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Exp Ther Med. 2015 Sep;10(3):1133-1138. Epub 2015 Jun 24.

Lipid emulsion mitigates local anesthesia-induced central nervous system toxicity in rats.

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Department of Anesthesiology and Pain, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, P.R. China.


The aim of the present study was to investigate the effect of intravenously administered lipid emulsion on local anesthetic (LA)-induced central nervous system (CNS) toxicity. A total of 100 male Sprague Dawley rats were allocated at random into the following groups: Sham (A), lidocaine (B), levobupivacaine (C) and ropivacaine (D). Groups B-D were each subdivided into three subgroups: Toxic, post-conditioning and pre-conditioning. Intracerebroventricular injections of 0.9% normal saline (sham group) or LA were administered via microsyringe; in addition, a 20% lipid emulsion was injected into tail vein prior to the LA injection (pre-conditioning subgroups) or following rat respiratory arrest (post-conditioning subgroups). The heart rate, blood pressure, neurological behavior scores, neuronal density and time from LA injection to respiratory arrest, apnea and start of arrhythmia were measured. Rats in the toxic groups died due to respiratory arrest following the injection of LA into the lateral ventricle. Rats in the post-conditioning subgroups were resuscitated from the LA-induced respiratory arrest, while the pre-conditioning subgroup rats exhibited no respiratory arrest. No significant differences in heart rate were observed between the toxic and post-conditioning subgroups in the levobupivacaine and ropivacaine groups (P>0.05); however, a significant difference was observed between these treatment groups and the rats treated with lidocaine (P<0.01). A significant difference was also observed in the time from the LA injection to the onset of arrhythmia among the rats in groups B, C and D (P<0.01). No significant differences in the neurological behavior scores and neuronal density were observed in the hippocampal CA1 zone among group C and D rats in the post- and pre-conditioning subgroups at various time-points following treatment. Beyond that, the same phenomena regarding neurological behavior scores was observed in post- and pre-conditioning subgroups of group B at 12 and 24 h treatment, contrasting with the statistically significant difference between post- and pre-conditioning subgroups at 6 h treatment (P<0.01). The results of the present study therefore indicate that pre- and post-conditioning with lipid emulsion effectively mitigates LA-induced CNS toxicity in rats.


central nervous system toxicity; intracerebroventricular injection; lipid emulsion; local anesthetics

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