title: Ventilator-induced coagulopathy in experimental Streptococcus pneumoniae pneumonia.
abstract: Pneumonia, the main cause of acute lung injury, is characterised by a local pro-inflammatory response and coagulopathy. Mechanical ventilation (MV) is often required. However, MV can lead to additional injury: so-called ventilator-induced lung injury (VILI). Therefore, the current authors investigated the effect of VILI on alveolar fibrin turnover in Streptococcus pneumoniae pneumonia. Pneumonia was induced in rats, followed 48 h later by either lung-protective MV (lower tidal volumes (LV(T)) and positive end-expiratory pressure (PEEP)) or MV causing VILI (high tidal volumes (HV(T)) and zero end-expiratory pressure (ZEEP)) for 3 h. Nonventilated pneumonia rats and healthy rats served as controls. Thrombin-antithrombin complexes (TATc), as a measure for coagulation, and plasminogen activator activity, as a measure of fibrinolysis, were determined in bronchoalveolar lavage fluid (BALF) and serum. Pneumonia was characterised by local (BALF) activation of coagulation, resulting in elevated TATc levels and attenuation of fibrinolysis compared with healthy controls. LV(T)-PEEP did not influence alveolar coagulation or fibrinolysis. HV(T)-ZEEP did intensify the local procoagulant response: TATc levels rose significantly and levels of the main inhibitor of fibrinolysis, plasminogen activator inhibitor-1, increased significantly. HV(T)-ZEEP also resulted in systemic elevation of TATc compared with LV(T)-PEEP. Mechanical ventilation causing ventilator-induced lung injury increases pulmonary coagulopathy in an animal model of Streptococcus pneumoniae pneumonia and results in systemic coagulopathy.
authors.affiliation: Interdepartmental Division of Critical Care Medicine, University of Toronto, Keenan Research Center, Li Ka Shing Knowledge Institute, St Michael's Hospital, 30 Bond Street, Queen Wing 4-042, Toronto, ON, M5B 1W8 Canada. jack.haitsma@utoronto.ca
authors.forename: J J
authors.initials: JJ
authors.lastname: Haitsma
authors.forename: M J
authors.initials: MJ
authors.lastname: Schultz
authors.forename: J-J H
authors.initials: JJ
authors.lastname: Hofstra
authors.forename: J W
authors.initials: JW
authors.lastname: Kuiper
authors.forename: J
authors.initials: J
authors.lastname: Juco
authors.forename: R
authors.initials: R
authors.lastname: Vaschetto
authors.forename: M
authors.initials: M
authors.lastname: Levi
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: A S
authors.initials: AS
authors.lastname: Slutsky