title: Electrophysiologic and proarrhythmic effects of intravenous inotropic agents.
abstract: Intravenous inotropic agents promote increased myocardial contractility via elevation of myocyte calcium concentrations, a mechanism that is also known to promote the development of cardiac arrhythmias. The purpose of this article is to review the electrophysiologic effects and relative potential for proarrhythmia associated with dobutamine, dopamine, and the phosphodiesterase inhibitors amrinone and milrinone. Dobutamine increases sinoatrial node automaticity and decreases atrial and atrioventricular (AV) node refractoriness and AV nodal conduction time. The drug also decreases ventricular refractoriness in both healthy and ischemic myocardium. Dobutamine has been shown to increase heart rate in a dose-related fashion in animals and in humans. In humans, dobutamine has been reported to induce ventricular ectopic activity (VEA) in 3% to 15% of patients, although VEAs are often asymptomatic, requiring no intervention. Ventricular tachycardia (VT) associated with dobutamine appears to occur rarely. Patients with underlying arrhythmias or heart failure or those receiving excessive doses of dobutamine are at greatest risk for proarrhythmia. Dopamine increases automaticity in Purkinje fibers and has a biphasic effect on action potential duration. Dopamine has been reported to induce atrial or ventricular arrhythmias in animals. In humans, dopamine may be associated with dose-related sinus tachycardia but has also been reported to cause VEA, which is usually asymptomatic. Dopamine-associated VT appears to occur rarely. Dopamine produces greater elevations in heart rate or frequency of ventricular premature beats at a given value of cardiac index than does dobutamine. The phosphodiesterase inhibitors amrinone and milrinone increase conduction through the AV node and decrease atrial refractoriness. Intravenous administration of these drugs may result in sinus tachycardia in some patients and has been reported to cause VEA, which is often asymptomatic, in up to 17% of patients. VT has also been reported in association with short-term use of intravenous phosphodiesterase inhibitors. In summary, intravenous inotropic agents may be associated with proarrhythmic effects in some patients. The primary arrhythmias reported are sinus tachycardia and VEA, although other supraventricular or ventricular arrhythmias have been reported less commonly. However, clinically significant proarrhythmic effects associated with these agents appear to occur rarely, and, at conventional doses, intravenous inotropic agents are relatively safe with respect to proarrhythmic effects.
authors.affiliation: College of Pharmacy and Allied Health Professions, Wayne State University, Detroit, MI 48202, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Tisdale
authors.forename: R
authors.initials: R
authors.lastname: Patel
authors.forename: C R
authors.initials: CR
authors.lastname: Webb
authors.forename: S
authors.initials: S
authors.lastname: Borzak
authors.forename: B J
authors.initials: BJ
authors.lastname: Zarowitz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000676:Amrinone / Q000009:adverse effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004280:Dobutamine / Q000009:adverse effects; D004285:Dogs; D004298:Dopamine / Q000009:adverse effects; D004594:Electrophysiology; D006168:Guinea Pigs; D006801:Humans; D007275:Injections, Intravenous; D008875:Middle Aged; D020105:Milrinone; D009200:Myocardial Contraction / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects; D011728:Pyridones / Q000009:adverse effects; D051381:Rats; D013268:Stimulation, Chemical
chemical_list: D002316:Cardiotonic Agents; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; D004280:Dobutamine; D020105:Milrinone; D000676:Amrinone; D004298:Dopamine