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Calcium Channel Blocker Toxicity Differential Diagnoses

  • Author: B Zane Horowitz, MD, FACMT; Chief Editor: Asim Tarabar, MD  more...
 
Updated: Oct 21, 2015
 
 

Diagnostic Considerations

The conditions listed below should be considered in the differential diagnosis of calcium channel blocker (CCB) toxicity.

The following are the main common toxicity-causing agents:

  • Ingestion of beta-blocking agents
  • Acute or chronic digoxin toxicity
  • Ingestion of clonidine or other central alpha-2 agonists
  • Ingestion of any plants containing digoxinlike compounds or other cardiotoxins (eg, grayanotoxin, oleander, foxglove)
  • Opioid toxicity
  • Ingestion of any sedative hypnotics, including benzodiazepines, barbiturates, and nonbarbiturate sedative hypnotics

Other medical conditions to be considered may include the following:

  • Head trauma with Cushing reflex
  • Pontine hemorrhage
  • Septicemia
  • Septic shock
  • Spinal shock
  • Typhoid
  • Allergic reaction
  • Trauma resulting in tamponade and tension pneumothorax
  • Respiratory arrest (infants)
  • Bacterial pericarditis
  • Viral pericarditis

Differentials

Head Trauma

Hypothermia, Circulatory Arrest and Cardiopulmonary Bypass

Hypothyroidism

Lactic Acidosis

Myocardial Infarction

Pericarditis, Constrictive

Plant Poisoning, Glycosides

Shock, Cardiogenic

Toxicity, Antidepressant

Toxicity, Antidysrhythmic

Toxicity, Beta-blocker

Toxicity, Clonidine

Toxicity, Digitalis

Toxicity, Ethanol

 
 
Contributor Information and Disclosures
Author

B Zane Horowitz, MD, FACMT Professor, Department of Emergency Medicine, Oregon Health and Sciences University School of Medicine; Medical Director, Oregon Poison Center; Medical Director, Alaska Poison Control System

B Zane Horowitz, MD, FACMT is a member of the following medical societies: American College of Medical Toxicology

Disclosure: Nothing to disclose.

Coauthor(s)

Derrick Lung, MD, MPH Assistant Clinical Professor, Department of Emergency Medicine, San Francisco General Hospital; Assistant Medical Director, California Poison Control System, San Francisco Division

Derrick Lung, MD, MPH is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians, American College of Medical Toxicology, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

Acknowledgements

John G Benitez, MD, MPH Associate Professor, Department of Medicine, Medical Toxicology, Vanderbilt University Medical Center; Managing Director, Tennessee Poison Center

John G Benitez, MD, MPH is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Medical Toxicology, American College of Preventive Medicine, Society for Academic Emergency Medicine, Undersea and Hyperbaric Medical Society, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Timothy E Corden, MD Associate Professor of Pediatrics, Co-Director, Policy Core, Injury Research Center, Medical College of Wisconsin; Associate Director, PICU, Children's Hospital of Wisconsin

Timothy E Corden, MD is a member of the following medical societies: American Academy of Pediatrics, Phi Beta Kappa, Society of Critical Care Medicine, and Wisconsin Medical Society

Disclosure: Nothing to disclose.

David C Lee, MD Research Director, Department of Emergency Medicine, Associate Professor, North Shore University Hospital and New York University Medical School

David C Lee, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Mark A Silverberg, MD, MMB, FACEP Assistant Professor, Associate Residency Director, Department of Emergency Medicine, State University of New York Downstate College of Medicine; Consulting Staff, Department of Emergency Medicine, Staten Island University Hospital, Kings County Hospital, University Hospital, State University of New York Downstate Medical Center

Mark A Silverberg, MD, MMB, FACEP is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, Council of Emergency Medicine Residency Directors, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Jeffrey R Tucker, MD Assistant Professor, Department of Pediatrics, Division of Emergency Medicine, University of Connecticut and Connecticut Children's Medical Center

Disclosure: Merck Salary Employment

John T VanDeVoort, PharmD Regional Director of Pharmacy, Sacred Heart and St Joseph's Hospitals

John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose .

References
  1. Derlet RW, Horowitz BZ. Cardiotoxic drugs. Emerg Med Clin North Am. 1995 Nov. 13(4):771-91. [Medline].

  2. Arroyo AM, Kao LW. Calcium channel blocker toxicity. Pediatr Emerg Care. 2009 Aug. 25(8):532-8; quiz 539-40. [Medline].

  3. Spiller HA, Meyers A, Ziemba T, Riley M. Delayed onset of cardiac arrhythmias from sustained-release verapamil. Ann Emerg Med. 1991 Feb. 20(2):201-3. [Medline].

  4. Laine K, Kivistö KT, Neuvonen PJ. Effect of delayed administration of activated charcoal on the absorption of conventional and slow-release verapamil. J Toxicol Clin Toxicol. 1997. 35(3):263-8. [Medline].

  5. Buckley N, Dawson AH, Howarth D, Whyte IM. Slow-release verapamil poisoning. Use of polyethylene glycol whole-bowel lavage and high-dose calcium. Med J Aust. 1993 Feb 1. 158(3):202-4. [Medline].

  6. Hung YM, Olson KR. Acute amlodipine overdose treated by high dose intravenous calcium in a patient with severe renal insufficiency. Clin Toxicol (Phila). 2007. 45(3):301-3. [Medline].

  7. Haddad LM. Resuscitation after nifedipine overdose exclusively with intravenous calcium chloride. Am J Emerg Med. 1996 Oct. 14(6):602-3. [Medline].

  8. Sim MT, Stevenson FT. A fatal case of iatrogenic hypercalcemia after calcium channel blocker overdose. J Med Toxicol. 2008 Mar. 4(1):25-9. [Medline].

  9. Adams BD, Browne WT. Amlodipine overdose causes prolonged calcium channel blocker toxicity. Am J Emerg Med. 1998 Sep. 16(5):527-8. [Medline].

  10. Mowry JB, Spyker DA, Cantilena LR Jr, McMillan N, Ford M. 2013 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 31st Annual Report. Clin Toxicol (Phila). 2014 Dec. 52 (10):1032-283. [Medline].

  11. Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Heard SE. 2007 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 25th Annual Report. Clin Toxicol (Phila). 2008 Dec. 46(10):927-1057. [Medline].

  12. Belson MG, Gorman SE, Sullivan K, Geller RJ. Calcium channel blocker ingestions in children. Am J Emerg Med. 2000 Sep. 18(5):581-6. [Medline].

  13. Brayer AF, Wax P. Accidental ingestion of sustained release calcium channel blockers in children. Vet Hum Toxicol. 1998 Apr. 40(2):104-6. [Medline].

  14. Ranniger C, Roche C. Are one or two dangerous? Calcium channel blocker exposure in toddlers. J Emerg Med. 2007 Aug. 33(2):145-54. [Medline].

  15. Benson BE, Spyker DA, Troutman WG, Watson WA, Bakhireva LN. Amlodipine toxicity in children less than 6 years of age: a dose-response analysis using national poison data system data. J Emerg Med. 2010 Aug. 39(2):186-93. [Medline].

  16. Koren G. Medications which can kill a toddler with one tablet or teaspoonful. J Toxicol Clin Toxicol. 1993. 31(3):407-13. [Medline].

  17. Lee DC, Greene T, Dougherty T, Pearigen P. Fatal nifedipine ingestions in children. J Emerg Med. 2000 Nov. 19(4):359-61. [Medline].

  18. Levine M, Boyer EW, Pozner CN, Geib AJ, Thomsen T, Mick N, et al. Assessment of hyperglycemia after calcium channel blocker overdoses involving diltiazem or verapamil. Crit Care Med. 2007 Sep. 35(9):2071-5. [Medline].

  19. Burkes R, Wendorf G. A multifaceted approach to calcium channel blocker overdose: a case report and literature review. Clin Case Rep. 2015 Jul. 3 (7):566-9. [Medline].

  20. Cantrell FL, Williams SR. Fatal unintentional overdose of diltiazem with antemortem and postmortem values. Clin Toxicol (Phila). 2005. 43(6):587-8. [Medline].

  21. Wilimowska J, Piekoszewski W, Krzyanowska-Kierepka E, Florek E. Monitoring of verapamil enantiomers concentration in overdose. Clin Toxicol (Phila). 2006. 44(2):169-71. [Medline].

  22. [Guideline] Olson KR, Erdman AR, Woolf AD, Scharman EJ, Christianson G, Caravati EM, et al. Calcium channel blocker ingestion: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila). 2005. 43(7):797-822. [Medline].

  23. Chin L, Picchioni AL, Bourn WM, Laird HE. Optimal antidotal dose of activated charcoal. Toxicol Appl Pharmacol. 1973 Sep. 26(1):103-8. [Medline].

  24. Walter FG, Frye G, Mullen JT, Ekins BR, Khasigian PA. Amelioration of nifedipine poisoning associated with glucagon therapy. Ann Emerg Med. 1993 Jul. 22(7):1234-7. [Medline].

  25. Chernow B, Zaloga GP, Malcolm D, Willey SC, Clapper M, Holaday JW. Glucagon's chronotropic action is calcium dependent. J Pharmacol Exp Ther. 1987 Jun. 241(3):833-7. [Medline].

  26. Doyon S, Roberts JR. The use of glucagon in a case of calcium channel blocker overdose. Ann Emerg Med. 1993 Jul. 22(7):1229-33. [Medline].

  27. Fant JS, James LP, Fiser RT, Kearns GL. The use of glucagon in nifedipine poisoning complicated by clonidine ingestion. Pediatr Emerg Care. 1997 Dec. 13(6):417-9. [Medline].

  28. Mahr NC, Valdes A, Lamas G. Use of glucagon for acute intravenous diltiazem toxicity. Am J Cardiol. 1997 Jun 1. 79(11):1570-1. [Medline].

  29. Stone CK, Thomas SH, Koury SI, Low RB. Glucagon and phenylephrine combination vs glucagon alone in experimental verapamil overdose. Acad Emerg Med. 1996 Feb. 3(2):120-5. [Medline].

  30. Wolf LR, Spadafora MP, Otten EJ. Use of amrinone and glucagon in a case of calcium channel blocker overdose. Ann Emerg Med. 1993 Jul. 22(7):1225-8. [Medline].

  31. Zaritsky AL, Horowitz M, Chernow B. Glucagon antagonism of calcium channel blocker-induced myocardial dysfunction. Crit Care Med. 1988 Mar. 16(3):246-51. [Medline].

  32. Ashraf M, Chaudhary K, Nelson J, Thompson W. Massive overdose of sustained-release verapamil: a case report and review of literature. Am J Med Sci. 1995 Dec. 310(6):258-63. [Medline].

  33. Hofer CA, Smith JK, Tenholder MF. Verapamil intoxication: a literature review of overdoses and discussion of therapeutic options. Am J Med. 1993 Oct. 95(4):431-8. [Medline].

  34. Sztajnkrycer MD, Bond GR, Johnson SB, Weaver AL. Use of vasopressin in a canine model of severe verapamil poisoning: a preliminary descriptive study. Acad Emerg Med. 2004 Dec. 11(12):1253-61. [Medline].

  35. Wood DM, Wright KD, Jones AL, Dargan PI. Metaraminol (Aramine) in the management of a significant amlodipine overdose. Hum Exp Toxicol. 2005 Jul. 24(7):377-81. [Medline].

  36. Kanagarajan K, Marraffa JM, Bouchard NC, Krishnan P, Hoffman RS, Stork CM. The use of vasopressin in the setting of recalcitrant hypotension due to calcium channel blocker overdose. Clin Toxicol (Phila). 2007. 45(1):56-9. [Medline].

  37. Kerns W 2nd. Management of beta-adrenergic blocker and calcium channel antagonist toxicity. Emerg Med Clin North Am. 2007 May. 25(2):309-31; abstract viii. [Medline].

  38. Koury SI, Stone CK, Thomas SH. Amrinone as an antidote in experimental verapamil overdose. Acad Emerg Med. 1996 Aug. 3(8):762-7. [Medline].

  39. Ramoska EA, Spiller HA, Myers A. Calcium channel blocker toxicity. Ann Emerg Med. 1990 Jun. 19(6):649-53. [Medline].

  40. Ramoska EA, Spiller HA, Winter M, Borys D. A one-year evaluation of calcium channel blocker overdoses: toxicity and treatment. Ann Emerg Med. 1993 Feb. 22(2):196-200. [Medline].

  41. Smilkstein MJ. Perfusion salad: making sense of verapamil overdose. Acad Emerg Med. 1996 Feb. 3(2):99-100. [Medline].

  42. Tuncok Y, Apaydin S, Kalkan S, Ates M, Guven H. The effects of amrinone and glucagon on verapamil-induced cardiovascular toxicity in anaesthetized rats. Int J Exp Pathol. 1996 Oct. 77(5):207-12. [Medline]. [Full Text].

  43. Engebretsen KM, Kaczmarek KM, Morgan J, Holger JS. High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning. Clin Toxicol (Phila). 2011 Apr. 49(4):277-83. [Medline].

  44. Mycyk MB, Bryant SM. Is simple bedside glucose assessment prognostic in calcium channel blocker overdose?. Crit Care Med. 2007 Sep. 35(9):2216-7. [Medline].

  45. Verbrugge LB, van Wezel HB. Pathophysiology of verapamil overdose: new insights in the role of insulin. J Cardiothorac Vasc Anesth. 2007 Jun. 21(3):406-9. [Medline].

  46. Patel NP, Pugh ME, Goldberg S, Eiger G. Hyperinsulinemic euglycemia therapy for verapamil poisoning: case report. Am J Crit Care. 2007 Sep. 16(5):520, 518-9. [Medline].

  47. Greene SL, Gawarammana I, Wood DM, Jones AL, Dargan PI. Relative safety of hyperinsulinaemia/euglycaemia therapy in the management of calcium channel blocker overdose: a prospective observational study. Intensive Care Med. 2007 Nov. 33(11):2019-24. [Medline].

  48. Kline JA, Leonova E, Raymond RM. Beneficial myocardial metabolic effects of insulin during verapamil toxicity in the anesthetized canine. Crit Care Med. 1995 Jul. 23(7):1251-63. [Medline].

  49. Yuan TH, Kerns WP 2nd, Tomaszewski CA, Ford MD, Kline JA. Insulin-glucose as adjunctive therapy for severe calcium channel antagonist poisoning. J Toxicol Clin Toxicol. 1999. 37(4):463-74. [Medline].

  50. Patel NP, Pugh ME, Goldberg S, Eiger G. Hyperinsulinemic euglycemia therapy for verapamil poisoning: a review. Am J Crit Care. 2007 Sep. 16(5):498-503. [Medline].

  51. Lheureux PE, Zahir S, Gris M, Derrey AS, Penaloza A. Bench-to-bedside review: hyperinsulinaemia/euglycaemia therapy in the management of overdose of calcium-channel blockers. Crit Care. 2006. 10(3):212. [Medline]. [Full Text].

  52. Hasin T, Leibowitz D, Antopolsky M, Chajek-Shaul T. The use of low-dose insulin in cardiogenic shock due to combined overdose of verapamil, enalapril and metoprolol. Cardiology. 2006. 106(4):233-6. [Medline].

  53. Ortiz-Muñoz L, Rodriguez-Ospina LF, Figueroa-Gonzalez M. Hyperinsulinemic-euglycemic therapy for intoxication with calcium channel blockers. Bol Asoc Med P R. 2005 Jul-Sep. 97(3 Pt 2):182-9. [Medline].

  54. Shepherd G, Klein-Schwartz W. High-dose insulin therapy for calcium-channel blocker overdose. Ann Pharmacother. 2005 May. 39(5):923-30. [Medline].

  55. Jang DH, Nelson LS, Hoffman RS. Methylene blue in the treatment of refractory shock from an amlodipine overdose. Ann Emerg Med. 2011 Dec. 58(6):565-7. [Medline].

  56. Young AC, Velez LI, Kleinschmidt KC. Intravenous fat emulsion therapy for intentional sustained-release verapamil overdose. Resuscitation. 2009 May. 80(5):591-3. [Medline].

  57. Perez E, Bania TC, Medlej K, Chu J. Determining the optimal dose of intravenous fat emulsion for the treatment of severe verapamil toxicity in a rodent model. Acad Emerg Med. 2008 Dec. 15(12):1284-9. [Medline].

  58. Tebbutt S, Harvey M, Nicholson T, Cave G. Intralipid prolongs survival in a rat model of verapamil toxicity. Acad Emerg Med. 2006 Feb. 13(2):134-9. [Medline].

  59. LipidRescue: resuscitation for cardiac toxicity. Available at http://www.lipidrescue.org. Accessed: July 29, 2013.

  60. Bania TC, Chu J, Perez E, Su M, Hahn IH. Hemodynamic effects of intravenous fat emulsion in an animal model of severe verapamil toxicity resuscitated with atropine, calcium, and saline. Acad Emerg Med. 2007 Feb. 14(2):105-11. [Medline].

  61. Franxman TJ, Al-Nabhan M, Cavallazzi RS, Speak AJ. Lipid emulsion therapy for verapamil overdose. Ann Intern Med. 2011 Feb 15. 154(4):292. [Medline].

  62. French D, Armenian P, Ruan W, Wong A, Drasner K, Olson KR, et al. Serum verapamil concentrations before and after Intralipid® therapy during treatment of an overdose. Clin Toxicol (Phila). 2011 Apr. 49(4):340-4. [Medline].

  63. French D, Smollin C, Ruan W, Wong A, Drasner K, Wu AH. Partition constant and volume of distribution as predictors of clinical efficacy of lipid rescue for toxicological emergencies. Clin Toxicol (Phila). 2011 Nov. 49(9):801-9. [Medline].

  64. American College of Medical Toxicology. ACMT position statement: interim guidance for the use of lipid resuscitation therapy. J Med Toxicol. 2011 Mar. 7(1):81-2. [Medline].

  65. Varpula T, Rapola J, Sallisalmi M, Kurola J. Treatment of serious calcium channel blocker overdose with levosimendan, a calcium sensitizer. Anesth Analg. 2009 Mar. 108(3):790-2. [Medline].

  66. Kolcz J, Pietrzyk J, Januszewska K, Procelewska M, Mroczek T, Malec E. Extracorporeal life support in severe propranolol and verapamil intoxication. J Intensive Care Med. 2007 Nov-Dec. 22(6):381-5. [Medline].

  67. Hendren WG, Schieber RS, Garrettson LK. Extracorporeal bypass for the treatment of verapamil poisoning. Ann Emerg Med. 1989 Sep. 18(9):984-7. [Medline].

  68. Durward A, Guerguerian AM, Lefebvre M, Shemie SD. Massive diltiazem overdose treated with extracorporeal membrane oxygenation. Pediatr Crit Care Med. 2003 Jul. 4(3):372-6. [Medline].

  69. Ezidiegwu C, Spektor Z, Nasr MR, Kelly KC, Rosales LG. A case report on the role of plasma exchange in the management of a massive amlodipine besylate intoxication. Ther Apher Dial. 2008 Apr. 12(2):180-4. [Medline].

  70. Pfaender M, Casetti PG, Azzolini M, Baldi ML, Valli A. Successful treatment of a massive atenolol and nifedipine overdose with CVVHDF. Minerva Anestesiol. 2008 Mar. 74(3):97-100. [Medline].

  71. Roberts DM, Roberts JA, Boots RJ, Mason R, Lipman J. Lessons learnt in the pharmacokinetic analysis of the effect of haemoperfusion for acute overdose with sustained-release diltiazem. Anaesthesia. 2008 Jul. 63(7):714-8. [Medline].

  72. Weinberg G. Lipid rescue resuscitation from local anaesthetic cardiac toxicity. Toxicol Rev. 2006. 25(3):139-45. [Medline].

  73. Rosenblatt MA, Abel M, Fischer GW, Itzkovich CJ, Eisenkraft JB. Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest. Anesthesiology. 2006 Jul. 105(1):217-8. [Medline].

  74. Litz RJ, Popp M, Stehr SN, Koch T. Successful resuscitation of a patient with ropivacaine-induced asystole after axillary plexus block using lipid infusion. Anaesthesia. 2006 Aug. 61(8):800-1. [Medline].

  75. Zimmer C, Piepenbrink K, Riest G, Peters J. [Cardiotoxic and neurotoxic effects after accidental intravascular bupivacaine administration. Therapy with lidocaine propofol and lipid emulsion]. Anaesthesist. 2007 May. 56(5):449-53. [Medline].

  76. Cave G, Harvey M, Graudins A. Intravenous lipid emulsion as antidote: a summary of published human experience. Emerg Med Australas. 2011 Apr. 23(2):123-41. [Medline].

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Calcium channel blocker; diltiazem.
Table. Recommendations for In-hospital Evaluation Based on Drug and Dosage of Calcium Channel Blocker Ingested
Drug Adult Dosage Pediatric Dosage
Amlodipine>10 mg>0.3 mg/kg
Diltiazem>120 mg immediate release formulation; >360 mg sustained release formulation>1 mg/kg
Felodipine>10 mg>0.3 mg/kg
Isradipine>20 mg>0.1 mg/kg
Nicardipine>40 mg immediate release; >60 mg sustained release>1.25 mg/kg
Nifedipine>30 mg immediate release; >120 mg sustained releaseAny amount
Nimodipine>60 mgAny amount
Nisoldipine>30 mgAny amount
Verapamil>120 mg immediate release; >480 mg sustained release>2.5 mg/kg
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