Predictors of intravenous amiodarone induced liver injury

Abstract

BackgroundIntravenous (IV) amiodarone may be associated with liver injury that may necessitate drug discontinuation. The prediction of amiodarone induced liver injury (AILI) and its severity may help careful patient monitoring or the choice of other measures alternative to amiodarone in high risk patients. Little is known regarding predictors of AILI.ObjectivesTo address the predictors of AILI and its severity.MethodsThe study included 180 patients indicated for IV amiodarone therapy who were divided into 2 groups: cases (90 patients) who developed AILI, and controls (90 patients) who did not develop AILI. AILI was defined as aminotransferase (ALT and AST) elevation by ⩾2 folds of baseline levels. Severe AILI was defined as enzyme elevation by >5 folds of baseline values.ResultsMultivariate analysis showed that the presence of cardiomyopathy (P = 0.032), congestive hepatomegaly (P = 0.001), increasing baseline total bilirubin (P < 0.0001), direct current cardioversion (P = 0.015), and increasing dose of amiodarone (P = 0.014) to be independent predictors for AILI. Regarding severity of AILI, inotropic support (P = 0.034), congestive hepatomegaly (P = 0.012), increasing baseline total bilirubin (P = 0.001), and increasing dose of amiodarone (P = 0.002) were found to be independent predictors for severe AILI. Among cases, linear regression analysis showed that baseline ALT was the only significant independent predictor of post-amiodarone ALT (P < 0.0001), while baseline AST (P < 0.0001) and EF (P = 0.012) were the only significant independent predictors of post-amiodarone AST.ConclusionsCompromised cardiac, hepatic, and hemodynamic conditions, with increasing dose of IV amiodarone were associated with AILI. Severity of liver injury had linear relationship with baseline aminotransferase levels and left ventricular systolic function.

Immediate oral amiodarone re-challenge following the development of parenteral-induced acute liver toxicity

“…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 have higher rates of mortality. [16] It is unclear whether IV amiodarone-induced hepatotoxic patients could be re-challenged with the oral formulation of amiodarone. The most well-established theory for amiodarone's toxicity is that polysorbate 80, a diluent in the parenteral formulation, and not the iodinated benzofurane molecule itself, is the toxic culprit.…”

Hyperammonemic Encephalopathy and Lipid Dysmetabolism in a Critically Ill Patient after A Short Course of Amiodarone

“…Steatosis during amiodarone therapy may result from impaired ß-oxidation [8][9]. By contrast, acute hepatotoxicity following intravenous loading appears exceptional, and the possible role of the solvent has been discussed [10][11][12][13][14][15]. Usually, liver injury is rapidly reversible after discontinuation of amiodarone [2].…”

Hemodynamic Instability During Liver Transplantation in Patients With End-stage Liver Disease: A Consensus Document from ILTS, LICAGE, and SATA

“…114 The use of amiodarone may be associated with significant hypotension and hepatotoxicity. 116,117…”