Multisociety guidelines published in 2018 on antiarrhythmic drugs provide an overview of clinical pharmacology and recommended monitoring parameters. Co-administration of amiodarone with digoxin, beta-blockers, verapamil, or diltiazem should be closely monitored due to increased risk of bradycardia, atrioventricular (AV) block, and hypotension; however, data supporting a dose-dependent relationship between amiodarone and hypotension or shock were not described in the guidelines. [1]
Due to administration of amiodarone in critically ill patients who were already hemodynamically unstable, an exact correlation between incidence of hypotension and amiodarone administration was difficult to discern. Thus, one 2003 randomized, double-blind, placebo-controlled trial investigated the acute cardiovascular effects of an intravenous (IV) loading dose of amiodarone in 30 adult patients undergoing non-emergent coronary artery bypass grafting. Participants were stratified based on their preoperative left ventricular ejection fraction (LVEF) into those with LVEF ≤30% or >30% and were randomly assigned to receive either 150 mg of intravenous amiodarone diluted in 100 mL of normal saline or an equivalent placebo over 10 minutes following sternal closure. Notably, hypotension requiring intervention occurred in 3 patients (20%) of the amiodarone cohort versus 0 of placebo (p= 0.22); hypotension episodes in the amiodarone arm were transient and resolved without significant hemodynamic compromise. [2]
A 2010 animal study investigated whether the hypotensive effect of intravenous (IV) amiodarone persists beyond the loading dose and into the maintenance infusion period, as well as whether hypotension occurs with maintenance-level dosing alone. In this study, anesthetized beagle dogs were administered a human-equivalent dosing regimen of IV amiodarone (n= 7 dogs; loading dose followed by maintenance infusion) or control (n= 7 dogs; 5% dextrose in water). Hemodynamic parameters, including mean aortic pressure, cardiac output, and the maximum rate of change of left ventricular pressure, were monitored for six hours. The control group showed no hemodynamic changes during the study. However, the amiodarone-treated group experienced rapid and significant reductions in hemodynamic parameters, which persisted throughout the maintenance infusion period. When amiodarone was administered at the maintenance dose alone, similar hemodynamic effects were observed, although their onset was delayed by approximately 60 minutes. Importantly, dosing with a cosolvent-free formulation of amiodarone (PM101) caused no hypotension or other hemodynamic changes, indicating that the cardiodepressant effects were attributable to the cosolvents in the standard formulation. These findings suggest that sustained hypotension during prolonged infusion may be a potential consequence of intravenous amiodarone. However, due to the use of an animal model, caution is warranted in the interpretation of these results. [3]
Other studies have further sought to elucidate the relationship between amiodarone dose and hypotension. In one 2008 study utilizing bolus dose IV amiodarone 300 mg for stable ventricular tachycardia, incidence of hypotension that required emergency direct current (DC) cardioversion was reportedly higher (17%; 95% confidence interval [CI] 8% to 32%) than historic trends observed with amiodarone 150 mg doses (6%; 95% CI 1% to 20%). In another 2017 study (PROCAMIO), use of 5 mg/kg IV bolus amiodarone for treatment of tolerated wide QRS complex tachycardia resulted in an approximate 43% rate of cardiac adverse events (15 patients) in the subsequent 40-minute follow-up; of these cases, five were hypotension. Still, more data is required to determine the exact correlation between amiodarone dose and hypotension/shock. [4], [5]