Intralipid Outperforms Sodium Bicarbonate in a Rabbit Model of Clomipramine Toxicity

Study objective

Previous investigators have demonstrated amelioration of lipid-soluble drug toxidromes with infusion of lipid emulsions. Clomipramine is a lipid-soluble tricyclic antidepressant with significant cardiovascular depressant activity in human overdose. We compare resuscitation with Intralipid versus sodium bicarbonate in a rabbit model of clomipramine toxicity.

Methods

Thirty sedated and mechanically ventilated New Zealand White rabbits were infused with clomipramine at 320 mg/kg per hour. At target mean arterial pressure of 50% initial mean arterial pressure, animals were rescued with 0.9% NaCl 12 mL/kg, 8.4% sodium bicarbonate 3 mL/kg, or 20% Intralipid 12 mL/kg. Pulse rate, mean arterial pressure, and QRS duration were sampled at 2.5-minute intervals to 15 minutes. In the second phase of the experiment, 8 sedated and mechanically ventilated rabbits were infused with clomipramine at 240 mg/kg per hour to a mean arterial pressure of 25 mm Hg. Animals received either 2 mL/kg 8.4% sodium bicarbonate or 8 mL/kg 20% Intralipid as rescue therapy. External cardiac compression and intravenous adrenaline were administered in the event of cardiovascular collapse.

Results

Mean difference in mean arterial pressure between Intralipid- and saline solution–treated groups was 21.1 mm Hg (95% confidence interval [CI] 13.5 to 28.7 mm Hg) and 19.5 mm Hg (95% CI 10.5 to 28.9 mm Hg) at 5 and 15 minutes, respectively. Mean difference in mean arterial pressure between Intralipid- and bicarbonate-treated groups was 19.4 mm Hg (95% CI 18.8 to 27.0 mm Hg) and 11.5 mm Hg (95% CI 2.5 to 20.5 mm Hg) at 5 and 15 minutes. The rate of change in mean arterial pressure was greatest in the Intralipid-treated group at 3 minutes (6.2 mm Hg/min [95% CI 3.8 to 8.6 mm Hg/min] Intralipid versus −0.25 mm Hg/min [95% CI −1.9 to 1.4 mm Hg/min] saline solution) and 5 minutes (4.4 mm Hg/min [95% CI 3.0 to 5.9 mm Hg/min] Intralipid versus 0.06 mm Hg/min [95% CI −0.9 to 1.1 mm Hg/min] saline solution). In the second phase of the experiment spontaneous circulation was maintained in all Intralipid-treated rabbits (n=4). All animals in the bicarbonate-treated group developed pulseless electrical activity and proved refractory to resuscitation at 10 minutes (n=4, P=.023).

Conclusion

In this rabbit model, Intralipid infusion resulted in more rapid and complete reversal of clomipramine-induced hypotension compared with sodium bicarbonate. Additionally, Intralipid infusion prevented cardiovascular collapse in a model of severe clomipramine toxicity.