+Model

TOXAC-127; No. of Pages 4 ARTICLE IN PRESS

Toxicologie Analytique & Clinique (2016) xxx, xxx—xxx

Disponible en ligne sur

ScienceDirect
www.sciencedirect.com

CASE REPORT

Lactic acidosis due to voluntary e-liquid

ingestion
Anne Garat a,b,c, Patrick Nisse c, Marie Kauv d,
Monique Mathieu-Nolf c, Delphine Allorge a,b,∗,
Daniel Mathieu d

a
CHU Lille, service de toxicologie-génopathies, F-59000 Lille, France
b
Univ. Lille, EA 4483,IMPECS—IMPact de l’Environnement Chimique sur la Santé humaine,
F-59000 Lille, France
c
CHU Lille, centre antipoison, F-59000 Lille, France
d
CHU Lille, centre de réanimation, F-59000 Lille, France

Received 23 October 2015; received in revised form 9 March 2016; accepted 5 May 2016

KEYWORDS Summary This case reports an acute poisoning with ‘‘e-liquid’’ together with its clinical and
Electronic cigarette; biological consequences. Toxicological investigations in blood and urine samples highlighted
Lactic acidosis; the presence not only of nicotine and cotinine, but also of propylene glycol. For the first
Propylene glycol time, we describe here an acute poisoning with e-liquid, followed with clinical and biological
manifestations due to propylene glycol and not nicotine toxicity.
© 2016 Société Française de Toxicologie Analytique. Published by Elsevier Masson SAS. All
rights reserved.

Introduction
Electronic cigarettes, also known as ‘‘e-cigarettes’’, are currently widely used by smokers
as smoking cessation help. Here, we describe an acute poisoning due to voluntary ingestion
of ‘‘e-liquid’’ and its biological and clinical consequences.

∗ Corresponding author. CHU Lille, service de Toxicologie-Génopathies, F-59000 Lille, France.

E-mail address: dallorge@univ-lille2.fr (D. Allorge).

http://dx.doi.org/10.1016/j.toxac.2016.05.001
2352-0078/© 2016 Société Française de Toxicologie Analytique. Published by Elsevier Masson SAS. All rights reserved.

Please cite this article in press as: Garat A, et al. Lactic acidosis due to voluntary e-liquid ingestion. Toxicologie Analytique
& Clinique (2016), http://dx.doi.org/10.1016/j.toxac.2016.05.001
+Model
TOXAC-127; No. of Pages 4 ARTICLE IN PRESS
2 A. Garat et al.
Case report
This case concerns a 44 years old man, 57 kg, with a
medical history of Lyme disease, a former consumption of
cannabis, and a current tobacco withdrawal. He deliberately
drank a declared quantity of 30 mL of solvent contained in
e-cigarette cartridges, currently called ‘‘e-liquid’’. Accord-
ing to the patient, the cartridges were from Poland, but
their proper identification remained unknown. Two hours
after ingestion (timing based on the patient’s declaration),
he was admitted to the emergency department. He was
suffering from headache, nausea, abdominal pain, ven-
tricular extrasystoles and tachypnea (29/min). Admission
laboratory investigations included Na+ : 141 mmol/L, Cl− :
105 mmol/L, K+ : 2.7 mmol/L, uremia: 0.48 g/L, serum creat-
inine: 10.9 mg/L, alcaline phosphatase: 58 U/L and creatine
kinase (CK) 80 U/L. Liver chemistry was slightly disturbed,
with increased aspartate aminotransferase (AST) (52 U/L)
and normal alanine aminotransferase (ALT) (28 U/L). Eight
hours after ingestion, a lactic acidosis associated to an ele-
vated anion gap (23) was diagnosed, with arterial pH at 7.3
and blood lactate concentration at 11.4 mmol/L. The first
toxicological investigations in urine samples were performed
using a Drug-Screen-Multi 9TB device (Nal von Minden,
Moers, Deutschland) and did not detect the presence of
benzodiazepines, tricyclic antidepressants, barbiturates,
cannabis, cocaine, amphetamines, ecstasy, methadone and
opiates. During the following hours, he developed a muscu-
lar paralysis prevailing on the lower limbs, and a hypotonic
anal sphincter. On the advice of the local Poison Center,
he was admitted in Intensive Care Unit for full support-
ive medical care and additional toxicological investigations,
especially determination of propylene glycol, nicotine and
cotinine concentrations in biological samples. Propylene gly-
col (PG) analysis was performed using a GC-FID (Thermo
Fischer Scientific, Villebon-sur-Yvette, France) equipped
with a CP-SIL 8CB 25 m × 0.25 mm × 0.25 ␮m column (Var-
ian, Middleburg, The Netherlands) after derivatization with
phenylboronic acid and using 1,3-propanediol as internal
standard. Data were analysed with Chromquest® soft-
ware (Thermo Fischer Scientific). Nicotine analysis was
performed with a UPLC-TQD (Waters® , Saint-Quentin-en-
Yvelines, France), with cotinine-D3 as internal standard,
after alcaline extraction with organic solvents. Chromato-
graphic separation was processed with an Acquity® HSS C18
1.8 ␮m, 2.1 mm × 150 mm column (Waters® ) with a gradi-
ent mixture of ammonium formiate pH 3/acetonitrile with
0.1% formic acid. Acquisition was performed with positive
ion electrospray ionization in multiple reaction monitoring
(MRM) mode, and data analysis with Masslynx® software
(Waters® ). Concerning the toxicological screening, after
liquid-liquid extraction, urine (after hydrolysis) and blood
samples were analysed using a UPLC-Q-TOF (Waters® , XEVO-
G2-Q-TOF) fitted with an electrospray ionization source (ESI)
operating under positive ion mode. Chromatographic sep-
aration was performed with an Acquity® HSS C18 1.8 ␮m,
2.1 mm × 150 mm column (Waters® ). Methylclonazepam and
beta-hydroxyethyltheophylline were used as internal stan-
dards. Mass spectra were acquired in MSE mode and data
analysis was performed with Masslynx® software (Waters® ).
Fourteen hours after the supposed time of e-liquid ingestion,
Please cite this article in press as: Garat A, et al. Lactic acidosis due to voluntary e-liquid ingestion. Toxicologie Analytique
& Clinique (2016), http://dx.doi.org/10.1016/j.toxac.2016.05.001
the concentration of PG was 300 mg/L in whole blood
and 1230 mg/L in urine samples, and concentrations of
nicotine and cotinine in blood were 21 and 102 ␮g/L, respec-
tively. Lactic acidosis persisted (pH 7.3), with an anion
gap remaining high (20.6). No other drug was detected.
Perfusion of 4-methylpyrazole (1000 mg/day, 4 days) was
started, as well as overhydration and alcalinization. At day
1, the blood concentration of PG was 294 mg/L, blood lac-
tate concentration decreased (2 mmol/L), and AST (74 U/L),
CK (2649 U/L) and lactate dehydrogenase (LDH) (266 U/L)
increased. Blood gas values were also normalized. At day 2,
PG blood level was 272 mg/L, AST: 139 U/L, CK: 6177 U/L and
LDH: 339 U/L. On day 3, PG blood level was 33 mg/L, AST:
171 U/L, CK: 6742 U/L, LDH: 412 U/L and acid lactic normal-
ized at 0.6 mmol/L. Nicotine and cotinine levels were 0.8
and 36 ␮g/L, respectively. The biological status improved
on day 4, with AST: 145 U/L and CK: 5448 U/L. On day 5,
PG was undetectable (< 30 mg/L), nicotine and cotinine lev-
els were 0.7 and 8.1 ␮g/L, respectively, and levels of AST
and CK were 97 and 2546 U/L, respectively. A breakdown of
patient biological data is presented in Table 1. From a clini-
cal point of view, the state of the patient gradually improved
and neurological symptoms declined.
Discussion
Over the last few years, the use of electronic nicotine deliv-
ery systems (ENDS), currently called electronic cigarettes,
can be considered as an alternative to smoking. Briefly, con-
sumers, also called ‘‘vapers’’, breathe in vapor produced by
the heating of a mixture of propylene glycol and glycerin,
various flavourings and with or without different concen-
trations of nicotine. ENDS are experiencing booming sales,
the global market for e-cigs being predicted to reach over
$ 3.2 billion by 2015, and over $ 10 billion by 2017 [1].
Thus, an increase in e-liquid poisonings is observed. A great
number of intoxications via various routes of exposure have
already been reported by American Poison Centers [2]. For-
tunately, these cases were not deleterious, except a death
following a self-injection of e-liquid. In the present case, the
absence or presence of nicotine, and its concentration, were
unknown in the ingested product, and nicotine and cotinine
levels in the patient blood samples appeared extremely low.
This could be explained by an ingestion of an e-liquid with
very low nicotine dosage, or ingestion of nicotine-free e-
liquid by a smoking patient. Accordingly, previously reported
nicotine levels in acute intoxications were far higher [3],
and the nicotine blood concentration found for our patient
(21 ␮g/L) is compatible with blood concentrations expected
after a single cigarette smoking (5 to 30 ␮g/L). Furthermore,
the patient did not present a typical nicotinic intoxica-
tion symptomatology (vomiting, diaphoresis, hypotension,
seizures, respiratory failure). Here, the observed symptoma-
tology and biological disturbances appear in accordance
with propylene glycol intoxication. An ion and/or osmolar
gap with or without lactic acidosis has been described in
several PG intoxication cases, most of them being related
to its use as a solvent in intravenous medications [4—12]
or, less frequently, after oral ingestion of PG-containing
products [13—15]. Plasma or serum concentrations of PG
+Model
TOXAC-127; No. of Pages 4 ARTICLE IN PRESS
Lactic acidosis due to voluntary e-liquid ingestion
Table 1 Main biological patient outcomes.
Supposed time after intake (h) 8 13.5
Propylene glycol (mg/L) 300 294
Nicotine (␮g/L) 21
Cotinine (␮g/L) 102
pH 7.3 7.3
Lactate (mmol/L) 11.4 5.8
LDH (U/L) 266
AST (U/L) 52 57
CK (U/L) 80 930 2649
varying from 120 to 6590 mg/L have been reported in intox-
ication cases [12,16], but it seems that toxic effects happen
for blood concentrations over 1 g/L [16]. In the present
case, a blood concentration of 300 mg/L of PG was deter-
mined 14 hours after ingestion, according to the patient’s
declaration. As PG elimination half-life is relatively short
(around 4 hours) [17], we can assume that the initial blood
concentration was higher than 1 g/L, although it has been
demonstrated that there is a large interindividual variabil-
ity in PG apparent total body clearance [17]. Considering
that the peak blood concentration occurs within 1 h after
oral administration and then declines monoexponentially
as a function of time [17], a peak blood PG concentra-
tion of 3600 mg/L can be estimated for our patient. This
relatively high blood PG concentration could appear not
compatible with the declared volume of e-liquid ingested
by the patient (30 mL of e-liquid would contain a maxi-
mum of 30 g of PG). In one of the rare published studies
on PG pharmacokinetics in humans, peak plasma PG con-
centrations ranging from 800 to 2000 mg/L were measured
in patients receiving 41.4 g of PG every 12 h for 3 days
[17]. Considering the volume of distribution of PG (0.5 L/kg)
[16] and the weight of the patient (57 kg), the ingested
dose of PG would have been around 100 g to reach a blood
concentration of 3600 mg/L. PG poisoning usually induces
limited clinical disruptions and patient care often consists
solely in stopping the exposure, although in case of severe
intoxications the administration of 4-methylpyrazole and/or
institution of dialysis could be warranted [7,11,12,16]. In
the present case, we can note extremely high CK levels,
which suggest severe rhabdomyolysis, probably due to cir-
culatory and metabolic disturbances, as well as an important
neurological impairment (paralysis) due to hypokalemia.
Other etiologies for rhabdomyolysis and lactic acidosis were
discarded. Finally, clinical and biological signs remained
moderate according to the Poisoning Severity Score (PSS2)
[18]. If intoxication had concerned a child, or in case of
a larger intake by an adult, effects could have been more
serious.
Conclusion
This case shows that, in case of acute poisoning with
e-liquid, poisoning with propylene glycol should be encom-
passed, besides nicotine poisoning. Also, we would like to
alert on the potential acute toxicity of electronic nicotine
Please cite this article in press as: Garat A, et al. Lactic acidosis due to voluntary e-liquid ingestion. Toxicologie Analytique
& Clinique (2016), http://dx.doi.org/10.1016/j.toxac.2016.05.001
3
Period of 4-methylpyrazole treatment
28.5 45 73 96.5 117
272 33 0
0.8 0.7
36 8.1
7.4 7.5 7.5 7.5
2 0,6
339 412 281
74 139 171 145 97
6177 6742 5448 2546
delivery systems, not only due to the presence of nico-
tine, but also to solvents used. Moreover, clinicians have
to keep in mind that toxicological investigations should not
be limited to methanol and ethylene glycol, but also include
propylene glycol, when a patient presents a metabolic acid-
osis with high anion and/or osmolal gaps.
Disclosure of interest
The authors declare that they have no competing interest.
References
[1] Tremblay MC, Pluye P, Gore G, Granikov V, Filion KB, Eisen-
berg MJ. Regulation profiles of e-cigarettes in the United
States: a critical review with qualitative synthesis. BMC Med
2015;13:130.
[2] Chatham-Stephens K, Law R, Taylor E, Melstrom P, Bun-
nell R, Wang B, et al. Centers for Disease Control and
Prevention (CDC). Notes from the field: calls to poison cen-
ters for exposures to electronic cigarette—United States,
September 2010—February 2014. MMWR Morb Mortal Wkly Rep
2014;63(13):292—3.
[3] Solarino B, Rosenbaum F, Riesselmann B, Buschmann CT, Tsokos
M. Death due to ingestion of nicotine-containing solution:
case report and review of the literature. Forensic Sci Int
2010;195:e19—22.
[4] Arbour R, Esparis B. Osmolar gap metabolic acidosis in a 60-
year-old man treated for hypoxemic respiratory failure. Chest
2000;18:545—6.
[5] Reynolds H, Teiken P. Hyperlactatemia, increased osmolar gap,
and renal dysfunction during continuous lorazepam infusion.
Crit Care Med 2000;28(5):1631—4.
[6] Cawley MJ. Short-term lorazepam infusion and concern for
propylene glycol toxicity: case report and review. Pharma-
cotherapy 2001;21:1140—4.
[7] Parker MG, Fraser GL, Watson DM, Riker RR. Removal of pro-
pylene glycol and correction of increased osmolar gap by
hemodialysis in a patient on high dose lorazepam infusion ther-
apy. Intensive Care Med 2002;28(1):81—4.
[8] Neale B, Mesler E, Young M, Rebuck J, Weise W. Propylene
glycol-induced lactic acidosis in a patient with normal renal
function: a proposed mechanism and monitoring recommenda-
tions. Ann Pharmacother 2005;39(10):1732—6.
[9] Wilson KC, Reardon C, Theodore AC, Harrison W. Propylene gly-
col toxicity: a severe iatrogenic illness in icu patients receiving
IV benzodiazepines: a case series and prospective, observa-
tional pilot study. Chest 2005;128(3):1674—81.
+Model
TOXAC-127; No. of Pages 4 ARTICLE IN PRESS
4 A. Garat et al.

[10] Tsao YT, Tsai WC, Yang SP. A life-threatening double gap
metabolic acidosis. Am J Emerg Med 2008;26(3):385.e5—6.
[11] Yan MT, Chau T, Cheng CJ, Lin SH. Hunting down a double gap
metabolic acidosis. Ann Clin Biochem 2010;47(3):267—70.
[12] Zosel A, Egelhoff E, Heard K. Severe lactic acidosis after
an iatrogenic propylene glycol overdose. Pharmacotherapy
2010;30(2):219.
[13] Jorens PG, Demey HE, Schepens PJ, Coucke V, Verpooten GA,
Couttenye MM, et al. Unusual D-lactic acid acidosis from pro-
pylene glycol metabolism in overdose. J Toxicol Clin Toxicol
2004;42(2):163—9.
[14] Brooks DE, Wallace KL. Acute propylene glycol ingestion. J
Toxicol Clin Toxicol 2002;40(4):513—6.
[15] Cunningham CA, Ku K, Sue GR. Propylene glycol poisoning
from excess whiskey ingestion: a case of high osmolal gap
metabolic acidosis. J Investig Med High Impact Case Rep 2015,
http://dx.doi.org/10.1177/2324709615603722.
[16] Kraut JA, Kurtz I. Toxic alcohol ingestions: clinical fea-
tures, diagnosis, and management. Clin J Am Soc Nephrol
2008;3(1):208—25.
[17] Yu DK, Elmquist WF, Sawchuk RJ. Pharmacokinetics of propyl-
ene glycol in humans during multiple dosing regimens. J Pharm
Sci 1985;74(8):876—9.
[18] Persson HE, Sjöberg GK, Haines JA, Pronczuk de Garbino J.
Poisoning severity score. Grading of acute poisoning. J Toxicol
Clin Toxicol 1998;36(3):205—13.

Please cite this article in press as: Garat A, et al. Lactic acidosis due to voluntary e-liquid ingestion. Toxicologie Analytique
& Clinique (2016), http://dx.doi.org/10.1016/j.toxac.2016.05.001