Methanol Poisoning
-
Odorless, colorless liquid
- Highly
toxic
Lethal
dose 30-50 ml (0.5 ml/kg)
Blindness
- as little as 10 ml
-
Poisoning most commonly occurs via oral ingestion (accidental or deliberate),
but also absorbed transdermally or by inhalation
- Peak
serum levels occur within 60 min.
- Levels
not correlated with symptom onset
- 12-36h latency period before symptoms occur
Products
containing methanol
-
Anti-freeze
-
De-icing solutions
- Varnish
- Paint
remover
-
Windshield wiper fluid
-
Photocopying fluid
- Picnic
fuels
Methanol
metabolism
-
Methanol is converted to formaldehyde by alcohol dehydrogenase (ADH). This
is the rate limiting step in the metabolism of methanol
-
formaldehyde is converted to formic acid by aldehyde dehydrogenase
- formic
acid is converted to CO2 and water, folate is a cofactor in this reaction
***
formic acid causes
the metabolic acidosis and CNS damage seen in methanol poisoning
- the
production of formic acid takes time, which explains the delay in onset of
symptoms
Symptoms
of methanol intoxication
Nausea /
vomiting, abdominal pain
Dyspnea
Headache,
dizziness
Visual
symptoms: blurring/dimming or blindness, flashes of light, “snowfield”
Unsteady
Confusion,
depressed LOC or coma
Seizures
Death
Signs
of methanol intoxication
Depressed
LOC / altered mental status
Decreased
visual acuity
Visual
field defects / scotomata
Mydriasis,
decreased pupillary response
Hyperemia
of optic discs, peripapillary and retinal edema (early) or normal
Glaucoma-like
cupped / atrophic discs (late)
Metabolic
effects of methanol intoxication
Metabolic
acidosis (secondary to formate / lactate)
Elevated
anion gap (secondary to formate / lactate)
Elevated
osmolar gap (secondary to methanol / formaldehyde)
Pancreatitis,
usually hemorrhagic
Acute
renal failure
CHF /
arrythmias
Rhabdomyolysis
Elevated
anion gap
- Anion
Gap = Na - (Cl + HCO3)
-
Represents contribution of ‘unmeasured anions’
-
Elevated anion gap > 12
- With
methanol poisoning, anion gap may be normal early on. As formate is produced,
anion gap rises
DDx of
elevated anion gap metabolic acidosis
M
methanol
U uremia
D DKA, ketones
P paraldehyde
I INH, Iron
L lactate
E Ethanol, Ethylene glycol
S salicylates
Elevated
osmolar gap
- Osmolar
gap = Serum OSM - Calculated OSM
-
Calculated OSM = “2 salts and a sticky BUN” = 2xNa + glucose + urea (mmol/L)
-
Elevated osmolar gap > 10 mmol/L
- DDx of
elevated osmolar gap: Ethanol, Methanol / Formaldehyde, Ethylene glycol,
Isopropanol (acid-base status usually normal), ketoacidosis, mannitol,
paraldehyde
NOTE:
*** in
late presentations of methanol poisoning, the osmolar gap may be normal since
the methanol and formaldehyde are metabolized to formic acid which does
contribute to the osmolar gap
Imaging
CT
Bilateral
putaminal hypodensity +/- hemmorhage
+/-
subcortical white matter hypodensity, primarily frontal and occipital
LATE – Basal
Ganglia calcifications
MRI
(T2-)
Hyperintense lesions in above distribution
DDx of
Bilateral BG hypodensity / hemorrhage
Methanol
(putamen)
Carbon
monoxide (globus pallidus)
Cyanide
Cerebral
hypoxia
Ischemic
Lacunar / small vessel disease
Internal cerebral vein thrombosis
Wilson’s
disease
Mitochondrial
disorders e.g Leigh’s, Kearns-Sayre
Management
1.
ABCs / supportive care
2.
Gastric lavage if
seen in first few hours
3.
Prevent metabolism of methanol
Ethanol
Fomepizole
/ Antizol
4.
Enhance removal of formic acid
Folate
1mg/kg IV q4h
5.
Correct acidosis
Dialysis
Sodium
bicarbonate
6.
Remove methanol
Dialysis
Ethanol
10-fold
greater affinity for ADH vs. other alcohols
Loading
dose: 10 ml/kg of 10% EtOH in D5W IV over 30 min. OR give PO/NG
Maintenance:
1-2 ml/kg/h
Ethanol
level: 100-130 mg/dL or >22 mmol/L
Continue
treatment until methanol decreases to non-detectable
Problems: requires large volumes, hourly
monitoring, CNS depressant, hypoglycemia (peds)
Fomepizole
/ Antizol
aka
4-methylpyrazole
8000x
greater affinity for ADH vs. ethanol
$3000 USD
per 1.5g vial
Use in
combination with dialysis
Loading
dose: 15 mg/kg in 100 ml D5W IV over 30 min., then 10 mg/kg q4h with dialysis
Continue
treatment until methanol levels <20 mg/dL
Prognosis
Mortality
>80% if present with either:
Severe metabolic acidosis (pH <7)
Seizures
Coma
Mortality
<6% in absence of above
***Morbiditiy
/ Mortality related to concentration and time between exposure and institution
of therapy
Long-term
sequelae of survivors
Optic
neuropathy / blindness
Dystonia
Toxic
encephalopathy / Dementia
Axonal
polyneuropathy
References
Poison
Control Center 1-800-267-1373
UpToDate
eMedicine
J. Emerg.
Med. 24:433-436, 2003
Last
update: August 2003
Reviewed
by: pending review
Neurological
Medicine Pocketbook
© 2003-2004
UWO Neurology Residents
http://www.uwo.ca/cns/resident
All
Rights Reserved