Prehospital Care
Patients with acute methamphetamine intoxication may be highly agitated and present a serious safety risk to themselves and prehospital personnel. Seek additional help from police or other emergency medical services (EMS) providers before the patient is transported, if possible.
Patients' mental function may be sufficiently impaired that they are unable to make an informed decision to refuse treatment and transport. Prehospital intravenous access is warranted with or without patient consent, allowing for treatment of seizures and agitation using intravenous sedatives according to medical direction or protocol.
Emergency Department Care
Most cases of methamphetamine toxicity can be managed supportively. In the case of a severe overdose, immediate supportive care, including airway control, oxygenation and ventilation support, and appropriate monitoring is required. Specific treatments for heavy metal toxicity caused by contaminants in some methamphetamine preparations may be needed.
For suspected toxic oral ingestions, polyethylene glycol (PEG) solution should be initiated if possible. Animal studies suggest that orally ingested amphetamine-like compounds can be decontaminated with oral activated charcoal. [66] In body packers, whole-bowel irrigation can be considered for removal of the ingested packets, although controlled data documenting improvement in clinical outcome with this technique are lacking. [67]
In severe overdoses, termination of methamphetamine-induced seizure activity and arrhythmias are of immediate importance. Correction of hypertension, hypotension, hyperthermia, metabolic and electrolyte abnormalities, and control of severe psychiatric agitation are indicated. Consider health maintenance activities, such as testing for viral hepatitis and HIV disease and rehabilitation follow-up.
Treatment of agitation
Because of the ability of methamphetamine to cause significant central nervous system (CNS) and psychiatric activation, patients who present to emergency departments (EDs) for acute intoxication often require physical restraint and pharmacologic intervention.
Treat hyperactive or agitated patients with droperidol or haloperidol, which are butyrophenones that antagonize CNS dopamine receptors and mitigate the excess dopamine produced from methamphetamine toxicity. [68] These medications should be administered intravenously (IV), with doses titrated to the symptoms (see Medication). However, obtaining IV access may be dangerous or impossible in violently agitated patients; in such cases, intramuscular administration of droperidol has been used, at doses as high as 10 mg. [69]
Multiple human and animal studies attest to the efficacy of droperidol and haloperidol in acute methamphetamine toxicity. [70, 71, 57] However, droperidol has been subject to a Black Box warning by the US Food and Drug Administration (FDA), based on concerns of QT prolongation and the potential for torsade de pointes. As a result, some institutions restrict its use. Nevertheless, a position statement by the American Academy of Emergency Medicine concluded that droperidol is effective and safe in the treatment of nausea, headache, and agitation, and that intramuscular doses of up to 10 mg appear to be as safe and as effective as other medications used for sedation of agitated patients; that the QT-prolonging effects have been shown to be transient, and that the risk of torsade de pointes is rare at the doses administered in the ED. [69]
The FDA advises that if the potential benefit of droperidol therapy is thought to outweigh the risk of arrhythmia, the patient should undergo a 12-lead electrocardiogram (ECG) prior to initiation of treatment, to assess for a prolonged QT interval (corrected QT > 440 msec for males or 450 msec for females), and if the QT inverval is normal and droperidol is used, ECG monitoring should be continued for 2 to 3 hours after completing treatment. The American Academy of Emergency Medicine position statement agrees that a pretreatment ECG should be obtained in patients at high risk for prolonged QT, but found that a literature search did not support mandating ECG or telemetry monitoring for droperidol doses < 2.5 mg. [69, 72]
Benzodiazepines diminish methamphetamine-induced behavioral and psychiatric intoxication. [68] This class of drug is also used to terminate methamphetamine-induced seizures. [70, 73] However, benzodiazepines may cause respiratory depression and often require repeated dosing to achieve adequate sedation.
In a study of 146 patients presenting to the ED agitated, violent, or psychotic from methamphetamine, droperidol produced more rapid and profound sedation than lorazepam. Both droperidol and lorazepam produced clinically significant reductions in pulse, systolic blood pressure, respiration rate, and temperature over a 60-minute period. [57]
Newer antipsychotics such as olanzapine and risperidone have been used to treat amphetamine psychosis. [74, 75, 76] A study of 58 patients comparing haloperidol to olanzapine demonstrated that both were effective, but olanzapine had fewer adverse side effects such as extrapyramidal symptoms. [74] To date, no large studies in the ED setting have been performed. [77]
Dexmedetomidine, a sedative with analgesic, sympatholytic, and anxiolytic effects, has been used to control agitation in several case series involving amphetamine toxicity and may be useful if available in the ED. This drug has an added advantage of causing minimal respiratory depression. [78, 79, 68]
Lipid-soluble beta-blockers (eg, metoprolol), which cross the blood-brain barrier, may also mitigate agitation as well as sympathomimetic symptoms. [80, 68]
After chemical restraint has been successfully implemented, physical restraints should be loosened or removed altogether. If physical and chemical restraint is unsuccessful, rapid sequence induction, paralysis, and intubation may be required in extreme cases.
Treatment of hypertension and tachycardia
If sedation fails to reduce blood pressure, antihypertensive agents such as beta-blockers and vasodilators are effective in reversing methamphetamine-induced hypertension and tachycardia.
With regard to choice of beta-blockers, labetalol is preferred because of combined anti–alpha-adrenergic and anti–beta-adrenergic effects. Labetalol has been shown to safely lower mean arterial pressure in cocaine-positive patients. [81] Carvedilol, which like labetalol is a nonselective beta-blocker with alpha-blocking activity, may also be effective for this indication. [82, 83] Esmolol is advantageous because of its short half-life but must be administered via IV drip. Metoprolol has excellent CNS penetration characteristics and may also ameliorate agitation, as previously mentioned.
These drugs should be given IV in smaller than usual doses and titrated to effect. The concern for "unopposed alpha stimulation," with sudden rise in blood pressure or coronary artery vasoaspasm after beta-blocker therapy, is theoretical and has never been demonstrated in patients with methamphetamine toxicity. [68] An extensive evidence-based systematic review of this topic demonstrated the safety and efficacy of beta-blockers for this indication. [68] At our institution, we routinely use beta-blockers for methamphetamine-induced tachycardia and hypertension with good results.
In rare instances, afterload reduction with agents such as hydralazine, nitroprusside, or fenoldopam may be necessary. [68]
Treatment of acute coronary syndrome
The approach to the patient with methamphetamine-induced cardiac ischemia should be no different than standard of care treatment for acute coronary syndrome (ACS). Nitrates, beta-blockers, aspirin, heparin, and morphine should be administered if indicated.
Based on the latest American College of Cardiology Foundation/American Heart Association guidelines, methamphetamine- and cocaine-using patients with chest pain and suspected ACS should also receive sublingual nitroglycerin if labetalol is used to treat hypertension (systolic blood pressure >150 mm Hg) or sinus tachycardia (pulse >100 beats per min). [84]
Patients with ST-segment elevation should be triaged to thrombolytic treatment and/or catheterization with cardiology consultation.
Treatment of seizures
Treat methamphetamine-induced seizures like other seizures of unknown etiology, as follows:
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Administer benzodiazepines IV (see Medication)
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In patients who do not have IV access, an agent with intramuscular absorption can be used (eg, lorazepam, midazolam)
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After control of the acute episode, longer-acting agents such as phenobarbital, may be necessary
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Patients with methamphetamine-induced seizures are at high risk for intracranial hemorrhage and should undergo computed tomography (CT) imaging as soon as possible
Treatment of rhabdomyolysis
Suspect rhabdomyolysis and follow creatine kinase (CK) levels in patients who present to the ED with severe agitation from methamphetamine or have had prolonged periods of immobilization. Management of rhabdomyolysis is as follows:
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Administer aggressive volume therapy with IV crystalloid
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Admit the patient to the hospital after obtaining nephrology consultation
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Closely monitor renal function, vital signs, and fluid input and output
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Administration of sodium bicarbonate prevents precipitation of myoglobin in renal tubules by preventing acidic urine pH
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Early and aggressive fluid and electrolyte treatment of potential rhabdomyolysis can improve the clinical outcome and decrease potential nephrotoxicity; however, hemodialysis may be necessary in certain severe cases
Hospitalization
Critical care management may be needed for patients with any of the following:
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Persistent hypertension
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Severe rhabdomyolysis
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Seizures
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Stroke
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Coma
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Hyperthermia
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Congestive heart failure
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Acute coronary syndrome
Consultations
For body-packers, body-stuffers, or "parachuters," consultation with surgery or gastroenterology specialists may be warranted. Consult with a regional poison control center or a local medical toxicologist (certified through the American Board of Medical Toxicology and/or the American Board of Emergency Medicine) to obtain additional information and patient care recommendations. Cardiology, nephrology, and psychiatry consultation may be indicated in certain cases.
Long-Term Monitoring
Referral to a drug treatment center and/or psychiatrist may be indicated. Methamphetamine addiction is notoriously difficult to treat successfully, as it is difficult to remove the patient from the subculture involved in the production, distribution, and abuse of the drug.
A study by McKetin et al attempted to evaluate the impact of community-based drug treatment on methamphetamine use. Participants were methamphetamine users entering community-based detoxification (n = 112) or residential rehabilitation (n = 248) services and a quasi-control group of methamphetamine users (n = 101) recruited from the community. Compared to the quasi-control group, detoxification did not reduce methamphetamine use at follow-up. Residential rehabilitation showed some efficacy in reducing methamphetamine use, but the decrease was time-limited. [85]
Studies of methamphetamine-dependent patients have found that methamphetamine withdrawal is marked by sleep disruption. Withdrawal symptoms typically resolve over 2 to 3 weeks, and particularly in the first week. Depression typically improves during that time, but anxiety may not. [86, 87]
To date, phase II trials have yet to identify a pharmacologic agent that is strongly effective in helping patients achieve abstinence from methamphetamine. However, agents with novel therapeutic targets appear promising. [88]
