Approach

Treatment of suspected amphetamine toxicity is initiated before receiving laboratory results. Management is predominantly supportive, aimed at reducing core body temperature, rehydration, sedation (if required), and cardiac monitoring.[7][15][21][36][37][59][60] Vital signs are monitored frequently because the patient's condition may change rapidly. In the most severe cases, intensive care unit care with multiorgan support, cardiac telemetry, mechanical ventilation, and close one-on-one observation may be necessary.

Initial treatment

If the patient presents within 1 hour of drug ingestion and is cooperative, activated charcoal is given orally. If intoxication is mild, the patient may be best managed by monitoring and observation in a quiet environment, with supportive measures (intravenous fluids, cooling) as needed.

With agitation

In the presence of agitation the first concern is to determine the level of cooperation of the patient and rapidly control any behavioral disturbance.[37][57][59] The aim is to insure irrational or aggressive behavior does not impede timely assessment and management of the condition, and to insure the safety of the patient, staff, and others. Nonpharmacologic measures may help to calm the patient and de-escalate a difficult situation. This may include assuring the patient (and family or friends) of confidentiality, quietly listening to the patient, calm and open-ended questioning and nonthreatening language, an even tone, using his or her name, allowing the patient as much space as practical, and avoiding too much eye contact (which can be interpreted as threatening if the patient is feeling hostile or paranoid).

If nonpharmacologic measures fail to calm the patient, urgent sedation may be necessary.[7][15][21][36][37][59][60] Benzodiazepines are the most commonly used drugs for this indication. Antipsychotics such as haloperidol, olanzapine, and droperidol are also useful and may be used in combination with benzodiazepines.[64][65][66] The synergistic use of these different sedatives has been shown to be more effective than monotherapy in clinical trials.[67][68][69] Droperidol has been shown to be safe and efficacious for treatment of agitation at low to moderate doses.[70][71] If possible, QT interval should be measured prior to administration of either droperidol or intravenous haloperidol. The Richmond Agitation-Sedation Scale (RASS) may be used to guide sedation.[1]

  • (+1 to 2): if the patient is mildly aroused, pacing, and irritable but is still cooperative and willing to talk and give a history, and vital signs are essentially normal, it is reasonable to give an oral benzodiazepine. If this is ineffective, repeated and higher doses of benzodiazepines or olanzapine can be given orally. Haloperidol may also be given orally.[37][57][59]

  • (+2 to 3): in a moderately aroused patient who is restless, agitated, vocal, unreasonable, hostile, and uncooperative, with tachycardia and hypertension, an oral protocol as above may be initiated. Progression to intravenous or intramuscular administration may follow if the oral protocol is refused or ineffective. Benzodiazepines may be given intravenously and repeated if necessary; antipsychotics are administered orally or intramuscularly. Physical restraint of the patient may be required at this stage and should involve multiple staff members, preferably one per limb plus an additional staff member to establish intravenous access and administer sedatives.

  • (+3 to 4): a highly aroused, distressed, fearful, highly agitated, abusive, noncooperative, and possibly violent patient requires sedation as soon as possible, initially with benzodiazepines and/or antipsychotics intravenously, repeated until sedation is adequate. Intramuscular administration may be necessary if a secure intravenous line cannot be obtained. If these measures are unsuccessful, rapid sequence intubation of the patient must be performed to protect patient and staff from harm and facilitate further testing, such as CT.

With volume depletion

Most patients who present with acute toxicity from amphetamines exhibit significant intravascular depletion and require rapid administration of intravenous fluids such as normal saline or lactated Ringer solution. Potassium administration is dictated by the patient's serum potassium concentration.

With rhabdomyolysis

Appropriate and timely fluid resuscitation is essential to the management of rhabdomyolysis. Rhabdomyolysis can be pronounced with peak creatine kinase levels in the region of 30,000 to 100,000 U/L.[23][72] The highest recorded peak creatine kinase in a rhabdomyolysis survivor is 555,000 U/L.[73] Maintaining urine output with hydration by intravenous fluids is the key to successful management of this condition.

With metabolic acidosis

Hyperthermia may lead to a clinical picture similar to that of severe heatstroke, with metabolic acidosis and other severe physiologic derangement. Sodium bicarbonate may be required to correct a severe metabolic acidosis. Electrolytes need to be monitored closely because hypernatremia and hypokalemia are a risk if substantial amounts of bicarbonate are given.

Some experts feel the urine should not be alkalinized because this will impair the pH-dependent renal excretion of amphetamines. However, the renal elimination of amphetamine does not have a large influence on amphetamine overdoses. Thus, bicarbonate is not contraindicated; nor is urinary acidification advocated because there is a risk of precipitation of myoglobin in the renal tubules at low pH.[23][72]

With hyperthermia

Rectal temperature measurement most closely approximates core body temperature. Active cooling is generally instituted when body temperature exceeds 100°F (38°C).[5][26][74] The simplest method to accomplish rapid cooling in any setting is the application of tepid mist and use of a fan for conductive, evaporative, and convective heat dissipation.[74] Additional measures include cooling blankets and ice packs. Care should be taken to monitor for hyponatremia. Benzodiazepines are given to relax muscles.

Hyperthermia above 103°F (39.5°C) indicates severe, potentially life-threatening toxicity and mandates immediate cooling (e.g., cooled intravenous fluids, sponge baths, ice packs) and sedation. This is best done in the intensive care unit with paralysis and ventilation.[7] Paralysis may need to be prolonged to prevent re-emergence of drug-induced hyperthermia and is usually accomplished with a nondepolarizing neuromuscular blocker with moderate duration of action, such as pancuronium. Patients must be intubated before initiation of paralysis.

With cardiac dysrhythmia

Death due to cardiac dysrhythmia from overdose of amphetamines has been reported in the presence of underlying ischemic heart disease and conduction defects.[47][75][76] ECG and cardiac monitoring is prudent in all patients who have toxicity from amphetamines with chest pain or dysrhythmia. Most tachycardia is sinus in origin and resolves over several hours. However, treatment is beneficial because prolonged tachycardia places the patient at risk of myocardial ischemia from increased myocardial oxygen demand.[59]

Benzodiazepines are first-line agents but may not reliably control sinus tachycardia resulting from amphetamines. For patients with concomitant tachycardia and hypertension, or if there are concerns regarding unopposed alpha-stimulation, the mixed alpha/beta-blocker labetalol has been shown to be safe and effective.[37] In normotensive patients, the beta-blocker metoprolol may be considered for treatment of sinus tachycardia.[37]

Supraventricular tachycardias associated with hemodynamic compromise are best treated with short-acting beta-blockade (e.g., intravenous esmolol).[7][54]

Ventricular tachycardia may be treated conventionally with antiarrhythmic medication (e.g., amiodarone) or cardioversion.

With seizures

Seizures may be managed with an intravenous benzodiazepine initially and repeated as necessary.[37] Barbiturates and possibly general anesthesia may be indicated for status epilepticus unresponsive to escalating doses of benzodiazepines.

With subarachnoid hemorrhage

Subarachnoid hemorrhage may be treated conventionally by giving nimodipine and expedited transfer to a center for management of neurosurgical emergencies.[77]

With hypertension

Benzodiazepines may not effectively mitigate hypertension in certain patients with amphetamine-related toxicity. If hypertension persists, labetalol may be used.[37][59]

Nitric oxide-mediated vasodilators such as nitroprusside and nitroglycerin are also useful for the treatment of isolated hypertension, as is the alpha-blocker phentolamine. The calcium-channel blocker nicardipine may also be useful.[78]

With hypotension

Hypotension is a late-stage phenomenon that may occur if the patient is severely dehydrated or has depleted catecholamines. An immediate temporizing effect may be obtained by placing the patient into the Trendelenburg position. Copious intravenous fluid administration is warranted. These measures are usually effective in resolving hypotension; however, use of pressors such as dopamine or norepinephrine may be required in extreme cases.

With serotonin toxicity

In patients with suspected serotonin toxicity, observation and supportive care in a hospital environment yields the best therapeutic results. Specific treatment may include benzodiazepines or cyproheptadine (if available).[27][45] Consultation with clinical staff at a poison center can prove critically important if serotonin toxicity is suspected. [Figure caption and citation for the preceding image starts]: Activated charcoalFrom the collection of Dr Alison Jones [Citation ends].com.bmj.content.model.Caption@175d38ed

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