CALL US...TM

The Official Newsletter of the California Poison Control System
Volume 3, Number 2.
Summer 2005

Nicotine Poisoning

Lee Cantrell, Pharm D.

 

Introduction

Nicotine is a water-soluble alkaloid found primarily in plants of the Nicotiana species, although it is also found in lower quantities in other members of the Solanaceae (nightshade) family.  It is a colorless, bitter-tasting liquid that is an extremely potent toxin with a probable oral lethal dose in humans of less than 5 milligrams/kilogram.  Nicotine was first isolated in 1828, however its use as a recreational drug in tobacco products dates back centuries.  In more recent times nicotine has been used in medicinal preparations, insecticides and in tanning.  While serious poisonings are rare, nicotine can cause a wide array of symptoms in poisoning victims that can be difficult for clinicians to interpret.

 

Case presentation

A 2 year-old girl was brought to the emergency department by her parents approximately 20 minutes after chewing on a large wad of nicotine gum.  An empty package of 48 pieces was found at home and the child had vomited 3-4 times in route.  Upon initial examination, the child was agitated, drooling excessively, diaphoretic, tachycardic and hypertensive. Twenty minutes later, the child had a generalized seizure that was treated with diazepam.  She rapidly became less responsive, had precipitous drops in her blood pressure, heart and respiratory rates and was intubated endotracheally. She was admitted to the PICU where her condition gradually improved over the next 16 hours and she was successfully extubated.  She was discharged home the following day without apparent sequelae. 

 

Questions:

1.      What are the mechanisms by which nicotine exerts its effects?

2.      What spectrum of clinical symptoms can be expected following a nicotine poisoning?

3.      What treatment options are available for nicotine toxicity?

 

Epidemiology

In 2004, 557 cases of exposure to nicotine-containing substances were reported to the California Poison Control System. The vast majority (85%) involved children aged 5 years and younger.  Recreational tobacco products (cigarettes, chewing tobacco, etc.) were involved in 481 cases (86%), pharmaceutical preparations (patches, gum, lozenges) in 72 cases (13%) and nicotine-containing plants in 4 cases (1%).  Although none of these patients experienced severe or lethal poisonings, historically, both serious and lethal poisonings have been described with ingestions of raw plant material, nicotine insecticides, pharmaceutical/medicinal preparations, and commercially prepared tobacco products such as cigarettes and nicotine chewing gum (References: Malizia E, Andreucci G, & Alfani F: Acute intoxication with nicotine alkaloids and cannabinoids in children from ingestion of cigarettes.  Human Toxicol 1983; 2:315-316, and Smolinske SC, Spoerke DG, & Spiller SK: Cigarette and nicotine chewing gum toxicity in children.  Human Toxicol 1988; 7:27-31). Severe poisonings have also resulted from acute dermal exposures to pharmaceutical and insecticidal nicotine preparations while occupational dermal exposures are responsible for green tobacco sickness.  Additionally, a report exists of severe nicotine poisoning secondary to the administration of a tobacco extract enema.  While most reported cases are unintentional in nature, a substantial number involve intentional exposures.  Examples range from topical self-treatment of scabies with concentrated nicotine insecticides to extracting nicotine from plants for recreational use to suicide attempts by chewing nicotine gum and patches or ingesting raw tobacco plant material.

 

Pathophysiology

Nicotine is well absorbed via the lungs, buccal mucosa, skin, rectum and gastrointestinal tract, although the acidic environment of the stomach decreases absorption.  It has an elimination half-life of 2 hours and a volume of distribution of roughly 1 L/kg. The toxicity of nicotine is a result of its stimulation of nicotinic acetylcholine receptors in the autonomic nervous system, central nervous system, and at the neuromuscular junction.  The symptoms of nicotine toxicity are dose-dependent and can vary depending on the bioavailability of the nicotine-containing substance. In the peripheral nervous system, lower doses of nicotine produce stimulation of both sympathetic and parasympathetic autonomic ganglia, while higher doses rapidly produce ganglionic blockade.  This “biphasic” action also occurs in the adrenal medulla, with lower doses of nicotine resulting in catecholamine release and larger doses resulting in inhibition of release.  In the central nervous system, low doses of nicotine produce weak analgesia and respiratory stimulation, while larger doses result in seizures and respiratory depression. Stimulation of neuromuscular end plates causes fasciculations that progress to weakness and respiratory arrest due to neuromuscular blockade.

 

Clinical presentation

Initial clinical symptoms typically develop within 15-90 minutes of an acute exposure and include: nausea, vomiting, salivation, dizziness, confusion, and diaphoresis.  Early cardiopulmonary symptoms consist of hypertension, tachycardia and hyperpnea.  These stimulatory symptoms can be indicative of a relatively mild poisoning or the transient early stages of a more severe poisoning.  From this stage, patients can rapidly progress to more serious symptoms including muscle twitching, weakness, seizures, hypotension, bradycardia, respiratory depression, coma and paralysis.  The duration of clinical effects is typically 1-2 hours in minor poisonings and up to 24 hours in severe poisonings.  Death is usually attributed to paralysis of respiratory muscles or circulatory collapse and usually occurs within 1 hour after an acute exposure.  Green tobacco sickness secondary to prolonged dermal exposure to wet tobacco (eg. in tobacco workers) is characterized by nausea, vomiting, headaches, dizziness and diaphoresis.  The onset of the illness is 3 to 17 hours after exposure with duration of one to three days.

 

Diagnosis

Obtaining a history of exposure to a nicotine-containing substance in a patient with correlating (often non-specific) clinical findings is the best approach to diagnosing nicotine poisoning.  While nicotine or its metabolite cotinine can be detected in comprehensive urine toxicology screens, interpretation of positive findings is difficult due to their qualitative nature and the relative ubiquity of tobacco smoke.  Serum levels can be performed but are also difficult to interpret and are unlikely to be available rapidly enough to be useful in an acute poisoning. 

 

Treatment

Patients arriving soon after potentially toxic nicotine ingestions should receive gastrointestinal decontamination with activated charcoal.  Charcoal administration in these cases may be difficult since vomiting is frequently seen early in the clinical course of nicotine poisoning, and can be dangerous in the presence of seizures and coma.  Symptomatic dermal exposures should be thoroughly decontaminated with soap and water.  There is no specific antidote for nicotine poisoning and treatment should be geared towards clinical symptoms.  Benzodiazepines are usually effective for treating seizures.  Hypotension should be treated with fluids initially and with a vasopressor for refractory cases.  Atropine can be considered for the treatment of clinically significant muscarinic symptoms or bradycardia.  Respiratory compromise may require intubation and mechanical ventilation.  A minimum observation time of 4-6 hours after oral and dermal exposures should be considered, although ingestions involving intact nicotine patches or plant material may warrant longer observation periods.

 

Summary and discussion of case questions

1.    The toxicity of nicotine is a result of its stimulation of nicotinic acetylcholine receptors in the autonomic nervous system, central nervous system, and at the neuromuscular junction.

2.    Initial symptoms typically reflect the stimulatory effects of nicotine on various central and peripheral nervous system receptors and include nausea and vomiting, dizziness and confusion in mild cases, and muscle twitching and seizures in more serious exposures.  The stimulatory phase is followed by an often pronounced inhibitory phase marked by decreased catecholamine release, neuromuscular blockade, CNS and respiratory depression.

3.    Early decontamination of potentially dangerous ingestions with oral activated charcoal may be beneficial, but might be difficult to achieve due to the common presence of gastrointestinal symptoms and the risk of seizures and coma.  No specific antidote exists and treatment consists of symptomatic and supportive care.

 

Consultation assistance

Consultation with a specialist in poison information or with a medical toxicologist can be obtained free of charge by calling the California Poison Control System at 1-800-411-8080.

This issue of CALL US... was written by Lee Cantrell, Pharm D.


CALL US... is published by the California Poison Control System. Editorial Board: Executive Director, Stuart E. Heard, PharmD; CPCS Medical Directors Timothy E. Albertson, MD, Richard Clark, MD, Richard Geller, MD, Kent R. Olson, MD; CPCS Managing Directors Judith Alsop, PharmD, Thomas E. Kearney, PharmD, Lee Cantrell, PharmD. Managing Editor: Richard Clark, M.D.

The California Poison Control System is operated by the School of Pharmacy, University of California, San Francisco.

 

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