Local anesthetics: importance of mode of application, concentration and adrenaline for the appearance of nerve lesions. An experimental study of axonal degeneration and barrier damage after intrafascicular injection or topical application of bupivacaine (Marcain).

Local anesthetics are designed for application in or close to nerve tissue. In spite of their wide clinical use, surprisingly few investigations deal with the neural toxicity of modern local anesthetics. In this experimental study, the effects were investigated of intrafascicular or topical application of the long-acting local anesthetic bupivacaine on the rabbit sciatic nerve. Axonal degeneration was histologically evaluated and a fluorescence-microscopic technique used to detect lesions in the blood-nerve barrier. Topical application of bupivacaine in clinically recommended concentrations around the nerve caused no detectable nerve injury, while intrafascicular injections caused considerable axonal degeneration and damaged the blood nerve barrier. Axonal degeneration was the same after injection of physiologic saline solution and bupivacaine 0.5%, but it increased with increasing bupivacaine concentration and especially with the addition of adrenaline. On the other hand, the acute effects of intrafascicular injection, as visualized in the barrier experiments, changed little with the addition of adrenaline, indicating that it is the injection trauma itself which is deleterious. It is concluded that intraneural injections should be avoided and that plain bupivacaine solutions should be routinely used.