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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.
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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.
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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.
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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
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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
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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
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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,
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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
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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.
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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
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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.
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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]