Calcium Channel Blocker Overdose Research Articles

Role of intravenous lipid emulsions in the management of calcium channel blocker and β-blocker overdose: 3 years experience of a university hospital

Objectives: The objective of this study was to assess the efficacy of lipid emulsion as antidotal therapy in severe calcium channel blocker (CCB) and β-blocker (BB) intoxications. Patients and methods: This is a retrospective study in which we have summarized data of patients who were admitted to a university-based emergency department in a period of 3 years and were given intravenous lipid emulsion (ILE) to manage cardiogenic shock due to CCB and BB overdose. Results: We identified 15 patients who received ILE therapy for CCB and BB toxicity. Hospitalization durations variated between 3 and 33 days (mean 7.46 ± 7.41 days). Drug exposures included CCBs (n = 8, 53.3%), CCBs and paracetamol (n = 1, 6.6%), and BBs (n = 6, 40%). ILE therapy was effective in 12 patients (80%). Three patients (20%) had resistant hypotension, one of whom progressed to pulmonary edema. Adverse effects of ILE therapy were seen in three patients (20%). Two patients underwent mechanical ventilation. Two patients developed hypoxic ischemic encephalopathy, one patient died, and 14 patients (93.3%) were discharged from hospital. Conclusion: There was 93.3% survival in patients receiving ILE for drug-induced cardiovascular collapse. Clinically significant adverse effects were uncommon. We suggest ILE administration for the treatment of cardiogenic shock due to CCB and BB overdose.

Treatment of near-fatal beta blocker and calcium channel blocker intoxication with hyperinsulinemic euglycemia, intravenous lipid emulsions and high doses of norepinephrine

Background. Treatment of combined beta blocker and calcium channel blocker intoxication remains challenging due to a profound and treatment-resistant circulatory collapse. Along with standard therapy (calcium, glucagon, mechanical ventilation, vasopressors), two novel approaches are increasingly being reported as successful: hyperinsulinemic euglycemia and intravenous lipid emulsion.Case Report. Our patient: a 66-year-old Caucasian male who ingested approximately 450 mg of bisoprolol, 300 mg of amlodipine, 200 mg of doxazosin and smaller amounts of nifedipine, torasemide, acetysaliclic acid and ibuprofen in a suicide attempt. The patient was hypotensive and bradycardic on admission with left-ventricular ejection fraction estimated at 10-15%. By combining standard therapy (intubation, mechanical ventilation, vasopressors, calcium and glucagon) and new therapies (hyperinsulinemic euglycemia and intravenous lipid emulsions) in a stepwise approach we normalized systolic function and treated bradycardia within 2 hours of admission. However, severe hypotension persisted requiring extremely high doses of norepinephrine (14 mcg/kg/min) and vasopressin (0.03 U/min) to maintain his blood pressure over the following three days. He was discharged home after prolonged in-hospital treatment and rehabilitation (62 days) and extensive physical and psychiatric rehabilitation.Why should an emergency physician be aware of this? Aggressive medical therapy including hyperinsulinemic euglycemia, intravenous lipid emulsions and high doses of norepinephrine could be considered for multidrug intoxication with a predominant clinical picture of beta blocker and calcium channel blocker intoxication in patients presenting with severe hemodynamic compromise.

Noncardiogenic Pulmonary Edema after Amlodipine Overdose without Refractory Hypotension and Bradycardia

Amlodipine overdose can be life-threatening when manifesting as noncardiogenic pulmonary edema. Treatment remains challenging. We describe a case of noncardiogenic pulmonary edema without refractory hypotension and bradycardia after ingestion of 500 milligram amlodipine with suicidal intent. Mechanical ventilation, dexamethasone, atrovent HFA (ipratropium), pulmicort inhalation, and antibiotic therapy were used for the management. Length of hospital stay was 11 days. The patient was discharged with full recovery.

Amlodipine intoxication complicated by acute kidney injury and rhabdomyolysis

Amlodipine, a calcium channel blocker of the dihydropyridine group, is commonly used in management of hypertension, angina, and myocardial infarction. Amlodipine overdose, characterized by severe hypotension, arrythmias, and pulmonary edema, has seldom been reported in Korean literature. We report on a fatal case of amlodipine intoxication with complications including rhabdomyolysis and oliguric acute kidney injury. A 70-year-old woman with a medical history of hypertension was presented at the author's hospital 6 hours after ingestion of 50 amlodipine (norvasc) tablets (total dosage 250 mg) in an attempted suicide. Her laboratory tests showed a serum creatinine level of 2.5 mg/dL, with elevated serum creatine phosphokinase and myoglobin. The patient was initially treated with fluids, alkali, calcium gluconate, glucagon, and vasopressors without a hemodynamic effect. High-dose insulin therapy was also started with a bolus injection of regular insulin (RI), followed by continuous infusion of RI and 50% dextrose with water. Despite intensive treatment including insulin therapy, inotropics, mechanical ventilation, and continuous venovenous hemodiafiltration, the patient died of refractory shock and cardiac arrest with no signs of renal recovery 116 hours after her hospital admission.

Noninvasive ventilation in a patient with noncardiogenic pulmonary edema following amlodipine poisoning.

Noninvasive ventilation in a patient with noncardiogenic pulmonary edema following amlodipine poisoning.

Intoxication aigüe au vérapamil : attention à l’effet retard

Intoxication with calcium channel inhibitory drugs is rare but mortality rates reach 10%. We report the case of a 5-year-old girl who had ingested five 240-mg tablets of extended-release verapamil (VLP) and a tablet of bromazepam. Thirty hours after the ingestion she had a vasoplegic shock, heart conduction disorders, and metabolic complications. She was treated in pediatric intensive care with continuous epinephrine and insulin and recovered completely 60h after the ingestion. This case underlines the danger of calcium channel blocker overdose, increased by the extended-release mechanism: the drug effect is to slow down gastric motility -which explains the latency of the symptoms- but this also increases the drug absorption, inducing a vicious circle. These mechanisms in calcium blocker intoxication need to be kept in mind in order to decrease the mortality of such accidents.

Efficacy of Methylene Blue in an Experimental Model of Calcium Channel Blocker–Induced Shock

Calcium channel blocker poisonings account for a substantial number of reported deaths from cardiovascular drugs. Although supportive care is the mainstay of treatment, experimental therapies such as high-dose insulin-euglycemia and lipid emulsion have been studied in animal models and used in humans. In the most severe cases, even aggressive care is inadequate and deaths occur. In both experimental models and clinical cases of vasodilatory shock, methylene blue improves hemodynamic measures. It acts as a nitric oxide scavenger and inhibits guanylate cyclase that is responsible for the production of cyclic guanosine monophosphate (cGMP). Excessive cGMP production is associated with refractory vasodilatory shock in sepsis and anaphylaxis. The aim of this study is to determine the efficacy of methylene blue in an animal model of amlodipine-induced shock. Sprague-Dawley rats were anesthetized, ventilated, and instrumented for continuous blood pressure and pulse rate monitoring. The dose of amlodipine that produced death within 60 minutes was 17 mg/kg per hour (LD50). Rats were divided into 2 groups: amlodipine followed by methylene blue or amlodipine followed by normal saline solution, with 15 rats in each group. Rats received methylene blue at 2 mg/kg during 5 minutes or an equivalent amount of normal saline solution in 3 intervals from the start of the protocol: minutes 5, 30, and 60. The animals were observed for a total of 2 hours after the start of the protocol. Mortality risk and survival time were analyzed with Fisher's exact test and Kaplan-Meier survival analysis with the log rank test. Overall, 1 of 15 rats (7%) in the saline solution-treated group survived to 120 minutes compared with 5 of 15 (33%) in the methylene blue-treated group (difference -26%; 95% confidence interval [CI] -54% to 0.3%). The median survival time for the normal saline solution group was 42 minutes (95% CI 28.1 to 55.9 minutes); for the methylene blue group, 109 minutes (95% CI 93.9 to 124.1 minutes). Pulse rate and mean arterial pressure (MAP) differences between groups were analyzed until 60 minutes. Pulse rate was significantly higher in the methylene blue-treated group beginning 25 minutes after the start of the amlodipine infusion (95% CI 30 to 113 minutes) that was analyzed until 60 minutes. MAP was significantly higher in the methylene blue-treated group starting 25 minutes after the amlodipine infusion (95% CI 2 to 30 minutes) that was analyzed until 60 minutes. Methylene blue did not result in a significant difference in mortality risk. There was an increased pulse rate, MAP, and median survival time in the methylene blue group.

Management of calcium channel blocker overdoses.

Calcium channel blockers (CCBs) are some of the most commonly used medications in clinical practice to treat hypertension, angina, cardiac arrhythmias, and some cases of heart failure. Recent data show that CCBs are the most common of the cardiovascular medications noted in intentional or unintentional overdoses.(1) Novel treatment approaches in the form of glucagon, high-dose insulin therapy, and intravenous lipid emulsion therapies have been tried and have been successful. However, the evidence for these are limited to case reports and case series. We take this opportunity to review the various treatment options in the management of CCB overdoses with a special focus on high-dose insulin therapy as the emerging choice for initial therapy in severe overdoses.

High dose insulin therapy, an evidence based approach to beta blocker/calcium channel blocker toxicity

Poison-induced cardiogenic shock (PICS) as a result of beta-blocker (β-blocker) or calcium channel blocker (CCB) overdose is a common and potentially life-threatening condition. Conventional therapies, including fluid resuscitation, atropine, cardiac pacing, calcium, glucagon, and vasopressors often fail to improve hemodynamic status. High-dose insulin (HDI) is an emerging therapeutic modality for PICS. In this article, we discuss the existing literature and highlight the therapeutic success and potential of HDI. Based on the current literature, which is limited primarily to case series and animal models, the authors conclude that HDI can be effective in restoring hemodynamic stability, and recommend considering its use in patients with PICS that is not responsive to traditional therapies. Future studies should be undertaken to determine the optimal dose and duration of therapy for HDI in PICS.

Management of calcium channel blocker overdose

The management of patients who have overdosed with calcium channel blockers (CCBs), which are commonly prescribed for hypertension, arrhythmia and angina, can be difficult but early initiation of the correct treatment increases the likelihood of good outcomes. This article refers to a case study to illustrate the unpredictable nature of overdose with CCBs and describes the treatment needed to reverse their effects.

High-Dose Insulin and Intravenous Lipid Emulsion Therapy for Cardiogenic Shock Induced by Intentional Calcium-Channel Blocker and Beta-Blocker Overdose: A Case Series

BackgroundRecently, high-dose insulin (HDI) and intravenous lipid emulsion (ILE) have emerged as treatment options for severe toxicity from calcium-channel blocker (CCB) and beta blocker (BB). ObjectiveOur aim was to describe the use and effectiveness of HDI and ILE for the treatment of CCB and BB overdose. Case ReportsWe describe 2 patients presenting to the emergency department after intentional ingestions of CCBs and BBs. A 35-year-old man presented in pulseless electrical activity after ingesting amlodopine, verapamil, and metoprolol. A 59-year-old man presented with cardiogenic shock (CS) after ingesting amlodopine, simvastatin, lisinopril, and metformin. Both patients were initially treated with glucagon, calcium, and vasopressors. Shortly after arrival, HDI (1 unit/kg × 1; 1 unit/kg/h infusion) and ILE 20% (1.5 mL/kg × 1; 0.25 mL/kg/min × 60 min) were initiated. This led to hemodynamic improvement and resolution of shock. At the time of hospital discharge, both patients had achieved full neurologic recovery. ConclusionsHDI effectively reverses CS induced by CCBs and BBs due to its inotropic effects, uptake of glucose into cardiac muscle, and peripheral vasodilatation. ILE is theorized to sequester agents dependent on lipid solubility from the plasma, preventing further toxicity. To our knowledge, these are the first two successful cases reported using the combination of HDI and ILE for reversing CS induced by intentional ingestions of CCBs and BBs.

Treatment of Calcium Channel Blocker Poisoning: Should We Reprioritize Our Potpourri of Treatment Options?: Answers to the September 2013 Journal Club Questions

Treatment of Calcium Channel Blocker Poisoning: Should We Reprioritize Our Potpourri of Treatment Options?: Answers to the September 2013 Journal Club Questions

Refractory Hypodynamic Shock: Role of Insulin in Toxodromes

Calcium channel blocker (CCB) and beta blocker (BB) toxicities are considered the most common lethal prescription drug overdoses. Awareness regarding implementation of insulin-euglycemia state in treatment of anti-hypertensive overdose is limited in clinical practice. We report a similar case of a 56 years old male who presented with CCB and BB overdose and responded exceptionally well to aforementioned regimen. This case further emphasizes that it is imperative for clinicians to recognize that prompt initiation of high-dose insulin therapy has significant morbidity and mortality benefits in these toxodromes. J Med Cases. 2014;5(8):427-429 doi: http://dx.doi.org/10.14740/jmc1851w

Evaluation of the Treatment Approaches and Complications of Calcium Channel Blocker Intoxications

Objective: Calcium channel blockers (CCBs) are used in the treatment of angina, hypertension, arrhythmias, and prevention of migraines. The incidence of accidental or intentional calcium channel blocker intoxication has increased in recent years, which is thought to be related to more frequent use. Calcium channel blockers intoxications may progress to mortality. In our study, we investigated the treatments of suicidal or accidental calcium channel blocker intoxications and the relationships between the complications and these therapies. Material and Methods: The data of this retrospective study were obtained from the patient files. The patients who had been admitted to the Konya Training and Research Hospital with excessive intake of calcium channel blockers and been followed-up in the toxicology and emergency critical intensive care units between 2010 and 2012 were sequentially included in the study. No cases were excluded from the study. Results: A total of 15 patients were included in the study. Eight patients had taken verapamil, 4 patients had taken amlodipine, and 3 patients had taken nifedipine. The treatment included 0.9% normal saline infusion for all patients. Ten patients were given calcium replacement and 4 were given renal replacement therapy. ILE infusion was begun in six patients. Six patients were given glucagon. Five patients had developed hyperglycemia, 4 of whom underwent high-dose insulin-glucose treatment. Various complications were observed in 10 of the 15 cases. Hyperglycemia and non-cardiogenic pulmonary oedema were observed in 33.3% of the patients, metabolic acidosis was observed in 40% and block was observed in 26.7%. Cardiac arrest was observed in two patients, one of whom died. Conclusion: According to our results, none of the treatments had any priority over another. In order to prevent the possible complications, we suggest the application of multi-treatment strategies in the early period, particularly in high dose CCB intakes. (JAEM 2013; 12: 189-94)

Intravenous lipid emulsion in the management of amlodipine overdose.

To report a case of amlodipine overdose successfully treated with intravenous lipid emulsion (ILE). A 47-year-old, 110 kg female ingested at least 350 mg of amlodipine with an unknown amount of ethanol. Initial blood pressure was 103/57 mm Hg, mean arterial pressure (MAP) 72 mm Hg, and heart rate 113 beats per minute. In the early clinical course, activated charcoal, intravenous fluid, and calcium boluses were administered. Worsening hypotension prompted a 100 mL bolus of 20% ILE. Stable hemodynamics were maintained for 2 hours. Subsequently, profound hypotension and shock developed (MAP 38 mm Hg), which failed to fully respond to 3 vasopressor agents, calcium, and glucagon. With continuing shock despite optimized vasopressors, an infusion of 2,300 mL 20% ILE was administered over 4.5 hours (20.9 mL/kg infusion total). By completion of the infusion, 2 vasopressors were tapered off and MAP remained above 70 mm Hg; within 12 hours, no further interventions were required. Possible adverse events of ILE, lipemia and hypoxia, were experienced but quickly resolved. The patient survived to hospital discharge within 8 days. Toxicity of amlodipine presents similar to distributive shock as both are due to marked peripheral vasodilation. There are numerous interventions in the management of amlodipine overdose, despite which many patients continue to suffer life-threatening shock as observed with this patient. ILE has been used with promising preliminary results as salvage therapy in case reports of other lipophilic molecules. This is the first report of lone amlodipine overdose treated with ILE. ILE is a novel antidote for overdoses of lipophilic substances and demonstrated efficacy in this case of amlodipine overdose without the use of hyperinsulinemic euglycemia.

Hypocalcaemia after an Occult Calcium Channel Blocker Overdose: A Case Report and Literature Review

Hypocalcaemia is a rare complication of calcium channel blocker overdose, having been reported only once previously (J Toxicol Clin Toxicol, 1992, 30, 309). In this article, we report a case of a 37-year-old woman who developed hypocalcaemia after a verapamil overdose, review the literature and propose a mechanism for this rare finding.

Lipid Rescue Therapy and High-Dose insulin Euglycemic Therapy are Effective for Severe Refractory Calcium Channel Blocker Overdose: Case Report and Review of Literature

Background: High-Dose Insulin Euglycemic Therapy (HIET) and Lipid Rescue Therapy (LRT) are new alternative treatments for acute poisoning with calcium channel blockers. In this report a severely poisoned patient with verapamil and furosemide who was successfully treated with these two treatments is presented. Case report: A 27-year-old woman was brought to “Mother Theresa” Clinical Center in Skopje with a history of consumption of 24 grams (100 pills) sustained-release verapamil and 4 grams (10 pills) furosemide. She was alert and oriented with 60/35 mmHg blood pressure (BP), her respiratory rate was 25 breaths/min and heart rate was 40 beats/min with first degree atrioventricular (AV) block on electrocardiogram (ECG). In the first 90 minutes, she received activated charcoal, 1 liter of 0.9% saline, 60 mL of calcium chloride (CaCl2), 40 mg potassium and subsequently dopamine and 100 mg noradrenaline. However, there was no significant improvement in her hemodynamic status (BP = 70/50 mmHg) and she developed second degree AV block. Temporary pace maker was implanted. In the next one hour, the patient had stable vital signs, when she again became hypotensive (BP = 60/35 mmHg) with prolonged QRS complex (20 msec). During this period she was treated with epinephrine (9mg), atropine (2mg), isoprenalin, bicarbonate, CaCl2 and intravenous fluid. Unsuccessful conventional treatments indicated administration of HIET and LRT. Three hours later, the BP was normalized (110/75mm) and 36 hours later, all ECG disturbances disappeared. She left the Clinic without any sequels, four days later. Conclusion: LRT in addition to HIET are effective treatments for CCB overdose. LRT can be considered as a standard treatment for CCB overdose. Nevertheless, further investigations are necessary to establish the real value of these treatments. How to cite this article: Bekjarovski NG. Lipid Rescue Therapy and High-Dose insulin Euglycemic Therapy are Effective for Severe Refractory Calcium Channel Blocker Overdose: Case Report and Review of Literature. Asia Pac J Med Toxicol 2013;2:114-6.

Treatment of Calcium Channel Blocker Poisoning: Should We Re-Prioritize Our Potpourri of Treatment Options?

Treatment of Calcium Channel Blocker Poisoning: Should We Re-Prioritize Our Potpourri of Treatment Options?

Venoarterial extracorporeal membrane oxygenation for the management of massive amlodipine overdose

A 50-year-old man was admitted to the intensive care unit with respiratory failure and shock after suffering a massive overdose of amlodipine, lisinopril and hydrochlorothiazide. Despite mechanical ventilation, vasopressors, calcium gluconate, hyperinsulinemia-euglycemia therapy, methylene blue and intravenous fat emulsion, the patient's respiratory and hemodynamic status deteriorated. Venoarterial extracorporeal membrane oxygenation (ECMO) was initiated to provide cardiopulmonary support in the setting of profound respiratory failure and refractory shock. The patient was placed on ECMO 19 hours after arrival to the hospital, after which vasopressor and ventilatory requirements decreased significantly. The patient was decannulated from ECMO after 8 days and was discharged home after a 56-day hospitalization. Early institution of ECMO should be considered for the management of respiratory failure and refractory shock in the setting of calcium channel blocker overdose when medical therapies are insufficient.

Non-cardiogenic Pulmonary Edema and Life-Threatening Shock Due to Calcium Channel Blocker Overdose: A Case Report and Clinical Review

Calcium channel blockers (CCBs) overdose can be life-threatening when manifest as catastrophic shock and non-cardiogenic pulmonary edema. We describe a case of massive overdose of multiple medications, including sustained-release verapamil, which was resistant to conventional support. Initial treatment for CCB overdose is primarily supportive, and includes fluid resuscitation. The mechanism of non-cardiogenic pulmonary edema is not well known, and reported cases have been successfully treated with mechanical ventilation. Circulatory shock may fail to respond to atropine, glucagon, and calcium in severely poisoned patients, and vasopressors are usually required. Attempting to overcome calcium-channel antagonism with the supra-therapeutic doses of calcium salts is clinically indicated to reverse hypotension and bradycardia. There is evidence that hyperinsulinemia-euglycemia therapy is superior to other therapies for CCB poisoning, and the mechanism is thought to be the insulin-mediated active transport of glucose into the cells, which counters the CCB-induced intra-cellular carbohydrate-deficient state. Conventional decontamination measures are ineffective in accelerating clearance of CCB. Experience with intravenous lipid emulsion for lipophilic drug overdose, such as verapamil, is limited, but has been proposed as a rescue therapy and might improve cardiac inotropy through intravascular sequestration of the lipophilic CCB.