Methanol Intoxication

Bramantono
Department of Internal Medicine
Airlangga University School of Medicine-Dr. Soetomo Hospital Surabaya
Introduction
Methanol (methyl alcohol)
Also known as wood alcohol
Colorless, volatile liquid, odour similar to alcohol,
burning taste.
Paint removers, solvents, varnishes, windshield washing
fluid
Well absorbed from the GI tract
Peak levels 30-90 minutes after ingestion
Presentation may be delayed 12-18 hours (longer if
EtOH co-ingested)
Toxicity is the result of the metabolites
Formaldehyde & formate
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WHO (2014) Report
There have been numerous outbreaks of methanol
poisoning in recent years in several countries, including
Cambodia, Czech Republic, Ecuador, Estonia, India,
Indonesia, Kenya, Libya, Nicaragua, Norway, Pakistan,
Turkey and Uganda. The size of these outbreaks has
ranged from 20 to over 800 victims, with case fatality
rates of over 30% in some instances.
Some common names for these drinks include: hooch/
moonshine (USA), changaa/kumi kumi (Kenya),
tonto/waragi (Uganda), tuak/tapai (Malaysia), samogon
(Russia), talla (Ethiopia) and cukrik (Indonesia)

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Surabaya

Data from patients who come

to the emergency ward dr
Sutomo Surabaya in 2016
found 19 patients, 7 of whom
died.
The mortality rate is high, so
that the required accuracy in
diagnosing, referring and
appropriate treatment.
Unpublished data

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 MECHANISM OF ACTION

Methanol
Alcohol
dehydrogenase
Formaldehyde 33 times more
Formaldehyde toxic than methanol.
Aldehyde Formic Acid is 6 times more
dehydrogenase
toxic than methanol.
Formic acid
Folate

CO2 & H2O

Kruse JA, Intenvise Care 1992;18;391-397

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Mechanism of Action
Formic acid
Metabolic acidosis
Inhibits cytochrome oxidase:
Decreased ATP production
Increased anaerobic glycolysis & lactate

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 MECHANISM OF ACTION
METHANOL

OCULAR FORMALDEHYDE
TOXICITY
INHIBITION OF MITOCHONDRIAL RESPIRATION

INCREASED FORMIC ACID TOXICITY FORMIC

ACID
CIRCULATORY
FAILURE

TISSUE CIRCULUS
ACIDOSIS ACIDOSIS
HYPOXIA HYPOXICUS

LACTIC ACID
PRODUCTION Early stage
of poisoning
GENERAL TOXICITY

7
Sign And Symptoms

Produces symptoms of drunkenness like ethyl alcohol.

Appearance of symptoms: 1 hour 24 hours
Initial inebriation - especially if ethanol coingested
After 12 - 24 hour delay - progression to acidosis and
other signs and symptoms
May be further delay with continued ingestion of
ethanol
Fatal Dose: 60-120 ml

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Sign And Symptoms
CNS - inebriation progressing to coma, convulsions
RETINAL- blurred vision, photophobia, visual acuity
loss, dilated non-reactive pupils, optic nerve
hyperaemic - becoming oedematous,blindness
GIT- nausea, vomiting, abdominal pain, pancreatitis
Cardiac- tachycardia, hypertension progressing to
hypotension and cardiogenic shock
RESPIRATORY tachypnoea, kussmaul, death may
occur from respiratory depression

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Sign and Symptoms
Urine is strongly acidic and contains
- albumin
- acetone
- formic acid
Death is mainly due to metabolic acidosis resulting
from production of organic acids mainly, Formic
Acid.
CNS depression leading to respiratory depression.

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Laboratory Findings

AcidBase Disturbances : Differential Diagnosis

Endogenous hydrogen ion production:
metabolic acidosis ketoacidosis
lactic acidosis

pH < & 7.0 strongest Metabolism of toxins

salicylate overdose

predictor of mortality methanol

ethylene glycol

Mortality increased 20 Decreased renal excretion

uremia

times pH < 7.0 Vs > 7.0 renal tubular acidosis (type 1)

distal

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Laboratory Findings
Methanoltests are not readily
available in most laboratories.
When methanol poisoning is
suspected, a serum osmolality test is
ordered and the osmolar gap is
calculated.
The osmolar gap is the increase in the
number of particles in the blood
beyond what is considered normal and Calculated osmolality (mOsm/kg) =
will be increased when ethanol, 2(Na+) + (glucose/18) + (blood urea
methanol, or ethylene glycol are nitrogen [BUN]/2.8)
present in the blood.
Elevated anion gap
Fujita m et al, Internal Medicine, 2004;43(8);750-754

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 DDx of elevated DDx of elevated
Anion Gap Osm Gap
Methanol With anion gap metabolic acidosis
Uremia Methanol ingestion
DKA, SKA, AKA End-stage renal disease (GFR <10)
Diabetic ketoacidosis
Paraldehyde Alcoholic ketoacidosis
Isoniazid/Iron Paraldehyde ingestion
Lactate Lactic acidosis
Ethylene glycol Ethylene glycol ingestion
Formaldehyde ingestion
Salicylates

Fujita m et al, Internal Medicine, 2004;43(8);750-754

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Investigation Methanol Intoxication
Blood methanol level
ABG - metabolic acidosis
Osmolal gap - increased (methanol)
Anion gap - increased (formic acid, lactic acid)
Blood ethanol
Magnesium, amylase, potassium

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 Methanol Toxic Optic Neuropathy
During the period of January 2013 until December
2014, 31 patients were diagnosed with methanol
toxic optic neuropathy

Right (a) and left (b) fundal pictures showing pale optic discs with extending
atrophic changes to retinal nervefibers layers suggesting optic atrophy

Y Ardiella et al, Ophtamol Ina 2016;42(1);38-44

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 CT Scan

Non contrast axial CT head (a) showing hypodense areas involving bilateral lentiform nuclei with
hyperdensespecks within and T1 weighted axial MR Image of brain showing hypointense lesions
with centralhy perintensities (arrows) in putamina, suggesting bilateral putaminal hemorrhagic
necrosis

Nand et al, JAPI 2016;62 :96-99

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Diagnosis
History
Physical findings
Kussmaul respirations
Faint odor of methanol on breath
Visual disturbances
Nausea, vomiting, abdominal pain
Altered sensorium
Laboratory findings
Elevated anion gap
Metabolic acidosis
Elevated osmol gap
Positive serum methanol assay

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Methanol Toxicity Differential Diagnoses

Conditions to consider in the differential diagnosis of

methanol intoxication include the following:
Arsenic poisoning
Cocaine poisoning
Inhalant poisoning
Complex partial seizures
Ethylene glycol intoxication
Carbon monoxide poisoning
Pseudoseizure
Any cause of altered mental status with acidosis and
potential cardiovascular collapse

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Treatment
Stabilising airway, breathing and circulation,
limiting acidosis and reducing uptake of and
removing methanol
Traditionally the use of ethanol has been the basis
of treatment however, where available, 4-Methyl
pyrazole (fomepizole) should be used first
Haemodialysis

Kraut JA, Am J Kidney Dis 2016;02;1-7

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Treatment with Ethanol or Fomipizole

CH3OH CH2O CHOOH

ADH FDH F-THF-S
Methanol Formaldehyde Formic CO2 + H2O
acid
Ethanol Folate
Fomepizole

ADH : alcohol dehydrogenase; FDH : formaldehyde dehydrogenase

F-THF-S : 10-formyl tetrahydrofolate synthetase

Kraut JA, Am J Kidney Dis 2016;02;1-7

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Management priorities for methanol poisoning

American Academy of Clinical Toxicology Practice Guidelines

on the Treatment of Methanol Poisoning,
Clinical Toxicology, 40(4), 415446 (2002)

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 Recomended Therapeutic Doses of Ethanol Based Average
Pharmecokinetic Values ( Table 3)
Amount Volume Volume
absolute (43% Oral Solution) (10% IV Solution)
Ethanol
Loading dose 600mg/kg 1.8 mL/kg 7.6 mL/kg

Standart maintenance dose 66 mg/kg/h 0.2 mL/kg/h 0.83 ml/kg/h

(nondrinker)

Standart maintenance dose (ethanol 154 mg/kg/h 0.46 mL/kg/h 1.96 ml/kg/h
abuser)

Mantenance dose during dialysis 169 mg/kg/h 0.5 mL/kg/h 2.13 ml/kg/h
(nondrinker)

Mantenance dose during dialysis 257 mg/kg/h 0.77 mL/kg/h 3.26 ml/kg/h
(ethanol abuser)

Clinical Toxicology, 40(4), 415446 (2002)

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Ethanol vs Fompepizole
Ethanol: Fomepizole:
- Oral or IV - IV
- CNS depression - No CNS depression
- Easy dosing
- Difficult titration
- No levels to monitor
- Frequent levels
- More predictable
- Hypoglycemia
pharmacokinetcs
- No Hypoglycemia
- Cost

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Rietjens et al. The Neth Jour of Med, 2014;72;73-79

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Reffering Px
Managed patients at a tertiary facility
Manage airway and asisist ventilation as needed
If severe respiratory distress or SpO2 <90, give oxygen
If hypotension or shock give IV fluids rapidly and titrete
to maintain good urine output.
Give strong alcoholic drink (e.g. brand-named vodka or
wishky, not informally distilled spirit) to block
metabolism. Oral loading dose (by NG tube) : 1.8 ml/kg
of a 40-43% alcoholic drink over 15-30 minutes
(diluted).
Transfer at this stage if necessasry.
WHO 2011, Guidelines for the management of common illnesses with limited resources

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Indication for Hemodialysis
American academy of clinical toxicology practice
guidelines
pH <7.25 to 7.35
Or visual signs and/or symptoms
Or decreases vital signs despite intensive supportive care of
kidney failure
Or substantial electrolyte disturbances unresponsive to
supportive care
Or serum methanol concentration >50 mg/dL

Kraut JA, Am J Kidney Dis 2016;02;1-7

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Indication for Hemodialysis
Extracorporeal treatment in poisoning workgroup
pH <7.15
Severe visual defects
Or coma
Or worsening vital signs despite intensive
supportive care
Or kidney failure
Or serum methanol
>70 mg/dL with femopizole
>60 mg/dL with ethanol
>50 mg/dL absence of inhibitor

Kraut JA, Am J Kidney Dis 2016;02;1-7

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How to Discontinue Tx Ethanol
The clinician can used this estimated serum
methanol concentration to assess the clearance of
methanol from the body.
When serum osmolal gap is decreased to 6
mOsm/kg (equivalent to serum methanol
concentration of 20 mg/dL),
Dialysis therapy and treatment with inhibitor can
theoretically be discontinued.

Kraut JA, Am J Kidney Dis 2016;02;1-7

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Teaching Points
Symptoms including abdominal pain, nausea, vomiting,
and decrease vision, methabolic acidosis and can occur
hours to days after exposure.
An increase in serum osmolality and/or anion gap can
be clues for methanol intoxication
Definitive diagnosis of methanol intoxication presently
a laborious
Treatment can be included administrastion of ethanol
or fomepizole, 2 inhibitor of alcohol dehydrogenase
Hemodialysis can remove both methanol and formate

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Thank You

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Indication Of Ethanol

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Dose of Ethanol

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Dose of Ethanol

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Ethanol

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Metabolism

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The Osmolar Gap

Measured Serum Osmolarity

Minus
Calculated Serum Osmolarity
[ 2(NA) + BUN/2.8 + Glucose/18+Etoh/4.6]

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 The Osmolar Gap
Compound Concentration (mg/L) Osmolal Contribution
(mOsm/kg H2O)
Propylene glycol 1000 (13 mmol/L) 13
Ethylene glycol 1000 (16 mmol/L) 16
Isopropanol 1000 (17 mmol/L) 17
Acetone 1000 (18 mmol/L) 18
Ethanol 1000 (22 mmol/L) 22
Methanol 1000 (34 mmol/L) 34

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mEq/L mOsm

0 Time since Ingestion

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Anion Gap

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