Ph. Rosenberg et al., COMPARISON OF ACUTE CENTRAL-NERVOUS-SYSTEM AND CARDIOVASCULAR TOXICITY OF 2-CHLOROPROCAINE AND PRILOCAINE IN THE RAT, Acta anaesthesiologica Scandinavica, 37(8), 1993, pp. 751-755
In this study, we compared the central nervous system and cardiovascul
ar 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 pro
duced the predetermined toxic endpoints (i.e. seizure activity on EEG,
isoelectric EEG, cardiac arrhythmia on ECG, asystole on ECG) at signi
ficantly lower doses than 2-chloroprocaine (P < 0.05). The mean dose o
f 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 rat
e of decrease of mean arterial blood pressure during the infusion was
significantly faster with prilocaine (P < 0.01). Typically, arrhythmia
s did not appear until just before asystole, suggesting that neither o
f the local anaesthetics possessed marker arrhythmogenic properties. I
t is concluded that prilocaine is slightly more toxic than 2-chloropro
caine 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).