Bupivacaine inhibits whole blood coagulation in vitro.
OBJECTIVE
Epidural anesthesia decreases the risk of postoperative deep venous thrombosis in selected patients. Intravascular local anesthetic levels resulting from epidural anesthesia may contribute to this effect by impacting coagulation. We studied the effects of bupivacaine (1-10 micromol/L) on whole blood coagulation measured by thrombelastography (TEG) and activated clotting time (ACT).


METHODS
We incubated whole blood with bupivacaine (1, 2, and 10 micromol/L) or Tyrode's solution (control) for 60 minutes and measured TEG and ACT clotting parameters.


RESULTS
Bupivacaine (1 or 10 micromol/L) prolonged ACT when compared with control. The thromboxane A2 (TX) receptor antagonist SQ29548 also prolonged ACT significantly. The combination of SQ29548 and bupivacaine was equally effective as bupivacaine alone, compatible with the hypothesis that bupivacaine at these concentrations blocks TX signaling. Because SQ29548 + bupivacaine prolonged ACT more than did SQ29548 alone, bupivacaine likely inhibits processes in addition to TX signaling. This was evaluated further using TEG. After incubation with 2 microm bupivacaine, TEG reaction time and clot growth time increased significantly, and maximal amplitude decreased.


CONCLUSIONS
Bupivacaine in clinically relevant concentrations influences whole blood clotting characteristics as measured by TEG and ACT. Thromboxane receptor antagonism increases ACT, confirming a role for TX in coagulation. Bupivacaine may also inhibit TX signaling, but seems to block additional factors as well. These findings might partly explain the beneficial effects of epidural anesthesia on postoperative thrombotic events.
Kohrs
R
R
Department of Anesthesiology, University of Virginia Health System, Charlottesville 22906-0010, USA.
Hoenemann
C W
CW
Feirer
N
N
Durieux
M E
ME
D000767:Anesthesia, Epidural; D000779:Anesthetics, Local / Q000494:pharmacology*; D000925:Anticoagulants / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002045:Bupivacaine / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors / Q000502:physiology; D013916:Thrombelastography; D014914:Whole Blood Coagulation Time
D000779:Anesthetics, Local; D000925:Anticoagulants; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D017482:Receptors, Thromboxane; C045749:SQ 29548; D002045:Bupivacaine