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Toxicity, Antidysrhythmic: Differential Diagnoses & Workup

Author: Joshua B Gaither, MD, Chief Resident, Department of Surgery, Section of Emergency Medicine, Yale New Haven Hospital
Coauthor(s): Carin M Van Gelder, MD, Assistant Professor, Department of Surgery, Section of Emergency Medicine, Yale University; Consulting Staff and EMS Physician, SHARP Team, Division of Emergency Medical Services, Section of Emergency Medicine, Yale-New Haven Medical Center
Contributor Information and Disclosures

Updated: Jul 9, 2008

Differential Diagnoses

Myocardial Infarction
Toxicity, Antihistamine
Torsade de Pointes
Toxicity, Beta-blocker
Toxicity, Anticholinergic
Toxicity, Calcium Channel Blocker
Toxicity, Antidepressant
Toxicity, Cyclic Antidepressants

Workup

Laboratory Studies

  • Disopyramide - Class IA: Specific laboratory studies to determine disopyramide levels are highly technical and rarely useful for management of toxicity in the ED. Tests include quantitation and identification of disopyramide by chromatography and serum blood levels.
  • Procainamide - Class IA
    • Specific laboratory studies to determine levels are highly technical and not useful for management of toxicity in the ED; these include modified enzyme-mediated immunoassay and blood level tests. Procainamide levels are 12-16 mg/mL for mild toxicity and greater than 16 mg/mL for serious toxicity.
    • Total procainamide and N -acetyl procainamide (NAPA) therapeutic levels are 5-30 mg/mL; junctional tachycardia and conduction defects occur when levels are 42 mg/mL; severe hypotension and lethargy occur at levels greater than 60 mg/mL.
  • Quinidine - Class IA
    • Therapeutic levels are 2-6 mg/mL, with toxic levels greater than 8 mg/mL. Levels above 14 mg/mL have been found to cause cardiac toxicity in most patients.
    • An increase of 50% in the QT interval or QRS complex indicates significant toxicity. Check electrolyte levels.
  • Lidocaine - Class IB
    • Tests for lidocaine levels and its metabolite, monoethylglycylxylidide (MEGX), are available.
    • Effective plasma concentrations are 1.5-5 mg/mL. CNS toxicity is seen with 7 mg/mL. Fatal concentration is greater than 15 mg/mL for an adult and at least 3.8 mg/mL for a child.
  • Mexiletine and tocainide - Class IB, lidocaine analogs: Blood level tests are available and are cited most frequently in postmortem. Blood level tests are not useful in acute management.
  • Encainide - Class IC: Blood and urine level tests are available but are not useful in acute management.
  • Flecainide - Class IC: Blood level tests are available. Most serum ranges are derived from postmortem blood samples. A fluorescence polarization immunoassay also is available.
  • Propafenone - Class IC: Blood level tests are performed by liquid chromatography.
  • Ajmaline, cibenzoline, detajmium - Class IC: Cibenzoline blood level tests are performed using liquid chromatography.
  • Amiodarone - Class III
    • Obtain appropriate cultures to rule out an infectious etiology if the patient presents with ARDS and/or pulmonary fibrosis. Obtain thyroid function tests, including triiodothyronine (T3) and free T3, because thyroxine (T4), free T4, and thyroid-stimulating hormone (TSH) may remain elevated despite drug withdrawal.
    • Liver function tests are recommended, even though severe hepatic failure is rare. Torsade de pointes is a common proarrhythmia in older patients and patients with hypertrophic cardiomyopathies, although generally rare with amiodarone.
  • Bretylium - Class III: Serum concentration measurements are available but do not play a role in acute management of poisoning.
  • N -acetyl procainamide - Class III: Blood level tests are available but not useful for acute management.
  • Sotalol, ibutilide, and dofetilide - Class III: Testing for these agents still is under investigation.
  • Adenosine: No tests are available.

Imaging Studies

  • A chest x-ray (CXR) may be obtained for patients with cardiopulmonary signs and symptoms.

Other Tests

  • Electrocardiogram (ECG): Measurements of the QT interval and QRS prolongation, together with hypotension, are sensitive for serious poisoning.

More on Toxicity, Antidysrhythmic

Overview: Toxicity, Antidysrhythmic
Differential Diagnoses & Workup: Toxicity, Antidysrhythmic
Treatment & Medication: Toxicity, Antidysrhythmic
Follow-up: Toxicity, Antidysrhythmic
References
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References

  1. ATMAI. Effect of prophylactic amiodarone on mortality after acute myocardial infarction and in congestive heart failure: meta-analysis of individual data from 6500 patients in randomised trials. Amiodarone Trials Meta-Analysis Investigators. Lancet. Nov 15 1997;350(9089):1417-24. [Medline].

  2. Bacaner M, Brietenbucher J, LaBree J. Prevention of ventricular fibrillation, acute myocardial infarction (myocardial necrosis), heart failure, and mortality by bretylium: is ischemic heart disease primarily adrenergic cardiovascular disease?. Am J Ther. Sep-Oct 2004;11(5):366-411. [Medline].

  3. Connolly SJ, Schnell DJ, Page RL, et al. Dose-response relations of azimilide in the management of symptomatic, recurrent, atrial fibrillation. Am J Cardiol. Nov 1 2001;88(9):974-9. [Medline].

  4. Ellenhorn MJ, ed. Antidysrhythmic agents toxicity. In: Ellenhorn's Medical Toxicology - Diagnosis and Treatment of Human Poisoning. 2nd ed. Lippincott Williams & Wilkins; 1997:498-551.

  5. Goldfrank L. Antidysrhythmic agent toxicity. In: Goldfrank's Toxicology Emergencies. McGraw-Hill;1994:715-25.

  6. Hoffman BF. Arrhythmias and antiarrhythmic drugs. Mt Sinai J Med. Mar 1997;64(2):136-41. [Medline].

  7. Hohnloser SH. Proarrhythmia with class III antiarrhythmic drugs: types, risks, and management. Am J Cardiol. Oct 23 1997;80(8A):82G-89G. [Medline].

  8. Juurlink DN, Mamdani M, Kopp A, et al. Drug-drug interactions among elderly patients hospitalized for drug toxicity. JAMA. Apr 2 2003;289(13):1652-8. [Medline].

  9. Kowey PR, Marinchak RA, Rials SJ, Bharucha D. Pharmacologic and pharmacokinetic profile of class III antiarrhythmic drugs. Am J Cardiol. Oct 23 1997;80(8A):16G-23G. [Medline].

  10. MacNeil DJ. The side effect profile of class III antiarrhythmic drugs: focus on d,l- sotalol. Am J Cardiol. Oct 23 1997;80(8A):90G-98G. [Medline].

  11. Naccarelli GV, Wolbrette DL, Khan M, et al. Old and new antiarrhythmic drugs for converting and maintaining sinus rhythm in atrial fibrillation: comparative efficacy and results of trials. Am J Cardiol. Mar 20 2003;91(6A):15D-26D. [Medline].

  12. Ravishankar R, Samuels LE, Kaufman MS, et al. Amiodarone-associated hemoptysis. Am J Med Sci. Dec 1998;316(6):390-2. [Medline].

  13. Wyman MG, Wyman RM, Cannom DS, Criley JM. Prevention of primary ventricular fibrillation in acute myocardial infarction with prophylactic lidocaine. Am J Cardiol. Sep 1 2004;94(5):545-51. [Medline].

  14. Joshi S, Raiszadeh F, Pierce W, Steinberg JS. Antiarrhythmic induced electrical storm in Brugada syndrome: a case report. Ann Noninvasive Electrocardiol. Jul 2007;12(3):274-8. [Medline].

  15. Batcher EL, Tang XC, Singh BN, Singh SN, Reda DJ, Hershman JM. Thyroid function abnormalities during amiodarone therapy for persistent atrial fibrillation. Am J Med. Oct 2007;120(10):880-5. [Medline].

  16. Tzivoni D, Banai S, Schuger C, Benhorin J, Keren A, Gottlieb S, et al. Treatment of torsade de pointes with magnesium sulfate. Circulation. Feb 1988;77(2):392-7. [Medline].

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Further Reading

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Keywords

antidysrhythmic drug toxicity, antidysrhythmic drug poisoning, antidysrhythmic drug exposure, class I drugs, sodium channel blockers, class II drugs, beta-adrenergic blockers, class III drugs, potassium channel blockers, class IV drugs, calcium channel blockers, antiarrhythmic exposures

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Contributor Information and Disclosures

Author

Joshua B Gaither, MD, Chief Resident, Department of Surgery, Section of Emergency Medicine, Yale New Haven Hospital
Joshua B Gaither, MD is a member of the following medical societies: American College of Emergency Physicians, Society for Academic Emergency Medicine, and Wilderness Medical Society
Disclosure: Nothing to disclose.

Coauthor(s)

Carin M Van Gelder, MD, Assistant Professor, Department of Surgery, Section of Emergency Medicine, Yale University; Consulting Staff and EMS Physician, SHARP Team, Division of Emergency Medical Services, Section of Emergency Medicine, Yale-New Haven Medical Center
Carin M Van Gelder, MD is a member of the following medical societies: American College of Emergency Physicians, Massachusetts Medical Society, National Association of EMS Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Medical Editor

Miguel C Fernandez, MD, FAAEM, FACEP, FACMT, Associate Clinical Professor; Medical and Managing Director, South Texas Poison Center, Department of Surgery/Emergency Medicine and Toxicology, University of Texas Health Science Center at San Antonio
Miguel C Fernandez, MD, FAAEM, FACEP, FACMT is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, Society for Academic Emergency Medicine, and Texas Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

John T VanDeVoort, PharmD, ABAT, Director of Pharmacy, Sacred Heart Hospital
John T VanDeVoort, PharmD, ABAT is a member of the following medical societies: American Academy of Clinical Toxicology and American Society of Health-System Pharmacists
Disclosure: Nothing to disclose.

Managing Editor

Michael J Burns, MD, Instructor, Department of Emergency Medicine, Harvard University Medical School, Beth Israel Deaconess Medical Center
Michael J Burns, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians, American College of Medical Toxicology, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD, Assistant Professor, Department of Surgery, Section of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital
Disclosure: Nothing to disclose.

 
 
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