eMedicine Specialties > Emergency Medicine > Toxicology

Toxicity, Methamphetamine

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
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

Updated: Nov 18, 2009

Introduction

Background

Over the past 25 years, methamphetamine use has increased rapidly throughout the world. In the United States, all regions have experienced a significant increase in the number of persons using the drug as well as medical complications seen in emergency departments (EDs). Methamphetamine and related compounds can produce euphoria and stimulant effects and share many of the same toxic clinical effects seen with other stimulants such as cocaine. The ease of synthesis from inexpensive and readily obtainable chemicals has led to the widespread and rampant abuse of this dangerous drug.
 
The euphoria produced by methamphetamine is similar to that produced by cocaine. Methamphetamine may be taken orally, intravenously, snorted, or smoked. Patients who inhale the smokable form of methamphetamine (ie, ice) experience an immediate euphoria similar to that of crack cocaine, but the effects may last much longer.^1,2 North American methamphetamine abusers are predominantly Caucasian males in their 30s and 40s. Recently, epidemic abuse has been described in adolescents; they cite availability, low cost, and a longer duration of action than cocaine as reasons for their drug preference.
 
The medical history of amphetamine-like compounds extends back nearly 100 years. A Japanese pharmacologist first synthesized methamphetamine in 1919. A more detailed analysis of the pharmacology of amphetamine derived from the basic phenylethylamine structure was reported in 1930. In the 1930s, amphetamine was introduced in the form of inhalers for rhinitis and asthma treatment. The stimulant, euphoric, and anorectic effects of amphetamine were quickly recognized, leading to its abuse. In 1937, a report that amphetamine enhanced intellectual performance and wakefulness further contributed to its popularity. Amphetamines were used extensively by Allied and Axis armed forces during World War II and during Operation Desert Storm to increase wakefulness and attention.^3,2  

In the late 1950s, initial federal controls were enacted; however, in spite of additional regulation and increased enforcement, amphetamines continued to be used by students, athletes, shift workers, long haul drivers, and for weight loss. The Controlled Substance Act of 1970 stringently regulated the manufacture of amphetamine. Despite attempts to decrease production, illicit methamphetamine use continues to increase.²

Pathophysiology

Amphetamines stimulate the central nervous system (CNS), which results in several clinical effects such as inducing euphoria, intensifying emotions, altering self-esteem, and increasing alertness, aggression, and sexual appetite.² In the CNS, presynaptic reuptake of catecholamines (ie, dopamine, norepinephrine) is blocked, causing hyperstimulation at selected postsynaptic neuron receptors. Indirect sympathomimetic effects of amphetamines are also caused by blocking presynaptic vesicular storage and by reducing cytoplasmic destruction of catecholamines by inhibiting mitochondrial monoamine oxidase. Indirectly, these hyperstimulated neurons can stimulate various other noncatecholaminergic central and peripheral nervous pathways. Changes in mood, excitation, motor movements, sensory perception, and appetite appear to be mediated more directly by CNS dopaminergic alterations. It has been postulated that serotonin alterations also contribute to mood changes, psychotic behavior, and aggressiveness.
 
In humans, the half-life of methamphetamine ranges from 10-20 hours, depending on the urine pH, history of recent use, and dosage. Metabolism occurs faster in acidic urine. Methamphetamine has greater CNS effects compared with D-amphetamine of equal milligram quantity. Methamphetamine has more effective absorption into critical behavior-controlling neurons in the CNS and has a prolonged half-life. The majority of methamphetamine is metabolized to amphetamine, which provides further CNS stimulation. Methamphetamine is absorbed readily from the gut, airway, nasopharynx, muscle, placenta, and vagina. Peak plasma levels are observed approximately 30 minutes after intravenous or intramuscular routes and 2-3 hours after ingestion. Rapid tissue redistribution occurs with steady-state cerebrospinal fluid levels at 80% of plasma levels. Hepatic conjugation pathways with glucuronide and glycine addition result in inactivation and urine excretion of metabolites.
 
When methamphetamine is used with ethanol, increased psychological and cardiac effects are observed. This is presumed to be the result of pharmacodynamic rather than pharmacokinetic interactions. Similarly, the increased toxicity of concomitant opioids and amphetamines (ie, speedballing), appear to result from pharmacodynamic interactions. The euphoric effects produced by methamphetamine, cocaine, and various designer amphetamines are similar and may be difficult to clinically differentiate. A distinguishing clinical feature is the longer pharmacokinetic and pharmacodynamic half-life of methamphetamine, which may be as much as 10 times longer than cocaine. Because of the variability in quality and concentration of illicitly purchased methamphetamines, the clinical observation of toxic effects is more relevant than estimated total ingested dose.

Frequency

United States

Methamphetamine use is widespread, predominantly in Midwest, Southwest, Northwest, and Western States.

International

Methamphetamine use is widespread, predominantly in North America, Eastern Europe, and Southeast Asia.

Mortality/Morbidity

Acute methamphetamine overdose may result in sympathetic overdrive, cardiovascular collapse, rhabdomyolysis, ventricular tachyarrhythmia, and death.

Chronic methamphetamine use may result in atherosclerosis, hypertension, myocardial infarction, congestive heart failure, soft tissue infection, periodontal disease, sepsis, changes in cognitive CNS function, and personality disorders.

Race

In North America, methamphetamine use is predominantly by Caucasians.

Sex

Males are more likely to abuse methamphetamine than females.

Age

Peak methamphetamine use is observed in the 20- to 40-year-old range.

Clinical

History

Signs and symptoms of methamphetamine use:

• Cardiovascular:
  • Chest pain,⁴ aortic dissection, myocardial ischemia/infarction
  • Palpitations, tachyarrhythmia
  • Dyspnea and edema
  • Hypertension 
• Central nervous system:
  • Agitation, violent behavior, self-harm
  • Coma
  • New-onset seizure
  • Emotional lability, confusion, psychosis, paranoia, hypersexuality, and hallucinations
  • Headache
• Respiratory:
  • Dyspnea
  • Wheezing
  • Pneumothorax
• Skin:
  • Delusional parasitosis
  • Abscess, cellulitis
• Gastrointestinal:
  • Abdominal pain
  • Obstruction
• Dental: Caries, peridental abscess

Physical

• Cardiovascular:
  • Tachycardia and hypertension is frequently observed.
  • Atrial and ventricular arrhythmias may occur.
  • Chest pain from cardiac ischemia and infarction following methamphetamine use has been reported. Patients are at risk because of accelerated atherosclerosis from chronic use. Acute aortic dissection or aneurysm has been associated with methamphetamine abuse.
  • Hypotension may be observed with methamphetamine overdose with profound depletion of catecholamines.
  • Acute and chronic cardiomyopathy results directly from methamphetamine cardiac toxicity and indirectly from chronic hypertension and ischemia. Intravenous use may result in endocarditis. Patients may present with dyspnea, edema, and other signs of acute congestive heart failure (CHF) exacerbation.
• Central nervous system:
  • New-onset seizures may occur from direct CNS methamphetamine toxicity.
  • Acute and chronic methamphetamine exposure has been associated with a jerking, choreoathetoid movement disorder. These repetitive movements, hyperactivity, and inability to focus thought have been referred to as "tweaking."
  • Headache and cerebrovascular accidents with focal neurologic deficits may be caused by hemorrhage or vasospasm, cerebral edema, and cerebral vasculitis.
  • Acute psychosis, agitation, violence, and paranoia frequently results from alteration in CNS dopamine, serotonin, and glutamate pathways.
  • Coma may result from depletion of catecholamine stores and/or concomitant ingestion of sedatives such as ethanol or narcotics.
• Respiratory:
  • Barotrauma, including pneumomediastinum, pneumothorax, and pneumopericardium may result from forceful inhalation.
  • Acute noncardiogenic pulmonary edema and pulmonary hypertension may result from acute and chronic use, as well as from adulterants introduced during intravenous use such as talc or cornstarch.
  • Wheezing from reactive airway disease may be induced by methamphetamine.
• Gastrointestinal:
  • Hepatocellular damage has been reported with methamphetamine after acute and chronic abuse. Direct effects such as hypotension, hepatotoxic contaminants, hepatic vasoconstriction, lipid peroxidation, occult viral causes, necrotizing angiitis have been postulated.
  • Severe abdominal pain may result from acute mesenteric vasoconstriction. Methamphetamine has also been associated with the formation of ulcers and ischemic colitis.
  • Necrotizing angiitis with arterial aneurysms and sacculations have been observed in the liver, pancreas, and small bowel of methamphetamine drug abusers.

• Renal:
  • Renal failure associated with amphetamines has been related to hypoxemia, rhabdomyolysis, necrotizing angiitis, acute interstitial nephritis, and cardiovascular shock with subsequent acute tubular necrosis.
• Skin:
  • Delusions of parasitosis and chronic skin-picking may result in neurotic excoriations and prurigo nodularis ("speed bumps").
  • Methamphetamine injectors frequently present with abscess and cellulitis, which is frequently blamed on a "spider bite."
  • Lab workers involved with illicit methamphetamine production may present with extensive thermal and/or chemical burns.
• Dental:
  • Severe caries, especially of the maxillary teeth, is commonly seen in chronic methamphetamine users ("meth mouth") and results from maxillary artery vasoconstriction, xerostomia, and poor hygiene.^5,6
• Pregnancy:
  • Methamphetamine use during pregnancy can be fatal to the mother and fetus.^7,8 Methamphetamine has been shown to cause placental vasoconstriction and interfere with placental monoamine transporters resulting in spontaneous abortion.⁹
  • Methamphetamine is present in the breastmilk of postnatal women abusers. A case of infant death from methamphetamine-toxic breastmilk ingestion has been reported.

Causes

• Illicit production of methamphetamine
  • Methamphetamine is relatively easy and inexpensive to synthesize, and illicit production occurs in home kitchens, workshops, recreational vehicles, and rural cabins. Instructions for synthesis can be found on the Internet and the precursors are not difficult to obtain.
  • Methamphetamine is a derivative of phenylethylamine. The substances differ structurally in that a methyl group attaches to the terminal nitrogen to form methamphetamine.
  • The federal government and some states have enacted laws decreasing the availability of necessary precursor chemicals such as ephedrine. Many of these agents can still be obtained in other countries.
  • A common method of synthesis begins with ephedrine, which is reduced to methamphetamine using hydriodic acid and red phosphorus.
  • Alternative approaches include using a different acid, a different catalyst, or a substituted ephedrine (eg, chloroephedrine, methylephedrine).
  • The methamphetamine produced by ephedrine reduction is a lipid-soluble pure base form, which is fairly volatile and can evaporate if left exposed to room air temperature. This product is converted to the water-soluble form, methamphetamine hydrochloride (HCl) salt.
  • Illicitly synthesized methamphetamine is frequently contaminated by nonstimulant organic or inorganic impurities. Poisoning from heavy metals, such as lead and mercury, or from carcinogenic solvents used in the synthesis process, has been reported.
  • Street methamphetamine may be mixed with other drugs, including cocaine and phencyclidine.
  • Making ice, the smokable form of methamphetamine, from standard quality methamphetamine HCl is essentially a purification process.

Differential Diagnoses

Workup

Laboratory Studies

• Laboratory studies should be obtained based on the patient's symptoms. Although hair and saliva analysis may be obtained, most toxicological monitoring or testing is performed with urine and blood samples.
• Obtain a complete blood count (CBC) and chemistry panel to assess renal and electrolyte function.
• Measure creatine kinase (CK) and/or myoglobin levels to exclude rhabdomyolysis. Obtain serial troponin levels if there is concern for myocardial ischemia, and a beta natriuretic peptide (BNP) level if acute congestive heart failure (CHF) is suspected.
• Obtain a pregnancy test in women of childbearing age.
• Toxicology screens are useful for patients who cannot or will not disclose drug use history and for pediatric patients with new-onset seizure.

Imaging Studies

• Order a chest radiograph for patients with pulmonary symptoms or chest trauma.
• In patients with altered mental status, perform a head CT scan to exclude intracranial bleeding. Such bleeding may be the result of either methamphetamine-induced hypertension or associated head trauma.
• Patients who are suspected body-packers should undergo abdominal imaging.

Other Tests

• Obtain an ECG for patients with chest pain, altered mental status, and tachycardia.

Procedures

• Lumbar puncture may be indicated in patients with altered mental status to rule out meningitis or subarachnoid hemorrhage.

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. 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. 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.
  • 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.
  • 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.

Dosing

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

Interactions

Reduces effectiveness and absorption of oral medications

Contraindications

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

Precautions

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.

Dosing

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

Interactions

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

Contraindications

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

Precautions

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.

Dosing

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

Interactions

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

Contraindications

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

Precautions

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.

Dosing

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

Interactions

May increase toxicity of CNS depressants

Contraindications

Documented hypersensitivity; Parkinsonism; patients who have prolonged QT interval

Precautions

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.

Dosing

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

Interactions

May cause profound sedation with other CNS depressants

Contraindications

Documented hypersensitivity

Precautions

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.

Dosing

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

Interactions

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

Contraindications

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

Precautions

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.

Dosing

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

Interactions

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

Contraindications

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

Precautions

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.

Dosing

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

Interactions

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

Contraindications

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

Precautions

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

Follow-up

Further Inpatient Care

• Critical care management may be needed for patients with persistent hypertension, severe rhabdomyolysis, seizures, stroke, coma, hyperthermia, CHF, or acute coronary ischemic syndrome.

Further Outpatient Care

• Referral to drug treatment center and/or psychiatrist may be indicated

Deterrence/Prevention

• Methamphetamine addiction is notoriously difficult to treat successfully, as it is difficult to remove the patient from the subculture that surrounds the production, distribution, and abuse of the drug.

Complications

• Complications of methamphetamine use include the following:
  • Rhabdomyolysis
  • Renal failure
  • Seizures
  • Stroke with permanent deficits
  • Coma
  • Acute coronary ischemia or infarction
  • Congestive heart failure (CHF)
  • Ventricular arrhythmias
  • Psychosis
  • Death
  • HIV and viral hepatitis
  • Periodontal disease
  • Skin infections

Prognosis

• Prognosis is generally good with rapid and appropriate treatment, assuming that the patient does not present with one of the above complications.

Patient Education

• For excellent patient education resources, visit eMedicine's Poisoning - First Aid and Emergency Center, Mental Health and Behavior Center, and Substance Abuse Center. Also, see eMedicine's patient education articles Drug Dependence & Abuse, Substance Abuse, Poisoning, Club Drugs, and Activated Charcoal.
• For more information, see Medscape's Addiction Resource Center.

Miscellaneous

Medicolegal Pitfalls

• Failure to diagnose and treat patients with methamphetamine toxicity if they have hyperthermia or rhabdomyolysis
• Failure to obtain a head CT scan in patients with methamphetamine toxicity who present with mental status changes that do not normalize with pharmacologic treatment; thus, failing to diagnose an intracerebral hemorrhage
• Failure to diagnose myocardial infarction or unstable angina in methamphetamine-intoxicated patients
• Failure to consider other cause of altered mental status which may be concomitant with methamphetamine use

Special Concerns

• Consider the possibility of methamphetamine or amphetamine toxicity in children who present with first-time seizures; several studies have noted amphetamine-positive drug screens in this patient population.
• Healthcare personnel should be aware regarding blood-borne exposure and risk of HIV, hepatitis B, and hepatitis C.

References

1. Beebe DK, Walley E. Smokable methamphetamine ('ice'): an old drug in a different form. Am Fam Physician. Feb 1 1995;51(2):449-53. [Medline].

2. Derlet RW, Heischober B. Methamphetamine. Stimulant of the 1990s?. West J Med. Dec 1990;153(6):625-8. [Medline].

3. Emonson DL, Vanderbeek RD. The use of amphetamines in U.S. Air Force tactical operations during Desert Shield and Storm. Aviat Space Environ Med. Mar 1995;66(3):260-3. [Medline].

4. Diercks DB, Kirk JD, Turnipseed SD, Amsterdam EA. Evaluation of patients with methamphetamine- and cocaine-related chest pain in a chest pain observation unit. Crit Pathw Cardiol. Dec 2007;6(4):161-4. [Medline].

5. Richards JR, Brofeldt BT. Patterns of tooth wear associated with methamphetamine use. J Periodontol. Aug 2000;71(8):1371-4. [Medline].

6. Hamamoto DT, Rhodus NL. Methamphetamine abuse and dentistry. Oral Dis. Jan 2009;15(1):27-37. [Medline].

7. Stewart JL, Meeker JE. Fetal and infant deaths associated with maternal methamphetamine abuse. J Anal Toxicol. Oct 1997;21(6):515-7. [Medline].

8. Catanzarite VA, Stein DA. 'Crystal' and pregnancy--methamphetamine-associated maternal deaths. West J Med. May 1995;162(5):454-7. [Medline].

9. Ramamoorthy JD, Ramamoorthy S, Leibach FH, Ganapathy V. Human placental monoamine transporters as targets for amphetamines. Am J Obstet Gynecol. Dec 1995;173(6):1782-7. [Medline].

10. Albertson TE, Walby WF, Derlet RW. Stimulant-induced pulmonary toxicity. Chest. Oct 1995;108(4):1140-9. [Medline].

11. Bashour TT. Acute myocardial infarction resulting from amphetamine abuse: a spasm- thrombus interplay?. Am Heart J. Dec 1994;128(6 Pt 1):1237-9. [Medline].

12. Burton BT. Heavy metal and organic contaminants associated with illicit methamphetamine production. NIDA Res Monogr. 1991;115:47-59. [Medline].

13. Cherner M, Letendre S, Heaton RK. Hepatitis C augments cognitive deficits associated with HIV infection and methamphetamine. Neurology. 2005;64:1343-47. [Medline].

14. Conn C, Dawson M, Baker AT, et al. Identification of n-acetylmethamphetamine in a sample of illicitly synthesized methamphetamine. J Forensic Sci. Jul 1996;41(4):645-7. [Medline].

15. Das-Douglas M, Colfax G, Moss AR, Bangsberg DR, Hahn JA. Tripling of Methamphetamine/Amphetamine Use among Homeless and Marginally Housed Persons, 1996-2003. J Urban Health. Dec 27 2007;[Medline].

16. Davis GG, Swalwell CI. Acute aortic dissections and ruptured berry aneurysms associated with methamphetamine abuse. J Forensic Sci. Nov 1994;39(6):1481-5. [Medline].

17. Derlet RW, Albertson TE, Rice P. Protection against d-amphetamine toxicity. Am J Emerg Med. Mar 1990;8(2):105-8. [Medline].

18. Derlet RW, Rice P, Horowitz BZ, Lord RV. Amphetamine toxicity: experience with 127 cases. J Emerg Med. Mar-Apr 1989;7(2):157-61. [Medline].

19. Gold MS, Kobeissy FH, Wang KK, Merlo LJ, Bruijnzeel AW, Krasnova IN, et al. Methamphetamine- and trauma-induced brain injuries: comparative cellular and molecular neurobiological substrates. Biol Psychiatry. July 2009;66:118-27. [Medline].

20. He SY, Matoba R, Fujitani N, et al. Cardiac muscle lesions associated with chronic administration of methamphetamine in rats. Am J Forensic Med Pathol. Jun 1996;17(2):155-62. [Medline].

21. Hendrickson RG, Cloutier R, McConnell KJ. Methamphetamine-related emergency department utilization and cost. Acad Emerg Med. Jan 2008;15(1):23-31. [Medline].

22. Katsumata S, Sato K, Kashiwade H, et al. Sudden death due presumably to internal use of methamphetamine. Forensic Sci Int. Dec 1993;62(3):209-15. [Medline].

23. Logan BK. Methamphetamine and driving impairment. J Forensic Sci. May 1996;41(3):457-64. [Medline].

24. MacKenzie RG, Heischober B. Methamphetamine. Pediatr Rev. Sep 1997;18(9):305-9. [Medline].

25. Matteucci MJ, Auten JD, Crowley B, Combs D, Clark RF. Methamphetamine exposures in young children. Pediatr Emerg Care. Sep 2007;23(9):638-40. [Medline].

26. Nestor TA, Tamamoto WI, Kam TH, Schultz T. Crystal methamphetamine-induced acute pulmonary edema: a case report. Hawaii Med J. Nov 1989;48(11):457-8, 460. [Medline].

27. Rhee KJ, Albertson TE, Douglas JC. Choreoathetoid disorder associated with amphetamine-like drugs. Am J Emerg Med. Mar 1988;6(2):131-3. [Medline].

28. Richards JR, Bretz SW, Johnson EB, Turnipseed SD, Brofeldt BT, Derlet RW. Methamphetamine abuse and emergency department utilization. West J Med. Apr 1999;170(4):198-202. [Medline].

29. Richards JR, Derlet RW, Duncan DR. Methamphetamine toxicity: treatment with a benzodiazepine versus a butyrophenone. Eur J Emerg Med. Sep 1997;4(3):130-5. [Medline].

30. Richards JR, Johnson EB, Stark RW, Derlet RW. Methamphetamine abuse and rhabdomyolysis in the ED: a 5-year study. Am J Emerg Med. Nov 1999;17(7):681-5. [Medline].

31. Schermer CR, Wisner DH. Methamphetamine use in trauma patients: a population-based study. J Am Coll Surg. Nov 1999;189(5):442-9. [Medline].

32. Turnipseed SD, Richards JR, Kirk JD. Frequency of acute coronary syndrome in patients presenting to the emergency department with chest pain after methamphetamine use. J Emerg Med. May 2003;24(4):369-73. [Medline].

33. Watts DJ, McCollester L. Methamphetamine-induced myocardial infarction with elevated troponin I. Am J Emerg Med. Jan 2006;24(1):132-4. [Medline].

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

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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