Download Toxic alcohols

Toxicology symposia – Review Article
Toxic alcohols
Meera Ekka, Praveen Aggarwal
Abstract
Ethanol ingestion with alcoholic intoxication is one of the commonest emergencies followed by “alcohol
withdrawal syndrome” in chronic alcoholics presenting to the emergency department with medical conditions.
Isolated toxic alcohol (other than ethanol) ingestion cases may report to the emergency department when
inadvertently methanol or ethylene glycol is ingested. In areas with prohibition occasionally outbreaks of toxic
alcohol ingestion are observed. As an emergency physician, it is important to identify toxic alcohol ingestion as
timely treatment will prevent morbidity and mortality.
Keywords: Alcohol ingestion, ethylene glycol, methanol, toxic alcohol
Introduction
The term toxic alcohol has generally referred to
isopropanol, methanol, and ethylene glycol (EG).[1]
However, any alcohol can be toxic if ingested in large
quantities. Early recognition and treatment of patients
intoxicated with these substances in the emergency
department (ED) can reduce the morbidity and
mortality associated with these alcohols.
Ethyl Alcohol (Ethanol)
Ethanol is a low molecular weight hydrocarbon.
It is widely available both as a beverage and as
an ingredient in food extracts, cough and cold
medications, and mouthwashes. Ethanol intoxication
is common in modern society, largely because of its
widespread availability. It is a common co-ingestant
in suicide attempts. The morbidity is often from
co-ingestants or coexisting injuries and illnesses
Access this article online
Quick Response Code:
Website:
www.jmgims.co.in
DOI:
10.4103/0971-9903.151733
as ethanol greatly increases the risk of trauma,
especially trauma due to motor vehicle collisions or
violent crimes.[2]
Toxicokinetics
Ethanol is rapidly absorbed across both the gastric
mucosa and the small intestines, reaching a peak
concentration 20-60 min after ingestion. Once
absorbed, it is converted to acetaldehyde by the enzyme
alcohol dehydrogenase (ADH). Acetaldehyde is then
converted to acetate, which is converted to acetyl CoA,
and ultimately carbon dioxide and water.[3]
Genetic polymorphisms coding for ADH, the amount
of alcohol consumed, and the frequency 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, drinkers
who do not chronically abuse the ethanol eliminate
it at a rate of 15 mg/dL/h, whereas chronic abusers
eliminate it around 20-25 mg/dL.
Clinical features
Acute alcohol intoxication is defined as the pathological
state produced by the ingestion of alcohol. Binge
drinking, which is generally defined as consuming ≥5
alcoholic drinks on a single occasion, generally results
in acute intoxication.[4] The character of symptoms
Department of Emergency Medicine, All India Institute of Medical Sciences, New Delhi, India
Address for correspondence:
Dr. Praveen Aggarwal, Department of Emergency Medicine, All India Institute of Medical Sciences, New Delhi, India.
E-mail: [email protected]
Journal of Mahatma Gandhi Institute of Medical Sciences
March 2015 | Vol 20 | Issue 1
Ekka and Aggarwal: Toxic alcohols
39
associated with intoxication varies with severity and
symptoms depend on both the serum concentration
as well as the pattern of drinking. Levels <25 mg/dL
are associated with a sense of warmth and well-being.
Euphoria and decreased judgment occur at levels
between 25 and 50 mg/dL. At levels of 50-100 mg/dL,
incoordination, decreased reaction time/reflexes, and
ataxia occur. Cerebellar dysfunction (i.e., ataxia, slurred
speech, nystagmus) are common at levels of 100-250 mg/
dL. Coma can occur at levels of >250 mg/dL, whereas
respiratory depression, loss of protective reflexes, and
death occurs at levels >400 mg/dL. Hypotension and
tachycardia may occur as a result of ethanol-induced
peripheral vasodilation, or secondary to volume loss.
[5]
Acute alcohol intoxication can also induce multiple
metabolic derangements, including hypoglycemia,
lactic acidosis, hypokalemia, hypomagnesemia,
hypocalcemia, and hypophosphatemia.[6] Children are
at higher risks of developing hypoglycemia following
a single ingestion than are adults.
primarily supportive. Hypoglycemia and respiratory
depression are two important issues to address
promptly. Hypoglycemia should be promptly
detected by rapid bedside glucose determination in
all intoxicated patients and should receive dextrose
infusion. Patients presenting with coma should
receive at least 100 mg of parenteral thiamine
to prevent or treat Wernicke’s encephalopathy,
along with dextrose. Intravenous (IV) crystalloids
and vasopressures are used to treat hypotension,
if present. Patient with altered sensorium can be
agitated, violent, and uncooperative. Chemical
sedation like benzodiazepines may be needed to
prevent the patient from harming themselves or
others. However, caution must be taken as these
drugs can worsen the respiratory depression caused
by alcohol. Metadoxine, is a new, specific drug
useful in the treatment of acute alcohol intoxication,
which accelerate ethanol excretion.[6]
Laboratory investigations
Hypoglycemia is common. Holiday heart syndrome
may occur in patients with acute intoxication, in which
dysrrhythmias, especially atrial fibrillation, occur.
Other complications in heavy intoxications include
acute pancreatitis, severe myocardial depression,
Hypotension, lactic acidosis, pulmonary edema,
cardiovascular collapse, and sudden death.
The single most important laboratory test in a patient
who appears intoxicated with ethanol is a blood
glucose level by bedside finger prick test. Serum
ethanol concentration and basic electrolytes, blood
gas analysis is also required though measurement of
serum ethanol concentrations is controversial and is
not readily available in many centers. Anion gap (AG)
and osmolal gap (OG) should be calculated to rule
poisoning with other toxic alcohols. Urine drug testing
should be done to rule out other coingestants.
Diagnosis
Alcohol intoxication as a cause of altered mental status
is a diagnosis of exclusion and should be considered
only after ruling out more serious conditions such as
head trauma, hypoxia, hypoglycemia, hypothermia,
hepatic encephalopathy, and other metabolic and
physiologic derangements. However, intoxication can
be diagnosed more typically by history of ethanol intake,
clinical presentation and by using the measurement of
serum ethanol concentrations. However, 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.
Management in the emergency department
Initial treatment should be focused on the airway,
breathing, and circulation. Gastric decontamination
is rarely necessary for any of the alcohols. The
treatment for isolated acute ethanol intoxication is
March 2015 | Vol 20 | Issue 1
Complications
Isopropanol
Isopropanol is a clear, colorless liquid with a fruity
odor and a mild bitter taste. Most commonly found
domestically as rubbing alcohol, isopropanol is
also found in numerous household and commercial
products including cleaners, disinfectants, antifreezes,
cosmetics, solvents, inks, and pharmaceuticals. The
majority of isopropanol exposures are suicidal, but,
unintentional in children <6 years of age can occur.
Although isopropanol poisoning appears to be a
reasonably common occurrence, deaths are rare,
but can result from injury due to inebriant effects,
untreated airway compromise due to coma, or rarely,
cardiovascular depression and shock following massive
ingestion. Supportive care can avert most morbidity
and mortality.
Toxicokinetics
Isopropanol is rapidly and completely absorbed
following ingestion with peak plasma concentrations
occurring within 30 min. Significant absorption
can occur following inhalation or dermal exposure,
especially in infant.[7] Isopropanol is metabolized by
Journal of Mahatma Gandhi Institute of Medical Sciences
Ekka and Aggarwal: Toxic alcohols
40
ADH to acetone. The elimination of isopropanol is
predominantly renal though some pulmonary excretion
of isopropanol and acetone occur. In the absence
of ethanol or fomepizole, the elimination half-life
of isopropanol is between 2.5 and 8.0 h, whereas
elimination of acetone is slower with a half-life
following the isopropanol ingestion of between 7.7 and
27 h.[8] Both isopropyl alcohol and acetone are rapidly
cleared by hemodialysis, with clearance rates in excess
of 200 mL/min.[9]
Mechanisms of toxicity
Isopropanol is a central nervous system (CNS) inebriant
and depressant; brain stem depression is thought to be
the predominant mechanism. In addition, it is irritating
to the GI tract causing hemorrhagic gastritis. Acetone
itself is a mild CNS depressant and may exacerbate
the CNS depression caused by isopropyl alcohol. The
most common metabolic effects are an increased OG,
ketonemia and ketonuria without any AG metabolic
acidosis unlike the toxic alcohols (methanol and EG).
The absence of a high AG metabolic acidosis 4-6 h
postingestion is useful to distinguish isopropyl alcohol
from methanol or EG intoxication in most cases. The
lethal dose is 250 mL in humans estimated from various
sources.
Clinical features
Clinical manifestations include varying degrees
of CNS depression, ranging from inebriation with
disinhibition, sedation, stupor and coma.[10] These
effects, due primarily to the parent alcohol, develop
shortly after exposure, and peak within the 1st h after
ingestion, however, it’s metabolite acetone, causes less
sedation. Steady improvement in the patient’s level of
consciousness is the expected clinical course in mild to
moderate poisoning. Severe poisoning due to massive
ingestion present as coma, respiratory depression,
hematemesis, pulmonary edema, hemorrhagic
tracheobronchitis, shock, and circulatory collapse.
Isopropanol concentrations of 50-100 mg/dL typically
result in intoxication, which can progress to dysarthria
and ataxia. Lethargy and coma can be seen with levels
above 150 mg/dL. Cardiovascular collapse can occur
with levels exceeding 450 mg/dL.[11]
Laboratory studies
The following tests and calculations should also be
performed in patients suspected of ingesting isopropyl
alcohol: Serum isopropyl alcohol and acetone levels
(or serum osmolality if direct serum drug levels are
unavailable). Basic electrolytes, with calculation of AG
Journal of Mahatma Gandhi Institute of Medical Sciences
and OG, blood urea nitrogen, and creatinine, serum and
urine ketones and Arterial or venous blood gas analysis
should be done.
Diagnosis
Poisoning can be diagnosed using the measurement
of isopropanol serum concentrations though these
may not be readily available and also of limited value.
Diagnosis is, therefore, more typically made on the
basis of the patient’s history and clinical presentation.
An osmol gap, ketonemia, and/or ketonuria without
metabolic acidosis, along with a fruity or sweet odor on
the breath and CNS depression support the diagnosis.
Ketone usually present in the serum as early as 30 min
after ingestion. If there is no coexisting ethanol
ingestion, the absence of ketones effectively rules
out the isopropanol ingestion.[11] However, starvation,
alcoholic and diabetic forms of ketoacidosis presenting
with depressed mental status and ketosis should be
ruled out in these patients.[10]
Management
Supportive care is the mainstay of management with
primary emphasis on assessment and stabilization of
the airway, breathing, and circulation.
Decontamination
There is no role for gastrointestinal (GI) decontamination
in most cases of isolated isopropyl alcohol intoxication.
Activated charcoal may be useful for coingestants.
Antidote
The primary metabolite acetone is less toxic than
isopropyl alcohol. Hence, there is no indication for
ADH inhibition with fomepizole or ethanol following
isopropyl alcohol exposure.[12] Because of the
hemorrhagic gastritis that can follow the isopropanol
ingestion, H2 blockade or proton-pump inhibitors may
be helpful.
Hemodialysis
Rare patients with massive intentional ingestions
may be hemodynamically unstable despite IV fluids
and vasopressors. These patients with hemodynamic
instability despite aggressive fluid resuscitation may
require hemodialysis.[9]
Complications
Severe isopropanol poisoning results in coma,
respiratory depression, hematemesis due to
hemorrhagic gastritis, pulmonary edema hemorrhagic
tracheobronchitis, shock, and circulatory collapse.[10]
March 2015 | Vol 20 | Issue 1
Ekka and Aggarwal: Toxic alcohols
Methyl Alcohol
Methyl alcohol is widely used as a solvent in many
household products, such as antifreeze, cleaning
solutions, dyes and paint remover. It is also used in
photocopying fluid, shellacs, and windshield-washing
fluids. Consumption of illegally produced or homemade
alcoholic beverages containing relatively high levels of
methanol poses risk and had caused several outbreaks
in the past.[13] Poisoning may occur through accidental
ingestion, attempted inebriation or suicide attempt.
It can also occur from prolonged inhalation or skin
absorption. Methyl alcohol poisoning is associated
with significant morbidity and mortality.
Toxicokinetics
Methanol is rapidly absorbed from the gastric mucosa,
and achieves a maximal concentration 30-90 min after
ingestion. Methanol is primarily metabolized in the
liver via ADH 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.
Methanol undergoes zero-order metabolism, and is
excreted at a rate of 8.5 mg/dL/h to 20 mg/dL/h in the
absence of competitive inhibition. In the presence of
competitive inhibitors like ethanol or fomepizole, the
metabolism changes to first order. In this later scenario,
the excretion half-life ranges from 22 to 87 h.
Mechanism of toxicity
Formic acid, the major toxic metabolite of methanol
is responsible for the majority of the toxicity. This
toxic metabolite is primarily responsible for the
retinal and optic nerve damage as well as metabolic
acidosis may be caused by disruption of mitochondrial
electron transport. Specific changes can occur in the
basal ganglia in the later stages. There are reports of
pancreatitis with this poisoning. The lethal dose of pure
methanol is estimated to be 1-2 mL/kg bodyweight.[1]
However, there are reports of permanent blindness and
deaths with 0.1 mL/kg bodyweight.[1]
Clinical features
Onset of symptoms ranges from 40 min to 72 h with an
average of 24 h depending on the co-ingestion of ethanol
as ethanol ingestion delayed the manifestation. Unlike
ethanol or isopropanol, it does not cause as much of an
inebriated state.[11] Early stage are mild and transient,
manifesting as mild euphoria or inebriation, followed
by a latent phase lasting from 6 to 30 h and during this
March 2015 | Vol 20 | Issue 1
41
stage toxic metabolites are formed.[1] The main systems
involved in methanol toxicity are the neurologic,
gastroenterologic, and ophthalmologic systems. Eye
involvement is seen approximately in (50%) of patients
and is associated with high methanol intake manifesting
at 6 h or more postingestion may be delayed up to 24 h.
Eye symptoms include blurred vision, photophobia,
visual hallucination (often described as a snow field),
partial to complete visual loss which are reversible in
many patients in the early stage.[14] Ocular examination
may reveal dilated pupils minimally or unreactive to light
with hyperemia of the optic disc, nystagmus, papilledema,
retinal edema and hemorrhages; but, over several days,
the red disc becomes pale, and the patient become blind.
Permanent visual sequelae have been described in severe
intoxication.[15] Regarding CNS symptoms, patient often
alert on presentation. However, altered sensorium,
confusion, severe headache, lethargy and ataxia are
not uncommon. In severe cases, coma and seizures
may occur. Parkinson-like extrapyramidal (magnetic
resonance imaging and/or computed tomography of
the brain may reveal basal ganglia infarct) symptoms
have also been reported.[16] Gastroenterological
manifestations include nausea, vomiting, flank pain,
abdominal pain, GI hemorrhage, diarrhea, liver function
abnormalities, and pancreatiti.[17] Patient may also
complain of breathlessness related to hyperventilation
as a consequence of severe metabolic acidosis.
Ethylene Glycol
Ethylene glycol is a colorless, odorless, sweet tasting
liquid, which is used in many manufacturing processes
and is a common component of antifreeze and de-icing
solutions around the house. It’s a low molecular weight
toxic alcohol that can result in serious morbidity and
mortality.
Toxicokinetics
Ethylene glycol itself is nontoxic; but, its metabolic
byproducts are toxic. EG is oxidized via ADH into
glycoaldehyde. Glycoaldehyde subsequently undergoes
metabolism via aldehyde dehydrogenase into glycolic
acid.[18] The glycolic acid is converted to glyoxylic
acid. This is slower process and the rate-limiting step in
the metabolism of EG. Glyoxylic acid is subsequently
metabolized into oxalic acid. The excretion half-life of
EG is approximately 3 h in patients with normal renal
function in absence of ethanol or fomepizole. However,
in the presence of these two antidotes, ADH undergoes
competitive inhibition, and the resulting excretion halflife increases to approximately 17-20 h.[11]
Journal of Mahatma Gandhi Institute of Medical Sciences
42
Mechanism of toxicity
The main toxicity of EG is related to the production
of oxalic acid and glycolic acid. The toxicity occurs
from both the ensuing metabolic acidosis as well as the
oxalate itself. The oxalic acid combines with calcium
to form insoluble calcium oxalate crystals, occasionally
leading to hypocalcemia. Hypocalcemia can cause
coma, seizure and dysrhythmias. These calcium oxalate
crystals deposit in various organs causing acute renal
failure and myocardial, neurological and pulmonary
dysfunction.[19,20] Lethal dose vary depending on the
individual susceptibility to the adverse effects of EG.
In human, it is reported to be 1.5 mL/kg body weight.[20]
Clinical features
Acute EG toxicity can occur through three distinct
stages.[11] The first stage (neurologic phase: CNS
depression), can occur within 30 min up to 12 h.
During this stage, the patient appears inebriated, mild
confusion or stupor may be present. 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.
As the intoxication progresses, neurological symptoms
can become more profound. EG may cause severe
neurological deficits, and even mimic a clinical state
of brain death.[21] The second stage (cardiopulmonary
stage), occurs between 12 and 24 h after ingestion.
During this stage, the patient commonly develops mild
tachycardia and hypertension. Acute respiratory distress
syndrome can also occur. Significant hypocalcemia
can occur leading to hyperreflexia and arrhythmias.[22]
Metabolic acidosis arises and patient compensate by
hyperventilation at this stage. The third stage (renal
stage), typically starts after 24-72 h. During this stage,
acute renal failure and flank pain manifest. In severe
intoxication, renal failure appears early and progress to
anuria and in severe cases multiorgan failure and death
can occur.[23]
Laboratory studies in ethylene glycol
and methanol poisoning
Serum methanol concentration should be obtained,
usually determined by gas chromatography, but this
technique is not widely available on 24 h basis in the
ED. The measurement of OG and AG can be useful in
the diagnosis. In the early phase of intoxication, serum
osmolality can be increased due to increase in methanol
level. An unexplained, large OG is presumptive
evidence of recent methanol exposure.[24] The higher
OG, especially if ≥20 mOsm/L, is specific for the
presence of alcohol.[25] As the metabolism of methanol
Journal of Mahatma Gandhi Institute of Medical Sciences
Ekka and Aggarwal: Toxic alcohols
progress, the OG decreases, and AG increases due to
accumulation of toxic metabolites. In the last stage,
only AG remains high and OG normalized.[14] If the
AG is unexplained and other possible causes have been
excluded, methanol poisoning should be suspected
and considered for empiric treatment of toxic alcohol
poisoning.[25] In EG poisoning, needle shaped and
envelop shaped oxalate crystal may be present in
urine.[20]
Treatment of methanol and ethylene glycol
poisoning
Methanol or EG poisoning is a lethal condition needs
immediate resuscitation in the ED. Moderate poisoning
required management in ward. However, severe and
life threatening poisoning required intensive care in
the Intensive Care Unit (ICU). Prompt consultation
with a poison control center is strongly recommended.
Treatment is divided into four categories. It includes
gastric decontamination, general supportive care, use
of antidotes, and hemodialysis.
Gastric decontamination
Gastric decontamination: gastric lavage or activated
charcoal is not recommended as absorption rate is very
rapid.
General supportive care
It includes IV fluids, mechanical ventilation, sodium
bicarbonate therapy, calcium gluconate (in EG)
and vasopressor indicated in severe poisoning. The
administration of sodium bicarbonate is recommended
in case of severe acidosis (pH ≤7.3) liberally.[22] Severe
hypocalcemia, due to formation of oxalate crystal,
causing symptoms such as muscle spasms or seizures
required calcium gluconate therapy.[22]
Therapy with antidotes
Antidotes are most effective when given in the early
phase of the intoxication, before significant levels
of toxic metabolites are formed. Antidotes therapy
increases the half-life of EG and methanol and prevent
formation of toxic metabolites. Currently, only two
antidotes are approved and used to block ADHmediated metabolism of EG and methanol: Ethanol, a
competitive ADH substrate, and fomepizole, an ADH
inhibitor.
Criteria for initiating antidotes therapy in EG and
methanol poisoning include:[22-24] (1) Documented
plasma concentration ≥20 mg/dL, or (2) documented
recent history of ingesting toxic amounts of EG/
March 2015 | Vol 20 | Issue 1
Ekka and Aggarwal: Toxic alcohols
menthol and OG ≥10 mOsm/L, or (3) suspected EG/
methanol ingestion and at least 3 (for EG) or 2 (for
methanol) of the following criteria: A. Arterial pH
<7.3, B. Serum bicarbonate <20 mmol/l, C. OG >10
mOsm/L and d. oxalate crystalluria (for EG only).
Fomepizole: Dosing scheme[22,23]
For patients not on hemodialysis
Loading dose 15 mg/kg, followed by 10 mg/kg
12 hourly for 4 doses. After 48 h, dose should be
increased to 15 mg/kg every 12 hourly. All doses are
administered intravenously over 30 min.[22,23]
For patient undergoing hemodialysis: Two proposed
protocols[22,23]
1. A reduction in time interval between fomepizole
doses: Loading dose 15 mg/kg followed by
10 mg/kg every 6 hourly for 4 doses and then
4 hourly.[22,23]
2. A continuous IV infusion of 1-1.5 mg/kg/h
following the initial loading dose of 15 mg/kg.[22,23]
Adverse effect of fomepizole
Fomepizole is generally well tolerated. However,
injection site irritation, dizziness, tachycardia,
headache, transaminitis, agitation and seizure are
reported.[22,23]
Ethanol
It is indicated for patients with a known fomepizole
allergy, or during nonavailability of fomepizole. IV
administration is preferred.
Dosing scheme
Target ethanol concentration is 100-150 mg/dL
(1-1.5%).
Loading dose
7.5-12.5 mL ethanol 10% solution in glucose/kg
intravenously (0.6-1.0 g/kg) or 2.5 mL/kg orally 40%
ethanol solution.
Maintenance dose (intravenously)
1.4 mL ethanol 10% solution in glucose/kg/h. During
hemodialysis (an additional dose of 1.9 mL ethanol
10% solution in glucose/kg/h should be administered
intravenously). In adult, 3.3 mL ethanol 10% solution
in glucose/kg/h.
Hemodialysis
It is considered the key element for the treatment in
severe EG and methanol poisoning and aimed at
March 2015 | Vol 20 | Issue 1
43
removing both the parent compound and its toxic
metabolites, to correct metabolic acidosis, and
electrolyte disturbances, thus reducing the duration
of hospitalization and antidotal treatment.[22] Current
indications for HD based on clinical experience only
includes:
1. Arterial pH <7.3,
2. A decline of arterial pH >0.05 despite bicarbonate
therapy,
3. pH <7.3 despite bicarbonate therapy,
4. Initial plasma EG or Methanol concentration
≥50 mg/dL,
5. Renal failure,
6.
Electrolyte
imbalances
unresponsive
to
conventional therapy,
7. Deterioration of vital signs despite intensive
supportive care, and
8. Visual disturbances (in methanol poisoning).[11,22,23]
Adjunctive (co-factor) therapies
In methanol poisoning, folinic acid or folic acid (if
folinic acid is not available) should be administered at
a dose of 1 mg/kg, with a maximum does of 50 mg
every 4 hourly. Folinic acid augment the conversion
of formic acid to carbon dioxide and water by the
tetrahydrofolate synthetase, an enzyme dependent
on folinic acid. In EG poisoning, Thiamine 100 mg
intravenously every 6 hourly and pyridoxine 50 mg
every 6 hourly should be given to shunt metabolism
of glyoxilic acid away from oxalate and favor the
formation of less toxic metabolites.[23,26]
Preferred antidote: Ethanol versus fomepizole
Fomepizole has higher potency to inhibit ADH
with longer duration of action, administration is
easy, dosing schedule is simple, may obviate the
need for hemodialysis in specific cases, and most
important there is no need for fomepizole blood
concentration and blood glucose monitoring as
required in ethanol. Therefore, has low overall
cost and better safety consideration. These
are the reasons to prefer for fomepizole as an
antidote instead of ethanol according to clinician
preference.[14] However, in one systemic review on
use of ethanol or fomepizole, the conclusion was
inconclusive.[27]
Ethanol therapy is labor intensive, require intensive
ICU monitoring. The overall cost of therapy is
higher than fomepizole when the cost of frequent
glucose monitoring and measurement of blood
ethanol concentrations are accounted. Again
Journal of Mahatma Gandhi Institute of Medical Sciences
44
in chronic alcoholics and during hemodialysis,
maintenance dose should be increased. During
therapy with this antidote, significant mental status
changes, hypoglycemia, liver toxicity or pancreatitis
can occur, therefore confuse the interpretation of the
already complex clinical course of EG and methanol
poisoning. However, despite these disadvantages,
due to its low costs, physician experience and ready
availability, ethanol is used as first line antidote in
some centers.[14,28]
Predictors of poor prognosis in methanol and
ethylene glycol poisonings
Poor prognostic signs include severe metabolic
acidosis (pH ≤7.0), cardiovascular shock, seizure
and coma at presentation.[1] Outcome is best
correlated with the severity of acidosis rather than
methanol concentration. According to study by
Coulter et al., a large OG, AG and low pH (<7.22)
were associated with increased mortality; and pH has
the highest predictive value.[29] Degree of acidosis at
presentation determine visual outcome in methanol
poisoning.[15]
Complications
Methanol poisoning
It is associated with blindness, metabolic acidosis,
coma, seizure, cardiovascular collapse, respiratory
failure and death.
Ethylene glycol poisoning
It is associated with renal failure, metabolic
acidosis, coma, seizure, hypocalcemia, myocarditis,
cardiovascular collapse and death.
References
1. Jammalamadaka D, Raissi S. Ethylene glycol, methanol
and isopropyl alcohol intoxication. Am J Med Sci
2010;339:276-81.
2. Meropol SB, Moscati RM, Lillis KA, Ballow S, Janicke DM.
Alcohol-related injuries among adolescents in the emergency
department. Ann Emerg Med 1995;26:180-6.
3. Hornfeldt CS. A report of acute ethanol poisoning in a child:
Mouthwash versus cologne, perfume and after-shave. J
Toxicol Clin Toxicol 1992;30:115-21.
4. Naimi TS, Brewer RD, Mokdad A, Denny C, Serdula MK, Marks JS.
Binge drinking among US adults. JAMA 2003;289:70-5.
5. Yost DA. Acute care for alcohol intoxication. Be
prepared to consider clinical dilemmas. Postgrad Med
2002;112:14-6, 21.
6. Vonghia L, Leggio L, Ferrulli A, Bertini M, Gasbarrini G,
Addolorato G, et al. Acute alcohol intoxication. Eur J Intern
Med 2008;19:561-7.
Journal of Mahatma Gandhi Institute of Medical Sciences
Ekka and Aggarwal: Toxic alcohols
7. Leeper SC, Almatari AL, Ingram JD, Ferslew KE. Topical
absorption of isopropyl alcohol induced cardiac and
neurologic deficits in an adult female with intact skin. Vet
Hum Toxicol 2000;42:15-7.
8. Monaghan MS, Ackerman BH, Olsen KM, Farmer C,
Pappas AA. The use of delta osmolality to predict serum
isopropanol and acetone concentrations. Pharmacotherapy
1993;13:60-3.
9. Rosansky SJ. Isopropyl alcohol poisoning treated with
hemodialysis: Kinetics of isopropyl alcohol and acetone
removal. J Toxicol Clin Toxicol 1982;19:265-71.
10. Available from: http://www.uptodate.com/contents/isopropylalcohol-poisoning. [Last accessed on 2014 Oct 10].
11. Available
from:
http://www.emedicine.medscape.com/
article/812411/Alcohol Toxicity. [Last accessed on 2014 Oct 10].
12. Bekka R, Borron SW, Astier A, Sandouk P, Bismuth C,
Baud FJ. Treatment of methanol and isopropanol poisoning
with intravenous fomepizole. J Toxicol Clin Toxicol
2001;39:59-67.
13. Lachenmeier DW, Rehm J, Gmel G. Surrogate alcohol: What
do we know and where do we go? Alcohol Clin Exp Res
2007;31:1613-24.
14. Rietjens SJ, de Lange DW, Meulenbelt J. Ethylene glycol or
methanol intoxication: Which antidote should be used,
fomepizole or ethanol? Neth J Med 2014;72:73-9.
15. Desai T, Sudhalkar A, Vyas U, Khamar B. Methanol
poisoning: Predictors of visual outcomes. JAMA Ophthalmol
2013;131:358-64.
16. Fontenot AP, Pelak VS. Development of neurologic symptoms
in a 26-year-old woman following recovery from methanol
intoxication. Chest 2002;122:1436-9.
17. Bennett IL Jr, Cary FH, Mitchell GL Jr, Cooper MN. Acute methyl
alcohol poisoning: A review based on experiences in an
outbreak of 323 cases. Medicine (Baltimore) 1953;32:431-63.
18. Cascallana JL, Gordo V, Montes R. Severe necrosis of
oesophageal and gastric mucosa in fatal methanol poisoning.
Forensic Sci Int 2012;220:e9-12.
19. Pomara C, Fiore C, D’Errico S, Riezzo I, Fineschi V. Calcium
oxalate crystals in acute ethylene glycol poisoning: A confocal
laser scanning microscope study in a fatal case. Clin Toxicol
(Phila) 2008;46:322-4.
20. Kraut JA, Kurtz I. Toxic alcohol ingestions: Clinical features,
diagnosis, and management. Clin J Am Soc Nephrol
2008;3:208-25.
21. Tobé TJ, Braam GB, Meulenbelt J, van Dijk GW. Ethylene
glycol poisoning mimicking Snow White. Lancet
2002;359:444-5.
22. Megarbane B. Treatment of patients with ethylene glycol
or methanol poisoning: Focus on fomepizole. Open Access
Emerg Med 2010;2:67-75.
23. Brent J. Fomepizole for ethylene glycol and methanol
poisoning. N Engl J Med 2009;360:2216-23.
24. Barceloux DG, Bond GR, Krenzelok EP, Cooper H, Vale JA,
American Academy of Clinical Toxicology Ad Hoc Committee
on the Treatment Guidelines for Methanol Poisoning.
American Academy of Clinical Toxicology practice guidelines
on the treatment of methanol poisoning. J Toxicol Clin
Toxicol 2002;40:415-46.
25. Al Aseri Z, Altamimi S. Keeping a high index of suspicion:
Lessons learned in the management of methanol ingestion.
BMJ Case Rep 2009;2009. pii: bcr09.2008.1013.
March 2015 | Vol 20 | Issue 1
Ekka and Aggarwal: Toxic alcohols
26. Brent J. Current management of ethylene glycol poisoning.
Drugs 2001;61:979-88.
27. Beatty L, Green R, Magee K, Zed P. A systematic review of
ethanol and fomepizole use in toxic alcohol ingestions.
Emerg Med Int 2013;2013:638057.
28. Sturkenboom M, van Rieke H, Uges D. Treatment of ethylene
glycol and methanol poisoning: Why ethanol? Neth J Crit
Care 2009;13:297-302.
March 2015 | Vol 20 | Issue 1
45
29. Coulter CV, Farquhar SE, McSherry CM, Isbister GK, Duffull SB.
Methanol and ethylene glycol acute poisonings — Predictors
of mortality. Clin Toxicol (Phila) 2011;49:900-6.
How to cite this article: Ekka M, Aggarwal P. Toxic alcohols. J
Mahatma Gandhi Inst Med Sci 2015;20:38-45.
Source of Support: Nil, Conflict of Interest: No conflict of interest.
Journal of Mahatma Gandhi Institute of Medical Sciences