Therapeutic indices for transchest defibrillator shocks: effective, damaging, and lethal electrical doses

Although prospective studies of defibrillator shock overdose cannot be performed in man, the therapeutic indices of various defibrillating current waveforms can be measured in animals. We determined the ratios TD50/ED50 and LD50/ED50 (where TD50 = median "toxic" or damage-inducing dose, ED50 = median effective or defibrillating dose, and LD50 = median lethal dose) as measures of the therapeutic index for damped sine wave defibrillator shocks in dogs. Death of an animal and/or any degree of cardiac damage found by gross or microscopic examination were defined as harmful effects of shock, analogous to drug toxicity. In terms of peak current, the ED50, TD50, and LD50 were 1.1, 5.8, and 24 amperes/kg.; the therapeutic indices were TD50/ED50 = 5 for morphologic damage and LD50/ED50 = 22 for death. In terms of delivered energy the ED50, TD50, and LD50 were 1.5, 30, and 470 joules/kg.; the therapeutic indices were TD50/ED50 = 20 for damage and LD50/ED50 = 320 for death. These data indicate a reasonable margin of safety for damped sine wave defibrillator shocks in dogs, and are consistent with reported incidences of suspected shock-induced damage in humans.