Intramuscular Bupivacaine Injection Dose-dependently Increases Glutamate Release and Muscle Injury in Rats

ObjectiveLocal anesthetics may cause reversible skeletal muscle injury, which is most common with bupivacaine. Glutamate is present in most skeletal muscles and may regulate muscular metabolic pathways. The aim of study was to examine the changes in intramuscular glutamate level and the severity of myopathy after intramuscular administration of bupivacaine.MethodsTwenty-four male Wistar rats were divided into four groups with six rats per group. A microdialysis probe was implanted in the right tibialis anterior (RTA) muscle in all rats. After equilibrating the microdialysis system for 2 hours, 0.2 mL of normal saline or 0.25%, 0.5% or 1% bupivacaine was injected into the RTA muscle and dialysate samples were collected every 30 minutes for 4 hours. Glutamate was measured by high-performance liquid chromatography. Three days later, the RTA muscle was dissected and the injection site was examined histologically to evaluate the severity of muscle damage on a four-point score, representing no damage to severe myonecrosis.ResultsBupivacaine significantly increase the level of glutamate in a dose- dependent manner in the RTA muscle. Histological assessment of the RTA muscle after bupivacaine administration revealed dose-dependent damage (mean score: normal saline, 0; 0.25% bupivacaine, 1.2±0.6; 0.5% bupivacaine, 1.8±0.7; 1% bupivacaine, 2.4±0.8; p<0.05).ConclusionA single intramuscular injection of bupivacaine induced dose-dependent increases in intramuscular glutamate levels and muscular damage.