What is the management for D-amphetamine (dextroamphetamine) toxicity?

Management of D-Amphetamine Toxicity

Immediate management of d-amphetamine toxicity is largely symptomatic, prioritizing aggressive sedation with benzodiazepines to control agitation and prevent life-threatening complications including hyperthermia, rhabdomyolysis, and seizures. 1

Initial Assessment and Stabilization

• Ensure standard airway management, support of breathing, and treatment of hypotension or dysrhythmias consistent with advanced life support protocols 2
• Contact a regional poison center (1-800-222-1222 in the US) for expert toxicology guidance, as board-certified toxicologists can provide specialized treatment recommendations 2
• Assess for specific toxic manifestations including restlessness, tremor, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations, panic states, and hyperpyrexia 1
• Monitor for cardiovascular effects including arrhythmias, hypertension or hypotension, and potential circulatory collapse 1

Primary Treatment: Aggressive Sedation

Benzodiazepines are the first-line treatment for amphetamine-induced agitation, psychosis, and hyperadrenergic symptoms. 3, 4

• Administer benzodiazepines (such as diazepam or lorazepam) in sufficient doses to control agitation, tremors, and prevent seizures 3, 4
• Titrate benzodiazepines aggressively to interrupt the sympathomimetic syndrome and prevent secondary complications 4
• Adequate sedation is critical to manage hyperthermia and acidosis, prevent rhabdomyolysis and injury, and allow proper evaluation for other life-threatening conditions 2

The evidence strongly supports benzodiazepines as first-line therapy, with high-quality studies demonstrating efficacy for controlling agitation and psychosis 3. While animal studies showed diazepam reduced seizure incidence but did not prevent death 5, human clinical experience demonstrates benzodiazepines are effective when used in adequate doses for the full sympathomimetic syndrome 3, 4.

Second-Line Pharmacologic Interventions

If agitation, delirium, and movement disorders remain unresponsive to benzodiazepines:

• Antipsychotics (haloperidol or ziprasidone) can be used as second-line agents 4
• Haloperidol (1.0-20.0 mg/kg in animal models) provided significant protection against amphetamine-induced death 5
• Chlorpromazine antagonizes the central stimulant effects of amphetamines and can treat amphetamine intoxication 1
• Dexmedetomidine (central alpha-adrenergic agonist) has been successfully used in case reports for refractory agitation 3
• Propofol may be considered for severe, refractory cases 4

High-quality evidence supports the use of butyrophenone and later-generation antipsychotics for amphetamine toxicity 3. Animal studies demonstrated that haloperidol combined with propranolol reduced death more than either agent alone 5.

Cardiovascular Management

For hypertension and tachycardia:

• Beta-blockers (such as propranolol) are recommended based on high-quality evidence for controlling hyperadrenergic cardiovascular symptoms 3
• Propranolol (20.0-30.0 mg/kg in animal models) provided significant protection against amphetamine-induced death 5
• Calcium channel blockers (particularly nicardipine) can improve blood flow and manage hypertension 6, 3
• For acute severe hypertension, intravenous phentolamine (alpha-blocker) has been suggested, though gradual blood pressure reduction typically occurs with adequate sedation 1

Avoid beta-blockers in isolation if unopposed alpha-adrenergic stimulation is a concern, though the evidence supports their overall safety and efficacy 3. Three high-quality studies support calcium channel blockers as an alternative 3.

Gastrointestinal Decontamination

• Gastric lavage may be considered if presentation is within 1-2 hours of ingestion 1
• Administer activated charcoal to reduce drug absorption 1
• Administer a cathartic as part of gastrointestinal decontamination 1
• Consider the prolonged release formulation of extended-release amphetamine products when treating overdose, as drug release may continue for extended periods 1

Critical Complications to Monitor and Manage

Hyperthermia:

• Provide aggressive cooling measures and intravenous fluids 7
• Hyperthermia is a life-threatening complication requiring immediate intervention 1, 7

Rhabdomyolysis:

• Administer intravenous fluids to maintain renal function and promote drug elimination 7
• Monitor for myoglobinuria, as acidification of urine increases amphetamine excretion but may increase risk of acute renal failure if myoglobinuria is present 1
• Due to this risk, urinary acidification is generally not recommended in current practice 1

Seizures:

• Control with benzodiazepines as first-line 7, 4
• Phenothiazines, pentobarbital, or propofol can be used for refractory seizures 7
• Fatal poisoning is usually preceded by convulsions and coma 1

Cardiovascular arrhythmias:

• Manage tachyarrhythmias with beta-blockers (propranolol) after adequate sedation 7
• Monitor for both hypertension and hypotension, as either may occur 1

Additional Supportive Measures

• Limit caffeine intake to less than 200mg per day, as it exacerbates vasoconstriction when combined with amphetamines 6
• Ensure adequate hydration to improve blood viscosity and flow 6
• Monitor vital signs frequently, particularly blood pressure and heart rate, as these indicate severity of systemic vasoconstriction 6
• Monitor for hypoglycemia, which has been reported in amphetamine intoxication 7

Ineffective or Contraindicated Treatments

• Hemodialysis or peritoneal dialysis: inadequate evidence to recommend 1
• Yohimbine: ineffective in preventing seizures or death in animal studies 5
• Urinary acidification is generally avoided due to rhabdomyolysis risk 1

Clinical Pearls and Pitfalls

Common pitfalls to avoid:

• Underestimating the need for aggressive benzodiazepine dosing—inadequate sedation leads to preventable complications 2, 4
• Delaying treatment while awaiting confirmatory toxicology testing—clinical presentation should guide immediate management 1, 4
• Using beta-blockers before adequate sedation, which may worsen hypertension through unopposed alpha effects 6

Key prognostic factors:

• The vast majority of amphetamine toxicity cases (90%) do not require pharmacologic treatment in the emergency department 8
• Only 10% of cases require hospital admission 8
• Prognosis depends on severity and duration of clinical signs at presentation 7
• Fatalities are rare with appropriate supportive care 4

Warning signs requiring intensive monitoring:

• Severe headache with visual symptoms may indicate cerebrovascular effects 6
• Signs of systemic sympathetic overstimulation (severe hypertension, tachycardia) warrant immediate intervention 6
• Persistent symptoms despite adequate treatment require escalation of care 6