The hypotensive effect of intravenous amiodarone is sustained throughout the maintenance infusion period.
1. Hypotension frequently occurs with use of intravenous amiodarone and is managed by slowing the rate of administration. This response has been attributed to the cosolvents in the formulation and is believed to be solely related to the initial loading dose. The present study was performed to determine whether intravenous amiodarone-induced hypotension persists beyond the loading dose and into the maintenance infusion period and also whether hypotension occurs with maintenance level dosing alone. 2. Anaesthetized beagle dogs (n = 7/group) were instrumented to assess haemodynamics. Animals were treated with the human-equivalent dosing regimen (loading dose followed by maintenance infusion) of intravenous amiodarone or control (5% dextrose in water). 3. No haemodynamic changes were observed in the control group during the 6 h study. In contrast, administration of the standard intravenous amiodarone regimen produced rapid and significant decreases in mean aortic pressure, cardiac output and maximum rate of change of left ventricular pressure that persisted throughout the 6 h maintenance infusion period. Administration of amiodarone as the maintenance infusion dose alone produced haemodynamic changes that were similar in magnitude to those observed with administration of the full dosing regimen, but were delayed in onset by approximately 60 min. 4. Dosing with a cosolvent-free formulation of amiodarone (PM101) caused no haemodynamic effects during the 6 h dosing period, indicating that the cardiodepressant effects of intravenous amiodarone were due to its cosolvents. 5. These data suggest that consideration should be given to intravenous amiodarone as a potential cause for sustained hypotension during prolonged infusion.
Cushing
Daniel J
DJ
Prism Pharmaceuticals, Inc., King of Prussia, Pennsylvania, USA. dcushing@prismpharma.com
Cooper
Warren D
WD
Gralinski
Michael R
MR
Lipicky
Raymond J
RJ
D000638:Amiodarone / Q000008:administration & dosage* / Q000633:toxicity*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007022:Hypotension / Q000139:chemically induced* / Q000503:physiopathology*; D007262:Infusions, Intravenous; D013997:Time Factors
D000638:Amiodarone