From evidence to clinical practice: Effective implementation of therapeutic hypothermia to improve patient outcome after cardiac arrest*
Year: 2006
Type: article
Abstract: OBJECTIVE: The coagulation and inflammatory cascades may be linked in the pathogenesis of acute lung injury and acute respiratory distress syndrome. However, direct evidence for the contribution of abnormalities in coagulation and fibrinolysis proteins to outcomes in patients with acute lung injury/acute respiratory distress syndrome is lacking. DESIGN: Retrospective measurement of plasma levels of protein C and plasminogen activator inhibitor-1 in plasma samples that were collected prospectively as part of a large multicenter clinical trial. The primary outcome was hospital mortality. To evaluate the potential additive value of abnormalities of these biomarkers, the excess relative risk of death was calculated for each combination of quartiles of protein-C and plasminogen activator inhibitor-1 levels. SETTING: Ten university medical centers. PATIENTS: The study included 779 patients from a multicenter clinical trial of a protective ventilatory strategy in acute lung injury/acute respiratory distress syndrome and 99 patients with acute cardiogenic pulmonary edema, as well as ten normal controls. MEASUREMENTS AND MAIN RESULTS: Compared with plasma from controls and patients with acute cardiogenic pulmonary edema, baseline protein-C levels were low and baseline plasminogen activator inhibitor-1 levels were elevated in acute lung injury/acute respiratory distress syndrome. By multivariate analysis, lower protein C and higher plasminogen activator inhibitor-1 were strong independent predictors of mortality, and ventilator-free and organ-failure-free days. Plasminogen activator inhibitor-1 and protein C had a synergistic interaction for the risk of death. CONCLUSIONS: Early acute lung injury/acute respiratory distress syndrome is characterized by decreased plasma levels of protein C and increased plasma levels of plasminogen activator inhibitor-1 that are independent risk factors for mortality and adverse clinical outcomes. Measurement of plasminogen activator inhibitor-1 and protein-C levels may be useful to identify those at highest risk of adverse clinical outcomes for the development of new therapies.
Source: Critical Care Medicine
Language: English
Subfield: Emergency Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1090100904, G1293636220, G1662962972, G1952629442, CLINICAL CENTERS--A NETWORK FOR THE TREATMENT OF ARD, CLINICAL CENTERS--A NETWORK FOR THE TREATMENT OF ARD, CLINICAL CENTERS--A NETWORK FOR THE TREATMENT OF ARD, G3382904653, G3429402575, RESOLUTION OF CLINICAL LUNG INJURY, G397676299, G4242618607, CENTER FOR CLINICAL NETWORK FOR ARDS TREATMENT, G4693699727, ASTHMA HEALTH OUTCOMES FOLLOWING INTENSIVE CARE, G5272020229, CCTG CLINICAL NETWORK FOR ARDS TREATMENT--CRITICAL CARE, CCTG CLINICAL NETWORK FOR ARDS TREATMENT--CRITICAL CARE, CLINICAL CENTERS--A NETWORK FOR THE TREAMENT OF ARD, G654368599, G7229621430, CCTG FOR CLINICAL NETWORK FOR ARDS TREATMENT, CCTG CLINICAL NETWORK FOR ARDS TREATMENT--CRITICAL CARE, SCCOR in translational research in Acute Lung Injury, Biomarker Profiles in the Diagnosis/Prognosis of ARDS, Alveolar Epithelium in Acute Lung Injury, CCTG CLINICAL NETWORK FOR ARDS TREATMENT--CRITICAL CARE, CCTG CLINICAL NETWORK FOR ARDS TREATMENT--CRITICAL CARE, G87186383, Resolution of Clinical Lung Injury, G969146605
OpenAlex ID: W2077647582