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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

Shigeki Kushimoto1*, Yasuhiko Taira2, Yasuhide Kitazawa3, Kazuo Okuchi4, Teruo Sakamoto5, Hiroyasu Ishikura6, Tomoyuki Endo7, Satoshi Yamanouchi1, Takashi Tagami89, Junko Yamaguchi10, Kazuhide Yoshikawa11, Manabu Sugita12, Yoichi Kase13, Takashi Kanemura14, Hiroyuki Takahashi15, Yuichi Kuroki16, Hiroo Izumino17, Hiroshi Rinka18, Ryutarou Seo19, Makoto Takatori20, Tadashi Kaneko21, Toshiaki Nakamura22, Takayuki Irahara23, Nobuyuki Saito24, Akihiro Watanabe8 and The PiCCO Pulmonary Edema Study Group

Author Affiliations

1 Division of Emergency Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan

2 Department of Emergency and Critical Care Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae, Kawasaki, Kanagawa 216-8511, Japan

3 Department of Emergency and Critical Care Medicine, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi City, Osaka 570-8506, Japan

4 Department of Emergency and Critical Care Medicine, Nara Medical University, 840 Shinjo-cho, Kashihara, Nara 634-8521, Japan

5 Department of Emergency and Critical Care Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume-shi, Fukuoka 830-0011, Japan

6 Department of Emergency and Critical Care Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka City, Fukuoka 814-0180, Japan

7 Advanced Emergency and Critical Care Center, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan

8 Department of Emergency and Critical Care Medicine, Nippon Medical School Hospital, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan

9 Department of Emergency and Critical Care Medicine, Aidu Chuo Hospital, 1-1 Tsuruga, Aiduwakamatsu, Fukushima 965-8611, Japan

10 Division of Emergency and Critical Care Medicine, Department of Acute Medicine, Nihon University School of Medicine, 30-1 Oyaguchi kamimachi, Itabashi-ku, Tokyo 173-8610, Japan

11 Shock Trauma and Emergency Medical Center, Tokyo Medical and Dental University Hospital, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan

12 Department of Emergency and Critical Care Medicine, Juntendo University Nerima Hospital, 3-1-10 Takanodai, Nerima-ku, Tokyo 177-8521, Japan

13 Department of Critical Care Medicine, Jikei University School of Medicine, 3-19-18 Nishi-shinbashi, Minato-ku, Tokyo 105-8471, Japan

14 Emergency and Critical Care Medicine, National Hospital Organization Disaster Medical Center, 3256 Midori-cho, Tachikawa-shi, Tokyo 190-0014, Japan

15 Department of Intensive Care Medicine, Saiseikai Yokohamashi Tobu Hospital, 3-6-1 Shimosumiyosi, Tsurumi-ku, Yokohama City, Kanagawa 230-8765, Japan

16 Department of Emergency and Critical Care Medicine, Social Insurance Chukyo Hospital, 1-1-10 Sanjo, Minami-ku, Nagoya City, Aichi 457-8510, Japan

17 Advanced Emergency and Critical Care Center, Kansai Medical University Takii Hospital, 10-15 Fumizono-machi, Moriguchi Cty, Osaka 570-8507, Japan

18 Emergency and Critical Care Medical Center, Osaka City General Hospital, 2-13-22, Miyakojima Hondori, Miyakojima, Osaka 534-0021, Japan

19 Department of Anesthesia, Kobe City Medical Center General Hospital, 2-2-1 Minatojimaminamimachi, Chuo-ku, Kobe City, Hyogo 650-0046, Japan

20 Department of Anesthesia and Intensive Care, Hiroshima City Hospital, 7-33 Motomachi, Naka-ku, Hiroshima-shi, Hiroshima 730-8518, Japan

21 Advanced Medical Emergency and Critical Care Center, Yamaguchi University Hospital, 1-1-1 Minamikogushi, Ube City, Yamaguchi 755-8505, Japan

22 Intensive Care Unit, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan

23 Department of Emergency and Critical Care Medicine, Nippon Medical School Tama Nagayama Hospital, 1-7-1 Nagayama, Tama-shi, Tokyo 206-8512, Japan

24 Department of Emergency and Critical Care Medicine, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamagari, Inzai-shi, Chiba 270-1694, Japan

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Critical Care 2012, 16:R232  doi:10.1186/cc11898

See related commentary by Perel,, related letter by Kushimoto,, and related Letter by Bai and Wang,

Published: 11 December 2012



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.


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.


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).


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

Trial registration