Calcium channel blockers (CCBs) are commonly used cardiovascular drugs known to cause potential toxicity due to overdose. Treating overdose of CCBs can be a challenge even to experienced physicians. One such underreported toxicity of CCB use is the development of acute respiratory distress syndrome (ARDS). Here, we present a 28-year-old previously healthy woman, having taken 25 tablets of 5-mg amlodipine with intent to self-harm. On presentation to emergency, the patient was in shock and hypoxia. Arterial blood gas showed type 1 respiratory failure, and chest X-ray showed bilateral homogenous opacities consistent with ARDS. The patient was managed in the intensive care unit with noninvasive ventilation support and intravenous infusion of noradrenaline, insulin-dextrose, and calcium gluconate. The patient ultimately made full recovery. Severe poisoning with CCBs can cause bradycardia, profound hypotension, conduction blocks, acute kidney injury, and ARDS. It is important for physicians to know the rare complication of CCB like ARDS as early recognition and appropriate treatment results in better outcome.
Keywords: Acute respiratory distress syndrome, amlodipine, hypotension, inotropes
|How to cite this URL:|
Chikkaveeraiah SK, Kumar H S, Venkatesh C R, Padamati AR, Ashraf A. Amlodipine overdose-induced acute respiratory distress syndrome: A common calcium channel blockers causing fatal complication. APIK J Int Med [Epub ahead of print] [cited 2022 Dec 4]. Available from: https://www.ajim.in/preprintarticle.asp?id=357556
| Introduction|| |
The American Association of Poison Control Centers has reported that cardiovascular drugs are the third fastest-growing category of substance exposures. The American Association of Poison Control Centers reported 11,764 calcium channel blocker (CCB) overdoses in adults, second only to beta-blockers in several overdose deaths from cardiovascular medications. Amlodipine, the long-acting (30–58 h) drug belonging to the dihydropyridine group of CCBs, is the commonly prescribed drug. The clinical manifestations of CCB toxicity are mainly due to peripheral vasodilation and myocardial depression resulting in profound hypotension, shock, bradycardia and conduction blocks, and acute respiratory distress syndrome (ARDS).
| Case Report|| |
We report a 28-year-old female with no prior comorbidities who was referred to our hospital from a local health-care center with shock following consumption of 25 tablets of 5 mg of amlodipine. Gastric lavage was given at a local center approximately 2 h after consumption of tablets. The patient developed hypotension and was transferred to our hospital 7 h after time of ingestion. She admitted to have consumed tablets with suicidal intent and denied concomitant consumption of alcohol or any other drugs.
At presentation, she was conscious and appeared anxious. Her peripheries were cold. Physical examination revealed blood pressure (BP) of 70/50 mmHg in supine position, heart rate of 90/min, respiratory rate of 26/min, and saturation 90% on room air. Her pulse was regular. Examination of respiratory system reveled: bilateral normal vesicular breath sounds, no added sounds heard. Cardiovascular system examination: S1 and S2 heard all areas, no S3 or S4 gallop. No murmurs. Per-abdomen: soft, nontender, no organomegaly. Central nervous system: conscious, oriented. No focal neurological deficits.
Adequate fluid resuscitation was done, and additionally, injection 10% calcium gluconate of 10 ml over 20 min was given and repeated after 20 min. Insulin (1 U/kg) bolus, followed by an infusion of 0.5 unit/kg/h and dextrose infusion of 0.5 g/kg/h, was given. Strict BP monitoring and capillary blood glucose were monitored at frequent intervals (every 30 min). Vasopressor support with noradrenaline was used to overcome refractory hypotension and titrated to maintain a mean arterial pressure of 65 mmHg. Intravenous glucagon 5 mg bolus was given and another 5 mg was repeated after 5 min to combat refractory hypotension. The patient was treated with oxygen in view of hypoxia and tachypnea. Serial arterial blood gas was done which showed type 1 respiratory failure.
Initial laboratory investigations showed blood glucose of 90 mg/dl; renal function test was normal with an estimated e-GFR of 87 ml/min/1.73m.2 Liver function test was normal. Complete blood count showed neutrophilic leukocytosis. Chest X-ray done at admission was normal. As hypoxia continued to worsen over the next 24 h. Chest X-ray was repeated which showed bilateral extensive opacities consistent with ARDS [Figure 1]. Electrocardiography at admission was within normal limits [Figure 2].
The patient was maintained on inotropes and noninvasive ventilation support for the next 3 days. From day 4 of admission, her clinical condition and hypoxia had improved. She was slowly weaned off oxygen, and inotropes were gradually tapered and stopped. On day 6 of admission, she completely recovered from hypotension and hypoxia and was shifted to ward. Repeat X-ray showed resolution of opacities. She was subsequently discharged after psychiatric evaluation and counseling.
| Discussion|| |
Acting through L-type calcium channels, CCBs cause vasodilation of peripheral vasculature and myocardial depression, which can result in profound hypotension, shock, bradycardia, and conduction blocks. Amlodipine belongs to the dihydropyridine group of CCBs. In the usual dose (10–20 mg/day), this group of drugs has greater affinity for smooth muscle than the myocardium, whereas this selective affinity is lost in the case of severe toxicity. Amlodipine toxicity (5–10 times the therapeutic dose) is seen within 0.5–1 h following consumption and its effect last for 30–58 h (long duration) compared to other generations of dihydropyridines. The mechanism behind CCB toxicity causing ARDS is unknown, but two mechanisms have been proposed: one suggests that CCBs inhibit endothelin-1-stimulated surfactant secretion by type II epithelial cells, leading to alveolar collapse, while another suggests that selective precapillary vasodilation causes excessive transudation of fluid from pulmonary capillaries into the alveoli. Although CCB-induced ARDS is a rare occurrence, the literature supports the notion that CCB intoxication can increase patient risk of developing ARDS.
The lowest reported toxic adult dose of amlodipine is 30 mg. Management of CCB toxicity often requires a multitude of pharmacological agents with scarce evidence for their use. Patients can deteriorate quickly, and prompt administration of medications is vital to achieve cardiovascular stability. Initial evaluation and management of life-threatening complications (e.g.: airway, breathing, and circulation) is necessary. Gastric lavage with activated charcoal is important for all large ingestions. The patient with altered mental status and respiratory distress should be intubated before gastric lavage. Calcium chloride/gluconate helps to overcome the competitive blockade of calcium channels. It improves hypotension, contractility, and conduction abnormalities. Continuous intravenous infusion of calcium chloride 20–40 mg/kg/h and Glucagon (5–10 mg intravenous). Stimulates adenylate cyclase and increases intracellular cyclic adenosine monophosphate. This improves cardiac contractility and heart rate. Various clinical observations support the use of the hyperinsulinemia/euglycemia technique in the management of CCB overdose. The proposed dosing of insulin in CCB toxicity is to give a regular insulin 1 IU/kg intravenous bolus followed by insulin infusion at the rate of 0.5 IU/kg/h. Blood glucose should be checked every half hour, and hypertonic glucose must be infused to maintain blood sugar in the upper normal range.
Amlodipine overdose may currently be a rare presentation, but with an increasing number of people now on CCBs, these cases may become more commonplace. It is important to have a structured approach to deal with amlodipine overdoses and to be aware of potentially life-threatening complications like ARDS.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Salhanick SD, Shannon MW. Management of calcium channel antagonist overdose. Drug Saf 2003;26:65-79.
Francis D. Calcium channel blockers. In: Flomenbaum NE, Goldfrank LR, Hoffman RS, Howland MA, Lewin NA, Nelson LS, editors. Goldfrank's Toxocologic Emergencies. 8th
ed. New York, USA: McGraw Hills; 2006. p. 912-20.
Rizvi I, Ahmad A, Gupta A, Zaman S. Life-threatening calcium channel blocker overdose and its management. BMJ Case Rep 2012;2012:bcr0120125643.
Russell RP. Side effects of calcium channel blockers. Hypertension 1988;11:I42-4.
Humbert VH Jr., Munn NJ, Hawkins RF. Noncardiogenic pulmonary edema complicating massive diltiazem overdose. Chest 1991;99:258-9.
Saravu K, Balasubramanian R. Near-fatal amlodipine poisoning. J Assoc Phys India 2004;52:156-7.
Magdalan J, Antończyk A, Kowalski K, Przewłocki M, Kochman K, Wasylko-Smolarek M. Severe pulmonary complications of massive intoxication with calcium channel blockers and isosorbide mononitrate – A case report. Przegl Lek 2004;61:405-7.
Harris NS. Case records of the Massachusetts General Hospital. Case 24-2006. A 40-year-old woman with hypotension after an overdose of amlodipine. N Engl J Med 2006;355:602-11.
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;10:212.
Ashika Reddy Padamati,
Department of General Medicine, Jss Medical College, JSS AHER, Mysuru - 570 015, Karnataka
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2]