Amphetamine Poisoning

Basics

Description

  • Increased release of norepinephrine, dopamine, and serotonin
  • Decreased catecholamine reuptake
  • Direct effect on α- and β-adrenergic receptors

Etiology

  • Prescription drugs:
    • Amphetamine (Benzedrine)
    • Dextroamphetamine (Dexedrine)
    • Diethylpropion (Tenuate)
    • Fenfluramine (Pondimin)
    • Methamphetamine
    • Methylphenidate (Ritalin)
    • Phenmetrazine (Preludin)
    • Phentermine
  • “Designer drugs”:
    • Variants of illegal parent drugs
    • Often synthesized in underground labs using unknown ingredients
    • “Crystal,” “Ice”, “Crank”:
      • Crystalline methamphetamine hydrochloride
      • Smoked, insufflated, or injected
      • Rapid onset; duration several hours
    • “Ecstasy” (3,4-methylenedioxymethamphetamine, MDMA, XTC, E, Molly):
      • Often used at dances and “rave” parties
      • Dehydration can lead to hyperthermia, hyponatremia, fatality
    • MDA (3,4-methylenedioxyamphetamine)
    • Methcathinone (“cat,” “Jeff,” “mulka”):
      • Derivative of cathinone, found in the evergreen tree Catha edulis
      • Frequently synthesized in home labs
      • Does not show up on urine toxicology screens
    • Mephedrone:
      • May be contained in “bath salts”

Diagnosis

Signs And Symptoms

  • CNS:
    • Agitation
    • Delirium
    • Hyperactivity
    • Tremors
    • Dizziness
    • Mydriasis
    • Headache
    • Choreoathetoid movements
    • Hyperreflexia
    • Cerebrovascular accident
    • Seizures and status epilepticus
    • Coma
  • Psychiatric:
    • Euphoria
    • Increased aggressiveness
    • Anxiety, paranoia
    • Hallucinations (visual, tactile)
    • Compulsive repetitive actions
  • Cardiovascular:
    • Palpitations
    • Hypertensive crisis
    • Tachycardia or (reflex) bradycardia
    • Dysrhythmias (usually tachydysrhythmias)
    • Cardiovascular collapse
  • Other:
    • Rhabdomyolysis
    • Myoglobinuria
    • Acute renal failure
    • Anorexia
    • Diaphoresis
    • Disseminated intravascular coagulation (DIC)

History

  • Determine the type, amount, timing, and route of amphetamine exposure
  • Assess for possible coingestants “hippie flip” (ecstasy and mushrooms) and “candy flip” (ecstasy and LSD)
  • Evaluate for symptoms of end organ injury:
    • Chest pain
    • Shortness of breath
    • Headache, confusion, and vomiting

Physical Exam

  • Common findings include:
    • Agitation
    • Tachycardia
    • Diaphoresis
    • Mydriasis
    • Bruxism
  • Severe intoxication characterized by:
    • Tachycardia
    • HTN
    • Hyperthermia
    • Agitated delirium
    • Seizures
    • Diaphoresis
    • Clonus
  • Hypotension and respiratory distress may precede cardiovascular collapse
  • Evaluate for associated conditions:
    • Cellulitis and soft tissue infections
    • Diastolic cardiac murmurs or unequal pulses
    • Examine carefully for trauma
    • Pneumothorax from inhalation injury
    • Focal neurologic deficits

Essential Workup

  • Vital signs:
    • Temperature >40 °C:
      • Core temperature recording essential
      • Peripheral temperature may be cool
      • Indication for urgent cooling
      • Ominous prognostic sign
    • BP:
      • Severe hypertension can lead to cardiac and neurologic abnormalities
      • Late in course, hypotension may supervene due to catecholamine depletion
  • ECG:
    • Signs of cardiac ischemia
    • Ventricular tachydysrhythmias
    • Reflex bradycardia

Diagnostic Tests And Interpretation

Lab

  • Urinalysis:
    • Blood
    • Myoglobin
  • Electrolytes, BUN/creatinine, glucose:
    • Hypoglycemia may contribute to altered mental status
    • Acidosis may accompany severe toxicity
    • Rhabdomyolysis may cause renal failure
    • Hyperkalemia – life-threatening consequence of acute renal failure
    • Hyponatremia – due to antidiuretic hormone release and excessive water intake
  • Coagulation profile to monitor for potential DIC:
    • INR, PT, PTT, platelets
  • Creatine phosphokinase (CPK):
    • Markedly elevated in rhabdomyolysis
  • Urine toxicology screen:
    • For other toxins with similar effects (eg, cocaine)
    • Some amphetamine-like substances (eg, methcathinone) may not be detected
  • Aspirin and acetaminophen levels if suicide attempt is a possibility
  • Arterial blood gas (ABG)

Imaging

  • Chest radiograph:
    • Adult respiratory distress syndrome
    • Noncardiogenic pulmonary edema
  • Head CT for:
    • Significant headache
    • Altered mental status
    • Focal neurologic signs
    • For subarachnoid hemorrhage, intracerebral bleed
  • Abdominal Imaging:
    • Body packers or body stuffers

Diagnostic Procedures/Surgery

Lumbar puncture for:

  • Suspected meningitis (headache, altered mental status, hyperpyrexia)
  • Suspected subarachnoid hemorrhage and CT normal

Differential Diagnosis

  • Sepsis
  • Thyroid storm
  • Serotonin syndrome
  • Neuroleptic malignant syndrome
  • Pheochromocytoma
  • Subarachnoid hemorrhage
  • Drugs that cause delirium:
    • Anticholinergics:
      • Belladonna alkaloids
      • Antihistamines
    • Tricyclic antidepressants
    • Cocaine
    • Ethanol withdrawal
    • Sedative/hypnotic withdrawal
    • Hallucinogens
    • Phencyclidine
  • Drugs that cause HTN and tachycardia:
    • Sympathomimetics
    • Anticholinergics
    • Ethanol withdrawal
    • Phencyclidine
    • Caffeine
    • Phenylpropanolamine
    • Ephedrine
    • Monoamine oxidase inhibitors
    • Theophylline
    • Nicotine
  • Drugs that cause seizures:
    • Carbon monoxide
    • Carbamazepine
    • Cyanide
    • Cocaine
    • Cholinergics (organophosphate insecticides)
    • Camphor
    • Chlorinated hydrocarbons
    • Ethanol withdrawal
    • Sedative/hypnotic withdrawal
    • Isoniazid
    • Theophylline
    • Hypoglycemics
    • Lead
    • Lithium
    • Local anesthetics
    • Anticholinergics
    • Phencyclidine
    • Phenothiazines
    • Phenytoin
    • Propoxyphene
    • Salicylates
    • Strychnine

Treatment

Prehospital

  • Patient may be uncooperative or violent
  • Secure IV access
  • Protect from self-induced trauma

Initial Stabilization/Therapy

  • ABCs
  • Establish IV 0.9% NS access
  • Cardiac monitor
  • Naloxone, dextrose (or Accu-Chek), and thiamine if altered mental status

Ed Treatment/Procedures

  • Decontamination:
    • Administration of activated charcoal
    • Whole-bowel irrigation with polyethylene glycol solution for body packers
  • Hypertensive crisis:
    • Initially administer benzodiazepines if agitated
    • α-Blocker (phentolamine) as 2nd-line agent
    • Nitroprusside for severe, unresponsive hypertension
    • Avoid β-blockers, which may exacerbate hypertension
  • Agitation, acute psychosis:
    • Administer benzodiazepines
  • Hyperthermia:
    • Benzodiazepines if agitated
    • Institution and site-specific active cooling adjunctive therapy if temperature >40 °C:
      • Tepid water mist
      • Evaporate with fan
      • Cooling blanket
      • Ice water bath
      • Apply ice packs to groin, axillae, neck and torso
      • Active cooling devices such as Artic Sun
      • Paralysis
      • Indicated if muscle rigidity and hyperactivity contributing to persistent hyperthermia
      • Nondepolarizing agent (eg, vecuronium)
      • Avoid succinylcholine
      • Intubation; mechanical ventilation
    • Apply cooling blankets
  • Rhabdomyolysis:
    • Administer benzodiazepines
    • Hydrate with 0.9% NS
    • Maintain urine output at 1–2 mL/min
    • Hemodialysis (if acute renal failure and hyperkalemia occur)
  • Seizures:
    • Maintain airway
    • Administer benzodiazepines
    • Phenobarbital if unresponsive to benzodiazepines
    • Phenytoin contraindicated
  • Hypotension:
    • May be late finding due to catecholamine depletion
    • Initially bolus with isotonic crystalloid solution
    • If no response, administer norepinephrine
    • Dopamine may not be effective

Medication

  • Activated charcoal: 1–2 g/kg up to 100 g PO
  • Dextrose: D50W 1 amp: 50 mL or 25 g (peds: D25W 2–4 mL/kg) IV
  • Diazepam (benzodiazepine): 5–10 mg (peds: 0.2–0.5 mg/kg) IV
  • Lorazepam (benzodiazepine): 1–6 mg (peds: 0.03–0.05 mg/kg) IV
  • Nitroprusside: 1–8 mcg/kg/min IV (titrated to BP)
  • Phenobarbital: 15–20 mg/kg IV at 25–50 mg/min until cessation of seizure activity
  • Phentolamine: 1–5 mg IV over 5 min (titrated to BP)
  • Vecuronium: 0.1 mg/kg IVP

Follow-Up

Disposition

Admission Criteria

  • Hyperthermia
  • Persistent altered mental status
  • Hypertensive crisis
  • Seizures
  • Rhabdomyolysis
  • Persistent tachycardia

Discharge Criteria

  • Asymptomatic after 6-hr observation
  • Absence of the above admission criteria

Follow-Up Recommendations

Patients may need referral for chemical dependency rehab and detoxification

Pearls And Pitfalls

  • Admit patients with severe or persistent symptoms
  • Monitor core temperature:
    • Hyperthermia >40 °C may be life threatening
    • Treat with aggressive sedation and active cooling
    • Recognize rhabdomyolysis and hyperkalemia
    • Avoid physical restraints in agitated patients if possible
  • Consider associated emergency conditions:
    • Patients with chest pain should be evaluated for acute coronary syndromes and treated accordingly
    • Consider infection in altered patients with fever and history of IV drug use
    • Methamphetamine abuse frequently associated with traumatic injury
  • Benzodiazepines are 1st-line therapy in symptomatic methamphetamine intoxication
  • Some newer stimulant drugs-of-abuse are chemically similar to amphetamines

Additional Readings

  1. Carvalho M, Carmo H, Costa VM, et al. Toxicity of amphetamines: An update. Arch Toxicol. 2012;86:1167–1231.  [PMID:22392347]
  2. Courtney KE, Ray LA. Clinical neuroscience of amphetamine-type stimulants: From basic science to treatment development. Prog Brain Res. 2016;223:295–310.  [PMID:26806782]
  3. Figurasin R, Lee VR, Maguire NJ. 3,4-Methylenedioxymethamphetamine (MDMA) toxicity. [Updated 2024 January 17]. In: StatPearls [Internet]. StatPearls Publishing; 2024. https://www.ncbi.nlm.nih.gov/books/NBK538482/
  4. Gray SD, Fatovich DM, McCoubrie DL, Daly FF. Amphetamine-related presentations to and inner-city tertiary emergency department: A prospective evaluation. Med J Aust. 2007;186:336–339.  [PMID:17407428]
  5. Hysek CM, Simmler LD, Schillinger N, et al. Pharmacokinetic and pharmacodynamic effects of methylphenidate and MDMA administered alone or in combination. Int J Neuropsychopharmacol. 2014;17(3):371–381.  [PMID:24103254]
  6. Kim DA, Lindquist BD, Shen SH, Wagner AM, Lipman GS. A body bag can save your life: A novel method of cold water immersion for heat stroke treatment. J Am Coll Emerg Physicians Open. 2020;1(1):49–52.  [PMID:33000014]
  7. Passie T, Benzenhöfer U. The History of MDMA as an underground drug in the United States, 1960–1979. J Psychoactive Drugs. 2016;48(2):67–75.  [PMID:26940772]
  8. Pesce AJ, Krock K. Designer drugs. Lab Med. 2023;54(6):553–554.  [PMID:37774399]
  9. Wasserman DD, Creech JA, Healy M. Cooling techniques for hyperthermia. [Updated 2022 Oct 17]. In: StatPearls [Internet]. StatPearls Publishing; 2024. https://www.ncbi.nlm.nih.gov/books/NBK459311/

See Also (Topic, Algorithm, Electronic Media Element)

Authors

James W. Rhee

Matthew Tiacharoen