No Antidotal Effect of Intravenous Lipid Emulsion in Experimental Amitriptyline Intoxication Despite Significant Entrapment of Amitriptyline

Abstract

Intravenous lipid emulsion has been used in the resuscitative treatment of intoxications caused by local anaesthetics and tricyclic antidepressants with seemingly beneficial results. We studied the effect of intravenous lipid emulsion on the plasma concentration of amitriptyline and haemodynamic recovery in a pig model of amitriptyline intoxication. Twenty pigs were anaesthetized (1% isoflurane in 21% O 2) and given amitriptyline 15mg/kg intravenously for 15min. In random fashion immediately thereafter, either 20% lipid emulsion (ClinOleic ®, Lipid group) or Ringer's acetate (Control group) was infused for 30min.; first 1.5ml/kg for 1min., followed by 0.25ml/kg/min. for 29min. The amitriptyline concentration in total and lipid-poor plasma and haemodynamic parameters were measured until 30min. after the infusions. Lipid infusion prevented the decrease in plasma total amitriptyline concentration, resulting in a 90% higher (p<0.001) total concentration and significantly (p=0.014) lower free fraction of plasma amitriptyline in the Lipid group (1.1%) compared with the Control group (3.0%) at 30min. Haemodynamic recovery from the intoxication as measured by heart rate, arterial pressure or cardiac output was similar in both groups. However, five pigs in the Lipid group and two pigs in the Control group died. In conclusion, a marked entrapment of amitriptyline by intravenous lipid emulsion was observed but this did not improve the pigs' haemodynamic recovery from severe amitriptyline intoxication. Care should be exercised in the antidotal use of lipid emulsion until controlled human studies indicate its efficacy and safety. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.