High-dose antithrombin III treatment of severely injured patients: results of a prospective study.
BACKGROUND
Antithrombin III (AT III) treatment has been shown to reduce disseminated intravascular coagulation and to inhibit thrombin, which plays a central role in the activation of platelets and other inflammatory systems in conditions with severe inflammation. The objective of this study was to evaluate the influence of early and high-dose administration of AT III to patients with severe multiple injuries on the inflammatory response and outcome.


METHODS
In a placebo-controlled, double-blind study, 40 consecutive patients with Injury Severity Scores of 29 or greater who met the inclusion criteria were randomized to receive either AT III or placebo within 360 minutes after trauma. Twenty patients were administered AT III for a period of 4 days, aiming to achieve AT III concentrations of 140% of normal.


RESULTS
The AT III and placebo groups were comparable with respect to Injury Severity Score, age, incidence of blood pressure less than 80 mm Hg on admission, initial base deficit, and start of the test drug. The patients in the AT III group received a total of about 20,000 IU during the first 4 days. AT III levels of 130 to 140% could be achieved by this regimen, whereas in the control group the AT III concentration averaged about 70%. In the AT III group prothrombin tended to be elevated and prothrombin fragment F1+2 as well as thrombin-AT III complex tended to be lower on the first day. No differences between groups, however, could be observed with respect to partial thromboplastin time, prothrombin time, platelets, plasminogen activator inhibitor I, soluble tumor necrosis factor receptor II, neutrophil elastase, interleukin (IL)-1 receptor antagonist, IL-6, and IL-8. Mortality (15 vs. 5%), incidence of respiratory failure (55 vs. 55%), duration of mechanical ventilation (13 vs. 12 days), and length of stay in the surgical intensive care unit (19 vs. 21 days) were also similar in both treatment groups. The duration of organ failure, however, was shorter in the patients receiving AT III.


CONCLUSIONS
The early and high-dose administration of AT III to patients with severe blunt trauma appears not to attenuate the posttraumatic inflammatory response or to significantly improve outcome.
Waydhas
C
C
Department of Surgery, Klinikum Innenstadt, Ludwig-Maximilians-University, Munich, Germany.
Nast-Kolb
D
D
Gippner-Steppert
C
C
Trupka
A
A
Pfundstein
C
C
Schweiberer
L
L
Jochum
M
M
D000328:Adult; D000990:Antithrombin III / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007249:Inflammation; D015601:Injury Severity Score; D007902:Length of Stay / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000209:etiology; D009104:Multiple Trauma / Q000150:complications / Q000188:drug therapy*; D011446:Prospective Studies; D012121:Respiration, Artificial / Q000706:statistics & numerical data; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D013997:Time Factors
D015842:Serine Proteinase Inhibitors; D000990:Antithrombin III