This study was funded by a grant from the Waikato Medical Research Foundation.
Correlation of Plasma and Peritoneal Diasylate Clomipramine Concentration with Hemodynamic Recovery after Intralipid Infusion in Rabbits
Article first published online: 6 JAN 2009
© 2009 by the Society for Academic Emergency Medicine
Academic Emergency Medicine
Volume 16, Issue 2, pages 151–156, February 2009
How to Cite
Harvey, M., Cave, G. and Hoggett, K. (2009), Correlation of Plasma and Peritoneal Diasylate Clomipramine Concentration with Hemodynamic Recovery after Intralipid Infusion in Rabbits. Academic Emergency Medicine, 16: 151–156. doi: 10.1111/j.1553-2712.2008.00313.x
- Issue published online: 27 JAN 2009
- Article first published online: 6 JAN 2009
- Received August 19, 2008; revision received October 13, 2008; accepted October 14, 2008.
- lipid emulsion;
Objectives: Drug sequestration to an expanded plasma lipid phase has been proposed as a potential mechanism of action for lipid emulsions in lipophilic cardiotoxin overdose. The authors set out to document plasma and peritoneal diasylate clomipramine concentration after resuscitation with lipid emulsion in a rabbit model of clomipramine-induced hypotension.
Methods: Twenty sedated mechanically ventilated New Zealand White rabbits were allocated to receive either 12 mL/kg 20% Intralipid or 12 mL/kg saline solution, following clomipramine infusion to 50% baseline mean arterial pressure (MAP). Hemodynamic parameters and serum clomipramine concentration were determined to 59 minutes. Peritoneal dialysis with 20% Intralipid or saline solution was evaluated for clomipramine concentration.
Results: Mean arterial pressure was greater in lipid-treated animals as assessed by repeated-measures analysis of variance (F[1,14] = 6.84; p = 0.020). Lipid infusion was associated with elevated plasma clomipramine concentration and reduced initial volume of distribution (Vd; 5.7 [±1.6] L/kg lipid vs. 15.9 [±7.2] L/kg saline; p = 0.0001). Peritoneal diasylate clomipramine concentration was greater in lipid-treated animals (366.2 [±186.2] μg/L lipid vs. 37.7 [±13.8] μg/L saline; p = 0.002).
Conclusions: Amelioration of clomipramine-induced hypotension with lipid infusion is associated with reduced initial Vd and elevated plasma clomipramine concentration consistent with intravascular drug–lipid sequestration. Concomitant peritoneal dialysis with lipid emulsion enhances clomipramine extraction.