Concomitant Acute Hepatic Failure and Renal Failure Induced by Intravenous Amiodarone: A Case Report and Literature Review

Abstract

Hepatotoxicity caused by chronic oral amiodarone is well documented with around 15-20% incidence rate. However, acute liver failure due to intravenous (IV) amiodarone is rare clinical presentation with 3% incidence rate. Incidence of concomitant renal failure is even rarer. There is no full explanation for the underlying mechanism. Herein, we are presenting a rare case of concomitant acute hepatic failure and acute-on-chronic renal injury induced by use of IV amiodarone. A 67-year-old man with past medical history of coronary artery disease s/p coronary artery bypass graft (CABG), history of alcoholism, and chronic kidney disease stage 3 presented with chest pain for 1 week. In the emergency department (ED), he was found to have atrial flutter. Due to unresponsiveness to IV β-blocker and diltiazem, the patient was loaded with IV amiodarone and continued IV amiodarone drip. His liver function tests (LFTs) and renal functions at the time of administration of IV amiodarone were aspartate transaminase (AST) 176 (10-42 IU/L) and alanine transaminase (ALT) 208 (10-60 IU/L), international normalized ratio (INR) 1.39 (reference value 2-3), blood urea nitrogen (BUN) 37 (5-25 mg/dL), and creatinine 1.85. Sixteen hours later patient developed acute hepatic failure with AST 4,250 (reference value 10-42 IU/L), ALT 2,422 (10-60 IU/L), INR 2.28, and acute renal failure with creatinine of 3.2 mg/dL (0.44-1.0 mg/dL), and BUN of 44 mg/d (5-25 mg/dL). Patient was intubated due to acute hepatic encephalopathy and sent to intensive care unit (ICU). IV amiodarone was stopped immediately. All workup for other causes of acute hepatic failure came back negative. He was started on IV N-acetylcysteine and required hemodialysis for acute-on-chronic renal failure. LFTs peaked 72 h after discontinuation of amiodarone. Kidney functions started to improve 5 days after discontinuation of amiodarone and patient came off hemodialysis. Acute hepatic failure as result of IV amiodarone is a rare presentation; however, it has a high mortality. Risk factors include low ejection fraction, hepatic congestion and pre-existing hepatic dysfunction. No obvious underlying mechanism to this presentation has been fully explained. Acute renal failure can be associated with this presentation which is even rarer. Stopping IV amiodarone, administering N-acetylcysteine and good supportive care can lead to favorable outcome.

Low-Dose Intravenous Amiodarone-Induced Acute Hepatic Failure

“…N-acetylcysteine has been used as the treatment of hepatotoxicity in several case reports. 2,5,10,11 One study showed the use of n-acetylcysteine may have a role in promoting transplant-free survival in patients with early-stage nonacetaminophen acute liver failure (specific causes not listed). 11 There are case reports showing the patient tolerated rechallenge with oral amiodarone once abnormalities resolved.…”

“…4,5 First, long-chain fatty acids are transported into the cytoplasm through the plasma membrane, and longchain acyl-CoA is produced from long-chain fatty acids by acyl-CoA synthase. 4,5 Long-chain acyl-CoA interacts with carnitine to form long-chain acylcarnitine through the enzymatic action of carnitine palmitoyltransferase I, which is transported from the cytoplasm to the inner side of the outer mitochondrial membrane. 4,5 Second, long-chain acylcarnitine is transported into the mitochondrial matrix through the action of carnitine acylcarnitine translocase.…”

“…2 Long-chain fatty acids contribute to b-oxidation in the mitochondrial matrix, which provides 50%-70% of adenosine triphosphate in an adult heart. 4,5 There are 3 steps involved in long-chain fatty acids transport from the cytoplasm to the mitochondrial matrix. 4,5 First, long-chain fatty acids are transported into the cytoplasm through the plasma membrane, and longchain acyl-CoA is produced from long-chain fatty acids by acyl-CoA synthase.…”

“…There are reported cases of intravenous amiodarone-induced liver injury as well as concomitant hepatic and renal toxicity. 1–5 The general trend of these cases reported was downtrending transaminases after cessation of infusion. Given its long half-life, it was believed that the hepatic toxicity associated with amiodarone infusion was due to polysorbate 80, a diluent used in its preparation, although some suggested the metabolites played a role as well.…”

Drug-Induced Liver Injury: Highlights and Controversies in the Recent Literature

“…ALF acute liver failure, HLA human leukocyte antigen, HTN hypertension, IV intravenous, MI myocardial infarction, MS multiple sclerosis, NAFLD non-alcoholic fatty live disease, RUCAM Roussel Uclaf Causality Assessment Method, TMP-SMX trimethoprim-sulfamethoxazole, VBDS vanishing bile duct syndrome Anti-arrhythmic agents Amiodarone 67-year-old male patient who was treated with IV amiodarone for atrial flutter [183] Hepatocellular Yes None Anti-platelet Clopidogrel 78-year-old male patient with a history of an MI [184] Mixed Yes None…”