eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Toxicology

Toxicity, Calcium Channel Blocker: Differential Diagnoses & Workup

Author: Mark A Silverberg, MD, FACEP, MMB, Assistant Professor, Assistant 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 at Brooklyn
Contributor Information and Disclosures

Updated: May 14, 2009

Differential Diagnoses

Diabetic Ketoacidosis
Pericarditis, Bacterial
Endocarditis, Bacterial
Pericarditis, Constrictive
Endocarditis, Fungal
Pericarditis, Viral
Head Trauma
Substance Abuse: Cocaine
Hypothermia, Circulatory Arrest and Cardiopulmonary Bypass
Toxicity, Digitalis
Hypothyroidism
Toxicity, Ethanol

Other Problems to Be Considered

Beta-blocker ingestion
Ingestion of any sedative hypnotics, including benzodiazepines, barbiturates, and nonbarbiturate sedative hypnotics (eg, glutethimide)
Ingestion of any alcohols or cyclic esters
Clonidine ingestion
Ingestion of any plants containing digoxin-like compounds (eg, grayanotoxin, oleander, foxglove)
Narcotic toxicity
Septicemia
Septic shock
Spinal shock
Typhoid
Allergic reaction
Trauma resulting in tamponade and tension pneumothorax
Respiratory arrest (infants)

Workup

Laboratory Studies

  • Basic chemistries: Look for hyperglycemia, hypokalemia, and a decreased serum bicarbonate level secondary to acidosis in patients with suspected calcium channel blocker (CCB) toxicity. Obtain a baseline calcium level before intravenously (IV) administering calcium, unless the patient requires immediate detoxification due to severe poisoning.
  • ABG: Consider this test in severely affected patients. In patients with significant toxicity, ABGs can be used to assess the acid-base status and respiratory function.
  • CBC count: An elevated WBC count may suggest infection.
  • Aspirin level: Determine the aspirin level of all patients who present to the ED after a suicide attempt.
  • Acetaminophen level: Determine the acetaminophen level of all patients who present to the ED after a suicide attempt.
  • Serum level of ingested medication: Determining the serum drug level of the ingested medication is not always feasible and is usually not helpful.
  • Urine toxicology: Look for co-ingestions with illicit substances that may alter treatment protocols.

Imaging Studies

  • Chest radiography is not routinely indicated unless physical findings suggest lung pathology.
  • An abdominal flat plate may be obtained if a co-ingestion with a radio-opaque tablet is also suspected.

Other Tests

  • Perform ECG in all patients who present to the ED who may have ingested any cardiac medication.
  • Perform ECG in every patient who presents with a suicide gesture to evaluate for the signs of tricyclic antidepressant (TCA) overdose. This results in a positive deflection in the augmented voltage unipolar right arm lead (aVR) in the terminal 40 microseconds of the complex. TCA toxicity can rapidly progress to malignant arrhythmia if left untreated.
  • ECG changes are neither sensitive nor specific for calcium channel blocker toxicity.
  • ECG may reveal bradycardia; tachycardia; first-degree, second-degree, or third-degree atrioventricular (AV) block; any type of bundle-branch block; and nonspecific ST-T wave changes.

Procedures

  • Gastric lavage
    • The usefulness of gastric lavage is still debated.
    • Weigh the risk of aspiration against the probability of removing undigested medications remaining in the stomach.
    • Calcium channel blocker agents slow gastric motility; therefore, gastric lavage may be advisable. Lavage is especially important for patients who may have taken a large dose of medication or for those who have ingested sustained-release preparations.
    • After gastric lavage is completed, the nasogastric (NG) or orogastric (OG) tube can also deliver activated charcoal and a cathartic.
    • An endotracheal tube cuff protects the airway during the lavage, thus placing patients at lower risk of aspiration by intubating them.
  • Foley catheter placement: This may be indicated to monitor urine output in severely poisoned patients.

More on Toxicity, Calcium Channel Blocker

Overview: Toxicity, Calcium Channel Blocker
Differential Diagnoses & Workup: Toxicity, Calcium Channel Blocker
Treatment & Medication: Toxicity, Calcium Channel Blocker
Follow-up: Toxicity, Calcium Channel Blocker
Multimedia: Toxicity, Calcium Channel Blocker
References
Further Reading
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References

  1. 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). Dec 2008;46(10):927-1057. [Medline].

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

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

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

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

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

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

  8. Abbruzzi G, Stork CM. Pediatric toxicologic concerns. Emerg Med Clin North Am. Feb 2002;20(1):223-47. [Medline].

  9. al Edreesi M, Caille G, Dupuis C, Theoret Y, Paradis K. Safety, tolerability, and pharmacokinetic actions of diltiazem in pediatric liver transplant recipients on cyclosporine. Liver Transpl Surg. Nov 1995;1(6):383-8. [Medline].

  10. Anthony T, Jastremski M, Elliott W, Morris G, Prasad H. Charcoal hemoperfusion for the treatment of a combined diltiazem and metoprolol overdose. Ann Emerg Med. Nov 1986;15(11):1344-8. [Medline].

  11. Berg AM, Snell L, Mahle WT. Home inotropic therapy in children. J Heart Lung Transplant. May 2007;26(5):453-7. [Medline].

  12. Braunwald E. Mechanism of action of calcium-channel-blocking agents. N Engl J Med. Dec 23 1982;307(26):1618-27. [Medline].

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

  14. Bryant S, Singer J. Management of toxic exposure in children. Emerg Med Clin North Am. Feb 2003;21(1):101-19. [Medline].

  15. 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. Feb 1 1993;158(3):202-4. [Medline].

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

  17. Cimpello LB, Craig S, Lawrence E, Baker MD. A calcium channel blocker and ibuprofen overdose. Curr Opin Pediatr. Jun 1998;10(3):303-7. [Medline].

  18. Devis G, Somers G, Van Obberghen E, Malaisse WJ. Calcium antagonists and islet function. I. Inhibition of insulin release by verapamil. Diabetes. Jun 1975;24(6):247-51. [Medline].

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

  20. Erickson FC, Ling LJ, Grande GA, Anderson DL. Diltiazem overdose: case report and review. J Emerg Med. Sep-Oct 1991;9(5):357-66. [Medline].

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

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

  23. Howarth DM, Dawson AH, Smith AJ, Buckley N, Whyte IM. Calcium channel blocking drug overdose: an Australian series. Hum Exp Toxicol. Mar 1994;13(3):161-6. [Medline].

  24. Humbert VH Jr, Munn NJ, Hawkins RF. Noncardiogenic pulmonary edema complicating massive diltiazem overdose. Chest. Jan 1991;99(1):258-9. [Medline].

  25. Innes CA, Wagstaff AJ. Levosimendan: a review of its use in the management of acute decompensated heart failure. Drugs. 2003;63(23):2651-71. [Medline].

  26. 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].

  27. Kardevandian E, Marcus S. "Accidental ingestion of sustained release calcium channel blockers in children". Vet Hum Toxicol. Aug 1998;40(4):237-8; author reply 238-9. [Medline].

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

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

  30. Kline JA, Tomaszewski CA, Schroeder JD, Raymond RM. Insulin is a superior antidote for cardiovascular toxicity induced by verapamil in the anesthetized canine. J Pharmacol Exp Ther. Nov 1993;267(2):744-50. [Medline].

  31. Korstanje C, Jonkman FA, Van Kemenade JE, Van Zwieten PA. Bay k 8644, a calcium entry promoter, as an antidote in verapamil intoxication in rabbits. Arch Int Pharmacodyn Ther. May 1987;287(1):109-19. [Medline].

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

  33. Lai MW, Klein-Schwartz W, Rodgers GC, et al. 2005 Annual Report of the American Association of Poison Control Centers' national poisoning and exposure database. Clin Toxicol (Phila). 2006;44(6-7):803-932. [Medline].

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

  35. Michael JB, Sztajnkrycer MD. Deadly pediatric poisons: nine common agents that kill at low doses. Emerg Med Clin North Am. Nov 2004;22(4):1019-50. [Medline].

  36. Olson KR, Erdman AR, Woolf AD, 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].

  37. Osterhoudt KC, Henretig FM. How much confidence that calcium channel blockers are safe?. Vet Hum Toxicol. Aug 1998;40(4):239. [Medline].

  38. Passal DB, Crespin FH Jr. Verapamil poisoning in an infant. Pediatrics. Apr 1984;73(4):543-5. [Medline].

  39. Pearigen PD, Benowitz NL. Poisoning due to calcium antagonists. Experience with verapamil, diltiazem and nifedipine. Drug Saf. Nov-Dec 1991;6(6):408-30. [Medline].

  40. Pearl JM. "Accidental ingestion of sustained release calcium channel blockers in children". Vet Hum Toxicol. Aug 1998;40(4):238; author reply 238-9. [Medline].

  41. Plewa MC, Martin TG, Menegazzi JJ, Seaberg DC, Wolfson AB. Hemodynamic effects of 3,4-diaminopyridine in a swine model of verapamil toxicity. Ann Emerg Med. Mar 1994;23(3):499-507. [Medline].

  42. Pohler HF. A little goes a long way: Clinical management of calcium channel blocker overdose. J Emerg Nurs. Aug 2006;32(4):347-9. [Medline].

  43. Proano L, Chiang WK, Wang RY. Calcium channel blocker overdose. Am J Emerg Med. Jul 1995;13(4):444-50. [Medline].

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

  45. Roper TA, Sykes R, Gray C. Fatal diltiazem overdose: report of four cases and review of the literature. Postgrad Med J. Jun 1993;69(812):474-6. [Medline].

  46. Shah AR, Passalacqua BR. Case report: sustained-release verapamil overdose causing stroke: an unusual complication. Am J Med Sci. Dec 1992;304(6):357-9. [Medline].

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

  48. Tom PA, Morrow CT, Kelen GD. Delayed hypotension after overdose of sustained release verapamil. J Emerg Med. Sep-Oct 1994;12(5):621-5. [Medline].

  49. Tuncok Y, Apaydin S, Gelal A, Ates M, Guven H. The effects of 4-aminopyridine and Bay K 8644 on verapamil-induced cardiovascular toxicity in anesthetized rats. J Toxicol Clin Toxicol. 1998;36(4):301-7. [Medline].

  50. Watling SM, Crain JL, Edwards TD, Stiller RA. Verapamil overdose: case report and review of the literature. Ann Pharmacother. Nov 1992;26(11):1373-8. [Medline].

  51. Wax PM. Intestinal infarction due to nifedipine overdose. J Toxicol Clin Toxicol. 1995;33(6):725-8. [Medline].

  52. Wells TG, Graham CJ, Moss MM, Kearns GL. Nifedipine poisoning in a child. Pediatrics. Jul 1990;86(1):91-4. [Medline].

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

  54. 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].

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

  56. Zimmerman JL. Poisonings and overdoses in the intensive care unit: general and specific management issues. Crit Care Med. Dec 2003;31(12):2794-801. [Medline].

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Further Reading

The AAPCC has released the following clinical guidelines: Calcium channel blocker ingestion: an evidence-based consensus guideline for out-of-hospital management.

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Keywords

calcium channel blocker, Ca+ 2 channel blocker, calcium channel antagonist, slow channel blocker, CCB, nifedipine, diltiazem, verapamil, congenital heart malformations, arrhythmias, hypertension, congestive heart failure, subarachnoid hemorrhage, suicide, bradycardia, hepatomegaly, hepatojugular reflux, enteric dysmotility, hyperglycemia, phenylkalkylamine, dihydropyridine, cerebral ischemia, torsades de pointes, hypokalemia, treatment, diagnosis, overdose

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Contributor Information and Disclosures

Author

Mark A Silverberg, MD, FACEP, MMB, Assistant Professor, Assistant 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 at Brooklyn
Mark A Silverberg, MD, FACEP, MMB 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.

Medical Editor

William T Zempsky, MD, Associate Director, Assistant Professor, Department of Pediatrics, Division of Pediatric Emergency Medicine, University of Connecticut and Connecticut Children's Medical Center
William T Zempsky, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Jeffrey R Tucker, MD, Assistant Professor, Department of Pediatrics, Division of Emergency Medicine, University of Connecticut and Connecticut Children's Medical Center
Jeffrey R Tucker, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Pediatrics, and Massachusetts Medical Society
Disclosure: Merck Salary Employment

CME Editor

Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System
Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Chief Editor

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.

 
 
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