Pathophysiology

Ethanol

Ethyl alcohol (ethanol; CH3 -CH2 -OH) is a low molecular weight hydrocarbon that is derived

from the fermentation of sugars and cereals. It is widely available both as a beverage and as

an ingredient in food extracts, cough and cold medications, and mouthwashes.

Ethanol is rapidly absorbed across both the gastric mucosa and the small intestines, reaching

a peak concentration 20-60 minutes after ingestion. Once absorbed, it is converted to

acetaldehyde. This conversion involves three discrete enzymes: the microsomal cytochrome

P450 isoenzyme CYP2E1, the cytosol-based enzyme alcohol dehydrogenase (ADH), and the

peroxisome catalase system. Acetaldehyde is then converted to acetate, which is converted to

acetyl Co A, and ultimately carbon dioxide and water.[2]

Genetic polymorphisms coding for alcohol dehydrogenase, the amount of alcohol consumed,

and the rate at which ethanol is consumed all affect the speed of metabolism. Chronic

alcoholics and those with severe liver disease have increased rates of metabolism. However,

as a general rule, ethanol is metabolized at a rate of 20-25 mg/dL in the nonalcoholic but at

an increased rate in chronic alcoholics.

Isopropanol

Isopropyl alcohol (isopropanol; CH3 -CHOH-CH3) is a low molecular weight hydrocarbon. It

is commonly found as both a solvent as well as a disinfectant.[3] It can be found in many

mouthwashes, skin lotions, rubbing alcohol, and hand sanitizers. Because of its widespread

availability, lack of purchasing restrictions, and profound intoxicating properties, it is

commonly used as an ethanol substitute.

Isopropanol is rapidly absorbed across the gastric mucosa and reaches a peak concentration

approximately 30-120 minutes after ingestion. Isopropanol is primarily metabolized via

alcohol dehydrogenase to acetone. A small portion of isopropanol is excreted unchanged in

the urine. The peak concentration of acetone is not present until approximately 4 hours after

ingestion. The acetone produces CNS depressant effects and a fruity odor on the breath.[4]

Methanol

Methyl alcohol (methanol; CH3 OH) is widely used as an industrial and marine solvent and

paint remover. It is also used in photocopying fluid, shellacs, and windshield-washing fluids.

Although toxicity primarily occurs from ingestion, it can also occur from prolonged

inhalation or skin absorption.[5, 6, 7] Methanol is rapidly absorbed from the gastric mucosa, and

achieves a maximal concentration 30-90 minutes after ingestion.[8]

Methanol is primarily metabolized in the liver via alcohol dehydrogenase into formaldehyde.

Formaldehyde is subsequently metabolized via aldehyde dehydrogenase into formic acid,

which ultimately is metabolized to folic acid, folinic acid, carbon dioxide, and water. A small

portion is excreted unchanged by the lungs.

Formic acid is responsible for the majority of the toxicity associated with methanol. Without

competition for alcohol dehydrogenase, methanol undergoes zero-order metabolism, and is

thus is excreted at a rate of 8.5 mg/dL/h to 20 mg/dL/h. Once methanol experiences

competitive inhibition, from either ethanol or fomepizole, the metabolism changes to first

order. In this later scenario, the excretion half-life ranges from 22-87 hours.

Ethylene glycol

Ethylene glycol (CH2 OH-CH2 OH) is an odorless, colorless, sweet-tasting liquid, which is

used in many manufacturing processes. Domestically, it is probably most commonly

encountered in antifreeze. It is absorbed somewhat rapidly from the gastrointestinal tract, and

peak concentrations are observed 1-4 hours after ingestion.[7]

Ethylene glycol itself is nontoxic, but it is metabolized into toxic compounds. Ethylene glycol

is oxidized via alcohol dehydrogenase into glycoaldehyde, which then undergoes metabolism

via aldehyde dehydrogenase into glycolic acid.[9] The conversion to glycolic acid is somewhat

rapid. In contrast, the conversion of glycolic acid to glyoxylic acid is slower and is the rate-

limiting step in the metabolism of ethylene glycol.

Glyoxylic acid is subsequently metabolized into several different products, including oxalic

acid (oxalate), glycine, and alpha-hydroxy-beta-ketoadipate. The conversion to glycine

requires pyridoxine as a cofactor, while the conversion to alpha-hydroxy-beta-ketoadipate

requires thiamine as a cofactor. The oxalic acid combines with calcium to form calcium

oxalate crystals.

In the presence of normal renal function and no competitive inhibition for alcohol

dehydrogenase, the excretion half-life of ethylene glycol is approximately 3 hours. However,

in the presence of fomepizole or ethanol, alcohol dehydrogenase undergoes competitive

inhibition, and the resulting excretion half-life increases to approximately 17-20 hours.

Epidemiology

Frequency

Alcohol intoxication is common in modern society, largely because of its widespread

availability. More than 8 million Americans are believed to be dependent on alcohol, and up

to 15% of the population is considered at risk. In some studies, more than half of all trauma

patients are intoxicated with ethanol at the time of arrival to the trauma center. In addition,

ethanol is a common coingestant in suicide attempts.

Mortality/Morbidity

Acute intoxication with any of the alcohols can result in respiratory depression, aspiration,

hypotension, and cardiovascular collapse.

Ethanol

Although many patients present with ethanol intoxication as their sole issue, many other

patients have ethanol intoxication as part of a larger picture. Thus, the morbidity is often from

coingestants or coexisting injuries and illnesses.

Chronic use results in hepatic and gastrointestinal injuries. Coma, stupor, respiratory

depression, hypothermia, and death can result from high concentrations of acute ethanol

intoxication. Chronic alcoholics, as well as children, are at risk for hypoglycemia.

Isopropanol, methanol, and ethylene glycol

In 2012, 16,458 cases of isopropanol ingestions, 8773 cases of isopropanol toxicity (from

sources including rubbing alcohol, cleaning agents, and hand sanitizers) were reported to US

Poison Control Centers. Of these, 65 patients were classified as experiencing "major"

morbidity, with one patient dying.[10]

In the same year, 1,612 cases of methanol ingestion and 5,869 cases of ethylene glycol

ingestion were reported. Of those intoxicated with methanol, 26 patients were classified as

experiencing "major" disability, and 6 additional patients died. For those patients who were

intoxicated with ethylene glycol, 205 patients were classified as having "major" disability,

with an additional 23 patients dying.[10] It is important to recognize that these numbers likely

underestimate the true incidence of exposure, however, because of both a failure to recognize

the ingestion as well as a failure to report the suspected or known ingestion to a poison

control center.

The primary toxicity with isopropanol is CNS depression. These CNS manifestations can

include lethargy, ataxia, and coma. In addition, isopropanol is irritating to the GI tract.

Therefore, abdominal pain, hemorrhagic gastritis, and vomiting can be observed. Unlike

methanol and ethylene glycol, isopropanol does not cause a metabolic acidosis.

The toxicity with methanol occurs from both the ensuing metabolic acidosis, as well as the

formate anion (formic acid) itself.[11] Although the eye is the primary site of organ toxicity, in

the later stages of severe methanol toxicity, specific changes can occur in the basal ganglia as

well. Pancreatitis has been reported following methanol ingestion. Hyperventilation will

occur as a compensatory mechanism to counteract the acidosis.

As previously stated, ethylene glycol itself is nontoxic. The majority of the metabolic

acidosis occurs from glycolic acid. One form of morbidity occurs when oxalate combines

with calcium to form calcium oxalate crystals, which accumulate in the proximal renal

tubules, thereby inducing renal failure. Hypocalcemia can ensue, and cause coma, seizures,

and dysrhythmias. Autopsy studies have confirmed that the calcium oxalate crystals are

deposited not only in the kidneys but in many other organs, including the brain, heart, and

lungs.

Age

Ethanol intoxication is common in older teenagers through adulthood. The toxic dose for an

adult is 5 mg/dL, whereas the toxic dose in a child is 3 mg/dL. Children are at higher risks of

developing hypoglycemia following a single ingestion than are adults.

Most isopropanol ingestions occur in children younger than 6 years. Most methanol and

ethylene glycol ingestions occur in adults older than 19 years.

History

A history of inebriation with associated slurred speech, ataxia, and impaired judgment is

common in the initial stages of intoxication of each of these alcohols. Depending on the dose

ingested, this may be followed by progressive levels of CNS depression, coma, and

premorbid multiorgan failure. The history that can be obtained varies with the timing of

presentation. The onset of the later stages of toxic alcohol intoxication can also be delayed if

ethanol is coingested, prolonging the time it takes to develop metabolic acidosis and other

symptoms. The following focuses on symptoms that may be unique to each alcohol.

Ethanol ingestion

The history itself can often point to a diagnosis of ethanol intoxication. An associated history

of chronic alcoholism alters metabolism, associated comorbidities, and the expected course of

recovery. A detailed discussion of this topic is beyond the scope of this article (see Ethanol

Toxicity).

Attempting to elicit what has changed recently may reveal the immediate reason for

presentation. A history of coingestants may also alter the patient's course.

Isopropanol ingestion

Following an isopropanol ingestion, the patient may not complain of anything specific.

Rather, the patient may simply appear intoxicated, as with ethanol intoxication.

A history of abdominal pain, nausea, and sometimes hematemesis may be obtained.

Methanol ingestion

Following methanol ingestion, a patient is initially inebriated as with the other alcohols.

Other symptoms can be delayed for up to 12-24 hours.

The patient may complain of headache, nausea, or anorexia. Occasionally, the patient may

complain of shortness of breath related to hyperventilation.

Because one of the primary end-organs involved in methanol is the eye, the patient may

complain of difficulty seeing. Specifically, vision is often described as a "snow field," though

a variety of visual complaints may be verbalized.

Ethylene glycol ingestion

Ethylene glycol toxicity occurs in three stages, as follows:

The first stage, called the neurologic phase, can occur in less than 1 hour after ingestion and lasts up to 12 hours. During this stage, the patient appears inebriated. The patient may not

have any other significant findings during this stage. Occasionally, hypocalcemia can occur at this point and induce muscle spasms and abnormal reflexes.

The second stage, which occurs between 12 and 24 hours after ingestion, is referred to as the cardiopulmonary stage. During this stage, the patient frequently develops mild tachycardia and hypertension. Acute respiratory distress syndrome (ARDS) can also occur. These findings are believed to result from calcium oxalate crystal deposition in the lung parenchyma and myocardium. Significant hypocalcemia can occur at this stage, with QT prolongation and associated arrhythmias. Expect hyperventilation as metabolic acidosis progresses.

The third stage, also called the renal stage, typically starts after 24 hours. During this stage, flank pain and acute renal failure can occur. A premorbid patient with ethylene glycol toxicity typically presents comatose, hyperventilating, and in multiorgan failure.

Physical

Ethanol ingestion o The symptoms of ethanol intoxication depend on both the serum concentration as

well as the frequency at which an individual ingests ethanol. Thus, a person who consumes large amounts of ethanol on a daily basis may appear sober at the same serum ethanol level at which a novice drinker exhibits cerebellar dysfunction.

o As a general rule, levels less than 25 mg/dL are associated with a sense of warmth and well-being. Euphoria and decreased judgment occur at levels between 25-50 mg/dL. Incoordination, decreased reaction time/reflexes, and ataxia occur at levels of 50-100 mg/dL. Cerebellar dysfunction (ie, ataxia, slurred speech, nystagmus) are common at levels of 100-250 mg/dL. Coma can occur at levels of greater than 250 mg/dL, whereas respiratory depression, loss of protective reflexes, and death occur at levels greater than 400 mg/dL.

Isopropanol ingestion o As previously stated, the patient who consumes isopropanol may appear inebriated,

as with ethanol. Isopropanol concentrations of 50-100 mg/dL typically result in intoxication, which can progress to include symptoms such as dysarthria and ataxia, while lethargy or coma can be seen with levels exceeding 150 mg/dL. Cardiovascular depression can occur with levels exceeding 450 mg/dL.

o The presence of acetone may induce a fruity odor on the patient's breath. Methanol ingestion

o Unlike ethanol or isopropanol, methanol does not cause nearly as much of an inebriated state. If a patient has coingested ethanol, signs or symptoms specific to methanol intoxication are delayed.

o The patient may be hyperventilating. o If vision is impaired, ocular examination may reveal dilated pupils that are minimally

or unreactive to light with hyperemia of the optic disc. Over several days, the red disc becomes pale, and the patient may become blind. Typically, subjective complaints precede physical findings in the eye.

Ethylene glycol ingestion o The physical findings depend on the stage of the presentation. Thus, the patient may

present simply inebriated or progressively more acidotic as renal failure, cardiovascular dysfunction, and coma develop.

o Examination findings correlate with the symptoms, as previously described. o In patients who survive severe intoxication, calcium oxalate crystal deposition may

occur in the brain parenchyma and can induce cranial neuropathies. These findings

typically occur as the patient is recovering from the initial intoxication. The cranial nerves most commonly involved include cranial nerve II, V, VII, VIII, IX, X, and XII.

Differential Diagnoses

Alcoholic Ketoacidosis

Depression and Suicide

Diabetic Ketoacidosis

Encephalitis

Hyperosmolar Hyperglycemic Nonketotic Coma

Hypoglycemia

Meningitis

Metabolic Acidosis

Pancreatitis

Stroke, Hemorrhagic

Subarachnoid Hemorrhage

Toxicity, Barbiturate

Toxicity, Benzodiazepine

Toxicity, Ethylene Glycol

Toxicity, Gamma-Hydroxybutyrate

Toxicity, Heroin

Toxicity, Isoniazid

Toxicity, Lithium

Toxicity, Narcotics

Toxicity, Sedative-Hypnotics

Toxicity, Valproate

Laboratory Studies

Following consumption of any type of alcohol, the extent of the workup depends partly on

the history. However, because the patient's sensorium is likely to be altered and a history

unobtainable or inaccurate, a thorough physical examination is important to evaluate for

occult injuries; laboratory clues can also become invaluable.

If the possibility of a suicide attempt is raised, an electrocardiogram and basic toxicology

screen, including measurement of salicylate and acetaminophen concentrations, become

important.

In addition, if ingestion of a toxic alcohol is suspected, a serum ethanol level and basic

electrolytes, including a serum bicarbonate level are vital, as the latter are needed to calculate

an anion gap. In such a situation, specific serum toxic alcohol levels immensely help guide

management. If these are unavailable, calculation of an osmolar gap can sometimes be

helpful, though its exclusive use is fraught with pitfalls.[12] These issues are best discussed

with the local poison control center. Arterial blood gases and other tests that measure

associated organ dysfunction also become important in cases of poisoning with toxic

alcohols.

An important point is that laboratory abnormalities vary dramatically over the course of the

patient's presentation and any laboratory abnormalities must be interpreted with the time

frame of the patient's presentation in mind. Failing to do so is a common and important

pitfall. Thus, early in the course of intoxication with a toxic alcohol, a patient will have

neither an anion gap nor an osmolar gap though their serum toxic alcohol level will be

highest shortly after ingestion. However, as metabolism of the toxic alcohol occurs, the anion

and osmolar gaps develop as metabolites are formed and the toxic alcohol level drops.[13]

Other laboratory abnormalities also develop as end-organ damage occurs. Coingestion of

alcohol delays all the laboratory value changes as well as the signs and symptoms of toxic

alcohol-induced injury.

Ethanol

The single most important laboratory test in a patient who appears intoxicated with ethanol is

a serum glucose level. Hypoxia, head injury, seizures, and other metabolic disturbances must

be excluded by either history or physical examination or sought with the appropriate tests.

The routine use of a serum blood alcohol level is controversial, largely because it is unlikely

to affect management in a patient who is awake and alert. Many clinicians consider the

patient safe for discharge once they are clinically (not numerically) no longer intoxicated.

In patients who are chronic alcoholics, anemia, thrombocytopenia, elevation of hepatic

transaminase levels, and a prolongation of the prothrombin time can be observed. These need

not be routinely checked in a patient who presents simply for alcohol intoxication but may be

useful if changes from baseline are suspected.

Isopropanol

Serum levels of isopropanol can be obtained but are somewhat of limited value, as the

treatment is largely supportive. However, they can be useful in confirming the diagnosis.

After correcting for all other variables, including ethanol, the serum isopropanol level can be

estimated by multiplying the remaining osmolar gap by 6.0. Serum ketones will often be

positive, although the patient should not be acidotic. Because ketones will be present in the

serum as early as 30 minutes after ingestion, if there is no coexisting ethanol ingestion, the

absence of ketones effectively rules out isopropanol ingestion.

Depending on the assay used in the laboratory, significant ketosis can cause interference with

the creatinine assay. As such, the serum creatinine level can be falsely elevated.

Methanol

Serum methanol levels should be obtained when this diagnosis is suspected. As previously

stated, both the osmolar and anion gap should be obtained. After correcting for all other

variables, including ethanol, the serum methanol level can be estimated by multiplying the

remaining osmolar gap by 3.2.

Ethylene glycol

A serum ethylene glycol level should be obtained when this diagnosis is suspected. The

osmolar gap and anion gap should also be obtained. After correcting for other variables,

including ethanol, the serum ethylene glycol level can be estimated by multiplying the

remaining osmolar gap by 6.2.

A baseline creatinine and BUN level should be obtained in all cases of ethylene glycol

intoxication. These values can then be followed to check for the development of renal failure.

In addition, the urine can be examined for evidence of fluorescence. In antifreeze, fluorescein

is added to the liquid to permit mechanics to identify the source of a fluid leaking from a car.

However, fluorescein is excreted in the urine faster than ethylene glycol. Thus, fluorescence

can be eliminated before the patient even arrives in the emergency department. As such, the

presence of fluorescence of urine under a Wood's lamp is not a sensitive test. In addition,

because certain containers themselves fluoresce, the presence of fluorescence is neither

sensitive nor specific. Despite this, a positive test that differentiates urine fluorescence from

that of its container may be a quick bedside clue pointing toward ethylene glycol intoxication.

Both a serum calcium level and an electrocardiogram should be obtained, since hypocalcemia

may occur as calcium combines with oxalate in the form of calcium oxalate crystals.

Osmolar Gap

Measuring the osmolar gap is important when toxic alcohols ingestion is suspected. The

osmolar gap is determined by subtracting the calculated osmolality from the measured

osmolality. The serum osmolality should be determined by freezing point depression rather

than by heat of vaporization.

The serum osmolality can be calculated by the following formula:

Osm = (2) (Na+) + BUN/2.8 + Glucose/18 + EtOH/4.6 + Isopropanol/6.0 + MeOH/3.2 +

Ethylene glycol/6.2

In the above formula, if, for example, an ingestion of methanol is suspected, the osmolality

should be calculated using the sodium, BUN, and glucose. The ethanol level is also measured

and then factored into the equation. If isopropanol and ethylene glycol are not suspected, they

can be eliminated from the equation. Then, once the osmolar gap is determined, multiply the

osmolar gap by 3.2 to determine the estimated methanol level.

It is important to recognize that neither the presence nor absence of an osmolar gap can be

used to confirm or exclude a toxic alcohol ingestion. With both methanol and ethylene glycol,

the alcohols are metabolized from an alcohol to an aldehyde, and ultimately to an acid. As

such, shortly after an ingestion, the patient may have an osmolar gap without an anion gap.

Similarly, in the later stages of an ingestion, a patient may have an anion gap without an

osmolar gap.

Prehospital Care

The prehospital care provider has several important interventions available. First, the

prehospital provider should search for any empty containers near the patient. In addition, a

blood sugar level should be obtained on anyone who appears intoxicated. Local protocols and

the skill level of the provider dictate additional prehospital care for patients with altered

mental status.

Emergency Department Care

As with all emergency patients, initial treatment should focus on the airway, breathing, and

circulation. Gastric decontamination is rarely necessary for any of the alcohols. An exception

to this may be a patient who presents immediately after ingestion of a toxic alcohol in whom

one might reasonably expect to be able to recover a significant amount of the toxin via

aspiration through a nasogastric tube.

Treatment of ethanol and isopropanol intoxication is largely supportive.[14] Because of

the hemorrhagic gastritis that can follow isopropanol ingestion, H2 blockade or

proton-pump inhibitors may be helpful. Hemodialysis, while effective, is rarely

indicated, and should only be used in the setting of profound hemodynamic

compromise.[4]

Once either methanol or ethylene glycol intoxication are suspected, treatment should

be initiated without delay. Fortunately, since both alcohols are metabolized by alcohol

dehydrogenase, the treatment is the same, and differentiating which of the two toxic

alcohols is responsible is not necessary before implementing treatment.[14]

o The primary antidotal treatment of methanol or ethylene glycol involves

blocking alcohol dehydrogenase. This enzyme can be inhibited by either

ethanol or fomepizole.[15, 16, 17] Toxic alcohol levels are frequently not

immediately available. Thus, ideally, if methanol or ethylene glycol poisoning

is suspected, the patient should receive a loading dose of fomepizole while the

levels are being obtained. Because the next dose of fomepizole is not due for

an additional 12 hours, this strategy allows 12 hours for the blood to be

processed at a reference laboratory before additional treatment is needed.

Inhibition of alcohol dehydrogenase with ethanol may be substituted for

treatment with fomepizole (see below), though recent studies have highlighted

the greater safety of fomepizole as a treatment, when available.[11, 9] In some

patients, treatment with fomepizole alone may represent definitive treatment

and can prevent the need for hemodialysis.[18]

o In addition to blocking alcohol dehydrogenase, significant metabolic acidosis

should be treated with sodium bicarbonate infusions. If methanol is suspected,

folinic acid should be administered at a dose of 1 mg/kg, with a maximal dose

of 50 mg. It should be repeated every 4 hours. If folinic acid is not

immediately available, folic acid can be substituted at the same dose. If

ethylene glycol overdose is suspected, the patient should also receive 100 mg

of intravenous thiamine every 6 hours and 50 mg of pyridoxine every 6 hours.

The purpose of the thiamine and pyridoxine is to shunt metabolism of

glyoxylic acid away from oxalate and favor the formation of less toxic

metabolites.

o In methanol overdose, sodium bicarbonate should be administered liberally,

with the goal being to completely reverse the acidosis. Based on experimental

studies, formate appears to be excreted in the kidneys at a much higher rate

when the patient is not acidotic. In addition, when the patient is not acidotic,

formic acid dissociates to formate at lower rates so that less formate crosses

the blood-brain barrier. Thus, in methanol intoxication, correcting the acidosis

actually speeds up elimination of the toxic compound and decreases toxicity.

o If ethanol is used, the recommended target serum concentration is 100-150

mg/dL. Because ethanol inhibits gluconeogenesis, hypoglycemia is common

in patients on an ethanol infusion.[19] Hypoglycemia is particularly prevalent in

pediatric patients on such drips. Thus, serum glucose levels must be checked

frequently, at least every 2 hours. In addition, because it is difficult to attain a

steady serum concentration of ethanol, the ethanol level also must be checked

frequently, and titrations made.

A 5% or 10% ethanol solution can be made in the pharmacy. If giving

ethanol, a loading dose of 600 mg/kg should be given, followed by a

drip of 66-154 mg/kg/h with chronic alcoholics requiring doses at the

higher end of the scale. Ethanol can be given either intravenously or

orally.

In addition to hypoglycemia, additional adverse effects from ethanol

infusion include inebriation, CNS depression, pancreatitis, and local

phlebitis. Because of the phlebitis that occurs with ethanol infusions,

some advocate that ethanol should only be administered via a central

venous line.

Ethanol infusions are not only labor intensive, but once the costs of the frequent blood

glucose and serum ethanol levels are accounted for, ethanol antidotal therapy is

frequently more expensive than fomepizole. Thus, because of the lower overall cost

and the ease of administration and safety considerations, fomepizole has become the

preferred antidote for methanol or ethylene glycol poisoning.[20]

Fomepizole should be administered as a loading dose of 15 mg/kg. Subsequent doses

should be at 10 mg/kg every 12 hours for 4 doses. Because fomepizole actually

induces its own metabolism after 48 hours of treatment, if additional doses are

needed, the dose should be increased to 15 mg/kg. Fomepizole needs to be re-dosed

during hemodialysis. The package insert or local poison center can help with the re-

dosing strategy. Fomepizole should be continued until the serum ethylene glycol or

methanol concentrations are less than 20 mg/dL.

Hemodialysis is frequently required in patients with significant methanol or ethylene

glycol ingestions.[14, 18] Indications for hemodialysis include (1) arterial pH < 7.10, (2)

a decline of >0.05 in the arterial pH despite bicarbonate infusion, (3) pH < 7.3 despite

bicarbonate therapy, (4) rise in serum creatinine level by 90 mmol/L, and (5) initial

plasma methanol or ethylene glycol concentration 50 mg/dL.

Consultations

For patients with ethanol intoxication who appear to have issues with dependence or

abuse, one can consider referral to an alcohol detoxification facility. Consult a

toxicologist for all known or suspected cases of isopropanol, methanol, or ethylene

glycol ingestion. If a toxicologist is not immediately available at the medical center

where the patient is located, the regional poison control center can be contacted at

(800) 222-1222.

Consult a nephrologist for any known or suspected cases of methanol or ethylene

glycol intoxication to assist in the decision making for hemodialysis.

Medication Summary

Fomepizole (eg, 4-methylpyrizole, 4-MP, Antizol) has greater affinity for alcohol

dehydrogenase than ethanol or methanol and has a considerably better safety profile than

ethanol. Fomepizole has been approved by the US Food and Drug Administration (FDA) for

ethylene glycol poisoning, but it is also useful for managing methanol poisoning.

Pharmacologic antidotes

Class Summary

These agents prevent formation of toxic metabolites in methanol ingestions (not useful with

isopropanol or ethanol ingestions). Therapy generally is maintained until methanol levels are

less than 20 mg/dL.

View full drug information

Fomepizole (4-MP, Antizol)

DOC for ethylene glycol and methanol poisoning because of ease of administration and better

safety profile than ethanol. Inhibitor of alcohol dehydrogenase. In contrast to ethanol, 4-MP

levels do not require monitoring during therapy.

Begin fomepizole treatment immediately upon suspicion of methanol/ethylene glycol

ingestion based on the patient's history or anion gap metabolic acidosis, increased osmolar

gap, oxalate crystals in the urine, or a documented serum methanol/ethylene glycol level.

Adjust dosing during hemodialysis; see package insert.

View full drug information

Ethanol

Has 10-20 times greater affinity for enzyme alcohol dehydrogenase than methanol does,

blocking production of toxic metabolites.

Believed to inhibit ADH when serum levels exceed 0.05 g/dL (50 mg/dL). Titration to serum

levels between 0.10 g/dL (100 mg/dL) and 0.15 g/dL (150 mg/dL) typically used.

Measure patient's initial blood level. May be administered PO/IV.

View full drug information

Folic acid (Folvite)

Adjunctive agent in methanol ingestion. Member of vitamin B-complex that may enhance

elimination of toxic metabolite formic acid produced when methanol is metabolized. Useful

in methanol and possibly ethylene glycol toxicity. Leucovorin (folinic acid) is active form of

folate and may be substituted for folic acid.

Folic acid should be administered for several days to enhance folate-dependent metabolism of

formic acid to carbon dioxide and water.

Further Inpatient Care

Patients with significant ingestions of toxic alcohols require hospital admission in a

closely monitored setting such as the intensive care unit.

Patients who are chronic alcoholics may be at risk of alcohol withdrawal if admitted

to the hospital.

Transfer

Patients with ethanol intoxication can be observed until they are no longer clinically

intoxicated and then discharged.

Patients with isopropanol ingestion may require observation in the hospital.

Patients with known or suspected methanol or ethylene glycol intoxication should be

monitored closely, probably in an intensive care unit.

Complications

Ethanol ingestion complications:

o Hypoglycemia is common.[19] The etiology is multifactorial but largely related

to decreased glycogen stores and malnutrition in children and chronic

alcoholics, as well as ethanols inhibition of glycogenolysis. o Patients with acute intoxication may exhibit "holiday heart," in which

dysrhythmias, especially atrial fibrillation, occur following a heavy drinking

episode. Ethanol lowers the threshold for developing atrial fibrillation.

o Cirrhosis, esophageal varices, and erosive gastritis are common in patients

who use ethanol on a frequent basis.

Ingestion of isopropanol is associated with hemorrhagic gastritis.

Ingestion of methanol is associated with blindness, acidosis, coma, cardiovascular

collapse, and death.

Ingestion of ethylene glycol is associated with renal failure, acidosis, coma,

cardiovascular collapse, and death.[15]