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

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Abstract

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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Acknowledgments

The investigators wish to thank Kristin Engebretsen, PharmD, for her assistance with nifedipine preparation and dosing and David McLaughlin and Edwards Lifesciences for the in-kind donation of the Edwards Lifesciences EV1000®.

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Authors and Affiliations

  1. Department of Emergency Medicine, Division of Medical Toxicology, Carolinas Medical Center, Charlotte, NC, USA

    Christine M. Murphy & William P. Kerns II

  2. Department of Emergency Medicine, Division of Research, Carolinas Medical Center, Charlotte, NC, USA

    Cliff Williams

  3. Department of Comparative Medicine, Carolinas Medical Center, Charlotte, NC, USA

    Michael E. Quinn & Brian Nicholson

  4. United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD, USA

    Thomas Shoe

  5. Carolinas Poison Center, Charlotte, NC, USA

    Michael C. Beuhler

Authors
  1. Christine M. Murphy
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  2. Cliff Williams
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  3. Michael E. Quinn
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  4. Brian Nicholson
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  5. Thomas Shoe
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  6. Michael C. Beuhler
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  7. William P. Kerns II
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Corresponding author

Correspondence to Christine M. Murphy.

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Funding

Funding for this research was provided by the Carolinas Healthcare Foundation and the John A. Marx, MD Fund.

Conflicts of Interest

The authors have no conflicts of interest to disclose.

Additional information

Previous Presentation: An abstract of this study was presented as a poster and as a platform at the American College of Medical Toxicology 2013 Annual Scientific Meeting (Murphy CM, Williams C, Quinn ME, Nicholson B, Shoe T, Beuhler MC, Kerns WP. Pilot trial of lipid rescue in a swine model of severe nifedipine toxicity. J Med Toxicol. 2013;9:82).

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Murphy, C.M., Williams, C., Quinn, M.E. et al. Pilot Trial of Intravenous Lipid Emulsion Treatment for Severe Nifedipine-Induced Shock. J. Med. Toxicol. 12, 380–385 (2016). https://doi.org/10.1007/s13181-016-0572-6

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  • DOI: https://doi.org/10.1007/s13181-016-0572-6

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