Epinephrine increases the neurotoxic potential of intrathecally administered lidocaine in the rat. (Department of Anesthesia and Preoperative Care, University of California, San Francisco, CA) Anesthesiology. 2001;94:876–881.

This study investigated whether adding epinephrine increases functional impairment or histologic damage induced by spinal administration of lidocaine in the rat. Eighty rats were divided into 4 groups to receive an intrathecal injection of normal saline containing 5% lidocaine, 5% lidocaine with 0.2 mg/mL of epinephrine, 0.2 mg/mL of epinephrine, or normal saline alone. Animals were assessed for persistent sensory impairment using the tail‐flick test administered 4 to 7 days after infusion. Animals were then killed, and the spinal cord and nerve roots were prepared for neuropathologic evaluation. Rats given 5% lidocaine developed persistent sensory impairment and histologic damage, and the addition of epinephrine resulted in a further significant increase in injury. Sensory function in animals given epinephrine without anesthetic was similar to baseline and did not differ from saline. Histologic changes in animals treated with epinephrine alone did not differ significantly from saline controls. Conclude the neurotoxicity of intrathecally administered lidocaine is increased by the addition of epinephrine. When making clinical recommendations for maximum safe intrathecal dose of this anesthetic, one may need to consider whether the solution contains epinephrine. Comment by Octavio Calvillo, M.D., Ph.D. The authors studied the neurotoxicity of epinephrine added to lidocaine injected intrathecally in rats. The animals were allocated to four groups of 20 rats each, receiving: normal saline alone, normal saline and 5% lidocaine, 5% lidocaine with epinephrine [0.2 mg/ml] in saline or epinephrine 0.2 mgml in saline. The animals were assessed for sensory deficits 4 and 7 days after infusion and then sacrificed. The spinal cords and nerve roots were prepared for neuropathological evaluation. Sections obtained from animals treated with lidocaine, lidocaine with epinephrine. Rats given 5% lidocaine developed persistent sensory impairment and histological evidence of damage, the addition of epinephrine, resulted in further damage. Histological changes in animals treated with epinephrine alone did not differ significantly from saline controls. The authors concluded that the neurotoxicity of intrathecally‐administered lidocaine is increased by the addition of epinephrine. They raised the possibility that the neurotoxicity of commercially available epinephrine may be due to the bisulfite contained therein, this chemical has been associated with neurotoxicity.