Sympathomimetic Poisoning, Emergency Medicine

Basics

Description

Direct or indirect stimulation of adrenergic receptors in sympathetic and central nervous systems
Often no correlation between dosage and degree of toxicity
Cocaine may also block sodium channels of cardiac myocytes, leading to "tricyclic " or class 1a " type dysrhythmias.

Sympathomimetic poisoning in children may present similarly to meningitis or other systemic illness.
Urinary toxicology screening may be only way to discover sympathomimetic poisoning in children presenting with altered mental status.
Methylphenidate (Ritalin, Concerta) and other sympathomimetics used for ADHD may cross-react with altered mental status.

Etiology

Sympathomimetic toxicity can result from use of any sympathetically active drug, including:
- All amphetamines, methamphetamines, and derivatives (ecstasy, MDMA)
- Cocaine
- Synthetic cathinones "Bath Salts "
- Phencyclidine (PCP)
- Lysergic acid diethylamide (LSD)
- Decongestants (rare)
Drug delivery routes: Inhalation, injection, snorting, or ingestion

Diagnosis

Signs and Symptoms

Vital signs:
- Tachycardia:
  - Bradycardia possible for cocaine and some other decongestants
- Increased BP:
  - Severely intoxicated patients may be hypotensive.
- Tachypnea
- Hyperthermia:
  - Often present, may be severe, and is often overlooked
CNS:
- Anxiety
- Headache
- Agitation
- Altered mentation
- Diaphoresis
- Seizures
- Stroke
- Dystonia (rare)
Cardiovascular:
- Palpitations
- Chest pain
- Myocardial ischemia or infarction
- Tachydysrhythmias
- Cardiovascular collapse
- Murmur (e.g., endocarditis)
Other:
- Dilated pupils
- Dry mucous membranes
- Urinary retention may cause enlarged bladder.
- Needle track marks or abscesses on extremities should be sought.
- Increased or decreased bowel sounds
- The presence of diaphoresis and bowel sounds may help to differentiate sympathomimetic toxicity from anticholinergic poisoning.

History

Assess history for possible sympathomimetic agents:
- Cold preparations
- Prescription amphetamines
- Recreational drug use
Assess for possible coingestions
Evaluate for symptoms of end organ injury:
- Chest pain
- Shortness of breath
- Headache, confusion, and vomiting

Physical Exam

Common findings include:
- Agitation
- Tachycardia
- Diaphoresis
- Mydriasis
Severe intoxication characterized by:
- Tachycardia
- Hypertension
- Hyperthermia
- Agitated delirium
- Seizures
- Diaphoresis
Hypotension and respiratory distress may precede cardiovascular collapse
Evaluate for associated conditions:
- Cellulitis and soft tissue infections
- Diastolic cardiac murmurs or unequal pulses
- Examine carefully for trauma
- Pneumothorax from inhalation injury
- Focal neurologic deficits

Essential Workup

Monitor vital signs:
- Increased temperature (>40 °C possible):
  - Core temperature recording essential
  - Peripheral temperature may be cool
  - Indication for urgent cooling
  - Ominous prognostic sign
- BP:
  - Severe hypertension can lead to cardiac and neurologic abnormalities.
  - Late in course, hypotension may supervene.
ECG:
- Signs of cardiac ischemia
- Ventricular tachydysrhythmias
- Reflex bradycardia

Diagnosis Tests & Interpretation

Lab

Urinalysis for:
- Blood
- Myoglobin
Electrolytes, BUN/creatinine, glucose:
- Hypoglycemia may contribute to altered mental status.
- Acidosis may accompany severe toxicity.
- Rhabdomyolysis may cause renal failure.
- Hyperkalemia " life-threatening consequence of acute renal failure
Coagulation profile to monitor for potential disseminated intravascular coagulation (DIC):
- INR, PT, PTT, platelets
Creatine phosphokinase (CPK):
- Markedly elevated in rhabdomyolysis
Urine toxicology screen:
- For other toxins with similar effects (e.g., cocaine)
- Some amphetamine-like substances (e.g., synthetic cathinones, MDMA) may not be detected.
Salicylate and acetaminophen levels if suicide attempt a possibility or if OTC medications ingested (e.g., cough, cold)
Venous blood gas, ABG

Imaging

CXR:
- Adult respiratory distress syndrome
- Noncardiogenic pulmonary edema
Head CT for:
- Significant headache
- Altered mental status
- Focal neurologic signs
- Subarachnoid hemorrhage, intracerebral bleed

Diagnostic Procedures/Surgery
Lumbar puncture for:

Suspected meningitis (headache, altered mental status, hyperpyrexia)
Suspected subarachnoid hemorrhage and CT normal

Differential Diagnosis

Sepsis
Thyroid storm
Serotonin syndrome
Neuroleptic malignant syndrome
Pheochromocytoma
Subarachnoid hemorrhage
Drugs that cause delirium:
- Anticholinergics
- Tricyclic antidepressants
- Sympathomimetics
- Ethanol withdrawal
- Sedative/hypnotic withdrawal
- Hallucinogens
- PCP
Drugs that cause hypertension and tachycardia:
- Sympathomimetics
- Anticholinergics
- Ethanol withdrawal
- PCP
- Caffeine
- Monoamine oxidase inhibitors
- Theophylline
- Nicotine
Drugs that cause seizures:
- Camphor
- Carbamazepine
- Carbon monoxide
- Chlorinated hydrocarbons
- Cholinergics
- Cyanide
- Ethanol withdrawal
- Hypoglycemics
- Isoniazid
- Lead
- Lithium
- Local anesthetics
- Phenothiazines
- Propoxyphene
- Salicylates
- Sedative/hypnotic withdrawal
- Strychnine
- Sympathomimetics
- Theophylline
- Tricyclic antidepressants

Treatment

Pre-Hospital

Patient may be uncooperative or violent.
Secure IV access.
Protect from self-induced trauma.

Initial Stabilization/Therapy

ABCs
Establish IV 0.9% NS access
Cardiac monitor
Naloxone, dextrose (or Accu-Chek), and thiamine if altered mental status

Ed Treatment/Procedures

Decontamination:
- Gastric lavage not routinely recommended:
  - May consider if recent (within 1 hr) of life-threatening ingestion.
  - Activated charcoal not routinely recommended.
  - Consider activated charcoal with sorbitol in 1st dose if administered.
  - Consider activated charcoal with body stuffer or body packer ingestions.
- Whole-bowel irrigation with polyethylene glycol solution " electrolyte solution for body packers
Hypertensive crisis:
- Initially administer benzodiazepines if agitated.
- α-blocker (phentolamine) as 2nd-line agent
- Nicardipine or nitroglycerin IV for severe HTN unresponsive to benzodiazepines
- Nitroprusside can also be used for severe, unresponsive HTN
- Avoid ²-blockers, which may exacerbate HTN due to unopposedα activity
Agitation, acute psychosis:
- Administer benzodiazepines.
- Use butyrophenones (e.g., haloperidol) with caution to manage agitation:
  - May lower seizure thresholds and may prolong QT duration
Dysrhythmias:
- Sodium bicarbonate IV push is treatment of choice for ventricular dysrhythmias indicative of sodium channel blocking (i.e., widened QRS complex).
- Lidocaine for ventricular dysrhythmias refractory to alkalinization, benzodiazepines, and supportive care
Hyperthermia:
- Benzodiazepines if agitated
- Active cooling if temperature >40 °C:
  - Tepid water mist
  - Evaporate with fan
Paralysis:
- Indicated if muscle rigidity and hyperactivity contributing to persistent hyperthermia
- Nondepolarizing paralytic preferred
Rhabdomyolysis:
- Administer benzodiazepines.
- Hydrate with 0.9% NS.
- Maintain urine output at 1 " 2 mL/min
- Hemodialysis (if acute renal failure and hyperkalemia occur)
Seizures:
- Maintain airway
- Administer benzodiazepines
- Phenobarbital if unresponsive to benzodiazepines

Medication

Activated charcoal: 1 " 2 g/kg up to 100 g PO
Dextrose: D50W 1 amp: 50 mL or 25 g (peds: 1 to 2 mL/kg of D25W; infants: 2.5 to 5.0 mL/kg of D10%) IV
Diazepam (benzodiazepine): 5 " 10 mg (peds: 0.2 " 0.5 mg/kg) IV. Not recommended <6 months of age
Lorazepam (benzodiazepine): 2 " 6 mg (peds: 0.03 " 0.05 mg/kg) IV
Nicardipine IV infusion at 5 mg/h titrate by 2.5 mg/h q5min to max. 15 mg/h
Nitroprusside: 0.5 " 10 Όg/kg/min IV (titrated to BP)
Phenobarbital: 15 " 20 mg/kg at 25 " 50 mg/min until cessation of seizure activity; monitor for respiratory depression. Safety not established <6 years of age
Phentolamine: 1 " 5 mg IV over 5 min (titrated to BP)
Sodium bicarbonate: 1 or 2 amps (50 mEq/amp) (peds: 1 " 2 mEq/kg) IV push

Follow-Up

Disposition

Admission Criteria

Admit all body packers or stuffers to hospital.
Severe manifestations of toxicity to monitored bed:
- Seizures
- Dysrhythmias
- Hyperthermia
- Rhabdomyolysis
- Severe hypertension
- Altered mental status
Ischemic chest pain

Discharge Criteria
Mildly intoxicated patients can be observed and treated in ED until resolution of clinical manifestations.

Followup Recommendations

Patients may need referral for chemical dependency rehab and detoxification

Pearls and Pitfalls

Admit patients with severe or persistent symptoms
Hyperthermia above 40 °C may be life threatening:
- Treat with aggressive sedation and active cooling
Recognize rhabdomyolysis and hyperkalemia
Avoid physical restraints in agitated patients if possible
Consider associated emergency conditions:
- Chest pain " acute coronary syndrome
- Infection in altered patients with fevers and history of IV drug use
- Traumatic injury with methamphetamine abuse
Benzodiazepines are 1st-line therapy in symptomatic sympathomimetic intoxication

Additional Reading

Carvalho M, Carmo H, Costa VM, et al. Toxicity of amphetamines: An update. Arch Toxicol. 2012;86:1167 " 1231.
Greene SL, Kerr F, Braitberg G. Review article: Amphetamines and related drugs of abuse. Emerg Med Australas. 2008;20:391 " 402.
Prosser JM, Nelson LS. The toxicology of bath salts: A review of synthetic cathinones. J Med Toxicol. 2012;8:33 " 42.
Schep LJ, Slaughter RJ, Beasley DM. The clinical toxicology of metamfetamine. Clin Toxicol (Phila). 2010;48:675 " 694.

Codes

ICD9

971.2 Poisoning by sympathomimetics [adrenergics]

ICD10

T44.901A Poisn by unsp drugs aff the autonm nervous sys, acc, init

SNOMED

45536007 poisoning by sympathomimetic drug (disorder)

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