Intralipid Prolongs Survival in a Rat Model of Verapamil Toxicity

Tebbutt, Simon; Harvey, Martyn; Nicholson, Tonia; Cave, Grant

doi:10.1197/j.aem.2005.08.016

Cited by 101 publications

(81 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

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

“…There has furthermore been considerable laboratory and some clinical reporting of beneficial effect for ILE in toxicity from other lipophilic agents including calcium channel blockers [3,4], tricyclic antidepressants [5][6][7] and β-blockers [4,[8][9][10]. While the exact mechanism of action for ILE is at present uncertain, three main hypotheses have been forwarded to explain the effects of ILE as antidote.…”

Section: Introductionmentioning

confidence: 99%

Intravenous Lipid Emulsion Does Not Augment Blood Pressure Recovery in A Rabbit Model of Metoprolol Toxicity

2010

View full text Add to dashboard Cite

Intravenous lipid emulsion (ILE) has been demonstrated to be an effective treatment for systemic toxicity associated with local anaesthetics and increasingly non-local anaesthetic agents of high lipophilicity. Effect for ILE has been demonstrated in animal models of propranolol poisoning; however, any benefit for ILE in more hydrophilic β-blockers remains uncertain. We determined to examine the effect of ILE on haemodynamic recovery following induction of hypotension with the relatively hydrophilic β-blocker, metoprolol. Twenty sedated, invasively monitored and mechanically ventilated adult New Zealand white rabbits underwent metoprolol infusion to mean arterial pressure (MAP) 60% baseline. Intravenous rescue was given according to the following groups: 6 mL/kg 20% lipid emulsion or 6 mL/kg 0.9% saline solution over 4 min. Haemodynamic parameters were obtained in 15 min. MAP was 70 (interquartile range (IQR), 58-82) mmHg saline group and 79 (IQR,(72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85)(86)(87)(88)(89) mmHg ILE group at baseline, and 38 (IQR, 33-40) mmHg saline group and 41 (IQR, 40-43) mmHg ILE group, respectively, following metoprolol infusion. No statistically significant difference between ILE and saline-treated groups was observed in MAP, or pulse rate, at any time point following rescue therapy. ILE was not effective in reversal of metoprolol-induced hypotension in this rabbit model. These findings lend inferential support for the 'lipid sink' as principal mechanism for the beneficial effect observed with ILE administration in other models of lipophilic β-blocker-induced toxicity.

show abstract

“…Lipid emulsion therapy has been studied for verapamil toxicity with impressive results in several animal models [4][5][6]. It has also been used to treat calcium channel antagonist toxicity in at least 20 published human cases, primarily involving verapamil and diltiazem [7][8][9][10][11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

View full text Add to dashboard Cite

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.

show abstract

Intralipid Prolongs Survival in a Rat Model of Verapamil Toxicity

Abstract: Intralipid treatment prolongs survival and doubles median lethal dose in a rat model of verapamil toxicity. The mechanism of action remains to be elucidated.

Cited by 101 publications

References 21 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

Intravenous Lipid Emulsion Does Not Augment Blood Pressure Recovery in A Rabbit Model of Metoprolol Toxicity

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

Contact Info

Product

Resources

About