DISCUSSION

Despite its ubiquitous and clinically important role as a central antiarrhythmic agent, amiodarone’s significant toxicity and side effect profile represent a considerable challenge to practitioners in the emergency and intensive care settings. The drug is available in two formulations: oral and IV. The oral pharmacology and its mechanism of hepatic metabolism, accumulation, and incidence of toxicity were described through a series of case reports and translational pathologic studies from the 1960s to the 1980s, and shown to have an injury pattern similar to that of alcohol-induced liver disease.[6, 7] Although transient elevations in hepatic laboratory studies are common, the incidence of liver injury warranting the discontinuation of treatment is seen in roughly 1% of patients taking the oral formulation.[8] Generally, elevations in liver enzymes greater than twice the normal levels should prompt concern for true liver toxicity and warrant discontinuing the medication. Over several decades, a series of case reports have highlighted the incidence of a rare (< 0.01%) and unique type of acute liver injury secondary to the IV infusions of amiodarone.[9] Unlike the oral formulary, abnormalities are often seen within hours of administration and improved within weeks after discontinuing the medication.[10] This process is considered to have a unique mechanism attributed to either ischemic hepatitis, idiosyncratic toxicity, hypersensitivity, or toxicity of the vehicle (polysorbate 80) causing direct cell toxicity, free radical formation, and centrilobular necrosis.[11-13] Since the early 2000s, several case reports have been published with accompanying literature reviews considering the relationship between IV amiodarone and liver toxicity. Rätz Bravo et al [12] reported a series of three cases while describing 25 additional cases dating back to 1986. In 2013, Nasser et al [13] presented one case report and a literature review of 33 previously reported cases (28 cases were previously reported by Rätz Bravo et al [12]). This report was the first to comprehensively review cases in which patients were able to be re-challenged with oral amiodarone without further compromising their acute liver injury. Despite IV amiodarone’s regular use in the ED setting, the emergency medicine literature is more limited. A case report out of an ED in Torino, Italy, described the acute development of transaminase elevation with evidence of functional liver toxicity secondary to parenteral administration of amiodarone. The decision was made to discontinue the medication leading to eventually resolution of liver injury.[14] A second case from the University of Genova reported an ED administration of IV amiodarone for acute arrhythmia, which subsequently led to the development of hepatic toxicity.[15] These two cases served to highlight the importance of this disease process in emergency and critical care practice.

When taken together, the existing case literature has enabled practitioners to develop broad definitions for understanding the presentation, management, and clinical course of this pathologic process. It is generally accepted that acute hepatotoxicity secondary to IV amiodarone develops within hours to days of the drug’s initial administration. It is not uncommon for liver enzymes to rise as high as the thousands U/L, with or without the development of functional liver failure. Discontinuation of the infusion is the first-line treatment and often leads to complete liver recovery within a period of several days to weeks. There is, however, a considerable cohort of patients, who are secondary to initial hepatic insult or overall burden of comorbidities and are more at risk for developing this toxicity and …