Influence of long-term continuous intravenous administration of pentoxifylline on endothelial-related coagulation in critically ill patients.
OBJECTIVE
To determine the influence of pentoxifylline on endothelial-associated coagulation.


METHODS
Prospective, randomized, placebo-controlled study.


METHODS
A surgical intensive care unit of a university hospital.


METHODS
Consecutive patients (n = 60) with trauma or sepsis secondary to major (nontrauma) surgery. All patients received controlled mechanical ventilation.


METHODS
According to a randomized sequence, the patients either received pentoxifylline continuously over 5 days (1.5 mg/kg/hr iv) (trauma-pentoxifylline group [n = 15], sepsis-pentoxifylline group [n=15] or saline solution as placebo (trauma-control group [n = 15], sepsis-control group [n = 15].


RESULTS
In addition to the standard coagulation screen, thrombomodulin, protein C, (free) protein S, and thrombin-antithrombin plasma concentrations were measured by enzyme-linked immunosorbent assays. Intensive care therapy, hemodynamics, and changes of Acute Physiology and Chronic Health Evaluation II score were comparable for pentoxifylline-treated and nontreated patients. An average dose of 2.5 g/day of pentoxifylline (range 2.2 to 2.9) was infused into the pentoxifylline-treated patients. At baseline, plasma thrombomodulin concentrations were higher in the septic patients than in the trauma patients. Thrombomodulin plasma concentrations increased significantly more in the control patients (trauma: from 38.9 +/- 10.5 to 59.9 +/- 10.1 ng/mL; sepsis: from 49.7 +/- 12.1 to 72.3 +/- 11.2 ng/mL) than in the pentoxifylline-treated patients (trauma: from 37.9 +/- 11.9 to 50.2 +/- 9.2 ng/mL; sepsis from 51.9 +/- 10.1 to 63.3 +/- 10.2). Starting from similar baseline values, protein C concentration increased significantly more in the sepsis-pentoxifylline patients (from 52.0 +/- 11.1% to 69.1 +/- 11.1%) than in the untreated septic patients (from 50.1 +/- 10.0% to 52.5 +/- 9.5%). There were no significant differences between the pentoxifylline-treated and nontreated groups for protein S and thrombin-antithrombin concentrations. Standard coagulation parameters (fibrinogen, activated partial thromboplastin time, antithrombin III) did not differ between these groups either.


CONCLUSIONS
Continuous intravenous administration of pentoxifylline for 5 days beneficially influenced the thrombomodulin/protein C/protein S system in both the trauma and septic patients.
Boldt
J
J
Department of Anesthesiology and Intensive Care Medicine, Justus-Liebig-University Giessen, Germany.
Müller
M
M
Heyn
S
S
Welters
I
I
Hempelmann
G
G
D018806:APACHE; D000328:Adult; D000368:Aged; D001777:Blood Coagulation / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D015601:Injury Severity Score; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D010431:Pentoxifylline / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D011486:Protein C / Q000187:drug effects / Q000378:metabolism; D017293:Protein S / Q000187:drug effects / Q000378:metabolism; D018805:Sepsis / Q000097:blood / Q000628:therapy*; D018180:Thrombomodulin / Q000187:drug effects / Q000378:metabolism; D014947:Wounds and Injuries / Q000097:blood / Q000628:therapy*
D011486:Protein C; D017293:Protein S; D018180:Thrombomodulin; D010431:Pentoxifylline