IQR 42.1-60.8 pg/ml] versus 29.3 pg/ml [IQR 25.5-33.3 pg/ml], p<0.0001), and it was higher in both of two groups than in the health control group. ET-1 also showed some degree of agreement with EVLWI on judging severity. It is shown that the plasma concentration of ET-1 may correlate with the severity of lung injury and outcomes in patients with ALI/ARDS.Conclusions:1 Baseline PaO₂/FiO₂ ratio do not reflect severity and predict mortality in patients with ALI/ARDS. The PaO₂/FiO₂ ratio based on AECC definition for ALI/ARDS has limitation in estimating the severity of lung injury.2 EVLWI may be more reliable and more sensitive for evaluating the severity of lung injury and the degree of lung edema in patients with ALI/ARDS as compared with PaO₂/FiO₂ ratio, chest x-ray, and LIS. And EVLWI may be helpful to predict outcomes (that EVLWI>10 ml/kg may indicate high mortality).3 EVLWI should not be used at a single point in time but rather as a method to follow the changes in the degree of lung edema in ALI/ARDS.4 PVPI may be helpful for assessing pulmonary permeability and the severity of lung injury in ALI/ARDS, but further studies are needed.5 ET-1 may be helpful as a molecular marker for judging the severity of lung injury in ALI/ARDS.