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Correspondence  |   November 2004
Questioning the Mechanism of Nerve Injury
Author Affiliations & Notes
  • Norihito Kitagawa, M.D
    *
  • * Saga Medical School, Nabeshima, Saga, Japan.
Article Information
Correspondence
Correspondence   |   November 2004
Questioning the Mechanism of Nerve Injury
Anesthesiology 11 2004, Vol.101, 1249-1250. doi:
Anesthesiology 11 2004, Vol.101, 1249-1250. doi:
In Reply:—
We thank Lambert et al.  for their interest in our article1 and stimulating comments. We would like to take the opportunity to address the issues raised by their insights.
Lambert et al.  suggest that the mechanism of local anesthetic neurotoxicity is unrelated to membrane disruption caused by the detergent nature of highly concentrated local anesthetics, instead resulting from breakdown of the sodium conductance system (i.e.  , absence of compound action potential generation) despite the presence of an intact membrane structure and normal ionic gradients and compound resting potential. The basis for their contention is that, although both compound action potential and compound resting potential in excised sciatic nerves of the bullfrog disappear permanently after bathing in sodium lauryl sulfate (typical detergent) solution,2 compound resting potential recovers without compound action potential recovery after bathing in 5% lidocaine solution for 15 min, as noted in their earlier electrophysiologic study.3 
However, the study cited as grounds for their question about our conclusions seems to have an inherent limitation in that the period for bathing the specimen in 5% lidocaine is 15 min. Kanai et al.  4 reported a similar study using a single crayfish axon and demonstrated that although resting potential recovers after bathing in 80 mm lidocaine solution for 15 min, resting potential permanently disappears after bathing for 30 min. They suggested that highly concentrated lidocaine causes membrane disruption and indicated in that time-dependent study that sufficient exposure (≥ 30 min) was needed for membrane disruption to be induced by lidocaine. Ready et al.  5 also demonstrated successfully that lidocaine at a concentration of 4% or higher induces histopathologic changes in spinal nerves during a dose-dependent study of a spinal anesthesia model in rabbits. The fact that highly concentrated lidocaine causes membrane disruption is thus not in doubt.
We advocated in our article that the mechanism of membrane disruption induced by highly concentrated local anesthetics would result from the detergent nature of these agents.1 From the perspective of results from various investigators, including Lambert et al.  , we speculate that an intermediate step may exist in the membrane disruption dynamics induced by 5% lidocaine, with resting membrane potential maintained despite permanent inhibition of action potential. The electrophysiologic phenomena described by Lambert et al.  may represent an early phase in the sequence of neurotoxic dynamics induced by 5% lidocaine.
* Saga Medical School, Nabeshima, Saga, Japan.
References
Kitagawa N, Oda M, Totoki T: Possible mechanism of irreversible nerve injury caused by local anesthetics: Detergent properties of local anesthetics and membrane disruption. Anesthesiology 2004; 100:962–7Kitagawa, N Oda, M Totoki, T
Lambert LA, Lambert DH, Strichartz GR: Irreversible conduction block in isolated nerve by high concentrations of local anesthetics. Anesthesiology 1994; 80:1082–93Lambert, LA Lambert, DH Strichartz, GR
Rando TA, Wang GK, Strichartz GR: The interaction between the activator agents batrachotoxin and veratridine and the gating processes of neuronal sodium channels. Mol Pharmacol 1986; 29:467–77Rando, TA Wang, GK Strichartz, GR
Kanai Y, Katsuki H, Takasaki M: Graded, irreversible changes in crayfish giant axon as manifestations of lidocaine neurotoxicity in vitro. Anesth Analg 1998; 86:569–73Kanai, Y Katsuki, H Takasaki, M
Ready LB, Plumer MH, Haschke RH, Austin E, Sumi SM: Neurotoxicity of intrathecal local anesthetics in rabbits. Anesthesiology 1985; 63:364–70Ready, LB Plumer, MH Haschke, RH Austin, E Sumi, SM