Investigation of the effects of lipid treatment on levobupivacaine induced cardiotoxicity in rats

The effects of 20% lipid infusion on treatment of levobupivacaine induced cardiotoxicity and on the results of resuscitation were investigated in this randomized, controlled, experimental study in anesthetized rats.Twenty eight adult, male Sprague-Dawley rats were divided into four groups. A tracheotomy was performed and controlled ventilation was started in anesthetized rats. Cannulation for invasive monitorization was instituted. Baseline values for heart rate, systolic blood pressure, diastolic blood pressure, mean blood pressure and the duration of QRS complex were recorded. The animals in Group A (n = 7) received 1,5 mL.kg-1 20% lipid emulsion as a bolus dose. Rats in Group B (n = 7) received 3 mg.kg-1.min-1 levobupivacaine infusion. They were administered 1,5 mL.kg-1 20% lipid emulsion as bolus dose upon a decrease of 50% in mean blood pressure and levobupivacaine infusion was continued till development of asystole; resuscitation was started afterwards. In Group C (n = 7) levobupivacaine infusion was started at a dose of 3 mg.kg-1.min-1 and continued until asystole. Standard resuscitation was begun immediately along with 1,5 mL.kg-1 20% lipid emulsion. In Group D levobupivacaine infusion was continued till asystole developed and standard resuscitation was started while levobupivacaine infusion discontinued (n = 7).Time to the first QRS modification, 50% reduction in heart rate and mean arterial pressure and asystole defined as absence of pressure pulse on the arterial blood pressure trace, levobupivacaine consumption and success in resuscitation were recorded. Kruskal-Wallis and Mann Whitney U tests were performed for statistical analysis. A p value <0.05 was considered to be statistically significant.Baseline measurements were similar in all of the groups. No hemodynamic change except an increase in mean arterial pressure in the 2nd minute was observed in rats receiving only lipid infusion. Levobupivacaine consumption in Group B was more than Groups C and D (8,9 ± 10,2 mg, 2,5 ± 0,7 mg, 4,8 ± 3,2 mg; respectively) (p = 0,049). There were no statistical differences in the period before the decrease in mean arterial pressures and heart rates, QRS widening and development of asystole between the groups. It was observed that the time to development of asystole was longer in Group B compared to Groups C and D (426,4 ± 649,8 s; 54,7 ± 17,7 s; 53,0 ± 34,7 s; respectively). There were 4 successful resuscitations in Group B. Spontaneous cardiac activity was provided in all rats in Group C; but continued in only one rat for 20 minutes. Spontaneous cardiac activity could not be provided in rats in Group D.These results suggest that administration of lipid emulsion may prevent cardiac arrest due to levobupivacaine cardiotoxicity and lipid infusion along with standard resuscitation in cardiac arrest due to levobupivacaine may improve survival.Key words: levobupivacaine, cardiotoxycity, lipid, rat