ILLUSTRATIVE CASE
A Rare Cause of Metabolic Acidosis
Fatal Transdermal Methanol Intoxication in an Infant
Zumrut Sahbudak Bal, MD,* Fulya Kamit Can, MD,† Ayse Berna Anil, Asc PD,† Alkan Bal, MD,‡
Murat Anil, Asc PD,‡ Gamze Gokalp, MD,‡ Onder Yavascan, Asc PD,§ and Nejat Aksu, Asc PD§
Abstract: Oral methanol intoxication is common, but dermal intoxica-
tion is rare. We report a previously healthy 19-month-old female infant
admitted to the emergency department (ED) with vomiting and tonic-
clonic seizure. On physical examination, she was comatose and presented
signs of decompensated shock with Kussmaul breathing. Her left thigh was
edematous, with purple coloration. Methanol intoxication was suspected
due to high anion gap metabolic acidosis (pH, 6.89; HCO3, <3 meq/L)
and exposure to spirit-soaked bandages (%96 methanol) for 24 hours and
3 days. The patient's serum methanol level was 20.4 mg/dL. She was treated
with fomepizole and continuous venovenous hemodialysis (CVVHD) in
the pediatric intensive care unit, and methanol levels decreased to 0 mg/dL
after 12 hours. During follow-up, massive edema and subarachnoid hemor-
rhage in the occipital lobe were detected by computed tomography of the
brain. The patient died after 7 days.
Although methanol intoxication occurs predominantly in adults, it must
be considered in children with high-anion gap metabolic acidosis. This
case report demonstrates that fatal transdermal methanol intoxication can
occur in children, and it is the second report in the English literature of
transdermal methanol intoxication in an infant.
Key Words: transdermal methanol intoxication, metabolic acidosis
(Pediatr Emer Care 2015;00: 00–00)
M ethanol poisoning by ingestion is a common problem world-
wide, but cases of poisoning after inhalation or dermal ab-
sorption are rare.1 Methanol is found commonly in antifreeze,
perfumes, solvents, and commercial formaldehyde. In the United
States, at least, most automotive products containing methanol are
actually windshield washer fluids rather than radiator antifreezes.2
It is colorless and has only a faint odor.2 Manifestations of methanol
poisoning include visual disturbance, central nervous system
(CNS) depression leading to respiratory failure, and severe meta-
bolic acidosis.2 Here, we report the second known pediatric patient
with symptoms of severe transdermal methanol intoxication.3
CASE
A 19-month-old female infant was admitted to the ED with
vomiting and generalized tonic–clonic seizure 1 hour before ad-
mission. The first physical vital signs were as follows: regular
heartbeat of 160 beats/min, respiration rate of 72 breaths/min,
blood pressure of 65/35 mm Hg with a capillary refill of 5 seconds,
oxygen saturation of 95% with mask oxygen, and body tempera-
ture of 35.5°C. On neurological examination, she was comatose,
From the *Department of Pediatric Infectious Disease, Medical School of Ege
University; †Department of Pediatric Intensive Care, ‡Department of Pediatric
Emergency Care, and §Department of Pediatric Nephrology, Izmir Tepecik
Training and Research Hospital, Izmir, Turkey.
Disclosure: The authors declare no conflict of interest.
Reprints: Zumrut Sahbudak Bal, MD, Department of Pediatric Infectious
Disease, Medical School of Ege University, Bornova, Izmir, Turkey
(e‐mail: z.sahbudak@gmail.com).
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ISSN: 0749-5161
Pediatric Emergency Care • Volume 00, Number 00, Month 2015
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with a Glasgow Coma Scale score of 6. She had normal deep-
tendon reflexes with no pathological reflexes, and her pupillary
light reflex was weak bilaterally. She was intubated immediately.
Intraosseous crystalloid infusion (20 ml/kg 0.9% NaCl) was
then commenced.
In the ED, she developed secondary generalized tonic–clonic
seizure. The capillary glucose finger-stick test was136 mg/dL.
Midazolam was given at 0.1 mg/kg intraosseously, followed by
phenytoin infusion (15 mg/kg). The seizure lasted 10 minutes.
Auscultation of the lung was normal, and heart sounds showed
no abnormalities. Her left thigh was edematous and purple in
color, but her peripheral pulse was palpable, and Doppler ultrasonog-
raphy of the femoral and popliteal veins was normal. Arterial blood
gas analysis revealed metabolic acidosis (pH 6.89, paCO2 14 mm Hg,
PaO2 245 mm Hg, 3 mmol/L bicarbonate, 34.6 mmol/L anion gap,
and 2.7 mmol/L lactate). Capillary blood glucose was 138 mg/dl.
Complete blood cell counts revealed 11.5 g/dL hemoglobin, white
blood cell count of 18,700/mL with a differential analysis of
84.3% neutrophils, 13.7% lymphocytes, 0.7% monocyte, and
1.3% eosinophils, and platelet count of 573,000/mL. Plasma bio-
chemical analysis showed 39 mg/dL urea, 0.5 mg/dL creatinine,
142 mg/dL blood glucose, 143 mmol/L sodium, 5.34 mmol/L po-
tassium, 115 mmol/L chloride, and <0.105 mg/dL C-reactive pro-
tein. All coagulation parameters were normal.
The patient was transferred to the pediatric intensive care
unit. Subclavian central venous access was obtained, and the pa-
tient was infused with bicarbonate, fluids, and 10 mcg/kg/minute
dopamine. Because of the possibility of sepsis, empiric broad-
spectrum antibiotics were started. Although the clinical findings
of the injection site were not suggestive of bacterial infection,
blood and urine cultures obtained revealed no microorganisms.
However, lumbar puncture to analyze the cerebrospinal fluid and
cranial computed tomography (CT) could not be performed due
to her hemodynamic instability. After the first assessment and
secure the patient's airway, breathing, and circulation, her medical
history was reviewed. The patient had a history of upper respiratory
tract infection, and a primary care physician prescribed antibiotic
(sulbactam-ampisilin) 3 days previously. She received antibiotic
therapy for 3 days via the intramuscular route. Her family reported
swelling and a rash at the injection site, so they wrapped two third of
her thigh with a spirit- soaked bandage (96% methanol) for three days
and almost 24 hours. In Turkey, spirit-soaked bandages are infre-
quently offered by traditional care providers as analgesic and anti-
pyretic medications, but its exact frequency is not known in our
country and also in the world.
A suspicion of methanol intoxication was reached based
on the high-anion gap metabolic acidosis and the use of the
spirit-soaked bandage. Measured methanol level was 20.4 mg/dL,
demonstrating methanol intoxication. Despite bicarbonate infu-
sion, metabolic acidosis persisted (pH 6.80, 17 mm Hg paCO2,
150 mm Hg PaO2, <3 meq/L bicarbonate, and 9.8 mmol/L lac-
tate). Therefore, continuous venovenous hemodialysis (CVVHD)
was initiated, combined with a maintenance dose of 10 mg/kg per
hour fomepizole after a 15 mg/kg bolus at the same dose with the
patients not hemodialyzed but the interval of doses of fomepizole
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Bal et al
were shortened (4 hours) during CVVHD, all doses were admin-
istered intravenously over a 30-minute period, and Ca leucoverin
was administered 50 mg/dose every 6 hours intravenously. Oph-
thalmologic examination revealed no optic atrophy on the first
day, therefore, she did not recover consciousness, vision could
not be evaluated. Twelve hours after CVVHD began, the anion
gap decreased to 10.4, blood gas analysis reached normal levels
(pH 7.35, 150 mm Hg PO2, 38 mm Hg PCO2, and 0.8 mmol/L
lactate), and blood methanol levels were 0 mg/dL. Continuous
venovenous hemodialysis and fomepizole were then discontinued,
but the patients' neurological status did not improve. Twenty-four
hours after admission, a cranial CT scan revealed massive edema
and subarachnoid hemorrhage in the occipital lobe. The MRI
could not be performed because of requirement mechanical venti-
lation. Complete blood counts, biochemistry, and coagulation pa-
rameters were normal, and blood cultures were negative. We
initiated mannitol therapy for brain edema. However, the patient
died after 7 days due to neurological impairment.
DISCUSSION
It is well known that fatal methanol poisoning can result from
many sources and routes. Although most reported cases are due to
oral ingestion, transdermal absorption can also lead to intoxica-
tion. Initially, we did not prioritize methanol intoxication because
of her young age until her medical history was reviewed. To date
transdermal intoxication has rarely been reported.2–6 Avella et al.6
described a case of suicide jumping from second floor. The patient
was found dead with number of injuries, lying naked in partially
evaporated methanol. Therefore, the cause of death was deter-
mined to be blunt impact trauma and transdermal methanol poi-
soning. Işcan et al.4 reported a 54-year old woman with total
bilateral optic nerve atrophy after local application of methanol-
containing spirit. Karaduman et al.2 reported a case of intoxication
in a 47 year old female who had wrapped her ankle with a spirit-
soaked bandage due to an ankle injury. They hypothesized that the
duration of exposure was the most important factor influencing
the severity of intoxication. Soysal et al.5 described a 51-year
old woman with transdermal methanol intoxication who used
spirits to massage her head on several occasions due to headaches.
They concluded that the surface of dermal exposure is the most
important factor due to the fact that vascular and lymphatic drain-
age impact transdermal absorption. In this study, our patient had a
history of transdermal intoxication after the application of a spirit-
soaked bandage (containing 96% methanol) for 3 days to heal the
soft tissue damage resulting from injections. To our opinion, in ac-
cordance with these arguments, both the ratio of the size of the
methanol exposure surface to the total body surface area and the
duration of exposure influence the severity of intoxication.
Normally, sepsis and/or metabolic diseases should be consid-
ered first in an infant with a history of 3-day antibiotic use who
presents with shock and seizure. However, laboratory findings,
such as high-anion gap metabolic acidosis, the history of using
methanol-containing spirit-soaked bandages, and high levels of
serum methanol confirmed the diagnosis.
Methanol is a CNS depressant that is potentially toxic after
ingestion, inhalation, or transdermal exposure.1–4 Manifestations
of methanol poisoning include visual disturbance, central nervous
system depression, and severe metabolic acidosis.4 Despite effi-
cient treatment, methanol poisoning has a high morbidity and
mortality. Therefore, rapid diagnosis and early treatment are of
the utmost importance.7 The poor prognostic characteristics in our pa-
tient were coma on admission, severe metabolic acidosis (<3 meq/L
bicarbonate and blood pH <7), time elapsed before admission (72 h),
and no coingestion of ethanol. Increased pCO2 in severely acidotic
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Pediatric Emergency Care • Volume 00, Number 00, Month 2015
patients due to a lack of compensatory hyperventilation has also
been suggested as a potential new diagnostic marker.7–9
Methanol poisoning causes neurological symptoms of vari-
able severity, including cerebral and intraventricular hemorrhage,
cerebellar necrosis, diffuse cerebral edema, and bilateral subcor-
tical white matter necrosis.1 A cranial CT of our patient revealed
massive edema and subarachnoid hemorrhage in the occipital
lobe. However, MRI could not be performed because of her ongo-
ing requirement of mechanical ventilation.
The treatment of methanol intoxication commonly includes eth-
anol, fomepizole, and hemodialysis. Fomepizole (4-methylpyrazole)
is a competitive inhibitor of alcohol dehydrogenase that prevents
the formation of metabolites of ethylene glycol and methanol. It
is most effective when given early, before significant quantities of
metabolites are formed.10 Although hemodialysis is much more
effective in clearing methanol, CVVHD is preferred in hemody-
namically unstable patients.11 Some previous studies reported the
use of CVVHD.7,11 Epker et al11 reported a case of severe methanol
intoxication who was treated with CVVHD due to hemodynamic
instability. Although blood methanol levels decreased to 0 mg/dL
after 48 hours of admission, their patient died due to neurological
impairment, as is the case in our patient. In this particular case,
we used CVVHD to treat methanol intoxication and then methanol
levels were decreased 12 hours after initiating treatment. During
CVVHD treatment, our patient received fomepizole at usual dose
but shorter intervals. Although methanol levels decreased, the pa-
tient died because of neurological impairment.
In conclusion, the diagnosis of methanol intoxication should be
considered in patients with high-anion gap metabolic acidosis. Re-
gardless of age, transdermal exposure should be kept in mind in the
absence of a history of oral methanol ingestion to ensure prompt di-
agnosis and management. Continuous venovenous hemodialysis
may be a good alternative treatment if the patient is not hemodynam-
ically stable, but it is not recommended routinely because of its
slower clearance rate compared with conventional hemodialysis.
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