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Toxicity, Methamphetamine: Treatment & Medication

Author: Robert W Derlet, MD, Professor of Emergency Medicine, University of California at Davis School of Medicine; Chief Emeritus, Emergency Department, University of California at Davis Health System
Coauthor(s): Timothy E Albertson, MD, MPH, PhD, Professor of Pharmacology and Toxicology, Division Chief and Professor of Medicine, Division of Pulmonary and Critical Care Medicine, Vice-Chair, Department of Internal Medicine, University of California, Davis, School of Medicine; Professor of Anesthesiology, Associate Dean, Academic Clinical Programs, University of California, Davis Health System; Professor of Emergency Medicine and Clinical Toxicology, Davis Medical Center; Chief of Pulmonary and Critical Care, Veterans Affairs, Northern California Health Care System; Medical Director of Poison Control System, University of California at San Francisco, School of Pharmacy.; John R Richards, MD, FAAEM, Professor of Emergency Medicine, University of California at Davis School of Medicine
Contributor Information and Disclosures

Updated: Dec 4, 2009

Treatment

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 EMS providers before the patient is transported, if possible. The patient's mental function may be sufficiently impaired, precluding the patient from making 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. Animal studies suggest orally ingested amphetamine-like compounds can be decontaminated with oral activated charcoal.50 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.

  • Agitation
    • Because of the ability of methamphetamine to cause significant CNS and psychiatric activation, patients who present to EDs for acute intoxication often require physical restraint and pharmacologic intervention.
    • Treat hyperactive or agitated patients with droperidol or haloperidol, butyrophenones which antagonize CNS dopamine receptors and mitigate the excess dopamine produced from methamphetamine toxicity. Multiple human and animal studies attest to the efficacy of droperidol and haloperidol in acute methamphetamine toxicity.51,52,39 However, droperidol has been subject to a Black Box warning by the US Food and Drug Administration (FDA), and, as a result, some institutions restrict its use. The doses of these medications should be titrated to the symptoms and should be administered intravenously (see Medication).
    • Benzodiazepines enhance GABA neurotransmission and sedation, diminishing methamphetamine-induced behavioral and psychiatric intoxication. This class of drug is also used to terminate methamphetamine-induced seizures.51,53
    • 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. Droperidol and lorazepam produced clinically significant reductions in pulse, systolic blood pressure, respiration rate, and temperature over a 60-minute period.39
    • More recent antipsychotics such as olanzapine and risperidone have been used to treat amphetamine psychosis.54,55,56 A study of 58 patients comparing haloperidol to olanzapine demonstrated both were effective, but olanzapine had fewer adverse side effects such as extrapyramidal symptoms.54 To date, no large studies in the setting of the ED have been performed.
    • If physical and chemical restraint is unsuccessful, rapid sequence induction, paralysis, and intubation may be required in extreme cases.
    • After chemical restraint has been successfully implemented, physical restraints should be loosened or removed altogether.
  • 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.
    • With regard to choice of beta-blockers, labetalol is preferred because of combined anti–alpha-adrenergic and anti–beta-adrenergic effects. 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. These drugs should be given IV in smaller than usual doses and titrated to effect.
    • In rare instances, afterload reduction with agents such as hydralazine, nitroprusside, or fenoldopam may be necessary.
    • Patients with chest pain and suspected ACS should also receive sublingual nitroglycerin if their blood pressure is normal or elevated.
  • Myocardial infarction
    • The approach to the patient with methamphetamine-induced cardiac ischemia should be no different than standard of care ACS treatment. Nitrates, beta-blockers, aspirin, heparin, and morphine should be administered if indicated. Patients with ST-segment elevation detected on their ECG should be triaged to thrombolytic treatment and/or catheterization with cardiology consultation.
  • Seizures
    • Treat methamphetamine-induced seizures like other seizures of unknown etiology.
    • Administer benzodiazepines IV (see Medication).
    • In those patients who do not have IV access, an agent with IM absorption can be used (eg, lorazepam, midazolam).
    • After control of the acute episode, longer-acting agents such as phenobarbital, may be necessary.
    • Patients with methamphetamine-induced seizures are at high risk for intracranial hemorrhage and should undergo CT imaging as soon as possible.
  • Rhabdomyolysis
    • Suspect rhabdomyolysis and follow CK levels in patients who present to the ED with severe agitation from methamphetamine or have had prolonged periods of immobilization.
    • Aggressively treat patients with rhabdomyolysis with IV crystalloid and admit them to the hospital after obtaining nephrology consultation.
    • Closely monitor renal function, vital signs, and fluid input and output. By preventing acidic urine pH, the addition of sodium bicarbonate prevents precipitation of myoglobin in renal tubules.
    • 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.

Consultations

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.

Medication

The goals of pharmacotherapy are to reduce the toxic effects of the drug, reduce morbidity, and prevent complications.

GI decontaminant

Empirically used to minimize systemic absorption of the toxin.


Polyethylene glycol (PEG) solution

Laxative with strong electrolyte and osmotic effects. Cathartic actions in GI tract. May be indicated in treatment of methamphetamine ingestion in people who carry methamphetamine packages in their body. Must administer after activated charcoal. Liquid reconstituted per package instructions.

Adult

240 mL (8 oz) PO/NG q10min, to 4 L total or until rectal effluent clear and packets removed

Pediatric

Not established; recommended dose 25-40 mL/kg/h PO/NG for 4-10 h or until rectal effluent clear and packets removed

Reduces effectiveness and absorption of oral medications

Documented hypersensitivity; colitis; megacolon; bowel perforation; gastric retention; GI obstruction

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in ulcerative colitis and hot-loop polypectomy; adverse events (eg, fluid and sodium retention) rare


Activated charcoal (Liqui-Char)

Most useful if administered within 4 h of ingestion. Repeat doses may be used, especially with ingestion of sustained-release agents. Limited outcome studies exist, especially when administration is more than 1 h postingestion.
Administration of charcoal by itself (in aqueous solution), as opposed to coadministration with a cathartic, is becoming the current practice standard. This is because studies have not shown benefit from cathartics, and, while most drugs and toxins are absorbed within 30-90 min, laxatives take hours to work. Dangerous fluid and electrolyte shifts have occurred when cathartics are used in small children.
When ingested dose is known, charcoal may be administered at 10 times ingested dose of agent over 1 or 2 doses.

Adult

1 g/kg PO/NG (50-75 g usual dose); may administer 0.5 g/kg PO/NG as repeat dose if desired
Cathartic not recommended

Pediatric

Administer as in adults (12.5-25 g usual dose); cathartic not recommended

May inactivate ipecac syrup if used concomitantly; effectiveness of other medications decreases with coadministration; decreased levels occur when administered with sherbet, milk, or ice cream

Documented hypersensitivity; poisoning or overdose of mineral acids and alkalies; unprotected airway with absent gag reflex

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Protect airway before administration in patients with absent gag reflex or a depressed level of consciousness; when considering repeat dosing, monitor for active bowel sounds to minimize risk of charcoal ileus

Sedatives

Neuroleptic agents are CNS dopamine antagonists that are useful for control of agitated patients. By increasing the action of GABA, which is a major inhibitory neurotransmitter in the brain, benzodiazepines depress all levels of CNS, including limbic and reticular formation.


Haloperidol (Haldol)

DOC for patients with acute psychosis when no contraindications are present. Parenteral dosage form may be admixed in syringe with 2-mg lorazepam for better anxiolytic effects. May be administered IM if unable to establish IV access.

Adult

2.5 mg IV/IM initial for mildly agitated patients
5 mg IV/IM initial for more severely agitated patients
additional doses q5-10min; may titrate up to 10-15 mg prn

Pediatric

<3 years: Not established
3-12 years: 0.05-0.15 mg/kg/d divided/bid/tid
>12 years: Administer as in adults

May increase TCA serum-concentrations and hypotensive action of antihypertensive agents; phenobarbital or carbamazepine may decrease effects; coadministration with anticholinergics may increase intraocular pressure; encephalopathylike syndrome associated with concurrent administration with lithium

Documented hypersensitivity; narrow-angle glaucoma, bone marrow suppression, severe cardiac or liver disease, severe hypotension, or subcortical brain damage; Parkinsonism

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Severe neurotoxicity manifesting as rigidity or inability to walk or talk may occur in patients with thyrotoxicosis also receiving antipsychotics; if IV/IM, monitor for hypotension; caution in CNS depression or cardiac disease; if history of seizures, benefits must outweigh risks; significant increase in body temperature may indicate intolerance to antipsychotics (discontinue if this occurs); do not use decanoate salt IV


Droperidol (Inapsine)

Somewhat faster-acting and more sedating than haloperidol but more likely to cause hypotension. May exert antipsychotic activity through dopaminergic system. Evidence suggests that it alters dopamine action in CNS. Administer IV in small boluses and titrate to effect. IM route may also be used if IV access is not yet established.

Adult

2.5 mg IV initial for mildly agitated patients
5 mg IV initial for more severely agitated patients
Additional doses q5-10min; may titrate up to 20 mg prn

Pediatric

<12 years: Not established
>12 years: Administer as in adults

May increase toxicity of CNS depressants

Documented hypersensitivity; Parkinsonism; patients who have prolonged QT interval

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Some individuals are highly sensitive and may require only one initial dose; hypovolemic patients may experience hypotension; may decrease pulmonary arterial pressure; tardive dyskinesia in patients receiving droperidol is 40%; elderly persons may experience high rate of extrapyramidal reactions; life-threatening arrhythmias may occur


Diazepam (Valium)

Administered IV. Additional doses are titrated to effect. Less effective than the butyrophenones in controlling agitation.

Adult

5 mg IV bolus; titrate upward to effect, giving additional drug q5-10min; in very severe cases, up to 50 mg may be required

Pediatric

0.1-0.2 mg/kg IV q15-20min

May cause profound sedation with other CNS depressants

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Monitor for excess CNS or respiratory depression with higher doses


Lorazepam (Ativan)

Sedative hypnotic with short onset of effects and relatively long half-life.
Benzodiazepine of choice in the ED. Can be given PO or SL (for rapid effect in panic attack) and IM or IV (mixed in the same syringe with the antipsychotic). Has longer CNS effects than diazepam and is preferred over antipsychotics for treatment of psychosis secondary to acute intoxication with hallucinogens, cocaine, PCP, and stimulants. Can be used as adjunctive therapy in nonorganic acute psychosis in which DOC is a high potency antipsychotic.
If given IM, may take 30-60 min to observe desired effect.

Adult

1 mg IV bolus; may give additional doses q10-15min; not to exceed 8 mg

Pediatric

0.05-0.1 mg/kg IV over 1-2 min; may repeat, if needed

Toxicity of benzodiazepines in CNS increases when used concurrently with alcohol, phenothiazines, barbiturates, and MAOIs

Documented hypersensitivity; preexisting CNS depression, hypotension, and narrow-angle glaucoma

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, or Parkinson disease; watch for excess CNS or respiratory depression with higher doses


Midazolam (Versed)

Used as alternative in termination of refractory status epilepticus. Because water soluble, takes approximately 3 times longer than diazepam to peak EEG effects. Thus, clinician must wait 2-3 min to fully evaluate sedative effects before initiating procedure or repeating dose. Has twice the affinity for benzodiazepine receptors than diazepam. May be administered IM if unable to obtain vascular access.

Adult

0.01-0.05 mg/kg IV (usually 0.5-4 mg, up to 10 mg) slowly over several min; may repeat q10-15min until adequate response achieved

Pediatric

<32 weeks: 0.5 mcg/kg/min IV infusion
>32 weeks: 1 mcg/kg/min IV infusion
Children: 0.05-0.2 mg/kg IV over 2-3 min, followed by 1-2 mcg/kg/min IV continuous infusion
Status epilepticus (refractory to standard therapy), >2 months and children: 0.15 mg/kg IV followed by continuous infusion of 1 mcg/kg/min IV, titrating dose upward q5min until seizures controlled

Sedative effects may be antagonized by theophyllines; narcotics, cimetidine, ethanol, and erythromycin may accentuate sedative effects because of decreased clearance; reduce dose of thiopental by 15% when using together

Documented hypersensitivity; preexisting hypotension, narrow-angle glaucoma, and sensitivity to propylene glycol (diluent)

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in congestive heart failure, pulmonary disease, renal impairment, hepatic failure, neuromuscular disease, hypotension, and patients >60 y; monitor for respiratory depression with high or repeated doses; consider lower dosages with organic brain syndrome, and patients who may have inhibition of benzodiazepine metabolism and clearance (eg, using nicotine, taking cimetidine)

Cardiovascular agents

Used to control catecholamine-induced hypertension and tachycardia.


Labetalol (Normodyne, Trandate)

Blocks beta1-, alpha-, and beta2-adrenergic receptor sites, decreasing blood pressure. When given IV, acts primarily as a beta-receptor antagonist.

Adult

Lower than usual starting dose: 10 mg IV over 2 min initial; may repeat 10 mg IV q5-10min until BP control is obtained; not to exceed 300 mg/dose

Pediatric

Not established

Decreases effect of diuretics and increases toxicity of methotrexate, lithium, and salicylates; may diminish reflex tachycardia, resulting from nitroglycerin use, without interfering with hypotensive effects; cimetidine may increase levels in blood; glutethimide may decrease effects by inducing microsomal enzymes

Documented hypersensitivity; cardiogenic shock, pulmonary edema, bradycardia, atrioventricular block, uncompensated congestive heart failure, reactive airway disease, and severe bradycardia

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in impaired hepatic function; discontinue therapy if signs of liver dysfunction are present; in elderly patients, a lower response rate and higher incidence of toxicity may be observed

More on Toxicity, Methamphetamine

Overview: Toxicity, Methamphetamine
Differential Diagnoses & Workup: Toxicity, Methamphetamine
Treatment & Medication: Toxicity, Methamphetamine
Follow-up: Toxicity, Methamphetamine
References
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Further Reading

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Keywords

amphetamine, meth toxicity, methamphetamine abuse, signs of methamphetamine use, ice, crystal meth, meth overdose, methamphetamine poisoning, meth side effects, methamphetamine use, stimulant, euphoria, methamphetamine intoxication, speedballing

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Contributor Information and Disclosures

Author

Robert W Derlet, MD, Professor of Emergency Medicine, University of California at Davis School of Medicine; Chief Emeritus, Emergency Department, University of California at Davis Health System
Robert W Derlet, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Association for the Advancement of Science, Infectious Diseases Society of America, Society for Academic Emergency Medicine, and Wilderness Medical Society
Disclosure: Nothing to disclose.

Coauthor(s)

Timothy E Albertson, MD, MPH, PhD, Professor of Pharmacology and Toxicology, Division Chief and Professor of Medicine, Division of Pulmonary and Critical Care Medicine, Vice-Chair, Department of Internal Medicine, University of California, Davis, School of Medicine; Professor of Anesthesiology, Associate Dean, Academic Clinical Programs, University of California, Davis Health System; Professor of Emergency Medicine and Clinical Toxicology, Davis Medical Center; Chief of Pulmonary and Critical Care, Veterans Affairs, Northern California Health Care System; Medical Director of Poison Control System, University of California at San Francisco, School of Pharmacy.
Timothy E Albertson, MD, MPH, PhD is a member of the following medical societies: American College of Chest Physicians and Sigma Xi
Disclosure: Nothing to disclose.

John R Richards, MD, FAAEM, Professor of Emergency Medicine, University of California at Davis School of Medicine
John R Richards, MD, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Medical Editor

Edward A Michelson, MD, Program Director, Associate Professor, Department of Emergency Medicine, University Hospital Health Systems in Cleveland
Edward A Michelson, MD is a member of the following medical societies: American College of Emergency Physicians, National Association of EMS Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

John T VanDeVoort, PharmD, Regional Director of Pharmacy, Sacred Heart & St. Joseph's Hospitals
John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists
Disclosure: Nothing to disclose.

Managing Editor

Fred Harchelroad, MD, FACMT, FAAEM, FACEP, Chair, Department of Emergency Medicine, Director of Medical Toxicology - Allegheny General Hospital, Associate Professor, Department of Emergency Medicine, Drexel University College of Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD, Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital
Disclosure: Nothing to disclose.

 
 
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