Treatment and prevention of ventricular fibrillation: Are there better agents?

Abstract

Ventricular fibrillation occurs in diverse clinical settings and differing pathogenic mechanisms make it unlikely that a single drug treatment will be universally effective. Drugs may be used as an adjunct to electrical defibrillation in circulatory collapse, to prevent recurrence after successful resuscitation or as a prophylactic treatment in high-risk patients. Various drugs are available for intravenous administration in the acute management of ventricular fibrillation and the choice among them will depend on several factors: proven efficacy, comparative efficacy and their safety including haemodynamic effects. Although several drugs have been shown to suppress ventricular ectopic beats and ventricular tachycardia, ventricular fibrillation and sudden death can occur despite abolition of these less serious ventricular arrhythmias [ 11. Animal studies have suggested the concept of separate ‘antiarrhythmic’ and ‘antilibrillatory’ action of drugs. Drugs with antifibrillatory properties increase the energy threshold for production of ventricular fibrillation while many conventional antiarrhythmic drugs have no effect [2,3]. However, an effect on fibrillation threshold does not necessarily indicate a reduction in energy requirements for successful electrical defibrillation. The major criticism of such models is that the substrate for generation of ventricular fibrillation is usually different in clinical ventricular fibrillation. Lignocaine and bretylium are the current standard drugs for management of acute ventricular fibrillation. This review examines the claims of other antiarrhythmic drugs to supplant or supplement these agents (Table I). Figure 1 shows a representation of the normal cardiac action potential. Initial depolarisation (phase 0) is achieved by rapid influx of sodium ions which is slowed by agents which belong to class 1 of the Vaughan Williams and Singh classification. These compounds are subdivided by their effect on the duration of the action potential: Class la drugs lengthen it, Class lb shorten it, while Class lc have no effect. Class II drugs are the beta blockers which have no direct effect on the action potential but antagonise myocardial stimulation by catecholamines. The Class III agents delay phase 3 repolarisation and prolong the duration of the action potential. Class IV drugs are calcium channel blockers which reduce the influx of calcium into cells, in particular reducing the spontaneous depolarisation of phase 4 in the atrio-