THE GUIDELINES FOR MANAGEMENT OF ETHANOL, METHANOL AND ETHYLENE GLYCOL POISONING AT THE EMERGENCY ROOM
Niru Prasad, M.D., F.A.A.P., F.A.C.E.P.
Department of Emergency Medicine
Henry Ford Hospital
West Bloomfield Center
Department of Ambulatory Pediatrics
St. Joseph Mercy Hospital
Pontiac
Ethanol Overdose
Introduction
Pharmacokinetics
Absorption and Metabolism
Clinical Symptoms Produced by Ethanol Overdose
Diagnosis, Laboratory Analysis and Treatment
Ethanol is the most commonly abused drug in the United States, with approximately 10 percent of
the adult population qualifying as alcoholics. Approximately 40 percent of the medical hospital
admissions are related to ethanol abuse and multisystem organ dysfunctions secondary to chronic
alcohol intake. The chronic alcohol intake can lead to numerous metabolic complications such as
hypoglycemia, ketoacidosis, electrolyte disorders, neurologic disorders, withdrawal seizures,
delirium tremens, gastritis, hepatitis, pancreatitis, as well as hematologic disorders. It is very
important for the emergency physicians to recognize these patients. The adolescents and young
adult suicide rates are frequently associated with ethanol abuse and overdose. It is also important to
remember that the depressed level of consciousness in alcoholics could also be due to subdural
hematoma, meningitis, and other central nervous systems lesions. Alcohol abuse is often associated
with suicide,homicide, drowning, physical abuse, and motor vehicle accidents.
The forms of alcohols are:
Ethyl alcohol (ethanol)
Ethylene glycol
Isopropyl alcohol (isopropanol)
Methyl alcohol
Propylene glycol
Diethylene glycol
All of these forms of alcohol are low molecular weight, water soluble substances with prominent
multiorgan toxicity.
Pharmacokinetics of Ethanol
Ethanol is absorbed in an unaltered state from the stomach and small intestine, metabolized by the
liver and excreted through the kidneys. It has been recently postulated that the presence of
alcoholic dehydrogenase in gastric mucosa degrades some of the absorbed ethanol, and histamine
H-2 antagonist inhibits alcohol dehydrogenase hence patients taking acid suppressing drugs are
more prone to alcohol toxicity with ethanol intake. Several hepatic enzymes convert ethanol to
acetaldehyde. These enzymes are cytoplasmic alcohol dehydrogenase, catalase, and a microsomal
ethanol oxidizing system.
Metabolism of Ethanol
Ethanol
¯ (alcohol dehydrogenase)
Acetaldehyde
¯ (alcohol dehydrogenase)
Acetic acid
¯ (Kreb's cycle)
¯
Carbon dioxide and water
The alcohol dehydrogenase pathway is the predominant system for alcohol metabolism. The
second pathway is the microsomal ethanol oxidizing system located in the endoplasmic reticulum.
This system may be associated with cytochrome P-450 mixed function oxidase system in the liver.
The third system involves the catalase located in the prioxisomes.
The rate of metabolism of ethanol is in the rage of 15 to 25 milligrams per deciliter per hour.
12 mg/dl/hour in nondrinkers
15 mg/dl/hour in social drinkers
30 mg/dl/hour in alcoholics
A 150 pound person metabolizes 10 ounces of beer in one hour. Effects Produced by Ethanol Metabolism
1. Drug Interactions
2. Carbohydrate Metabolism
A. Hypoglycemia in the presence of inadequate food intake.
B. Inhibition of galactose metabolism
C. Hyperglycemia
D. Hypomagnesemia.
3. Protein Metabolism
A. Increased synthesis of lipoproteins
B. Decreased synthesis of albumin and other proteins.
4. Lipid Metabolism
A. Increase in liver lipids (fatty liver)
B. Increase in serum triglycerides
5. Increase in Lactate Production
A. Lactic acidosis
B. Decrease in uric acid secretion and resultant Hyperuricemia.
6. Other Effects
A. Ketoacidosis
B. Increased catecholamine release
C. Interference with citric acid cycle
D. Decreased serum level of phosphate
The acute organ toxicity directly related to ethanol:
A. Central nervous system
Acute intoxication syndromes Withdrawal syndromes.
B. Gastrointestinal system
Acute gastritis
Acute pancreatitis
Acute fatty liver of alcoholism
Alcoholic hepatitis
C. The other common manifestations
Alcoholic cardiomyopathy
Alcoholic skeletal myopathy
Hematologic abnormalities
Endocrine disorders
The early manifestation of intoxication such as altered mood and impaired cognition are seen at an alcohol blood level of
25 to 50 mg/dl. Impaired performance and judgement are seen in individuals with alcohol levels of 40 to 60 mg/dl.
The legal intoxicated blood level of alcohol is 100 mg/dl. When ethanol concentration exceeds 250 mg/dl patient is at High
risk of coma. A level about 450 to 500 mg/ml may be fatal. The symptoms of acute ethanol ingestion are further
complicated by the use of other drugs, sedatives, or other toxic alcohols such as isopropyl alcohol.
The Acute Symptoms Related to Ethanol Blood Level
Symptoms Concentration
(mg per 100 ml)
Mild muscle incoordination 50 -100 mg/ml
Slow react ion time
Blurred vision
Incoordination
Decreased inhibition 50 mg/100 ml
Decreased motor skill 100 - 300 mg/ml
Stupor
Hypoglycemia
Hypothermia 300 - 400 mg/ml
Coma
Respiratory failure
Death >400 mg/ml
The initial management of the overdosed patient is control of airways, intravenous
fluids, drawing blood for electrolytes and alcohol level and drug screening, gastric
lavage, activated charcoal, and close monitoring of vital signs. If patient presents
with altered mental status, 2 mg of Naloxone, 25 gm of glucose and 50 to 100 mg of
thiamine should be given. A continuous infusion of glucose saline should be
administered with multivitamins.
Treatment of Ethyl Alcohol Overdose
Condition Treatment
Altered mental status Naloxone
Glucose
Thiamine
Hypoventilation Mechanical
ventilation
Ketoacidosis Glucose
Normal saline
Hypotension Normal saline
Trendelenburg's
position;
Vasopressor
Alcohol Withdrawal Seizures
The withdrawal seizures occur in an estimated 5 to 33 percent of alcoholic and consist of one or
more generalized tonic clonic convulsion. Since the withdrawal seizures are self-limited, patients
generally do not need treatment. However, patients with a prior history of seizures, Head injuries,
status epilepticus, need treatment with intravenous Valium, Ativan and Dilantin. A recommended
regimen consists of intravenous Valium 2 mg every two minutes, or 1 mg of Ativan I.V., followed
by Dilantin I.V. 40 mg per minute for a total dose of 15 mg/kg.
Delirium tremens is the most serious and delayed manifestation of ethanol withdrawal that usually
occurs two to four days after cessation of drinking, and is characterized by severe confusion state
with delirium, visual and sensory Hallucinations and sign of increased autonomic activities like
tachycardia, Hyperpyrexia, and diaphoresis. The symptoms usually subside in two to three days and
may be fatal in 5 to 15 percent of patients.
1. I.V. Fluids
2. Valium 5 to 10 mg or Ativan 2 mg frequent I.V. injections until symptoms subside.
3. Haldol 5 mg I.V. every six hours as needed
4. Propranolol 0.5 to 1 mg I.V., or 40 to 80 mg po to control tremors.
5. Atenolol up to 100 mg po per day with Valium shorten the duration of withdrawal syndrome.
Dehydration is due to profound agitation, decreased oral intake, and diaphoresis, and is corrected
by I.V. fluid therapy.
Wernicke's encephalopathy is another fatal complication of alcoholism and is characterized by
cerebellar ataxia, mental confusion, and oculomotor disturbance. The patient should receive 100
mg I.V. thiamine. However, severely malnourished alcoholics might need up to 1000 mg of
thiamine I.V. to reverse the ophthalmoplegia. Since thiamine is a co-factor in glucose
metabolism, the administration of glucose to a thiamine deficient patient may exacerbate this
deficiency; hence, patient should receive thiamine before glucose. Since Hypomagnesemia may
cause thiamine resistance, intramuscular magnesium 1 to 2 cc of 50 percent solution should be
given with thiamine.
Drug Interaction
Ethanol is synergistic with narcotics and sedative-hypnotics. Abuse of combinations of drug with
alcohol may lead to respiratory arrest and coma.
Disuifiram, a drug used for detoxification, blocks the activity of the enzyme aldehyde
dehydrogenase, leading to accumulation of acetaldehyde in the blood. Within five to ten minutes
of ethanol ingestion, the patients on Antabuse develop headache, nausea, flushing, tachycardia, and
hypotension secondary to vomiting and dehydration. Treatment is supportive with intravenous
fluids and norepinephrine for severe hypotension.
Isopropyl Alcohol
This is the second most commonly ingested alcohol and is present in rubbing alcohol, skin and hair
products and antifreeze. Children might suffer toxicity from inhalation, and from transdermal
absorption during sponging
Pharmacology and Metabolism
The absorption of isopropyl alcohol is rapid, and within 30 minutes of ingestion, 80 percent of the
alcohol circulates in the blood, leading to CNS depression. The potential lethal dose of isopropyl
alcohol is 2 to 4 cc/kg.
Isopropyl Alcohol
¯
alcohol dehydrogenase
¯
Acetone
¯ ¯
Lungs Kidneys
Clinical Symptoms
These patients present to the emergency room with headache, dizziness, poor coordination, mental
confusion due to alcohol and acetone. The abdominal pain, vomiting, hematemesis, are due to
local gastric irritation. These patients do not have the breath odor of ethanol. The obtunded
patients might also have hypoglycemia, ketosis, myoglobinuria, and rhabdomyolysis.
Laboratory Investigations
These include CBC, electrolytes with BUN, creatinine, serum osmolality, ketones, arterial blood
gasses, and urinalysis.
Treatment and Disposition
1. Gastric lavage and emesis if ingestion is within two hours.
2. Activated charcoal for multi-drug ingestion
3. I.V. Fluids to correct high anion gap acidosis and
hypoglycemia
4. Hemodialysis is indicated for serum isopropyl alcohol level
greater than 400 mg/cc, refractor Hypotension and
deteriorating vital signs.
Methanol Ingestion
Methanol is a highly toxic alcohol obtained from distillation of wood. Methanol is present in
antifreeze and windshield washer fluid, carburetor fluids, glass cleaners, Sterno, paint strippers,
and gasoline substitutes. Methanol ingestion can cause serious sequelae due to multiorgan damage,
including permanent blindness, and death.
Pharmacology and Metabolism
Methanol is rapidly absorbed from the gastrointestinal tract and blood levels peak 30 to 90 minutes
after absorption. The smallest lethal dose reported is 15 cc of 40 percent methanol. This is
metabolized by the liver and excreted through the kidneys.
Methanol
¯
Formaldehyde
¯
Formic acid
¯
Folate
¯
C02 and H20
Clinical Manifestations of Methanol Intoxication
General
Mental Confusion
Metabolic acidosis
Long latent period, often 12 to 24 hours
Gastrointestinal
Nausea
Vomiting
Severe abdominal pain
Neurologic
Headache
Dizziness
Seizures, stupor, coma
Visual
Diminished sensation of light
Photophobia burred vision
Retinal edema
Hyperemia of optic disk
Laboratory Investigation
These include: CBC, electrolytes, calcium, amylase, serum osmolality, ethanol and methanol
levels, arterial blood gases and urinalysis. A severe anion gap metabolic acidosis is the
significant finding of methanol ingestion.
Osmolal gap = measured serum osmolality - calculated serum
osmolality
Calculated serum osmolality (mosm/kg) = 2 (na+) + glucose + BUN
18 2.8
The normal osmolal gap is less than 10 mosm/1. A High osmolal gap indicates the
presence of ethanol, ethylene glycol, methanol, isopropyl alcohol, mannitol, or glycerol in
blood. Patients with peak methanol level below 20 mg/di are asymptomatic; a level
greater than 25 to 50 mg/di have serious ingestions needing therapy, and those with levels
above 150 mg/di often die if not treated early.
These same investigations are suggested for patients with ethylene glycol ingestion and the
treatment for these two conditions is very similar.
Ethylene Glycol Ingestion
It is a colorless, odorless substance and the ethylene glycol intoxication is usually due to
suicide attempt, accidental ingestion, or due to consumption as ethanol substitute. The
sources of ethylene glycol are: antifreeze, brake fluid, coolant, windshield fluids, some
detergents, lacquers, and polishes.
Pharmacology and Metabolism
Ethylene glycol
¯ Alcohol dehydrogenase
Glycolaidehyde
¯ Alcohol dehydrogenase
¯
Glycolic acid Lactic dehydrogenase
¯ Glycolic acid oxidase
¯
Pyridoxine Glyoxylic acid Thiamine
¯ ¯ ¯ ¯
Glycine ¿ Oxalic acid Formic acid aHydroxy-
bKetoadipate
Stage I (30 minutes to 12 hours)
Intoxicated patient with no alcohol odor
Nausea and vomiting
Metabolic acidosis
Crystalluria
Myoclonus
Seizure and death
Stage II (12 to 24 hours)
Tachypnea, tachycardia
Hypertension
Cyanosis
Pulmonary edema
Bronchopneumonia
Cardiac Enlargement
Stage III (36 to 48 hours)
Crystalluria
Costovertebral angle tenderness
Tubular necrosis with oliguria
Renal failure
Treatment of Methanol and Ethylene Glycol Toxicity
1. Prevent further absorption by Ipecac or lavage, activated charcoal and cathartics.
2) Alkalinization by 2 to 3 mg/kg of intravenous sodium bicarbonate.
3. Ethanol therapy
4. Calcium chloride I.V. gm for ethylene glycol ingestion.
5. Thiamine 50 mg to 100 mg for ethylene glycol
6. pyridoxine 2 to 5 gm I.V. for ethylene glycol
7. Folic acid 50 to 100 mg I.V. for methanol
8. Dialysis
Ethyl Alcohol Therapy
Ethyl alcohol therapy is suggested for management of ethylene glycol and methanol ingestion because it completes with alcohol
dehydrogenase--the enzyme responsible for breakdown of methanol and ethylene glycol. Ethyl alcohol saturates this enzyme, increases
the half-life of ethylene glycol from 3 to 17 Hours. Therefore, the administration of ethanol leads to increased excretion of unchanged
compound through kidneys, hence prevents the body organ damage due to toxic metabolites.
Dose 95% Ethanol 40% Ethanol 10% Ethanol
Loading 1 cc/kg 2.5 cc/kg 100 cc/kg
Maintenance
w/o dialysis 0.1 cc/kg/hr 0.3 cc/kg/hr l cc/kg/Hr
Maintenance
with dialysis 0.3 cc/kg/hr 1 cc/kg/hr 3 cc/kg/hr
In summary, the author has discussed the management of ethanol, isopropyl alcohol, methanol,
ethylene glycol poisonings with particular emphasis on early diagnosis and proper management of
these patients. The Hospitalization, psychiatric, and social service evaluations should be made on
these overdosed patients with proper emphasis on long-term management and guidance of the
patient.
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