Abstract
Transdermal nicotine patches (TNPs) are widely used in substitution therapy after cessation of smoking. Toxic concentrations of nicotine and cotinine, its main metabolite, are poorly reported in the literature, either in cases of misuse or in fatal contexts. We report here an exceptional fatal case due to a massive exposition of TNPs without any other apparent cause. A 41-years-old male was found dead by his cellmate with 7 TNPs (21 mg/24 h) on his body. In total, 14 TNPs and 5 empty blisters of 1.5 mg nicotine capsules were found in the bin. Autopsy findings did not reveal any pathology that could explain death. No evidence of violence was highlighted. No signs of trauma were noticeable and no arteriosclerosis was observed. In addition, histological investigation did not show any other element concluding on the death circumstances. Various biological samples were collected at autopsy for toxicological analysis. Toxicological screening was performed for ethanol (GC-FID), drugs and illicit drugs (LC-DAD, GC-MS, LC-MS/MS) on the biological samples. Nicotine and cotinine analyses were performed on an Agilent 5977B GC-MS system after liquid-liquid extraction in alkaline condition. Chromatographic separation was achieved using an Agilent capillary column VF-5ms. Any fatal case related to the nicotine substitution medication was explored using the French pharmacovigilance and the French poison control centers databases. Nicotine and cotinine concentrations are described in the Table 1 . A nicotine blood concentration above 1000 ng/mL is assumed to be lethal [1] . The analyses yielded therapeutic concentrations of cyamemazine, lormetazepam, nordiazepam, oxazepam, buprenorphine and its metabolite. THC and its metabolites were also detected reflecting a use of cannabis. The databases exploration did not reveal any other fatal case exclusively related to the nicotine substitution medication. According to the autopsy findings and the toxicological analyses, death was caused by a suicidal or accidental acute nicotine intoxication. This observation directs attention to the potential risk of nicotine poisoning from nicotine patches.
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