Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Critical Care
Published in: Critical Care 2/2008

Open Access 01-04-2008 | Research

Biomarkers of inflammation, coagulation and fibrinolysis predict mortality in acute lung injury

Authors: Dana McClintock, Hanjing Zhuo, Nancy Wickersham, Michael A Matthay, Lorraine B Ware

Published in: Critical Care | Issue 2/2008

Login to get access

Abstract

Background

Acute lung injury (ALI) is a major cause of acute respiratory failure with high mortality despite lung-protective ventilation. Prior work has shown disordered inflammation and coagulation in ALI, with strong correlations between biomarker abnormalities and worse clinical outcomes. We measured plasma markers of inflammation, coagulation and fibrinolysis simultaneously to assess whether these markers remain predictive in the era of lung-protective ventilation.

Methods

Plasma samples and ventilator data were prospectively collected from 50 patients with early ALI. Plasma biomarkers of inflammation (IL-6, IL-8, intercellular adhesion molecule 1), of coagulation (thrombomodulin, protein C) and of fibrinolysis (plasminogen activator inhibitor 1) were measured by ELISA. Biomarker levels were compared between survivors (n = 29) and non-survivors (n = 21) using Mann–Whitney analysis.

Results

The tidal volume for the study group was 6.6 ± 1.1 ml/kg predicted body weight and the plateau pressure was 25 ± 7 cmH2O (mean ± standard deviation), consistent with lung-protective ventilation. All markers except IL-6 were significantly different between survivors and nonsurvivors. Nonsurvivors had more abnormal values. Three biomarkers – IL-8, intercellular adhesion molecule 1 and protein C – remained significantly different by multivariate analysis that included age, gender, Simplified Acute Physiology Score II and all biomarkers that were significant on bivariate analysis. Higher levels of IL-8 and intercellular adhesion molecule 1 were independently predictive of worse outcomes (odds ratio = 2.0 and 5.8, respectively; P = 0.04 for both). Lower levels of protein C were independently associated with an increased risk of death (odds ratio = 0.5), a result that nearly reached statistical significance (P = 0.06).

Conclusion

Despite lung-protective ventilation, abnormalities in plasma levels of markers of inflammation, coagulation and fibrinolysis predict mortality in ALI patients, indicating more severe activation of these biologic pathways in nonsurvivors.
Appendix
Available only for authorised users
Literature
1.
Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, Stern EJ, Hudson LD: Incidence and outcomes of acute lung injury. N Engl J Med 2005, 353: 1685-1693. 10.1056/NEJMoa050333PubMedCrossRef
2.
Moss MD, Gillespie MK, Ackerson L, Moore FA, Moore EE, Parsons PE: Endothelial cell activity varies in patients at risk for the adult respiratory distress syndrome. Crit Care Med 1996, 24: 1782-1786. 10.1097/00003246-199611000-00004PubMedCrossRef
3.
Conner ER, Ware LB, Modin G, Matthay MA: Elevated pulmonary edema fluid concentrations of soluble intercellular adhesion molecule-1. Biological and clinical significance. Chest 1999, 116: 83S-84S. 10.1378/chest.116.suppl_1.83SPubMedCrossRef
4.
Flori HR, Ware LB, Glidden D, Matthay MA: Early elevation of plasma soluble intercellular adhesion molecule-1 in pediatric acute lung injury identifies patients at increased risk of death and prolonged mechanical ventilation. Pediatr Crit Care Med 2003, 4: 315-321. 10.1097/01.PCC.0000074583.27727.8EPubMedCrossRef
5.
Parsons PE, Eisner MD, Thompson BT, Matthay MA, Ancukiewicz M, Bernard GR, Wheeler AP: Lower tidal volume ventilation and plasma cytokine markers of inflammation in patients with acute lung injury. Crit Care Med 2005, 33: 1-6. 10.1097/01.CCM.0000149854.61192.DCPubMedCrossRef
6.
Ranieri VM, Suter PM, Tortorella C, De Tullio R, Dayer JM, Brienza A, Bruno F, Slutsky AS: Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome. JAMA 1999, 282: 54-61. 10.1001/jama.282.1.54PubMedCrossRef
7.
Ware LB, Fang X, Matthay MA: Protein C and thrombomodulin in human acute lung injury. Am J Physiol Lung Cell Mol Physiol 2003, 285: L514-L521.PubMedCrossRef
8.
Bertozzi P, Astedt B, Zenzius L, Lynch K, LeMaire F, Zapol W, Chapman H: Depressed bronchoalveolar urokinase activity in patients with adult respiratory distress syndrome. N Engl J Med 1990, 322: 890-897.PubMedCrossRef
9.
Prabhakaran P, Ware L, White K, Cross M, Matthay M, Olman M: Elevated levels of plasminogen activator inhibitor-1 in pulmonary edema fluid are associated with mortality in acute lung injury. Am J Physiol Lung Cell Mol Physiol 2003, 285: L20-L28.PubMedCrossRef
10.
Ware LB, Matthay MA, Parsons PE, Thompson BT, Januzzi JL, Eisner MD, The National Heart Lung and Blood Institute's ARDS Clinical Trials Network: Pathogenetic and prognostic significance of altered coagulation and fibrinolysis in acute lung injury/acute respiratory distress syndrome. Crit Care Med 2007, 35: 1821-1828. 10.1097/01.CCM.0000221922.08878.49PubMedPubMedCentralCrossRef
11.
Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, Legall JR, Morris A, Spragg R: The American–European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994, 149: 818-824.PubMedCrossRef
12.
Acute Respiratory Distress Syndrome Network: Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000, 342: 1301-1308. 10.1056/NEJM200005043421801CrossRef
13.
Knaus WA, Draper EA, Wagner DP, Zimmerman JE: APACHE II: a severity of disease classification system. Crit Care Med 1985, 13: 818-829. 10.1097/00003246-198510000-00009PubMedCrossRef
14.
LeGall J, Lemshow S, Saulnier F: A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 1993, 270: 2957-2963. 10.1001/jama.270.24.2957CrossRef
15.
Nuckton TJ, Alonso JA, Kallet RH, Daniel BM, Pittet J-F, Eisner MD, Matthay MA: Pulmonary dead-space fraction as a risk factor for death in the acute respiratory distress syndrome. N Engl J Med 2002, 346: 1281-1286. 10.1056/NEJMoa012835PubMedCrossRef
16.
Ware LB: Prognostic determinants of acute respiratory distress syndrome in adults: impact on clinical trial design. Crit Care Med 2005,33(3 Suppl):S217-S222. 10.1097/01.CCM.0000155788.39101.7EPubMedCrossRef
17.
Frank J, Gutierrez J, Jones K, Allen L, Dobbs L, Matthay M: Low tidal volume reduces epithelial and endothelial injury in acid-injured rat lungs. Am J Respir Crit Care Med 2002, 165: 242-249.PubMedCrossRef
18.
Choi G, Wolthuis EK, Bresser P, Levi M, van der Poll T, Dzoljic M, Vroom MB, Schultz MJ: Mechanical ventilation with lower tidal volumes and positive end-expiratory pressure prevents alveolar coagulation in patients without lung injury. Anesthesiology 2006, 105: 689-695. 10.1097/00000542-200610000-00013PubMedCrossRef
19.
Weinert CR, Gross CR, Marinelli WA: Impact of randomized trial results on acute lung injury ventilator therapy in teaching hospitals. Am J Respir Crit Care Med 2003, 167: 1304-1309. 10.1164/rccm.200205-478OCPubMedCrossRef
20.
Brun-Buisson C, Minelli C, Bertolini G, Brazzi L, Pimentel J, Lewandowski K, Bion J, Romand J-A, Villar J, Thorsteinsson A, Damas P, Armaganidis A, Lemaire F, ALIVE Study Group: Epidemiology and outcome of acute lung injury in European intensive care units. Intensive Care Med 2004, 30: 51-61. 10.1007/s00134-003-2022-6PubMedCrossRef
Metadata
Title
Biomarkers of inflammation, coagulation and fibrinolysis predict mortality in acute lung injury
Authors
Dana McClintock
Hanjing Zhuo
Nancy Wickersham
Michael A Matthay
Lorraine B Ware
Publication date
01-04-2008
Publisher
BioMed Central
Published in
Critical Care / Issue 2/2008
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc6846

Other articles of this Issue 2/2008

Critical Care 2/2008 Go to the issue

Commentary

Noninvasive mechanical ventilation during the weaning process: facilitative, curative, or preventive?

Commentary

The inflammation–coagulation axis as an important intermediate pathway in acute lung injury

Commentary

Steroids in sepsis: another swing of the pendulum in our clinical trials

Review

Clinical review: Medication errors in critical care

Research

Anemia, transfusions and hospital outcomes among critically ill patients on prolonged acute mechanical ventilation: a retrospective cohort study

Research

Respiratory effects of different recruitment maneuvers in acute respiratory distress syndrome