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Correspondence  |   October 2007
Decreased Alveolar Fibrinolysis in Patients with Ventilator-associated Pneumonia: A Species-specific Event
Author Affiliations & Notes
  • Ali A. El Solh, M.D., M.P.H.
    *
  • *Western New York Respiratory Research Center, State University of New York at Buffalo, Buffalo, New York.
Article Information
Correspondence
Correspondence   |   October 2007
Decreased Alveolar Fibrinolysis in Patients with Ventilator-associated Pneumonia: A Species-specific Event
Anesthesiology 10 2007, Vol.107, 677. doi:10.1097/01.anes.0000281981.78659.26
Anesthesiology 10 2007, Vol.107, 677. doi:10.1097/01.anes.0000281981.78659.26
To the Editor:—
In a recent issue of Anesthesiology, Song et al.  1 examined the relation between plasminogen activator inhibitor 1 (PAI-1) in bronchoalveolar fluid and mortality in patients with ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa  . Although the authors found no difference in the concentration of PAI-1 levels between patients with VAP and those without VAP, there was a positive correlation between the levels of PAI-1 and the risk of mortality. Whether P. aeruginosa  was responsible for more severe derangement in the fibrinolytic system compared with other VAP-responsible pathogens was hitherto unknown.
In a recent investigation, we demonstrated a bacteria-specific activation of the tissue factor–dependent procoagulant system.2 Our observations paralleled those of Song et al.  in documenting a profound shift toward procoagulant activity when P. aeruginosa  was the culprit. Infection with methicillin-sensitive Staphylococcus aureus  , methicillin-resistant S. aureus  , and Escherichia coli  induced similar coagulation imbalance, but the derangement was less severe in terms of intraalveolar fibrin deposition. More importantly, the restoration of the hemostatic balance was delayed in cases of P. aeruginosa  VAP despite adequate antimicrobial therapy. However, the study did not assess the role of PAI-1 as a function of bacterial pathogens. Therefore, to evaluate whether the observed coagulation derangement may be due to species-specific inhibition of fibrinolysis, we tested our bronchoalveolar samples collected at the onset of VAP and at day 4 and day 8 after treatment for PAI-1 levels. Figure 1shows that PAI-1 levels were elevated for all pathogens at the onset of VAP compared with controls (P  < 0 .001). However, the concentrations of PAI-1 levels in bronchoalveolar fluid were more pronounced in those patients infected with P. aeruginosa  than in those observed in the other infectious categories and continued to be elevated for the duration of the study. The PAI-1 levels did not correlate with the bacterial burden at any specific time point, but there was a correlation between the total bacterial load and the concentrations of PAI-1 for each of the organisms over the study period (r  = 0.76, P  < 0.001). This finding confirms the hypothesis that the extent of local disturbance in alveolar hemostasis is species specific and is attributed not only to the activation of the tissue factor–dependent pathway but also to down-regulation of fibrinolysis via  increased PAI-1 levels.
Fig. 1. Serial bronchoalveolar lavage fluid of plasminogen activator inhibitor 1 (PAI-1) at onset of ventilator-associated pneumonia and at day 4 and day 8 after onset of ventilator-associated pneumonia caused by  Pseudomonas aeruginosa  , methicillin-resistant  Staphylococcus aureus  (MRSA),  Escherichia coli  , and methicillin-sensitive  S. aureus  (MSSA) compared with controls (C). *  P  < 0.05 compared with controls. †  P  < 0.05 compared with MRSA. Analysis of variance results among the four groups for days 0, 4, and 8 are 0.04, 0.02, and 0.002, respectively. 
Fig. 1. Serial bronchoalveolar lavage fluid of plasminogen activator inhibitor 1 (PAI-1) at onset of ventilator-associated pneumonia and at day 4 and day 8 after onset of ventilator-associated pneumonia caused by  Pseudomonas aeruginosa  , methicillin-resistant  Staphylococcus aureus  (MRSA),  Escherichia coli  , and methicillin-sensitive  S. aureus  (MSSA) compared with controls (C). *  P  < 0.05 compared with controls. †  P  < 0.05 compared with MRSA. Analysis of variance results among the four groups for days 0, 4, and 8 are 0.04, 0.02, and 0.002, respectively. 
Fig. 1. Serial bronchoalveolar lavage fluid of plasminogen activator inhibitor 1 (PAI-1) at onset of ventilator-associated pneumonia and at day 4 and day 8 after onset of ventilator-associated pneumonia caused by  Pseudomonas aeruginosa  , methicillin-resistant  Staphylococcus aureus  (MRSA),  Escherichia coli  , and methicillin-sensitive  S. aureus  (MSSA) compared with controls (C). *  P  < 0.05 compared with controls. †  P  < 0.05 compared with MRSA. Analysis of variance results among the four groups for days 0, 4, and 8 are 0.04, 0.02, and 0.002, respectively. 
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It is clear that the derangement of the local alveolar coagulation system seems to be a universal reaction to invading pathogens, but whether local and/or systemic intervention aiming at preventing local alveolar fibrin deposition can translate into improved outcome remains an unanswered question.
*Western New York Respiratory Research Center, State University of New York at Buffalo, Buffalo, New York.
References
Song Y, Lynch SV, Flanagan J, Zhuo H, Tom W, Dotson RH, Baek MS, Rubio-Mills A, Singh G, Kipnis E, Glidden D, Brown R, Garcia O, Wiener-Kronish JP: Increased plasminogen activator inhibitor-1 concentrations in bronchoalveolar lavage fluids are associated with increased mortality in a cohort of patients with Pseudomonas aeruginosa  . Anesthesiology 2007; 106:252–61Song, Y Lynch, SV Flanagan, J Zhuo, H Tom, W Dotson, RH Baek, MS Rubio-Mills, A Singh, G Kipnis, E Glidden, D Brown, R Garcia, O Wiener-Kronish, JP
El Solh AA, Choi G, Schultz MJ, Pineda LA, Mankowski C: Clinical and hemostatic responses to treatment in ventilator-associated pneumonia: Role of bacterial pathogens. Crit Care Med 2007; 35:490–6El Solh, AA Choi, G Schultz, MJ Pineda, LA Mankowski, C
Fig. 1. Serial bronchoalveolar lavage fluid of plasminogen activator inhibitor 1 (PAI-1) at onset of ventilator-associated pneumonia and at day 4 and day 8 after onset of ventilator-associated pneumonia caused by  Pseudomonas aeruginosa  , methicillin-resistant  Staphylococcus aureus  (MRSA),  Escherichia coli  , and methicillin-sensitive  S. aureus  (MSSA) compared with controls (C). *  P  < 0.05 compared with controls. †  P  < 0.05 compared with MRSA. Analysis of variance results among the four groups for days 0, 4, and 8 are 0.04, 0.02, and 0.002, respectively. 
Fig. 1. Serial bronchoalveolar lavage fluid of plasminogen activator inhibitor 1 (PAI-1) at onset of ventilator-associated pneumonia and at day 4 and day 8 after onset of ventilator-associated pneumonia caused by  Pseudomonas aeruginosa  , methicillin-resistant  Staphylococcus aureus  (MRSA),  Escherichia coli  , and methicillin-sensitive  S. aureus  (MSSA) compared with controls (C). *  P  < 0.05 compared with controls. †  P  < 0.05 compared with MRSA. Analysis of variance results among the four groups for days 0, 4, and 8 are 0.04, 0.02, and 0.002, respectively. 
Fig. 1. Serial bronchoalveolar lavage fluid of plasminogen activator inhibitor 1 (PAI-1) at onset of ventilator-associated pneumonia and at day 4 and day 8 after onset of ventilator-associated pneumonia caused by  Pseudomonas aeruginosa  , methicillin-resistant  Staphylococcus aureus  (MRSA),  Escherichia coli  , and methicillin-sensitive  S. aureus  (MSSA) compared with controls (C). *  P  < 0.05 compared with controls. †  P  < 0.05 compared with MRSA. Analysis of variance results among the four groups for days 0, 4, and 8 are 0.04, 0.02, and 0.002, respectively. 
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