Effects of lidocaine and mexiletine on defibrillation energy requirements in animals treated with flecainide

Abstract 

We previously reported that mexiletine alone did not increase the ventricular defibrillation threshold (DFT). However it has been stressed that the interaction of antiarrythmic drugs may be one of the cause of sudden death in patients taking flecainide or encainide. In the present study, the effect of lidocaine and mexiletine combined with flecainide on DFT was investigated. Experiments were performed on 27 mongrel dogs. Flecainide 2 mg kg⁻¹ was administered i.v. as a loading dose and repeated for maintenance. Lidocaine (n=10) or mexiletine (n=10), was cumulatively administered 15 min later. Saline was administered in control group (n=7). In these groups, fibrillation/defibrillation trials were repeated. The flecainide concentration ranged from 0.84 to 1.02 μg ml⁻¹. The lidocaine and mexiletine concentrations increased up to 12.54 and 7.47 μg ml⁻¹, respectively. DFT₁₅, 15 min after the administration of flecainide, increased from 2.0 to 3.2 J in lidocaine group (mean±S.E.M.; P<0.05), from 2.1 to 3.7 J in mexiletine group (mean±S.E.M.; P<0.05). DFT increased with lidocaine concentrations of 3.42 μg ml⁻¹ or higher, and mexiletine of 3.60 μg ml⁻¹ or higher (P<0.05). In conclusion, both lidocaine and mexiletine elevated the DFT in the dog treated with flecainide, especially with lidocaine in a therapeutic concentration.

Keywords:  Antiarrhythmic drugs, Ventricular defibrillation threshold (DFT), Lidocaine, Mexiletine, Flecainide