RESUMEN
INTRODUCTION: New defibrillation techniques are often compared to standard approaches using the defibrillation threshold. However, inference from thresholding data necessitates extrapolation from reactions to relatively ineffective shocks, an error prone procedure requiring large sample sizes for hypothesis testing and large safety margins for defibrillator implantation. In contrast, this article presents a clinically validated statistical model of a minimum error, four-shock defibrillation testing protocol for estimating the 80% effective defibrillation strength for a given patient (ED80). METHODS AND RESULTS: A Bayesian statistical model was constructed assuming that the defibrillation dose-response curve is sigmoidal, and the ED80 is between 150 and 750 V. The model was used to design a minimum predicted error testing protocol and estimates. To prospectively validate the testing protocol and estimates, 170 patients received voltage-programmed biphasic testing. Four fibrillation episodes were induced and terminated in each patient according to the Bayesian up-down protocol. In addition, a validation attempt was made at the estimated ED80 rounded up to the nearest 50 V. In order to estimate the safety margin, in 136 patients, a defibrillation attempt was made at the rounded ED80 + 100 V. Of the 170 attempts at the rounded ED80, 143 (84%) attempts terminated fibrillation. Of the 136 attempts at the rounded ED80 + 100 V, 133 (98%) were effective. CONCLUSIONS: The four-shock Bayesian up-down protocol is the first clinical protocol to accurately predict an ED80 voltage. A 100 V increment above the ED80 provides an adequate safety margin. This simple and accurate method for estimating a highly effective defibrillation dose may be a valuable tool for population-based clinical hypothesis testing, as well as defibrillator implantation.
Asunto(s)
Desfibriladores Implantables/normas , Cardioversión Eléctrica , Modelos Teóricos , Fibrilación Ventricular/terapia , Adulto , Anciano , Anciano de 80 o más Años , Teorema de Bayes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Lysophosphoglycerides accumulate in ischemic myocardium and induce electrophysiologic alterations in normoxic tissue in vitro closely resembling those seen with ischemia in vivo. Delayed afterdepolarizations and triggered activity may be particularly important in the pathogenesis of arrhythmias in the ischemic heart. The present study was performed to determine whether lysophosphatidylcholine (LPC), at concentrations comparable to those present in ischemic myocardium, can induce delayed afterdepolarizations and/or triggered activity in normoxic canine Purkinje fibers. In the present study, as little as 75 microM LPC was found to induce delayed afterdepolarizations and as little as 100 microM LPC was found to induce delayed afterdepolarizations and triggered activity even at low cycle lengths. The amplitude of the induced delayed afterdepolarizations was enhanced by augmentation of the extracellular concentration of calcium (7 mM) or by exogenous epinephrine (10(-9) to 10(-6) M). The amplitude was decreased by verapamil (1 mg/l) or Mn++ (2.5 mM). Epinephrine at a concentration of 10(-6) M also initiated triggered activity in Purkinje fibers exposed to LPC (75 microM), a response blocked by l-propranolol (2 X 10(-7) M and 10(-6) M) but not by the alpha 1-adrenergic blocking agent BE-2254 (10(-6) M). Delayed afterdepolarizations induced by LPC (75 microM) and epinephrine (10(-6) M) persisted even in the presence of acidosis (pH 6.7) and hyperkalemia ([K+]o = 7 mM). Thus, delayed afterdepolarizations and triggered activity induced by LPC may contribute to the induction and/or maintenance of arrhythmias early after the onset of myocardial ischemia. However, because of the reversal of these effects after superfusion with media devoid of LPC, they may occur with ischemia in vivo but not be seen in tissue isolated from ischemic regions and evaluated in vitro.