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Emulsified Isoflurane Increases Convulsive Thresholds of Lidocaine and Produces Neural Protection After Convulsion in Rats

BACKGROUND:Local anesthetic–induced convulsions remain a concern of anesthesiologists when performing regional anesthesia. Our previous study found that the lidocaine requirement for IV regional anesthesia was reduced with coadministration of emulsified isoflurane. We designed this study to examine whether emulsified isoflurane could increase the convulsive threshold of lidocaine and produce protection after a lidocaine-induced convulsion. METHODS:In experiment 1, the median convulsive dose of lidocaine with or without the addition of emulsified isoflurane was determined using the up-and-down method. In experiment 2, emulsified isoflurane (0.032 mL/kg for isoflurane), midazolam (1.6 mg/kg), 30% Intralipid (solvent of emulsified isoflurane) or saline was infused to treat lidocaine-induced convulsions, respectively. Convulsive behavior was scored by the modified Racine scale. Cognitive function and the pathology of hippocampus cornu ammonis 3 pyramid neurons of rats were evaluated on days 1, 3, 5, and 7 after convulsions. RESULTS:In experiment 1, the median convulsive dose of lidocaine alone producing convulsions was 18.7 ± 2.6 mg/kg, and it was increased to 22.7 ± 2.6 (P = 0.010) and 26.7 ± 2.6 mg/kg (P < 0.001) with coadministration of emulsified isoflurane at doses of 0.016 and 0.032 mL/kg isoflurane, respectively. In experiment 2, both emulsified isoflurane and midazolam significantly suppressed lidocaine-induced tonic-clonic seizures. Rats treated with emulsified isoflurane regained full consciousness (convulsive score = 0) significantly earlier than rats treated with midazolam (8.7 ± 2.4 vs 19.5 ± 3.9 minutes, P < 0.001). Cognitive impairment and hippocampus cornu ammonis 3 pyramid neuron abnormalities were found after convulsions and improved with the administration of both emulsified isoflurane and midazolam. CONCLUSION:Emulsified isoflurane increased the convulsive threshold of lidocaine and preserved neurological function in rats experiencing lidocaine-induced convulsions.