Hemodynamic Effects of Intravenous Fat Emulsion in an Animal Model of Severe Verapamil Toxicity Resuscitated with Atropine, Calcium, and Saline

Bania, Theodore C.; Chu, Jason; Perez, Eric; Su, Mark K.; Hahn, In‐Hei

doi:10.1111/j.1553-2712.2007.tb01752.x

Cited by 86 publications

(80 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

View full text Add to dashboard Cite

show abstract

“…As the animals' blood pressure approached a MAP of 55 mmHg, the dose was halved and then titrated until a MAP of 50-55 mmHg was maintained for a period of 5 min at the same infusion rate. The approach of titrating verapamil dosing to a temporary steady state was adapted from the protocol used in canine poisoning by Bania et al [6]. The verapamil infusion was maintained at that rate throughout the experiment to mimic continual absorption in a massive overdose.…”

Section: Methodsmentioning

confidence: 99%

“…This action results in depressed chronotropy and inotropy as well as peripheral vasodilation. Current therapeutic strategies for CCB toxicity have produced inconsistent clinical effects [2][3][4][5][6][7]. Thyroid hormone, however, may represent a novel therapeutic approach.…”

Section: Introductionmentioning

confidence: 99%

Survival of Verapamil-Poisoned Rats Treated with Triiodothyronine

et al. 2010

View full text Add to dashboard Cite

Life-threatening toxicity due to calcium channel blocker ingestion is commonly encountered by emergency medicine physicians and toxicologists. Despite a vast array of research on its treatment, results have proven inconsistent. The goal of this study is to evaluate potential vasopressor effects of triiodothyronine (T3) in rats poisoned with verapamil. Following anesthesia and intubation, ten Sprague-Dawley rats were given intravenous verapamil infusion of 10 mg/kg/h. This dose was titrated until a mean arterial pressure (MAP) of 50-55 mmHg was achieved and maintained for a period of at least 5 min. The verapamil infusion was then maintained at that rate. Five rats were randomized to receive a T3 bolus of 0.4 mcg/kg preceding an infusion of 1.5 mcg/kg/day which was doubled every 2 min until any of the following endpoints: systolic blood pressure of 100 mmHg, an elapsed time of 60 min, or death. The other five received an equal volume of normal saline solution. The primary outcome measure was survival with secondary outcomes of MAP and heart rate. The T3 group did have a slightly longer, yet not statistically significant, average time to cessation of electrical activity-30.0±14.4 min versus 23.8±9.5 min in the placebo group. Average MAP decreased nearly identically in the two groups. Heart rates were not reliable indicators of toxicity in this rat model as there was little decrease until immediately prior to death in most animals. Despite significant variability in toxicity among individual animals, no statistically significant difference in survival time, heart rate, or MAP was found between groups treated with T3 and those receiving saline.

show abstract

“…Subsequent preclinical experiments exploring the effect of ILE in lipophilic drug toxicity from a variety of nonlocal anesthetic agents have on balance suggested benefit [13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

LIPAEMIC Report: Results of Clinical Use of Intravenous Lipid Emulsion in Drug Toxicity Reported to an Online Lipid Registry

et al. 2014

View full text Add to dashboard Cite

The use of intravenous lipid emulsion (ILE) as an antidote has prompted significant academic and clinical interest. Between August 2009 and August 2012, data from cases of ILE use in intoxicated patients in different hospitals on different continents were voluntarily entered into a registry based on the world wide web (www.lipidregistry.org). Here, we report data from this project. Participating centers were given access to the registry following institutional subscription. Specifically sought were details of the individual patients' presenting condition, indications for ILE use, ILE administration regimen, potential complications, and of clinical outcome. Forty-eight uses of ILE were reported from 61 participating centers. Ten cases of local anesthetic systemic toxicity were reported; all (10/10) survived. Thirtyeight cases of intoxication by other agents were reported [30 decreased conscious state, 8 cardiovascular collapse (3 deaths)]. There was an elevation in GCS (p<0.0001) and increased systolic blood pressure (p=0.012) from immediately prior to ILE administration to 30 min after use. One serious and two minor adverse effects of ILE use were recorded in 48 reported cases (one case of bronchospastic reaction, one case of hyperamylasemia and one case of interference with laboratory testing). In this series of cases reported to the registry, improvements were seen for GCS in patients with central nervous system toxicity and in systolic blood pressure in shocked patients over a short time frame after the injection of ILE. Few adverse effects were recorded. Clinical trials and the reporting of drug concentrations after ILE use are necessary to further elucidate the role of ILE in clinical toxicology.

show abstract

Hemodynamic Effects of Intravenous Fat Emulsion in an Animal Model of Severe Verapamil Toxicity Resuscitated with Atropine, Calcium, and Saline

Abstract: Standard resuscitation and IFE increase MAP and survival in an animal model of severe verapamil toxicity compared with standard resuscitation alone.

Cited by 86 publications

References 18 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

Survival of Verapamil-Poisoned Rats Treated with Triiodothyronine

LIPAEMIC Report: Results of Clinical Use of Intravenous Lipid Emulsion in Drug Toxicity Reported to an Online Lipid Registry

Contact Info

Product

Resources

About