Procoagulant and fibrinolytic activity in ventilator-associated pneumonia: impact of inadequate antimicrobial therapy

Intensive Care Med. 2004 Oct;30(10):1914-20. doi: 10.1007/s00134-004-2391-5. Epub 2004 Jul 23.

Abstract

Objective: To determine the homeostatic balance of patients with ventilator-associated pneumonia (VAP) with respect to the adequacy of antimicrobial therapy.

Design and setting: Descriptive observational study in a 12-bed medical intensive care unit in a university-affiliated hospital.

Patients: Twenty-nine patients with VAP documented by quantitative culture of bronchoalveolar secretions and a control group of eight mechanically ventilated patients.

Methods: Serial bronchoalveolar lavage fluid (BALF) samples were assayed for prothrombin activation fragment (F1+2), thrombin-antithrombin (TAT) complex, fibrinolytic activity, urokinase-type plasminogen activator (u-PA), and plasminogen activator inhibitor type 1 (PAI-1) on days 1, 4, and 7 after VAP onset.

Results: Pathogens isolated from patients with inadequate empirical antimicrobial coverage included methicillin-resistant Staphylococcus aureus (n=2), Pseudomonas aeruginosa (n=4), and Acinetobacter baumannii (n=1). Compared to those who received adequate antibiotic therapy, TAT, F1+2, and PAI-1 levels increased while u-PA levels remained unchanged. Despite antibiotic adjustment on day 4, TAT levels remained elevated in those who lacked adequate antimicrobial coverage and were significantly correlated with PaO(2)/FIO(2). The procoagulant activity was accompanied by a local depression of fibrinolytic capacity that was attributed mainly to increased BALF PAI-1 levels. Nonsurvivors showed significantly higher levels of TAT and PAI-1 than survivors. No significant correlation between the bacterial burden and the homeostatic derangements was documented.

Conclusions: The lung inflammatory response seems to promulgate a local procoagulant activity associated with hypoxemia in those with inadequate antibiotic therapy. The homeostatic derangement seems to be independent of the lung bacterial burden.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / therapeutic use
  • Blood Coagulation / drug effects
  • Cross Infection / blood
  • Cross Infection / drug therapy*
  • Cross Infection / etiology
  • Cross Infection / microbiology
  • Drug Utilization / standards*
  • Female
  • Hemostasis / drug effects*
  • Humans
  • Intensive Care Units
  • Male
  • Pneumonia / blood
  • Pneumonia / drug therapy*
  • Pneumonia / etiology
  • Prognosis
  • Prospective Studies
  • Treatment Outcome
  • Ventilators, Mechanical / adverse effects*
  • Ventilators, Mechanical / microbiology

Substances

  • Anti-Bacterial Agents