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Continuous Calcium Chloride Infusion for Massive Nifedipine Overdose* FREE TO VIEW

Yui-Ming Lam, MB; Hung-Fat Tse, MD; Chu-Pak Lau, MD, FCCP
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*From the Division of Cardiology, Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China.

Correspondence to: Hung-Fat Tse, MD, Division of Cardiology, Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China; e-mail: hftse@hkucc.hku.hk



Chest. 2001;119(4):1280-1282. doi:10.1378/chest.119.4.1280
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A 37-year-old woman presented with persistent hypotension and noncardiogenic pulmonary edema after massive nifedipine overdose. Judicious use of continuous and prolonged high-dose IV calcium infusion was administered to provide sustained increases in serum ionic calcium level (approximately 2 mmol/L) and was able to improve the hemodynamic status without any major adverse reaction.

Figures in this Article

Nifedipine, a calcium-channel blocker (CCB), has been widely used in the management of various cardiovascular conditions, such as hypertension, angina pectoris, and Raynaud’s phenomenon. Although serious side effects are uncommon, massive overdose of CCB may result in hemodynamic instability and, rarely, death.14 In this article, we describe a case of massive overdose of sustained-release preparation of nifedipine resulting in prolonged refractory hypotension and noncardiogenic pulmonary edema, which were successfully treated with continuous IV CaCl infusion.

A 37-year-old woman with history of diabetes mellitus, hypertension, and paranoid schizophrenia was bought to the emergency department 1 h after taking 210 20-mg tablets of nifedipine for a suicide attempt. On arrival, she developed hypotension (BP, 80/45 mm Hg) and sinus tachycardia (pulse rate, 115 beats/min). She was initially treated with gastric lavage, activated charcoal, IV fluid therapy, and two doses of IV bolus injection of calcium gluconate (10 mL of 10% solution). However, she had persistent hypotension and developed progressive increasing shortness of breath. She was then transferred to the coronary care unit for further management.

After admission to the coronary care unit, she developed circulatory shock, with a BP of 70/30 mm Hg. Physical examination and chest radiography showed acute pulmonary edema, and a 12-lead ECG revealed sinus tachycardia without any ischemic changes. Laboratory studies revealed normal liver and renal function, with a serum glucose and ionic calcium level of7.8 mmol/L and 1.14 mmol/L (normal range, 1.12 to 1.23 mmol/L), respectively. Blood and urine toxicology screens were negative. Echocardiography showed normal left ventricular systolic function with ejection fraction of 62%. Her BP failed to improve with multiple doses of bolus injection of calcium gluconate (10 mL of 10% solution). The average dosage of calcium gluconate administrated within 24 h was 0.3 mg/h, and the serum ionic calcium level was increased to 1.27 mmol/L. High doses of IV infusion of dopamine and noradrenaline were administrated to maintain a mean arterial pressure of 60 mm Hg (Fig 1 ).

Subsequently, continuous IV infusion of CaCl at a rate of 20μ g/min was started at 25 h after overdose, and the dose was titrated to maintain the serum ionic calcium level around 2 mmol/L. The serum concentration of nifedipine measured 40 h after overdose was 209 μg/L (therapeutic range, 25 to 100 μg/L). The estimated plasma level of nifedipine at 25 h after overdose was about 600 μg/L, and the estimated peak level was up to 2,000 μg/L.5 Her BP improved shortly after the infusion of the CaCl solution, and the inotropes could be successfully reduced over the next 48 h (Fig 1). With the use of continuous CaCl infusion and diuretic therapy, the pulmonary edema subsided. IV CaCl infusion was stopped 60 h after admission. Unfortunately, she developed skin necrosis over the peripheral drip site due to extravasation of CaCl, which required debridement and skin grafting.

Initial treatment of nifedipine overdose should consist of gastric lavage and administration of activated charcoal to reduce GI absorption. Since nifedipine is highly protein bound, hemofiltration or dialysis is of no value. Although IV calcium is the initial pharmacotherapy for CCB overdose, its clinical efficacy is inconsistent67 and the dosage required is unclear. As demonstrated in this case, repeated bolus injection of calcium gluconate failed to reverse the toxicity of massive CCB overdose, and sustained-release preparation of CCB can result in prolonged hemodynamic instability. In animal experiments, doubling the serum calcium level is required for treatment of severe CCB toxicity.8 In this case, continuous and prolonged high-dose IV calcium infusion was administered to provide sustained increases in serum ionic calcium level (approximately 2 mmol/L) and was able to improve the hemodynamic status without any major adverse reaction. However, the risk of extravasation should be minimized by infusion using a central venous line. CaCl is preferable to calcium gluconate as the percentage of calcium ion available is higher (13.6 mEq vs 4.5 mEq in 10 mL of 10% solution). In patients with massive CCB overdose, additional catecholamine infusion may be required to maintain the hemodynamic status.1 Furthermore, glucagon injection may be useful in those who are refractory to other treatment.9

Occasionally, hyperglycemia, bradyarrhythmias, and noncardiogenic pulmonary edema may complicate CCB overdose.1,4,10 In this patient, only noncardiogenic pulmonary edema was observed. The exact mechanism of noncardiogenic pulmonary edema associated with CCB overdose is unclear but may be attributed to selective precapillary vasodilation and excessive fluid resuscitation for treatment of hypotension. Continuous calcium infusion and diuretic therapy can lead to resolution of the noncardiogenic pulmonary edema.

In conclusion, massive CCB overdose can be lethal and the adverse effects are significantly prolonged if a sustained-release preparation has been taken. Judicious use of continuous CaCl infusion is a safe and effective treatment for patients with hemodynamic instability due to massive CCB overdose.

Abbreviation: CCB = calcium-channel blocker

Figure Jump LinkFigure 1. The dosage and effect of IV infusion of dopamine (micrograms per kilogram per minute), noradrenaline (micrograms per minute), and CaCl (micrograms per minute) on the mean arterial BP after admission. The arrows indicate the administration of bolus injection of calcium gluconate (10 mL of 10% solution, 1 g).Grahic Jump Location
Ramoska, EA, Spiller, HA, Winter, M, et al (1993) A one-year evaluation of calcium channel blocker overdoses: toxicity and treatment.Ann Emerg Med22,196-200. [CrossRef] [PubMed]
 
MacDonald, D, Alguire, PC Case report: fatal overdose with sustained-release verapamil.Am J Med Sci1992;303,115-117. [CrossRef] [PubMed]
 
Cosbey, SH, Carson, DJ A fatal case of amlodipine poisoning.J Anal Toxicol1997;21,221-222. [PubMed]
 
Stanek, EJ, Nelson, CE, DeNofrio, D Amlodipine overdose.Ann Pharmacother1997;31,853-856. [PubMed]
 
Kleinbloesem, CH, van Brummelen, P, van de Linde, JA, et al Nifedipine: kinetics and dynamics in healthy subjects.Clin Pharmacol Ther1984;35,742-749. [CrossRef] [PubMed]
 
Crump, BJ, Holt, DW, Vale, JA Lack of response to intravenous calcium in severe verapamil poisoning.Lancet1982;2,939-940. [PubMed]
 
Luscher, TF, Noll, G, Sturmer, T, et al Calcium gluconate in severe verapamil intoxication.N Engl J Med1994;330,718-719. [CrossRef] [PubMed]
 
Hariman, RJ, Mangiardi, LM, McAllister, RG, et al Reversal of the cardiovascular effects of verapamil by calcium and sodium: differences between electrophysiologic and hemodynamic responses.Circulation1979;59,797-804. [CrossRef] [PubMed]
 
Fant, JS, James, LP, Fiser, RT, et al The use of glucagon in nifedipine poisoning complicated by clonidine ingestion.Pediatr Emerg Care1997;13,417-419. [CrossRef] [PubMed]
 
Herrington, DM, Insley, BM, Weinmann, GG Nifedipine overdose.Am J Med1986;81,344-346. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. The dosage and effect of IV infusion of dopamine (micrograms per kilogram per minute), noradrenaline (micrograms per minute), and CaCl (micrograms per minute) on the mean arterial BP after admission. The arrows indicate the administration of bolus injection of calcium gluconate (10 mL of 10% solution, 1 g).Grahic Jump Location

Tables

References

Ramoska, EA, Spiller, HA, Winter, M, et al (1993) A one-year evaluation of calcium channel blocker overdoses: toxicity and treatment.Ann Emerg Med22,196-200. [CrossRef] [PubMed]
 
MacDonald, D, Alguire, PC Case report: fatal overdose with sustained-release verapamil.Am J Med Sci1992;303,115-117. [CrossRef] [PubMed]
 
Cosbey, SH, Carson, DJ A fatal case of amlodipine poisoning.J Anal Toxicol1997;21,221-222. [PubMed]
 
Stanek, EJ, Nelson, CE, DeNofrio, D Amlodipine overdose.Ann Pharmacother1997;31,853-856. [PubMed]
 
Kleinbloesem, CH, van Brummelen, P, van de Linde, JA, et al Nifedipine: kinetics and dynamics in healthy subjects.Clin Pharmacol Ther1984;35,742-749. [CrossRef] [PubMed]
 
Crump, BJ, Holt, DW, Vale, JA Lack of response to intravenous calcium in severe verapamil poisoning.Lancet1982;2,939-940. [PubMed]
 
Luscher, TF, Noll, G, Sturmer, T, et al Calcium gluconate in severe verapamil intoxication.N Engl J Med1994;330,718-719. [CrossRef] [PubMed]
 
Hariman, RJ, Mangiardi, LM, McAllister, RG, et al Reversal of the cardiovascular effects of verapamil by calcium and sodium: differences between electrophysiologic and hemodynamic responses.Circulation1979;59,797-804. [CrossRef] [PubMed]
 
Fant, JS, James, LP, Fiser, RT, et al The use of glucagon in nifedipine poisoning complicated by clonidine ingestion.Pediatr Emerg Care1997;13,417-419. [CrossRef] [PubMed]
 
Herrington, DM, Insley, BM, Weinmann, GG Nifedipine overdose.Am J Med1986;81,344-346. [CrossRef] [PubMed]
 
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