CASE REPORT

Jin Hui Paik1, Soo Kang1, Areum Durey1, Ji Hye

Kim1, Ah Jin Kim1
Symptomatic bradycardia due to nicotine
intoxication
Bradicardia sintomática causada por intoxicação por nicotina

1. Department of Emergency Medicine, Inha ABSTRACT

University School of Medicine - Incheon, orally ingested a high concentration of
Republic of Korea. Nicotine is a dangerous substance liquid nicotine from e-cigarette liquid.
extracted from tobacco leaves. When The patient presented with bradycardia
nicotine is absorbed in excessive amounts, and hypotension, which are symptoms
it can lead to respiratory failure and of parasympathetic stimulation,
cardiac arrest. The commercialization together with impaired consciousness.
of electronic cigarettes (e-cigarettes) He recovered following treatment with
has allowed users to directly handle atropine and a vasopressor.
e-cigarette liquid. Consequently, the
risk of liquid nicotine exposure has Keywords: Electronic cigarettes/
increased. We describe our experience adverse effects; Nicotine/poisoning;
of managing the case of a patient who Atropine; Bradycardia

INTRODUCTION

Nicotine is a dangerous substance extracted from tobacco leaves, and when

it is ingested in excessive amounts, it can lead to respiratory failure and cardiac
arrest. Nicotine poisoning symptoms result from exposure to normal cigarettes
or tobacco leaves. Although there have been reports overseas of nicotine
poisoning symptoms resulting from liquid nicotine exposure, clinical reports of
liquid nicotine poisoning among Korean adults are lacking.
Conflicts of interest: None. Since e-cigarettes have been commercialized in Korea, users have direct
access to e-cigarette liquid from e-cigarette stores, which has led to an increased
This work was supported by an Inha University
Research Grant risk of exposure to liquid nicotine. E-cigarette liquid, which contains a mixture
of nicotine and scents, is more expensive than pure liquid nicotine; therefore,
Submitted on May 28, 2017 many individuals buy liquid nicotine and add the scents themselves.
Accepted on July 14, 2017
Clinically, liquid nicotine poisoning presents similarly to nicotine poisoning
Corresponding author: caused via other routes. Severe nicotine poisoning has a characteristic biphasic
Ah Jin Kim
response, with initial excitatory symptoms, such as salivation, nausea, increased
Department of Emergency Medicine,
Inha University Hospital, 27, Inhang-Ro, Jung-Gu, bronchial secretions, tachycardia, hypertension, anxiety, muscle spasms, and
Incheon 22332 seizures, followed by symptoms of paradoxical inhibition, including dyspnea,
Republic of Korea
E-mail: emjin23@[Link]
bradycardia, hypotension, lethargy, and paralysis. In rare cases, rhabdomyolysis
can develop as a complication.(1)
Responsible editor: Leandro Utino Taniguchi
DOI: 10.5935/0103-507X.20180018

Rev Bras Ter Intensiva. 2018;30(1):121-126 This is an open access article under the CC BY license [Link]
122 Paik JH, Kang S, Durey A, Kim JH, Kim AJ

According to the National Poison Data System gap, lactic acid, and ketone body levels were 13.6mEq/L,
(NPDS), 169 cases of intentional liquid nicotine 6.1mmol/L, and 176µmol/L, respectively. General blood
poisoning were reported in 2015.(2) There have been no chemistry test results showed that the levels of blood
clinical reports of intentional liquid nicotine poisoning by urea nitrogen, creatinine, aspartate transaminase, alanine
oral ingestion in Korea thus far. We believe that this is the transaminase, creatinine kinase, creatine kinase MB
first reported case of intentional liquid nicotine poisoning fraction (CK-MB), and troponin-I were within normal
by oral ingestion in a Korean adult. limits (Table 1). A blood cotinine concentration of
1,296ng/mL was measured at the time of arrival at the
CASE REPORT emergency medical center (Siemens Immulite 2000 XP-I,
A 53-year-old male with no known medical illness Siemens Nicotine metabolite).
was discovered in a state of impaired consciousness, and Liquid nicotine poisoning was suspected, and the
the emergency medical service was called immediately. patient was administered a normal saline infusion for
At the time, a commercial liquid nicotine bottle was the hypotension and lactic acidosis and a single dose
found together with a cup filled with liquid suspected to of atropine (0.5mg) for symptoms of parasympathetic
be nicotine. The patient showed symptoms of impaired stimulation, namely, bradycardia, sweating, tachypnea,
consciousness, diarrhea, and vomiting. and salivation. The patient was given 50g of activated
The emergency medical service providers arrived charcoal; thereafter, he was able to open his eyes, and his
approximately 50 minutes after ingestion and found that systemic weakness gradually improved. After 10 minutes,
the patient was conscious enough to respond when called. his symptoms of dyspnea, sweating, and salivation also
His vital signs included a blood pressure of 120/60mmHg, showed improvement. Therefore, more atropine was not
a pulse rate of 71 beats/minute, a respiratory rate of 18 added. At this time, his blood pressure was 100/60mmHg,
breaths/minute, a body temperature of 36.5°C, and an his pulse rate was 78 beats/minute, his respiration rate was
oxygen saturation of 100%. 24 breaths/minute, and his oxygen saturation was 100%.
It took 15 minutes to transport the patient to the A central venous catheter was inserted to measure his
emergency medical center at the hospital. Upon arrival, central venous pressure (8cmH2O). The volume of normal
his vital signs deteriorated to the following: a blood saline required for 6 hours of resuscitation was 1,960mL.
pressure of 96/62mmHg, a pulse rate of 56 beats/min, and The patient was given dopamine and admitted to the
a respiratory rate of 22 breaths/minute. Oxygen saturation intensive care unit for observation. While hospitalized,
was maintained at 100%, while his body temperature was the patient stated that he had acquired liquid nicotine
36.0°C. At this point, although the patient responded to for e-cigarettes (trade name: Pure Nicotine) from an
questions, he could not open his eyes properly, and he was acquaintance and that he had ingested 3mL of this liquid
sweating profusely. He complained of dyspnea, nausea, with the intention of committing suicide. The patient’s
and severe generalized weakness. blood pressure normalized within 18 hours of admission,
On physical examination, his pupil sizes were normal and he was discharged after 3 days (Figure 1).
and his pupillary light reflexes were intact. His lung sounds DISCUSSION
were clear bilaterally, and his bowel sounds were slightly
increased. Electrocardiography revealed sinus bradycardia, We report a case of acute nicotine poisoning in a
with a QTc of 436ms. An initial arterial blood gas analysis patient who orally ingested a high concentration of
showed a pH of 7.65, a PaCO2 of 12.2mmHg, a PaO2 of liquid nicotine used in e-cigarettes. There have been
117.0mmHg, a bicarbonate of 13.5mmol/L, and a base several studies on nicotine poisoning including cases of
excess of -4mmol/L. General blood test results showed unintentional exposure involving workers in the cigarette
a white blood cell count of 11,970/mm3, a hemoglobin industry who developed green tobacco sickness and cases
of 15.5g/dL, a hematocrit of 44.8%, and a platelet of children who ingested cigarettes.(3,4) Cases of poisoning
count of 320,000/mm3. Electrolyte testing revealed a due to intentional exposure have included people who
serum sodium level of 141mEq/L, a potassium level of ingested nicotine solution extracted from cigarettes and
3.8mEq/L, and a chloride level of 102mEq/L. The anion who simultaneously used multiple nicotine patches.(5)

Rev Bras Ter Intensiva. 2018;30(1):121-126

 Symptomatic bradycardia due to nicotine intoxication 123

Table 1 - Hemodynamic and laboratory variables over time in a case of acute nicotine poisoning
Time Baseline* 6 hours 12 hours 24 hours 40 hours
Systolic blood pressure (mmHg) 96 116 125 127 130
Diastolic blood pressure (mmHg) 62 72 77 77 86
Heart rate (beats/min) 56 79 64 54 60
Respiratory rate (breaths/min) 22 18 18 31 20
Body temperature (ºC) 36 37.2 36.8 36.4 36.7
Dopamine dose (µ/kg/min) 0 10 7 0 0
Central venous pressure (cmH2O) 8
Cumulative infusion volume (mL, for 24 hours) 0 1430 2400 3360
pH 7.65 7.38 7.41 7.4
PaCO2 (mmHg) 12.2 30.4 36 37
PaO2 (mmHg) 117 105 89 93
HCO3 -
(mmol/L) 13.5 17.4 22.8 22.9
Base excess (mmol/L) -4 -6.1 -1.4 -1.6
O2 saturation (%) 99.1 97.4 97 97
Na+ (mEq/L) 140 141 141
K+ (mEq/L) 3.4 4.1 3.9
Cl -
(mEq/L) 113 115 106
Lactic acid (mEq/L) 6.1 5.2
Hemoglobin (g/dL) 15.5 13.9
Hematocrit (%) 44.8 42
WBC (/mm ) 3
11,970 13,190
Platelet (×103/mm3) 320 259
BUN (mg/dL) 14.1 9.7 9.9
Creatinine (mg/dL) 0.8 0.58 0.76
AST (IU/L) 17 18 23
ALT (IU/L) 18 19 19
CK (IU/L) 45 127 126
CK-MB (ng/mL) 0.8
Ketone body (µmol/L) 176
pH - potential of hydrogen; PaCO2 - partial pressure carbon dioxide; PaO2 - partial pressure oxygen; HCO3- - bicarbonate; O2 - oxygen; Na+ - sodium; K+ - potassium; Cl- - chloride; WBC - white
blood cell; BUN - blood urea nitrogen; AST - aspartate transaminase; ALT - alanine transaminase; CK - creatinine kinase; CK-MB - creatinine kinase MB. * Arrival at the emergency department.

Figure 1 - The progression of systolic blood pressure, diastolic blood pressure, heart rate, and respiratory rate from the
pre-hospitalization phase to hospital discharge in a case of acute nicotine poisoning. SBP - systolic blood pressure; DBP - diastolic blood
pressure; HR - heart rate; RR - respiratory rate.

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124 Paik JH, Kang S, Durey A, Kim JH, Kim AJ

Cases of poisoning by liquid nicotine have been amount of nicotine that is absorbed is smaller; second,
reported since the commercialization of e-cigarettes in there are individual differences in nicotine metabolism
2004, and since the NPDS began recording data for and, particularly for oral ingestion, the first-pass effect
e-cigarettes in 2010, there has been an increase in the decreases the bioavailability of nicotine by 30 - 40%.(9)
number of cases every year.(2) In the present case, the patient ingested liquid
In 2010, Solarino et al. measured nicotine and nicotine from a bottle labeled “Pure Nicotine,” with
cotinine levels in a patient who died after ingesting no precise concentration indicated. Since there was no
liquid nicotine and found a concentration of 2,200ng/ liquid remaining in the bottle, it was not possible to
mL.(6) Chen et al. described a patient who had blood accurately measure the concentration; however, according
nicotine and cotinine levels of over 1,000ng/mL with to the study by Kim et al., the nicotine concentration of
prolongation of the QTc on electrocardiography upon commercially available liquid nicotine in Korea under the
admission to the emergency room. The patient presented trade name of “Pure Nicotine” is 150 ± 7.9mg/mL.(10)
with myoclonic jerking and cardiovascular collapse before Assuming that the patient ingested liquid nicotine
dying 3 days later.(7) Sommerfeld et al. reported a case of with a similar concentration, he would have ingested
intentional ingestion and a case of intravascular injection. approximately 450mg. Since the patient vomited multiple
The patient who underwent treatment after ingesting times immediately after ingestion, the actual dose of
372mg of liquid nicotine showed initial symptoms of nicotine absorbed into his body would have been lower
confusion and vomiting, followed by delayed symptoms than this.
of hypotension, upper eyelid weakness, and pale skin. Nicotine is mostly metabolized in the liver, and the
However, he recovered and was discharged after 40 hours main metabolic product is cotinine.(11) As cotinine remains
of treatment.(8) in the blood for a relatively long time, it is measured when
In the present case, the patient exhibited tachycardia, determining the dose of nicotine exposure, and it is also
vomiting, diarrhea, and sweating without hypotension used as a marker to diagnose nicotine poisoning and to
before admission to the emergency room. However, 1 hour evaluate its severity to some degree.(12) However, according
after ingestion, he developed bradycardia, hypotension, to clinical reports on nicotine poisoning, clinical patterns
and severe weakness. While the patient showed no and survival rates do not show a consistent pattern based
impairments in autonomous breathing or oxygen on cotinine concentration. Sommerfeld et al. reported on
saturation, he had dyspnea and difficulty opening his eyes a case of acute liquid nicotine poisoning by oral ingestion.
due to weakness. The patient reported an improvement in The patient had a peak blood cotinine concentration of
the subjective dyspnea after being given atropine, a change 4,400ng/mL and survived.(8) However, blood cotinine
for which three possible explanations can be hypothesized. levels ranging from 900 to 2200ng/mL have been reported
The dyspnea may have been caused by increased bronchial in patients who died due to liquid nicotine poisoning.(6-8)
secretions, which was alleviated by atropine. Alternatively, We were not able to measure the nicotine concentration
the dyspnea may have resulted from impairment in in the current patient, but the cotinine concentration
respiratory muscle function due to the action of nicotine measured approximately 1 hour after oral exposure was
at the neuromuscular junction, an effect that may have 1,296ng/mL. This value is not high compared to those
faded over time. reported previously; however, a few studies have shown
Additionally, the dyspnea may have been caused by that this amount of nicotine can be fatal if proper treatment
metabolic acidosis due to lactic acidosis. The patient’s is not provided promptly.(13) Thus, while blood cotinine
blood gas analysis showed an anion gap metabolic acidosis concentration can be used as a reference for diagnosing
with respiratory alkalosis. Additionally, his lactic acid levels and treating acute nicotine poisoning, it is more important
were increased. We were not able to ascertain if the lactic to diagnose and treat based on an understanding of the
acidosis was due to shock or the direct effects of nicotine. patient’s medical history and clinical symptoms.
Schneider et al. estimated that the total dose of The management of acute liquid nicotine intoxication
nicotine that could result in the death of an adult was consists of the provision of supportive care. The
40 - 60mg; however, they also provided two reasons why it cardiovascular and respiratory symptoms caused by
was possible to survive after ingesting a greater dose. First, parasympathetic stimulation should be monitored.
because nicotine stimulates the vomiting reflex, the actual Normal saline should be administered for hypotension.

Rev Bras Ter Intensiva. 2018;30(1):121-126

 Symptomatic bradycardia due to nicotine intoxication 125

If hypotension continues, norepinephrine and dopamine decree.(17) Due to its classification as chemical substances,
should be considered. Atropine should be given for when liquid nicotine is sold for use in e-cigarettes, it is
bradycardia or dyspnea due to pulmonary secretion. not regulated according to the Tobacco Business Act; thus,
In the case of dyspnea with pulmonary secretion, 0.5 - there is no obligation to display the nicotine content.
1.0mg of atropine should be given repeatedly in 5 - 10
minute intervals. Seizures are rare; however if they do CONCLUSION
occur, lorazepam, diazepam, or barbiturate should be Each country has different laws and regulations
administered. Gastric lavage or irrigation should be regarding e-cigarettes; in the United States, the Food
considered for acute liquid nicotine ingestion because of and Drug Administration manages cigarette products,
nicotine-induced vomiting. However, it is better to remove including e-cigarettes. In Korea, cigarette-related
materials that release nicotine.(14) It is also imperative to legislation is currently under the jurisdiction of the
maintain adequate urine output, as nicotine is excreted Ministry of Strategy and Finance. We believe that this
into the kidneys. Activated charcoal may be effective in limits profound consideration of the public health risks
decreasing the concentration of nicotine in the blood of cigarettes. Allowing the general public to purchase
because nicotine is enterohepatically circulated.(15) high-concentrations of liquid nicotine for use in
Korean law stipulates that e-cigarette liquids containing e-cigarettes should be recognized as increasing the risk
a mixture of nicotine and scents must display the nicotine of acute, life-threatening toxicity. There is a need for
content, in accordance with the Tobacco Business Act and additional, multi-faceted regulations that account for the
enforcement decree.(16) However, pure nicotine solutions unique risks of e-cigarettes, as they differ from commercial
are categorized and managed as poisonous substances, cigarettes.
according to the Chemical Control Act and enforcement

RESUMO
elevada concentração de nicotina líquida contida em líquido
A nicotina é uma substância perigosa, extraída das folhas de para e-cigarros. O paciente apresentava bradicardia e hipoten-
fumo. Quando absorvida em quantidade excessiva, ela pode le- são, que são sintomas de estimulação parassimpática, além de
var à insuficiência respiratória e à parada cardíaca. A comerciali- comprometimento da consciência. O paciente teve recuperação
zação de cigarros eletrônicos (e-cigarros) permite que os usuários após tratamento com atropina e vasopressor.
manuseiem diretamente o líquido, com consequente aumento
do risco de exposição à nicotina líquida. Descrevemos nossa ex- Descritores: Cigarros eletrônicos/efeitos adversos; Nicoti-
periência no tratamento do caso de um paciente que ingeriu na/envenenamento; Atropina; Bradicardia

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