Guidelines
Consensus Guidelines for Calcium Channel Blocker Poisoning- St-Onge M, Anseeuw K, Cantrell FL, Gilchrist IC, Hantson P, Bailey B, Lavergne V, Gosselin S, Kerns W 2nd, Laliberté M, Lavonas EJ, Juurlink DN, Muscedere J, Yang CC, Sinuff T, Rieder M, Mégarbane B. Experts Consensus Recommendations for the Management of Calcium Channel Blocker Poisoning in Adults. Crit Care Med. 2017 Mar;45(3):e306-e315. doi: 10.1097/CCM.0000000000002087. PMID: 27749343; PMCID: PMC5312725.Wax PM, Erdman AR, Chyka PA, Keyes DC, Caravati EM, Booze L, Christianson G, Woolf A, Olson KR, Manoguerra AS, Scharman EJ, Troutman WG. beta-blocker ingestion: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila). 2005;43(3):131-46. PMID: 15906457.
Primary Literature
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. doi: 10.1016/s0196-0644(05)80202-1. PMID: 8427431.
Levine M, Curry SC, Padilla-Jones A, Ruha AM. Critical care management of verapamil and diltiazem overdose with a focus on vasopressors: a 25-year experience at a single center. Ann Emerg Med. 2013 Sep;62(3):252-8. doi: 10.1016/j.annemergmed.2013.03.018. Epub 2013 May 1. PMID: 23642908.
Laine K, Kivistö KT, Laakso I, Neuvonen PJ. Prevention of amlodipine absorption by activated charcoal: effect of delay in charcoal administration. Br J Clin Pharmacol. 1997 Jan;43(1):29-33. doi: 10.1111/j.1365-2125.1997.tb00029.x. PMID: 9056049.
Lashari, B. H., Minalyan, A., Khan, W., Naglak, M., & Ward, W. (2018). The Use of High-dose Insulin Infusion and Lipid Emulsion Therapy in Concurrent Beta-blocker and Calcium Channel Blocker Overdose. Cureus , 10 (11), e3534. https://doi.org/10.7759/cureus.3534
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. doi: 10.1016/s0196-0644(05)80997-7. PMID: 8517580.
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. doi: 10.1016/s0196-0644(05)80996-5. PMID: 8517579.
Seegobin K, Maharaj S, Deosaran A, Reddy P. Severe beta blocker and calcium channel blocker overdose: Role of high dose insulin. Am J Emerg Med. 2018 Apr;36(4):736.e5-736.e6. doi: 10.1016/j.ajem.2018.01.038. Epub 2018 Jan 10. PMID: 29331270.
Rosser G, Dubrey SW. Massive calcium channel blocker overdose: intravenous insulin and glucose as a therapy. BMJ Case Rep. 2012 Jun 5;2012:bcr0320126114. doi: 10.1136/bcr.03.2012.6114. PMID: 22675147; PMCID: PMC4543241.
Kerns W 2nd, Schroeder D, Williams C, Tomaszewski C, Raymond R. Insulin improves survival in a canine model of acute beta-blocker toxicity. Ann Emerg Med. 1997 Jun;29(6):748-57. doi: 10.1016/s0196-0644(97)70196-3. PMID: 9174520.
Holger JS, Engebretsen KM, Fritzlar SJ, Patten LC, Harris CR, Flottemesch TJ. Insulin versus vasopressin and epinephrine to treat beta-blocker toxicity. Clin Toxicol (Phila) . 2007 May;45(4):396-401. doi: 10.1080/15563650701285412. PMID: 17486481.
Holger JS, Stellpflug SJ, Cole JB, Harris CR, Engebretsen KM. High-dose insulin: a consecutive case series in toxin-induced cardiogenic shock. Clin Toxicol (Phila). 2011 Aug;49(7):653-8. doi: 10.3109/15563650.2011.593522. Epub 2011 Aug 8. PMID: 21819291.
Page C, Hacket LP, Isbister GK. The use of high-dose insulin-glucose euglycemia in beta-blocker overdose: a case report. J Med Toxicol. 2009 Sep;5(3):139-43. doi: 10.1007/BF03161225. PMID: 19655287; PMCID: PMC3550395.
Stellpflug SJ, Harris CR, Engebretsen KM, Cole JB, Holger JS. Intentional overdose with cardiac arrest treated with intravenous fat emulsion and high-dose insulin. Clin Toxicol (Phila). 2010 Mar;48(3):227-9. doi: 10.3109/15563650903555294. PMID: 20141425.
Love JN, Sachdeva DK, Bessman ES, Curtis LA, Howell JM. A potential role for glucagon in the treatment of drug-induced symptomatic bradycardia. 1998 Jul;114(1):323-6. doi: 10.1378/chest.114.1.323. PMID: 9674488.
Doepker B, Healy W, Cortez E, Adkins EJ. High-dose insulin and intravenous lipid emulsion therapy for cardiogenic shock induced by intentional calcium-channel blocker and Beta-blocker overdose: a case series. J Emerg Med. 2014 Apr;46(4):486-90. doi: 10.1016/j.jemermed.2013.08.135. Epub 2014 Feb 13. PMID: 24530120.
Meaney CJ, Sareh H, Hayes BD, Gonzales JP. Intravenous lipid emulsion in the management of amlodipine overdose. Hosp Pharm. 2013 Nov;48(10):848-54. doi: 10.1310/hpj4810-848. PMID: 24421438; PMCID: PMC3859284.
McLean M, Van Donselaar K, Thomas P, Tilney PVR. A 42-Year-Old Woman with a Beta Blocker Overdose. Air Med J. 2018 May-Jun;37(3):147-150. doi: 10.1016/j.amj.2017.11.001. Epub 2018 Mar 5. PMID: 29735223.
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. doi: 10.1213/ane.0b013e3181931737. PMID: 19224785.
St-Onge M, Ajmo I, Poirier D, Laliberté M. L-Carnitine for the treatment of a calcium channel blocker and metformin poisoning. J Med Toxicol. 2013 Sep;9(3):266-9. doi: 10.1007/s13181-013-0301-3. PMID: 23636657; PMCID: PMC3771002.
Cohen V, Jellinek SP, Fancher L, Sangwan G, Wakslak M, Marquart E, Farahani C. Tarka® (trandolapril/verapamil hydrochloride extended-release) overdose. J Emerg Med . 2011 Mar;40(3):291-5. doi: 10.1016/j.jemermed.2008.10.015. Epub 2009 Feb 26. PMID: 19249183.
Erickson FC, Ling LJ, Grande GA, Anderson DL. Diltiazem overdose: case report and review. J Emerg Med. 1991 Sep-Oct;9(5):357-66. doi: 10.1016/0736-4679(91)90380-x. PMID: 1940240.
Watling SM, Crain JL, Edwards TD, Stiller RA. Verapamil overdose: case report and review of the literature. Ann Pharmacother . 1992 Nov;26(11):1373-8. doi: 10.1177/106002809202601106. PMID: 1477440.
Izdes S, Altintas ND, Soykut C. Acute respiratory distress syndrome after verapamil intoxication: case report and literature review. Acta Clin Belg. 2014 Apr;69(2):116-9. doi: 10.1179/2295333714Y.0000000007. Epub 2014 Mar 4. PMID: 24724751.
Roper TA, Sykes R, Gray C. Fatal diltiazem overdose: report of four cases and review of the literature. Postgrad Med J. 1993 Jun;69(812):474-6. doi: 10.1136/pgmj.69.812.474. PMID: 8208646; PMCID: PMC2399841.
Sauder P, Kopferschmitt J, Dahlet M, Tritsch L, Flesch F, Siard P, Mantz JM, Jaeger A. Les intoxications aiguës par le vérapamil. A propos de 6 cas. Revue de la littérature [Acute verapamil poisoning. 6 cases. Review of the literature]. J Toxicol Clin Exp. 1990 Jul-Aug;10(4):261-70. French. PMID: 2262922.
Karbek Akarca F, Akceylan E, Kıyan S. Treatment of Amlodipine Intoxication with Intravenous Lipid Emulsion Therapy: A Case Report and Review of the Literature. Cardiovasc Toxicol. 2017 Oct;17(4):482-486. doi: 10.1007/s12012-017-9421-3. PMID: 28766181.
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. PMID: 7503108.
Price D, Radke J, Albertson T. Hypocalcaemia after an occult calcium channel blocker overdose: a case report and literature review. Basic Clin Pharmacol Toxicol. 2014 Feb;114(2):217-21. doi: 10.1111/bcpt.12121. Epub 2013 Sep 18. PMID: 24034162.
Forster V, Luciani P, Leroux JC. Treatment of calcium channel blocker-induced cardiovascular toxicity with drug scavenging liposomes. Biomaterials. 2012 May;33(13):3578-85. doi: 10.1016/j.biomaterials.2012.01.042. Epub 2012 Feb 11. PMID: 22330848.
Review Articles
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. doi: 10.1016/j.emc.2007.02.001. PMID: 17482022.
Shepherd G. Treatment of poisoning caused by beta-adrenergic and calcium-channel blockers. Am J Health Syst Pharm. 2 006 Oct 1;63(19):1828-35. doi: 10.2146/ajhp060041. Erratum in: Am J Health Syst Pharm. 2008 Sep 1;65(17):1592. PMID: 16990629.
De Roos FJ. : Calcium channel blockers. Goldfrank’s Toxicologic Emergencies. 8th edition. Goldfrank LR, Flomenbaum NE, Lewin NA, Howland MA, Nelson L, Hoffman RS (eds.). Appleton and Lange, Norwalk, CN, 2005.
Brubacher J.R. (2015). Β-adrenergic antagonists. Hoffman R.S., & Howland M, & Lewin N.A., & Nelson L.S., & Goldfrank L.R.(Eds.), Goldfrank’s Toxicologic Emergencies, 10e. McGraw Hill. https://accessemergencymedicine.mhmedical.com/content.aspx?bookid=1163§ionid=65096471
Boyd, R., & Ghosh, A. (2003). Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Glucagon for the treatment of symptomatic beta blocker overdose. Emergency medicine journal : EMJ , 20 (3), 266–267. https://doi.org/10.1136/emj.20.3.266
Lheureux, P. E., Zahir, S., Gris, M., Derrey, A. S., & Penaloza, A. (2006). Bench-to-bedside review: hyperinsulinaemia/euglycaemia therapy in the management of overdose of calcium-channel blockers . Critical care (London, England) , 10 (3), 212. https://doi.org/10.1186/cc4938
Graudins A, Lee HM, Druda D. Calcium channel antagonist and beta-blocker overdose: antidotes and adjunct therapies. Br J Clin Pharmacol. 2 016 Mar;81(3):453-61. doi: 10.1111/bcp.12763. Epub 2015 Oct 30. PMID: 26344579; PMCID: PMC4767195.
Krenz JR, Kaakeh Y. An Overview of Hyperinsulinemic-Euglycemic Therapy in Calcium Channel Blocker and β-blocker Overdose. Pharmacotherapy . 2018 Nov;38(11):1130-1142. doi: 10.1002/phar.2177. Epub 2018 Oct 4. PMID: 30141827.
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. doi: 10.3109/15563650.2011.582471. PMID: 21563902.
Palatnick W, Jelic T. Calcium channel blocker and beta blocker overdose, and digoxin toxicity management. Emerg Med Pract. 2020 Sep 15;22(Suppl 9):1-42. PMID: 33136356.
Reingardiene D. Apsinuodijimas beta adrenerginiu receptoriu blokatoriais [Beta-adrenergic receptor blocker poisoning]. Medicina (Kaunas ). 2007;43(7):587-93. Lithuanian. PMID: 17768375.
Bailey B. Glucagon in beta-blocker and calcium channel blocker overdoses: a systematic review. J Toxicol Clin Toxicol. 2003;41(5):595-602. doi: 10.1081/clt-120023761. PMID: 14514004.
Palatnick W, Jelic T. Emergency department management of calcium-channel blocker, beta blocker, and digoxin toxicity. Emerg Med Pract. 2014 Feb;16(2):1-19; quiz 19-20. Update in: Emerg Med Pract. 2020 Sep 15;22(Suppl 9):1-42. PMID: 24883458.
Kerns W 2nd, Kline J, Ford MD. Beta-blocker and calcium channel blocker toxicity. Emerg Med Clin North Am. 1994 May;12(2):365-90. PMID: 7910555.
Langemeijer JJ, de Wildt DJ, de Groot G, Sangster B. Intoxication with beta-sympathicolytics. Neth J Med. 1992 Jun;40(5-6):308-15. PMID: 1359436.
DeWitt CR, Waksman JC. Pharmacology, pathophysiology and management of calcium channel blocker and beta-blocker toxicity. Toxicol Rev. 2004;23(4):223-38. doi: 10.2165/00139709-200423040-00003. PMID: 15898828.
Friis-Hansen LJ, Gøtze JP, Kastrup J. Forgiftning med betablokkere og calciumantagonister. To kardiologiske problemer med endokrinologiske løsninger? [Beta-blocker and calcium antagonist poisoning. Two cardiological problems with an endocrinological solution? ]. Ugeskr Laeger. 2004 Sep 27;166(40):3483-7. Danish. PMID: 15518000.
Leatham EW, Holt DW, McKenna WJ. Class III antiarrhythmics in overdose. Presenting features and management principles. Drug Saf. 1993 Dec;9(6):450-62. doi: 10.2165/00002018-199309060-00008. PMID: 8129865.
Bouchard J, Shepherd G, Hoffman RS, Gosselin S, Roberts DM, Li Y, Nolin TD, Lavergne V, Ghannoum M; EXTRIP workgroup. Extracorporeal treatment for poisoning to beta-adrenergic antagonists: systematic review and recommendations from the EXTRIP workgroup. Crit Care. 2021 Jun 10;25(1):201. doi: 10.1186/s13054-021-03585-7. PMID: 34112223; PMCID: PMC8194226.
Salam S, Nornhold B, Mallat J. Massive metoprolol overdose requiring ECMO: brief review of the evidence behind recommended treatments. BMJ Case Rep. 2021 May 5;14(5):e232130. doi: 10.1136/bcr-2019-232130. PMID: 33952561; PMCID: PMC8103398.
Bartlett JW, Walker PL. Management of Calcium Channel Blocker Toxicity in the Pediatric Patient. J Pediatr Pharmacol Ther. 2019 Sep-Oct;24(5):378-389. doi: 10.5863/1551-6776-24.5.378. PMID: 31598101; PMCID: PMC6782123.
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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. doi: 10.1186/cc4938. Epub 2006 May 22. PMID: 16732893; PMCID: PMC1550937.
Pentel PR, Salerno DM. Cardiac drug toxicity: digitalis glycosides and calcium-channel and beta-blocking agents. Med J Aust. 1 990 Jan 15;152(2):88-94. doi: 10.5694/j.1326-5377.1990.tb124464.x. PMID: 1967483.
Stephen VS, Pluymers NA, Gauton SJ. Emergency management of calcium channel blocker overdose. S Afr Med J. 2019 Aug 28;109(9):635-638. doi: 10.7196/SAMJ.2019.v109i9.13704. PMID: 31635586.
Mann S. Management of calcium channel blocker overdose. Emerg Nurse. 2014 Mar;21(10):36-9. doi: 10.7748/en2014.03.21.10.36.e1287. PMID: 24597819.
Shenoy S, Lankala S, Adigopula S. Management of calcium channel blocker overdoses. J Hosp Med. 2014 Oct;9(10):663-8. doi: 10.1002/jhm.2241. Epub 2014 Jul 28. PMID: 25066023.
Salhanick SD, Shannon MW. Management of calcium channel antagonist overdose. Drug Saf. 2003;26(2):65-79. doi: 10.2165/00002018-200326020-00001. PMID: 12534324.
Shepherd G, Klein-Schwartz W. High-dose insulin therapy for calcium-channel blocker overdose. Ann Pharmacother. 2005 May;39(5):923-30. doi: 10.1345/aph.1E436. Epub 2005 Apr 5. PMID: 15811898.
Siddiqi TA, Hill J, Huckleberry Y, Parthasarathy S. Non-cardiogenic pulmonary edema and life-threatening shock due to calcium channel blocker overdose: a case report and clinical review. Respir Care . 2014 Feb;59(2):e15-21. doi: 10.4187/respcare.02244. Epub 2013 May 14. PMID: 23674813.
Rietjens SJ, de Lange DW, Donker DW, Meulenbelt J. Practical recommendations for calcium channel antagonist poisoning. Neth J Med. 2016 Feb;74(2):60-7. PMID: 26951350.
Wong A, Hoffman RS, Walsh SJ, Roberts DM, Gosselin S, Bunchman TE, Kebede S, Lavergne V, Ghannoum M; EXTRIP workgroup. Extracorporeal treatment for calcium channel blocker poisoning: systematic review and recommendations from the EXTRIP workgroup. Clin Toxicol (Phila). 2021 May;59(5):361-375. doi: 10.1080/15563650.2020.1870123. Epub 2021 Feb 8. PMID: 33555964.
Pohler HF. A little goes a long way: Clinical management of calcium channel blocker overdose. J Emerg Nurs. 2006 Aug;32(4):347-9. doi: 10.1016/j.jen.2006.04.008. Erratum in: J Emerg Nurs. 2007 Feb;33(1):82. PMID: 16863888.
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. PMID: 17724247.
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Amorim S, Dias P, Rocha G, Gama G, de Campos M, Pires S. Poisoning with calcium channel blockers–a case report and review of the literature. Rev Port Cardiol. 2001 Dec;20(12):1249-57. English, Portuguese. PMID: 11865685.
Pearigen PD, Benowitz NL. Poisoning due to calcium antagonists. Experience with verapamil, diltiazem and nifedipine. Drug Saf. 1991 Nov-Dec;6(6):408-30. doi: 10.2165/00002018-199106060-00003. PMID: 1793522.
Cantrell FL, Clark RF, Manoguerra AS. Determining triage guidelines for unintentional overdoses with calcium channel antagonists. Clin Toxicol (Phila). 2005;43(7):849-53. doi: 10.1080/15563650500357511. PMID: 16440512.
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. doi: 10.1016/0002-9343(93)90314-f. PMID: 8213877.
Shepherd G. Treatment of poisoning caused by beta-adrenergic and calcium-channel blockers. Am J Health Syst Pharm . 2006 Oct 1;63(19):1828-35. doi: 10.2146/ajhp060041. Erratum in: Am J Health Syst Pharm. 2008 Sep 1;65(17):1592. PMID: 16990629.
Podcasts & Medical Blogs
Rabbit Hole: CCB & BB Toxicity
