Comparison of Intravenous Lipid Emulsion, Bicarbonate, and Tailored Liposomes in Rabbit Clomipramine Toxicity

Abstract

Liposome (LIP)-like lipid dispersions have emerged as useful detoxification vehicles in vitro. The authors compare resuscitation with tailored LIPs, 20% intravenous lipid emulsion (ILE), and sodium bicarbonate (BIC), in a rabbit model of clomipramine toxicity. Sedated, instrumented New Zealand white rabbits underwent clomipramine infusion at 3.2mg/kg/min to 50% baseline mean arterial pressure (MAP) and then at 1.6mg/kg/min for 30minutes. BIC (3mL/kg 8.4%), ILE (3mL/kg 20%), or LIP (24mg/kg) were infused as rescue treatments at toxicity and were repeated at 10minutes (n=5 in each group). Thirty-minute MAP was greatest in ILE-treated animals: 61mmHg ILE (interquartile range [IQR]= 49 to 64mmHg), 43mmHg LIP (IQR= 36.5 to 49mmHg), and 10mmHg BIC (IQR= 10 to 44mmHg; all p=0.02). Two of the five BIC-treated animals survived to 30minutes, compared with all five of the ILE-treated animals and all five of the LIP-treated animals (p=0.044). Both ILE and LIPs improved hemodynamic recovery compared with bicarbonate in clomipramine-induced cardiotoxicity in rabbits. Greater 30-minute MAP was observed in the ILE group.