Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Ilias, W; List, W; Decruyenaere, J; Lignian, H; Knaub, S; Schindel, F; Keinecke, HO; Heinrichs, H; Thijs, LG.
Antithrombin III in patients with severe sepsis: a pharmacokinetic study.
Intensive Care Med. 2000; 26(6):704-715
Doi: 10.1007%2Fs001340051236
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- Abstract:
- OBJECTIVES: To evaluate the safety, pharmacokinetics, and the practicability of two different antithrombin III (AT III) high-dose regimens in patients with severe sepsis. DESIGN: Prospective, open, randomized, 2 parallel groups, multinational clinical trial. SETTING: Eleven academic medical center intensive care units (ICU) in Austria, Belgium, Denmark, Germany, Norway and Sweden. PATIENTS: Thirty-three patients with severe sepsis who received standard supportive care and antimicrobial therapy, in addition to the administration of AT III. INTERVENTIONS: Patients received an intravenous loading dose of 6,000 IU AT III followed by either intermittent bolus infusions of 1,000 IU AT III every 4 h or a continuous infusion of 250 IU AT III/h for 4 days, resulting in a total dose for both dosage regimens of 30,000 IU AT III. MEASUREMENTS: All patients were evaluated for safety and all but one for pharmacokinetics. RESULTS AND CONCLUSIONS: The administration of AT III was safe and well tolerated. The overall 28-day all-cause mortality was 30% (43% intermittent bolus infusions; 21% continuous infusion). The mean probability of dying according to the SAPS II was 48%. The difference in mortality between both groups was within the range of chance. AT III plasma levels were elevated from low baseline levels to above 120% soon after onset of AT III therapy and remained at these levels for the treatment phase of 4 days. Functional and immunologic levels of AT III corresponded very well. With an overall median volume of distribution of 4.5 l (range: 2.4-6.5 l), AT III only moderately extended beyond plasma. The overall median elimination half-life was 18.6 h (range: 5.1-37.4). Overall, median response was 1.75% per IU/kg (range: 1.14-2.8). The variability of elimination parameters was quite noteworthy (CV = 41-59%), whereas distribution-related parameters showed a moderate variability (CV = 24%). In spite of this variability, both high-dose IV regimens reliably provided AT III levels above 120% for all but one patient. An increased mortality was observed for patients with a distribution volume exceeding 4.5 l (or a response < 1.7% per IU/kg). AT III distribution volumes above 4.5 l might indicate a capillary leak phenomenon. The continuous infusion regimen was slightly preferred by the investigators with regard to practicability.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Aged -
- Aged, 80 and over -
- Antithrombin III - pharmacokinetics
- Area Under Curve - pharmacokinetics
- Biotransformation - pharmacokinetics
- Europe - epidemiology
- Female - epidemiology
- Half-Life - epidemiology
- Humans - epidemiology
- Infusions, Intravenous - epidemiology
- Male - epidemiology
- Middle Aged - epidemiology
- Prognosis - epidemiology
- Sepsis - diagnosis
- Serine Proteinase Inhibitors - pharmacokinetics
- Survival Rate - pharmacokinetics
- Find related publications in this database (Keywords)
- antithrombin III
- sepsis
- pharmacokinetics
- clinical trial