Efficacy of lidocaine or bupivacaine combined with ephedrine in rat sciatic nerve block

Background and Objectives: The adrenergic drug ephedrine inhibits Na+ current in cultured cells expressing Na+ channels and provides dose-dependent reversible rat sciatic nerve blockade. The dosage required for peripheral nerve blockade in humans would cause unacceptable cardiovascular side effects. We therefore hypothesized that either lidocaine or bupivacaine would show synergy with ephedrine in a rat sciatic nerve block model, allowing a dose reduction and limiting side effects while improving efficacy. Methods: Sciatic nerves of anesthetized rats were exposed by lateral incision of the thighs; 0.2 mL of different concentrations of the following drugs was injected subfascially: bupivacaine, lidocaine, and ephedrine alone and bupivacaine or lidocaine combined with ephedrine (n = 8 per group). After animals recovered from anesthesia, a blinded investigator evaluated motor blockade (push against a balance) and sensory/nociceptive blockade (to pinch of the fifth toe) at predefined time intervals. Results: Ephedrine combined with bupivacaine interacted additively for both motor and sensory blockade, and ephedrine combined with lidocaine interacted antagonistically (subadditive) for sensory blockade and additively for motor blockade. Conclusions: A combination of ephedrine with either lidocaine or bupivacaine is unlikely to allow a significant dose reduction because of a lack of synergy. Furthermore, the cardiovascular side effects will limit the maximal tolerable dosage of ephedrine.