A new challenge: suicide attempt using nicotine fillings for electronic cigarettes

Electronic cigarettes are gaining popularity as an alternative to traditional cigarettes, with sales increasing from $283 million in 2012 to $537 million in 2013 in the USA 1. Although they are considered relatively safe, the highly concentrated nicotine fillings (‘e-liquid’) can cause potentially lethal poisoning when ingested. Information about intoxications with e-liquid is scarce 2-4. Recent reports show a significant increase in the number of reported cases of poisoning with fillers from electronic cigarettes 5, 6, representing both accidental and intentional poisonings. Recently, a previously healthy 27-year-old man with a borderline personality disorder presented at our emergency department 1 h after ingestion of five e-liquid fillings in an suicide attempt. He had also consumed five units of wine. The e-liquid fillings contained a total of 420 mg of nicotine and unknown amounts of propyleneglycol and glycerine (Figure 1). Before arrival at the emergency department, the patient had vomited three times, but upon arrival he was free of complaints. The patient denied ingestion of other substances (aside from the reported ethanol). The paramedics found no other empty containers in the patient's house, nor were there any drugs visible in the vomitus. The serum concentration of acetaminophen was also not detectable (<2.8 mg l−1). Initial evaluation showed a sinus tachycardia of 117 beats min−1, a blood pressure of 144/99 mmHg and normal oxygen saturation at 98%. Besides sinus tachycardia, the electrocardiogram showed no abnormalities. The patient was afebrile (36.1°C). Apart from excessive salivation, physical examination was unremarkable. Laboratory examination revealed a high anion gap [16 mmol l−1 (normal, 8–12 mmol l−1)] lactic acidosis with a pH of 7.33 and lactic acid of 3.8 mmol l−1. The osmolality gap was 30 mOsm kg−1 H2O (normally <10 mOsm kg−1 H2O) and ethanol 3.9‰. Activated charcoal was administered and repeated twice (because of enterohepatic circulation of nicotine). According to the literature 7, we advised a 24 h observation period. During the actual observational period of 30 h, no adverse events occurred, and the metabolic acidosis disappeared within 10 h after admission. The patient was discharged after psychiatric consultation. An e-cigarette filler on the left and the liquid nicotine solution it contains on the right Serum concentrations of nicotine and its main metabolite cotinine were measured by liquid chromatography–tandem mass spectrometry in two samples. The serum concentration of nicotine was 50 μg l−1 at 2 h and <50 μg l−1 (not detectable) at 4 h after ingestion. The concentration of cotinine was 250 μg l−1 at 2 h and 180 μg l−1 at 4 h after ingestion (toxicity concentration of nicotine + cotinine in smokers, >1000 μg l−1 and in nonsmokers, >300 μg l−1). Nicotine is readily absorbed through all routes of exposure (gastrointestinal, dermal, intranasal and inhalational), has a high degree of first-pass metabolism (70–90%) and most probably has an enterohepatic circulation. Nicotine is metabolized in the liver, primarily by cytochrome P450 2A6, generating cotinine, which is probably inactive. The half-life of nicotine averages 2 h, while the half-life of cotinine averages 16 h. Owing to the short half-life of nicotine, cotinine is widely used as a quantitative marker for exposure to nicotine (for example, as a diagnostic test for the use of tobacco) 8, 9. Nicotine acts as an agonist at nicotinic acetylcholine receptors. Acute nicotine intoxication follows a biphasic pattern. At lower levels, stimulation of the nicotinic receptor results in vomiting, abdominal pain, hypertension, tachycardia and excessive salivation. At higher levels or with more sustained exposures, autonomic ganglionic blockade can occur, leading to hypotension, bradycardia, dyspnoea and, eventually, coma and respiratory failure 9. The information on the concentration of e-liquids reported by the manufacturers is often not accurate 10. Calculation of the ingested dose of nicotine on the basis of the manufacturer's information is therefore not reliable. That is why measurement of serum levels of nicotine can be useful in order to objectify the amount suggested to have been ingested by the patient and to estimate the severity of the nicotine intoxication. However, this laboratory test is not rapidly and universally available. Our patient potentially ingested up to 420 mg of nicotine, which is well above the internationally accepted lethal limit of 60 mg (corresponding to 0.18 mg l−1 nicotine plasma concentration). However, a recent article by Mayer shows that this limit is questionable 11. He suggests that the lethal dose for adults is 0.5 g, corresponding to 6.5 mg (kg bodyweight)−1 of orally ingested nicotine. The lower limit of lethal nicotine serum concentrations is ∼4 mg l−1. Despite large amounts of ingested e-liquid, our patient developed mild toxicity, which was confirmed by the measured nicotine and cotinine serum concentrations. Management of nicotine intoxication consists of general supportive measures and repeated administration of activated charcoal in combination with a laxative. Haemodialysis is not useful. Proton-pump inhibitors are contraindicated because they increase nicotine absorption in the gastrointestinal tract. In conclusion, ingestion of e-liquid can lead to potentially lethal nicotine poisoning. Given the increasing popularity of electronic cigarettes, the frequency of nicotine intoxications is likely to rise in the future. Physicians working in the emergency department and general practice should become familiar with this intoxication. All authors have completed the Unified Competing Interest form at http://www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work.