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Comparison of acute central nervous system and cardiovascular toxicity of 2‐chloroprocaine and prilocaine in the rat
Author(s) -
Rosenberg P. H.,
Zou J.,
Heavner J. E.
Publication year - 1993
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/j.1399-6576.1993.tb03803.x
Subject(s) - medicine , prilocaine , toxicity , central nervous system , anesthesia , pharmacology , local anesthetic
In this study, we compared the central nervous system and cardiovascular system toxicity of i.v. administered 0.5% 2‐chloroprocaine (N=10) and 0.5% prilocaine (N=10) in lightly anaesthetised rats. Arterial blood pressure, ECG and EEG were continuously recorded. Prilocaine produced the predetermined toxic end‐points (i.e. seizure activity on EEG, isoelectric EEG, cardiac arrhythmia on ECG, asystole on ECG) at significantly lower doses than 2‐chloroprocaine ( P < 0.05). The mean dose of prilocaine producing asystole was 166 mg · kg ‐1 (± 45 mg · kg ‐1 , s.d.) vs. 255 mg · kg ‐1 (± 42 mg · kg ‐1 ) for 2‐chloroprocaine ( P < 0.01). The rate of decrease of mean arterial blood pressure during the infusion was significantly faster with prilocaine ( P < 0.01). Typically, arrhythmias did not appear until just before asystole, suggesting that neither of the local anaesthetics possessed marker arrhythmogenic properties. It is concluded that prilocaine is slightly more toxic than 2‐chloroprocaine in the rat, but that both local anaesthetics have a wide margin of safety. Doses producing seizure activity on the EEG (prilocaine 53 mg · kg ‐1 and 2‐chloroprocaine 70 mg · kg ‐1 , on average) are much higher than those used in clinical practice (usually < 10 mg · kg ‐1 ).