calcium channel blocker overdose treatment

Amlodipine is a dihydropyridine calcium-channel blocker (CCB) and a potent vasodilator that preferentially blocks the influx of calcium into cells via L-type calcium channels in the vasculature. Amlodipine overdose typically presents with arterial vasodilation, hypotension, and reflex tachycardia. At higher doses, the vascular selectivity can be lost, and toxicity may affect cardiac contractility and conduction. Rapid onset of refractory hypotension and bradycardia may be encountered, especially in nondihydropyridine CCB (diltiazem, verapamil) overdose. Treatment for CCB overdose has not been well studied; therefore, management strategies are based on expert opinion and case reports and its known effects on vascular smooth muscle, cardiac myocytes, cardiac conduction tissue, and pancreatic β cells. IV calcium, high-dose insulin, and lipid emulsion therapy are recommended in symptomatic CCB overdose. As CCBs interfere with intracellular transport of calcium, calcium may be ineffective and require higher doses. In severe cases, high-dose continuous infusion of calcium has been used with reported success. High-dose insulin therapy has been shown to increase ionized calcium and inotropy in the setting of CCB toxicity. Prior to initiating high-dose insulin therapy, hypokalemia must be corrected, and if the baseline serum glucose is <200 mg/dL (11.10 mmol/L), IV dextrose should be administered. Close monitoring of serum glucose and potassium is critical during high-dose insulin therapy. High-dose insulin therapy has an initial bolus of 1 U/kg of regular, short-acting insulin IV, followed by a continuous infusion at 0.5 to 1 U/kg/h IV and titrated up to a maximum of 10 U/kg/h. As this patient remains hypotensive despite calcium and intravascular fluids, high-dose insulin therapy should be initiated. It is important to note that the hemodynamic response may take 30 to 60 min after initiation of high-dose insulin therapy.

In 2017, an expert consensus statement was published recommending a stepwise approach to the management of CCB poisoning in adults. First-line therapy for symptomatic CCB poisoning includes IV calcium, high-dose insulin therapy, vasopressors (norepinephrine, epinephrine) in the presence of shock, and atropine in the presence of bradycardia or conduction disturbances. If a patient is refractory to first-line therapy, the working group recommends incremental doses of high-dose insulin therapy, a pacemaker in the presence of bradycardia or high-grade atrioventricular block, and IV lipid emulsion therapy. The use of IV lipid emulsion to treat toxicity of anesthetics, such as bupivacaine, is well accepted. Its use in overdoses, including CCB, is recommended, but, as with high-dose insulin therapy, it has not been well studied. For patients in refractory shock, consideration for venoarterial extracorporeal membrane oxygenation in the presence of cardiogenic shock in addition to IV calcium, high-dose insulin therapy, and IV lipid emulsion therapy should be made. 

Glucagon increases intracellular cyclic adenosine monophosphate, resulting in increased inotropy, chronotropy, and cardiac conduction but appears to have minimal effect on mean arterial pressure. Glucagon is first-line therapy for β-blocker overdose and has traditionally been recommended in CCB overdose; however, the 2017 consensus statement does not recommend the use of glucagon in CCB poisoning, as the available data have variable results and more effective interventions for CCB overdoses are available. Furthermore, in this patient with isolated hypotension, administering glucagon prior to initiating high-dose insulin would not be the best next step in his management. Amlodipine is extensively protein bound, with a large volume of distribution, making it not amenable to removal by dialysis. Methylene blue is first-line therapy for methemoglobinemia and is not recommended in CCB overdose.123456

Footnotes

  1. SEEK Questionnaires ↩

  2. American College of Medical Toxicology. ACMT position statement: guidance for the use of intravenous lipid emulsion. J Med Toxicol. 2017;13(1):124-125. PubMed ↩

  3. Engebretsen KM, Kaczmarek KM, Morgan J, et al. High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning. Clin Toxicol (Phila). 2011;49(4):277-283. PubMed ↩

  4. Lam YM, Tse HF, Lau CP. Continuous calcium chloride infusion for massive nifedipine overdose. Chest. 2001;119(4):1280-1282. PubMed ↩

  5. Shepherd G. Treatment of poisoning caused by beta-adrenergic and calcium-channel blockers. Am J Health Syst Pharm. 2006;63(19):1828-1835. PubMed ↩

  6. St-Onge M, Anseeuw K, Cantrell FL, et al. Experts consensus recommendations for the management of calcium channel blocker poisoning in adults. Crit Care Med. 2017;45(3):e306-e315. PubMed ↩