Methanol Toxicity

Methanol Toxicity
Dr Babak masoumi
Assistant Professor of Emergency Medicine,
Emergency Department, Alzahra General Hospital,
Isfahan University Of Medical Sciences
slightly sweet-tasting alcohol.
It is a product of :
natural fermentation
originally was manufactured
the distillation of wood.
Certain products found in the home:
windshield washer fluid;
dry gas;
carburetor fluid;
duplicator fluid;
glass cleaners
hobby engine fuel;
thinners for shellacs
may contain high concentrations of methanol.
Methanol is a precursor in the manufacture of plastics, films,
and dyes.
Methanol is also found in formalin and embalming fluid.
windshield washer fluid:
Illicit alcohol production remains a global
source of methanol poisoning from products
such as chang’aa (Kenya), raki (Turkey), and
tuica (Romania).
chang’aa (Kenya):
raki (Turkey):
In Turkey, raki is the unofficial “national drink”. To serve
raki it must be mixed with cold water; when it is mixed
with water it turns to milky-white color. Because of that
color raki is called as “aslan sütü” which means “lion’s
Treatment delay is associated
with increased morbidity,
making early recognition of clinical
and laboratory clues crucial.
Methanol is absorbed rapidly from
the gastrointestinal tract,
blood levels
30 to 60 minutes
after ingestion.
respiratory tract absorption
also has resulted in
especially in infants.
Certain occupations, including
lithography, and
are at high risk for inhalational exposure to
Inhalational abuse of methanol is a recent trend that
can result in toxic serum levels.
• In adults,
the smallest lethal dose
reported is
15 mL of 40% methanol;
•4 mL of pure methanol has
led to blindness.
With appropriate, timely treatment,
survival without loss of eyesight has
been reported
despite extremely high levels.
From a pediatric perspective,
the ingestion of only 1.5 mL of 100% methanol
in a toddler (0.15 mL/kg)
is sufficient to produce
a toxic blood level of 20 mg/dL.
Any suggested pediatric
methanol ingestion warrants
aggressive evaluation and
Methanol itself has little toxicity,
CNS depression
than ethanol.
Metabolites of the parent alcohol
are extremely
toxic, however.
Although small amounts of methanol are
eliminated via renal and pulmonary
routes, 90% is metabolized
Methanol is oxidized by
alcohol dehydrogenase (ADH) to
formaldehyde, which is rapidly converted by
aldehyde dehydrogenase to
formic acid.
• Formic acid is the primary toxicant and accounts for
much of the anion gap metabolic acidosis and
ocular toxicity peculiar to methanol ingestion.
Through a folate-dependent pathway, formic
acid is degraded to carbon dioxide and
Metabolism of Methanol:
Optic neuropathy
putaminal necrosis
are the
two main complications
severe methanol poisoning.
Long-term morbidity:
• takes the form of:
visual impairment,
parkinsonian motor dysfunction,
characterized by:
• The primary sites of ocular injury are the
retrolaminar optic nerve and retina.
• Methanol adversely affects other areas of the CNS,
specifically the basal ganglia.
Bilateral, symmetrical putaminal hypodensities,
hemorrhages, or cystic lesions are characteristic,
occurring in 13.5% of patients.
Necrosis is described in the:
subcortical white matter,
spinal cord anterior horn cells,
Acute signs and symptoms may be lacking or may take
several days to develop, despite the presence of these
radiographic findings.
Clinical Features:
• With individual cases of methanol poisoning,
the history may be
• The diagnosis should be considered in patients with
altered mental status,
visual complaints, or
metabolic acidosis or
in patients with occupations
that put them at high risk for exposure.
• The typical 12- to 24-hour latency may be
shorter when large amounts are consumed or
longer when ethanol is co-ingested (range 40 min
to 72 hr).
• When symptoms manifest, they are primarily
gastrointestinal, or
• Although methanol is less inebriating than ethanol,
• early symptoms of methanol poisoning are:
depressed mental status,
Nonspecific complaints of:
• In severe cases,
seizures may be seen.
abdominal pain
commonly result from mucosal irritation, the
absence of gastrointestinal complaints does not
rule out a serious ingestion
• Visual disturbances are seen in 50% of patients,
and their development may precede or parallel that
of other clinical symptoms.
• Patients may complain of
indistinct, or
misty vision or
may note yellow spots
• The most common acute field defect is a dense
central scotoma.
• Some patients compare their visual symptoms
with “stepping out into a snowstorm,” a
complaint unique to methanol ingestion.
• Patients can have a complete lack of light
perception and total loss of vision.
• Prognosis after methanol ingestion seems to
correlate with:
the degree of acidosis,
time to presentation,
initiation of treatment within 8 hours of exposure
• Poor prognosis is associated with
arterial pH less than 7.0.
• A recent large outbreak was associated with a
fatality rate of 44%
• Patients surviving the acute phase of toxicity may
be left with:
permanent blindness or
neurologic deficits, such as:
toxic encephalopathy,
cognitive dysfunction,
transverse myelitis,
primitive reflexes, or
Diagnostic Strategies:
• A severe anion gap metabolic acidosis is the
hallmark of methanol poisoning. In some cases,
this sign may be the only diagnostic clue.
• Because the onset of acidosis may be delayed 12
to 24 hours, the presence of a normal anion gap
does not rule out methanol exposure.
• Absence of high anion gap acidosis has
been described in cases with:
In methanol toxicity, this anion gap is due primarily to
formic acid, with a variable
contribution from lactic acid.
the presence of
• Another classic laboratory finding in methanol
toxicity is an elevated osmol
osmolal gap is defined as follows:
gap. The
Osmol gap= measured serum osmolality- calculated serum osmolality
An osmol gap significantly greater than 10 mOsm/kg may be a useful aid
in the diagnosis of toxic alcohol ingestion.
• delayed presentation after toxic alcohol
ingestion may be associated with prior metabolism
of most of the parent alcohol.
• Because only the parent compound is osmotically
active, and
• Because the charged metabolites are electrically
balanced by sodium,
there may
be little or no osmol gap
elevation in this setting.
• If there is clinical suggestion of toxic alcohol
ingestion, direct measurement of the serum
toxic alcohol level is necessary, and if not
readily available, empirical treatment is warranted.
pancreatitis, and
metabolic derangements, such as:
are also described with methanol poisoning.
• Computed tomography may be indicated in
an intoxicated patient with altered mental status.
• For any significant history of exposure,
treatment should be initiated pending a
confirmatory toxic alcohol blood level.
• Because methanol is absorbed rapidly from the GI
tract, gastric emptying is restricted to
patients who have ingested a substantial volume
and arrive in the emergency department within
30 to 60 minutes of ingestion.
Activated charcoal is
not useful.
• Forced diuresis is of no value and may
cause pulmonary edema and ARDS.
Early intubation may be indicated to
protect the airway against aspiration and in
anticipation of further deterioration in mental
• Three treatment goals exist for patients
with methanol toxicity:
(1) correction of metabolic acidosis with
(2) ADH enzyme blockade, which
inhibits the metabolism of methanol to toxic
metabolites; and
(3) removal of the parent alcohol and its
metabolites by hemodialysis.
• Depending on the severity of the patient's acidosis,
IV bicarbonate can be administered by
intermittent boluses, an initial bolus followed by
an infusion, or infusion alone.
• Boluses of 1 to 2 mEq/kg to attain a target
serum pH of 7.45 to 7.50 followed by an
infusion of 150 mEq/L of sodium bicarbonate in
5% dextrose at 1.5 to 2 times the maintenance
fluid rate are suggested.
• To prevent further production of the toxic and
acidic metabolites of methanol and ethylene
glycol, metabolism of the parent compounds by
the enzyme ADH must be blocked by either
ethanol or fomepizole (Antizol).
• After significant toxic alcohol exposure, ADH
blockade should be carried out in any adult or child
with symptoms or with methanol or ethylene
glycol levels greater than 20 mg/dL, even if
• If ethanol is used to block ADH,
the goal is to maintain
the blood ethanol level between 100 and 150 mg/dL,
which completely saturates ADH.
The affinity of ADH for ethanol is 10 to 20 times
greater than for methanol and 100 times greater
than for ethylene glycol.
• When methanol or ethylene glycol
metabolism is blocked by ethanol,
their half-lives increase to more
than 30 hours or 17 hours.
• When dosing ethanol, it also is important to
measure the patient's initial blood ethanol level.
• If it is greater than 100 mg/dL, a loading dose is
unnecessary, and the patient can be started on a
maintenance infusion.
• The required maintenance dose of ethanol may
nearly triple during hemodialysis because ethanol
also is efficiently removed.
• Ethanol may be given orally or intravenously.
• Potential side effects of IV administration include
CNS and respiratory depression,
hypoglycemia, and
although even in children, adverse effects are limited.
Oral ethanol loading may be associated with gastritis.
Initial close monitoring of serum ethanol
and glucose levels every 1 to 2 hours is
essential until a steady-state level of 100 to
150 mg/dL is achieved.
• Levels should be checked every 2 to 4 hours
Monitoring of ethanol therapy ideally is
accomplished in the intensive care unit.
Standard Range of Therapeutic Doses of Ethanol
Based on Average Pharmacokinetic Values:
• Mixing 50 mL of absolute ethanol with 450 mL
isotonic glucose yields a 10% solution if a 10% ethanol
solution for IV use is unavailable.
• With this solution, a
bolus of 8 mL/kg (over 0.5
hour), followed by 1.5 mL/kg/hr, will produce the
desired ethanol concentration. The maintenance infusion should
be increased or decreased according to frequently measured
ethanol levels.
• As a rule of thumb, the
maintenance dose of ethanol
should be doubled during hemodialysis. If not,
methanol metabolism can resume when the ethanol level drops,
resulting in worsening toxicity despite hemodialysis.
• Similar to ethanol, fomepizole blocks the
metabolism of methanol and ethylene glycol by
ADH and prevents the formation of toxic
• When methanol or ethylene glycol metabolism is
blocked by fomepizole, their half-lives increase
to an average of 52 and 17 hours.
• Fomepizole is a
pregnancy category C drug;
• although not approved for use in
children, its use has been reported.
• Simply blocking toxic alcohol
metabolism does not alter the
toxicity of preformed metabolites.
The use of neither fomepizole nor
ethanol supplants the need for
 Approved by FDA for E.G. poisoning in
1997, and for methanol poisoning in 2000
• Fomepizole has an affinity for the enzyme
that is 8000 times that of ethanol.
• In addition, it does not produce central
nervous system depression or metabolic
toxicity, and it does not require the
monitoring of levels and dosage
• The dose is 15 mg/kg followed by 10 mg/kg every
12 hours for four doses.
• After five doses, the dose increases to 15 mg/kg
every 12 hours until the Methanol concentration is
undetectable or less than 20 mg/dL and the
patient is asymptomatic with a normal arterial pH.
• Dosing changes are required during hemodialysis.
Side effects of fomepizole:
inflammation at the site of infusion,
mild, reversible transaminase elevation.
• Rapid removal of the methanol or ethylene glycol
through hemodialysis before they have been
metabolized remains the cornerstone of therapy.
hemodialysis is indicated in:
patients who have metabolic acidosis,
renal compromise,
visual symptoms (methanol),
deterioration despite intensive supportive care,
electrolyte imbalances unresponsive to conventional
a blood level of either substance greater than 50 mg/dl
but in patients with normal kidneys, prolonged
fomepizole treatment alone has been used without
Indications for Dialysis with
Methanol Poisoning :
The endpoint for hemodialysis:
• an undetectable serum ethylene glycol or
methanol concentration &
• the disappearance of acid-base
abnormalities &
• the disappearance of signs of systemic
• Closure of the anion gap also may serve as
an endpoint for hemodialysis in situations in
which levels are not available or reliable (i.e.,
in patients with delayed presentation).
• If methanol analyses are unavailable:
hemodialysis should be continued for
at least 8 hours
until the osmolal gap is normal
in two samples 1 hour apart.
• In methanol poisoning, the rate of the final
degradation reaction of formic acid to carbon
dioxide and water depends on the cofactor folate.
• 50 mg of leucovorin (folinic acid) should
be given IV every
methanol toxicity.
4 hours to adults with
• If folinic acid is unavailable, folic acid, in the same
dose, can be used.
Thank You for your attention

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