Insulin Is a Superior Antidote for Cardiovascular Toxicity Induced by Verapamil in the Anesthetized Canine

Kline, Jeffrey A.; Tomaszewski, Christian; Schroeder, J. D.; Raymond, Richard M.

doi:10.1097/00132586-199410000-00011

Cited by 45 publications

(86 citation statements)

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“…Although there are no therapies that consistently reverse cardiovascular collapse caused by CCB poisoning, both high-dose insulin/euglycemia (HIE) therapy [2][3][4] and intravenous lipid emulsion (ILE) [5][6][7] have been shown to improve hemodynamics and survival following intravenous administration of verapamil in animals. On the other hand, while several case reports indicate amelioration of CCB-induced cardiotoxicity by the administration of ILE [8][9][10][11], others report no benefit [12].…”

Section: Introductionmentioning

confidence: 99%

In Vitro Studies Indicate Intravenous Lipid Emulsion Acts as Lipid Sink in Verapamil Poisoning

et al. 2015

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Intravenous lipid emulsion (ILE), a component of parenteral nutrition, consists of a fat emulsion of soy bean oil, egg phospholipids, and glycerin. Case reports suggest that ILE may reverse hypotension caused by acute poisoning with lipophilic drugs such as verapamil, but the mechanism remains unclear. The methods used are the following: (1) measurement of ILE concentration in serum samples from a patient with verapamil poisoning treated with ILE, (2) measurement of free verapamil concentrations in human serum mixed in vitro with increasing concentrations of ILE, and (3) measurement of murine ventricular cardiomyocyte L-type Ca 2+ currents, intracellular Ca 2+ , and contractility in response to verapamil and/or ILE. Maximum patient serum ILE concentration after infusion of 1 L ILE over 1 h was approximately 1.6 vol%. In vitro GC/ MS verapamil assays showed that addition of ILE (0.03-5.0 vol%) dose-dependently decreased the free verapamil concentration in human serum. In voltage-clamped myocytes, adding ILE to Tyrode's solution containing 5 μM verapamil recovered L-type Ca 2+ currents (I Ca ). Recovery was concentration dependent, with significant I Ca recovery at ILE concentrations as low as 0.03 vol%. ILE had no effect on I Ca in the absence of verapamil. In field-stimulated intact ventricular myocytes exposed to verapamil, adding ILE (0.5 %) resulted in a rapid and nearly complete recovery of myocyte contractility and intracellular Ca 2+ . Our in vitro studies indicate that ILE acts as a lipid sink that rapidly reverses impaired cardiomyocyte contractility in the continued presence of verapamil.

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Section: Introductionmentioning

confidence: 99%

In Vitro Studies Indicate Intravenous Lipid Emulsion Acts as Lipid Sink in Verapamil Poisoning

et al. 2015

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“…It has been successfully used in prior cardiotoxic drug models performed at our institution and hemorrhagic swine models [26][27][28][29]. We tested the alphachloralose in several animals prior to initiation of the full study and confirmed a lack of direct hemodynamic effect.…”

Section: Limitationsmentioning

confidence: 74%

Pilot Trial of Intravenous Lipid Emulsion Treatment for Severe Nifedipine-Induced Shock

et al. 2016

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Animal studies and human case reports show promise in using lipid rescue to treat refractory calcium channel antagonist toxicity. However, the majority of research and clinical experience has focused on non-dihydropyridine agents. Thus, we sought to investigate the value of lipid emulsion (ILE) therapy for dihydropyridine-induced shock. This IACUC-approved study utilized seven swine that were sedated with alpha-chloralose, mechanically ventilated, and instrumented for drug delivery and hemodynamic measures. After stabilization and basal measures, nifedipine (0.01875 mg/kg/ min) was infused until imminent cardiac arrest (seizure, end tidal CO2 < 10 mmHg, bradydysrhythmia, or pulseless electrical activity). Animals then received a 7 mL/kg bolus of 20% lipid emulsion via central catheter. Lipid circulation was visually confirmed by the presence of fat in peripheral arterial blood. Hemodynamics were continuously monitored until 10 min after lipid bolus. Surviving animals were euthanized. Pre-and post-lipid treatment parameters were analyzed using the Wilxocon signed rank test (p <0.05 significant). Nifedipine toxicity was characterized by vasodilatory hypotension, impaired vascular contractility, and tachycardia with terminal bradycardia. The median time to imminent cardiac arrest from start of nifedipine infusion was 218 min. Lipid treatment did not improve hemodynamics or restore circulation in any animal. There was no benefit from lipid rescue in this model of nifedipine toxicity. Further study of ILE for dihydropyridine toxicity is warranted but initial animal model results are not promising.

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“…CCB poisonings are prone to developing severe bradydysrhythmias and hypotension and other complications, including pulmonary edema and heart failure [55]. Specific pharmacologic therapy includes the use of atropine, calcium, glucagon, insulin, sodium bicarbonate, or various catecholamines [56,57].…”

Section: Managementmentioning

confidence: 99%

ECG Manifestations: The Poisoned Patient

Holstege

Eldridge

Rowden

2006

Emergency Medicine Clinics of North America

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Emergency physicians routinely evaluate and manage poisoned patients. In 2003, more than 2 million human exposure cases were reported to poison centers throughout the United States [1]. Of those cases, 22% were treated in a health care facility with most of those cases evaluated in the emergency department. Cardiovascular drugs were listed as the fifteenth most frequently encountered human exposure (66,401) and the fifth leading cause of poisoning deaths.Drug-induced changes and abnormalities on the 12-lead electrocardiogram (ECG) are common. There are numerous drugs that can cause ECG changes and lead to cardiac dysrhythmias. The diagnoses and subsequent management of patients manifesting ECG changes following poisonings can challenge even the most experienced physician. Drugs that are advocated in Advanced Coronary Life Support protocols for cardiac dysrhythmias may not apply or may even worsen the condition of overdose patients [2].Despite that drugs have widely varying indications for therapeutic use, many unrelated drugs share a common cardiac pharmacologic effect if taken in overdose. The purpose of this article is to group together agents that cause similar electrocardiographic effects, review their pharmacologic actions, and discuss the electrocardiographic findings reported in the medical literature. The five main categories reviewed include potassium (Kþ) efflux blockers, sodium (Naþ) channel blockers, sodium-potassium adenosine-triphosphatase (Naþ/Kþ ATPase) blockers, calcium channel blockers (CCB), and beta-adrenergic blockers (BB). It is important to keep in mind, however, that many medications have actions that involve more than one of these

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Insulin Is a Superior Antidote for Cardiovascular Toxicity Induced by Verapamil in the Anesthetized Canine

Cited by 45 publications

References 0 publications

In Vitro Studies Indicate Intravenous Lipid Emulsion Acts as Lipid Sink in Verapamil Poisoning

In Vitro Studies Indicate Intravenous Lipid Emulsion Acts as Lipid Sink in Verapamil Poisoning

Pilot Trial of Intravenous Lipid Emulsion Treatment for Severe Nifedipine-Induced Shock

ECG Manifestations: The Poisoned Patient

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