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CALL US...TM
The
Official Newsletter of the
Volume 3, Number 2.
Summer 2005
Nicotine Poisoning
Lee Cantrell, Pharm D.
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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.
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