NOVEMBER 2023 | VOLUME 25 | ISSUE 11

Emergency Medicine Practice Evidence-Based Education • Practical Application

CLINICAL CHALLENGES:
• How can agitation in patients with
methamphetamine intoxication be
successfully managed?
• What are the first-line treatments
for the dangerous complications
of methamphetamine toxicity?
• What is the appropriate
disposition of patients with
methamphetamine intoxication?

Authors
Sherell Hicks, MD
Assistant Professor, Assistant Residency Program
Director, Department of Emergency Medicine,
University of Alabama at Birmingham Heersink
School of Medicine, Birmingham, AL

Briana D. Miller, MD

Fellow and Clinical Instructor, Department of
Emergency Medicine, University of Alabama
at Birmingham Heersink School of Medicine,
Birmingham, AL
Peer Reviewers
Adam Blumenberg, MD, MA
Assistant Professor, Department of Emergency
Medicine, Columbia University Medical Center,
New York, NY
Jennifer S. Love, MD, MSCR
Assistant Professor of Emergency Medicine,
Icahn School of Medicine at Mount Sinai, New
York, NY
Prior to beginning this activity, see “CME
Information” on page 2.
Emergency Department
Management of
Methamphetamine Toxicity
n Abstract
Management of patients who are acutely intoxicated with
methamphetamine (a member of the substituted amphetamine
class of drugs) can be resource-intensive for most emergency
departments. Clinical presentations of the methamphetamine
sympathomimetic toxidrome range from mild agitation to
rhabdomyolysis, acute kidney injury, seizures, and intracranial
hemorrhage. High-quality evidence on how to best manage these
patients is lacking, and most research focuses on symptomatic
interventions to control patients‘ agitation and hemodynamics.
This review analyzes the best available evidence on the diagnosis
and management of emergency department patients with
substituted amphetamine toxicity and offers best-practice
recommendations on treatment and disposition.

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 CME Information
Date of Original Release: November 1, 2023. Date of most recent review: October 10, 2023. Termination date: November 1, 2026.
Accreditation: EB Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide
continuing medical education for physicians.
EVIDENCE-BASED

Credit Designation: EB Medicine designates this enduring material for a maximum of 4 AMA PRA Category 1 CreditsTM. Physi-
cians should claim only the credit commensurate with the extent of their participation in the activity.
PEER-REVIEWED
Specialty CME: Included as part of the 4 credits, this CME activity is eligible for 1 Pharmacology CME credit.
ACEP Accreditation: Emergency Medicine Practice is approved by the American College of Emergency Physicians for 48 hours of ACEP Cat-
egory I credit per annual subscription.
AAFP Accreditation: The AAFP has reviewed Emergency Medicine Practice, and deemed it acceptable for AAFP credit. Term of approval is from
07/01/2023 to 06/30/2024. Physicians should claim only the credit commensurate with the extent of their participation in the activity. This session,
Emergency Department Management of Methamphetamine Toxicity is approved for 4.0 enduring material AAFP Prescribed credits.
AOA Accreditation: Emergency Medicine Practice is eligible for 4 Category 2-B credit hours per issue by the American Osteopathic Association.
Needs Assessment: The need for this educational activity was determined by a practice gap analysis; a survey of medical staff, including the
editorial board of this publication; review of morbidity and mortality data from the CDC, AHA, NCHS, and ACEP; and evaluation responses from
prior educational activities for emergency physicians.
Target Audience: This enduring material is designed for emergency medicine physicians, physician assistants, nurse practitioners, and residents.
EVIDENCE-BASED

Goals: Upon completion of this activity, you should be able to: (1) identify areas in practice that require modification to be consistent with current
evidence in order to improve competence and performance; (2) develop strategies to accurately diagnose and treat both common and critical ED
presentations;PEER-REVIEWED
and (3) demonstrate informed medical decision-making based on the strongest clinical evidence.
CME Objectives: Upon completion of this activity, you should be able to: (1) describe the clinical presentations of methamphetamine toxicity; (2)
discuss alternative diagnoses of a sympathomimetic toxidrome; (3) list the common complications associated with substituted amphetamines and
interventions for their symptomatic relief; and (4) plan patient disposition based on clinical response.
Discussion of Investigational Information: As part of the activity, faculty may be presenting investigational information about pharmaceutical
products that is outside Food and Drug Administration approved labeling. Information presented as part of this activity is intended solely as
continuing medical education and is not intended to promote off-label use of any pharmaceutical product.
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 Case Presentations
The triage nurse asks you for assistance with an agitated patient who is pacing the floor…
• When you approach the patient, you find an 18-year-old woman who gives you her name but does
not respond appropriately to orienting questions. She is cooperative at first, but then starts to become
CASE 1

increasingly agitated when you try to obtain further history.

• Her vital signs are: temperature, 37°C; blood pressure, 170/99 mm Hg; heart rate, 120 beats/min; and
respiratory rate, 16 breaths/min. She is diaphoretic, but neurologically intact and without any evidence
of trauma.
• She becomes uncooperative and starts to threaten the staff. Your attempts at de-escalation with
redirection and relocation fail, and you wonder what the best pharmacologic intervention would be...

A 22-year-old man presents after developing chest pain while dancing at a club....
• He admits to taking an “upper,” but says that he is unsure of the specific substance.
CASE 2

• His vital signs are: temperature, 36.6°C; blood pressure, 170/110 mm Hg; heart rate, 115 beats/min;
and respiratory rate, 14 breaths/min. His electrocardiogram is negative for ischemic changes.
• He denies any cardiac history or risk factors for pulmonary embolism. You wonder whether this young
man needs to have a cardiac workup . . .

A 25-year-old woman arrives via emergency medical services, after having had a seizure…
• The EMTs report that the patient is otherwise healthy and had a witnessed seizure in front of family. Her
family denies any prior history of seizure.
CASE 3

• Upon arrival, the patient is disoriented and unable to provide further history. Her vital signs are:
temperature, 37.1°C; blood pressure, 190/120 mm Hg; heart rate, 116 beats/min; and respiratory rate,
12 breaths/min.
• You wonder whether her depressed consciousness is due to the seizure or if something else could be
going on . . .

n Introduction were more likely to require pharmacologic interven-

Patients under the influence of methamphetamine
represent a small but resource-intensive group of
emergency department (ED) patients. ED visits
related to methamphetamine use started to rise in
2009, increasing by over 50% in the span of 2 years.1
The prevalence continues to rise globally, with an
estimated increase of 500,000 users from 2016 to
2018, and an increase of 11% in ED visits for metham-
phetamine-related complaints from 2015 to 2016.2 A
recent paper also describes the “fourth wave” of
the opioid epidemic in the United States, as deaths
have increased due to rising co-use of stimulants
and opioids. Methamphetamine has been shown to
be the predominant co-ingested stimulant in most
regions of the United States.3
The presentation of methamphetamine-related
complications ranges from fairly benign skin and
dental complaints to severe conditions such as
rhabdomyolysis and acute kidney injury, and even
life-threatening seizures, aortic dissection, myocar-
dial ischemia, and intracranial hemorrhage.4 These
patients also have a high incidence of agitation and
psychosis. A retrospective chart review showed that
patients who tested positive for methamphetamine
tions and physical restraints and had a longer ED
length of stay than other patients.5 Inappropriate
management in the ED could lead to increased harm
to both patients and healthcare workers as well as
potentially missed life-threatening complications.
Historically, management of these patients has been
variable, based on clinician experiences and anec-
dotal evidence. This issue of Emergency Medicine
Practice focuses on diagnosing methamphetamine
toxicity, recognizing potential life-threatening compli-
cations, and discussing the evidence regarding effec-
tive management of acute methamphetamine toxicity
in the ED.
n Critical Appraisal of the Literature
A literature search using PubMed produced 134
articles with the search terms amphetamines and
emergency department, narrowed down to only
15 articles using search terms methamphetamines
and emergency department. An additional search
of 2 of the major toxicology journals resulted in
132 articles from Clinical Toxicology and 59 articles
from Journal of Medical Toxicology using the terms

NOVEMBER 2023 • www.ebmedicine.net 3 © 2023 EB MEDICINE. ALL RIGHTS RESERVED.

methamphetamines and emergency department.
Additional searches were performed within PubMed
to focus on specific complications associated with
methamphetamine toxicity.
The literature consists mostly of case reports
and review articles with a few retrospective case-
control and prospective observational studies.
Regarding the strength of the literature, the clinical
evidence is considered to be weak to moderately
strong, which is expected, since large randomized
controlled trials related to this topic are typically
not feasible to conduct. There is a lack of evidence-
based guidelines, as interventions are focused on
supportive treatment of methamphetamine toxicity
targeting management of patients’ hemodynamics
and potential agitation.
use. These symptoms are illustrated in Figure 1
and include tachycardia, hypertension, tachypnea,
hyperthermia, diaphoresis, mydriasis, gastrointestinal
upset, seizures, paranoia, mania, and psychosis.4
A 2008 prospective observational study at a sin-
gle large academic hospital found the most common
presenting conditions for methamphetamine-related
visits to be mental health concerns (18.7%), trauma
(18.4%), skin infections (11.1%), and dental-related
diagnoses (9.6%).8 The mechanism leading to the
high incidence of methamphetamine-related dental
complaints, colloquially known as “meth mouth,” is
not completely understood but is likely multifactorial
and includes xerostomia due to vasoconstriction of
salivary gland vasculature, decreased rates of tooth
brushing, bruxism, and poor diet with increased in-
take of sugary beverages.9

n Etiology And Pathophysiology Dangerous Complications of

Amphetamines have been present in human history Methamphetamine Use
for hundreds of years. Traditional Chinese medicine Though the euphoric effects and physiologic changes
uses the plant, ma huang, which contains ephedrine.4 experienced when using methamphetamine can be
Methamphetamine, the more lipophilic N-methyl ana- self-limiting, emergency clinicians must be well-versed
log of amphetamine, was first synthesized in Japan in in the potentially dangerous complications of meth-
1893 but became popular in the United States in the amphetamine use in order to recognize these compli-
1960s.6 Patients may refer to methamphetamine by cations and treat them appropriately. Dangerous com-
its many street names, which are noted Table 1. plications can incude rhabdomyolysis, acute kidney
Many substituted amphetamines, such as synthet- injury, cardiovascular, and cerebrovascular conditions.
ic cathinones, are sold as “bath salts” or “plant food”
and labeled as “not for human consumption” in order
for the manufacturers to avoid drug legislation.7 Be- Figure 1. Features of the
cause of this (similar to all illegally sold drugs), it is dif- Sympathomimetic Toxidrome
ficult to determine the quality or purity of ingredients,
which makes these drugs very dangerous. However,
identifying the particular substance ingested does not
change acute management.
There are multiple routes of exposure for both
methamphetamine and synthetic cathinones,
including oral, nasal, rectal, inhalation, or injection.
Methamphetamine acts by triggering increased
release of the biogenic amine neurotransmitters
dopamine, norepinephrine, and serotonin.4 These
neurotransmitters act mainly on the mesolimbic,
mesocortical, and nigrostriatal pathways of the brain
that control reward centers, motor control, and
emotional responses.4 The resulting hyperadrenergic
surge is responsible for the sympathomimetic
toxidrome that is characteristic of methamphetamine

Table 1. Common Street Names for

Methamphetamine
• Meth
• Ice
• Crystal
• Chalk
• Speed
• Tweak
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Rhabdomyolysis and Acute Kidney Injury
Rhabdomyolysis is a potentially life-threatening
condition in which damaged muscle tissue releases
its contents into the bloodstream, causing electro-
lyte abnormalities, renal injury, and cardiac damage.
Rhabdomyolysis is a known common complication
of methamphetamine use; in a 2020 retrospective
chart review, 20% of patients who tested positive
for methamphetamine use on a urine drug screen
were also found to be in rhabdomyolysis (as defined
by a creatine kinase [CK] >4 times the upper limit of
normal of the institution’s standard laboratory test, or
>1000 U/L in this study).10 The clinical presentation
of methamphetamine use has traditionally been used
to explain the high frequency of rhabdomyolysis, as
patients exhibit psychomotor agitation, hyperthermia,
increased likelihood for the need for physical re-
straints, and increased likelihood of seizures. How-
ever, rhabdomyolysis can develop in patients who are
not seizing, agitated, or restrained, suggesting that
methamphetamine has direct toxicity on myocytes.10
While rhabdomyolysis can precipitate severe
hyperkalemia and acute kidney injury or even renal
failure, patients who use methamphetamines are
at risk for acute kidney injury even in the absence
of rhabdomyolysis. A 2020 prospective case series
showed that while 12% of patients presenting to
the ED after using methamphetamine had acute
kidney injury, only 44% of that patient population
had concurrent rhabdomyolysis.11 This is likely due
to a combination of decreased fluid intake/volume
depletion, tachycardia, hyperthermia, diaphoresis,
and the vasoconstrictive effects of methamphetamine.
Cardiovascular and Cerebrovascular Complications
Cardiovascular and cerebrovascular complications
from methamphetamine use, while rare, can be po-
tentially devastating. Due to alpha-1 stimulation from
the methamphetamine-induced catecholamine surge,
vasoconstriction and vasospasm can cause myocar-
dial and cerebral ischemia. There are case reports of
dysrhythmias and complications from hypertensive
emergencies, including aortic dissection.4 In case-
control and registry studies, methamphetamine use
has been associated with dilated cardiomyopathy,
causing decompensated heart failure.12,13
Patients using methamphetamine are also at
a higher risk for both ischemic and hemorrhagic
stroke than the general population.14 The etiology
of ischemic stroke in methamphetamine use is
thought to be due to the catecholamine-induced
vasoconstriction of cerebral arteries as well as direct
toxicity to vessels, leading to changes in vessel
caliber.14 Hemorrhagic strokes in methamphetamine
users are hypothesized to be due to transient
increases in blood pressure, similar to hemorrhagic
strokes seen in hypertensive emergencies from other
etiologies.14 These hemorrhagic strokes can present
NOVEMBER 2023 • www.ebmedicine.net
as either subarachnoid hemorrhages or intracerebral
hemorrhages, although intracerebral hemorrhage
is more common.15 In a cross-sectional analysis of
812,247 stroke service discharges, methamphetamine
use increased the risk for hemorrhagic stroke by
almost 5 times compared to the general population.15
Methamphetamine use was also associated with
younger age, longer hospital stay, more intensive
care unit days, and higher mortality in intracerebral
hemorrhage.15,16
Methamphetamine Withdrawal
According to the Diagnostic and Statistical Manual of
Mental Disorders, Fifth Edition (DSM-5), the symp-
toms of amphetamine withdrawal include fatigue,
vivid or unpleasant dreams, insomnia or hypersomnia,
increased appetite, and psychomotor retardation
and agitation.17 This syndrome is thought to be due
to a depletion of presynaptic biogenic amines, such
as norepinephrine, as well as downregulation of
receptors due to prolonged hyperadrenergic state.18
A 2005 cross-sectional study further characterized
amphetamine withdrawal into an acute phase lasting
7 to 10 days from cessation of the drug that is marked
by extreme hypersomnia and more severe symptoms
of increased appetite and depression.19 The second
and third weeks of the withdrawal period, or the sub-
acute phase, showed persistence of sleep disturbanc-
es and increased appetite but less severe anhedonia,
dreams, irritability, and psychomotor retardation.19
Unlike alcohol and opioid withdrawal, amphetamine
withdrawal is not associated with significant changes
in heart rate or blood pressure.19 Also, unlike alcohol
withdrawal, amphetamine withdrawal is not physi-
ologically life-threatening.19
n Differential Diagnosis
The clinical presentation of patients using meth-
amphetamine is broad, placing methamphetamine
toxicity on the differential diagnosis of a variety of
presentations. (See Table 2, page 6.) Diagnosis and
management may be complicated by drug-induced
mania, paranoia, and/or aggressive behavior.
In the absence of a patient report of recent use,
methamphetamine intoxication is somewhat of a
diagnosis of exclusion. For example, infection can
precipitate encephalopathy, especially in the setting
of meningitis and encephalitis, and can also cause hy-
perthermia, tachycardia, and diaphoresis, all of which
are also seen in patients with methamphetamine tox-
icity. Of note, hyperthermia caused by methamphet-
amine toxicity tends to result in higher temperatures
than infectious fevers (>40°C), and it is not responsive
to antipyretics.20,21 If a history is available (potentially
from family, friends, or emergency medical services
[EMS]), the timing of the encephalopathy and hyper-
thermia may help, in that infection would typically
5 © 2023 EB MEDICINE. ALL RIGHTS RESERVED.
have a more insidious onset than acute methamphet-
amine intoxication. Another differentiating factor
is change in mental status over time, as a person
acutely intoxicated with methamphetamine would be
expected to return to their neurologic baseline within
24 hours, whereas patients who have a central ner-
vous system infection will likely not have an improve-
ment in mentation without appropriate treatment.
Traumatic injuries, especially intracranial patholo-
gy, may mimic acute methamphetamine intoxication.
Patients using methamphetamine are at higher risk for
experiencing assault, law enforcement altercations,
and domestic violence, and they may be exhibiting
signs of both trauma and acute intoxication, likely
due, in part, to agitation, poor judgment, and behav-
ioral effects of the drug.22 A matched cohort analysis
showed that patients using methamphetamine were
also more likely to sustain penetrating trauma and
more likely to require immediate operative interven-
tion than those who did not use methamphetamine.23
A thorough physical examination is indicated for all
patients with suspected methamphetamine toxicity,
and patients should be fully undressed and examined
for signs of trauma.
Medication-induced conditions such as
neuroleptic malignant syndrome and serotonin
syndrome may also cause hyperthermia and encepha-
lopathy. Key physical examination findings include
“lead pipe” muscular rigidity in neuroleptic malignant
syndrome and clonus in serotonin syndrome, which
may help differentiate these conditions from meth-
amphetamine intoxication even if a full medication
history is not immediately available.
Intoxication with other drugs that produce a
sympathomimetic toxidrome, such as amphetamine
analogs (eg, 3,4-methyl​enedioxy​methamphetamine
[MDMA], attention-deficit hyperactivity disorder
medications, ephedrine), cocaine, and phencyclidine
(PCP) may also mimic methamphetamine intoxication.
Alcohol and benzodiazepine withdrawal should also
be considered, as they may precipitate delirium
tremens. When there is concern for concomitant
alcohol withdrawal, serial Clinical Institute Withdrawal
Assessment (CIWA) scoring can be used to evaluate
severity of withdrawal and guide management.
n Prehospital Care
In the prehospital setting, controlling agitation of
patients with methamphetamine intoxication is
imperative for patient and clinician safety. A sur-
vey of nurses, medical residents, and attending

Table 2. Differential Diagnosis for Patients With Methamphetamine Toxicity With Altered
Mentation
Differential Diagnosis for Altered Mental
Status
Trauma (traumatic brain injury, intracranial
hemorrhage, acute blood loss)
Infection (sepsis, meningitis, encephalitis,
urinary tract infection, intracranial abscess)
Metabolic disturbance (hypoglycemia, diabetic
ketoacidosis, hyponatremia, uremia, hepatic
encephalopathy, hyperthermia)
Medication-induced conditions (neuroleptic
malignant syndrome, serotonin syndrome,
withdrawal syndromes)
Respiratory failure (hypoxia, hypercapnia)
Primary psychiatric diagnosis (schizophrenia,
bipolar disorder with psychotic features)
History and Physical Examination Findings to Diagnostic Testing
Direct Evaluation
• EMS or police reports of trauma; ecchymoses, • CBC
abrasions, lacerations • CT head (or x-rays/other CT imaging
• Decreased Glasgow Coma Scale score, unequal as directed by primary and secondary
pupils, extreme hypertension or hypotension survey)
• Extremes of age, immunocompromise • CBC, CMP, urinalysis, blood cultures,
• History of slowly worsening encephalopathy lactate, ESR, CRP
• Exposure to infected individuals • Chest x-ray
• Rashes, hyperthermia, tachycardia • CT head (consider contrasted study)
• Lumbar puncture
• History of diabetes, end-stage renal disease, or • Point-of-care glucose, CMP, ammonia
cirrhosis level, blood gas
• Abnormal diet
• Alcohol or other illicit substance use, ketone odor,
asterixis
• Medication review • Largely clinical diagnoses
• Hyperthermia
• History of depression, history of antipsychotic use
• “Lead pipe” rigidity (neuroleptic malignant
syndrome)
• Clonus (serotonin syndrome)
• Decreased respiratory rate, hypoxia on pulse • Blood gas
oximetry, wheezing or stridor on examination • End-tidal CO2 monitoring
• Slower time of onset of symptoms • Clinical diagnosis; diagnoses of
exclusion

Abbreviations: CBC, complete blood cell count; CMP, comprehensive metabolic panel; CO2, carbon dioxide; CRP, C-reactive protein; CT, computed
tomography; EMS, emergency medical services; ESR, erythrocyte sedimentation rate.
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physicians conducted at an urban academic Level
I trauma center found that these patients required
more prehospital resources and were more likely to
be violent, compared with nonusers.24 In addition to
ensuring safety for patients and clinicians, the overall
goal of prehospital care is to stabilize the patient as
much as possible prior to and during transport. Us-
ing physical restraint or medications may be neces-
sary to assist with controlling agitation. If the patient
is too agitated to obtain intravenous (IV) access,
intramuscular (IM) medications should be given.
Evidence surrounding prehospital interventions
for methamphetamine users is limited; however,
the literature available for prehospital treatment of
agitated patients, in general, can be applied to this
patient population.24
Medications
Commonly used medications to treat agitation are
benzodiazepines and antipsychotics. In a prospec-
tive observational trial performed on all agitated
patients managed by EMS (not necessarily restrict-
ed to those intoxicated with methamphetamine),
patients who were treated with midazolam rather
than haloperidol had adequate sedation about 11
minutes faster, a clear advantage in the prehospital
setting.25 Benzodiazepine dosages should be
adjusted based on the level of agitation, route
of administration, and potential adverse effects,
which are discussed further in the “Treatment” sec-
tion, beginning on page 9. EMS systems will have
guidelines to follow that vary, but clinicians should
call the hospital for recommendations from medical
control if circumstances fall outside of their estab-
lished directives.
Restraints
Physical restraints can assist with limiting patient
interference with care and can give the IM medica-
tions time to take effect. If the patient is severely
agitated to the point that EMS is unable to transport
safely, giving repeat doses of benzodiazepines can be
helpful to facilitate transport to the ED. If the patient
becomes overly sedated or minimally responsive,
EMS can ventilate the patient via bag-valve mask
until arriving at the hospital or perform intubation for
airway protection, if necessary.
Gathering On-Scene Information
In addition to controlling agitation, EMS should ob-
tain as much information as possible on-scene to as-
sist with workup, especially if the patient is unable to
relay any information. For example, EMS can report
whether drugs were observed on scene, if family or
friends were present, or if anyone provided a history
about what occurred prior to EMS arrival. Although
history of substance use on-scene is important, EMS
should be cautious of anchoring on methamphet-
NOVEMBER 2023 • www.ebmedicine.net
amine intoxication and consider all reversible causes
of altered mental status by obtaining a point-of-care
glucose level and determining whether naloxone
should be given for suspected co-ingestion.
n Emergency Department Evaluation
History
All clinicians should obtain as much background in-
formation from EMS as possible, including where the
patient is coming from (eg, found down, nightclub,
home, abandoned building), any significant bystander
information, and what was done prior, especially in
cases in which the patient is too altered or incapaci-
tated to provide meaningful history. Direct ques-
tions should be asked about social history, including
asking about specific illicit substances in order get
the patient to disclose their drug use. In a study at an
academic center analyzing 318 methamphetamine
users, their self-report rate of drug use was 52% when
compared to their toxicology screen.24 Some patients
are fearful of consequences if they admit to illicit drug
use, including social stigma and encounters with law
enforcement. It is imperative to place emphasis on
their medical treatment and reassure the patients that
the information will not be used in an incriminating
manner. Furthermore, determining the time of inges-
tion and route of administration is important, as it can
help estimate when effects will be most noticeable. It
is difficult to know the amount ingested, as the purity
of drug products is variable.7
A detailed history should be obtained about why
the patient is presenting to the ED, asking whether
they experienced any trauma, such as a fall, assault,
or motor vehicle crash, or whether there were any
co-ingestions. Since treatment is supportive, questions
should be directed at what symptoms the patient is
currently experiencing to better evaluate the risk for
complications. For example, if a patient is experiencing
chest pain, ask about associated symptoms and risk
factors to determine risk for acute coronary syndromes
(ACS) or aortic dissection. Also, asking about the
patient‘s mental health is useful to determine whether
they were using methamphetamines for recreational
use or for self-harm.
Physical Examination
An initial assessment of ABCs (airway, breathing,
circulation) should be performed when first encoun-
tering the patient, so any issues can be addressed. In
this patient population, tachycardia and hypertension
are 2 of the most common vital sign abnormalities,
although tachycardia is typically more pronounced
and obvious than hypertension.26 If the patient is un-
able to cooperate with obtaining an oral temperature,
another method needs to be used to obtain a core
temperature (eg, rectal or temperature-sensing Foley)
to ensure hyperthermia is not missed.
7 © 2023 EB MEDICINE. ALL RIGHTS RESERVED.
 A thorough physical examination is performed
next. Recognizing the sympathomimetic toxidrome
is based purely on examination, and is more easily
remembered with the mnemonic MD PATHS, which
highlights the classic signs.27 (See Table 3 and Fig-
ure 1, page 4.) The patient should be fully exposed
to assess for trauma, as these patients may often be
unaware of their injuries due to their intoxication or
altered mentation. Assessing for myoclonus or rigid-
ity helps differentiate sympathomimetic syndrome
from serotonin syndrome. If the patient is unable to
provide a history, looking for track marks or finding
drug paraphernalia in their pockets or belongings
can provide clues of a drug ingestion. It is important
to consider these findings during examination but
to not anchor on them when determining the ap-
propriate clinical workup. This patient population
commonly presents with agitation and may not follow
commands to assist with a full neurological examina-
tion; however, even with an uncooperative patient, a
neurologic examination can be performed through
observation to assess for focal neurologic deficits.
Other findings on examination that could further
elucidate history of methamphetamine use are poor
dentition from neglect and/or poor diet/hygiene, as
well as excoriations from picking due to delusional
parasitosis from psychosis.4 However, these findings
are associated with chronic abuse and do not direct
acute management.
n Diagnostic Studies
The diagnostic workup for a patient who presents
with methamphetamine intoxication varies depending
on the severity of symptoms, the ability of the patient
to provide a history, and the patient’s hemodynamics.
No direct evidence to inform decision-making is
available, but based on accepted practice, recom-
mendations for the workup are summarized in Table
4. All patients presenting with any encephalopathic
Table 3. MD PATHS: Mnemonic for
Sympathomimetic Toxidrome
M Mydriasis
D Diaphoresis
P Pallor
A Agitation
T Tachycardia
H Hypertension/hyperthermia
S Seizures
Reprinted from Clinical Pediatric Emergency Medicine, Volume 20,
Issue 1. Shan Yin. Adolescents and drug abuse: 21st century synthetic
substances. Pages 17-24. Copyright 2019, with permission from
Elsevier. https://www.sciencedirect.com/journal/clinical-pediatric-
emergency-medicine
NOVEMBER 2023 • www.ebmedicine.net
symptoms—including the mania and agitation seen
with methamphetamine use—should have a point-of-
care glucose test performed as soon as possible to
evaluate for potentially reversible causes of encepha-
lopathy. All persons of child-bearing age with a uterus
should be tested for pregnancy. A urinalysis may be
considered to screen for infection.
Electrocardiogram
All patients with suspected methamphetamine
intoxication should have an electrocardiogram
(ECG) performed to evaluate for arrhythmias, acute
ischemia, and QRS or QTc prolongation. Not only
does the ECG evaluate for potential life-threatening
complications of methamphetamine use, but it can
help guide treatment for symptom control, because
many antipsychotics that may be used for treatment
of methamphetamine-induced agitation can cause
QTc prolongation. However, a randomized controlled
trial observing the effect of 2 high-dose administra-
tions of IM haloperidol (7.5 mg and 10 mg) and IM
ziprasidone (20 mg and 30 mg) on QTc intervals
showed only a mild increase in QTc. No QTc >480
msec was recorded, suggesting these medications
are largely well-tolerated in patients who are without
pre-existing prolonged QT intervals.28
Urine Drug Screen
A urine drug screen seems an obvious test to obtain
in a patient suspected of using methamphetamines;
however, the false-positive and false-negative rates
for methamphetamine in a standard urine drug screen
assay are very high. In a literature review, commonly
prescribed medications such as chlorpromazine,
promethazine, selegiline, and bupropion as well as
over-the-counter medications such as ranitidine and
cough and cold medications containing ephedrine
Table 4. Emergency Department Workup
for Methamphetamine Toxicity
Patient Population Diagnostic Test
All patients • Point-of-care glucose
• Electrocardiogram
• Urine pregnancy test (for patients of
child-bearing age with a uterus)
• Urine drug screen*
Patients with severe or • Additional laboratory testing: CBC, CMP,
atypical symptoms, troponin, creatine kinase, AST/ALT, lactic
altered mentation, acid, urinalysis
hemodynamic • Imaging: chest x-ray, CT head, CT
instability, or external angiography
signs of trauma
*Can be obtained but should not delay care.
Abbreviations: AST, aspartate transaminase; ALT, alanine transaminase;
CBC, complete blood cell count; CMP, comprehensive metabolic panel;
CT, computed tomography.
www.ebmedicine.net
8 ©2023 EB MEDICINE
were all found to result in positive amphetamine
screens.29 Some patients use prescribed amphet-
amines for medical conditions such as narcolepsy and
attention-deficit/hyperactivity disorder, so a positive
urine drug screen may reflect appropriate use of their
prescribed medications and not substance misuse.
Even a true positive test for methamphetamine does
not necessarily mean the patient’s current presentation
is due to methamphetamine use and does not rule out
other disorders in the differential diagnosis. Meth-
amphetamine toxicity is a diagnosis based on clinical
presentation, and while a urine drug screen may be
obtained as collateral information, it should not delay
care and should not falsely reassure clinicians against
other etiologies of the patient’s symptoms.
Additional Laboratory Studies
If the patient is able to provide a history, has
mild symptoms, and has no findings concerning
for severe complications, a clinical diagnosis of
methamphetamine toxicity may be made. However,
patients are often unable to provide a reliable history,
and additional diagnostic laboratory tests and
imaging must be obtained to rule out life-threatening
conditions. A comprehensive metabolic panel (CMP)
is recommended for any encephalopathic patient,
as it gives valuable information regarding electrolyte
abnormalities, renal function, liver function, and
blood urea nitrogen (BUN). As discussed previously,
patients using methamphetamine have a high risk for
acute kidney injury and rhabdomyolysis, so a creatine
kinase (CK) level may also be obtained. Although
these tests may not be necessary for every patient
presenting after methamphetamine use, they should
be strongly considered for patients with extreme
hemodynamic changes, psychomotor agitation or
need for physical restraints, or evidence of hematuria
Table 5. Intravenous and Intramuscular Medications for Acute Agitation and Psychosis33
Medication Class Medication
Benzodiazepines Midazolam
Lorazepam
Diazepam
Antipsychotics Haloperidol
Droperidol
Olanzapine
Alternative agents (lower Ketamine
evidence level, fewer expert
recommendations)
Dexmedetomidine
Abbreviations: IM, intramuscular; IV, intravenous.
NOVEMBER 2023 • www.ebmedicine.net
or oliguria. Patients using methamphetamine may
also have inconsequential elevations in CK without
true rhabdomyolysis or impaired renal function, so
these results must be interpreted with caution. If
the patient is hyperthermic and infection is on the
differential, a complete blood cell count (CBC) to
evaluate for leukocytosis may be helpful, although
this is nonspecific.
Imaging Studies
A chest x-ray to evaluate for possible sources of
infection may also be considered. If the patient is
lethargic, has focal neurologic deficit, or external
signs of trauma, an emergent head computed
tomography (CT) scan is indicated, especially if the
patient is severely hypertensive. If the patient reports
additional symptoms, such as chest pain or dyspnea,
a cardiac workup with chest x-ray and troponin should
also be obtained, as a retrospective study showed
up to a 25% incidence of ACS in patients who were
hospitalized after presenting with chest pain after
methamphetamine use.30 A thorough examination
should be performed to determine whether advanced
imaging is needed to evaluate for dissection.
n Treatment
Treatment of the methamphetamine-intoxicated
patient is largely supportive, as there are no spe-
cific antidotes. There is very little direct evidence in
the literature on treating acute methamphetamine
intoxication; recommendations are compiled from
consensus-based guidelines, case studies, and expert
opinion. Therefore, the evidence regarding treatment
recommendations is weak. The IV/IM medications
commonly suggested in general practice for acute
agitation and psychosis and their dosing and notable
attributes are summarized in Table 5.
Dosage Comments
2-5 mg IV or IM, repeat after 5-10 • Risk for oversedation when doses are repeated
min if needed too quickly or at very high doses
• Antiepileptic properties
2-4 mg IV, repeat after 5-10 min if
• When IM administration is needed, midazolam
needed
should be used due to better absorption
5-10 mg IV, repeat after 5-10 min if
needed
5-10 mg IM; onset ~20-30 min • QT prolongation
• Extrapyramidal side effects
2.5-5 mg IM; onset ~10 min
5-10 mg IM; onset ~60 min
5 mg/kg IM • Laryngospasm
• Risk for catecholamine surge
1 mcg/kg IV over 10 min followed by • No respiratory depression
infusion of 0.2-0.7 mcg/kg/hr • Lowers heart rate and blood pressure
• Requires continuous IV access
9 © 2023 EB MEDICINE. ALL RIGHTS RESERVED.
 This review focuses on recognizing common com-
plications associated with methamphetamine toxicity,
but the treatment of these complications—includ-
ing acute kidney injury, rhabdomyolysis, intracranial
hemorrhage, seizure, and myocardial ischemia—are
beyond the scope of this review.
The published data regarding treatment of acute
methamphetamine intoxication are focused largely in
2 areas: (1) treatment of acute agitation and psycho-
sis and (2) treatment of vital sign abnormalities and
hemodynamic instability.
Treatment of Acute Agitation and Psychosis
Benzodiazepines and Antipsychotic Agents
When treating an agitated patient, verbal de-esca-
lation and creating a quiet, calming environment
without antagonizing factors should be attempted
first. If physical restraints are required, chemical seda-
tion with medications should also be considered, as
patients struggling against restraints can precipitate
rhabdomyolysis and potentially cause injury and
airway obstruction if the restraints are applied incor-
rectly.23,24 In an acutely agitated patient, initial IV
access may be unsafe to attempt and IM medications
should be used to facilitate safe IV access.
Benzodiazepines and antipsychotics are the
most commonly recommended medications
for treatment of patients with agitation. Benzo-
diazepines have classically been the first-line
treatment for methamphetamine-induced agitation
and psychosis due to their ease of administration,
predictable pharmacokinetics, and favorable side-
effect profile.25,26
Antipsychotics carry varying degrees of risk
for QT prolongation, temperature dysregulation,
and extrapyramidal side-effects and thus may be
used with caution as second-line agents in combi-
nation with benzodiazepines for patients who are
normothermic and have no cardiovascular risk fac-
tors.31 Although the risk for QTc prolongation with
antipsychotic medications is commonly cited, a
randomized controlled trial showed only a modest
change in QTc after IM haloperidol (7.5 mg or 10 mg)
or IM ziprasidone (20 mg),without adverse events or
dysrhythmias, indicating that a single dose is unlikely
to cause clinically significant changes in QTc.28 In a
case series of 18 pediatric patients treated for meth-
amphetamine intoxication, 12 of the 18 patients were
treated with both benzodiazepines and haloperidol,
with improvement in their agitation, with no adverse
events reported, including dystonic reactions or QTc
prolongation.32 However, the limitations of these
studies should be taken into consideration when de-
ciding whether or not to use antipsychotics, as some
of these agents have a United States Food and Drug
Administration boxed warning for QTc prolongation.
A randomized controlled trial of 146 patients
using methamphetamine requiring sedation di-
NOVEMBER 2023 • www.ebmedicine.net
rectly compared benzodiazepines (lorazepam) and
an antipsychotic (droperidol). Patients receiving
lorazepam required more frequent re-dosing and
patients receiving droperidol had longer-lasting ad-
equate sedation.34 However, in another prospective
observational trial performed on agitated patients
(not necessarily intoxicated with methamphetamine)
treated by EMS clinicians, patients who were treated
with midazolam rather than haloperidol had adequate
sedation about 11 minutes faster.25 Benzodiazepines
have the advantage that they can be frequently re-
dosed and titrated to effect.
When IM administration is required, midazolam
should be used instead of lorazepam or diazepam
due to more reliable and quicker absorption, with
an onset of about 10 minutes, allowing for re-dosing
without dose stacking. Lorazepam has an onset of
around 30 minutes when given IM, making it much
harder to titrate. If IV access is obtained, the onset
between midazolam, lorazepam, or diazepam is simi-
lar. Depending on the clinical scenario, quicker onset
may be more beneficial in a severely agitated patient,
while long-acting antipsychotics may have more utility
in patients who are mildly agitated but redirectable.
Adjunct Medications
Adjuncts to benzodiazepines and antipsychotics may
be used for severely agitated patients. Ketamine,
a dissociative agent that antagonizes N-methyl-D-
aspartate (NMDA) receptors, has gained popularity
in the past several decades and may be used in the
prehospital setting; however, high-quality data exam-
ining the use of ketamine in patients using metham-
phetamines are lacking. Ketamine can also produce
a catecholamine surge, which would be counterpro-
ductive in efforts to treat the hyperadrenergic state
caused by methamphetamines.
Another option published in a pediatric case se-
ries of amphetamine toxicity (not methamphetamine)
is dexmedetomidine, an alpha agonist that inhibits
central nervous system sympathetic outflow.35 This
case series described several pediatric patients who
were agitated after ingesting dextromethorphan-
containing medications who were treated with
dexmedetomidine and had decreased violent behav-
ior, outbursts, and lower requirements for physical re-
straints. Dexmedetomidine has the added benefit of
lowering heart rate and blood pressure through its al-
pha agonist properties.35 However, dexmedetomidine
is administered as a continuous infusion and constant
IV access is often challenging to maintain for patients
who are agitated or psychotic. Dexmedetomidine
also has not been studied in adults or specifically in
methamphetamine-intoxicated patients.
Airway Manaagement
Airway management must be closely monitored in
patients with acute intoxication but also in those who
10 ©2023 EB MEDICINE
require high doses of sedating medications. End-
tidal CO2 should be used for close monitoring of
respiratory status, and intubation can be considered
for those at risk for aspiration, hypoventilation, or
airway compromise due to oversedation. If agitation
cannot be controlled with escalating doses of
sedatives, intubation may be necessary for patient
and staff safety.
Treatment of Vital Sign Abnormalities
Control of the extreme abnormalities of the
sympathomimetic toxidrome—intracranial hemor-
rhage, tachydysrhythmias, and rhabdomyolysis—is
key to preventing potentially life-threatening compli-
cations of methamphetamine toxicity.
Benzodiazepines are the first-line agents to treat
hemodynamic abnormalities and may be dosed as
shown in Table 5, page 9. There are no high-quality
studies comparing benzodiazepines to alternate
means of hemodynamic control in methamphetamine
use. In most cases of tachycardia and hypertension
due to methamphetamine use, benzodiazepines and
a calm, nonstimulating environment along with IV
crystalloid fluid rehydration and correction of electro-
lyte abnormalities are likely to be sufficient treatment.
Antihypertensives
In cases of severe hypertension refractory to
benzodiazepine administration with evidence of
end-organ damage, adjuncts can be added to treat
hypertensive emergencies. Although there are few
data comparing different adjunctive measures, text-
books and review articles suggest an alpha antago-
nist such as phentolamine, or vasodilators such as
nitroglycerin.4,36 However, phentolamine has limited,
if any, place in clinical practice. There is limited
methamphetamine-specific literature examining the
effect of nitroglycerin on hypertension and tachycar-
dia, but there have been case reports published on
the amphetamine analog, pseudoephedrine, that
describe resolution of chest pain and STEMI findings
on ECG with nitroglycerin administration.37,38
Beta blockers were once thought to be
contraindicated for methamphetamine intoxication,
with concern for unopposed alpha stimulation that
could lead to extreme hypertension. However, a
systematic review found multiple case studies and
case series of patients using methamphetamine
who were given beta blockers, with improvement
in hemodynamics and only one case report of an
adverse hypertensive event.39 Labetalol (5-20 mg
IV over 2 minutes) may be an appropriate option
because it has both alpha and beta blocking
properties (though not equal effects on both) and was
shown to be effective at lowering blood pressure and
heart rate in a case study of ephedrine ingestion.40
A small randomized controlled trial published in
2012 also suggested carvedilol (50 mg orally) was
NOVEMBER 2023 • www.ebmedicine.net
associated with improvements in blood pressure,
heart rate, and body temperature in subjects using
MDMA (ecstasy), which has stimulant properties
similar to methamphetamine.41
Antipyretics
Antipyretics are not effective for methamphetamine-
induced hyperthermia. Active cooling measures such
as cooled IV crystalloid fluids, ice packs in groin and
axilla, and ice baths should be initiated. In extreme
hyperthermia not responsive to benzodiazepines
and active cooling, the patient may be sedated,
intubated, and neuromuscularly paralyzed.42 Sero-
tonin syndrome must also be considered high on the
differential for any extreme hyperthermia in the set-
ting of methamphetamine use.
Treatment of Withdrawal
There are very limited data, with mixed results,
regarding the treatment of amphetamine withdrawal
states. A 2023 meta-analysis of the available ran-
domized controlled trials analyzed data regarding
the use of amineptine (withdrawn from the market
in 1999), mirtazapine, modafinil, and amantadine
in treating amphetamine withdrawal symptoms and
found no significant improvement with any medica-
tion in reducing withdrawal symptoms or improving
discontinuation rates.43
n Special Populations
Elderly Patients
The elderly population is at higher risk for developing
complications from substituted amphetamines due
to their higher likelihood of having a significant
past medical history (eg, coronary artery disease
or comorbidities related to cardiovascular disease).
These patients need to have a more thorough workup
to assess for end-organ damage and complications
associated with methamphetamine use.
Pediatric Patients
If pediatric patients present with concerns for
methamphetamine intoxication, these cases are most
likely accidental ingestion from their surroundings or
intentional poisoning from caregivers. These patients
would benefit from confirmatory testing by both urine
and serum analysis for definitive diagnosis. Either
way, these cases need to be evaluated formally by
Child Protective Services (CPS).
Pregnant Patients
In pregnant patients, methamphetamine use does
have adverse effects on the fetus, with newborns
most commonly experiencing decreased birth weight,
likely due to the vasoconstrictive effects on the
placenta or by crossing the placenta directly.4 Meth-
amphetamine use is also associated with increased
11 © 2023 EB MEDICINE. ALL RIGHTS RESERVED.
placental insufficiency and placental abruption.4
When pregnant patients present to the ED with meth-
amphetamine toxicity, they need to have their fetus
evaluated by bedside ultrasound in the ED to detect
fetal heart tones. Ideally, an obstetrician should be
consulted; if the patient is asymptomatic and fetal
heart tones are within normal limits (120-160 beats/
min), they should be given resources for substance
use treatment/prenatal care and follow-up on an
outpatient basis. If the patient has a viable pregnancy
(≥24 weeks) and is experiencing vaginal bleeding, ab-
dominal or pelvic pain, decreased fetal movement, or
has undetectable fetal heart tones, they need to be
transferred to labor and delivery for fetal monitoring
and evaluation, as they are at higher risk for prema-
ture delivery and fetal death.4
n Controversies and Cutting Edge
Some substituted amphetamines are not detected by
standard toxicology screening; however, being unable
to detect substituted amphetamines does not limit
patient care in the majority of cases, as treatment is
directed toward clinical presentation and symptoms.
It is possible to send blood samples to a laboratory
that specializes in diagnostic detection of substituted
amphetamines, but diagnostic testing would be use-
ful in only a few scenarios. These situations include
differentiating between acute substance-induced
psychosis versus primary psychiatric illness as well as
determining the etiology of new-onset seizures in an
otherwise healthy young patient.26 In both of these
scenarios, treatment would be drastically different if
substance use was the inciting factor.
Additionally, if a new substance is readily avail-
able and is causing a public health threat leading
to increased mortality, diagnostic testing would be
useful to identify the particular structure to assist
with public policy efforts to limit availability.7,26 As
mentioned previously, diagnostic testing for amphet-
amine toxicity in pediatric patients would be useful to
confirm exposure. In other more common situations,
determining the specific substance has little benefit.
n Disposition
A 2013 federal report found that 64% of patients pre-
senting to the ED with a complaint related to meth-
amphetamine use were able to be discharged from
the ED.1 Once a patient who had used methamphet-
amine returns to their neurologic baseline and has
normal hemodynamics, a thorough re-evaluation and
tertiary survey should be done to ensure there were
no missed injuries or complaints compared with their
initial presentation. Once this is done, the patient can
likely be discharged with strict return precautions.
Patients using methamphetamine are at a higher like-
lihood of experiencing housing instability and poor
NOVEMBER 2023 • www.ebmedicine.net
access to medical care, so at discharge, resources
regarding local shelters, substance use centers, and
reduced-cost clinics should be provided. Prior to dis-
charge, all patients also need to be educated on the
risks of using methamphetamine and other drugs and
offered resources for rehabilitation programs.
If a patient has not returned to their neurologic
baseline while in the ED or if they required high
doses of sedation for agitation or delirium, they may
require an observation or inpatient stay to fully return
to baseline. Patients requiring airway management or
monitoring should be admitted to an intensive care
unit that has continuous end-tidal CO2 and telemetry
monitoring capabilities. In cases of complications of
methamphetamine use such as acute kidney injury
or rhabdomyolysis, supportive care and IV crystalloid
fluids in the ED may be appropriate. Patients whose
metabolic derangements have not resolved with IV
crystalloid fluids while in the ED may require inpatient
admission. In a retrospective study in 2020, 60% of
patients using methamphetamine who had an initial
CK >1000 IU/L were admitted.10 Often these patients
have limited access to healthcare and may be unable
to return to a primary care physician to ensure their
acute kidney injury is improving as an outpatient, so
they may have a lower threshold for admission.
Patients experiencing more severe complications
of methamphetamine use such as intracranial
hemorrhage, myocardial ischemia, or seizures will
require intensive care unit-level care and potentially
specialist involvement.
Patients exhibiting methamphetamine withdrawal
symptoms are not at risk for seizures or other life-
threatening events, unlike patients experiencing
withdrawal from alcohol or benzodiazepines, and they
do not require an inpatient admission. However, they
should undergo screening for withdrawal from these
substances as well as mental health screenings for
suicidal or homicidal ideation. These patients will also
likely benefit from resources regarding local addiction
support and treatment centers.
n Summary
Patients using methamphetamine are becoming
increasingly common in EDs and can be resource-
intensive. There is a lack of evidence regarding
many aspects of the care of the methamphetamine-
intoxicated patient. They can often present with acute
agitation and hemodynamic disturbances, and their
course may be complicated by rhabdomyolysis and
acute kidney injury. Less commonly, life-threatening
conditions can develop, including seizure, intracranial
hemorrhage, aortic dissection, and myocardial
ischemia, and clinicians need to keep a high index of
suspicion to avoid missing these complications.
The diagnostic approach to a patient using
methamphetamine is largely clinical. Glucose,
12 ©2023 EB MEDICINE
 Case Conclusions
For the 18-year-old patient who became agitated and combative…
The agitated patient was physically restrained and was given 5 mg midazolam IM, and a second dose of 2
CASE 1

mg IM midazolam after 30 minutes, after which her agitation improved. She was monitored on ETCO2 and
her restraints were removed once she was interacting appropriately. Laboratory results were unremarkable.
On reassessment, she was alert and oriented, ambulatory, and tolerating oral intake. She admitted to
using methamphetamine. She was deemed stable for discharge home with family and given resources for
outpatient rehabilitation.

For the 22-year-old man who presented after developing chest pain while dancing at a club...
The patient reported a history of recent methamphetamine use. You initially attributed his abnormal vital
CASE 2

signs to his substance use disorder, but he said he had never experienced these symptoms before. You
decided to perform a more thorough examination, and he was noted to have unequal peripheral pulses.
You determined that he needed further workup with advanced imaging. CT angiography imaging confirmed
aortic dissection. You started appropriate treatment for hemodynamic stabilization, and the patient was
taken to the operating room for repair.

For the 25-year-old woman who arrived via EMS, after having had a seizure…
The patient remained post-ictal. Laboratory results revealed rhabdomyolysis with acute kidney injury, with
Cr 2.0 and CK elevated to 10,000. The patient was aggressively rehydrated with 2-L boluses of IV crystalloid
CASE 3

fluids in the ED and started on a high maintenance rate, with IV crystalloid fluids titrated to a goal of 200
mL/hr of urine output. CT head imaging was unremarkable, and spot electroencephalogram showed the
patient was not in status epilepticus. She was admitted to neurology for long-term electroencephalogram
and further workup. You sent off drug testing, and a week later, it resulted positive for a substituted
5
amphetamine, supporting a diagnosis of a substance-induced seizure and not Recommendations
epilepsy. The patient was
encouraged to refrain from substance use to prevent further seizures. She was To not
Apply in Practice
started on antiepileptics.

5 Recommendations
To Apply in Practice

ECG, and urine pregnancy test should be obtained

on all patients with a known or suspected history
of methamphetamine use presenting with
encephalopathy or hemodynamic abnormalities.
There is little evidence to guide which patients
require screening for metabolic abnormalities such as
acute kidney injury and rhabdomyolysis, but patients
who have severe hypertension, tachycardia, or
hyperthermia or who are unable to provide a history
would likely benefit. Patients who are severely altered
or lethargic, have external signs of trauma, have a
focal neurologic deficit, or whose mental status does
not improve while in the ED should be evaluated with
a head CT for intracranial hemorrhage. Appropriate
workup for any associated symptoms should be
performed prior to attributing their presentation to
methamphetamine toxicity.
Acute agitation in the methamphetamine-
intoxicated patient should be treated with
benzodiazepines as a first-line agent, which often
improves hemodynamics as well. Antipsychotics can
also be used as an adjunct treatment. Close airway
management is required in patients who are sedated.
Further studies comparing different treatment
modalities are needed.
5 Things
5 That Will Change
Recommendations
Your Practice
To Apply in Practice
1. Consider substituted amphetamine
intoxication in an otherwise healthy, young
patient presenting with a seizure.
2. Though laboratory testing can be helpful
with diagnosis and management, recognition
of acute substituted amphetamine toxicity
depends initially on the history and physical
examination.
3. Benzodiazepines should be given early
and titrated rapidly to higher doses than
are usually used to treat other causes of
agitation.
4. Hyperthermia needs to be treated with
cooling measures, not antipyretics (unless
there is concern for infection).
5. Antipsychotics are an adjunct to consider
when managing agitation in patients
presenting with acute psychosis, as mental
illness and methamphetamine toxicity may
present similarly.

NOVEMBER 2023 • www.ebmedicine.net 13 © 2023 EB MEDICINE. ALL RIGHTS RESERVED.

 Risk Management Pitfalls for Emergency Department
Patients With Methamphetamine Intoxication
1. “The urine drug screen is negative, so
drug intoxication is unlikely.” Substituted
amphetamines are not detected on routine urine
drug screen. The patient's clinical presentation
and physical examination help confirm the
diagnosis if the patient is unable to provide the
history.
2. “The patient denies any history of illicit
substance use.” Patients are not always honest
or aware of using illicit substances. This can be
for multiple reasons, including fear of getting in
trouble, stigma, or they may have been drugged
unknowingly.
3. “Her agitation is not improving after 2
doses of 5 mg IM midazolam, so I’m going
to switch to another medication.” Patients
with amphetamine toxicity usually require
higher doses of benzodiazepine in order to
achieve clinical effect. As long as the patient
is not over-sedated and is protecting their
airway, it is appropriate to continue giving more
benzodiazepines.
4. “He is altered, but his friends said he was
using meth tonight, so we will observe him
until he is back to baseline. No workup
is needed.” Methamphetamine toxicity is a
diagnosis of exclusion. Avoid anchoring on
methamphetamine intoxication as the cause
of symptoms of altered mental status. Patients
need to be evaluated for additional etiologies
of symptoms if they are not at their baseline
mentation. Obtain a point-of-care-glucose level,
consider CT imaging, and consider co-ingestions.
5. “The workup was negative for infection,
and I suspect his high temperature is due to
hyperthermia. I will give him acetaminophen.”
Antipyretics are not effective with hyperthermia
due to substituted amphetamine toxicity. Cooling
measures should be started as soon as possible.
NOVEMBER 2023 • www.ebmedicine.net
6. “He has tachycardia that is likely driven by
agitation. I will hold on IV crystalloid fluids.”
These patients are typically dehydrated from
decreased oral intake from multi-day binges and
need fluid resuscitation for hemodynamic stability
and to avoid preventable complications.
7. “I’ll treat the hypertension first, then give
additional sedation medications for his
agitation.” In most cases, sedative medications
will improve hemodynamics, and anti-
hypertensives are not required.
8. “The patient has only mild acute kidney injury,
so I’ll give IV crystalloid fluids and discharge
her. No need to check a CK.” Rhabdomyolysis
is one of the most common complications
associated with substituted amphetamine use,
and it is important to evaluate the acute kidney
injury further with a CK to avoid missing a
diagnosis and worsening kidney dysfunction.
9. “There is no point in sending out definitive
drug testing for this 22-year-old woman
who presented with acute psychosis and
subsequent seizure in the ED.” Typically, testing
for specific substituted amphetamines is not
warranted, but it can be helpful if a clinician is
trying to differentiate between primary versus
substance-induced psychosis or epilepsy versus
drug-induced seizure.
10. “The patient admits to using meth but denies
remembering any trauma. I did not fully
undress the patient for a trauma evaluation.”
These patients are at high risk for trauma-
related injuries but often do not remember
any trauma due to their agitation/intoxication.
Emergency clinicians need to perform a thorough
examination, with the patient fully exposed, to
avoid missing any injuries.
14 ©2023 EB MEDICINE
n Time- and Cost-Effective Strategies
• Managing these patients’ agitation can develop
into a resource-intensive encounter, leading to a
longer stay in the ED while waiting for the pa-
tients to return to baseline. Proactive treatment
of agitation, with frequent reassessments and
redosing of medications early on can help save
time and resources. Strategies include starting
with higher doses of benzodiazepines upon ar-
rival and performing frequent reassessments at
regular short intervals (based on route of admin-
istration) to determine whether additional medi-
cation is needed to achieve the desired effect.
Using this strategy will save time, energy, and
resources in the ED, as the patient’s agitation will
be controlled in a shorter amount of time.
• A cost-effective strategy involves relying on
the history and physical examination to dictate
the workup. If the patient is young, healthy,
able to provide a history of substance abuse,
and is otherwise neurologically intact, this pa-
tient can be observed in the ED until they are
hemodynamically stable/asymptomatic, and they
do not need the same workup as an undifferenti-
ated patient would.
• Risk Management Caveat: If in a resource-limit-
ed setting and unable to quickly control the pa-
tient without using significant personnel, consider
intubation to facilitate workup, protect the patient
and staff, and limit resource consumption.
n References
Evidence-based medicine requires a critical appraisal
of the literature based upon study methodology and
number of subjects. Not all references are equally
robust. The findings of a large, prospective, random­
ized, and blinded trial should carry more weight than
a case report.
To help the reader judge the strength of each
reference, pertinent information about the study will
be included in bold type following the ref­erence,
where available. In addition, the most informative
references cited in this paper, as determined by the
author, are noted by an asterisk (*) next to the number
of the reference.
1. Mattson ME. Emergency department visits involving metham-
phetamine: 2007 to 2011. Rockville, MD: Center for Behavioral
Health Statistics and Quality, Substance Abuse and Mental
Health Services Administration; 2013. (Government report)
2. Vivolo-Kantor AM, Hoots BE, Seth P, et al. Recent trends and
associated factors of amphetamine-type stimulant over-
doses in emergency departments. Drug Alcohol Depend.
2020;216:108323. (Secondary data analysis; 33,506,645 ED
visits)
3. Friedman J, Shover CL. Charting the fourth wave: geo-
graphic, temporal, race/ethnicity and demographic trends in
polysubstance fentanyl overdose deaths in the United States,
NOVEMBER 2023 • www.ebmedicine.net
2010-2021. Addiction. 2023. (Population-based study of
national death records, 2010-2021)
4.* Schep LJ, Slaughter RJ, Beasley DM. The clinical toxicology
of metamfetamine. Clin Toxicol (Phila). 2010;48(7):675-694.
(Review) DOI: 10.3109/15563650.2010.516752
5. Schultz BR, Lu BY, Onoye JM, et al. High resource utilization of
psychiatric emergency services by methamphetamine users.
Hawaii J Med Public Health. 2018;77(12):312-314. (Retrospec-
tive; 16,018 patients)
6. Panenka WJ, Procyshyn RM, Lecomte T, et al. Methamphet-
amine use: a comprehensive review of molecular, preclinical
and clinical findings. Drug Alcohol Depend. 2013;129(3):167-
179. (Review)
7.* Prosser JM, Nelson LS. The toxicology of bath salts: a review of
synthetic cathinones. J Med Toxicol. 2012;8(1):33-42. (Review)
DOI: 10.1007/s13181-011-0193-z
8. Hendrickson RG, Cloutier R, McConnell KJ. Methamphetamine-
related emergency department utilization and cost. Acad
Emerg Med. 2008;15(1):23-31. (Prospective observational
study; 353 patients)
9. Clague J, Belin TR, Shetty V. Mechanisms underlying meth-
amphetamine-related dental disease. J Am Dent Assoc.
2017;148(6):377-386. (Case-control study; 571 participants)
10. Richards JR, Wang CG, Fontenette RW, et al. Rhabdomyolysis,
methamphetamine, amphetamine and MDMA use: associated
factors and risks. J Dual Diagn. 2020;16(4):429-437. (Retro-
spective; 957 patients)
11. Isoardi KZ, Mudge DW, Harris K, et al. Methamphetamine
intoxication and acute kidney injury: a prospective observa-
tional case series. Nephrology (Carlton). 2020;25(10):758-764.
(Prospective case series; 50 patients)
12. Diercks DB, Fonarow GC, Kirk JD, et al. Illicit stimulant use
in a United States heart failure population presenting to the
emergency department (from the Acute Decompensated Heart
Failure National Registry Emergency Module). Am J Cardiol.
2008;102(9):1216-1219. (Comparative study of registry data;
594 patients)
13. Yeo KK, Wijetunga M, Ito H, et al. The association of metham-
phetamine use and cardiomyopathy in young patients. Am J
Med. 2007;120(2):165-171. (Case-control study; 107 cases,)
14. Ho EL, Josephson SA, Lee HS, et al. Cerebrovascular com-
plications of methamphetamine abuse. Neurocrit Care.
2009;10(3):295-305. (Retrospective; 30 patients)
15. Westover AN, McBride S, Haley RW. Stroke in young
adults who abuse amphetamines or cocaine: a population-
based study of hospitalized patients. Arch Gen Psychiatry.
2007;64(4):495-502. (Cross-sectional; 1935 patients)
16. Swor DE, Maas MB, Walia SS, et al. Clinical characteristics
and outcomes of methamphetamine-associated intracerebral
hemorrhage. Neurology. 2019;93(1):e1-e7. (Retrospective; 41
patients)
17. American Psychiatric Association. The Diagnostic and Statistical
Manual of Mental Disorders, Fifth Edition, Text Revision. Wash-
ington, DC: American Psychiatric Association; 2022. (Book)
18. Barr AM, Panenka WJ, MacEwan GW, et al. The need for
speed: an update on methamphetamine addiction. J Psychiatry
Neurosci. 2006;31(5):301-313. (Review)
19. McGregor C, Srisurapanont M, Jittiwutikarn J, et al. The nature,
time course and severity of methamphetamine withdrawal.
Addiction. 2005;100(9):1320-1329. (Cross-sectional study; 21
patients)
20. Eyer F, Zilker T. Bench-to-bedside review: mechanisms and
management of hyperthermia due to toxicity. Crit Care.
2007;11(6):236. (Review)
21. Bernheim HA, Block LH, Atkins E. Fever: pathogen-
esis, pathophysiology, and purpose. Ann Intern Med.
15 © 2023 EB MEDICINE. ALL RIGHTS RESERVED.
 1979;91(2):261-270. (Review)
22. Swanson SM, Sise CB, Sise MJ, et al. The scourge of meth-
amphetamine: impact on a level I trauma center. J Trauma.
2007;63(3):531-537. (Retrospective registry review; 4932
consecutive trauma patients)
23. Grigorian A, Martin M, Schellenberg M, et al. Methamphet-
amine use associated with gun and knife violence: a matched
cohort analysis. Surg Open Sci. 2023;13:71-74. (TQIP database
analysis of drug screens; 4191 patients)
24.* Richards JR, Hawkins JA, Acevedo EW, et al. The care of
patients using methamphetamine in the emergency depart-
ment: perception of nurses, residents, and faculty. Subst Abus.
2019;40(1):95-101. (Survey)
DOI: 10.1080/08897077.2018.1449170
25. Isenberg DL, Jacobs D. Prehospital agitation and sedation trial
(PhAST): a randomized control trial of intramuscular haloperidol
versus intramuscular midazolam for the sedation of the agitated
or violent patient in the prehospital environment. Prehosp
Disaster Med. 2015;30(5):491-495. (Prospective randomized
controlled trial; 10 patients)
26.* Banks ML, Worst TJ, Rusyniak DE, et al. Synthetic cathinones
(“bath salts”). J Emerg Med. 2014;46(5):632-642. (Review)
DOI: 10.1016/j.jemermed.2013.11.104
27. Yin S. Adolescents and drug abuse: 21st century synthetic sub-
stances. Clin Pediatr Emerg Med. 2019;20(1):17-24. (Review)
28. Miceli JJ, Tensfeldt TG, Shiovitz T, et al. Effects of high-dose
ziprasidone and haloperidol on the QTc interval after intramus-
cular administration: a randomized, single-blind, parallel-group
study in patients with schizophrenia or schizoaffective disorder.
Clin Ther. 2010;32(3):472-491. (Randomized controlled trial;
59 patients)
29. Brahm NC, Yeager LL, Fox MD, et al. Commonly prescribed
medications and potential false-positive urine drug screens. Am
J Health Syst Pharm. 2010;67(16):1344-1350. (Review)
30. Turnipseed SD, Richards JR, Kirk JD, et al. Frequency of acute
coronary syndrome in patients presenting to the emergency de-
partment with chest pain after methamphetamine use. J Emerg
Med. 2003;24(4):369-373. (Retrospective study; 33 patients)
31. Whelan KR, Dargan PI, Jones AL, et al. Atypical antipsychotics
not recommended for control of agitation in the emergency
department. Emerg Med J. 2004;21(5):649. (Review)
Class of Evidence Definitions
Each action in the clinical pathways section of Emergency Medicine Practice receives a score based on the following definitions.
Class I Class II
• Always acceptable, safe • Safe, acceptable
• Definitely useful • Probably useful
• Proven in both efficacy and effectiveness
Level of Evidence:
Level of Evidence: • Generally higher levels of evidence
• One or more large prospective studies • Nonrandomized or retrospective stud-
are present (with rare exceptions) ies: historic, cohort, or case control
• High-quality meta-analyses studies
• Study results consistently positive and • Less robust randomized controlled trials
compelling • Results consistently positive
This clinical pathway is intended to supplement, rather than substitute for, professional judgment and may be changed depending upon a patient’s individual
needs. Failure to comply with this pathway does not represent a breach of the standard of care.
Copyright © 2023 EB Medicine. www.ebmedicine.net. No part of this publication may be reproduced in any format without written consent of EB Medicine.
NOVEMBER 2023 • www.ebmedicine.net 16
32. Ruha AM, Yarema MC. Pharmacologic treatment of acute
pediatric methamphetamine toxicity. Pediatr Emerg Care.
2006;22(12):782-785. (Retrospective chart review; 18 patients)
33. Wodarz N, Krampe-Scheidler A, Christ M, et al. Evidence-based
guidelines for the pharmacological management of acute
methamphetamine-related disorders and toxicity. Pharmaco-
psychiatry. 2017;50(3):87-95. (Review)
34. Richards JR, Derlet RW, Duncan DR. Methamphetamine toxic-
ity: treatment with a benzodiazepine versus a butyrophenone.
Eur J Emerg Med. 1997;4(3):130-135. (Systemic review)
35. Tobias JD. Dexmedetomidine to control agitation and delirium
from toxic ingestions in adolescents. J Pediatr Pharmacol Ther.
2010;15(1):43-48. (Case series)
36. Spyres MB, Jang DH. Amphetamines. In: Nelson LS, Howland
MA, Lewin NA, et al., eds. Goldfrank’s Toxicologic Emergencies,
11e. New York, NY: McGraw-Hill Education; 2019. (Review)
37. Akay S, Ozdemir M. Acute coronary syndrome presenting
after pseudoephedrine use and regression with beta-blocker
therapy. Can J Cardiol. 2008;24(11):e86-88. (Case report)
38. Wiener I, Tilkian AG, Palazzolo M. Coronary artery spasm and
myocardial infarction in a patient with normal coronary arteries:
temporal relationship to pseudoephedrine ingestion. Cathet
Cardiovasc Diagn. 1990;20(1):51-53. (Case report)
39. Richards JR, Albertson TE, Derlet RW, et al. Treatment of toxic-
ity from amphetamines, related derivatives, and analogues: a
systematic clinical review. Drug Alcohol Depend. 2015;150:1-
13. (Review)
40. Mariani PJ. Pseudoephedrine-induced hypertensive emergen-
cy: treatment with labetalol. Am J Emerg Med. 1986;4(2):141-
142. (Case report)
41. Hysek C, Schmid Y, Rickli A, et al. Carvedilol inhibits the cardio-
stimulant and thermogenic effects of MDMA in humans. Br J
Pharmacol. 2012;166(8):2277-2288. (Randomized controlled
trial; 16 patients)
42. Callaway CW, Clark RF. Hyperthermia in psychostimulant over-
dose. Ann Emerg Med. 1994;24(1):68-76. (Review)
43. Acheson LS, Williams BH, Farrell M, et al. Pharmacological treat-
ment for methamphetamine withdrawal: A systematic review and
meta-analysis of randomised controlled trials. Drug Alcohol Rev.
2023;42(1):7-19. (Meta-analysis; 6 trials, 186 patients)
Class III Indeterminate
• May be acceptable • Continuing area of research
• Possibly useful • No recommendations until further
• Considered optional or alternative research
treatments
Level of Evidence:
Level of Evidence: • Evidence not available
• Generally lower or intermediate levels • Higher studies in progress
of evidence • Results inconsistent, contradictory
• Case series, animal studies, • Results not compelling
consensus panels
• Occasionally positive results
©2023 EB MEDICINE
 Clinical Pathway for Management of Emergency
Department Patients With Methamphetamine Intoxication

Patient presents with examination consistent with

methamphetamine intoxication

Is the patient exhibiting agitated

YES Administer IM or IV benzodiazepines
or aggressive behavior?

NO
• Re-dose IM or IV benzodiazepine
(Class II)
Obtain vital signs, including temperature Adequate sedation • May consider antipsychotics as
YES NO
and blood glucose level, and ECG achieved? adjunct sedation (Class III)

Manage simultaneously

External signs of trauma, lethargy, or Extreme tachycardia or hypertension,

NO Manage symptomatically
focal neurologic deficit? AND/OR extreme hypothermia?

YES NO YES

• Administer IM or IV benzodiazepines
Obtain CT head
(Class II)
• Re-dose IM or IV benzodiazepines
(Class II)
• Consider nitroglycerin, labetalol,
Consider laboratory workup, including Improved vital signs? NO carvedilol for refractory hypertension
BMP, CK, CBC, troponin, urinalysis (Class III/IV)
• Consider active cooling measures
YES for hyperthermia

• Evidence of trauma-related injuries,
rhabdomyolysis, AKI?
• Evidence of hypertensive
emergency, including intracerebral
hemorrhage, arrhythmia, aortic
dissection?
YES
Has the patient returned to neurologic • Consider observation or admission
NO baseline with normal vital signs? NO • Consider alternate diagnoses
YES
Discharge with resources
for addiction recovery

• Treat abnormalities
• Admit to appropriate level of care

Abbreviations: AKI, acute kidney injury; BMP, basic metabolic panel; CBC, complete blood cell count; CK, creatine kinase; CT, computed tomography;
ECG, electrocardiogram; IM, intramuscular; IV, intravenous.
For Class of Evidence definitions, see page 16.

NOVEMBER 2023 • www.ebmedicine.net 17 © 2023 EB MEDICINE. ALL RIGHTS RESERVED.

n CME Questions 6. What is the most common vital sign abnormal-
Current subscribers receive CME credit ity associated with methamphetamine toxicity?
absolutely free by completing the a. Tachycardia
following test. Each issue includes 4 AMA b. Hypothermia
PRA Category 1 CreditsTM, 4 ACEP c. Hyperthermia
Category I credits, 4 AAFP Prescribed d. Hypotension
credits, and 4 AOA Category 2-B credits.
Online testing is available for current and archived 7. What is the first-line treatment for managing
issues. To receive your free CME credits for this agitation due to methamphetamine toxicity?
issue, scan the QR code below with your a. Benzodiazepines
smartphone or visit www.ebmedicine.net/1123 b. Antipsychotics
c. Intravenous crystalloid fluids
d. Intubation

8. How should methamphetamine-induced

hyperthermia be managed if there is no
concern for infection?
a. Acetaminophen
1. What is the primary mechanism of action of b. Ibuprofen
substituted amphetamines? c. Naproxen
a. Triggering increased release of dopamine, d. Active cooling measures
norepinephrine, and serotonin
b. Acting on opioid receptors 9. What effect does methamphetamine use
c. Blocking the removal of dopamine in the during pregnancy have on the fetus?
synapse a. Reduced fetal movement
d. Enhancing the effects of gamma-aminobutyric b. Decreased birth weight
acid (GABA) c. Decreased heart rate
d. Increased contractions
2. What is the toxidrome associated with
methamphetamine toxicity? 10. The following patients present to the
a. Anticholinergic ED with urine drug screens negative for
b. Sympathomimetic methamphetamines and denying history of
c. Cholinergic illicit drug use. Which patient warrants further
d. Opioid diagnostic testing to determine whether
methamphetamine use is contributing to their
3. What is a common and potentially life- clinical presentation?
threatening complication associated with a. A 50-year-old man with past medical history
methamphetamine toxicity? of epilepsy presenting with seizure
a. “Meth mouth” b. A 35-year-old woman with past medical
b. Delusional parasitosis history of schizophrenia presenting with
c. Leukocytosis psychosis
d. Rhabdomyolysis c. An 18-year-old man with no past medical
history presenting with a second seizure
4. How does serotonin syndrome differ from d. A 23-year-old woman with no past medical
methamphetamine toxicity? history presenting with chest pain
a. Diaphoresis
b. Sedation
c. Myoclonus
d. Seizures

5. Which of the following is a diagnostic study

that is necessary for all patients upon initial
evaluation?
a. Urine drug screen
b. Computed tomography scan of the head
c. Point-of-care glucose
d. Troponin

NOVEMBER 2023 • www.ebmedicine.net 18 ©2023 EB MEDICINE

The Emergency Medicine Practice Editorial Board
EDITOR-IN-CHIEF
Andy Jagoda, MD, FACEP
Professor and Chair Emeritus,
Department of Emergency
Medicine; Director, Center for
Emergency Medicine Education
and Research, Icahn School of
Medicine at Mount Sinai, New
York, NY
ASSOCIATE EDITOR-IN-CHIEF
Kaushal Shah, MD, FACEP
Assistant Dean of Academic
Advising, Vice Chair of
Education, Professor of
Clinical Emergency Medicine,
Department of Emergency
Medicine, Weill Cornell School of
Medicine, New York, NY
COURSE DIRECTOR
Daniel J. Egan, MD
Associate Professor of
Emergency Medicine, Harvard
Medical School; Program
Director, Harvard Affiliated
Emergency Medicine Residency;
Massachusetts General Hospital/
Brigham and Women's Hospital,
Boston, MA
EDITORIAL BOARD
Saadia Akhtar, MD, FACEP
Associate Professor, Department
of Emergency Medicine,
Associate Dean for Graduate
Medical Education, Program
Director, Emergency Medicine
Residency, Mount Sinai Beth
Israel, New York, NY
William J. Brady, MD, FACEP,
FAAEM
Professor of Emergency Medicine
and Medicine; Medical Director,
Emergency Management,
UVA Medical Center; Medical
Director, Albemarle County Fire
Rescue, Charlottesville, VA
Calvin A. Brown III, MD
Chair of Emergency Medicine,
Lahey Hospital and Medical
Center, Burlington, MA
Peter DeBlieux, MD
Professor of Clinical Medicine,
Louisiana State University School
of Medicine; Chief Experience
Officer, University Medical
Center, New Orleans, LA
NOVEMBER 2023 • www.ebmedicine.net
Deborah Diercks, MD, MS,
FACEP, FACC
Professor and Chair, Department
of Emergency Medicine,
University of Texas Southwestern
Medical Center, Dallas, TX
Marie-Carmelle Elie, MD
Professor and Chair, Department
of Emergency Medicine
University of Alabama at
Birmingham, Birmingham, AL
Nicholas Genes, MD, PhD
Clinical Assistant Professor,
Ronald O. Perelman Department
of Emergency Medicine, NYU
Grossman School of Medicine,
New York, NY
Michael A. Gibbs, MD, FACEP
Professor and Chair, Department
of Emergency Medicine,
Carolinas Medical Center,
University of North Carolina
School of Medicine,
Chapel Hill, NC
Steven A. Godwin, MD, FACEP
Professor and Chair, Department
of Emergency Medicine,
Assistant Dean, Simulation
Education, University of
Florida COM-Jacksonville,
Jacksonville, FL
Joseph Habboushe, MD MBA
Assistant Professor of Clinical
Emergency Medicine,
Department of Emergency
Medicine, Weill Cornell School
of Medicine, New York, NY; Co-
founder and CEO, MDCalc
Eric Legome, MD
Chair, Emergency Medicine,
Mount Sinai West & Mount Sinai
St. Luke's; Vice Chair, Academic
Affairs for Emergency Medicine,
Mount Sinai Health System, Icahn
School of Medicine at Mount
Sinai, New York, NY
Keith A. Marill, MD, MS
Associate Professor, Department
of Emergency Medicine, Harvard
Medical School, Massachusetts
General Hospital, Boston, MA
Angela M. Mills, MD, FACEP
Professor and Chair, Department
of Emergency Medicine,
Columbia University Vagelos
College of Physicians &
Surgeons, New York, NY
19
Charles V. Pollack Jr., MA, MD,
FACEP, FAAEM, FAHA, FACC,
FESC
Clinician-Scientist, Department
of Emergency Medicine,
University of Mississippi School
of Medicine, Jackson MS
Ali S. Raja, MD, MBA, MPH
Executive Vice Chair, Emergency
Medicine, Massachusetts General
Hospital; Professor of Emergency
Medicine and Radiology, Harvard
Medical School, Boston, MA
Robert L. Rogers, MD, FACEP,
FAAEM, FACP
Assistant Professor of Emergency
Medicine, The University of
Maryland School of Medicine,
Baltimore, MD
Alfred Sacchetti, MD, FACEP
Assistant Clinical Professor,
Department of Emergency
Medicine, Thomas Jefferson
University, Philadelphia, PA
Robert Schiller, MD
Chair, Department of Family
Medicine, Beth Israel Medical
Center; Senior Faculty, Family
Medicine and Community
Health, Icahn School of Medicine
at Mount Sinai, New York, NY
Scott Silvers, MD, FACEP
Senior Vice President,
Optum Health National
Clinical Performance; Chief
Medical Officer, Knowledge
Management, Optum Health
Corey M. Slovis, MD, FACP,
FACEP
Professor and Chair Emeritus,
Department of Emergency
Medicine, Vanderbilt University
Medical Center, Nashville, TN
Stephen H. Thomas, MD, MPH
Department of Emergency
Medicine, Beth Israel Deaconess
Medical Center and Harvard
Medical School, Boston, MA
Ron M. Walls, MD
Professor and COO, Department
of Emergency Medicine, Brigham
and Women's Hospital, Harvard
Medical School, Boston, MA
© 2023 EB MEDICINE. ALL RIGHTS RESERVED.
CRITICAL CARE EDITORS
William A. Knight IV, MD,
FACEP, FNCS
Associate Professor of
Emergency Medicine and
Neurosurgery, Medical Director,
EM Advanced Practice Provider
Program; Associate Medical
Director, Neuroscience ICU,
University of Cincinnati,
Cincinnati, OH
Scott D. Weingart, MD, FCCM
Editor-in-Chief, emCrit.org
PHARMACOLOGY EDITOR
Aimee Mishler, PharmD, BCPS
Emergency Medicine Pharmacist,
St. Luke's Health System,
Boise, ID
RESEARCH EDITOR
Joseph D. Toscano, MD
Chief, Department of Emergency
Medicine, San Ramon Regional
Medical Center, San Ramon, CA
INTERNATIONAL EDITORS
Peter Cameron, MD
Academic Director, The Alfred
Emergency and Trauma Centre,
Monash University, Melbourne,
Australia
Andrea Duca, MD
Attending Emergency Physician,
Ospedale Papa Giovanni XXIII,
Bergamo, Italy
Suzanne Y.G. Peeters, MD
Attending Emergency Physician,
Flevo Teaching Hospital, Almere,
The Netherlands
Edgardo Menendez, MD,
FIFEM
Professor in Medicine and
Emergency Medicine; Director of
EM, Churruca Hospital of Buenos
Aires University, Buenos Aires,
Argentina
Dhanadol Rojanasarntikul, MD
Attending Physician, Emergency
Medicine, King Chulalongkorn
Memorial Hospital; Faculty
of Medicine, Chulalongkorn
University, Thailand
Edin Zelihic, MD
Head, Department of Emergency
Medicine, Leopoldina Hospital,
Schweinfurt, Germany
 Points & Pearls
QUICK READ
NOVEMBER 2023 | VOLUME 25 | ISSUE 11
Points
• Methamphetamine (substituted amphetamine)
use can cause the sympathomimetic toxidrome.4
Figure 1 illustrates the body systems affected.
• Because the substances causing sympatho-
mimetic toxidrome cannot be determined, ED
patients are treated according to clinical presen-
tation; identifying the substance ingested will not
change acute management.
• The most common presenting conditions for
methamphetamine-related ED visits include men-
tal health concerns, trauma, skin infections, and
dental-related diagnoses.8
• Assessing for myoclonus or rigidity helps differ-
entiate sympathomimetic syndrome from sero-
tonin syndrome.
• Table 2 outlines the differential diagnosis, clinical
findings, and diagnostic testing for patients with
methamphetamine toxicity who are displaying
signs of altered mentation.
• Table 4 notes the diagnostic workup for metham-
phetamine toxicity.
• Dangerous complication of methamphetamine
use include rhabdomyolysis/acute kidney in-
jury and cardiovascular and cerebrovascular
complications, including seizures, aortic dis-
section, myocardial and cerebral ischemia, and
intracranial hemorrhage.4
• 20% of patients who tested positive for metham-
phetamine were found to be in rhabdomyolysis,
and it can develop in patients who are not seiz-
ing, agitated, or restrained.10
• Methamphetamine use increases the risk for
hemorrhagic stroke by almost 5 times, compared
to the general population.15
• Although amphetamine withdrawal is not
life-threatening, symptoms include fatigue,
hypersomnia or insomnia, vivid or unpleasant
dreams, increased appetite, and psychomotor
retardation and agitation.17
• Hyperthermia from methamphetamine use can
cause temperatures higher than infectious fevers,
and it is not responsive to antipyretics. It is es-
sential to monitor temperature and initiate active
cooling measures.
NOVEMBER 2023 • www.ebmedicine.net
Emergency Department
Management of
Methamphetamine Toxicity
Pearls
• In the prehospital and ED setting, controlling
patients‘ agitation is imperative for clinician
and patient safety. Table 5 outlines medica-
tions that can be used for managing acute
agitation and psychosis.33
• In an acutely agitated patient, IV access may
be unsafe to attempt and IM medications
should be used to facilitate IV access.
• Benzodiazepines are first-line treatment for
agitation and psychosis due to their ease of
administration, predictable pharmacokinetics,
and favorable side-effect profile.25,26
• Antipsychotics may provide longer-lasting
sedation; however, they may have more side
effects. (See Table 5.)
• End-tidal CO2 should be used to monitor se-
dated patients.
• Benzodiazepines, a calm environment, IV crys-
talloid fluid rehydration, and correction of elec-
trolyte abnormalities are likely to be sufficient
treatments for patients with methamphetamine
intoxication.
• Patients using methamphetamine are at higher risk
for experiencing assault, law enforcement alterca-
tions, and domestic violence. Patients should be
examined full for signs of trauma.22
• Clinicians should attempt to elicit as much his-
tory of substance use as possible, emphasizing its
importance to their medical treatment and that the
information will not be used to incriminate them.
• Urine drug screens are not accurate and should
not be performed. For pediatric patients, urine and
serum testing should be performed for evaluation
by Child Protective Services.
• Because patients using methamphetamine are
at higher likelihood to be experiencing housing
instability and decreased access to medical care,
discharge should include referral for shelters, sub-
stance abuse centers, and healthcare resources.
20 ©2023 EB MEDICINE