Correlation of Plasma and Peritoneal Diasylate Clomipramine Concentration with Hemodynamic Recovery after Intralipid Infusion in Rabbits

Authors

  • Martyn Harvey FACEM, MBChB, BHB,

    1. From the Department of Emergency Medicine, Waikato Hospital (MH, KH), Hamilton; University of Otago, Wellington School of Medicine & Health Sciences (GC), Wellington; and Hutt Hospital (GC), Lower Hutt, New Zealand.
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  • Grant Cave FACEM, MBChB, BHB,

    1. From the Department of Emergency Medicine, Waikato Hospital (MH, KH), Hamilton; University of Otago, Wellington School of Medicine & Health Sciences (GC), Wellington; and Hutt Hospital (GC), Lower Hutt, New Zealand.
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  • Kerry Hoggett MBBS

    1. From the Department of Emergency Medicine, Waikato Hospital (MH, KH), Hamilton; University of Otago, Wellington School of Medicine & Health Sciences (GC), Wellington; and Hutt Hospital (GC), Lower Hutt, New Zealand.
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  • This study was funded by a grant from the Waikato Medical Research Foundation.

Address for correspondence and reprints: Martyn Harvey, FACEM, MBChB, BHB; e-mail: harveym@waikatodhb.govt.nz.

Abstract

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.

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