The clinical usefulness of extravascular lung water and pulmonary vascular permeability index to diagnose and characterize pulmonary edema: a prospective multicenter study on the quantitative differential diagnostic definition for acute lung injury/acute respiratory distress syndrome

Abstract

Introduction: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by features other than increased pulmonary vascular permeability. Pulmonary vascular permeability combined with increased extravascular lung water content has been considered a quantitative diagnostic criterion of ALI/ARDS. This prospective, multi-institutional, observational study aimed to clarify the clinical pathophysiological features of ALI/ARDS and establish its quantitative diagnostic criteria.

Methods: The extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI) were measured using the transpulmonary thermodilution method in 266 patients with PaO2/FiO2 ratio ≤ 300 mmHg and bilateral infiltration on chest radiography, in 23 ICUs of academic tertiary referral hospitals. Pulmonary edema was defined as EVLWI ≥ 10 ml/kg. Three experts retrospectively determined the pathophysiological features of respiratory insufficiency by considering the patients' history, clinical presentation, chest computed tomography and radiography, echocardiography, EVLWI and brain natriuretic peptide level, and the time course of all preceding findings under systemic and respiratory therapy.

Results: Patients were divided into the following three categories on the basis of the pathophysiological diagnostic differentiation of respiratory insufficiency: ALI/ARDS, cardiogenic edema, and pleural effusion with atelectasis, which were noted in 207 patients, 26 patients, and 33 patients, respectively. EVLWI was greater in ALI/ARDS and cardiogenic edema patients than in patients with pleural effusion with atelectasis (18.5 ± 6.8, 14.4 ± 4.0, and 8.3 ± 2.1, respectively; P < 0.01). PVPI was higher in ALI/ARDS patients than in cardiogenic edema or pleural effusion with atelectasis patients (3.2 ± 1.4, 2.0 ± 0.8, and 1.6 ± 0.5; P < 0.01). In ALI/ARDS patients, EVLWI increased with increasing pulmonary vascular permeability (r = 0.729, P < 0.01) and was weakly correlated with intrathoracic blood volume (r = 0.236, P < 0.01). EVLWI was weakly correlated with the PaO2/FiO2 ratio in the ALI/ARDS and cardiogenic edema patients. A PVPI value of 2.6 to 2.85 provided a definitive diagnosis of ALI/ARDS (specificity, 0.90 to 0.95), and a value < 1.7 ruled out an ALI/ARDS diagnosis (specificity, 0.95).

Conclusion: PVPI may be a useful quantitative diagnostic tool for ARDS in patients with hypoxemic respiratory failure and radiographic infiltrates.

Trial registration: UMIN-CTR ID UMIN000003627.

Figure 1

Patient enrollment, exclusion, and classification. ALI, acute lung injury; ARDS, acute respiratory distress syndrome; COPD, chronic obstructive pulmonary disorder; EVLWI, extravascular lung water index.

Figure 2

Comparison of extravascular lung water indexed to predicted body weight. Comparison of extravascular lung water indexed to predicted body weight of patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), cardiogenic edema, and pleural effusion with atelectasis on the day of enrollment and the maximal value during the study period. (A) Extravascular lung water indexed to predicted body weight (EVLWI) on the day of enrollment was significantly higher in ALI/ARDS patients than in pleural effusion with atelectasis patients and cardiogenic edema patients. EVLWI was also higher in cardiogenic edema patients than in pleural effusion with atelectasis patients. (B) Differences were found when the maximal EVLWI value was compared between day 0 and day 2. Data presented as median (interquartile range). *P < 0.01 vs. pleural effusion with atelectasis. **P < 0.01 vs. cardiogenic edema. EVLWI-0, extravascular lung water index on day of enrollment; maxEVLWI, maximal value of extravascular lung water index from days 0 to 2.

Figure 3

Comparison of pulmonary vascular permeability index. Comparison of pulmonary vascular permeability index (PVPI) of patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), cardiogenic edema, and pleural effusion with atelectasis on the day of enrollment and the maximal value during the study period. (A) PVPI was higher in ALI/ARDS patients than in cardiogenic edema and pleural effusion with atelectasis patients. There was no difference in the index between cardiogenic edema and pleural effusion with atelectasis patients. (B) Differences were found when the maximal index value was compared between day 0 and day 2. Data presented as median (interquartile range). *P < 0.01 vs. pleural effusion with atelectasis and cardiogenic edema. PVPI-0, pulmonary vascular permeability index on the day of enrollment; maxPVPI, maximal value of pulmonary vascular permeability index from days 0 to 2.

Figure 4

Extravascular lung water index and pulmonary vascular permeability index/intrathoracic blood volume correlation in ALI/ARDS patients. Correlation between extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) and that between EVLWI and intrathoracic blood volume (ITBV) in patients with acute lung injury/acute respiratory distress syndrome. There was a strong correlation between EVLWI and PVPI (r = 0.729, P < 0.01) (A) and a weak correlation between EVLWI and ITBV (r = 0.236, p < 0.01) (B). EVLWI-0, extravascular lung water index on the day of enrollment; PVPI-0, pulmonary vascular permeability index on the day of enrollment; ITBV-0, intrathoracic blood volume on the day of enrollment.

Figure 5

Extravascular lung water index and pulmonary vascular permeability index/intrathoracic blood volume correlation in non-ALI/ARDS patients. Correlation between extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) and that between EVLWI and intrathoracic blood volume (ITBV) in patients with non-acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). For this analysis, cardiogenic edema and pleural effusion with atelectasis patients were combined as non-ALI/ARDS. EVLWI had a moderate correlation with PVPI (r = 0.464, P < 0.01) (A) and with ITBV (r = 0.493, P < 0.01) (B). EVLWI-0, extravascular lung water index on the day of enrollment; PVPI-0, pulmonary vascular permeability index on the day of enrollment; ITBV-0, intrathoracic blood volume on the day of enrollment.

Figure 6

Correlation between extravascular lung water index and PaO₂/FiO₂ ratio. There was a negative and weak correlation between extravascular lung water index (EVLWI) and PaO₂/FiO₂ (P/F) ratio in all patients except for pleural effusion with atelectasis patients (r = -0.213, P < 0.01) (A). In acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) patients (n = 207), a weak correlation between EVLWI and P/F ratio was observed (r = -0.215, P < 0.01) (B). No correlation between EVLWI and pulmonary vascular permeability index was observed in cardiogenic edema patients (n = 26; r = -0.176, P = 0.39) (C). EVLWI-0, extravascular lung water index on the day of enrollment; P/F-0, PaO₂/FiO₂ ratio on the day of enrollment.

Figure 7

Receiver operating characteristic curves for pulmonary vascular permeability index and intrathoracic blood volume. Receiver operating characteristic curves for pulmonary vascular permeability index (PVPI) and intrathoracic blood volume (ITBV) on the day of enrollment for the differential diagnosis of acute lung injury/acute respiratory distress syndrome. The area under the curve for PVPI (0.886; confidence interval, 0.836 to 0.935) was significantly larger than that for ITBI (0.425; confidence interval, 0.359 to 0.529; P < 0.01). PVPI-0, pulmonary vascular permeability index on the day of enrollment; ITBV-0, intrathoracic blood volume on the day of enrollment.