Intravenous Administration Of Amiodarone Research Articles

Acute low back pain during intravenous administration of amiodarone: a report of two cases

Amiodarone represents an effective antiarrhythmic drug for cardioversion of recent-onset atrial fibrillation (AF) and maintenance of sinus rhythm. We briefly describe two patients suffering from recent-onset atrial fibrillation, who experienced an acute devastating low back pain a few minutes after initiation of intravenous amiodarone loading. Notably, this side effect has not been ever reported in the medical literature. Clinicians should be aware of this reaction since prompt termination of parenteral administration leads to complete resolution.

Time course of fibrillation and defibrillation thresholds after an intravenous bolus of amiodarone--an experimental study.

Experimental studies have described an increase in ventricular fibrillation threshold (VFT) by intravenous amiodarone. The aim of this study was to examine the early time course of changes in VFT and defibrillation thresholds (DFT) after an intravenous bolus of amiodarone in an experimental pig model of transient myocardial ischemia. VFT and relative effective ventricular refractory period (ERP) were measured in 15 anaesthetized open-chest pigs after 3 min of regional coronary ischaemia before (time 0) and 2, 15, 30, 60, and 90 min after the intravenous injection of normal saline (group A, n = 5) or amiodarone, 5 mg/kg over 15 s (group B, n = 10). DFT was measured by increasing the strength of DC shocks until defibrillation was accomplished. Amiodarone caused an increase in VFT, starting at 2 min after the infusion (11.4 +/- 8.4 mA versus 9.2 +/- 4.6 mA, P = 0.03), became significant at 15 min (13.7 +/- 6.5 mA, P = 0.009), continued to rise at 30 min (34.2 +/- 28.7 mA, P = 0.03) and reached a plateau at 60 min (50.3 +/- 37.8 mA, P = 0.008). An increase was also observed in the ERP (204 +/- 25 ms at 2 min versus 197 +/- 26 ms at baseline, P = 0.074, 211 +/- 38 ms at 15 min, P = 0.084, 212 +/- 40 ms at 30 min, P = 0.037, 220 +/- 34 ms at 60 min, P = 0.002, and 227 +/- 32 ms at 90 min, P = 0.008). No change was observed in DFT after amiodarone administration. No significant change in VFT, ERP, or DFT occurred in the control group. In this porcine model, the intravenous administration of amiodarone increased VFT and ERP over 60 min after the injection, without effect on DFT.

Arrhythmias in the intensive care patient.

Atrial fibrillation, atrial flutter, AV-nodal reentry tachycardia with rapid ventricular response, atrial ectopic tachycardia, and preexcitation syndromes combined with atrial fibrillation or ventricular tachyarrhythmias are typical arrhythmias in intensive care patients. Most frequently, the diagnosis of the underlying arrhythmia is possible from the physical examination, the response to maneuvers or drugs, and the 12-lead surface electrocardiogram. In all patients with unstable hemodynamics, immediate DC-cardioversion is indicated. Conversion of atrial fibrillation to sinus rhythm is possible using antiarrhythmic drugs. Amiodarone has a conversion rate in atrial fibrillation of up to 80%. However, caution in the use of short-term administration of intravenous amiodarone in critically ill patients with recent-onset atrial fibrillation is absolutely necessary, and the duration of therapy should not exceed 24 to 48 hours. Ibutilide represents a relatively new class III antiarrhythmic agent that has been reported to have conversion rates of 50% to 70%; it seems that ibutilide is even successful when intravenous amiodarone failed to convert atrial fibrillation. Newer studies compared the outcome of patients with atrial fibrillation and rhythm- or rate-control. Data from these studies (AFFIRM, RACE) clearly showed that rhythm control is not superior to rate control for the prevention of death and morbidity from cardiovascular causes. Therefore, rate-control may be an appropriate therapy in patients with recurrent atrial fibrillation after DC-cardioversion. Acute therapy of atrial flutter in intensive care patients depends on the clinical presentation. Atrial flutter can most often be successfully cardioverted to sinus rhythm with energies less than 50 joules. Ibutilide trials showed efficacy rates of 38-76% for conversion of atrial flutter to sinus rhythm compared with conversion rates of 5-13% when intravenous flecainide, propafenone, or verapamil was administered. In addition, a high dose (2 mg) of ibutilide was more effective than sotalol (1.5 mg/kg) in conversion of atrial flutter to sinus rhythm (70% versus 19%). There is general agreement that bystander first aid, defibrillation, and advanced life support is essential for neurologic outcome in patients after cardiac arrest due to ventricular tachyarrhythmias. The best survival rate from cardiac arrest can be achieved only when (1) recognition of early warning signs, (2) activation of the emergency medical services system, (3) basic cardiopulmonary resuscitation, (4) defibrillation, (5) management of the airway and ventilation, and (6) intravenous administration of medications occurs as rapidly as possible. Public access defibrillation, which places automatic external defibrillators in the hands of trained laypersons, seems to be an ideal approach in the treatment of ventricular fibrillation. The use of automatic external defibrillators by basic life support ambulance providers or first responder in early defibrillation programs has been associated with a significant increase in survival rates. Drugs such as lidocaine, procainamide, sotalol, amiodarone, or magnesium were recommended for treatment of ventricular tachyarrhythmias in intensive care patients. Amiodarone is a highly efficacious antiarrhythmic agent for many cardiac arrhythmias, ranging from atrial fibrillation to malignant ventricular tachyarrhythmias, and seems to be superior to other antiarrhythmic agents.

Amiodarone: an emergency medicine perspective.

Amiodarone is a highly efficacious antiarrhythmic agent for many cardiac arrhythmias, ranging from atrial fibrillation to malignant ventricular rhythm disturbances. Significant interest has developed in recent years with the publication of randomized controlled trials supporting the efficacy of amiodarone over placebo and lignocaine for improving survival to hospital in patients with shock-resistant ventricular fibrillation. Amiodarone has complex pharmacological and pharmacokinetic properties. It has significant long-term adverse effects, but short-term administration of intravenous amiodarone is generally well tolerated. This article will explore issues related to the clinical use of amiodarone from an emergency medicine perspective.

Intravenous bolus amiodarone administration exhibits an immediate and gradual increase in ventricular fibrillation threshold: experimental study

Intravenous bolus amiodarone administration exhibits an immediate and gradual increase in ventricular fibrillation threshold: experimental study

The Response to Antiarrhythmia Therapy with Amiodarone in Diabetic Patients Undergoing Coronary Artery Bypass Grafting

Background: The immediate response obtained following intravenous amiodarone administration, has made amiodarone to be the first choice for arrhythmia treatment occurring after coronary artery bypass grafting. However, whether the response is the same with all the patients undergoing coronary artery bypass grafting is unknown. Methods: We investigated the response to amiodarone therapy in diabetic and nondiabetic patients who developed arrhythmia after coronary artery bypass grafting operation. The response to amiodarone therapy in 25 Type II (noninsulin-depending) diabetic patients was compared with that in 25 non-diabetic patients (i.e. controls). Results: In the diabetic group, atrial fibrillation was observed in 19 patients, and premature ventricular contractions and supraventricular tachycardia were observed in 4 and 2 patients, retrospectively. Atrial fibrillation and premature ventricular contractions were observed in 21 and 4 patients in the control group. In case of arrhythmia, the mean heart rate was 140.92±21.73 beats/min and 141.16±20.31 beats/min in diabetic patients, and the control group, respectively. Upon intravenous amiodarone administration, the mean heart rate was decreased to 87.04±6.11 beats/min in diabetic patients and to 85.92±6.86 beats/min in the control group. The mean response time to the amiodarone therapy was statistically significantly different in diabetic patients (20.8±16.95 hours) when compared with the response time in the control group (7.2±2.39 hours) (p<0.05). Conclusion: The response to amiodarone therapy for arrhythmia was found to be delayed in diabetic patients compared with that in non-diabetic patients undergoing coronary artery bypass grafting operation.

Incidence of and Predicting Factors for Torsades de Pointes during Intravenous Administration of Amiodarone

Objective: There is considerable knowledge of the incidence of torsades de pointes (TdP) during the administration of amiodarone The aim of our study was to determine the incidence of TdP during the loading phase of intravenous administration of amiodarone, intended to reverse paroxysmal atrial fibrillation (PAF) to sinus rhythm (SR), and to test the hypothesis that their prevalence is greater among women than men, as reported earlier. We also sought to determine factors predisposing to the occurrence of TpD, such as atrium size and hyperglycemia. Methods: We evaluated 189 patients (M = 107, F = 82, mean age = 56 ± 19 years), who were admitted for PAF, and for whom amiodarone was selected as the first-choice drug for PAF reversion. During the first 24 h of the loading phase (300 mg rapid i.v. administration within 20 min and 1,500 mg i.v. for 24 h) we recorded all ventricular arrhythmias. All patients were on anticoagulant treatment and all of them were evaluated for corrected QT (QTc), as well as additional risk factors (atrial size, serum glucose, hypopotassemia, hypomagnesemia, severe bradycardia). Patients with heart failure, hypertrophic obstructive cardiomyopathy, a history of coronary artery disease or ventricular tachycardia, as well as those treated with drugs prolonging the QT interval, were excluded from the study. Results: 108 patients (57.1%) experienced successful conversion of PAF into SR on amiodarone. Five patients (2.6%), all female, mean age 53.0 ± 1.2 years, developed TpD. All episodes occurred at the end of the loading phase (21–24 h) of amiodarone administration. None of them had hypopotassemia, hypomagnesemia, or bradycardia (HR <55 bpm). Two of the TpD patients had elevated glucose levels, and all of them had prolonged QTc immediately prior to the TpD. Conclusion: We confirm that women are at increased risk of developing TpD during the administration of amiodarone. TpD develop towards the end of the intravenous loading phase; the electrocardiographic changes should be closely monitored towards the end of the loading phase. The presence of diabetes mellitus or temporal hyperglycemia and prolonged QTc seems to be predicting factors for TpD during i.v. amiodarone administration.

Intravenous amiodarone in intensive care. Time for a reappraisal?

Amiodarone is widely used in intensive care units for the treatment of a variety of arrhythmias. It is currently the drug of choice for supraventricular tachyarrhythmias in many units because of its combination of efficacy and safety. This review summarises the current state of knowledge regarding the short-term administration of intravenous amiodarone to control arrhythmias in perioperative, coronary care and intensive care patients. It outlines the electrophysiology, haemodynamics, pharmacokinetics and toxicity of the drug. In particular, it examines the recent concerns regarding acute pulmonary toxicity.

Uso de amiodarona oral como tratamiento crónico en un paciente con hepatitis fulminante previa por amiodarona intravenosa

Acute hepatitis for intravenous amiodarone is an uncommon problem with scarce appearances in medical literature. Sometimes, it has postulated that the vehicle of the intravenous preparation and not the active principle is the possible cause of this complication. We report a patient with fulminating hepatitis and severe encephalopathy following the administration of intravenous amiodarone. We present also the clinical evolution of the patient after reintroduction of oral amiodarone. In the end, we make a review of the associated literature with our case.

Time course of myocardial amiodarone uptake in the piglet heart using a chronic animal model.

This investigation sought to study single dose pharmacokinetics of amiodarone in a chronic animal model. We developed a new chronic animal model that allows serial direct access to the heart of the immature piglet via an implanted acrylic thoracic window. Following instrumentation and 72-hour recovery, amiodarone (5 mg/kg) was administered as a single intravenous bolus in immature piglets. Timed paired serum samples and myocardial biopsies for amiodarone level were obtained prior to, and up to 72 hours following, amiodarone administration. Peak concentrations of amiodarone in both serum (3.60 +/- 1.02 micrograms/ml) and tissue (84.2 +/- 6.50 ng/mg) occurred within 5 minutes of drug administration. As reported by others, this study demonstrated that the volume of distribution (VD) of amiodarone was large (33.31 +/- 35.21 L/kg), and the clearance (Cl) was low (13.6 +/- 4.4 ml/min/kg). Marked prolongation of both the serum t1/2 (29.98 +/- 29.26 hours) and the myocardial t1/2 (29.20 +/- 29.49 hours) were noted as well. The early, rapid myocardial peak of amiodarone in the immature myocardium corresponds with recent clinical observations of onset of antiarrhythmic efficacy 5 to 10 minutes following intravenous amiodarone administration in young children.

Clinical Study of the Intravenous Amiodarone in Acute Myocardial Infarction with Life-Threatening Refractory Ventricular Tachyarrhythmias

Background:Recently, the amiodarone has emerged as a promising antiarrhythmic agent and its efficacy and safety has been widely accepted with many literatures. But there was no general agreement regarding the dosage and indication of intravenous (IV) amiodarone in acute myocardial infarction with life-threatening refractory ventricular tachyarrhythmias. Method:From October 1995 through October 1997, we recruited retrospectively 9 patients of acute myocardial infarction who had received IV amiodarone for life-threatening refractory ventricular tachyarrhythmias and analyzed the initial response, adverse effect, and loading dose. Results:1) Acute efficacy:Eight of 9 patients promptly restored normal sinus rhythm immediately after intravenous amiodarone administration. 2) In-Hospital Mortality:One patients died due to ventricular tachyarrhythmias refractory to aggressive management and 5 in 8 patients who had responded promptly with IV amiodarone discharged alive and other 3 patients died due to cardiogenic shock with normal sinus rhythm. 3) Immediate adverse effects:Five patients experienced immediate adverse effects after IV amiodarone;3 patients of hypotension, 1 patient of first degree AV block, and the other of Morbitz type 2 AV block. 4) Long term follow-up:Among 5 patients discharged alive, one died as unexpected consequence. Other 4 patients have been still alive without maintenance medication. Conclusion:The IV amiodarone for suppression of life-threatening ventricular tachyarrhythmias in patients with acute myocardial infarction seemed to be an effective second-line therapeutic drug and have acceptable adverse effects. In the future, the large scale study regarding the dosage and indication might be warrented. (Korean Circulation J 1998;28(8):1314-1321)

I.V. Amiodarone: What Do We Really Know About It?

The mechanism of amiodarone’s antiarrhythmic action is not known. In vitro and clinical studies have demonstrated that it has multiple actions that could potentially contribute to an antiarrhythmic response. These include block of ion channels (sodium, potassium and calcium), receptors (alpha adrenergic, beta adrenergic and muscarinic) and intracellular transduction pathways (phospholipase and thyroid hormone). It is generally speculated that the drug’s large number of actions is responsible for the broad spectrum of arrhythmias that respond to orally administered amiodarone. However, all of these actions may not e operative during i.v. therapy. Numerous studies have demonstrated the electrophysiologic differences between acute and chronically administered amiodarone. Comparison of i.v and oral amiodarone is complicated by the slow tissue accumulation of amiodarone, the possible effects of its active desethyl metabolite, potential anti-thyroid effects and the potential action of the diluent in the intravenous formulation, polysorbate 80 (Tween-80). Although most comparisons of acute and chronically administered amiodarone found greater effects with chronic administration, a recent report found amiodarone to clock L-type calcium channels acutely in cell culture but not in cells harvested from chronically treated animals [1]. The potential importance of this action is supported by a report by Kojima, et al [2] in which they concluded that amiodarone’s anti~brillatory action in isolated perfused rat hearts was due to a reduction in intracellular calcium. Some, but not all, of the known actions of amiodarone can be observed clincally. In some cases the action is not temporally correlated with antiarrhythmic response. For example, QT prolongation (a marker of Class III antiarrhythmic action or potassium channel block) is not seen after acute intravenous administration. High intravenous dosages, $300 mg, have been observed to cause hypotension, heart block or excessive bradycardia but these reactions may be due to Tween-80. The bradycardia that is seen during chronic therapy is most likely due to non-competitive inhibition of beta adrenergic receptors. The electrophysiological actions of amiodarone in humans depend on the route of administration and the duration of therapy. Following acute intravenous amiodarone administration, prolongation of the AH interval and an increase in the refractory periods of the AV node and bypass tracts are seen, but again this may be due to the effects of the Tween-80. No acute changes occur in either sinus rate or atrial or ventricular repolarization or refractoriness, whereas these are prolonged during chronic oral therapy.

Intravenous amiodarone for therapy of atrial fibrillation and flutter in critically ill patients with severely depressed left ventricular function.

A retrospective review was done to determine the efficacy and hemodynamic effects of slow intravenous amiodarone administration on invasively monitored patients with acute onset of atrial fibrillation or atrial flutter and left ventricular ejection fractions < 15%. Eight patients met predefined inclusion criteria. All received 300 mg amiodarone intravenously over 1 hour. Seven reverted to sinus rhythm within 1 hour, with return of most hemodynamic variables to baseline. Before reversion, each patient experienced a beneficial slowing of heart rate (mean, 28%) resulting in significant improvement of stroke volume index (mean, 49%) and left ventricular stroke work index (mean, 61%). No patient had hemodynamic deterioration attributable to amiodarone infusion. Slow intravenous infusion of amiodarone appears to be an effective and hemodynamically well-tolerated therapy for atrial fibrillation and atrial flutter in critically ill patients with marked depression of left ventricular systolic function.

Efficacy of Intravenously Administered Amiodarone for Short-Term Control of Serious Arrhythmias

Intravenously administered amiodarone exerts substantial antiarrhythmic activity that is based on several different electrophysiologic mechanisms. Of these, the most important consists of an antitachycardic effect together with a significant prolongation of repolarization. The acute intravenous administration of amiodarone has been found to be effective in supraventricular and ventricular tachyarrhythmias resistant to conventional antiarrhythmic agents. Because amiodarone is free of detrimental hemodynamic effects in the majority of patients, intravenous administration of this compound seems to be particularly suitable in patients with serious arrhythmias in the setting of compromised left ventricular function.

Efficacy of Intravenously Administered Amiodarone for Short-Term Control of Serious Arrhythmias

Summary: Intravenously administered amiodarone exerts substantial antiarrhythmic activity that is based on several different electrophysiologic mechanisms. Of these, the most important consists of an antitachycardic effect together with a significant prolongation of repolarization. The acute intravenous administration of amiodarone has been found to be effective in supraventricular and ventricular tachyarrhythmias resistant to conventional antiarrhythmic agents. Because amiodarone is free of detrimental hemodynamic effects in the majority of patients, intravenous administration of this compound seems to be particularly suitable in patients with serious arrhythmias in the setting of compromised left ventricular function.

The Use‐Dependent Effects of Acute and Chronic Amiodarone Administration on His‐Purkinje Conduction and the Interaction of β‐Adrenergic Stimulation

Use‐Dependent Effects of Amiodarone. Amiodarone is a highly effective antiarrhythmic agent. However, its exact mechanism of action remains uncertain. Prior studies suggest that intravenous amiodarone produces different electrophysiologic effects than chronic amiodarone administration. In addition, the effects of other antiarrhythmic agents and β‐adrenergic stimulation on the electrophysiologic effects of amiodarone have not been well defined. In this study, we sought to evaluate the use‐dependent effects of intravenous (acute) versus oral (chronic) amiodarone administration on His‐Purkinje conduction in a closed‐chest canine model. We also sought to evaluate the effects of intravenous lidocaine and isoproterenol on the use‐dependent effects of chronically administered oral amiodarone. We found: (1) Acutely administered intravenous amiodarone (5 mg/kg bolus, followed by a 0.05 mg/kg/min infusion) does not produce a significant use‐dependent effect on His‐Purkinje conduction (serum amiodarone level 2.7 ± 1.1 mg/L), and acute beta blockade did not enhance use‐dependent effects of amiodarone; (2) Chronically administered oral amiodarone (1,000 mg/day ± 2 weeks) produced significant use‐dependent effects on His‐Purkinje conduction at similar serum drug concentrations (mean level 2.6 ± 1.5 mg/L; (3) Intravenous lidocaine (10 mg/kg bolus, 0.2 mg/kg/min infusion) produced significant additional use‐dependent effects to that of chronic oral amiodarone but only at rapid paced rates (cycle length 300‐210 msec); and (4) Isoproterenol (5 μg/min infusion) significantly attenuated the use‐dependent effects of chronically administered amiodarone. The mechanism of action of acutely administered intravenous amiodarone appears to be different from that of chronic oral amiodarone. In addition, the marked use‐dependent effects observed after chronic amiodarone administration were reversed after catecholamine administration suggesting that attenuation of use dependence by sympathetic stimulation may negate some of salutary effects of amiodarone.

Electrocardiographic and antiarrhythmic effects of intravenous amiodarone: Results of a prospective, placebo-controlled study

The antiarrhythmic efficacy of intravenously administered amiodarone was examined in a prospective, randomized, placebo-controlled study that involved 77 patients after coronary artery bypass surgery. Amiodarone was given after surgery in a loading bolus of 300 mg for 2 hours followed by 1200 mg every 24 hours for 2 days and 900 mg every 24 hours for the next 2 days. Amiodarone suppressed both supraventricular and ventricular arrhythmias within 12 hours after the start of therapy. Particularly, the incidence of atrial fibrillation (5% vs 21% in the control group;p < 0.05) and of nonsustained ventricular tachycardia (3% vs 16%;p < 0.05) was reduced by amiodarone. Heart rate was slowed (p < 0.001) and repolarization—as judged by JTc interval—was prolonged compared with the control group (p < 0.01). In two patients, amiodarone infusion was stopped because of excessive QTc prolongation. No detrimental hemodynamic effects of the drug were observed. Thus the intravenous administration of amiodarone appears to be suitable for patients in whom rapid suppression of symptomatic supraventricular and ventricular arrhythmias is warrented in the presence of left ventricular dysfunction.

Early Hepatitis during Intravenous Amiodarone Administration

Two patients with acute changes suggesting acute hepatitis after parenteral amiodarone administration are described. No other explanation for liver damage was found in these patients. Normalization of liver function in spite of continuation of drug infusion was observed.

Clinical efficacy of intravenous amiodarone in the short term treatment of recurrent sustained ventricular tachycardia and ventricular fibrillation.

The clinical efficacy of intravenous amiodarone in terminating sustained ventricular tachycardia and in preventing recurrences of ventricular tachycardia and ventricular fibrillation was evaluated in 26 patients. All of them presented with organic heart disease accompanied by depressed left ventricular function. Intravenous amiodarone terminated spontaneous ventricular tachycardia in eight of 19 patients. Fifteen of the 26 patients had had at least one episode of ventricular tachycardia or ventricular fibrillation each day in the period immediately before the intravenous administration of amiodarone. Amiodarone controlled ventricular tachycardia or ventricular fibrillation in nine of these 15 patients; in three further cases it was successful when supplemented by additional administration of a previously ineffective antiarrhythmic drug and ventricular pacing. Two patients died despite these measures. In one, the amiodarone infusion had to be stopped because of an arrhythmogenic effect. Sustained deterioration of haemodynamic function or of pre-existing intraventricular conduction disturbances was never seen. Intravenous amiodarone was effective in terminating sustained ventricular tachycardia and in preventing frequent episodes of ventricular arrhythmia that were refractory to other antiarrhythmic drugs.

The Effect of Chronic Oral and Acute Intravenous Amiodarone Administration on Ventricular Defibrillation Threshold Using Implanted Electrodes in Dogs

The effect of acute intravenous administration and chronic oral loading of amiodarone on defibrillation threshold was evaluated in normal anesthetized dogs using implanted superior vena caval spring and left ventricular patch electrodes. The effect of oral loading with amiodarone was evaluated by comparing three groups of six dogs each that received either no drug, 200 mg/day for 9 days, or 400 mg/day for 9 days. Defibrillation threshold was evaluated by administering a fixed sequence of shocks with increasing energies until defibrillation was successful. Defibrillation was determined 13 times in each animal. The mean defibrillation threshold (plus or minus standard error of the mean) was 7.5 +/- 0.3 J in the control group, 15.4 +/- 0.6 J in the group receiving amiodarone 200 mg/day, and 17.9 +/- 0.8 J for the group receiving 400 mg/day. These values are significantly different using analysis of variance and Tukey's test. The acute effect of intravenous amiodarone, 5 mg/Kg was evaluated in five dogs using each dog as its own control. The mean defibrillation threshold during control period was 10.8 +/- 0.4 J, and during the first two hours after amiodarone administration was 10.8 +/- 0.4 J. There was no significant difference. Thus, in this study oral administration of a loading dose of amiodarone comparable to that used in patients produced a dose dependent increase in defibrillation threshold, whereas no change in defibrillation threshold was observed acutely after intravenous administration.