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

Labs148 102 23

5.4 26 2.7150 15 245

34

AST = 148 IU/L

ALT = 36 UY.K

Total Bili = 0.6 mg/dL

INR = 1.0

PTT = 35 sec

UA = large blood

0-2 RBC

no ketones

“UDS” = + amphetamines

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–Clobenzorex

• Illicit drugs:–Methylenedioxymethamphetamine –Paramethoxyamphetamine–Methamphetamine

Ripped Fuel Xenedrine Metabolife

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. Amphetamine – like agent

2. MAOI (selegiline)

3. Dinitrophenol

4. Salicylate

Final Answer….

• Overdose of a weight loss supplement detected on UDS as an amphetamine

Ma Huang – Ephedrine alkaloids