To the Editor:—
In a recent issue of Anesthesiology, Song et al. 1examined 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.2Our 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.
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. email@example.com