Antithrombin III supplementation in severe sepsis: beneficial effects on organ dysfunction.
Activation of thrombin and of the coagulation system plays an important role in the pathophysiology of sepsis-associated organ dysfunction. Antithrombin III (AT III) is a natural inhibitor of thrombin, a central procoagulatory factor with pleiotropic activities. Experimental supplementation of AT III improved coagulation parameters and ameliorated organ dysfunction. To determine whether long-term AT III supplementation has beneficial effects on organ function, we conducted a randomized, prospective study in surgical patients with severe sepsis. The study evaluated the long-term effect of AT III supplementation (duration of treatment: 14 days). After randomization (AT III vs. control group), AT III was infused continuously over 14 days to obtain plasma AT III activities > 120%. Forty consecutive patients were recruited (20 AT III/20 control group). Eleven patients had a rapid fatal course and did not met the criterion of a 14 day treatment period. From these 11 patients, 8 patients (5 AT III/3 control group) died within 72 h due to septic shock. The remaining 14 AT III patients and 15 controls survived 14 days and showed no differences in baseline parameters of organ function. AT III caused a disappearance of disseminated intravascular coagulation (DIC) in all patients with DIC, whereas in control patients, the frequency of DIC remained constant (p < .05). In AT III patients a progressive increase in oxygenation index (PaO2/FiO2 ratio) and a continuous decrease in pulmonary hypertension index (mean pulmonary artery pressure/mean arterial pressure (PAP/MAP) ratio) indicated an improvement of lung function (p < .05 vs. control). AT III prevented the continuous rise in total serum bilirubin concentration observed in control patients and diminished the frequency of artificial renal support therapy (p < .05). Long-term supplementation with AT III may improve lung function and prevent the development of septic liver and kidney failure in patients with severe sepsis.
Inthorn
D
D
Department of Surgery, Klinikum Grosshadern, Munich, Germany.
Hoffmann
J N
JN
Hartl
W H
WH
Mühlbayer
D
D
Jochum
M
M
D000328:Adult; D000368:Aged; D000990:Antithrombin III / Q000008:administration & dosage / Q000627:therapeutic use*; D001663:Bilirubin / Q000097:blood; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy / Q000209:etiology; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008099:Liver / Q000187:drug effects / Q000503:physiopathology; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D011446:Prospective Studies; D018805:Sepsis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology
D000990:Antithrombin III; D001663:Bilirubin