title: Pilot Trial of Intravenous Lipid Emulsion Treatment for Severe Nifedipine-Induced Shock.
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.
authors: Department of Emergency Medicine, Division of Medical Toxicology, Carolinas Medical Center, Charlotte, NC, USA. christine.murphy66@gmail.com.
authors: Christine M
authors: CM
authors: Murphy
authors: Department of Emergency Medicine, Division of Research, Carolinas Medical Center, Charlotte, NC, USA.
authors: Cliff
authors: C
authors: Williams
authors: Department of Comparative Medicine, Carolinas Medical Center, Charlotte, NC, USA.
authors: Michael E
authors: ME
authors: Quinn
authors: Department of Comparative Medicine, Carolinas Medical Center, Charlotte, NC, USA.
authors: Brian
authors: B
authors: Nicholson
authors: United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD, USA.
authors: Thomas
authors: T
authors: Shoe
authors: Carolinas Poison Center, Charlotte, NC, USA.
authors: Michael C
authors: MC
authors: Beuhler
authors: Department of Emergency Medicine, Division of Medical Toxicology, Carolinas Medical Center, Charlotte, NC, USA.
authors: William P
authors: WP
authors: Kerns
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia / Q000209:etiology; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000506:poisoning*; D004095:Dihydropyridines / Q000008:administration & dosage / Q000506:poisoning; D004195:Disease Models, Animal; D005217:Fat Emulsions, Intravenous / Q000627:therapeutic use*; D005260:Female; D006324:Heart Arrest, Induced; D006801:Humans; D055442:Metabolome / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009543:Nifedipine / Q000008:administration & dosage / Q000506:poisoning*; D010865:Pilot Projects; D012769:Shock / Q000139:chemically induced* / Q000628:therapy*; D013552:Swine; D013610:Tachycardia / Q000209:etiology
chemical_list: D001786:Blood Glucose; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D005217:Fat Emulsions, Intravenous; C038806:1,4-dihydropyridine; D009543:Nifedipine
keywords: Calcium channel blocker; Lipid emulsion; Nifedipine