Methamphetamine Toxicity Treatment & Management
- Author: John R Richards, MD, FAAEM; Chief Editor: Asim Tarabar, MD more...
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.
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. These medications should be administered intravenously (IV), with doses titrated to the symptoms (see Medication).
Multiple human and animal studies attest to the efficacy of droperidol and haloperidol in acute methamphetamine toxicity.[55, 56, 42] 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 torsades de pointes. As a result, some institutions restrict its use. It is important to note that the Black Box warning specifies dementia-related psychosis and is not supported by the literature for doses below 2.5 mg.
Benzodiazepines diminish methamphetamine-induced behavioral and psychiatric intoxication. This class of drug is also used to terminate methamphetamine-induced seizures.[55, 58] 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.
Newer antipsychotics such as olanzapine and risperidone have been used to treat amphetamine psychosis.[59, 60, 61] 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. To date, no large studies in the setting of the ED have been performed.
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.[63, 64, 54]
Lipid-soluble beta-blockers (eg, metoprolol), which cross the blood-brain barrier, may also mitigate agitation as well as sympathomimetic symptoms.[65, 54]
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. Carvedilol, which like labetalol is a nonselective beta-blocker with alpha-blocking activity, may also be effective for this indication.[67, 68] 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. An extensive evidence-based systematic review of this topic demonstrated the safety and efficacy of beta-blockers for this indication. 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.
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).
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:
Administer benzodiazepines IV (see Medication)
In patients who do not have IV access, an agent with intramuscular 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 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:
Administer aggressive volume therapy with IV crystalloid
Admit the patient to the hospital after obtaining nephrology consultation
Closely monitor renal function, vital signs, and fluid input and output
Administration of sodium bicarbonate prevents precipitation of myoglobin in renal tubules by preventing acidic urine pH
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
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.
United Nations Office on Drugs and Crime (UNODC). World Drug Report 2015. Available at http://www.unodc.org/documents/wdr2015/World_Drug_Report_2015.pdf. Accessed: September 11, 2015.
Drug Abuse Warning Network (DAWN). 2011: National Estimates of Drug-Related Emergency Department Visits. Available at http://www.samhsa.gov/data/2k13/DAWN2k11ED/DAWN2k11ED.pdf. Accessed: September 11, 2015.
Vearrier D, Greenberg MI, Miller SN, Okaneku JT, Haggerty DA. Methamphetamine: history, pathophysiology, adverse health effects, current trends, and hazards associated with the clandestine manufacture of methamphetamine. Dis Mon. 2012 Feb. 58(2):38-89. [Medline].
Richards JR. Amphetamine derivatives. Cole SM. New research on street drugs. New York: Nova; 2006. chap 5.
Hendrickson RG, Horowitz BZ, Norton RL, Notenboom H. "Parachuting" meth: a novel delivery method for methamphetamine and delayed-onset toxicity from "body stuffing". Clin Toxicol (Phila). 2006. 44(4):379-82. [Medline].
Richards JR, Bretz SW, Johnson EB, Turnipseed SD, Brofeldt BT, Derlet RW. Methamphetamine abuse and emergency department utilization. West J Med. 1999 Apr. 170(4):198-202. [Medline].
Hendrickson RG, Cloutier R, McConnell KJ. Methamphetamine-related emergency department utilization and cost. Acad Emerg Med. 2008 Jan. 15(1):23-31. [Medline].
Uhlmann S, Debeck K, Simo A, Kerr T, Montaner JS, Wood E. Crystal methamphetamine initiation among street-involved youth. Am J Drug Alcohol Abuse. 2013 Nov 5. [Medline].
Kenagy DN, Bird CT, Webber CM, Fischer JR. Dextroamphetamine use during B-2 combat missions. Aviat Space Environ Med. 2004 May. 75(5):381-6. [Medline].
Panenka WJ, Procyshyn RM, Lecomte T, MacEwan GW, Flynn SW, Honer WG, et al. Methamphetamine use: a comprehensive review of molecular, preclinical and clinical findings. Drug Alcohol Depend. 2013 May 1. 129(3):167-79. [Medline].
Volkow ND, Fowler JS, Wang GJ, Shumay E, Telang F, Thanos PK, et al. Distribution and pharmacokinetics of methamphetamine in the human body: clinical implications. PLoS One. 2010 Dec 7. 5(12):e15269. [Medline]. [Full Text].
Cruickshank CC, Dyer KR. A review of the clinical pharmacology of methamphetamine. Addiction. 2009 Jul. 104(7):1085-99. [Medline].
Katsumata S, Sato K, Kashiwade H, et al. Sudden death due presumably to internal use of methamphetamine. Forensic Sci Int. 1993 Dec. 62(3):209-15. [Medline].
Kashani J, Ruha AM. Methamphetamine toxicity secondary to intravaginal body stuffing. J Toxicol Clin Toxicol. 2004. 42(7):987-9. [Medline].
Kirkpatrick MG, Gunderson EW, Levin FR, Foltin RW, Hart CL. Acute and residual interactive effects of repeated administrations of oral methamphetamine and alcohol in humans. Psychopharmacology (Berl). 2011 Jul 12. [Medline].
Zhang JX, Zhang da M, Han XG. Identification of impurities and statistical classification of methamphetamine hydrochloride drugs seized in China. Forensic Sci Int. 2008 Nov 20. 182(1-3):13-9. [Medline]. [Full Text].
DrugFacts: Methamphetamine. National Institute on Drug Abuse. Available at http://www.drugabuse.gov/publications/drugfacts/methamphetamine. Accessed: October 8, 2014.
National Survey of Drug Use and Health. National Institute on Drug Abuse. Available at http://www.drugabuse.gov/national-survey-drug-use-health. Accessed: October 7, 2014.
Swanson SM, Sise CB, Sise MJ, Sack DI, Holbrook TL, Paci GM. The scourge of methamphetamine: impact on a level I trauma center. J Trauma. 2007 Sep. 63(3):531-7. [Medline].
Carvalho M, Carmo H, Costa VM, Capela JP, Pontes H, Remião F, et al. Toxicity of amphetamines: an update. Arch Toxicol. 2012 Aug. 86(8):1167-231. [Medline].
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. 2007 Dec. 6(4):161-4. [Medline].
Hawley LA, Auten JD, Matteucci MJ, Decker L, Hurst N, Beer W, et al. Cardiac complications of adult methamphetamine exposures. J Emerg Med. 2013 Dec. 45(6):821-7. [Medline].
Won S, Hong RA, Shohet RV, Seto TB, Parikh NI. Methamphetamine-Associated Cardiomyopathy. Clin Cardiol. 2013 Aug 27. [Medline].
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. 2003 May. 24(4):369-73. [Medline].
Watts DJ, McCollester L. Methamphetamine-induced myocardial infarction with elevated troponin I. Am J Emerg Med. 2006 Jan. 24(1):132-4. [Medline].
Davis GG, Swalwell CI. Acute aortic dissections and ruptured berry aneurysms associated with methamphetamine abuse. J Forensic Sci. 1994 Nov. 39(6):1481-5. [Medline].
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]. [Full Text].
Rhee KJ, Albertson TE, Douglas JC. Choreoathetoid disorder associated with amphetamine-like drugs. Am J Emerg Med. 1988 Mar. 6(2):131-3. [Medline].
Bowyer JF, Thomas M, Schmued LC, Ali SF. Brain region-specific neurodegenerative profiles showing the relative importance of amphetamine dose, hyperthermia, seizures, and the blood-brain barrier. Ann N Y Acad Sci. 2008 Oct. 1139:127-39. [Medline].
Albertson TE, Walby WF, Derlet RW. Stimulant-induced pulmonary toxicity. Chest. 1995 Oct. 108(4):1140-9. [Medline].
Nestor TA, Tamamoto WI, Kam TH, Schultz T. Crystal methamphetamine-induced acute pulmonary edema: a case report. Hawaii Med J. 1989 Nov. 48(11):457-8, 460. [Medline].
Thompson CA. Pulmonary arterial hypertension seen in methamphetamine abusers. Am J Health Syst Pharm. 2008 Jun 15. 65(12):1109-10. [Medline].
Cohen AL, Shuler C, McAllister S, Fosheim GE, Brown MG, Abercrombie D, et al. Methamphetamine use and methicillin-resistant Staphylococcus aureus skin infections. Emerg Infect Dis. 2007 Nov. 13(11):1707-13. [Medline].
Johnson TD, Berenson MM. Methamphetamine-induced ischemic colitis. J Clin Gastroenterol. 1991 Dec. 13(6):687-9. [Medline].
Richards JR, Brofeldt BT. Patterns of tooth wear associated with methamphetamine use. J Periodontol. 2000 Aug. 71(8):1371-4. [Medline].
Hamamoto DT, Rhodus NL. Methamphetamine abuse and dentistry. Oral Dis. 2009 Jan. 15(1):27-37. [Medline].
Haning W, Goebert D. Electrocardiographic abnormalities in methamphetamine abusers. Addiction. 2007 Apr. 102 Suppl 1:70-5. [Medline].
Smit AA, Wieling W, Voogel AJ, Koster RW, van Zwieten PA. Orthostatic hypotension due to suppression of vasomotor outflow after amphetamine intoxication. Mayo Clin Proc. 1996 Nov. 71(11):1067-70. [Medline].
Yeo KK, Wijetunga M, Ito H, Efird JT, Tay K, Seto TB, et al. The association of methamphetamine use and cardiomyopathy in young patients. Am J Med. 2007 Feb. 120(2):165-71. [Medline].
Richards JR, Derlet RW, Duncan DR. Methamphetamine toxicity: treatment with a benzodiazepine versus a butyrophenone. Eur J Emerg Med. 1997 Sep. 4(3):130-5. [Medline].
Cherner M, Letendre S, Heaton RK. Hepatitis C augments cognitive deficits associated with HIV infection and methamphetamine. Neurology. 2005. 64:1343-47. [Medline].
Richards JR, Johnson EB, Stark RW, Derlet RW. Methamphetamine abuse and rhabdomyolysis in the ED: a 5-year study. Am J Emerg Med. 1999 Nov. 17(7):681-5. [Medline].
Santos AP, Wilson AK, Hornung CA, Polk HC Jr, Rodriguez JL, Franklin GA. Methamphetamine laboratory explosions: a new and emerging burn injury. J Burn Care Rehabil. 2005 May-Jun. 26(3):228-32. [Medline].
Stewart JL, Meeker JE. Fetal and infant deaths associated with maternal methamphetamine abuse. J Anal Toxicol. 1997 Oct. 21(6):515-7. [Medline].
Catanzarite VA, Stein DA. Crystal' and pregnancy--methamphetamine-associated maternal deaths. West J Med. 1995 May. 162(5):454-7. [Medline].
Ramamoorthy JD, Ramamoorthy S, Leibach FH, Ganapathy V. Human placental monoamine transporters as targets for amphetamines. Am J Obstet Gynecol. 1995 Dec. 173(6):1782-7. [Medline].
Mother of baby killed by meth-contaminated breast milk gets 90 days. Available at http://www.sacbee.com/ourregion/story/1955191.html. Accessed: November 22, 2009.
New meth formula avoids anti-drug laws. Available at http://www.msnbc.msn.com/id/32542373/ns/us_news-crime_and_courts/. Accessed: November 22, 2009.
Burton BT. Heavy metal and organic contaminants associated with illicit methamphetamine production. NIDA Res Monogr. 1991. 115:47-59. [Medline].
Conn C, Dawson M, Baker AT, et al. Identification of n-acetylmethamphetamine in a sample of illicitly synthesized methamphetamine. J Forensic Sci. 1996 Jul. 41(4):645-7. [Medline].
McKinney PE, Tomaszewski C, Phillips S, Brent J, Kulig K. Methamphetamine toxicity prevented by activated charcoal in a mouse model. Ann Emerg Med. 1994 Aug. 24(2):220-3. [Medline].
Richards JR, Albertson TE, Derlet RW, Lange RA, Olson KR, Horowitz BZ. Treatment of toxicity from amphetamines, related derivatives, and analogues: a systematic clinical review. Drug Alcohol Depend. 2015 May 1. 150:1-13. [Medline].
Derlet RW, Albertson TE, Rice P. Protection against d-amphetamine toxicity. Am J Emerg Med. 1990 Mar. 8(2):105-8. [Medline].
Derlet RW, Rice P, Horowitz BZ, Lord RV. Amphetamine toxicity: experience with 127 cases. J Emerg Med. 1989 Mar-Apr. 7(2):157-61. [Medline].
Safety of Droperidol Use in the Emergency Department (9/7/2013). American Academy of Emergency Medicine (AAEM). Available at http://www.aaem.org/UserFiles/file/Safety-of-Droperidol-Use-in-the-ED.pdf. Accessed: 12/07/2013.
Matteucci MJ, Auten JD, Crowley B, Combs D, Clark RF. Methamphetamine exposures in young children. Pediatr Emerg Care. 2007 Sep. 23(9):638-40. [Medline].
Leelahanaj T, Kongsakon R, Netrakom P. A 4-week, double-blind comparison of olanzapine with haloperidol in the treatment of amphetamine psychosis. J Med Assoc Thai. 2005 Nov. 88 Suppl 3:S43-52. [Medline].
Misra LK, Kofoed L, Oesterheld JR, Richards GA. Olanzapine treatment of methamphetamine psychosis. J Clin Psychopharmacol. 2000 Jun. 20(3):393-4. [Medline].
Misra L, Kofoed L. Risperidone treatment of methamphetamine psychosis. Am J Psychiatry. 1997 Aug. 154(8):1170. [Medline].
Shoptaw SJ, Kao U, Ling W. Treatment for amphetamine psychosis. Cochrane Database Syst Rev. 2009 Jan 21. CD003026. [Medline].
Akingbola OA, Singh D. Dexmedetomidine to treat lisdexamfetamine overdose and serotonin toxidrome in a 6-year-old girl. Am J Crit Care. 2012 Nov. 21(6):456-9. [Medline].
Boehrer JD, Moliterno DJ, Willard JE, Hillis LD, Lange RA. Influence of labetalol on cocaine-induced coronary vasoconstriction in humans. Am J Med. 1993 Jun. 94(6):608-10. [Medline].
Hysek CM, Vollenweider FX, Liechti ME. Effects of a beta-blocker on the cardiovascular response to MDMA (Ecstasy). Emerg Med J. 2010 Aug. 27(8):586-9. [Medline].
Hysek C, Schmid Y, Rickli A, Simmler LD, Donzelli M, Grouzmann E, et al. Carvedilol inhibits the cardiostimulant and thermogenic effects of MDMA in humans. Br J Pharmacol. 2012 Aug. 166(8):2277-88. [Medline]. [Full Text].
Wright RS, Anderson JL, Adams CD, Bridges CR, Casey DE Jr, Ettinger SM, et al. 2011 ACCF/AHA focused update incorporated into the ACC/AHA 2007 Guidelines for the Management of Patients with Unstable Angina/Non-ST-Elevation Myocardial Infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the American Academy of Family Physicians, Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons. J Am Coll Cardiol. 2011 May 10. 57(19):e215-367. [Medline].
McKetin R, Najman JM, Baker A, Lubman DI, Dawe S, Ali R, et al. Evaluating the impact of community-based treatment options on methamphetamine use: findings from the Methamphetamine Treatment Evaluation Study (MATES). Addiction. 2012 May 7. [Medline].