pH-Dependent effects of lidocaine on defibrillation energy requirements in dogs

Abstract

Lidocaine increases the energy required for ventricular defibrillation in dogs. Because sodium channel-blocking agents that are weak bases have pH-dependent electrophysiologic effects, we investigated the pH dependence of lidocaine (pKa, 7.9) on internal defibrillation energy requirements in 28 dogs with atrial spring and left ventricular patch electrodes. Results of defibrillation testing were used to derive 50% and 90% successful energy requirements (ED50 and ED90) using logistic regression and were compared with analysis of variance. Acidosis produced by hydrochloric acid infusion decreased the arterial pH from 7..40 ± 0.05 (SD) to 7.18 ± 0.03 (n = 8, p < 0.01), but no significant change in ED90 was observed (14 ± 4 to 16 ± 6 J). Lidocaine infusion to therapeutic levels (4.2 ± 0.7 μg/ml) at normal pH (7.42 ± 0.02) increased ED90 from 13 ± 3 to 17 ± 3 J (n = 6, p < 0.05), and subsequent acidosis (pH 7.19 ± 0.02, p < 0.01) exacerbated this effect of lidocaine on ED90 (22 ± 5 J, p < 0.05). Alkalosis produced by respirator hyperventilation increased the arterial pH from 7.41 ± 0.03 to 7.60 ± 0.03 (n = 8, p < 0.01), with a fall in ED90 from 13 ± 4 to 8 ± 3 J (p < 0.01). Lidocaine infusion to high levels (7.4 ± 2 μg/ml) at normal pH (7.42 ± 0.02) increased ED90 from 15 ± 8 to 20 ± 9 J (n = 6, p < 0.05), and subsequent alkalosis (pH 7.61 ± 0.02, p < 0.01) reversed the effect of lidocaine on ED90 (12 ± 5 J, p < 0.05). We conclude that in dogs, the increase in defibrillation energy requirements by lidocaine are enhanced by acidosis and reversed by alkalosis consistent with its sodium channel-blocking properties. These data provide further evidence in support of the hypothesized direct link between drug effects on defibrillation and drug effects on individual ion channels.