Nicotine poisoning describes the symptoms of the toxic effects of nicotine following ingestion, inhalation, or skin contact. Nicotine poisoning can potentially be deadly, though serious or fatal overdoses are rare. More recent cases of poisoning typically appear to be in the form of Green Tobacco Sickness, or due to unintended ingestion of tobacco or tobacco products or consumption of nicotine-containing plants.
Standard textbooks, databases, and safety sheets consistently state that the lethal dose of nicotine for adults is 60 mg or less (30–60 mg), but there is overwhelming data indicating that more than 500 mg of oral nicotine is required to kill an adult. ingestion of more than this may cause a child to become severely ill. The nicotine in the e-liquid of an electronic cigarette can be hazardous to infants and children through accidental ingestion or skin contact. In some cases children have become poisoned by topical medicinal creams which contain nicotine.
People who harvest or cultivate tobacco may experience Green Tobacco Sickness (GTS), a type of nicotine poisoning caused by skin contact with wet tobacco leaves. This occurs most commonly in young, inexperienced tobacco harvesters who do not consume tobacco.
Signs and symptoms
thumb|300px|Symptoms of nicotine poisoning related to e-cigarette calls to US [[poison control centers|alt=The most common adverse effects in e-cigarette calls to US poison control centers: Ingestion exposure resulted in vomiting, nausea, drowsy, tachycardia, or agitation. Inhalation/nasal exposure resulted in nausea, vomiting, dizziness, agitation, or headache. Ocular exposure resulted in eye irritation or pain, red eye or conjunctivitis, blurred vision, headache, or corneal abrasion. Multiple routes of exposure resulted in eye irritation or pain, vomiting, red eye or conjunctivitis, nausea, or cough. Dermal exposure resulted in nausea, dizziness, vomiting, headache, or tachycardia.]]
Nicotine poisoning tends to produce symptoms that follow a biphasic pattern. The initial symptoms are mainly due to stimulatory effects and include nausea and vomiting, excessive salivation, abdominal pain, pallor, sweating, hypertension, tachycardia, ataxia, tremor, headache, dizziness, muscle fasciculations, and seizures.
Calls to US poison control centers related to e-cigarette exposures involved inhalations, eye exposures, skin exposures, and ingestion, in both adults and young children. Minor, moderate, and serious adverse effects involved adults and young children. 58% of e-cigarette calls to US poison control centers were related to children 5 years old or less. The majority of cases (65%) were in children under age five and 15% were in ages 5–24. However the widely used human LD<sub>50</sub> estimate of 0.5–1.0 mg/kg was questioned in a 2013 review, in light of several documented cases of humans surviving much higher doses; the 2013 review suggests that the lower limit causing fatal outcomes is 500–1000 mg of ingested nicotine, corresponding to 6.5–13 mg/kg orally. An accidental ingestion of only 6 mg may be lethal to children.
It is unlikely that a person would overdose on nicotine through smoking alone. The US Food and Drug Administration (FDA) stated in 2013: "There are no significant safety concerns associated with using more than one [over the counter] OTC [nicotine replacement therapy] NRT at the same time, or using an OTC NRT at the same time as another nicotine-containing product—including a cigarette." Ingestion of nicotine pharmaceuticals, tobacco products, or nicotine containing plants may also lead to poisoning.
The recent rise in the use of electronic cigarettes, many forms of which are designed to be refilled with nicotine-containing "e-liquid" supplied in small plastic bottles, has renewed interest in nicotine overdoses, especially the possibility of young children ingesting the liquids. Four adults died in the US and Europe, after intentionally ingesting liquid. Two children, one in the US in 2014 and another in Israel in 2013, died after ingesting liquid nicotine.
The discrepancy between the historically stated 60-mg dose and published cases of nicotine intoxication has been noted previously (Matsushima et al. 1995; Metzler et al. 2005). Nonetheless, this value is still widely accepted over the 500 mg figure as the basis for safety regulations of tobacco and other nicotine-containing products (such as the EU wide TPD, set at a maximum of 20 mg/ml).
Pathophysiology
The symptoms of nicotine poisoning are caused by effects at nicotinic cholinergic receptors. Nicotine is an agonist at nicotinic acetylcholine receptor which are present in the central and autonomic nervous systems, and the neuromuscular junction. At low doses nicotine causes stimulatory effects on these receptors, however, higher doses or more sustained exposures can cause inhibitory effects leading to neuromuscular blockade.
It is sometimes reported that people poisoned by organophosphate insecticides experience the same symptoms as nicotine poisoning. Organophosphates inhibit the enzyme acetylcholinesterase, causing a buildup of acetylcholine, excessive stimulation of all types of cholinergic neurons, and a wide range of symptoms. Nicotine is specific for nicotinic cholinergic receptors only and has some, but not all of the symptoms of organophosphate poisoning.
Diagnosis
Increased nicotine or cotinine (the nicotine metabolite) is detected in urine or blood, or serum nicotine concentrations increase.
Treatment
The initial treatment of nicotine poisoning may include the administration of activated charcoal to try to reduce gastrointestinal absorption. Treatment is mainly supportive and further care can include control of seizures with the administration of a benzodiazepine, intravenous fluids for hypotension, and administration of atropine for bradycardia. Respiratory failure may necessitate respiratory support with rapid sequence induction and mechanical ventilation. Hemodialysis, hemoperfusion or other extracorporeal techniques do not remove nicotine from the blood and are therefore not useful in enhancing elimination. although this is not recommended as it may cause complications of metabolic acidosis. It has been stated that if a patient survives nicotine poisoning during the first 4 hours, they usually recover completely. At least at "normal" levels, as nicotine in the human body is broken down, it has an approximate biological half-life of 1–2 hours. Cotinine is an active metabolite of nicotine that remains in the blood for 18–20 hours, making it easier to analyze due to its longer half-life.
See also
- Health effects of tobacco
- Nicotine dependence
- Nicotine withdrawal