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CPC Discussion Anne-Michelle Ruha, MD Department of Medical Toxicology Good Samaritan Regional Medical Center Phoenix, Arizona History • 24 year old man with altered mental status • Found on bed, fully clothed • History of depression • Use of weight loss supplement Physical Exam • • • • HR= 179 bpm RR= 24/min BP= 90/60 mmHg Temp 103ºF (core) Physical Exam • Awake, but confused and agitated • Non-verbal, not following commands • Dilated pupils (4-5 mm) • Slight diaphoresis • Active bowel sounds Physical Exam • Pertinent negative findings –Not comatose –Not rigid –Not hyperreflexic Tachycardic, hypotensive, and hyperthermic man who is awake but exhibits an agitated delirium. AMS and Hyperthermia: ‘Tox’ • Sympathomimetics – “Amines” – Cocaine – MAOIs • Anticholinergics • Dissociatives • Hallucinogens • Lithium • Neuroleptics • Neuroleptic Malignant Syndrome • Sedative Hypnotic Withdrawal • Serotonin Syndrome • Strychnine • Thyroid hormone • Uncouplers – Dinitrophenol – Salicylates ECG #1 Intervention • 3 ampules of sodium bicarbonate IV ECG #2 Possibilities… • Wide QRS secondary to sodium channel blockade • Wide QRS secondary to hyperkalemia • Ventricular tachycardia Toxins that produce Sodium Channel Blockade • • • • • • • • Amantadine Antihistamines Beta blockers Carbamazepine Chloroquine Class IA antiarrhythmics Class IC antiarrhythmics Cocaine • Cyclic Antidepressants • Local anesthetics • Orphenadrine • Phenothiazines • Propoxyphene • Quinine • Verapamil Toxins that produce Sodium Channel Blockade • • • • • • • Amantadine Antihistamines Beta blockers Carbamazepine Chloroquine Class IA antiarrhythmics Class IC antiarrhythmics • Cocaine • Cyclic Antidepressants • Local anesthetics • Orphenadrine • Phenothiazines • Propoxyphene • Quinine • Verapamil Course • Mild hyperglycemia (160 mg/dL) • Worsening agitation • APAP, IV droperidol, IV lorazepam • Blood and urine then collected Labs 148 102 23 5.4 26 2.7 150 AST = 148 IU/L ALT = 36 UY.K Total Bili = 0.6 mg/dL 15 245 34 INR = 1.0 PTT = 35 sec “UDS” = + amphetamines UA = large blood 0-2 RBC no ketones neg barbs/benzos/cocaine opiates/PCP neg APAP / EtOH Interpretation of labs • • • • • Hypovolemia/dehydration Renal insufficiency Rhabdomyolysis Hyperkalemia Salicylate level not reported + amphetamine screen • • • • • • • • • • • • • • Amphetamine (l,d) Amphetaminil Benzedrine Benzphetamine Biphetamine Clobenzorex Desoxyn Dexedrine Dimethylamphetamine Ephedrine Ethylamphetamine Famprofazone Fencamine Fenethylline • • • • • • • • • • • • • Fenproporex Furfenorex 3,4-MDMA 3,4-MDA Methamphetamine (l,d) Mefenorex Mesocarb Paramethoxyamphetamine Phentermine Phenylpropanolamine Prenylamine Pseudoephedrine Selegiline Weight Loss Agents • • • • • • • • • • • Bitter Orange extract Carnitine Chitosan Chromium Clobenzorex Dessicated thyroid Dexfenfluramine Dinitrophenol Fenfluramine Gamma linoleic acid Ginkgo biloba • • • • • • • • • • Ginseng Guarana Hydroxycitrate Ma Huang - ephedrine alkaloids Orlistat Phentermine Phenylpropanolamine Pyruvate Sibutramine Starch blocker Weight Loss Agents • • • • • • • • • • • Bitter Orange extract Carnitine Chitosan Chromium Clobenzorex Dessicated thyroid Dexfenfluramine Dinitrophenol Fenfluramine Gamma linoleic acid Ginkgo biloba • • • • • • • • • • Ginseng Guarana Hydroxycitrate Ma Huang - ephedrine alkaloids Orlistat Phentermine Phenylpropanolamine Pyruvate Sibutramine Starch blocker Further Course • Rapid Sequence Intubation –lidocaine, etomidate, succinylcholine • Activated charcoal • IVF at 200 cc/hr • CT brain: no acute changes • CXR: no acute disease • Worsening agitation • Temperature = 105ºF (core) • Vecuronium, rapid cooling measures • Temperature = 109ºF • ABG = 7.09 / 40 / 517 • serum K = 6.7 Final course • Hyperventilation • Treatment of hyperkalemia • Fatal cardiac arrest Etiology? • Primary toxin responsible for continued deterioration and death • Intervention contributed to worsening hyperthermia and subsequent death AMS and Hyperthermia: ‘Tox’ • Sympathomimetics – “Amines” – Cocaine – MAOIs • Anticholinergics • Dissociatives • Hallucinogens • Lithium • Neuroleptics • Neuroleptic Malignant Syndrome • Sedative Hypnotic Withdrawal • Serotonin Syndrome • Strychnine • Thyroid hormone • Uncouplers – Dinitrophenol – Salicylates AMS and Hyperthermia: ‘Tox’ • Sympathomimetics – “Amines” – Cocaine – MAOIs • Anticholinergics • Dissociatives • Hallucinogens • Lithium • Neuroleptics • Neuroleptic Malignant Syndrome • Sedative Hypnotic Withdrawal • Serotonin Syndrome • Strychnine • Thyroid hormone • Uncouplers – Dinitrophenol – Salicylates Sympathomimetic Amines • Support: – Symptoms, renal failure, severe hyperthermia – Positive urine screen – History of use of weight loss agent • Against: – No reported cases of QRS widening secondary to sodium channel blockade Which Agent? • Weight loss agents: – Ma Huang / ephedrine alkaloids – Phenylpropanolamine Ripped Fuel – Clobenzorex Xenedrine Metabolife • Illicit drugs: – Methylenedioxymethamphetamine – Paramethoxyamphetamine – Methamphetamine MAOIs • MAOI overdose or drug interaction with serotonergic weight loss agent or antidepressant • Support: – Tachycardia, agitation, diaphoresis – Selegiline, an antiparkinson drug, is metabolized to methamphetamine • Against: – Lack of neuromuscular findings (rigidity, hyperreflexia, tremor) Dinitrophenol • Support: – Uncouples oxidative phosphorylation and would be expected to produce hyperthermia despite paralysis – Tachypnea, diaphoresis, tachycardia consistent with poisoning – Recent experimentation with this agent documented on the internet Dinitrophenol • Against: – Would expect more acidosis early on in presentation Salicylate • Support: – Agitated delirium, tachypnea, tachycardia, diaphoresis – May produce severe hyperthermia • Against: – Not initially acidotic (CO2=26) – No ketones in urine Why did the patient deteriorate following paralysis? • Amphetamines and uncouplers can both produce hyperthermia independent of increased motor activity ? Succinylcholine – Malignant hyperthermia – Hyperkalemia – Rigidity and hyperthermia in salicylates Most likely culprits… 1. 2. 3. 4. Amphetamine – like agent MAOI (selegiline) Dinitrophenol Salicylate Final Answer…. • Overdose of a weight loss supplement detected on UDS as an amphetamine Ma Huang – Ephedrine alkaloids