title: Intravenous lipid emulsion sequesters amiodarone in plasma and eliminates its hypotensive action in pigs.
abstract: OBJECTIVE
  Our objective is to investigate to what extent amiodarone is sequestered by intravenously administered lipid emulsion in plasma of pigs and whether the lipid emulsion inhibits amiodarone-induced hypotension.
  
  
  METHODS
  Twenty anesthetized pigs received randomly 1.5 mL/kg bolus injection of olive/soybean oil-based 20% lipid emulsion (lipid group, n=10) or Ringer's acetate solution (control group, n=10) in 1 minute, followed by a continuous infusion of either solution for 30 minutes at 0.25 mL/kg per minute. Simultaneously with these continuous infusions, amiodarone hydrochloride was infused for 20 minutes at 1 mg/kg per minute in both groups. Plasma amiodarone concentration and mean arterial blood pressure were evaluated at predetermined intervals.
  
  
  RESULTS
  Plasma amiodarone concentration in the lipid group increased more steeply during the amiodarone infusion than in the control group, at 20 minutes being a median 96.8 mg/L (interquartile range [IQR] 85.4, 102.0 mg/L) in the lipid group and median 21.5 mg/L (IQR 18.9, 22.3 mg/L) in the control group (difference 75.3 mg/L; 95% confidence interval [CI] 65.3 to 85.3 mg/L). After the separation of lipids from plasma by differential centrifugation, less amiodarone was contained in the lipid-poor aqueous fraction. At 20 minutes, the median was 13.3 mg/L (IQR 12.0, 13.7 mg/L), and the difference compared with the total plasma amiodarone concentration was -83.6 mg/L (95% CI -93.3 to -73.8 mg/L). In the lipid group, mean arterial blood pressure was not altered during the continuous amiodarone infusion. In the control group, mean arterial blood pressure decreased from baseline at 11 minutes, and the median was 52 mm Hg (IQR 51, 80 mm Hg) and the difference from baseline was 26 mm Hg (95% CI 9 to 43 mm Hg). Mean arterial blood pressure at 21 minutes also remained below the baseline, and the median was 57 mm Hg (IQR 50, 68 mm Hg) and the difference from baseline was 21 mm Hg (95% CI 9 to 33 mm Hg).
  
  
  CONCLUSIONS
  Amiodarone was sequestered to a great extent by the intravenously administered lipids in plasma, which completely prevented the decrease in arterial blood pressure caused by amiodarone infusion. Further studies are needed to evaluate the clinical usefulness of intravenous lipid emulsion as an antidote in amiodarone overdoses.
authors.affiliation: Department of Anesthesiology, Helsinki University Hospital, Helsinki, Finland. niiya-tomo-mayu@nifty.com
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Niiya
authors.forename: Erik
authors.initials: E
authors.lastname: Litonius
authors.forename: Liisa
authors.initials: L
authors.lastname: Petäjä
authors.forename: Pertti J
authors.initials: PJ
authors.lastname: Neuvonen
authors.forename: Per H
authors.initials: PH
authors.lastname: Rosenberg
mesh_terms: D000638:Amiodarone / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced* / Q000517:prevention & control; D008297:Male; D010100:Oxygen / Q000097:blood; D013552:Swine; D014665:Vasodilator Agents / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D005217:Fat Emulsions, Intravenous; D014665:Vasodilator Agents; D000638:Amiodarone; D010100:Oxygen