Sympathomimetic Poisoning

Sympathomimetic Poisoning: Excerpt from The 5-Minute Pediatric Consult

Robert J. Hoffman, MDYuki Yasaka, MD

Sympathomimetic Poisoning - BASICS

Sympathomimetic Poisoning - description

• Excess autonomic stimulation by adrenergic agents produces the clinical syndrome typically described as “sympathomimetic.”
• Overdose from sympathomimetic agents occurs secondary to the use of prescription drugs, nonprescription drugs such as OTC cold medicine (e.g., pseudoephedrine), dietary supplements (e.g., ephedra, synephrine) and illicit drugs such as cocaine, amphetamine, and methamphetamine.
• The sequelae of sympathomimetic overdose are generally related to the neurological and cardiovascular systems.
• Severe problems may include agitation-induced hyperthermia, cardiac dysrrhythmia, hypertension, myocardial ischemia and infarction; CVA; seizure; and cardiovascular collapse.

Sympathomimetic Poisoning - epidemiology

• Cocaine, methamphetamine, and MDMA (ecstasy) are the 3 most common illicit drugs causing emergency visits in the US.
• Prescription stimulants such as methylphenidate and albuterol are often are frequent causes of intentional as well as unintentional poisoning.

Sympathomimetic Poisoning - risk factors

Prescription sympathomimetics, such as methylphenidate, pose some risk factor for both the recipient of the prescription as well as siblings.

Adolescents are at increased risk for using drugs of abuse.

Sympathomimetic Poisoning - pathophysiology

• Relevant pathophysiology is based on the adrenergic receptor type stimulated by the drug in question. The adrenergic receptors of relevance include alpha 1, beta 1, and beta 2 receptors.
• Ephedrine and pseudoephedrine stimulate both alpha and beta receptors:
  • Excessive cardiovascular stimulation results in symptoms qualitatively similar to those that occur with catecholamines.
  • Ephedrine and pseudoephedrine have weaker penetration of the CNS relative to drugs of abuse.
  • As a result, users may suffer from systemic
  • complications of the relatively larger doses necessary to achieve the CNS “high” of other stimulants.
• Non-elective beta adrenergic agonists
• Isoproterenol, rarely used, is the prototypical nonselective beta agonist causing the following:
  • Tachycardia, hypotension, tachydysrhythmias, myocardial ischemia and flushing due to its cardiostimulatory and vasodilatory properties
  • Commonly CNS effects of anxiety, fear, and headache occur.
• Selective beta 2 adrenergic agonists are commonly used, and these include albuterol, levalbuterol, salmeterol, terbutaline, and others.
• Common adverse effects include:
  • Tachycardia, palpitations, and tremor
  • Hypotension, often with widened pulse pressure
  • Nausea, vomiting, and sometimes diarrhea
  • Hyperglycemia and hypokalemia
  • Elevation of CPK as well as troponin, though myocardial infarction is never expected to occur in otherwise healthy children with selective beta 2 agonist exposure
  • Anxiety, fear, and headache also may occur.
• Alpha 1 selective agonists include phenylephrine and phenylpropanolamine, though the latter is no longer commercially produced in any meaningful quantity in the US.
  • Hypertension due to direct vasoconstrictive effects is the most common effect.
  • Reflex bradycardia may occur, particularly with phenylpropanolamine.
  • Headache due to elevated BP and even CVA may occur.

Sympathomimetic Poisoning - etiology

Causative agents:

• Agents with combined alpha and beta adrenergic activity: Epinephrine, norepinephrine,dopamine, ephedrine, and pseudoephedrine
• Alpha 1 adrenergic agonists: Phenylephrine, phenylpropanolamine
• Beta adrenergic agonists: Nonselective beta agonist isoproterenol
• Selective beta 1 agonists: Dobutamine
• Selective beta 2 agonists: Albuterol, salmeterol, terubutarine, ritodrine
• OTC agents: Ephedrine-containing cold medicine, ephedra, Ma Huang
• Illicit drugs: Cocaine, amphetamine, methamphetamine, MDMA (ecstasy)
• Theophylline and caffeine may cause a clinical syndrome of sympathomimetic poisoning.

Sympathomimetic Poisoning - associated conditions

• Many sympathomimetic agents are capable of producing psychiatric symptoms, particularly psychosis.
• This psychosis is similar to or indistinguishable from schizophrenia.
• 2 rare results of MDMA use include serotonin syndrome and SIADH with symptomatic hyponatremia.

Sympathomimetic Poisoning - DIAGNOSIS

Sympathomimetic Poisoning - signs & symptoms

• The clinical effects of these agents overdose vary based on their receptor selectivity.
• Most agents have some degree of combined alpha and beta adrenergic activity (ephedrine, pseudoephedrine).
  • Hypertension, tachycardia, dysrhythmia, acute coronary syndromes, pulmonary edema and cerebrovascular injury, anxiety, a sense of impeding doom, apprehension, fear, and headache.
  • At very high doses, agents cross the blood–brain barrier result in central nervous system symptoms, such as headache, seizures, and intracranial hemorrhage

Sympathomimetic Poisoning - history

• History of exposure may be helpful, but is often unavailable or deliberately concealed, particularly use of illicit drugs such as cocaine, methamphetamine, and ecstasy.
• The use of OTC medicines, such as multisymptom cold preparations or dietary supplements may be obtained.
• High suspicion of sympathomimetic overdose especially in patients with the sympathomimetic toxidrome.
• The onset of symptoms usually occurs within 1 hour.
  • Typically, prescription and OTC sympathomimetic agents are inhaled or orally administered.
  • Inhalation or injection results in immediate symptoms.
  • Cocaine, amphetamine, and methamphetamine or the sympathomimetics most commonly used in this manner.
  • Sympathomimetic toxicity following ingestion typically peaks 1–4 hours and last 4–8 hrs, but sustained-release preparations may alter this time course.

Sympathomimetic Poisoning - physical exam

Sympathomimetic toxicity is a clinical diagnosis.

• Vital sign derangement is the most common and most reliable indicator of toxicity.
• Mental status changes are also common though less reliable as they do not occur with the same regularity and may be the result of toxicologic or psychiatric phenomenon.
• The patient’s general appearance (e.g., agitation, diaphoretic, delirium, psychotic) is often suggestive of toxicity.
• HEENT: Headache, mydriasis, visual changes, epistaxis
• Chest: Chest pain due to dysrhythmia, myocardial ischemia, myocardial infarction, etc. may be a complaint.
• Tachycardia and hypertension are the most common vital sign abnormalities.
• Skin: Diaphoresis, flushing, the track marks associated with IV drug use.
• CNS: Focal neurologic findings may occur. Focal cranial nerve abnormalities are particularly concerning for the possibility of cerebrovascular accident. CNS stimulation or agitation is very common.

Sympathomimetic Poisoning - tests

• Sympathomimetic overdose is a clinical diagnosis and assays are only adjunctive.
• Unless there are specific forensic indications, such as malicious poisoning or child abuse, drug of abuse screening is not recommended and is not useful.
• Serum acetaminophen level should be considered in patients with ingestion with intent of self harm.
• The measurement of electrolytes, BUN, creatinine, and blood sugar may be useful.
• Cardiac markers (e.g., CPK-MB, troponin) are appropriate to screen for cardiac injury.
• An EKG should be obtained to assess for ischemia as well as dysrhythmias

Sympathomimetic Poisoning - imaging

A noncontrast head CT should be obtained in unresponsive patients or those with focal neurologic deficits.

Sympathomimetic Poisoning - differencial diagnosis

• Hyperthyroidism/Thyroid storm
• Anticholinergic syndrome
• Pheochromocytoma
• Withdrawal syndromes
• Mania
• Subarachnoid hemorrhage
• Serotonin syndrome
• Neuroleptic malignant syndrome
• Other situations of increased endogenous catecholamine release

Sympathomimetic Poisoning - TREATMENT

Sympathomimetic Poisoning - initial stabilization

Managing ABCs should be addressed 1st, but sympathomimetic toxicity usually does not result in illness requiring any specific airway, breathing, or circulation issues.

Sympathomimetic Poisoning - general measures

Maintaining vital signs within acceptable limits and controlling patient agitation are commonly required.

• Managing ABCs is paramount.
• If protocol permits, sedation of agitated patients with a benzodiazepine may be appropriate.
• Use of benzodiazepines is helpful to address both cardiovascular stimulation as well as psychomotor agitation.
• Use of specific cardiovascular medications may be needed.
• Use of antipsychotics, such as haloperidol or droperidol, is relatively contraindicated both because these medications may lower seizure threshold, impair heat dissipation, and increase risk of cardiac dysrhythmia.

Sympathomimetic Poisoning - activity

Patients with hyperthermia, psychomotor agitation, or psychiatric symptoms should have limited activity.

• Such patients may also initially require physical restraint that is expediently converted to chemical restraint.

Sympathomimetic Poisoning - special therapy

Severe hyperthermia should be treated with active cooling.

• Patients with core temperature of ≥107°F should be placed in an ice bath and have core temperature monitored.

Sympathomimetic Poisoning - iv fluids

Unless there is a contraindication, at least maintenance IV fluid should be administered.

This may serve to protect against rhabdomyolysis as well as potential dehydration that may occur with stimulant exposure.

Sympathomimetic Poisoning - medication

Agitation, vasoconstrictive effects, chronotropic and inotropic effects, and psychomotor agitation are the most common issues requiring mediation therapy for sympathomimetic toxicity.

Sympathomimetic Poisoning - first line

• Psychomotor agitation may be managed with benzodiazepines.
• The quantity of benzodiazepine required will directly depend on degree of adrenergic stimulation.
• In some cases, large doses may be required for sedation.
  • Lorazepam in doses of 0.1 mg/kg IV q15min titrated to effect is preferred due to predictable duration of action.
  • Diazepman 0.1 mg/kg IV q15min titrated to effect may also be used.
• Vasoconstricitve effects may be managed with a variety of medications.
  • Phentolamine 0.1 mg/kg/dose (up to 5 mg/dose) IV repeated q10min PRN
  • A dihydropyridine calcium channel blocker, such as nifedipine or amlodipine, may be used.
  • Sodium nitroprusside 0.3–10 mcg/kg/min IV, titrated to effect
• Chronotropic and inotropic effects may be managed with conduction-modulating calcium channel blockers such as diltiazem or verapamil.

Sympathomimetic Poisoning - second line

• A beta blocker may be used only if an alpha adrenergic antagonist is concomitantly administered.
• Use of a beta blocker without alpha blockade may result in paradoxical increase in BP and death.
  • Labetalol has some alpha adrenergic blockade and may be used alone as a second-line agent: 0.2–0.5 mg/kg/dose IV, maximal dose 20 mg, followed by infusion of 0.25–1 mg/kg/h
  • Esmolol: 500 mcg/kg/min IV bolus followed by infusion 50 mcg/kg/min titrated to effect up to 500 mcg/kg/min
• Severe cardiovascular symptoms resulting from beta agonists or methylxanthines such as theophylline or caffeine may be treated with a beta blocker.
  • Although this treatment may seem counter-intuitive in the management of hypotension
  • Severe beta 2 agonist effects resulting in hypotension may be counteracted by using a beta blocker.
  • Such therapy should only be undertaken under the direction of a medical toxicologist, intensivist, or other clinician familiar with and experienced with use of such cardiovascular medications.

Sympathomimetic Poisoning - FOLLOW UP

Sympathomimetic Poisoning - disposition

Sympathomimetic Poisoning - admission criteria

Any patient with severely deranged vital signs, end-organ manifestations such as chest pain, severe headache, focal neurologic deficit, or agitation should be admitted.

Sympathomimetic Poisoning - discharge criteria

Any patient with vital signs within safe limits, normal mental status, and no evidence of end-organ damage or manifestations may be discharged from the emergency department or inpatient unit.

Sympathomimetic Poisoning - issues for referral

• Patients with intentional substance abuse should be referred for drug counseling.
• Patients exposed to stimulants as a result of parental abuse or neglect should be referred to appropriate child protective authorities.

Sympathomimetic Poisoning - prognosis

If end-organ damage such as myocardial infarction or CVA are prevented, prognosis for full recovery to premorbid status is excellent.

Sympathomimetic Poisoning - complications

The most common catastrophic complications are cardiovascular, including dysrythmia, myocardial infarction, and CVA.

Sympathomimetic Poisoning - patient monitoring

Cardiac monitoring with frequent vital sign assessment is critical in assuring that vital signs are maintained within acceptable limits.

Sympathomimetic Poisoning - bibliography

Hoffman RJ, Nelson L. Poisoning by sympathomimetics. In: Brent J, Burkhart K, Donovan JW, et al., eds. Critical Care Toxicology, Diagnosis and Management of the Critically Poisoned Patient. New York: Mosby; 2005.

Sympathomimetic Poisoning - CODES

Sympathomimetic Poisoning - icd9

305.7 Amphetamine or related acting sympathomimetic abuse

Book Source Details

• Book Title: The 5-Minute Pediatric Consult
• Author(s): M. William Schwartz MD; et al.
• Year of Publication: 2008
• Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.

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More About This Book: Title: The 5-Minute Pediatric Consult Authors: M. William Schwartz MD; et al. Publisher: Lippincott Williams & Wilkins Copyright: 2008 ISBN: 0-7817-7577-9

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