Peritoneal lavage with activated protein C alters compartmentalized coagulation and fibrinolysis and improves survival in polymicrobial peritonitis
Department of Surgery (Surgical Laboratory), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Critical Care Medicine
(Impact Factor: 6.31).
11/2006; 34(11):2799-805. DOI: 10.1097/01.CCM.0000243795.04284.2A
During peritonitis, intra-abdominal fibrin entraps bacteria and hampers their elimination. Systemic administration of anticoagulant activated protein C improves survival in patients with severe sepsis, but its precise mode of action is unclear. This study in polymicrobial peritonitis assessed the effects of local activated protein C administration in peritoneal lavage fluid on coagulation, fibrinolysis, and survival.
Prospective, randomized study.
University-based research laboratory.
Twenty-four hours after induction of peritonitis by cecal ligation and puncture, mice underwent peritoneal lavage with activated protein C (1.0 microg/mL) or saline. Peritoneal lavage fluid, blood, and lungs were sampled after 24, 48, or 72 hrs (n = 8/group/time point). For survival analysis, maximum observation was 96 hrs (n = 22/group). Clotting time, tissue factor expression, thrombin-antithrombin complexes, fibrin degradation products (D-dimers), plasminogen activator, and plasminogen activator inhibitor were used to assess coagulation and fibrinolysis responses.
Activated protein C lavage reduced abdominal bacterial load, abdominal and pulmonary clotting times, D-dimers (p < .05 vs. saline), pulmonary tissue factor expression, and fibrin depositions, without clear effects on systemic thrombin generation. Activated protein C lavage decreased plasma and abdominal tissue plasminogen activator levels with increased inhibitor plasminogen activator inhibitor-1 levels (p < .05) but had reverse effects on pulmonary fibrinolysis. Survival improved from 55% (saline) to 80% after intra-abdominal activated protein C administration (p = .03).
Peritoneal lavage with activated protein C may rebalance coagulation and fibrinolysis within compartments and improve survival in polymicrobial peritonitis.
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