Massive diltiazem and metoprolol overdose rescued with extracorporeal life support.

The management of overdoses of cardioactive medications in the emergency department can be challenging. The reversal of severe toxicity from one or more types of cardioactive medication may fail maximal medical therapies and require extreme invasive measures such as transvenous cardiac pacing and extracorporeal life support. We present a case of massive diltiazem and metoprolol overdose refractory to maximal medical therapy, including intravenous calcium, glucagon, vasopressors, high dose insulin, and lipid emulsion. The patient experienced refractory bradydysrhythmia that responded only to transvenous pacing. Extracorporeal life support was initiated and resulted in successful organ perfusion and complete recovery of the patient. This case highlights the potential utility of extracorporeal life support in cases of severe toxicity due to multiple cardioactive medications.

A Critical Note on Treatment of a Severe Diltiazem Intoxication: High-Dose Calcium and Glucagon Infusions.

The morbidity and mortality of a severe calcium channel blocker intoxication is high due to serious toxic cardiac effects. Its treatment is supported by low-quality evidence from the heterogeneous literature. We describe a case of a severe diltiazem intoxication and critically appraise the efficacy and role of high-dose calcium and glucagon infusions. A 53-year-old woman was admitted to the emergency department with a cardiogenic shock with complete AV block, not responding to atropine, isoprenaline and an external pacemaker. Later on, it became clear that she had a severe diltiazem intoxication which was successfully treated with isotone fluids, inotropes, vasopressors and continuous infusion of high-dose calcium and glucagon. The patient developed, however, an acute, necrotizing pancreatitis, probably related to iatrogenic high calcium levels. This case demonstrates lack of consensus regarding target levels of serum calcium for treatment of a severe diltiazem intoxication. Goal-directed tapering of calcium should prevent side effects of iatrogenic hypercalcaemia. The contribution of glucagon infusions is doubtful due to the instability of solubilized glucagon. This might explain why the effect of glucagon is variable in the literature.

Intralipid Emulsion Rescue Therapy: Emerging Therapeutic Indications in Medical Practice.

Intralipid emulsion therapy is well-established for the treatment of local-anesthetic systemic toxicities. In recent years, its role has expanded as an important therapeutic agent in the reversal of other types of drug overdoses, including certain types of antipsychotics, antidepressants, antiarrhythmics, and calcium channel blockers. A literature review identified thirty-one case reports including forty-nine separate drug overdose cases involving ten separate drug classes which were successfully reversed with Intralipid. The present clinical case study describes an elderly unresponsive woman refractory to conventional treatments after ingesting a potentially lethal amount of 5.6 grams of diltiazem in a suicide attempt. After treatment with Intralipid over a twenty-four hour period, the patient's hemodynamic and metabolic derangements were corrected and stabilized completely. Intralipid emulsion rescue therapy provides another potential strategy for the reversal of many drug toxicities, most likely by providing a lipid layer safety net for drug overdose by passive diffusion. Clinicians are urged to embrace an expanded role of Intralipid emulsion rescue therapy, not only for local anesthetic drug toxicities, but also for other lipophilic drug overdoses.

Management of a mixed overdose of calcium channel blockers, ß-blockers and statins.

We describe a case of extreme mixed overdose of calcium channel blockers, ß-blockers and statins. The patient was successfully treated with aggressive resuscitation including cardiac pacing and multiorgan support, glucagon and high-dose insulin for toxicity related to calcium channel blockade and ß-blockade, and ubiquinone for treating severe presumed statin-induced rhabdomyolysis and muscle weakness.

The use of high-dose insulin therapy and intravenous lipid emulsion to treat severe, refractory diltiazem toxicosis in a dog.

OBJECTIVE: To describe the novel use of high-dose insulin (HDI) therapy and intravenous lipid emulsion (ILE) to treat refractory, severe diltiazem toxicosis in a dog. CASE SUMMARY: A 4-year-old Pomeranian was presented for treatment 2.5 hours following ingestion of a diltiazem extended-release capsule. Toxic ingestion was calculated at a maximum exposure of 79 mg/kg, with a reported canine LD50 of 50 mg/kg. Clinical signs of progressive hypotension and severe bradycardia with atrial standstill were observed, which persisted despite treatment with atropine, calcium, glucagon, and dopamine. The novel use of HDI and ILE as part of therapy for diltiazem toxicosis resulted in clinical resolution of life-threatening signs. Within 1 hour of initiating HDI therapy, the clinical signs improved, and with continued treatment, the patient remained normotensive and survived to discharge. NEW OR UNIQUE INFORMATION PROVIDED: To the authors' knowledge, this is the first reported clinical case describing the use of both HDI and ILE therapy in the treatment of severe refractory diltiazem toxicosis in veterinary medicine. No significant adverse effects were observed from the treatment. In veterinary patients with severe refractory calcium channel blocker toxicosis, the use of HDI and ILE should be considered for life-threatening clinical signs.

Diltiazem poisoning treated with hyperinsulinemic euglycemia therapy and intravenous lipid emulsion.

Intravenous lipid emulsion (ILE) has been proposed as a rescue therapy for severe local anesthetic drugs toxicity, but experience is limited with other lipophilic drugs. An 18-year-old healthy woman was admitted 8 h after the voluntary ingestion of sustained-release diltiazem (3600 mg), with severe hypotension refractory to fluid therapy, calcium salts, and high-dose norepinephrine (6.66 µg/kg/min). Hyperinsulinemic euglycemia therapy was initiated and shortly after was followed by a protocol of ILE (intralipid 20%, 1.5 ml/kg as bolus, followed by 0.25 ml/kg over 1h). The main finding attributed to ILE was an apparent rapid decrease in insulin resistance, despite a prolonged serum diltiazem elimination half-life. Diltiazem is a lipophilic cardiotoxic drug, which could be sequestered in an expanded plasma lipid phase. The mechanism of action of ILE is not known, including its role in insulin resistance and myocardial metabolism in calcium-channel blocker poisoning.

Diltiazem overdose: a role for high-dose insulin.

A 62-year-old man presented 6 h after a mixed intentional overdose of dilatizem (Adizem-SR), atorvastatin, aspirin and isosorbide mononitrate. He was symptomatic, with vomiting, blurred vision and unsteady gait. Despite initial fluid resuscitation and calcium chloride, glucagon, and high-dose ionotropic therapy, his hypotension remained refractory to treatment. A bolus of high-dose insulin (Actrapid) was administered, followed by a continuous infusion. Glucose was administered to maintain a state of euglycaemia. Over the following 24 h, the patient was given 1140 units of accumulative insulin. This resulted in a significant improvement in arterial blood pressure values and metabolic indices, allowing contiguous weaning off inotropes. This case supports the use of rescue hyperinsulinaemic euglycaemia in patients with an overdose of calcium channel blockers who remain hypotensive despite standard pharmacological measures.

[Successful treatment of polymedicamentous poisoning with metoprolol, diltiazem and cilazapril].

INTRODUCTION: Poisoning caused by drugs with cardiodepressive effects is an urgent condition in medicine which is associated with high mortality rate regardless of modern therapeutic methods. Accidental or intentional poisoning whit these drugs produces heart activity depression and cardiovascular collapse as consequences. Current therapy for severe poisoning caused by beta-blockers and calcium channel blockers includes both unspecific and specific antidote therapy whit glucagon, as well as application of adrenergic drugs, calcium, phosphodiesterase inhibitors and hyperinsulinemia/euglycemia therapy. However, even whit the application of these drugs, prompt measures of unspecific detoxication therapy and cardiopulmonary reanimation are crucial for survival of patients with severe poisoning. CASE REPORT: A 28-year-old female patient was hospitalized for cardiogenic shock and altered state of conscioussnes (Glasgow coma score = 4), caused by acute poisoning with 2 g of metoprolol (Presolol), 1.8 g of diltiazem (Cortiazem) and 50 mg of cilazapril (Zobox). Prolonged cardiopulmonary resuscitation was applied during the first 16 hours of hospitalization, including administration of crystaline solutions (8 L), 17 mg of adrenaline, 4 mg of atropine, 4 mg of glucagone and 1.6 g of dopamine, with electro-stimulation by temporary pacemaker and mechanical ventilation. In a defined time period, normalized state of consciousness was registered, mechanical ventilation was stopped and normal heart activity and hemodynamic stability were accomplished. During hospitalization the patient was treated for mild pneumonia and after ten days, completely recovered, was released and sent to home treatment. CONCLUSION: Prompt measures of cardiopulmonary resuscitation and multidisciplinary treatment in intensive care units significantly increase the chances of complete recovery of a patient with severe poisoning caused by drugs with cardiodepressive efects.

Massive diltiazem overdose treated with extracorporeal membrane oxygenation.

OBJECTIVE: To describe a case of massive diltiazem overdose with a good outcome achieved after early and aggressive supportive therapy. DESIGN: Case report. SETTING: Pediatric Critical Care Unit. PATIENT: Sixteen-year-old adolescent girl. MEASUREMENTS AND MAIN RESULTS: A 16-yr-old adolescent girl presented to the emergency department 6 hrs after the intentional ingestion of 40 300-mg sustained-release diltiazem tablets (12 g of Cardura CD). She was hypotensive and required a glucagon and epinephrine infusion despite initial fluid resuscitation with saline and intravenous calcium (1 g). Multiple asystolic cardiac arrests ensued which became increasingly refractory to high-dose epinephrine. Hemodynamic support was achieved with a 48-hr period of extracorporeal membrane oxygenation for atrial standstill. Severe multiorgan dysfunction ensued (cardiac, neurologic, renal, hepatic, gastrointestinal, hematologic, and metabolic). Plasma diltiazem and its metabolites were measured and its half-life was reported between 28 and 48 hrs. A sustained decline in plasma diltiazem levels and its metabolites was not observed after two periods of charcoal hemoperfusion. Recovery of organ function occurred with sinus rhythm noted on the ninth day. The patient made a full recovery and was discharged from the critical care unit after 15 days. CONCLUSIONS: Although massive calcium channel blocker overdose can produce profound and prolonged cardiac or multiorgan dysfunction, its toxic effects may be reversible. Supportive therapy, particularly of the cardiovascular system, is the most important goal.

Poisoning with calcium channel blockers--a case report and review of the literature.

The incidence of poisoning with calcium channel blockers, accidental or intentional, has increased in recent years, associated with more frequent use. We present a clinical case of bradycardia and shock of unknown cause, which came to be revealed a poisoning by 3240 mg of slow-release diltiazem, managed with temporary transvenous pacing and dopamine in high concentration. We make a review of the cardiovascular manifestations of the three classic calcium channel blockers: verapamil, diltiazem and nifedipine; namely, hypotension, rhythm and conduction disturbances. We point out the late appearance of the beginning of manifestations with the use of slow releasing formulations. The toxicity by calcium channel blockers can lead to a wide variety of manifestations in the central nervous system, gastrointestinal system, endocrine-metabolic, hematologic and respiratory systems. There is a high clinical suspicion when the following factors are present: hypotension with bradycardia, mental state disturbances, lactic acidosis, hyperglycemia, sinus pauses and refractory shock. Treatment is based on general measures of intoxication support, decreasing the drug absorption and improvement of cardiac function. The bradyarrhythmias are corrected with the use of intravenous calcium, glucagon, atropine and pacemaker. If the intoxication causes depression of cardiac contractility, the use of calcium or/and glucagon is indicated. If there is refractoriness with these measures, catecholamines should be employed. There are alternative and adjuvant drugs such as amrinone, insulin-glucose, 4-aminopyridine and calcium entry promoters. Charcoal hemoperfusion can be useful in the overdose of sustained release preparations, but hemodialysis is unworthy of therapeutical interest.

A one-year evaluation of calcium channel blocker overdoses: toxicity and treatment.

STUDY OBJECTIVE: To examine the cardiovascular toxicity of calcium channel blockers and the efficacy of various treatments. DESIGN: Case series collected prospectively over one year. SETTING: Three regional poison control centers. TYPE OF PARTICIPANTS: One hundred thirty-nine hospitalized patients who had ingested a calcium channel blocker. INTERVENTIONS: Calcium, dopamine, atropine, isoproterenol, glucagon, and pacemakers. MAIN RESULTS: Hypotension, sinus node suppression, and dysrhythmias often occur with calcium channel blocker overdoses, but atrioventricular nodal block occurs more often with verapamil (chi 2 test, P < .025). Calcium was administered to 23 patients and was efficacious in reversing depression of cardiac conduction and increasing blood pressure. Dopamine was administered to ten patients and was efficacious in increasing blood pressure. Atropine was administered to eight patients, but only two had a positive response. CONCLUSION: Atrioventricular nodal depression is more common with verapamil overdoses. Calcium and dopamine are useful in treating toxicity from calcium channel blocker overdose, whereas atropine is sometimes useful.