Top

Intensive Care Medicine

Published in:

01-01-2006 | Original

Alveolar plasminogen activator inhibitor-1 predicts ARDS in aspiration pneumonitis

Authors: Ali A. El Solh, Milapchand Bhora, Lilibeth Pineda, Alan Aquilina, Laurie Abbetessa, Eileen Berbary

Published in: Intensive Care Medicine | Issue 1/2006

Abstract

Objective

To test the hypothesis that alveolar plasminogen activator inhibitor-1 (PAI-1) can identify patients with witnessed aspiration at risk for progression to acute respiratory distress syndrome (ARDS).

Design

Prospective observational study.

Setting

Medical intensive care unit in a tertiary care center.

Patients

Fifty-one patients with witnessed aspiration who had a PaO₂/FIO₂<300 for a period no less than 4 h from admission.

Interventions

Alveolar fluid sampling was performed within 8 h of intubation via luminal suction of the distal airways using a 13-Fr catheter. Plasma levels were collected simultaneously by venipuncture.

Measurements and results

Alveolar PAI-1 antigen levels were more than five times higher in those who progressed to ARDS than in those with uncomplicated aspiration pneumonitis (2687±1498 ng/ml vs. 587±535 ng/ml, respectively; p<0.001), while plasma levels of PAI-1 antigen were not significantly different between the two groups. The measured activity of PAI-1 antigen paralleled the levels observed in both media. A cut-off level of alveolar PAI-1 >1518 ng/ml was found to be 82.4% (56.6%–96.0%) sensitive and 97.1% (84.6%–99.5%) specific in predicting progression to ARDS. There was also a significant inverse relationship between elevation of PAI-1 antigen levels and the degree of lung injury as assessed by the days of unassisted ventilation (r²=0.37; p<0.001).

Conclusions

Elevation of alveolar PAI-1 antigen levels postaspiration is the consequence of local rather than systemic activation of the fibrinolytic system. Measurement of alveolar PAI-1 antigen levels can be a useful clinical marker in predicting progression to ARDS after gastric aspiration.

Available only for authorised users

Roy TM, Ossorio MA, Cipolla LM, Fields CL. Snider HL, Anderson WH (1989) Pulmonary complications after tricyclic antidepressant overdose. Chest 96:852–856PubMed

Olsson GL, Hallen B, Hambraeus-Jonzon K (1986) Aspiration during anaesthesia: a computer-aided study of 185,358 anaesthetics. Acta Anaesthesiol Scand 30:84–92PubMed

Marik PE (2001) Aspiration pneumonitis and aspiration pneumonia. N Engl J Med 344:665–671CrossRefPubMed

Bynum L, Pierce A (1976) Pulmonary aspiration of gastric contents. Am Rev Respir Dis 114:1129–1136PubMed

Olman M, Mackman N, Gladson C, Moser K, Loskutoff DJ (1995) Changes in procoagulant and fibrinolytic gene expression during bleomycin induced lung injury in the mouse. J Clin Invest 96:1621–1630PubMed

Idell S, James KK, Levin EG, Schwartz BS, Manchanda N, Maunder RJ, Martin TR, McLarty J, Fair DS (1989) Local abnormalities in coagulation and fibrinolytic pathways predispose to alveolar fibrin deposition in the adult respiratory distress syndrome. J Clin Invest 84:695–705PubMed

Eitzman DT, McCoy RD, Zheng X, Fay WP, Shen T, Ginsburg D, Simon RH (1996) Bleomycin-induced pulmonary fibrosis in transgenic mice that either lack or overexpress the murine plasminogen activator-1 gene. J Clin Invest 97:232–237PubMed

Verghese GM, Ware LB, Matthay BA, and Matthay MA (1999) Alveolar epithelial fluid transport and the resolution of clinically severe hydrostatic pulmonary edema. J Appl Physiol 87:1301–1312PubMed

El-Solh AA, Pietrantoni C, Bhat A, Aquilina AT, Okada M, Grover V, Gifford N (2003) Microbiology of severe aspiration pneumonia in institutionalized elders. Am J Respir Crit Care Med 167:1650–1654CrossRefPubMed

10.

Smith PK, Krohn RI, Hermason GT, Mallia AK, Gartner FK, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC (1985) Measurement of protein using bicinchonimic acid. Anal Biochem 150:76–85CrossRefPubMed

11.

Murray JF, Matthay MA, Luce JM, Flick MR (1988) An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis 138:720–723PubMed

12.

Knaus WA, Draper EA, Wagner DP, Zimmerman JE (1985) APACHE II: a severity of disease classification system. Crit Care Med 13:818–829PubMed

13.

Bernard GR, Artigas A, Brigham K, Carlet J, Falke K, Hudson L, Lamy M, Le Gall JR, Morris A, Spragg R (1994) The American-European consensus conference on ARDS. Am J Respir Crit Care Med 149:818–824PubMed

14.

Schoenfeld DA, Bernard GR (2002) Evaluation of ventilator-free days as an efficacy measure in clinical trials of treatments for acute respiratory distress syndrome. Crit Care Med 30:1772–1777CrossRefPubMed

15.

Chmielewska J, Wiman B (1986) Determination of tissue plasminogen activator and its “fast” inhibitor in plasma. Clin Chem 32:482–485PubMed

16.

Kleinbaum DG, Kupper LL, Muller K (1998) Applied regression analysis and other multivariable methods, 3rd edn. Duxbury Press, Pacific Grove, CA, pp 228–237

17.

Gunther A, Mosavi P, Heinemann S, Ruppert C, Muth H, Markart P, Grimminger F, Walmrath D, Temmesfeld-Wollbruck B, Seeger W (2000) Alveolar fibrin formation caused by enhanced procoagulant and depressed fibrinolytic capacities in severe pneumonia: comparison with the acute respiratory distress syndrome. Am J Respir Crit Care Med 161:454–462PubMed

18.

Bertozzi P, Astedt B, Zenzius L, Lynch K, LeMaire F, Zapol W, Chapman HA Jr (1990) Depressed bronchoalveolar urokinase activity in patients with adult respiratory distress syndrome. N Engl J Med 322:890–897PubMed

19.

Idell S, Gonzalez K, Bradford H, Macarthur CK, Fein AM, Maunder RJ, Garcia JG, Griffith DE, Weiland J, Martin TR (1987) Procoagulant activity in bronchoalveolar lavage in the adult respiratory distress syndrome. Contribution of tissue factor associated with Factor VII. Am Rev Respir Dis 136:1466-1474PubMed

20.

El Solh AA, Okada M, Pietrantoni C, Aquilina A, Berbary E (2004) Procoagulant and fibrinolytic activity in ventilator-associated pneumonia: impact of inadequate antimicrobial therapy. Intensive Care Med 30:1914–1920CrossRefPubMed

21.

Schultz MJ, Millo J, Levi M, Hack CE, Weverling GJ, Garrard CS, van der Poll T (2004) Local activation of coagulation and inhibition of fibrinolysis in the lung during ventilator associated pneumonia. Thorax 59:130–135CrossRefPubMed

22.

Quax PH, van den Hoogen CM, Verheijen JH, Padro T, Zeheb R, Gelehrter TD, van Berkel TJ, Kuiper J, Emeis JJ (1990) Endotoxin induction of plasminogen activator and plasminogen activator inhibitor type 1 mRNA in rat tissues in vivo. J Biol Chem 265:15560–15563PubMed

23.

Prabhakaran P, Ware LB, White KE, Cross MT, Matthay MA, Olman MA (2003) Elevated levels of plasminogen activator inhibitor-1 in pulmonary edema are associated with mortality in acute lung injury. Am J Physiol Lung Cell Mol Physiol 285:L20–L28PubMed

24.

Chandrasekhar A, Timberlake G, Prabhakar G, Barringer L (2001) Elevation of alveolar cytokine response to aspiration of gastric contents. J Appl Res Clin Exp Therap 1(1):http://jrnlappliedresearch.com/articles/Vol1Iss1/Chendrasekhar.htm

25.

Fan J, Kapus A, Li H, Rizoli S, Marshall J, Rotstein O (2000) Priming for enhanced alveolar fibrin deposition following hemorrhagic shock: role of tumor necrosis factor. Am J Respir Cell Mol Biol 22:412–421PubMed

26.

Groeneveld AN, Kindt I, Raijmakers PG, Hack CE, Thijs LG (1997) Systemic coagulation and fibrinolysis in patients with or at risk for the adult respiratory distress syndrome. Thromb Haemost 78:1444–1449PubMed

27.

Westendorp RG, Hottenga JJ, Slagboom PE (1999) Variation in plasminogen-activator-inhibitor-1 gene and risk of meningococcal septic shock. Lancet 354:561–563CrossRefPubMed

Title: Alveolar plasminogen activator inhibitor-1 predicts ARDS in aspiration pneumonitis
Authors: Ali A. El Solh
Milapchand Bhora
Lilibeth Pineda
Alan Aquilina
Laurie Abbetessa
Eileen Berbary
Publication date: 01-01-2006
Publisher: Springer-Verlag
Published in: Intensive Care Medicine / Issue 1/2006
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-005-2847-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Alveolar plasminogen activator inhibitor-1 predicts ARDS in aspiration pneumonitis

Abstract

Objective

Design

Setting

Patients

Interventions

Measurements and results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Design

Setting

Patients

Interventions

Measurements and results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2006

Trends in sedation practices in Danish intensive care units in 2003: a national survey

Biochemical parameters of bronchoalveolar lavage fluid in fat embolism

Echocardiography in the ICU: time for widespread use!

Nurse involvement in end-of-life decision making: the ETHICUS Study

Selection of resistance during sequential use of preferential antibiotic classes

The use of drugs with a life-shortening effect in end-of-life care in neonates and infants