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Local anesthetic-induced toxicity may be modified by low doses of flumazenil
1Laboratoire de Pharmacologie Médicale, Faculté de Médecine de Marseille, France.
Abstract:
The purpose of this study was to investigate the influence of flumazenil on local anesthetic-induced acute toxicity. For each of the three tested anesthetics (etidocaine, mepivacaine and lidocaine) 6 groups of mice were treated by a single dose of flumazenil (0.125, 0.25, 0.5, 1 and 2 mg/kg), or an equal volume of saline, 15 minutes before the injection of the anesthetic (etidocaine: 50 mg/kg, mepivacaine: 110 mg/kg and lidocaine: 115 mg/kg). The convulsant activity, the time of latency to convulse and the mortality rate were assessed in each group. The local anesthetic-induced mortality was not significantly modified by flumazenil. The convulsant activity of lidocaine and mepivacaine was significantly increased by flumazenil but not for etidocaine. Also, increasing doses of flumazenil decreased the time of latency to obtain lidocaine-induced convulsions. This effect was not obtained with etidocaine or mepivacaine.
Insights
Flumazenil did not alter local anesthetic-induced mortality in mice. However, flumazenil increased the convulsant activity of lidocaine and mepivacaine, while decreasing the onset time for lidocaine convulsions.
Area of Science:
- Pharmacology
- Toxicology
- Neuroscience
Context:
- Local anesthetics are widely used for pain management.
- Acute toxicity, including seizures and cardiovascular collapse, can occur with high doses.
- Flumazenil is a benzodiazepine receptor antagonist.
Purpose:
- To determine the effect of flumazenil on the acute toxicity of etidocaine, mepivacaine, and lidocaine in a mouse model.
- To assess flumazenil's influence on mortality, convulsant activity, and latency to convulsions.
Summary:
- Mice received varying doses of flumazenil or saline before anesthetic injection.
- Flumazenil did not significantly affect the mortality rates induced by the tested local anesthetics.
- Flumazenil significantly enhanced the convulsant activity of lidocaine and mepivacaine, but not etidocaine.
- Increasing flumazenil doses reduced the latency to lidocaine-induced convulsions.
Impact:
- Flumazenil may potentiate the central nervous system side effects of certain local anesthetics like lidocaine and mepivacaine.
- Findings suggest careful consideration when using flumazenil in patients experiencing toxicity from these specific local anesthetics.
- Further research is needed to elucidate the mechanisms underlying flumazenil's pro-convulsant effects with certain anesthetics.