22/2/22, 22:31 Methanol and ethylene glycol poisoning: Management - UpToDate

Author: Marco L A Sivilotti, MD, MSc, FRCPC, FACMT, FAACT

Section Editors: Stephen J Traub, MD, Michele M Burns, MD, MPH
Deputy Editor: Jonathan Grayzel, MD, FAAEM

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Feb 2021. | This topic last updated: Jul 14, 2020.

INTRODUCTION

Methanol and ethylene glycol poisonings cause scores of fatal intoxications annually, and
even relatively small ingestions of these alcohols can produce significant toxicity. Rapid
recognition and early treatment, including alcohol dehydrogenase (ADH) inhibition,
are crucial. A summary table to facilitate emergency management is provided ( table 1).

Methanol and ethylene glycol are frequently found in high concentrations in automotive
coolant/antifreeze and de-icing solutions, windshield wiper fluid, solvents, cleaners, fuels,
and other industrial products. Most serious poisonings occur following ingestion;
inhalation and dermal exposures rarely cause toxicity [1]. Patients may ingest toxic alcohols
as an ethanol substitute, to inflict self-harm, or by accident, sometimes following transfer
from the original container. Multiple victim methanol poisonings can occur with illicit
distillation ("moonshine") or occult substitution for ethanol.

The management of methanol and ethylene glycol intoxication are reviewed here. While
there are differences between methanol and ethylene glycol poisoning, there is substantial
overlap in management, and both the similarities and differences are described. The
clinical manifestations, laboratory findings, and diagnosis of methanol and ethylene glycol
are discussed separately. (See "Methanol and ethylene glycol poisoning: Pharmacology,
clinical manifestations, and diagnosis".)

● Isopropyl alcohol intoxication is considerably different, and is discussed separately.

(See "Isopropyl alcohol poisoning".)

● The approach to the poisoned adult or child is reviewed in detail separately. (See
"General approach to drug poisoning in adults" and "Approach to the child with occult
toxic exposure" and "Initial management of the critically ill adult with an unknown
overdose".)

MANAGEMENT
uptodate.yabesh.ir/contents/methanol-and-ethylene-glycol-poisoning-management?search=Methanol and ethylene glycol poisoning: Pharmacol… 1/16
22/2/22, 22:31 Methanol and ethylene glycol poisoning: Management - UpToDate

Overview of emergency management — Rapid decision-making is critical in the

management of the patient poisoned with methanol or ethylene glycol. The clinician must
often make treatment decisions without definitive serum drug levels, based only upon
clinical suspicion and readily available laboratory data. A summary table to facilitate
emergency management is provided ( table 1).

The management of methanol and ethylene glycol poisoning involves the following:

● Securing the patient's airway, breathing, and circulation; and providing appropriate
supportive care

● Administering sodium bicarbonate to correct systemic acidosis, which limits the

penetration of toxic acids (eg, formic acid) into end-organ tissues such as the retina
by converting them to the anion (eg, formate), which cannot diffuse across cell
membrane

● Inhibiting the enzyme alcohol dehydrogenase (ADH) with either fomepizole

(preferred) or ethanol (if fomepizole is unavailable)

● Performing hemodialysis for elevated toxic alcohol levels, severe acid-base

derangements, or evidence of end-organ toxicity

● Treating with cofactors (folic

foli acid, thiamine, and pyridoxine) to optimize nontoxic
metabolic pathways for the elimination of the parent alcohol or its metabolites

We also recommend immediate consultation with a medical toxicologist or poison control

center if methanol or ethylene glycol intoxication is suspected. (See 'Additional resources'
below.)

Airway, breathing, circulation — The clinician must first assess and secure the patient's
airway, breathing, and circulation. Advanced cardiac life support measures are provided as
required. A discussion of fundamental management of the poisoned patient is found
elsewhere. (See "General approach to drug poisoning in adults".)

If endotracheal intubation is required, the patient should be hyperventilated if a significant

metabolic acidosis exists or is suspected. Arterial and/or venous blood gas analysis should
be performed frequently to evaluate pH and ensure adequate ventilation and oxygenation.
Large minute ventilations may be required to prevent profound acidemia (pH <7.1) in
patients with severe intoxication.

Gastrointestinal decontamination — There is little, if any, role for gastrointestinal

decontamination in methanol or ethylene glycol poisoning, as these simple alcohols are
rapidly absorbed. The rare patient known to have ingested a large amount of methanol or
ethylene glycol may benefit from gastric aspiration via flexible nasogastric tubing if
uptodate.yabesh.ir/contents/methanol-and-ethylene-glycol-poisoning-management?search=Methanol and ethylene glycol poisoning: Pharmacol… 2/16
22/2/22, 22:31 Methanol and ethylene glycol poisoning: Management - UpToDate

performed within 60 minutes of the ingestion. Activated charcoal, gastric lavage, and syrup
of ipecac have no role in the management of toxic alcohol exposures.

Treatment with sodium bicarbonate — Methanol is metabolized to formate; and

ethylene glycol to glycolate, glyoxylate, and oxalate. Acidemia leads to protonation of these
species to uncharged molecules (eg, formic acid), making them more likely to penetrate
end-organ tissues (such as the retina) and more likely to be reabsorbed across the renal
epithelium from the urine. Thus, patients with methanol or ethylene glycol poisoning fare
worse when systemic acidemia is present [2,3]. Treatment with sodium bicarbonate leads
to deprotonation of these acid species, making them less likely to penetrate end-organ
tissues and more likely to be excreted in the urine.

Despite this clear rationale, no clear evidence exists to determine how bicarbonate should
be given. We suggest initial treatment with 1 to 2 meq/kg of sodium bicarbonate via
intravenous (IV) bolus for any patient with a pH below 7.3 [4,5]. A maintenance infusion is
then prepared by mixing approximately 133 meq of sodium bicarbonate in 1 liter of D5W.
Infusion rates may range from 150 to 250 mL/hour in adults, or one to two times the
maintenance fluid rate in children. The appropriate rate depends upon the initial pH and
such parameters as fluid status and serum sodium concentration. The goal of treatment is
maintenance of an arterial or venous pH above 7.35, at which point the infusion is
discontinued.

Alcohol dehydrogenase inhibition

Approach and initiation — Inhibition of ADH blocks bioactivation of the parent alcohol to

its toxic acid metabolites. Early treatment is crucial since ADH inhibition does not prevent
toxicity if complete metabolism to acid species has already occurred.

Fomepizole or ethanol can be used to inhibit ADH ( table 2). We recommend treatment
with fomepizole. The American Academy of Clinical Toxicology practice guidelines provide
some guidance for the initiation of ADH inhibitor therapy [4,5]. (See 'Fomepizole' below.)

The American Academy of Clinical Toxicology's minimum treatment threshold of 20 mg/dL

of either methanol (SI equivalent 6.2 mmol/L) or ethylene glycol (SI equivalent 3.2 mmol/L)
is not evidence based and is necessarily conservative [3,6-8]. Parent alcohol concentrations
must be interpreted in clinical context. As an example, a patient with a methanol level of 25
mg/dL (or 7.8 mmol/L) and a normal acid-base status may only require one or two doses of
fomepizole and observation, whereas a patient with the same level but a significant
acidosis and vision deficits may require fomepizole, alkalinization, and hemodialysis.
Making such determinations can be difficult, and we recommend consultation with a
regional poison control center or medical toxicologist in such cases. (See 'Additional
resources' below.)

uptodate.yabesh.ir/contents/methanol-and-ethylene-glycol-poisoning-management?search=Methanol and ethylene glycol poisoning: Pharmacol… 3/16

22/2/22, 22:31 Methanol and ethylene glycol poisoning: Management - UpToDate

In the absence of confirmatory drug levels, which are rarely (if ever) available as in-house
laboratory tests, clinicians must rely upon their clinical judgment and readily available
laboratory tests when deciding whether to initiate therapy with an ADH inhibitor. However,
clinicians should be wary of initiating such therapy solely on the basis of an anion gap or
small osmolal gap without at least circumstantial evidence of toxic alcohol ingestion,
especially when ethanol therapy is contemplated. In addition, the clinician should not
ascribe metabolic acidosis to a toxic alcohol ingestion if coingested ethanol is present:
substantial oxidation of the toxic alcohol is highly unlikely in the presence of ethanol.

Fomepizole — Fomepizole has been used successfully for years to treat both methanol
and ethylene glycol poisoning [9-11] and is a superior antidote to ethanol [3,12-15].
Fomepizole is easy to dose and administer, and clinically significant adverse effects are rare
[16,17]. Its main disadvantage is its high cost. However, the cost compares favorably with
the total cost of managing patients treated with ethanol, including ethanol titration and
possibly hemodialysis and intensive care unit admission [14,18,19].

Fomepizole is loaded at 15 mg/kg IV, followed by 10 mg/kg every 12 hours, with

adjustments for hemodialysis or after more than two days of therapy. (See 'Hemodialysis'
below.)

Once begun, ADH inhibition with fomepizole should be continued until the diagnosis of
toxic alcohol ingestion has been ruled out or until blood pH is normal and serum alcohol
concentration is less than 20 mg/dL (SI units: methanol 6.2 mmol/L and ethylene glycol 3.2
mmol/L) in the presence of retinal or renal injury.

Ethanol — Historically, ethanol has been used as a competitive inhibitor of ADH, as ADH

has greater affinity for ethanol than for methanol or ethylene glycol. Although effective
[20,21], IV ethanol treatment creates several problems:

● Ethanol is difficult to dose, and appropriate levels are difficult to maintain; as a result,
frequent testing and infusion adjustments are often required.

● Ethanol requires compounding by the hospital pharmacy, irritates veins when

infused, and can complicate fluid balance in oliguric patients.

● Most limiting are the sedative and behavioral effects of ethanol, which can cause
obtundation, thereby increasing the risk of aspiration, and other complications [16].

● Ethanol therapy may pose risks in certain patients (eg, upper gastrointestinal
bleeding, first trimester pregnancy).

Thus, fomepizole is the preferred therapy. In the rare circumstance in which ethanol
therapy must be used, many sources cite an absolute ethanol level of 100 mg/dL (or 22

uptodate.yabesh.ir/contents/methanol-and-ethylene-glycol-poisoning-management?search=Methanol and ethylene glycol poisoning: Pharmacol… 4/16

22/2/22, 22:31 Methanol and ethylene glycol poisoning: Management - UpToDate

mmol/L) as the therapeutic target. A table summarizing the dilution, dosing, and titration
of IV ethanol is provided ( table 3). In the next paragraph, we also offer a simplified
approach to the loading and adjustment of IV ethanol, which aims to reduce confusion and
the potential for dosing errors that can occur when making precise calculations for an
antidote used infrequently and under time pressure. However, it should be noted that ADH
inhibition is competitive, and therefore, the target ethanol concentration should be based
on the estimated concentration of methanol or ethylene glycol. The appropriate target for
antidotal therapy with ethanol is a concentration of at least one-quarter to one-third the
serum methanol or ethylene glycol concentration expressed as mg/dL, rather than a single,
arbitrary concentration of 100 mg/dL. In other words, a modest ethanol concentration of
20 mg/dL will effectively inhibit the metabolism of 60 to 80 mg/dL of methanol or ethylene
glycol. Awareness of ethanol's antidotal potency often allows the dosing intensity of
ethanol to be reduced when this is the only antidote available.

An IV loading dose of 10 mL/kg of a 10 percent ethanol (volume/volume) solution in D5W

(ie, 800 mg/kg of ethanol) will raise serum ethanol concentrations by about 100 mg/dL. The
loading dose should be given over 60 minutes to avoid excessive side effects (eg,
hypotension, respiratory depression, somnolence). When treating patients who have
coingested ethanol, this loading dose can be scaled back in proportion to their current
serum ethanol concentration. A maintenance infusion of the 10 percent ethanol solution,
starting at 1 mL/kg per hour, is appropriate to maintain any current ethanol concentration,
as metabolism is zero order. This maintenance rate can be adjusted according to serial
ethanol concentrations and increased by about 50 percent during hemodialysis. Ethanol
concentrations should be measured every one to two hours initially, following any change
in dose or infusion rate, during and after hemodialysis (see 'Hemodialysis' below), and
every two to four hours otherwise.

Once begun, ADH inhibition with ethanol should be continued until the diagnosis of toxic
alcohol ingestion has been ruled out, or until blood pH is normal and the serum alcohol
concentration is less than 20 mg/dL (SI units: methanol 6.2 mmol/L and ethylene glycol 3.2
mmol/L) in the presence of retinal or renal injury.

Due to the risks associated with ethanol therapy, patients should be treated in a critical
care setting where their mental status and respiratory function can be closely monitored.
Whenever possible, ethanol should be administered by central venous catheter using an
infusion pump to limit venous irritation.

Should both fomepizole and pharmaceutical-grade IV ethanol be unavailable, ethanol can

also be administered orally, both to load and to maintain serum ethanol concentrations as
described above. Distilled spirits (40 to 50 percent volume/volume) intended for human
consumption can be diluted to a 20 percent solution and administered per os or via

uptodate.yabesh.ir/contents/methanol-and-ethylene-glycol-poisoning-management?search=Methanol and ethylene glycol poisoning: Pharmacol… 5/16

22/2/22, 22:31 Methanol and ethylene glycol poisoning: Management - UpToDate

nasogastric tube at half the volumes recommended above (ie, 5 mL/kg of a 20 percent
solution to raise serum concentrations by 100 mg/dL, and 0.5 mL/kg per hour for the initial
maintenance dose). Gastritis and vomiting are occasionally encountered when using the
enteral route for antidotal ethanol therapy, in addition to the other adverse effects of
ethanol.

There is no benefit to adding ethanol therapy to fomepizole therapy in methanol- and

ethylene glycol-poisoned patients.

Hemodialysis — Hemodialysis is the best method to rapidly remove both toxic acid

metabolites and parent alcohols, and it plays a fundamental role in treating severely
poisoned patients [4,5,22]. Emergency clinicians should initiate consultation with a
nephrologist immediately if they suspect a toxic alcohol ingestion and the patient has
evidence of end-organ dysfunction or acidemia, especially if transfer to a hemodialysis
center may be necessary.

In such cases, consultation should not be delayed until confirmatory methanol or ethylene
glycol levels are obtained. An arterial or venous blood gas is sufficient and serves as an
essential triage tool in this setting. This is particularly true when caring simultaneously for
multiple poisoned patients with limited hemodialysis capability [20,23].

We recommend immediate treatment with hemodialysis in the setting of a known

methanol or ethylene glycol ingestion if either of the following conditions is present:

● High anion gap metabolic acidosis, regardless of drug level

● Evidence of end-organ damage (eg, visual changes, renal failure)

In addition, we suggest treatment with hemodialysis in any patient with a suspected toxic
alcohol ingestion who has a severe, otherwise unexplained anion gap metabolic acidosis
and significant plasma osmolal gap. It is difficult to provide precise thresholds for
determining when hemodialysis should be performed when the ingestion is uncertain. If a
toxic ingestion is strongly suspected, a threshold pH of 7.3 is reasonable; if suspicion is
weaker, a pH of 7.1 may be more appropriate. (See "Methanol and ethylene glycol
poisoning: Pharmacology, clinical manifestations, and diagnosis", section on 'Laboratory
evaluation'.)

Interpreting available clinical information (eg, nature and intent of exposure, pH,
osmolarity) to decide whether to initiate hemodialysis can be challenging when
confirmatory methanol and ethylene glycol concentrations are unavailable [24]. We
encourage clinicians facing this difficulty to consult with a poison control center, medical
toxicologist, or other physician experienced in the management of suspected toxic alcohol
exposure.

uptodate.yabesh.ir/contents/methanol-and-ethylene-glycol-poisoning-management?search=Methanol and ethylene glycol poisoning: Pharmacol… 6/16

22/2/22, 22:31 Methanol and ethylene glycol poisoning: Management - UpToDate

For non-acidemic patients, hemodialysis can be used to remove the parent alcohol and
abbreviate the course of antidotal therapy. There is less urgency to treat with hemodialysis
if ADH inhibition is adequate. Hemodialysis is often unnecessary in patients with
unmetabolized ethylene glycol provided that [4,25]:

● Fomepizole is given (prolonged ethanol therapy is impractical)

● The serum pH is normal or near normal (ie, little glycolate is present)
● The serum creatinine remains normal

Patients with ethylene glycol concentrations greater than 300 mg/dL (48 mmol/L) have
been successfully treated with fomepizole alone when therapy was initiated before the
appearance of acidosis. Treatment with hemodialysis is still recommended for large
methanol ingestions because serum methanol elimination becomes extremely slow when
ADH is inhibited [5,26,27].

The hemodialysis prescription should include a large surface area dialyzer (>1.5 m²), a
blood flow rate in excess of 300 mL/min, and a bicarbonate bath. Hemodialysis should
continue until the serum pH is normal and parent alcohol concentrations are less than
approximately 25 mg/dL or 5 mmol/L. The duration of hemodialysis in hours can be
estimated using the formula -V ln (5/A)/0.06 k, where V is total body water in liters, A is the
initial alcohol concentration in mmol/L, and k is 80 percent of the dialyzer urea clearance in
mL/min at the observed blood flow rate [28-30]. Such a calculation provides only an
estimate, and the patient's clinical condition will also affect the dosing of hemodialysis.
Serum alcohol concentrations and acid-base status should always be verified near the end
of hemodialysis and again two hours post-hemodialysis to ascertain the adequacy of
treatment [24]. (See "Acute hemodialysis prescription".)

More than one round of hemodialysis may be necessary in massive overdoses and for
ethylene glycol-poisoned patients with renal failure. Renal function often recovers over a
period of days to months in survivors of ethylene glycol poisoning.

Fomepizole is dialyzable, and the frequency of its dosing should be increased to every four
hours during hemodialysis. An additional dose should be given at the beginning of
hemodialysis if six or more hours have elapsed since the prior dose.

If ethanol is used for ADH inhibition, adjustments in the dose must be made during
hemodialysis. A fall in ethanol levels can be avoided or ameliorated by increasing the rate
of ethanol infusion and possibly by adding ethanol directly to the dialysate [31,32]. In one
such case, a dialysate ethanol concentration of 100 mg/dL was prepared by administering
a 95 percent ethanol solution into the dialysate inlet tubing at a rate of 40 mL/h via an
infusion pump. The dialysate flow rate was maintained at 500 mL/min, and the dialyzer

uptodate.yabesh.ir/contents/methanol-and-ethylene-glycol-poisoning-management?search=Methanol and ethylene glycol poisoning: Pharmacol… 7/16

22/2/22, 22:31 Methanol and ethylene glycol poisoning: Management - UpToDate

blood flow averaged 280 mL/min. An average plasma ethanol level of 90 mg/dL was
obtained during the six-hour hemodialysis session.

Peritoneal dialysis and other forms of continuous renal replacement therapy are inefficient
at clearing toxic alcohols and their metabolites and are not recommended [24].

Cofactor therapy — All methanol patients treated with ADH inhibition should also receive
cofactor therapy: either leucovorin 50 mg IV or foli
folic acid 50 mg IV every six hours [5,33,34].
It is not known whether supplemental thiamine (100 mg IV) or pyridoxine (50 mg IV)
benefits patients poisoned with ethylene glycol, but we routinely administer both,
particularly if the patient's nutritional status is suspect.

Preterminal care — Severely poisoned patients who present in coma and profound

acidemia may not survive despite maximum intensive therapy [2,35,36]. Consideration
should be given to organ harvesting prior to withdrawal of support for such patients,
especially after severe methanol poisoning. Formate is a highly specific neurotoxin, and
case series support the viability of organs harvested from such patients [37,38]. (See
"Evaluation of the potential deceased organ donor (adult)".)

MULTIVICTIM OUTBREAKS

Methanol poisoning outbreaks with multiple victims are rare but continue to occur around
the globe [2,36,39-42]. When the supply of "alcohol" (ie, ethanol) is contaminated,
especially with methanol, a cluster of victims with a wide range of severities can easily
overwhelm available critical care and hemodialysis resources. The timing of presentation
and geographic range of victims will depend on the nature, distribution, and consumption
of the contaminated product.

A 2019 consensus statement from an international panel of clinical toxicologists

recommends that as few as three cases within 72 hours appearing in the same city or town
should be considered a methanol poisoning outbreak, triggering active case-finding by
public health and government authorities [36]. Triage elements should include level of
consciousness, visual disturbances, and blood gas testing if possible, with antidotal and
extracorporeal treatment allocated according to the severity of illness. The combination of
coma at presentation with a pH <6.74 is strongly associated with death or severe
neurologic sequelae in almost all cases [35,36]. On the other hand, a pH >7.2 at the time of
initial treatment is rarely associated with subsequent visual deterioration [43].

Regarding antidotal therapy in such outbreaks, we concur with the consensus statement,
which recommends a "use what you have" approach [36]. When both are available, we
prefer fomepizole over ethanol. When there is insufficient fomepizole to treat all victims,

uptodate.yabesh.ir/contents/methanol-and-ethylene-glycol-poisoning-management?search=Methanol and ethylene glycol poisoning: Pharmacol… 8/16

22/2/22, 22:31 Methanol and ethylene glycol poisoning: Management - UpToDate

we suggest using fomepizole preferentially for the more seriously ill, pregnant women, and
children younger than 14 years. Prehospital distribution of ethanol to suspected victims
has been used successfully in Estonia [41].

The oral bioavailability of fomepizole is excellent, allowing an alternative route of

administration when obtaining intravenous (IV) access is delayed or impossible [44,45].
Moreover, the effective duration of alcohol dehydrogenase (ADH) inhibition after the initial
15 mg/kg loading dose likely lasts longer than 24 hours in the absence of hemodialysis
[44]. While the expert panel did not reach consensus on the difficult issue of allocating
scarce fomepizole during such disasters, and while individual circumstances will need to be
considered with great care, a longer dosing interval, partitioning the loading dose, and
avoiding doses during hemodialysis should allow more victims to be treated and additional
time to prioritize hemodialysis and to confirm the diagnosis.

While many factors will determine the optimal approach, experience suggests that
mobilizing and transferring resources to increase the critical care, antidotal, and
hemodialysis capacity in a health care facility stretched thin with multiple sick patients is
usually preferable to the interfacility transport of critically ill patients [36]. More stable
patients (ie, alert, lack of visual symptoms, higher pH) are more suitable candidates for
redistribution to other health care facilities during an outbreak. Consultation with
toxicologists with specific expertise in methanol poisoning will be particularly important in
guiding management decisions during these rare events. (See 'Additional resources'
below.)

PEDIATRIC CONSIDERATIONS

Younger children — A common clinical presentation involves the child who may have
swallowed one or two mouthfuls of a concentrated methanol or ethylene glycol solution.
These children should not be managed at home [46].

Most victims of unintentional exposure present for evaluation shortly after ingestion and
do not manifest significant metabolic acidosis or any evidence of end-organ dysfunction.
The ideal approach is to measure the serum concentration of the specific alcohol in order
to quantify the absorbed dose and predict the clinical course. Unfortunately, such
concentrations are rarely available within a few hours of the ingestion, creating a
diagnostic and therapeutic dilemma.

One approach to this problem (described below) can be used if all of the following criteria
are met:

● The ingestion was unintentional and of small volume

uptodate.yabesh.ir/contents/methanol-and-ethylene-glycol-poisoning-management?search=Methanol and ethylene glycol poisoning: Pharmacol… 9/16

22/2/22, 22:31 Methanol and ethylene glycol poisoning: Management - UpToDate

● The product is accurately identified

● The patient is asymptomatic
● The patient has a normal pH and normal anion gap
● There is no coingestion or treatment with ethanol or fomepizole

If all conditions are met, the clinician can observe the patient and monitor venous blood
gases and electrolytes every one to two hours to exclude the development of a metabolic
acidosis or an increasing anion gap. If acidosis does not develop within eight hours of the
ingestion, a toxic alcohol poisoning can be excluded. Alcohol dehydrogenase (ADH)
inhibition with fomepizole or ethanol should not be initiated during this observation
period as such treatment will prevent the development of acidosis even in patients with
massive ingestions. In other words, the coingestion of ethanol or treatment with either
fomepizole or ethanol invalidates the above protocol.

Parents should be counseled about safe storage of household products and

pharmaceuticals prior to discharge.

For those pediatric patients who do demonstrate signs of methanol or ethylene glycol
poisoning, the diagnostic and treatment considerations described above for adults largely
hold. The limited published experience with fomepizole supports its safe and effective use
in children using the same dosing protocol given above [47].

Occasionally, infants with inherited metabolic disorders such as methylmalonic acidemia

present with features that resemble ethylene glycol poisoning, and vice versa [48,49]. The
clinician should obtain organic acid testing in all infants presenting with unexplained
metabolic acidosis. (See "Organic acidemias: An overview and specific defects".)

Adolescents — Groups of adolescents trying to become inebriated may consume toxic

alcohols knowingly or accidentally in contaminated beverages. When treating an
adolescent for a possible toxic alcohol ingestion, clinicians should always consider the
possibility of other as-yet unidentified victims.

ADDITIONAL RESOURCES

Regional poison control centers in the United States are available at all times for
consultation on patients who are critically ill, require admission, or have clinical pictures
that are unclear (1-800-222-1222). In addition, some hospitals have clinical and/or medical
toxicologists available for bedside consultation and/or inpatient care. Whenever available,
these are invaluable resources to help in the diagnosis and management of ingestions or
overdoses. Contact information for poison centers around the world is available at the
website in the following reference [50].

uptodate.yabesh.ir/contents/methanol-and-ethylene-glycol-poisoning-management?search=Methanol and ethylene glycol poisoning: Pharmaco… 10/16

22/2/22, 22:31 Methanol and ethylene glycol poisoning: Management - UpToDate

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and

regions around the world are provided separately. (See "Society guideline links: General
measures for acute poisoning treatment" and "Society guideline links: Toxic alcohol
poisoning".)

SUMMARY AND RECOMMENDATIONS

● Methanol and ethylene glycol poisonings are potentially fatal. Rapid recognition and
early treatment are crucial. A summary table to facilitate emergency management
is provided ( table 1). (See 'Overview of emergency management' above.)

● First assess and secure the patient's airway, breathing, and circulation. If mechanical
ventilation is required, large minute ventilations may be needed to prevent profound
acidemia (pH <7.1) in patients with severe intoxication. (See 'Airway, breathing,
circulation' above.)

● Patients with methanol or ethylene glycol poisoning fare worse when systemic
acidemia is present. For patients with a serum pH below 7.3, we recommend
treatment with sodium bicarbonate (Grade 1C). Begin treatment with 1 to 2 meq/kg
of sodium bicarbonate via intravenous (IV) bolus infusion. (See 'Treatment with
sodium bicarbonate' above.)

● We recommend that alcohol dehydrogenase (ADH) inhibition therapy with fomepizole

be initiated in any patient for whom the clinician has strong suspicion of poisoning
with either methanol or ethylene glycol coupled with an elevated plasma osmolal
gap, or acidemia, or a measured methanol or ethylene glycol concentration over 20
mg/dL (SI equivalent: methanol 6.2 mmol/L; ethylene glycol 3.2 mmol/L) (Grade 1B).
Fomepizole is loaded at 15 mg/kg IV, followed by 10 mg/kg every 12 hours, with
adjustments for hemodialysis or after more than two days of therapy. If fomepizole is
unavailable, we recommend treatment with ethanol in these same circumstances
(Grade 1B). We provide cofactor therapy to all patients receiving ADH inhibition. (See
'Alcohol dehydrogenase inhibition' above and 'Cofactor therapy' above.)

● We recommend immediate hemodialysis be performed in the setting of a known

methanol or ethylene glycol ingestion when the following conditions are present
(Grade 1B):

• Metabolic acidosis, regardless of drug level

uptodate.yabesh.ir/contents/methanol-and-ethylene-glycol-poisoning-management?search=Methanol and ethylene glycol poisoning: Pharmaco… 11/16

22/2/22, 22:31 Methanol and ethylene glycol poisoning: Management - UpToDate

• Elevated serum levels of methanol or ethylene glycol (more than 50 mg/dL [SI
equivalent: methanol 15.6 mmol/L; ethylene glycol 8.1 mmol/L]) unless arterial pH
is above 7.3

• Evidence of end-organ damage (eg, visual changes, renal failure)

We recommend treatment with hemodialysis if the clinician suspects a toxic

alcohol ingestion in a patient with a severe, unexplained anion gap metabolic
acidosis and significant osmolal gap (Grade 1B). We generally refrain from using
hemodialysis to treat patients with elevated ethylene glycol concentrations,
provided their serum pH is near normal, their renal function is normal, and
fomepizole is given; this strategy is less helpful for methanol given its prolonged
elimination with ADH inhibition. (See 'Hemodialysis' above.)

● Consultation with a medical toxicologist at a regional poison center is strongly

recommended for all suspected exposures and for cases in which fomepizole,
ethanol, or hemodialysis therapy may be used. Consultation with nephrology and
emergency hemodialysis should be immediately obtained for severely acidotic
patients in whom the diagnosis appears likely, especially if accompanied by visual or
renal impairment. (See 'Additional resources' above.)

● A young child suspected of swallowing methanol or ethylene glycol should be

brought immediately for medical evaluation; if the child appears well, antidotal
treatment with fomepizole or ethanol should not be empirically given provided they
meet explicit criteria provided in the text. (See 'Pediatric considerations' above.)

● Activated charcoal, gastric lavage, and syrup of ipecac have no role in the
management of toxic alcohol exposures. (See 'Gastrointestinal decontamination'
above.)

ACKNOWLEDGMENT

The editorial staff at UpToDate would like to acknowledge James Winchester, MD, who
contributed to an earlier version of this topic review.

Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES
1. Wallace EA, Green AS. Methanol toxicity secondary to inhalant abuse in adult men.
Clin Toxicol (Phila) 2009; 47:239.
uptodate.yabesh.ir/contents/methanol-and-ethylene-glycol-poisoning-management?search=Methanol and ethylene glycol poisoning: Pharmaco… 12/16
22/2/22, 22:31 Methanol and ethylene glycol poisoning: Management - UpToDate

2. Paasma R, Hovda KE, Hassanian-Moghaddam H, et al. Risk factors related to poor

outcome after methanol poisoning and the relation between outcome and antidotes--
a multicenter study. Clin Toxicol (Phila) 2012; 50:823.

3. McMartin K, Jacobsen D, Hovda KE. Antidotes for poisoning by alcohols that form toxic
metabolites. Br J Clin Pharmacol 2016; 81:505.

4. Barceloux DG, Krenzelok EP, Olson K, Watson W. American Academy of Clinical

Toxicology Practice Guidelines on the Treatment of Ethylene Glycol Poisoning. Ad Hoc
Committee. J Toxicol Clin Toxicol 1999; 37:537.

5. Barceloux DG, Bond GR, Krenzelok EP, et al. American Academy of Clinical Toxicology
practice guidelines on the treatment of methanol poisoning. J Toxicol Clin Toxicol
2002; 40:415.

6. Kostic MA, Dart RC. Rethinking the toxic methanol level. J Toxicol Clin Toxicol 2003;
41:793.

7. Porter WH, Rutter PW, Bush BA, et al. Ethylene glycol toxicity: the role of serum
glycolic acid in hemodialysis. J Toxicol Clin Toxicol 2001; 39:607.

8. De Leacy EA, Moxon LN, Ellis VM, et al. A report of accidental ethylene glycol ingestion
in 2 siblings. Pathology 1995; 27:273.

9. Baud FJ, Galliot M, Astier A, et al. Treatment of ethylene glycol poisoning with
intravenous 4-methylpyrazole. N Engl J Med 1988; 319:97.

10. Brent J, McMartin K, Phillips S, et al. Fomepizole for the treatment of ethylene glycol
poisoning. Methylpyrazole for Toxic Alcohols Study Group. N Engl J Med 1999;
340:832.

11. Brent J, McMartin K, Phillips S, et al. Fomepizole for the treatment of methanol
poisoning. N Engl J Med 2001; 344:424.

12. Shannon M. Toxicology reviews: fomepizole--a new antidote. Pediatr Emerg Care
1998; 14:170.

13. Battistella M. Fomepizole as an antidote for ethylene glycol poisoning. Ann

Pharmacother 2002; 36:1085.

14. Sivilotti ML. Ethanol: tastes great! Fomepizole: less filling! Ann Emerg Med 2009;
53:451.

uptodate.yabesh.ir/contents/methanol-and-ethylene-glycol-poisoning-management?search=Methanol and ethylene glycol poisoning: Pharmaco… 13/16

22/2/22, 22:31 Methanol and ethylene glycol poisoning: Management - UpToDate

15. Dart RC, Borron SW, Caravati EM, et al. Expert consensus guidelines for stocking of
antidotes in hospitals that provide emergency care. Ann Emerg Med 2009; 54:386.

16. Lepik KJ, Levy AR, Sobolev BG, et al. Adverse drug events associated with the
antidotes for methanol and ethylene glycol poisoning: a comparison of ethanol and
fomepizole. Ann Emerg Med 2009; 53:439.

17. Rasamison R, Besson H, Berleur MP, et al. Analysis of fomepizole safety based on a
16-year post-marketing experience in France. Clin Toxicol (Phila) 2020; 58:742.

18. Sivilotti ML, Burns MJ, McMartin KE, Brent J. Toxicokinetics of ethylene glycol during
fomepizole therapy: implications for management. For the Methylpyrazole for Toxic
Alcohols Study Group. Ann Emerg Med 2000; 36:114.

19. Boyer EW, Mejia M, Woolf A, Shannon M. Severe ethylene glycol ingestion treated
without hemodialysis. Pediatrics 2001; 107:172.

20. Paasma R, Hovda KE, Tikkerberi A, Jacobsen D. Methanol mass poisoning in Estonia:
outbreak in 154 patients. Clin Toxicol (Phila) 2007; 45:152.

21. Zakharov S, Pelclova D, Navratil T, et al. Fomepizole versus ethanol in the treatment of
acute methanol poisoning: Comparison of clinical effectiveness in a mass poisoning
outbreak. Clin Toxicol (Phila) 2015; 53:797.

22. Ghannoum M, Lavergne V, Gosselin S, et al. Practice Trends in the Use of

Extracorporeal Treatments for Poisoning in Four Countries. Semin Dial 2016; 29:71.

23. Naraqi S, Dethlefs RF, Slobodniuk RA, Sairere JS. An outbreak of acute methyl alcohol
intoxication. Aust N Z J Med 1979; 9:65.

24. Roberts DM, Yates C, Megarbane B, et al. Recommendations for the role of
extracorporeal treatments in the management of acute methanol poisoning: a
systematic review and consensus statement. Crit Care Med 2015; 43:461.

25. Levine M, Curry SC, Ruha AM, et al. Ethylene glycol elimination kinetics and outcomes
in patients managed without hemodialysis. Ann Emerg Med 2012; 59:527.

26. Burns MJ, Graudins A, Aaron CK, et al. Treatment of methanol poisoning with
intravenous 4-methylpyrazole. Ann Emerg Med 1997; 30:829.

27. Bekka R, Borron SW, Astier A, et al. Treatment of methanol and isopropanol poisoning
with intravenous fomepizole. J Toxicol Clin Toxicol 2001; 39:59.

28. Youssef GM, Hirsch DJ. Validation of a method to predict required dialysis time for
cases of methanol and ethylene glycol poisoning. Am J Kidney Dis 2005; 46:509.
uptodate.yabesh.ir/contents/methanol-and-ethylene-glycol-poisoning-management?search=Methanol and ethylene glycol poisoning: Pharmaco… 14/16
22/2/22, 22:31 Methanol and ethylene glycol poisoning: Management - UpToDate

29. McMurray M, Carty D, Toffelmire EB. Predicting methanol clearance during

hemodialysis when direct measurement is not available. CANNT J 2002; 12:29.

30. Burns AB, Bailie GR, Eisele G, et al. Use of pharmacokinetics to determine the duration
of dialysis in management of methanol poisoning. Am J Emerg Med 1998; 16:538.

31. Chow MT, Di Silvestro VA, Yung CY, et al. Treatment of acute methanol intoxication
with hemodialysis using an ethanol-enriched, bicarbonate-based dialysate. Am J
Kidney Dis 1997; 30:568.

32. Dorval M, Pichette V, Cardinal J, et al. The use of an ethanol- and phosphate-enriched
dialysate to maintain stable serum ethanol levels during haemodialysis for methanol
intoxication. Nephrol Dial Transplant 1999; 14:1774.

33. Ghosh A, Boyd R. Leucovorin (calcium foli

folinate) in "antifreeze" poisoning. Emerg Med J
2003; 20:466.

34. McMartin KE, Martin-Amat G, Makar AB, Tephly TR. Methanol poisoning. V. Role of
formate metabolism in the monkey. J Pharmacol Exp Ther 1977; 201:564.

35. Coulter CV, Farquhar SE, McSherry CM, et al. Methanol and ethylene glycol acute
poisonings - predictors of mortality. Clin Toxicol (Phila) 2011; 49:900.

36. Hassanian-Moghaddam H, Zamani N, Roberts DM, et al. Consensus statements on

the approach to patients in a methanol poisoning outbreak. Clin Toxicol (Phila) 2019;
57:1129.

37. Hantson P, Vanormelingen P, Lecomte C, et al. Fatal methanol poisoning and organ
donation: experience with seven cases in a single center. Transplant Proc 2000;
32:491.

38. López-Navidad A, Caballero F, González-Segura C, et al. Short- and long-term success

of organs transplanted from acute methanol poisoned donors. Clin Transplant 2002;
16:151.

39. Rostrup M, Edwards JK, Abukalish M, et al. Correction: The Methanol Poisoning
Outbreaks in Libya 2013 and Kenya 2014. PLoS One 2016; 11:e0157256.

40. Hassanian-Moghaddam H, Nikfarjam A, Mirafzal A, et al. Methanol mass poisoning in

Iran: role of case finding in outbreak management. J Public Health (Oxf) 2015; 37:354.

41. Zakharov S, Pelclova D, Urban P, et al. Use of Out-of-Hospital Ethanol Administration

to Improve Outcome in Mass Methanol Outbreaks. Ann Emerg Med 2016; 68:52.

uptodate.yabesh.ir/contents/methanol-and-ethylene-glycol-poisoning-management?search=Methanol and ethylene glycol poisoning: Pharmaco… 15/16

22/2/22, 22:31 Methanol and ethylene glycol poisoning: Management - UpToDate

42. Zakharov S, Rulisek J, Hlusicka J, et al. The impact of co-morbidities on a 6-year

survival after methanol mass poisoning outbreak: possible role of metabolic
formaldehyde. Clin Toxicol (Phila) 2020; 58:241.

43. Desai T, Sudhalkar A, Vyas U, Khamar B. Methanol poisoning: predictors of visual

outcomes. JAMA Ophthalmol 2013; 131:358.

44. Marraffa J, Forrest A, Grant W, et al. Oral administration of fomepizole produces

similar blood levels as identical intravenous dose. Clin Toxicol (Phila) 2008; 46:181.

45. Mégarbane B, Houzé P, Baud FJ. Oral fomepizole administration to treat ethylene
glycol and methanol poisonings: advantages and limitations. Clin Toxicol (Phila) 2008;
46:1097; author reply 1097.

46. Caravati EM, Erdman AR, Christianson G, et al. Ethylene glycol exposure: an evidence-
based consensus guideline for out-of-hospital management. Clin Toxicol (Phila) 2005;
43:327.

47. Brent J. Fomepizole for the treatment of pediatric ethylene and diethylene glycol,
butoxyethanol, and methanol poisonings. Clin Toxicol (Phila) 2010; 48:401.

48. Woolf AD, Wynshaw-Boris A, Rinaldo P, Levy HL. Intentional infantile ethylene glycol
poisoning presenting as an inherited metabolic disorder. J Pediatr 1992; 120:421.

49. Shoemaker JD, Lynch RE, Hoffmann JW, Sly WS. Misidentification of propionic acid as
ethylene glycol in a patient with methylmalonic acidemia. J Pediatr 1992; 120:417.

50. https://www.liquidglassnanotech.com/poison-emergency-center-contact-numbers/ (A
ccessed on December 09, 2020).

Topic 126052 Version 5.0

uptodate.yabesh.ir/contents/methanol-and-ethylene-glycol-poisoning-management?search=Methanol and ethylene glycol poisoning: Pharmaco… 16/16