Original Article

Hepatic Dysfunction in Patients Receiving Intravenous Amiodarone

Authors: Ali Hashmi, MD, Nicole R. Keswani, PharmD, Sharon Kim, MD, David Y. Graham, MD

Abstract

Objectives: Amiodarone is a commonly used antiarrhythmic drug. Hepatotoxicity following chronic oral administration occurs in 1% to 3% of patients. Hepatotoxicity following intravenous (IV) administration is infrequent but may be associated with dramatic increases in serum transaminases. We describe the incidence of liver toxicity among patients receiving IV amiodarone during a 5-year period.

Methods: This was a single-center retrospective review of patients receiving IV amiodarone for any cause. The outcome measures were development of elevated serum transaminases and the relation of transaminitis to all-cause 30-day mortality.

Results: A total of 1510 patients received amiodarone intravenously between 2005 and 2011; 77 (5%) developed elevated liver enzymes. Enzyme elevation was divided into mild (100–300 IU/L), moderate (300–1000 IU/L), and severe (>1000 IU/L). The median alanine aminotransferase was 189 (37–10,006) IU/L and aspartate aminotransferase was 253 (84–12,005) IU/L. The 30-day mortality among those with transaminitis was 22%; however, no patient died of amiodarone-related liver disease.

Conclusions: Amiodarone can cause severe elevation in liver enzymes. The incidence of severe transaminitis is low; deaths following IV amiodarone are rarely caused by drug-induced liver failure.

 

This content is limited to qualifying members.

Existing members, please login first

If you have an existing account please login now to access this article or view purchase options.

Purchase only this article ($25)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.

References

1. Goldschlager N, Epstein AE, Naccarelli G, et al. Practical guidelines for clinicians who treat patients with amiodarone. Practice Guidelines Subcommittee, North American Society of Pacing and Electrophysiology. Arch Intern Med 2000;160:1741-1748.
 
2. Goldschlager N, Epstein AE, Naccarelli GV, et al. A practical guide for clinicians who treat patients with amiodarone: 2007. Heart Rhythm 2007;4:1250-1259.
 
3. Roy D, Talajic M, Dorian P, et al. Amiodarone to prevent recurrence of atrial fibrillation. Canadian Trial of Atrial Fibrillation Investigators. N Engl J Med 2000;342:913-920.
 
4. Podrid PJ. Amiodarone: reevaluation of an old drug. Ann Intern Med 1995;122:689-700.
 
5. Lewis JH, Ranard RC, Caruso A, et al. Amiodarone hepatotoxicity: prevalence and clinicopathologic correlations among 104 patients. Hepatology 1989;9:679-685.
 
6. Hyatt RH, Sinha B, Vallon A, et al. Noncardiac side-effects of long-term oral amiodarone in the elderly. Age Ageing 1988;17:116-122.
 
7. Ratz Bravo AE, Drewe J, Schlienger RG, et al. Hepatotoxicity during rapid intravenous loading with amiodarone: description of three cases and review of the literature. Crit Care Med 2005;33:128-134.
 
8. Agozzino F, Picca M, Pelosi G. Acute hepatitis complicating intravenous amiodarone treatment. Ital Heart J 2002;3:686-688.
 
9. Rhodes A, Eastwood JB, Smith SA. Early acute hepatitis with parenteral amiodarone: a toxic effect of the vehicle? Gut 1993;34:565-566.
 
10. Huang X, Yang Y, Zhu J, et al. Clinical applications and acute hepatotoxicity of intravenous amiodarone. J Int Med Res 2009;37:1928-1936.
 
11. McGovern B, Garan H, Ruskin JN. Serious adverse effects of amiodarone. Clin Cardiol 1984;7:131-137.
 
12. Chan AL, Hsieh HJ, Hsieh YA, et al. Fatal amiodarone-induced hepatotoxicity: a case report and literature review. Int J Clin Pharmacol Ther 2008;46:96-101.
 
13. Pye M, Northcote RJ, Cobbe SM. Acute hepatitis after parenteral amiodarone administration. Br Heart J 1988;59:690-691.
 
14. Simon JP, Zannad F, Trechot P, et al. Acute hepatitis after a loading dose of intravenous amiodarone. Cardiovasc Drugs Ther 1990;4:1467-1468.
 
15. Maker AV, Orgill DP. Rapid acute amiodarone-induced hepatotoxicity in a burn patient. J Burn Care Rehabil 2005;26:341-343.
 
16. Nasser M, Larsen TR, Waanbah B, et al. Hyperacute drug-induced hepatitis with intravenous amiodarone: case report and review of the literature. Drug Healthc Patient Saf 2013;5:191-198.
 
17. Faniel R, Schoenfeld P. Efficacy of i.v. amiodarone in converting rapid atrial fibrillation and flutter to sinus rhythm in intensive care patients. Eur Heart J 1983;4:180-185.
 
18. Aravanis C. Acute thrombophlebitis due to IV use of amiodarone. Chest 1982;82:515-516.
 
19. Installe E, Schoevaerdts JC, Gadisseux P, et al. Intravenous amiodarone in the treatment of various arrhythmias following cardiac operations. J Thorac Cardiovasc Surg 1981;81:302-308.
 
20. Morady F, Scheinman MM, Shen E, et al. Intravenous amiodarone in the acute treatment of recurrent symptomatic ventricular tachycardia. Am J Cardiol 1983;51:156-159.
 
21. James PR, Hardman SM. Acute hepatitis complicating parenteral amiodarone does not preclude subsequent oral therapy. Heart 1997;77:583-584.
 
22. Souney PF, Cooper WD, Cushing DJ. PM101: intravenous amiodarone formulation changes can improve medication safety. Expert Opin Drug Saf 2010;9:319-333.
 
23. Gallik DM, Singer I, Meissner MD, et al. Hemodynamic and surface electrocardiographic effects of a new aqueous formulation of intravenous amiodarone. Am J Cardiol 2002;90:964-968.
 
24. Somberg JC, Bailin SJ, Haffajee CI, et al. Intravenous lidocaine versus intravenous amiodarone (in a new aqueous formulation) for incessant ventricular tachycardia. Am J Cardiol 2002;90:853-859.
 
25. Somberg JC, Timar S, Bailin SJ, et al. Lack of a hypotensive effect with rapid administration of a new aqueous formulation of intravenous amiodarone. Am J Cardiol 2004;93:576-581.
 
26. Lahbabi M, Aqodad N, Ibrahimi A, et al. Acute hepatitis secondary to parenteral amiodarone does not preclude subsequent oral therapy. World J Hepatol 2012;4:196-198.
 
27. Babatin M, Lee SS, Pollak PT. Amiodarone hepatotoxicity. Curr Vasc Pharmacol 2008;6:228-236.
 
28. Gluck N, Fried M, Porat R. Acute amiodarone liver toxicity likely due to ischemic hepatitis. Isr Med Assoc J 2011;13:748-752.