Basic Science (21)

Abstract

Neurotoxicity of intrathecally administered tetracaine commences at posterior roots near entry into the spinal cord. (Kitasato University, Kanagawa, Japan) Reg Anesth Pain Med 2000;25:372–379.This study examined the histopathologic effects of intrathecally administered tetracaine. Sixty Wistar rats randomly received either 20%, 10%, 5%, 3%, 1%, 0.5%, or 0% tetracaine dissolved in 10% glucose solution or no solution via a chronically implanted intrathecal catheter. The spinal cord at L1, posterior and anterior roots and cauda equina were excised 5 days later, sectioned, processed, and prepared for light and electron microscopic examinations. Rats treated with tetracaine at 10% or 20% developed lesions in the posterior white matter and posterior roots. Rats injected with 3% or 5% tetracaine developed lesions, which began in the posterior roots close to the spinal cord and extended to the posterior white matter. The lesions were characterized by axonal degeneration. Injections of 1% of tetracaine did not cause any pathological changes. The results suggest that the initial target of intrathecal tetracaine neurotoxicity may be the posterior roots at their entry into the spinal cord, where the axons are devoid of myelin sheath and thus represent a sensitive area for neurotoxic change. Comment by James E. Heavner, DVM, PhD.The reassuring aspect of this study is that no significant lesions were found when rats were given clinically used concentrations of tetracaine. The investigators do make a case that clinically used concentrations of tetracaine might be neurotoxic in humans based on the observation that the duration of action of tetracaine is shorter in rats than in humans. The distribution of the lesions is curious in that 10% tetracaine produced lesions in the posterior rootlets and in the posterior rootlet entry zone, but did not produce lesions in the fasciculus gracilis. The implication is that rootlets posterior to lamina L1 (the L1 segment that was examined) that were destroyed do not project into the fasciculus gracilis. One would expect that destruction of lamina L2 posterior rootlets that projected into the fasciculus gracilis would produce lesions visible at the EM level at L1 5 days after damage. The absence of lesions in the L1 fasciculus gracilis puzzles me. I am also puzzled by the suggestion that all posterior rootlets loose their myelin sheath just before entry into the posterior white matter of the spinal cord (Obersteiner‐Redlich zone). To my knowledge, most posterior rootlets do not have this nonmyelinated zone and; therefore, the absence of the myelin would make only a portion of the posterior rootlets vulnerable to tetracaine neurotoxicity as suggested by the authors. In short, there are some anatomical relationships that do not fit with the distribution of lesions described by the investigators.