Evaluation of the effects of epidural bupivacaine on coagulation system by using thromboelastometry in women with gynecologic malignancies

Purpose of investigation: In this study, epidural local anesthetic drugs are scheduled to examine their effects on the coagulation cascade. Materials and Methods: A total of 40 patients with gynecologic tumors were eligible. Epidural catheter was introduced into the epidural space of all patients. The patients were randomized into control and study groups. Before the induction of anesthesia, saline five cc, in control group and 25 mg bupivacaine was given via epidural catheter in study group. An epidural morphine infusion (0.2 mg/hour) was started in control group and an epidural infusion (0.2 mg/hour morphine + 0.75 mg/hour bupivacaine) was in study group. Before induction of anesthesia and postoperative 24 hours, thromboelastometry (TEG) analysis was performed. Results: Ellagic acid/phospholipid activation clotting time (INTEM CT), which was measured in the postoperative period, was significantly shorter in study group. Conclusion: Bupivacaine causes platelet dysfunction induced by various agonists, while neither this primary hemostatic abnormality nor other coagulation abnormalities can be detected by rotation thromboelastometry (ROTEM).

Thromboelastometry; Bupivacaine; Coagulation; Epidural analgesia.

[1] Moraca R.J., Sheldon D.G., Thirlby R.C.: “The role of epidural anesthesia and analgesia in surgical practise”. Ann. Surg., 2003, 238, 663.

[2] Tuman K.J., McCarthy R.J., March R.J., DeLaria G.A., Patel R.V., Ivankovich A.D.: “Effects of epidural anesthesia and analgesia on coagulation and outcame after major vascular surgery’’. Anesth. Analg., 1991, 73, 696.

[3] Alon E., Jaquenod M., Schaeppi B.: “Postoperative epidural versus intravenous patient controlled analgesia”. Minerva Anestesiol., 2003, 70, 443.

[4] Kohrs R., Hoenemann C.W., Feirer N., Durieux M.E.: “Bupivacaine inhibits whole blood coagulation in vitro”. Reg. Anesth. Pain Med., 1999, 24, 326.

[5] Borg T., Modig J.: “Potantial antithrombotic effects of local anaesthetics due to their inhibition of platelet aggregation”. Acta Anaesthesiol. Scand., 1985, 29, 739.

[6] Prowse C., Pepper D., Dawes J.: “Prevention of the platelet alphagranule release reaction by membrane-active drugs”. Thromb. Res., 1982, 25, 219.

[7] Feinstein M.B., Fiekers J., Fraser C.: “An analysis of the mechanism of local anesthetic inhibition of platelet aggregation and secretion”. J. Pharmacol. Exp. Ther., 1976, 197, 215.

[8] Honemann C.W., Podranski T., Lo B., Yanovitch M., Nasr N., Durieux M.: “Local anesthetics’ effects on thromboxane A2 signaling”. Anesthesiology, 1998, 3A, A886.

[9] Tobias M.D., Henry C., Augostide Y.G.: “Lidocaine and bupivacaine exert differential effects on whole blood coagulation”. J. Clin. Anesth., 1999, 111, 52.

[10] Benzon H.T., Wong C.A., Wong H.Y., Brooke C., Wade L.: “The effect of low-dose bupivacaine on postoperative epidural fentanyl analgesia and thromboelastography”. Anesth. Analg., 1994, 79, 911.

[11] Akay O.M., Ustuner Z., Canturk Z., Mutlu FS., Gulbas Z.: “Laboratory investigation of hypercoagulability in cancer patients using rotation thrombelastography”. Med. Oncol., 2008, 26, 358.

[12] Wehrum M.J., Hines J.F., Hayes E.B., Kost E.R., Hall K.L., Paidas M.J.: “Comparative assessment of hypercoagulability in women with and without gynecologic malignancies using the thromboelastography coagulation analyzer”. Blood Coagul. Fibrinolysis, 2010, 21, 140.

[13] Rodgers A., Walker N., Schug S., McKee A., Kehlet H., van Zundert A., et al.: “Reduction of postoperative mortality morbidity with epidural or spinal anaesthesia:results from overview of randomized trials”. Br. Med. J., 2000, 321, 1493.

[14] Gibbs N.M., Sear J.W.: “Effects of ketorolac, bupivacaine and lowdose heparin on thromboelastographic variables in vitro”. Br. J. Anaesth., 1995, 75, 27.

[15] Vasconceles A., Mathias L.A.: “Effects of pudental nerve, epidural and subarachnoid block on coagulation of pregnant women”. Rev. Bras. Anestesiol., 2008, 58, 95.

[16] Hsiao G., Shen M.Y., Fang C.L., Chou D.S., Lin C.H., Chen T.F., et al.: “Morphine-potentiated platelet aggregation in vitro and platelet plug formation in in vivo experiments” J. Biomed. Sci., 2003, 10, 292.