Canadian Journal of Anesthesia, Vol 30, 32-36, Copyright © 1983 by Canadian Anesthesiologists' Society

Flunitrazepam Protects Mice Against Lidocaine and Bupivacaine-Induced Convulsions

¹ Department of Anaesthesia, Hadassah University Hospital, Mount Scopus, Israel

Address Correspondence to: E. Vatashsky MD, Dept. of Anaesthesia, Hadassah University Hospital, Mount Scopus, POB 24035, Jerusalem 91240, Israel.

Flunitrazepam and diazepam in two different dosages (ED₅₀, ED₂₅) were compared for their ability to protect Sabra race mice from convulsions induced either by lidocaine or bupivacaine injected intraperitoneally. While 10 of 20 control mice injected with distilled water convulsed after both lidocaine and bupivacaine, nonconvulsed when pretreated with ED₅₀ flunitrazepam or ED₅₀ diazepam. Survival rates were, however, significantly different depending on the pretreatment. Forty per cent of mice died after the injection of lidocaine CD₅₀ (median convulsive dose) when pretreated with diazepam ED₅₀, while none died when flunitrazepam ED₅₀ was used. Similarly, with bupivacaine CD₅₀, mortality was higher (70 per cent) after pretreatment with diazepam ED₅₀ than with flunitrazepam ED₅₀ (20 per cent mortality). Diazepam ED₂₅ did not protect the mice against convulsions, which occurred in 30 per cent of animals, 20 per cent of whom died in both local anaesthetic groups. After flunitrazepam ED₂₅, convulsions occurred in ten per cent of the bupivacaine group, but in none of those administered lidocaine. No mice died in any of the groups pretreated with flunitrazepam. These data suggest that flunitrazepam might be a safer agent than diazepam in preventing central nervous system toxicity due to local anaesthetics.

Key Words: ANAESTHETICS, LOCAL: lidocaine, bupivacaine • ANTICONVULSANTS: flunitrazepam, diazepam • COMPLICATIONS: convulsions