HIGH-DOSE LIDOCAINE DOES NOT AFFECT DEFIBRILLATION EFFICACY - IMPLICATIONS FOR DEFIBRILLATION MECHANISMS

This study assessed the effect of low (10 mg.kg(-1).h(-1)) and very hi gh (18 mg.kg(-1).h(-1)) doses of lidocaine on defibrillation energy re quirements (DER) to relate changes in indexes of sodium-channel blocka de with changes in DER values using a dose-response study design. In g roup 1 (control; n = 6 pigs), DER values were determined at baseline a nd during treatment with 5% dextrose in water (D5W) and with D5W added to D5W. In group 2 (n = 7), DER values were determined at baseline an d during treatment with low-dose lidocaine followed by high-dose lidoc aine. Ingroup 3 (n = 3), DER values were determined at baseline and hi gh-dose lidocaine. Group 3 controlled for the order of lidocaine treat ment with the addition of high-dose lidocaine after baseline. DER valu es in group 1 did not change during D5W. In group 2, low-dose lidocain e increased DER values by 51% (P = 0.01), whereas high-dose lidocaine added to low-dose lidocaine reduced DER values back to within 6% of ba seline values (P = 0.02, low dose vs. high dose). DER values during hi gh-dose lidocaine in group 3 also remained near baseline values (16.2 +/- 2.7 to 12.9 +/- 2.7 J), demonstrating that treatment order had no impact on group 2. Progressive sodium-channel blockade was evident as incremental reduction in ventricular conduction velocity as the lidoca ine dose increased. Lidocaine also significantly increased ventricular fibrillation cycle length as the Lidocaine dose increased. However, t he greatest increase in DER occurred when ventricular fibrillation cyc le length was minimally affected, demonstrating a negative correlation (P = 0.04). In summary, lidocaine has an inverted U-shaped DER dose-r esponse curve. At very high lidocaine doses, DER values are similar to baseline and tend to decrease rather than increase. Increased refract oriness during ventricular fibrillation may be the electrophysiologica l mechanism by which high-dose lidocaine limits the adverse effects th at low-dose lidocaine has on DER values. However, there is a possibili ty that an unidentified action of lidocaine is responsible for these e ffects.