Double-Blind, Placebo-Controlled Study of Myotoxicity and Neurotoxicity of Bupivacaine in Rats

Abstract

When penetrating into the cell, local anesthetics affect some structures and processes, in addition to blocking sodium channels, leading to the development of cell damage. The aim of the article was to study the damaging effect of bupivacaine on the sciatic nerve and biceps femoris in rats. The study is double-blind and placebo-controlled. We used 0.9% sodium chloride as the placebo. The studied concentrations of bupivacaine were 0.2%, 0.5%, 0.75%, and 1%. We performed perineural introduction of 0.2 ml into the sciatic nerve and administered 0.2 ml into the biceps femoris muscle under the ultrasound guidance. The samples were taken twice: 1 hour after administration, and over 14 days. Cell necrosis or apoptosis were not found in the muscle and nerve after the 0.9% sodium chloride administration; occasional inflammatory cells were detected. Introduction of all concentrations of bupivacaine induced damage and inflammatory infiltration of muscle tissue and neural structures compared with 0.9% sodium chloride solution. Dystrophic changes and neutrophilic infiltration were detected in nerve fibers. Perimuscular edema, apoptosis, polychromasia, necrosis, disappearance of cross-striation of muscles, clusters of inflammatory cells were found in the biceps femoris. Signs of damage and inflammatory infiltration decreased, but continued to persist over 14 days. The study showed the presence of neurotoxicity and myotoxicity of all concentrations of bupivacaine compared to a 0.9% sodium chloride solution. It was revealed that signs of damage and inflammatory infiltration persisted 14 days after the administration of bupivacaine.

Keywords

• albino rats
• bupivacaine
• local anesthetic
• myotoxicity
• neurotoxicity
• skeletal muscle
• sciatic nerve