Etomidate and thiopental inhibit platelet function in patients undergoing infrainguinal vascular surgery.
BACKGROUND
Postoperative platelet hyperaggregability following general anesthesia has been reported in patients undergoing major vascular surgery. In contrast, since anesthetic agents inhibited platelet function both in vitro and in vivo, an increased risk for postoperative bleedings due to prolonged platelet dysfunction has been discussed. Nevertheless, data describing platelet-affecting properties of induction agents such as etomidate and thiopental in patients undergoing major vascular surgery are lacking.


METHODS
Platelet function was determined at 0, 2, 20, and 200 microg/ml thiopental and at 0, 0.2, 2, 20 microg/ml etomidate in vitro in blood samples drawn from 16 patients suffering from severe occlusive arterial disease. In addition, 30 patients undergoing vascular surgery were investigated before (PRE) and after anesthesia induction (T0) either with etomidate (ETO group, n=16) or thiopental (THIO group, n=14), and 2 h after the beginning of surgery (T2). Platelet function was determined according to platelet aggregation, in vitro bleeding time, and flow cytometric measurements.


RESULTS
In vitro, P-selectin expression was inhibited by etomidate at 2 and 20 microg/ml (-28% and -38%, respectively) and also by thiopental at 200 microg/ml (-27%). In patients undergoing vascular surgery, anesthesia induction in the ETO group resulted in a 31% prolongation of the in vitro bleeding time and an inhibition of ADP- and collagen-induced platelet aggregation (-30% and -17%, respectively) and of P-selectin expression (-25%) at T0. In the THIO group, only ADP-induced platelet aggregation was affected (-16%). At T2, all parameters had reached PRE level again in both groups. Furthermore, in comparison with the THIO group, operation time was significantly prolonged and transfusion volume was significantly increased in the ETO group. In addition, platelet count and hematocrit significantly decreased at T2, whereas levels of tPA, PAI-1, fibrinogen and antithrombin III and partial thromboplastin time remained unchanged in both groups during the study period.


CONCLUSIONS
In the present study, etomidate and, to a minor extent, thiopental offered significant platelet inhibitory properties. Anesthetic-induced platelet inhibition may lead to higher transfusion rates and prolonged operation times. Therefore, anesthetic-related platelet inhibitory properties should be considered when searching for the anesthetic agent of choice, especially in patients with compromised hemostasis and co-existing bleeding disorders.
Gries
A
A
Department of Anesthesiology, University of Heidelberg, Germany. ANDRE-GRIES@med.uni-heidelberg.de
Weis
S
S
Herr
A
A
Graf
B M
BM
Seelos
R
R
Martin
E
E
Böhrer
H
H
D000368:Aged; D018686:Anesthetics, Intravenous / Q000009:adverse effects*; D001157:Arterial Occlusive Diseases / Q000601:surgery; D001760:Bleeding Time; D004311:Double-Blind Method; D005045:Etomidate / Q000009:adverse effects*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006400:Hematocrit; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000096:biosynthesis; D010974:Platelet Aggregation / Q000187:drug effects*; D010976:Platelet Count; D011485:Protein Binding; D013874:Thiopental / Q000009:adverse effects*; D014656:Vascular Surgical Procedures
D018686:Anesthetics, Intravenous; D019007:P-Selectin; D005340:Fibrinogen; D013874:Thiopental; D005045:Etomidate