Electronic cigarettes

Background

  • Nicotine containing products that are currently not regulated by the FDA
  • On 4/25/14, the FDA proposed legislation to allow them to regulate e-cigarettes like other tobacco products[1]
  • Nicotine usually suspended in a propylene glycol or vegetable glycerin solution (labeled as %PG/%VG)[2][3]
  • From Sept 2010 - Feb 2014, there were 16,248 toxic exposures to traditional cigarettes and 2,405 toxic exposures to e-cigarettes[4]
  • Exposures to e-cigarettes increased from 1/month to 215/month over that time period

Product Types

  • Some are fixed products with no refill capabilities (Ex. Blu e-cigarettes) while others can be refilled with replacement nicotine fluid
  • Common strengths include 6mg/ml (low), 12mg/ml (medium-low), 18mg/ml (medium), 24mg/ml (high) and 36mg/ml (Ultra-high)
  • Common refill sizes range from 5ml to 30ml
  • Products come in a variety of flavors that can be enticing to children
  • Bubble gum, root beer, extreme soda, Ecto-cooler, Banana cream pie, toasted marshmallow, etc.

Pathophysiology

  • Fatal intoxications are rare and estimates suggest 60mg - 500mg as a lethal dose. Traditional cigarettes deliver approximately 2mg of nicotine [5]

Absorption

  • Absorbed transdermally, orally and via inhalation

Biphasic presentation

  • Initially excitation secondary to excitation of the presynaptic nAChR which facilitates release of neurotransmitters
  • Second phase characterized by desensitization of the receptors and decreased neurotransmitter release

Clinical Features

Postive Negative
Anxiolysis Gastrointestinal Distress
Congnitive Enhancement Hypothermia
Cerebrovasodilation Emesis
Neuroprotection Hypertension
Analgesia Seizures
Antipscyhotic Respiratory Distress

Eye Pain

  • Nicotine is also an irritant and eye pain is a frequent complaint

Fasciculations

  • Due to the neuromuscular nicotinic activation

Hypersalivation

At high doses nicotine will activate muscarinic receptors

Biphasic presentation

  • Initially present with excitation, N/V/D, salivation, tachycardia, hypertension, diaphoresis
  • Delayed presentation is hypotension, bradycardia, hypoventilation, fasiculations, seizures, coma, and death

Evaluation

  • Exposure to nicotine containing liquid
  • Toxidrome similar to nicotinism

Work-Up

Differential Diagnosis

Management

Decontamination

  • Providers should wear appropriate PPE during decontamination.
    • Neoprene or nitrile gloves and gown (latex and vinyl are ineffective)
  • Dispose of all clothes in biohazard container
  • Wash patient with soap and water

Supportive Care

  • IVF, O2, Monitor
  • Aggressive airway management is of utmost importance.
    • Intubation often needed due to significant respiratory secretions / bronchospasm.
    • Use nondepolarizing agent (Rocuronium or Vecuronium)
    • Succinylcholine is absolutely contraindicated
  • Benzodiazepines for seizures

Antidotes

  • Dosing with atropine and pralidoxime are time dependent and provides ability to reverse symptoms while awaiting agent metabolism
  • For exposure to nerve agents, manufactured IM autoinjectors are available for rapid administration:
    • Mark 1
      • Contains 2 separate cartridges: atropine 2 mg + 2-PAM 600 mg
      • Being phased out with newer kits
    • DuoDote
      • Single autoinjector containing both medications
      • Same doses as Mark 1: atropine 2 mg + 2-PAM 600 mg

Antidotes

Atropine

  • Competitively blocks muscarinic sites (does nothing for nicotinic-related muscle paralysis)
  • May require massive dosage (hundreds of milligrams)
  • Dosing[6]
  • Adult: Initial bolus of 2-6mg IV; titrate by doubling dose q5-30m until tracheobronchial secretions controlled
    • Once secretions controlled → start IV gtt 0.02-0.08 mg/kg/hr
    • Child: 0.05-0.1mg/kg (at least 0.1mg) IV; repeat bolus q2-30m until tracheobronchial secretions controlled
    • Once secretions controlled → start IV gtt 0.025 mg/kg/hr
  • No max dose, doses >400mg have been reported[7]

Pralidoxime

  • AKA 2-PAM
  • For Organophosphate poisoning only - reactivates AChE by removing phosphate group → oxime-OP complex then excreted by kidneys.
    • This must be done before "aging" occurs - conformational change that makes OP bond to AChE irreversible[8]
    • Pralidoxime can actually bind and inhibit AChE once all AChE enzymes have aged, and can make the toxicity worse
    • Window to aging depends on the agent, and is a matter of debate, but pralidoxime within 1-2 hours of exposure is the goal
  • Dosing[6]
    • Adult: 1-2gm IV over 15-30min; repeat in 1 hour if needed or 50 mg/hr infusion.
    • Child: 20-40mg/kg IV over 20min; repeat in 1 hour if needed or 10-20 mg/kg/hr infusion.

Disposition

  • Admit for symptomatic poisonings

See Also

Nicotine Poisoning

References

  1. Deeming Tobacco Products To Be Subject to the Federal Food, Drug, and Cosmetic Act, as Amended by the Family Smoking Prevention and Tobacco Control Act PDF
  2. PG e-liquid, VG e-liquid or PG/VG Mix e-liqud? http://www.bestecig.com/help.asp?id=57
  3. Carmines EL, Gaworski CL. Toxicological evaluation of glycerin as a cigarette ingredient. Food Chem Toxicol. 2005 Oct;43(10):1521-39
  4. CDC reports. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6313a4.htm
  5. Mayer B. How much nicotine kills a human? Tracing back the generally accepted lethal dose to dubious self-experiments in the nineteenth century. Arch Toxicol. 2014; 88: 5–7
  6. 6.0 6.1 Agency for Toxic Substances and Disease Registry, Case Studies in Environmental Medicine, Cholinesterase Inhibitors: Including Pesticides and Chemical Warfare Nerve Agents. Centers for Disease Control (CDC). PDF Accessed 06/21/15
  7. Hopmann G, Wanke H. Höchstdosierte Atropinbehandlung bei schwerer Alkylphosphatvergiftung [Maximum dose atropin treatment in severe organophosphate poisoning (author's transl)]. Dtsch Med Wochenschr. 1974;99(42):2106-2108. doi:10.1055/s-0028-1108097
  8. Eddleston M, Szinicz L, Eyer P, Buckley, N (2002) Oximes in Acute Organophosphate Pesticide Poisoning: a Systematic Review of Clinical Trials. QJM. 95(5): 275–283.