Effects of recombinant human activated protein C on the fibrinolytic system of patients undergoing conventional or tight glycemic control.
OBJECTIVE
Recombinant human activated protein C (rh-APC) and tight glycemic control (TGC) have been shown to reduce mortality in septic patients. Both interventions can reduce the plasma concentration and/or activity of the most powerful suppressor of fibrinolysis, plasminogen activator inhibitor-1 (PAI-1). Our aim was to evaluate the effects on the fibrinolytic system after the administration of rh-APC in septic patients undergoing conventional or TGC.


METHODS
Posthoc analysis of data was collected from 90 patients with severe sepsis/septic shock, randomized to either conventional or TGC groups. Independent of these treatments, patients with at least two organ dysfunctions simultaneously received rh-APC. Plasma levels of multiple biochemical markers for fibrinolysis, coagulation, and inflammation were determined every day for the 1st week and then on study days 9, 11, 13, 18, 23, and 28. Clinical data and sepsis-related organ failure assessment (SOFA) scores were also recorded.


RESULTS
Patients who had received rh-APC exhibited significantly more impairments in fibrinolysis at baseline (PAI-1 activity 49.76 [24.61-71.82] vs 21.92 [6.47-55-83] IU/mL, P=0.03). The reductions in plasma PAI-1 activity over time associated with rh-APC treatment were different according to whether the treatment was administered to patients undergoing conventional or TGC (P=0.01). However, the most prominent reductions were in patients undergoing conventional glycemic control. Significant interactions between the two study interventions were also found for PAI-1 concentration (P<0.001), C-reactive protein (P=0.02), and interleukin-6 levels (P<0.001).


CONCLUSIONS
Both rh-APC and TGC appear to improve fibrinolysis in septic patients. The reduction in the impairment of fibrinolysis associated with rh-APC treatment seems greater in patients undergoing conventional glycemic control than in those undergoing TGC.
Polli
F
F
Institute of Anesthesia and Intensive Care, University of Milan, Milan, Italy. gattinon@policlinico.mi.it
Savioli
M
M
Cugno
M
M
Taccone
P
P
Bellani
G
G
Spanu
P
P
Pesenti
A
A
Iapichino
G
G
Gattinoni
L
L
D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011486:Protein C / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D018805:Sepsis / Q000097:blood / Q000188:drug therapy; D016896:Treatment Outcome
D001786:Blood Glucose; D005343:Fibrinolytic Agents; D017395:Plasminogen Activator Inhibitor 1; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated