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[Emergency Care Journal 2013; 9:e18] [page 53]

Bad news about an old poison.
A case of nicotine poisoning
due to both ingestion and
injection of the content 
of an electronic cigarette refill
Gianfranco Cervellin,1 Michele Luci,1
Carlotta Bellini,1 Giuseppe Lippi2
1Emergency Department, Parma
University Hospital; 2Laboratory of
Clinical Chemistry and Haematology,
Parma University Hospital, Parma, Italy 

Abstract

There are increasing concerns about the
escalating use of electronic cigarettes (e-ciga-
rettes). In particular, smokers have been
advised by important agencies such as the US
Food and Drug Administration about the
potential harm to the health of these products,
being now considered as drug delivery devices.
The leading issues supporting this statement
include the repeated inhalation of propylene
glycol that is used as a diluent in refills, acci-
dental poisoning, as well as evidence that e-
cigarettes may promote continued smoking
since their use may compromise quitting moti-
vations. Some authors have minimized these
risks, considering the potential advantages of
these devices for public health. Here we
describe the first case of nicotine poisoning
due to both ingestion and intravenous injec-
tion of the content of an e-cigarette refill,
incorrectly mixed with methadone, bottled in a
generic vial. 

Case Report

A 22 year-old girl, chronically assuming
methadone for opioids addiction, has been
admitted to our emergency department (ED)
complaining for tachycardia, flushing, saliva-
tion and nausea. Her body weight was 47 kg.
She reported to have mixed the residual con-
tent of an electronic cigarette (e-cigarette)
refill (i.e. 10 mL of a 0.8% solution) with 60 mL
of methadone, and to have bottled the mixture
in a generic vial. She also admitted to have
injected about 2 mL of a the mixed solution,
and to have intentionally ingested about 60 mL
of it 2 h before ED visit. She was awake, tachy-
cardic, and in good general conditions, pupils
were myotic, there were many old venipunc-
ture scars on her arms and legs. Her vital signs
were: heart rate (HR) 115 beats per minute
(bpm; sinus tachycardia at the ECG), arterial
blood pressure (BP) 150/105 mmHg, body tem-

perature 36.8°C, and peripheral O2 saturation
(spO2) 100% in ambient air. Orogastric lavage
was promptly performed, and 50 g of activated
charcoal followed by 30 g of magnesium sul-
phate were administered via orogastric tube.
The toxicological standard panel used in our
Hospital was performed, resulting positive for
methadone, and negative for benzodiazepines,
cannabinoids, amphetamines, barbiturates,
cocaine, opioids and ecstasy (MDMA). The
patient was then monitored and kept under
clinical observation. The symptoms and vital
signs progressively improved, and nearly 3 h
after admission the clinical condition was dra-
matically improved, with vital signs as follows:
HR 82 bpm, arterial BP 105/60 mmHg, body
temperature 36.7°C, and spO2 100%. She was
discharged after a psychiatric consultation and
addressed to the addiction services of our
town. 
The refill of the e-cigarettes was in the

meantime brought to the ED, and the content
was quantified in 18 mg of nicotine per mL of
solution. It was then calculated that the patient
had globally assumed about 36 mg of nicotine,
2-3 mg intravenously (i.v.), and 33-34 mg per
os. The dose of methadone ingested was 60
mg, which corresponds to the usual dose
assumed by the patient.

Discussion

Nicotine is a natural alkaloid derived from
the dried leaves and stems of Nicotiana
tabacum and Nicotiana rustica, where it is
present in concentrations comprised between
0.5 and 8%.1 The name is directly derived from
that name of plants, which were originally clas-
sified by Jean Nicot de Villemain, the French
ambassador in Portugal, who sent tobacco and
seeds to Paris in 1560, and who promoted their
medicinal use. Nicotine is a hygroscopic, oily
liquid that is miscible with water in its base
form. It is a potentially addictive drug used in
cigarettes as well as in sniffing and chewing
tobacco. Gums and patches, as well as the
recently introduced e-cigarettes that are typi-
cally used for purpose of withdrawal from
smoking, also contain nicotine. The oral
bioavailability of nicotine is less than 20%, and
absorption from the oral mucosa is the princi-
pal site of nicotine absorption in subjects who
chew tobacco or nicotine gum.2 Nicotine dis-
tributes extensively into body tissues with a
volume of distribution ranging from 1.0 to 3.0
L/kg.2 The median lethal dose (LD50) of nico-
tine is 50 mg/kg for rats, and 3 mg/kg for mice,
but 30 to 60 mg (i.e. nearly 0.5 to 1.0 mg/kg)
can be a lethal dose for adult humans.3 The cig-
arettes typically contain 8 to 20 mg of nicotine
depending on the brand, but smokers actually

absorb only about 1 mg per cigarette.1 At vari-
ance with cigarettes, many brands of cigars
contain at least 10-20 times higher amount, in
exceptional cases approximating 50 times.4

Nicotine mainly acts on the parasympathetic
and sympathetic nervous system, where it
binds to specific nicotinic acetylcholine recep-
tors. The nicotine dose-response relationship
is complex. Low doses stimulate neural sys-
tems, triggering central or peripheral nervous
system stimulation with arousal and increase
in HR and arterial BP, whereas higher doses
produce an inhibitory effect acting through
ganglionic blockade and thereby finally result-
ing in bradycardia, hypotension, and
depressed mental status.1,5,6 Due to the
remarkably low LD50, nicotine can hence be
considered one of the most toxic poisons, with
very rapid onset of action despite a broad inter-
individual tolerance to the toxic effects.7 Toxic
symptoms might be observed with doses as low
as 2-5 mg, and non-fatal cases of intentional or
accidental nicotine poisoning have been
reported in the current scientific literature.8,9

In mild nicotine poisoning the leading clinical
signs and symptoms include nausea, headache
and dizziness, along with the possible onset of
vomiting and diarrhea. In more severe cases,
abdominal pain, diaphoresis, weakness, confu-
sion, seizures, and death due to respiratory
muscle paralysis might develop.
Cardiovascular signs of acute nicotine poison-
ing include tachycardia and hypertension at
low doses, whereas bradycardia and hypoten-
sion occur more specifically with high doses.3

Although nicotine is one of the most toxic
drugs of abuse, it rarely leads to fatalities.

Emergency Care Journal; volume 9:e18

Correspondence: Gianfranco Cervellin,
Emergency Department, Parma University
Hospital, via Gramsci 14, 43126 Parma, Italy.
Tel. +39.0521.703800 - Fax: +39.0521.703144.
E-mail: gcervellin@ao.pr.it

Key words: nicotine poisoning, electronic ciga-
rette, methadone, addiction.

Contributions: the authors contributed equally. 

Conflict of interests: the authors declare no
potential conflict of interests. 

Received for publication: 15 February 2013.
Revision received: 14 August 2013.
Accepted for publication: 26 August 2013.

This work is licensed under a Creative Commons
Attribution 3.0 License (by-nc 3.0).

©Copyright G. Cervellin et al., 2013
Licensee PAGEPress, Italy
Emergency Care Journal 2013; 9:e18
doi:10.4081/ecj.2013.e18

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[page 54] [Emergency Care Journal 2013; 9:e18]

Fatal poisoning from concentrated-nicotine
solution and pesticides have been
described,10,11 but only a few cases of fatal nico-
tine poisoning have been reported during the
past 20 years.10-12

Acute nicotine poisoning caused by injec-
tion of nicotine solution is extremely rare.
Hagiya et al. have recently described the case
of nicotine poisoning due to intravenous injec-
tion of cigarette soakage in a nurse who
soaked 20 cigarettes in 100 mL of tap water for
1 h, and intravenously injected 5 mL of ciga-
rette soakage solution, containing approxi-
mately 5.7 mg nicotine, in a suicidal attempt.
She survived and recovered completely in
nearly 24 h.13

Three cases of fatal multidrug poisoning
with nicotine and other agents have been
described so far, to the best of our knowl-
edge.14-16 Among these, a single case of fatal
multidrug poisoning involving nicotine has
been described in a 46-year-old man who was
found dead in his bed after attaching 25 trans-
dermal nicotine patches to his thorax and
abdomen and drinking two bottles containing
tobacco, nicotine and other drugs such as tra-
madol and diphenhydramine.16 Since both
nicotine and tramadol have the potential to
cause severe central nervous system depres-
sion accompanied by cardiovascular abnormal-
ities and sudden respiratory failure, this case
is the only one previously reported showing
some analogies with ours, the only difference
being the opioid drug (i.e. methadone vs tra-
madol). 
Recently, three cases of attempted suicide

by ingestion of nicotine liquid used in e-ciga-
rettes have been described, two of whom
occurring in the same woman. All the cases
have been successfully treated with activated
charcoal.17

Nicotine has also been reported as a poten-
tial chemical weapon, since it is highly toxic, it
can be purchased without restriction, and
there is no restriction for airline passengers.
The Norwegian fanatic extremist and terrorist
Anders Behring Breivik, before killing 77 peo-
ple,  published on-line a relatively simple
process to convert hollow projectiles into chem-
ical weapons, by injecting them with a biologi-
cal or chemical toxin… and, after careful con-
sideration of alternatives, including heroin,
various insecticides and cyanide, he concluded
that the ideal is nicotine.18

Conclusions
E-cigarette is a misleading term used to

identify an aerosolizing delivery device
equipped with a disposable cartridge which

contains nicotine in solution, usually diluted
with propylene glycol. Despite being marketed
as cigarettes, these devices resemble multi-
dose inhalers, nebulizers, or other devices
loaded with a drug (i.e. albuterol, used for
asthma treatment).19 As such, on April 25,
2011, the US Food and Drug Administration
announced the aim of regulating e-cigarettes
as tobacco products, having failed in its initial
attempt to regulate them as drug-delivery
devices.20 To the best of our knowledge, this
case is the very first describing multidrug poi-
soning with nicotine and methadone, due to
both ingestion and i.v. injection of the content
of an e-cigarette refill, incorrectly mixed with
methadone, that was bottled in a generic vial.
The patient had a favourable outcome, mainly
attributable to the relatively small dose of nico-
tine assumed. Moreover, we did not observe
any sign or symptom of methadone intoxica-
tion, probably due to the chronic addiction of
the patient. It should be considered, however,
that the small volumes of the refill’s content
makes it easy to ingest or inject higher and
potentially lethal doses and thereby poses seri-
ous threats for the future.21 E-cigarettes and
refill solutions can be easily purchased, also on
the Web through virtual stores that are poorly
regulated. This should raise additional con-
cerns about the increasing use of e-cigarettes,
that may hence be considered a new and easi-
ly available form of accidental or intentional
poisoning as uncontrolled forms of delivery of
high-dose nicotine or other potentially toxic
compounds. Emergency physicians should
hence clearly acknowledge the ingestion and
injection of the content of e-cigarette refills as
a new and potential form of acute poisoning.

References

1. Benowitz NL. Clinical pharmacology of
nicotine: implications for understanding,
preventing, and treating tobacco addic-
tion. Clin Pharmacol Ther 2008;835:31-41.

2. Svensson CK Clinical pharmacokinetics of
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40.

3. Schonwald S. Medical toxicology. Philadel -
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8. Centers for Disease Control and
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9. Schneider S, Diederich N, Appenzeller B,
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11. Takayasu T, Ohshima T, Lin Z, et al. An
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14. Churtavedi AK, Rao NG, McCoy FE. A
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15. Moriya F, Hashimoto Y. A fatal poisoning
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Forensic Sci Int 2005;149:167-70.

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CT, et al. Multidrug poisoning involving
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17. Christensen LB, van’t Veen T, Bang J.
Three cases of attempted suicide by inges-
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Clin Toxicol 2013;51:290.

18. Diethelm P, McKnee M. Nicotine: not just
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chemical weapon. Eur J Public Health
2011;21:681-3.

19. Cobb NK, Byron MJ, Abrams DB, et al.
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health: the rise of the “e-cigarette.” Am J
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20. Food and Drug Administration. Regulation
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Case Report

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