Lipid therapy for the treatment of a refractory amitriptyline overdose

Abstract

Tricyclic antidepressant (TCA) overdose is a leading cause of death among intentional overdoses. Intravenous lipid emulsion therapy is an emerging antidote for local anesthetic toxicity, and there is animal evidence that lipid therapy may be efficacious in TCA overdose. Furthermore, case reports in humans have described the use of lipid therapy to reverse the toxicity of other lipophilic drugs. Here we report a 25-year-old female presenting with coma and hemodynamic instability following intentional ingestion of amitriptyline. She had multiple episodes of pulseless wide-complex tachycardia despite conventional treatment with chest compressions, cardioversion, lidocaine, epinephrine, norepinephrine, magnesium sulphate, sodium bicarbonate, activated charcoal, and whole bowel irrigation. Twenty percent lipid emulsion was administered intravenously (an initial 150 mL bolus, followed by an infusion at 16 mL/h and a second bolus of 40 mL) over 39 hours (total dose 814 mL) yet resulted in no dramatic changes in hemodynamics or level of consciousness. However, there was a decrease in the frequency of wide-complex tachycardia during the lipid emulsion infusion and a recurrence of wide-complex tachycardia shortly after the infusion was stopped. The patient was discharged from the intensive care unit 11 days later with no lasting physiologic sequelae. Keywords: amitriptyline, intravenous fat emulsions, tricyclic antidepressive agentsTricyclic antidepressant (TCA) overdose is an important cause of mortality following intentional overdose despite timely and aggressive treatment.1 Intravenous lipid emulsion therapy is an exciting new treatment for lipophilic drug overdoses. Lipid therapy is widely advocated for local anesthetic toxicity 2 and is increasingly reported in the literature for overdoses of other pharmaceuticals. [2][3][4][5][6][7][8][9][10][11][12][13] We report the use of lipid therapy in a case of refractory pulseless wide-complex tachycardia resulting from an amitriptyline overdose. CASE REPORTA 50 kg, 25-year-old female was discovered unconscious in her house near several empty bottles of amitriptyline. The patient had a history of anorexia and depression and had stockpiled multiple amitriptyline prescriptions from different physicians specifically for the purpose of committing suicide. The total number and dose were not recorded, and there were possible coingestions of her regular medications, which included fluoxetine, escitalopram, olanzapine, quetiapine, and gabapentin. Paramedics found her to be unresponsive with a Glasgow Coma Scale score of 3, a heart rate of 60 beats/min, a wide QRS (186 ms), and a blood pressure of 60 mm Hg systolic. She was intubated without sedation and taken to the emergency department (ED).In the ED, the patient went into a pulseless widecomplex tachycardia three times over the next 2 hours. Each episode was treated with chest compressions, synchronized cardioversion, lidocaine, and epinephrine. After cardioversion, the patient reverted to sinus rhythm with a wide QRS dura...

Past, Present, and Future of Lipid Resuscitation Therapy

“…Many antipsychotic or antidepressant medications make sense as treatment targets with ILE because of the lipophilicity needed to cross the blood‐brain barrier and because of their structural similarity to local anesthetics. Since the first case report, a significant number of other toxicities have been treated with LRT, including amitriptyline, 111 ‐ 117 quetiapine, 106 , 114 lamotrigine, 78 , 79 , 88 , 114 bupropion, 88 , 118 ‐ 120 and doxepin 121 . Rabbit models have demonstrated the effectiveness of lipid as a treatment for IV clomipramine toxicity 122 .…”

Intravenous Lipid Emulsion Entraps Amitriptyline into Plasma and Can Lower its Brain Concentration – An Experimental Intoxication Study in Pigs

“…As amitriptyline is a highly lipid-soluble drug (logP 4.9 [7]), and there is no specific antidote for it, lipid emulsion could be a suitable treatment in amitriptyline intoxication. Lipid emulsion has, in fact, been given as an antidote in severe amitriptyline intoxications [13][14][15][16][17][18], as well as in other antidepressant intoxications [3,19,20]. In our previous controlled experimental study, intravenous lipid emulsion infusion, started immediately after an infusion of toxic dose of amitriptyline, was found to entrap amitriptyline in plasma, thus delaying its distribution into tissues [21].…”

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

“…1 More recently, intravenous lipid emulsion (ILE) preparations have been forwarded as adjuncts to standard management of TCA toxicity with successful reports of use in animal models 2 and human subjects. 3 Both pharmacokinetic and pharmacodynamic mechanisms have been forwarded to explain the beneficial effects of ILE. The widely held lipid sink theory is that lipid sequesters certain xenobiotics (such as TCAs) and reduces toxicity by decreasing the free serum concentration of the offending toxin.…”