Nicotine intoxication by e-cigarette liquids: a study of case reports and pathophysiology

Background: Electronic cigarettes (e-cigarettes), the smokeless alternative to conventional tobacco cigarettes, have become increasingly popular. E-cigarettes vaporise e-liquid, a solution of highly concentrated nicotine, propylene glycol (PG) and vegetable glycerine (VG). With the popularity of e-cigarettes, e-liquid refills have become easily accessible and several cases of intoxication due to the ingestion of e-liquid have been reported. We provide an overview of these cases, their pathophysiology and patients' characteristics.Methods: We carried out a retrospective evaluation of the scientific literature reporting on cases of liquid nicotine intoxication, using the following inclusion criteria: (1) the article is or contains a case report, (2) describes an intoxication with e-liquid, (3) the substance contains nicotine, and (4) intake is oral, intravenous or subcutaneous.Results: We found 26 case reports describing a total of 31 patients who suffered from e-liquid intoxication. All intoxications up to the age of six were reported as unintentional, whereas nearly all cases from ages 13 to 53 were due to suicide attempts. The three most prevalent symptoms of e-liquid intoxication were tachycardia, altered mental status and vomiting. Eleven cases resulted in the death of the patient. In the survivors, the highest plasma concentration of nicotine was 800 µg L^-1, while the lowest concentration in the non-survivors was 1600 µg L^-1.Conclusions: There is a mismatch between the generally accepted lethal oral nicotine dose of 60 mg, resulting in approximately 180 µg L^-1 plasma concentration, and the 4.4- to 8.9-fold higher lethal plasma concentrations we found in cases of e-liquid intoxication. In these severe intoxications, plasma cotinine concentration does not act as a more reliable indicator of nicotine intoxication than nicotine itself. The ages of the patients display a bimodal distribution. In patients above the age of 10, intoxication results mainly from suicide attempts rather than accidental ingestion. The role of PG and VG in e-liquid intoxications is remarkably unclear. However, the similarity across nicotine and PG toxicity symptoms leads us to believe a cumulative effect cannot be excluded.