Improvement of neurologic function following intravenous lipid emulsion administration in lamotrigine overdose Vasisht Srinivasan, MD1; Rachel Gorodetsky, PharmD1,2; Rachel Schult, PharmD1,2; Timothy Wiegand, MD1 Departments of Emergency Medicine1 and Pharmacy2, University of Rochester Medical Center

Case Series Background • 13 y/o girl presented following intentional overdose • Lamotrigine induced cardiovascular toxicity has been successfully treated with IVLE and there are data supporting improvement of cardiac function toxicity but few data exist on • Intentional ingestion involving fluoxetine and lamotrigine neurologic symptoms • Presented with autonomic hyperactivity, hallucinations and neuromuscular excitation • Lamotrigine has been described to cause a syndrome in toxic levels that mimics serotonin • Symptoms persisted despite lorazepam & cyproheptadine syndrome, but can be refractory to treatment with benzodiazepines • Labs: tCO2 15 mmol/L with increased anion gap, pH 7.3, lamotrigine: 20 µg/mL • IVLE was traditionally described as a treatment for local anesthetic toxicity. It has also • 75 mL of 20% Intravenous lipid emulsion (IVLE) given rapidly over 2 minutes been used to treat overdoses of other medications including tricyclic antidepressants, verapamil, propranolol, bupropion, lamotrigine, and other xenobiotics. • Complete resolution of symptoms after IVLE Lamotrigine • IVLEs mechanism-of-action is thought to be multifactorial including functioning as a “lipid sink” to sequester fat soluble drugs (e.g, local anesthetics), its fatty acids are thought to • 28 y/o woman is comatose after mixed drug OD including lamotrigine serve as a mitochondrial fuel source and it may facilitate calcium transport intracellularly. • Benztropine, haloperidol, quetiapine and lamotrigine tablets identified (and confirmed in comprehensive drug screen) Lamotrigine levels on y-axis in µg/mL. Discussion • Presented comatose, tachycardic, with flailing of extremities and in respiratory failure. Shaded area represents drug therapeutic range • All patients were severely ill and presented with altered mental status, CNS and • Despite intubation and sedation she had paroxysms of agitation with progressive respiratory depression, and neuromuscular excitation. They were all treated with neuromuscular excitation, hyperreflexia, and rigidity benzodiazepines and other sedatives, without resolution of symptoms. • Lamotrigine level: 14.3 µg/mL • Two patients were given cyproheptadine although this did not fully treat their muscle • 100 mL of 20% IVLE administered via rapid bolus over 1 minute. rigidity, tachycardia, and hyperreflexia, • Immediately after IVLE bolus she had resolution of agitation, relaxation of tone, and • All patients had rapid resolution of neuromuscular symptoms following administration of normalization of vital signs. IVLE • All patients were able to be discharged home after their hospitalization with no adverse neurologic sequelae • 21 y/o woman presented shortly after ethosuxamide and lamotrigine OD • Initially was alert, had normal vital signs and neurologic exam. • Had rapid decline in mental status, developed severe neuromuscular hyperactivity, Limitations tachycardia, diaphoresis, rigidity and was intubated for airway protection. • Limited to 3 patient retrospective case series • Labs: lamotrigine 38.2 µg/mL, tCO2 16 mmol/L with increased anion gap Mec hanis ms of IVLE action : (1) Lipid sink (2) • Concomitant effects of co-ingestions cannot be excluded Inc r eas ed mitochondrial up take of fr ee fat ty acids • Despite large doses of GABAergic agents (50 mg diazepam, 8 mg lorazepam, 910 • Beneficial effects of other antidotes and supportive therapies can confound interpretation (FFA) (3) me mbrane effect(4) cytoprotec tion via Ak t mg of phenobarbital, midazolam gtt) and fentanyl infusion she remained rigid. pathway activa tion (5) Inc r eas ed VD C C ac tivity (6) • 100 mL bolus of 20%IVLE given rapidly with improvement in neuromuscular tone. accelerated shun ting . Fro m Weinberg G . Lipid Conclusion • She was supported and sedated for 48 hours and then extubated after four days. Emu ls ion In fus ion. Resuscitation for Local Anes the tic and Other Drug Overdose. • IVLE can be used to successfully treat the neurologic side effects of lamotrigine toxicity • Patient regained full neurologic function. Phospholipid and glycerol Anes thes iology 2012; 117:180-7 components of IVLE which, in severe ingestions, can be refractory to other therapies. However, further studies are needed to determine if the effects are predictable, establish a dose-response curve, and identify specific symptoms that can better target therapy.