Methamphetamine in the ED Setting
- Jul 27th, 2020
- David Cisewski
Authors: David Cisewski, MD (@dhcisewski– EM Resident Physician, Icahn School of Medicine at Mount Sinai); Jonathan Schimmel, MD (Attending Medical Toxicologist, Emergency Physician, Icahn School of Medicine at Mount Sinai) // Reviewed by: Alex Koyfman, MD (@EMHighAK) and Brit Long, MD (@long_brit)
What do Hitler, hot sauce, Breaking Bad, South Dakota, and crystal meth all have in common? Read on….
What is methamphetamine?
Methamphetamine (MA) – aka, “speed,” “go,” “crank,” “uppers,” “crystal,” “ice,” “yaba,” (Thailand), or “shabu” (Philippines) – is a commonly abused psychostimulant used for the effects of increased energy, attention, and euphoria. Despite FDA-approved uses to treat ADHD in children and as an appetite suppressant in overweight adults, MA is a drug with high abuse potential.1, 2 Similar to cocaine and other stimulants, MA is a sympathomimetic amine that promotes the release of catecholamines from their storage sites in presynaptic nerve terminals (primarily dopamine and norepinephrine, but also serotonin), providing the euphoric and energetic effects desired from its use.3, 4 MA is also capable of producing extreme aggression/agitation, or a substance-induced psychosis difficult to distinguish from schizophrenia, which presents a diagnostic challenge in the emergency setting.5
Pharmacokinetics and metabolism of methamphetamine
MA is quickly absorbed following administration via intravenous (IV), oral (PO), intranasal (IN), or inhalational (INH) routes.6, 7 MA – similar to selegiline, MDMA (ecstasy), ephedrine, and bupropion – is a substituted amphetamine (SA), part of a broader group of substituted phenylethylamines. An SA is formed by the substitution of hydrogen atoms in the core structure with another substituent.8 For MA, a methyl group addition creates a highly lipophilic substance, which can readily cross the blood-brain barrier.4, 8 MA onset of effect varies from less than one minute (intravenous) to five minutes (inhaled) to twenty minutes (oral).4 MA’s elimination half-life ranges 12 to 34 hours, and while effects typically last 8-24 hours, they can occasionally persist longer.9
Almost half of MA is eliminated in the urine unchanged, while the liver metabolizes the rest to active and inactive metabolites (including amphetamine), which are then eliminated in the urine.10, 11 MA metabolism utilizes the P450 enzyme CYP2D6 – an enzyme with significant genetic polymorphisms, predisposing to potentially variable dose-response.12, 13 When used over an extended duration (“meth binge”) these metabolites may accumulate, resulting in prolonged effects.
Who is using methamphetamine?
More than you would think. MA use was popularized as an energy stimulant/work aid for construction, truck driving, factory floor work, or classically among military infantry during active duty. Hitler (and parts of the Nazi military) used Pervitin (brand name MA) as a supplemental aid for an endless supply of sleepless, maniacal days during World War II.
Hitler and the Nazi regime were believed to be avid users of Pervitin (brand name methamphetamine).
Despite the Controlled Substances Act of 1970 listing MA as a Schedule II substance, there are still nearly 2 million users per year across all age, demographic, and social classes.14 As opposed to cocaine, which is used relatively equally between African American and Caucasian populations in the United States, methamphetamine use is more prevalent among Caucasians.4
Why the ‘meth’ comeback?
MA has developed into a growing epidemic over the last decade.15, 16 The reason? Basic supply and demand. Despite the dramatization of Breaking Bad and the portrayal of a highly scientific process to synthesize meth, it’s a relatively easy stepwise process requiring only a handful of starter ingredients and basic supplies. As larger volumes of MA are smuggled across the Mexican border, more suppliers have flooded the market, providing a more reliable supply chain of cheaper product. Unfortunately, MA has also never been purer, cheaper, or more lethal. Unlike opioids, however, there is no analogous acute reversal agent or Medication-Assisted Treatment (MAT) to curb cravings, making addressing this use in the emergency department (ED) setting all the more challenging.
Since the early 2000s, a large percentage of MA flow into the US has occurred through California. As suppliers saturated the western markets of California, Oregon, and Washington, suppliers have begun to move east in search of new markets. Many communities have started to recognize the epidemic and have taken action to address the problem. Recently in South Dakota, the provocative “METH. I’M ON IT” campaign was designed to draw attention to the state’s epidemic. Despite polarizing views of the campaign – repeatedly criticized as a waste of taxpayer dollars – it’s succeeded in gaining attention on a national level.
METH. I’M ON IT: South Dakota campaign slogan to raise awareness around the MA epidemic.
Further attention has also surrounded the growing sophistication of MA production and distribution. Last year Siracha hot sauce became the ultimate ‘drug mule’ when an attempt was made to smuggle over $300 million of methamphetamine from the United States to Australia through America’s favorite condiment (a true crime against humanity and fish tacos everywhere).
Smuggled methamphetamine found hidden in Siracha hot sauce.
What are the presenting signs and symptoms of methamphetamine intoxication?
In the emergency setting, MA intoxication generally presents as a sympathomimetic toxidrome with signs and symptoms such as psychomotor agitation and autonomic hyperactivity.17, 18 Skin burns or clothing stains may be a further indication of exposure to hazardous chemicals used in MA production. See the table below for a system-based list of MA effects.
Of note, MA users are prone to a constellation of cardiovascular pathology – the leading cause of death among MA users – such as cardiomyopathy, malignant hypertension, and myocardial infarction.19 Acute coronary syndromes should be considered in all MA toxicity cases.
Effects of Methamphetamine By Organ System
What else should we consider on the differential diagnosis?
MA can present similarly to several other essential diagnoses that must be considered:
- Anticholinergic poisoning – dry skin and mucous membranes, urinary retention (vs. MA)
- Aspirin overdose – check serum aspirin level if uncertain; inquire about tinnitus
- Cocaine/PCP intoxication – shorter duration than MA; look for PCP-associated nystagmus
- Encephalitis – other stigmata of infection, nuchal rigidity
- Heatstroke – correlate to the environment, clinical scenario
- Hypoglycemia – check blood glucose
- Pheochromocytoma – waxing and waning hypertension and symptoms
- Psychosis/Schizophrenia – diagnosis of exclusion; autonomic hyperactivity less likely (vs. MA)
- Serotonin syndrome – inquire about serotonergic drugs
- Thyrotoxicosis – the presence of goiter, exophthalmos, pretibial edema
Are there specific populations we should consider?
Children are prone to accidental ingestion and will present with tachycardia, inconsolable crying or irritability, vomiting, and may develop rhabdomyolysis.34 Children exposed to MA production chemicals may exhibit skin blistering, oral mucosal burns, drooling, stridor, and dyspnea from caustic ingestion.35
MA intoxication during pregnancy may result in placental insufficiency, placental abruption, or early labor.36 Continuous use of sympathomimetics increases the risk of growth restriction and stillbirth as MA easily crosses the placental barrier.37, 38
How is methamphetamine intoxication treated?
As with all intoxicated patients presenting with agitation or psychosis, the primary focus is calming the patient and preventing secondary harm to the patient and staff. MA-intoxicated patients will benefit from a dimly-lit, low stimulation environment. Efforts should be made to avoid physical restraints, which may result in physical trauma, worsen agitation, and exacerbate rhabdomyolysis.39
Benzodiazepines are the first-line medication for MA agitation or aggressive behavior.40 Among select patients who are intoxicated but cooperative, oral formulations may be considered. In one case series, oral diazepam alone resulted in successful sedation in approximately two-thirds of MA-intoxicated patients.41 Among patients with moderate-to-severe symptoms, aggression, and unstable vital signs, parenteral alternatives are advised. Midazolam 2-2.5 mg IM or diazepam 5 mg IV are commonly used first-line regimens. Be aware of time to onset and peak effect of the sedative you use, to avoid potential dose stacking while awaiting onset.
Antipsychotics (droperidol, haloperidol) may also be used to avoid the over-sedation and respiratory depression associated with benzodiazepines, particularly if delusions or hallucinations are present.40, 42 Some concern exists that antipsychotics may lower the seizure threshold, or that antimuscarinic effects may worsen tachycardia or exacerbate hyperthermia by reducing diaphoresis. However, antipsychotics have demonstrated safety and efficacy in multiple studies. A systematic review including 330 patients with amphetamine toxicity found less than a 1% risk of serious adverse events with antipsychotic use.43 Either droperidol 2.5-5 mg IV (or IM) or haloperidol 5 mg IV (or 10 mg IM) may be considered among patients with concern for sympathomimetic toxicity.42, 43 Droperidol has been shown to result in faster onset and greater sedation, and less need for repeat dosing compared to lorazepam.46, 47 Droperidol has also been shown to have a more rapid onset and greater efficacy than haloperidol (droperidol 5 mg vs. haloperidol 10 mg) for acute psychosis or agitated behavior in the Emergency Dept.44, 45 The DORM Study (Droperidol OR Midazolam) demonstrated droperidol 10 mg IM was just as effective at reducing the duration of violent behavior compared to midazolam 10 mg IM (20 vs. 24 min), required less repeat dosing (33% vs. 62%), and was associated with less respiratory depression among intoxicated, agitated patients.48 The combination of midazolam 5 mg with droperidol 5 mg was shown to be more effective at attaining adequate sedation at 10 minutes compared to droperidol or olanzapine alone (75 vs. 50 vs. 50%).49 The addition of droperidol 5 mg (or olanzapine 5 mg) to midazolam 2.5-5 mg aliquots has also been shown to offer reduced time to sedation versus midazolam alone (21 vs. 14 vs. 68 min).50 Specific to MA-intoxication, retrospective data from Australia demonstrated that a combination of benzodiazepines and antipsychotics were able to sedate 98% of MA-intoxicated patients successfully.41 Of the one-third of patients who did not respond to oral benzodiazepines alone, droperidol was effective to achieve adequate sedation. Ultimately the use of antipsychotics over benzodiazepines is based on provider discretion and only following a consideration of the risks versus the benefits of use.
Note – although haloperidol administered intravenously has been shown to effectively treat delirium and agitation, it is FDA-approved for oral and intramuscular routes, and IV administration remains off-label.
IV fluid hydration is often necessary as rhabdomyolysis may be present in up to 30% of patients.41 Additionally, increased insensible fluid losses and appetite suppression may leave many patients severely dehydrated, which may worsen agitation and psychosis. If blood glucose is low, consider a dextrose-containing fluid for dual hydration and glucose repletion.
Hyperthermia management is critical to prevent associated sequelae. Although sedation with benzodiazepines will improve hyperthermia by reducing excessive muscle activity, active cooling may be used to expedite the process. Convection cooling (evaporative with mist and fans) and conductive cooling (cold-water submersion, ice packs in the axillae and groin, cooling blankets, cold saline flushes) may all be used once a patient is adequately sedated.51-53 Co-administration of benzodiazepines will also assist in shivering suppression.52 In rare cases in which the above regimen is still inadequate, pharmacologic paralysis should be initiated in addition to deep sedation. If hyperthermia is identified, the core temperature should be monitored (bladder, rectal, esophageal).
Co-ingestions should always be considered in the MA-intoxicated patient. A recent cross-sectional study found positive drug tests for non-prescribed fentanyl occurred in 7.9% of MA-positive patients – a 798% increase from 2013.54 Patients co-ingesting MA with a potent opioid, sedative-hypnotic, alcohol, or antipsychotic have an increased susceptibility to respiratory depression.
Supplemental oxygen is reserved for patients with respiratory depression secondary to sedation (or for concomitant respiratory pathology). In the event that patients are over-sedated or severely intoxicated and require endotracheal intubation, rocuronium may be preferred over succinylcholine for rapid sequence induction, due to the concern for rhabdomyolysis.
In all patients, treat concomitant injuries and pathology associated with intoxication. Frequent reassessments should be conducted in the undifferentiated patient in which MA-intoxication is suspected but cannot be confirmed. Cardiac monitoring is recommended for continued assessments in patients with autonomic hyperactivity.
See the algorithm below for a novel stepwise approach to the management of methamphetamine intoxication.
Approach to methamphetamine intoxication in the emergency setting. (Please refer to a pharmacy reference for further dosing information.)
Do methamphetamine-intoxicated patients require a workup?
Among patients with suspected MA-intoxication and normal vital signs, symptomatic treatment without further workup may be acceptable. However, patients with moderate to severe intoxication, hyperthermia, co-ingestion, or complaints such as chest pain, headache, or shortness of breath require further workup. Additionally, select acute MA features may overlap with encephalitis or sepsis, creating a diagnostic challenge that may warrant an early infectious workup. Each case requires the clinical judgment of the provider. When in doubt, the following workup should be considered:
- Labs – complete blood count, basic metabolic panel (Na, glucose), creatinine phosphokinase (CPK), troponin (if chest pain, dysrhythmia), acetaminophen and salicylate levels (if suspected co-ingestion)
- EKG (if chest pain, tachydysrhythmia)
- Echocardiogram (if suspicion for cardiomyopathy)
- Chest radiograph (if suspicion for pneumothorax, pneumonia)
- CT brain (head trauma, pre-lumbar puncture)
- Lumbar puncture (if suspected encephalitis)
- Urine drug screen (rarely useful in adults since treatment is based on clinical features. Consider in inconsolable babies and young children if suspicion)
- Urine pregnancy –in all women of child-bearing age
We worry about alcohol and opioid withdrawal – what about methamphetamine withdrawal?
Symptoms of MA withdrawal are relatively mild. However, a “crash” or “washout syndrome” may occur with symptoms of depression, anhedonia, irritability, poor concentration, insomnia, or marked somnolence.55 Although the majority of post-intoxication symptoms are transient and managed supportively, MA-induced psychosis may develop.40
What is the disposition following methamphetamine intoxication?
Patients with rhabdomyolysis, acute kidney injury, or those requiring multiple doses of sedation warrant admission for further workup and management. In the case of methamphetamine-induced psychosis, symptoms may last days following drug elimination, which may require a period of psychiatric management and observation.40 Those with mild agitation and vital sign improvement may be considered for discharge with close return precautions and outpatient follow up.
Before discharge, all patients should be assessed for suicidal or homicidal ideology. Consider counseling for substance use rehabilitation services and needle exchange programs.
- Methamphetamine (MA) is a highly addictive substance that has reached epidemic proportions;
- Unlike opioids, there is no analogous acute reversal agent or Medication-Assisted Treatment to curb cravings.
- MA is used by individuals of all ages, ethnicities, and socioeconomic classes.
- Maintain a suspicion for sympathomimetic drug use in patients presenting to the ED with acute psychosis.
- Benzodiazepines and antipsychotics are first-line treatments for acute MA toxicity.
- Treat hyperthermia and rhabdomyolysis aggressively to reduce sequelae.
- While diagnostic testing may be deferred in select low-risk patients, the multiorgan effects of MA should be considered.
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