Adverse Effects of Intravenous Amiodarone in 5 Dogs

Abstract

A 74.0-kg, 1.5-year-old, castrated male Newfoundland was presented for pharmacological cardioversion of atrial fibrillation. Three months before presentation, the dog was diagnosed with ''lone'' atrial fibrillation (ie, atrial fibrillation in the absence of detectable structural heart disease), underwent successful transthoracic electrical direct current (DC) cardioversion, and was treated with sotalol a (2.0 mg/kg PO q12h). Reversion to atrial fibrillation was confirmed 2 1 2 months later by ECG. At presentation, the dog was asymptomatic and receiving sotalol a (2.0 mg/kg PO q12h). Physical examination was normal except for an irregular heart rhythm, variable pulse quality, and pulse deficits. The biochemical profile was within reference intervals for the laboratory. Echocardiography was normal. An ECG confirmed atrial fibrillation with a ventricular response rate of 130-160 bpm. The dog was admitted to the hospital Intensive Care Unit for pharmacologic cardioversion.On the 1st day, the dog received 3 doses of lidocaine b (2 mg/kg IV q10min) with no change in rate or rhythm. Dofetilide c (6.76 mg/kg PO q12h) then was administered and the dosage subsequently increased to 6.76 mg/kg PO q8h on day 2. After 5 doses, the dog remained stable without a change in heart rate or underlying rhythm, but ventricular premature complexes (VPC) were noted including couplets and triplets. Dofetilide was discontinued on day 3 for presumed lack of efficacy and possible induction of ventricular ectopy, which resolved with discontinuation. The owner then elected pharmacologic conversion with IV amiodarone over other treatment options. On day 4, the dog was sedated with acepromazine d (0.02 mg/kg IM) and butorphanol e (0.2 mg/kg IM) for venous catheter placement. Amiodarone f was administered IV as a constant rate infusion (CRI) at 300 mg/kg/ min. Before beginning the CRI, the dog's systolic blood pressure was 115 mmHg. Two minutes after administration, injection site pain was noted and the CRI was decreased (150 mg/kg/min). After a total of 175 mg had been administered, the dog began salivating and pawing at its face. Its head and trunk became diffusely and severely erythematous, the muzzle and periorbital region became swollen, and severe weakness developed. Amiodarone was discontinued. The dog's systolic blood pressure, measured by Doppler, was 40-45 mmHg and atrial fibrillation remained with a ventricular response rate of 180-260 bpm. Because of a suspected anaphylactic reaction, IV Plasma Lyte 148 g and Hetastarch h fluids (total dose: 4 and 1 L, respectively), diphenhydramine i (1 mg/kg IV), and dexamethasone sodium phosphate j (0.8 mg/kg IV) were administered. A CRI of norepinephrine (0.3 mg/kg/min) was also begun. Over the next 2 hours, the dog's systolic blood pressure increased from 90 to 110 mmHg and the ventricular rate decreased from 120 to 150 bpm. The dog was discharged without antiarrhythmic therapy the next day and was started on digoxin and diltiazem administered orally for ventricular rate control 2 weeks later. D...

Letter to the Editor

“…Dear Editor I read with interest the report by Cober et al 1 describing adverse events in dogs receiving intravenously administered amiodarone (Amiodarone IV) containing the cosolvents polysorbate 80 and benzyl alcohol. The events described are quite similar to those we encountered during recent toxicology studies 2 designed to compare the currently marketed formulation utilized by Cober (containing the cosolvents polysorbate 80 and benzyl alcohol) with a recently approved formulation a that utilizes β‐cyclodextrin to solubilize amiodarone rather than the cosolvents.…”

General anesthesia with an injectable 8% v/v sevoflurane lipid emulsion administered intravenously to dogs

“…Also, histamine release due to hypersensitivity has been described in dogs receiving other drugs with polysorbate 80 (Cober et al. ). The production of lipid‐emulsified sevoflurane used 30% Intralipid, which is a non‐pyrogenic fat emulsion prepared with soybean oil, egg yolk phospholipids, and glycerin.…”

“…In one published study, polysorbate 80 was implicated in hypersensitivity when isoflurane-loaded nanoemulsion was administered to dogs (Krahn et al 2012). Also, histamine release due to hypersensitivity has been described in dogs receiving other drugs with polysorbate 80 (Cober et al 2009). The production of lipid-emulsified sevoflurane used 30% Intralipid, which is a non-pyrogenic fat emulsion prepared with soybean oil, egg yolk phospholipids, and glycerin.…”

Perioperative Monitoring of Heart Rate and Rhythm

“…Other drugs, such as IV amiodarone, might be more efficacious but are associated with a high risk of adverse side effects. 10,11 Therapeutic Options Therapeutic options include supportive measures and interventions to address transient imbalances as well as administration of antiarrhythmic drugs. Included in the supportive measures and interventions are the following:…”