Effects of lidocaine and verapamil on defibrillation in humans

doi:10.1016/0022-0736(91)90012-B

Journal of Electrocardiology

Volume 24, Issue 4, October 1991, Pages 299-305

https://doi.org/10.1016/0022-0736(91)90012-B Get rights and content

Abstract

Patients with automatic defibrillators frequently require chronic antiarrhythmic drug therapy or receive acute therapy with the onset of symptoms. The effects on energy requirements for defibrillation of lidocaine hydrochloride and verapamil hydrochloride, two commonly used antiarrhythmic agents, were examined in 20 successive patients undergoing corrective arrhythmia surgery. The minimum energy requirement for ventricular defibrillation before and 5 minutes after the administration of 150 mg of lidocaine intravenously (n = 8), or 10 minutes after 10 mg of verapamil intravenously (n = 12), were determined. Each patient was assigned to receive either verapamil or lidocaine. Three mesh coil defibrillating electrodes (Medtronic 6891, 6892) were sutured to the epicardium of the right and left ventricles. Ventricular fibrillation was induced using alternating current. After a minimum of 10 seconds of fibrillation, the minimum energy for defibrillation was established using sequential pulse defibrillation. The preselected drug was then infused and the ventricular defibrillation energy was again determined after 5 or 10 minutes circulation time. Lidocaine did not alter the minimum energy for defibrillation (3.0 ± 1.4 J vs. 3.0 ± 1.8 J, mean ± SD), despite plasma levels of lidocaine that averaged 13.2 ± 1.9 μmol/l. In contrast, verapamil significantly increased (3.9 ± 2.2 J vs. 6.5 ± 2.9 J) the minimum energy necessary for defibrillation. The difference in defibrillation energy was significantly correlated to the fall in systolic blood pressure induced by verapamil administration (r = 0.72). These data reinforce the necessity for determining efficacy of defibrillation when medication changes are instituted. Verapamil should be used with caution in patients with automatic defibrillators and marginal defibrillation threshold.

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Cited by (32)

Reconfirmation algorithms should be the standard of care in automated external defibrillators
2006, Resuscitation
Non-sustained and self-terminating arrhythmias pose a significant challenge during resuscitation. Delivery of a defibrillation shock to a non-shockable rhythm has a poorly understood effect on the heart. The importance of assessing rhythm right up until the delivery of a shock is of increased importance when “blind” shocks are being delivered by automatic defibrillators or minimally trained rescuers. Reconfirmation algorithms are common in current-generation implantable defibrillators but this investigation of current-generation AEDs shows that only 71% of devices presently available have reconfirmation algorithms. A case of spontaneous reversion of a non-sustained arrhythmia is presented. The implications of delivering a defibrillator shock to a non-shockable rhythm are discussed.
Intravenous sotalol decreases transthoracic cardioversion energy requirement for chronic atrial fibrillation in humans: Assessment of the electrophysiological effects by biatrial basket electrodes
2000, Journal of the American College of Cardiology
Citation Excerpt :
The effects of antiarrhythmic drugs on the defibrillation threshold were mostly studied in ventricular fibrillation while information regarding the drug’s effects on atrial defibrillation is sparse. In ventricular defibrillation, drugs with sodium channel blocking effect, including amiodarone, have been reported to increase the energy requirement in animals as well as in humans (10–17). In contrast, antiarrhythmic agents with potassium channel blocking effects, such as sotalol and ibutilide, have been shown to reduce the energy requirement (18–21).
OBJECTIVES
This study was undertaken to assess the effects of sotalol on the transthoracic cardioversion energy requirement for chronic atrial fibrillation (AF) and on the atrial electrograms during AF recorded by two basket electrodes.
BACKGROUND
The effects of sotalol infusion on transthoracic electrical cardioversion for chronic atrial fibrillation in humans have not been well investigated.
METHODS
We included 18 patients with persistent AF for more than three months. Atrial electrograms were recorded by two basket electrodes positioned in each atrium respectively. Transthoracic cardioversion was performed before and after sotalol 1.5 mg/kg IV infusion.
RESULTS
In the 14 patients whose AF could be terminated by cardioversion before sotalol infusion, the atrial defibrillation energy was significantly reduced after sotalol infusion (236 ± 74 jules [J] vs. 186 ± 77 J; p < 0.01). Atrial fibrillation was refractory to cardioversion in four patients at baseline and was converted to sinus rhythm by cardioversion after sotalol infusion in two of them. We further divided the patients into two groups. Group A consisted of 10 patients in whom the energy requirement was decreased by sotalol while group B consisted of eight patients in whom the energy requirement was not decreased. The mean A-A (atrial local electrogram) intervals during AF were significantly increased after sotalol infusion in both groups, but the increment of A-A interval was significantly larger in group A than it was in group B patients (36 ± 13 ms vs. 22 ± 8 ms for the right atrium; 19 ± 7 ms vs. 9 ± 7 ms for the left atrium; both p < 0.05). The spatial and temporal dispersions of A-A intervals were not significantly changed after sotalol infusion in both atria in both groups.
CONCLUSIONS
Sotalol decreases the atrial defibrillation energy requirement by increasing atrial refractoriness but not by decreasing the dispersion of refractoriness.
Ventricular fibrillation-induced intracellular Ca<sup>2+</sup> overload causes failed electrical defibrillation and post-shock reinitiation of fibrillation
1998, Journal of Molecular and Cellular Cardiology
Despite high efficacy, electrical defibrillation shocks can fail or ventricular fibrillation (VF) is reinitiated after the application of the initial shock. The goal of this study was to determine whether [Ca²⁺]_ioverload, induced by VF itself, can cause failed electrical defibrillation and post-shock reinitiation of VF. For this purpose, we simultaneously measured [Ca²⁺]_itransients (assessed by indo-1 fluorescence) and defibrillation energies (assessed by a modified implantable cardioverter defibrillator) in intact perfused rat hearts during pacing-induced sustained VF (10 min) in the absence of ischemia. We found that increasing [Ca²⁺]_iduring VF (by increasing [Ca²⁺]_ofrom 3 to 6 mm) increased the defibrillation threshold (DFT) from 1.9±0.6 to 3.5±0.5 J/g (P<0.05) and also increased the total defibrillation energy (TDE) required for stabilization of sinus rhythm from 15.6±7.7 to 48.6±7.42 J/g (P<0.05). In addition, both DFT and TDE correlated linearly with [Ca²⁺]_i(r=0.69 and 0.83,P<0.05). Furthermore, shortening the duration of VF from 10 to 1.5 min tended to limit [Ca²⁺]_ioverload and decreased TDE. Finally, all successful defibrillation shocks led to a sudden reduction of VF-induced [Ca²⁺]_ioverload (−115±3%). In contrast, failed shocks did not alter [Ca²⁺]_i. Incomplete reduction of [Ca²⁺]_ioverload after initially successful shocks were often followed by synchronized spontaneous [Ca²⁺]_ioscillations and subsequent reinitiation of VF. In conclusion, the present study showed for the first time that VF-induced [Ca²⁺]_ioverload can cause failed electrical defibrillation and post-shock reinitiation of VF. Because VF inevitably causes [Ca²⁺]_ioverload, this finding might be a crucial mechanism of failed defibrillation and spontaneous reinitiation of VF.
Effects of amiodarone and its active metabolite desethylamiodarone on the ventricular defibrillation threshold
1998, Journal of the American College of Cardiology
Objectives. We evaluated whether the reported difference in the ventricular defibrillation threshold (DFT) between short-term intravenous and oral amiodarone is due to the effect of amiodarone’s active metabolite desethylamiodarone (DEA).
Background. Amiodarone is frequently used in patients with implantable cardioverter-defibrillator devices (ICD). Long-term oral amiodarone raises the DFT, but intravenous amiodarone has not been shown to have this effect. DEA, an active metabolite of amiodarone, has different electrophysiologic properties than its parent compound and may be responsible for the observed different effects of intravenous and oral amiodarone on DFT.
Methods. We ascertained the DFT in 24 pigs randomized to receive intravenous amiodarone, DEA or vehicle. Defibrillation was delivered through a transvenous lead system using a biphasic waveform. The DFT was determined using an up-down DFT algorithm and defined as the average minimal energies resulting in successful defibrillation delivered from ascending and descending serial shocks.
Results. Amiodarone caused a dose-response increase in DFT (mean ± SD) from 22.7 ± 4.1 (baseline) to 26.1 ± 2.9 (10 mg/kg body weight), p = 0.11, to 34.9 ± 8.2 J (after an additional 15 mg/kg), p = 0.035. DEA (10 mg/kg) caused an increase in DFT from 20.5 ± 6.3 to 33.9 ± 13.6 J, p < 0.01. Addition of 15 mg/kg of DEA resulted in hemodynamic instability and thus DFT was not obtained. In the control group, DFT decreased from 26.8 ± 7.7 at baseline to 23.1 ± 7.4 (dose 1), p = 0.19, to 22.8 ± 6.2 J (dose 2), p = 0.18.
Conclusions. DEA increases DFT by a greater amount than its parent drug amiodarone. There is an effect of intravenous amiodarone on DFT that is dose dependent.
Effects of lidocaine and mexiletine on defibrillation energy requirements in animals treated with flecainide
1998, Resuscitation
We previously reported that mexiletine alone did not increase the ventricular defibrillation threshold (DFT). However it has been stressed that the interaction of antiarrythmic drugs may be one of the cause of sudden death in patients taking flecainide or encainide. In the present study, the effect of lidocaine and mexiletine combined with flecainide on DFT was investigated. Experiments were performed on 27 mongrel dogs. Flecainide 2 mg kg⁻¹ was administered i.v. as a loading dose and repeated for maintenance. Lidocaine (n=10) or mexiletine (n=10), was cumulatively administered 15 min later. Saline was administered in control group (n=7). In these groups, fibrillation/defibrillation trials were repeated. The flecainide concentration ranged from 0.84 to 1.02 μg ml⁻¹. The lidocaine and mexiletine concentrations increased up to 12.54 and 7.47 μg ml⁻¹, respectively. DFT₁₅, 15 min after the administration of flecainide, increased from 2.0 to 3.2 J in lidocaine group (mean±S.E.M.; P<0.05), from 2.1 to 3.7 J in mexiletine group (mean±S.E.M.; P<0.05). DFT increased with lidocaine concentrations of 3.42 μg ml⁻¹ or higher, and mexiletine of 3.60 μg ml⁻¹ or higher (P<0.05). In conclusion, both lidocaine and mexiletine elevated the DFT in the dog treated with flecainide, especially with lidocaine in a therapeutic concentration.
Interactions between drugs and devices: Experimental and clinical studies
1994, American Heart Journal
It is important to understand the potential interactions between the implantable cardioverter defibrillator (ICD) and antiarrhythmic therapy in patients who receive pharmacologic therapy as an adjunct to ICD therapy. In our cohort of 101 patients, antiarrhythmic agents were prescribed in 67% of the patients during long-term therapy for the following reasons: to suppress ventricular tachycardia/ventricular fibrillation episodes (50%), to lower the rate of ventricular tachycardia (19%), to prevent supraventricular tachyarrhythmia (21%), and for other reasons (10%). The potential influence of antiarrhythmic drugs on the defibrillation threshold (DFT) is the most important issue. In animal studies lidocaine increased the DFT in a dose-dependent manner. Quinidine, procainamide, propafenone, and flecainide did not affect the DFT or, in some cases, led to a small increase. Sotalol even decreased the energy requirements for internal defibrillation. In a prospective investigation we were able to document a significant increase of DFT (from 14.1 + 3.0 to 20.9 + 5.4 J, p < 0.001) by the use of amiodarone (400 mg/day), whereas this effect was not found in patients who received mexiletine (720 mg/day). In conclusion, the DFT or the safety margin for defibrillation should be known before antiarrhythmic agents are administered to patients with an ICD. In case of a small safety margin, the DFT should be reassessed after antiarrhythmic drug therapy is begun.

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^∗: Dr. G. J. Klein is a Distinguished Research Professor of the Heart and Stroke Foundation of Ontario.

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Original articleEffects of lidocaine and verapamil on defibrillation in humans

Abstract

J Am Coll Cardiol

Am Heart J

J Thorac Cardiovasc Surg

J Am Coll Cardiol

Am Heart J

Am J Cardiol

Am J Cardiol

J Am Coll Cardiol

Am J Cardiol

Am J Cardiol

Am Heart J

The automatic implantable cardioverter-defibrillator

PACE

The automatic implantable cardioverter defibrillator: the US experience

Worldwide clinical experience with the use of the automatic implantable cardioverter-defibrillator

New Trend Arrhythmia

The effects of newer antiarrhythmic drugs on defibrillation threshold

Crit Care Med

Beta-adrenergic modulation of direct defibrillation energy in anaesthetized dog heart

Am J Physiol

Original article
Effects of lidocaine and verapamil on defibrillation in humans