Safety Of Intravenous Amiodarone Research Articles

Efficacy and Safety of Intravenous Venous Amiodarone: A Single Center Experience

Background: Efficacy and safety of intravenous amiodarone (IV-AMD) for Japanese patients in a real clinical practice have not been well evaluated.Methods and Results: Between Feb. 2008 and Feb. 2011, a total of 69 patients received IV-AMD in Kyoto University Hospital. Mean age was 67±17 years, and 46 (67%) were male. Sixty six patients (96%) had structural heart diseases, including ischemic heart diseases in 38 (55%), non-ischemic cardiomyopathies in 11 (16%), and valve diseases in 9 (13%). The target arrhythmias were ventricular tachyarrhythmias in 39 (56.5%), and atrial tachyarrhythmias in 30 (43.5%). IV-AMD was administered for a median duration of 2.0 (1–11) days, which was effective in 69% of patients with ventricular tachyarrhythmia and in 70% of patients with atrial tachyarrhythmia. Adverse effects requiring discontinuation of the drug occurred in 9 patients (13.0%); bradycardia in 4 (5.8%), low blood pressure in 2 (2.9%), QT prolongation in 2 (2.9%), and torsade de pointes in 1 (1.4%). There was no interstitial pneumonia or hypothyroidism.Conclusions: IV-AMD was effective for both ventricular and atrial tachyarrhythmia in approximately 70% of patients with structural heart diseases. Care should be taken for adverse effects, especially for bradycardia, hypotension and QT prolongation.

Efficacy and safety of intravenous amiodarone in recent-onset atrial fibrillation: experience in patients admitted to a general internal medicine department

We examined the efficacy and safety of intravenous amiodarone in 20 unselected patients with recent-onset atrial fibrillation who were admitted to a general internal medicine department during a 6-month period....

Effectiveness and safety of intravenous amiodarone in drug-resistant tachyarrhythmias of children.

Experience with pediatric use of intravenous amiodarone is limited. In this study, our experiences with intravenous amiodarone in children with acute life-threatening or chronic tachyarrhythmias are reviewed. Twelve patients, with a mean age of 3.4 +/- 3.1 years, range 9 months-10 years (two with incessant ventricular tachycardia, one with ectopic atrial tachycardia, two with atrioventricular re-entrant tachycardia (three episodes), four with postoperative or congenital junctional ectopic tachycardia, two with bradycardia-tachycardia syndrome, one with atrial tachycardia) were treated with intravenous amiodarone during 13 tachycardia episodes. Left ventricular systolic functions were depressed in six patients. In 11 patients, a median of two drugs (range one-four), including adenosine infusion and in five cases direct current cardioversion were tried without success prior to intravenous amiodarone. The loading dose of amiodarone was 5 mg/kg in all episodes, infused over 1 h. Maintenance infusion was required in 12 episodes. In 10 episodes (77%), amiodarone was considered effective, in one (7.6%) partially effective (junctional ectopic tachycardia) and in two (15.4%) ineffective (sick sinus syndrome, atrial tachycardia). Therapeutic effect was obtained in a median period of 30 h (range 1-103 h). The mean effective maintenance dose was 10 +/- 4.7 micrograms/kg per min (range 5-15 micrograms/kg per min). In one patient, mild hypotension, and in three patients cellulitis occurred, but none of them necessitated termination of treatment. Intravenous amiodarone is found to be an effective and safe antiarrhythmic agent for children with acute life-threatening and chronic tachyarrhythmias and depressed left ventricular systolic functions.

Intravenous amiodarone: pharmacology, pharmacokinetics, and clinical use.

To review the clinical pharmacology, pharmacokinetics, and clinical efficacy and safety of intravenous amiodarone. Articles were identified through a computer search of the English-language literature using MEDLINE (KR Information OnDisc) and the search term amiodarone. Additional articles were identified through examination of the bibliographies of the articles initially retrieved. Relevant or representative animal studies, clinical trials, and case reports were selected for evaluation. Particular emphasis was placed on studies pertaining to the use of intravenous amiodarone in treatment-refractory ventricular fibrillation (VF) and hemodynamically unstable ventricular tachycardia (VT). The literature was assessed for adequate description of patients, study methodologies (e.g., study design, number of patients), and outcomes. Amiodarone is an unusual class III antiarrhythmic that produces each of the four main types of antiarrhythmic action in addition to other effects, such as vasodilatory, selective antithyroid, and other activities that may be therapeutically relevant. Amiodarone pharmacokinetics demonstrate extensive interpatient variability and are characterized by wide tissue distribution (steady-state volume of distribution 40-84 L/kg), slow total body clearance (90-158 mL/h/kg), long terminal elimination half-life (20-47 d), and extensive hepatic metabolism. The onset of maximal antiarrhythmic effect is a function of both amiodarone dosage and time. The high plasma concentrations achieved with intravenous dosing do not fully replicate the electrophysiologic effects observed following long-term oral administration, particularly with respect to class III activity. Available data suggest that intravenous amiodarone is associated with an efficacy rate of 50% or more in treatment-refractory VT/VF, and has a relatively rapid (2-24 h) onset of action. The drug is relatively well tolerated, but close hemodynamic, electrocardiographic, and hepatic function monitoring are required. The value of using amiodarone serum concentrations to guide therapy remains uncertain. Intravenous amiodarone is an effective, relatively safe antiarrhythmic for the treatment of recurrent, hemodynamically unstable VT/VF refractory to other drug therapy in the acute care setting.

Pediatric use of intravenous amiodarone: Efficacy and safety in critically III patients from a multicenter protocol

The purpose of this study was to analyze the efficacy and safety of intravenous amiodarone in young patients with critical, drug-resistant arrhythmias. Intravenous amiodarone has been investigated in adults since the early 1980s. Experience with the drug in young patients is limited. A larger pediatric study group was necessary to provide responsible guidelines for the drug's use before its market release. Eight centers obtained institutional approval of a standardized protocol. Other centers were approved on a compassionate use basis after contacting the primary investigator (J.C.P). Forty patients were enrolled. Standard management in all failed. Many patients had early postoperative tachyarrhythmias (25 of 40), with early successful treatment in 21 (84%) of 25. Twelve patients had ventricular tachyarrhythmias: seven had successful therapy, and six died, none related to the drug. Eleven patients had atrial tachyarrhythmias: 10 of 11 had immediate success, but 3 later died. Fourteen patients had junctional ectopic tachycardia, which was treated with success (sinus rhythm or slowing, allowing pacing) in 13 of 14, with no deaths. Three other patients had supraventricular tachycardias, with success in two and no deaths. The average loading dose was 6.3 mg/kg body weight, and 50% of patients required a continuous infusion. Four patients had mild hypotension during the amiodarone bolus. One postoperative patient experienced bradycardia requiring temporary pacing. There were no proarrhythmic effects. Deaths (9 [23%] of 40) were not attributed to amiodarone. Intravenous amiodarone is safe and effective in most young patients with critical tachyarrhythmia. Intravenous amiodarone can be lifesaving, particularly for postoperative junctional ectopic tachycardia, when standard therapy is ineffective.

Intravenous amiodarone for recurrent sustained hypotensive ventricular tachyarrhythmias

We sought to determine the response rate and safety of intravenous amiodarone in patients with ventricular tachyarrhythmias refractory to standard therapies. Numerous small retrospective reports suggest a response of refractory ventricular tachyarrhythmias to intravenous amiodarone, yet no controlled prospective trials exist. Two hundred seventy-three patients with recurrent hypotensive ventricular tachyarrhythmias refractory to lidocaine, procainamide and bretylium were randomized to receive one of three doses of intravenous amiodarone: 525, 1,050 or 2,100 mg/24 h (mean [+/- SE] dose 743.7 +/- 418.7, 1,175.2 +/- 483.7, 1,921.2 +/- 688.8 mg, respectively) by continuous infusion over 24 h. Of the 273 patients, 110 (40.3% response rate) survived 24 h without another hypotensive ventricular tachyarrhythmic event while being treated with intravenous amiodarone as a single agent (primary end point). A significant difference in the time to first recurrence of ventricular tachyarrhythmia (post hoc analysis) over the first 12 h was observed when the combined 1,050- and 2,100-mg dose groups were compared with the 525-mg dose group (p = 0.046). The number of supplemental (150 mg) infusions of intravenous amiodarone (given for breakthrough destabilizing tachyarrhythmias) during hours 0 to 6 (prespecified secondary end point) was significantly greater in the 525-mg dose group than in the 2,100-mg dose group (1.09 +/- 1.57 vs. 0.51 +/- 0.97, p = 0.0043). However, there was no clear dose-response relation observed in this trial with respect to success rates (primary end point), time to first recurrence of tachyarrhythmia (post hoc analysis) or mortality (secondary end point) over 24 h. Intravenous amiodarone is a relatively safe therapy for ventricular tachyarrhythmias refractory to other medications.

Clinical efficacy and safety of intravenous amiodarone in infants and children

The effectiveness and safety of intravenous amiodarone in children are not well established. This study reviewed its use in 30 infants and children for life-threatening tachyarrhythmias: 18 patients (19 episodes) with supraventricular tachycardia, and 12 with ventricular tachycardia. Eighteen patients had structural heart defects with arrhythmias that occurred after surgery. The mean loading dose was 5 mg/kg infused over 1 hour, with a starting maintenance dose of 5 μg/kg/min. In 18 treatment episodes, amiodarone was used alone or in combination with digoxin. Thirteen patients received amiodarone combined with other antiarrhythmic agents. Intravenous amiodarone was effective or partially effective in 94% of patients, achieving a therapeutic effect in a median time of 1 day (range 1 hour to 5 days). The mean effective maintenance dose was 9.5 μg/kg/min (13.7 mg/kg/day), and median treatment duration was 5 days (range 1 to 30). Adverse effects occurred in 18 patients (58%), however none necessitated termination of amiodarone therapy. Potentially significant electrocardiographic abnormalities occurred in 5 patients during combination antiarrhythmic therapy with propafenone. Sinus bradycardia requiring temporary postoperative pacing occurred in 3 patients treated with amiodarone alone. Intravenous amiodarone used alone or in combination therapy is an effective treatment for resistant, life-threatening arrhythmias in infants and children. Combination drug therapy with propafenone must be used cautiously. Potential bradycardia pacing may be necessary during administration of amiodarone after surgery.

Efficacy and safety of intravenous amiodarone in acute refractory arrhythmias.

Few data are available on intravenous amiodarone therapy in refractory arrhythmias. This retrospective study in 50 patients (14 with supraventricular and 36 with ventricular tachyarrhythmias) revealed a favorable effect of intravenous amiodarone in the treatment of life-threatening arrhythmias with an overall success rate of 76%. In the subgroup of patients with ventricular fibrillation and concomitant severe congestive heart failure success rate was low (25%, 2/8), whereas effectiveness in patients with ventricular tachycardias was high (greater than 90%) and proved to be independent of left ventricular function. If patients with recurrent ventricular fibrillation were excluded from the analysis, successful treatment with intravenous amiodarone was achieved in 90%, even in those patients with severely compromised myocardium.

Efficacy of intravenous amiodarone as short-term treatment for refractory ventricular tachycardia

The antiarrhythmic efficacy and safety of intravenous amiodarone were evaluated in 13 patients with recurrent sustained ventricular tachycardia. All patients had been refractory to at least three prior antiarrhythmic agents (mean, 3.3 per patient), and 11 had multiple direct current cardioversions. Intravenous amiodarone suppressed sustained tachycardia in seven patients; the concurrent use of procainamide resulted in suppression in two additional patients. Ventricular tachycardia recurred in three patients, two within 2 hours of initiation of amiodarone. Adverse effects necessitated the discontinuation of amiodarone in one patient because of significant hemodynamic deterioration. The use of intravenous amiodarone was associated with a significant fall in heart rate and cardiac output. Plasma amiodarone levels were high after initial bolus loading but declined to low or less than therapeutic levels within 60 minutes. Thus although we found intravenous amiodarone to be effective in the short-term treatment of refractory ventricular tachycardia, administration of amiodarone can be associated with significant hemodynamic deterioration. The dosing protocol used should be modified to a lower initial bolus and a higher early maintenance infusion rate.