Michael P. Kefer
All alcohols have toxic potential, either from the parent compound or toxic metabolites.
The presence of an osmolal gap suggests a low-molecular-weight substance such as ethanol, isopropanol, methanol, or ethylene glycol. An understanding of the osmolal gap is important in discussing the toxicity of these common alcohols.
The osmolal gap = osm measured–osm calculated (normal <10 mOsm/L).
Osm measured = Laboratory determination by freezing point depression
Osm calculated = 2 (Na) + BUN/2.8 + glucose/18
ETHANOL
EPIDEMIOLOGY
Ethanol is the most frequently ingested intoxicant in the United States and contributes to about 100,000 deaths per year. Roughly 3% of all ED visits are related to ethanol use.
PATHOPHYSIOLOGY
Ethanol is a central nervous system (CNS) and respiratory depressant through complex mechanisms. Although acute ethanol intoxication may cause death from respiratory depression, morbidity and mortality are usually related to accidental injury resulting from impaired cognitive function.
The major site of absorption is in the proximal small bowel, and is metabolized in the liver by alcohol dehydrogenase. Approximately 10% is excreted unchanged through the lungs and urine.
On average, nondrinkers eliminate ethanol from the bloodstream at a rate of 15 to 20 milligrams/dL/h and chronic drinkers at a rate of up to 30 milligrams/dL/h.
CLINICAL FEATURES
Signs and symptoms of ethanol intoxication include slurred speech, disinhibited behavior, CNS depression, and altered coordination. Lowering of blood pressure with reflex tachycardia may be seen.
DIAGNOSIS AND DIFFERENTIAL
Diagnosis is based on clinical presentation with confirmation of ethanol intake by history or serum ethanol level.
The differential diagnosis is broad and includes other CNS depressants such as benzodiazepines, barbiturates, narcotics, as well as other toxic alcohols. Head injury or hypoglycemia can present with altered mental status, and their identification can be complicated by ethanol intoxication.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
The mainstay of treatment is observation and supportive care.
Exclude hypoglycemia by measuring fingerstick glucose. IV glucose should be administered as needed, and is unlikely to precipitate acute Wernicke encephalopathy, although prior administration of thiamine (100 milligrams IV/IM) is commonly used in chronic alcoholics.
Complicating injury or illness must be excluded, and deterioration or lack of improvement during observation should be considered secondary to causes other than ethanol and managed accordingly.
IV fluids do not alter alcohol elimination and are not required for ethanol intoxication alone; there is little evidence to support the use of IV fluids containing magnesium, folate, thiamine, and multivitamins (“banana bag”) for acute intoxication.
Discharge criteria include sobriety to the extent that there is no threat of harm to self or others.
ISOPROPANOL
EPIDEMIOLOGY
Isopropanol is commonly found in rubbing alcohol, solvents, skin and hair products, paint thinners, and antifreeze.
PATHOPHYSIOLOGY
Most isopropanol is rapidly absorbed with peak blood levels 30 to 120 minutes after ingestion.
The CNS depressant effects are twice as potent and twice as long lasting as ethanol.
Isopropanol is metabolized in the liver to acetone. Acetone is further metabolized to acetate and formate, but not in amounts that cause a significant metabolic acidosis.
CLINICAL FEATURES
Isopropanol intoxication manifests similarly to that of ethanol except the duration is longer and the CNS depressant effects are more profound.
The smell of rubbing alcohol or the fruity odor of ketones may be noted on the patient’s breath.
Severe poisoning is marked by coma, respiratory depression, and hypotension.
Hemorrhagic gastritis is a characteristic finding that causes nausea, vomiting, abdominal pain, and upper gastrointestinal (GI) bleeding, which can be severe.
DIAGNOSIS AND DIFFERENTIAL
Diagnosis is based on clinical features and an elevated isopropanol level. Accumulation of acetone may cause mild ketonemia and ketonuria without hyperglycemia or glycosuria.
Mild acidosis may be present as well as an elevated osmolar gap.
Isopropanol intoxication is typically distinguished from that of other alcohols by the significant osmolal gap without a significant anion gap metabolic acidosis and a negative ethanol level.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
General supportive measures are indicated, including consideration of administration of glucose, thiamine, and naloxone as with any patient who presents with altered mental status.
Hypotension usually responds to IV fluids, but vaso-pressors may be necessary.
Severe hemorrhagic gastritis may require transfusion.
Hemodialysis removes both isopropanol and acetone and is indicated for refractory hypotension or a serum isopropanol level greater than 400 milligrams/dL.
Patients with prolonged CNS depression require admission. Those who are asymptomatic after 4 to 6 hours of observation can be discharged or referred for psychiatric evaluation if indicated.
METHANOL AND ETHYLENE GLYCOL
EPIDEMIOLOGY
Methanol is commonly found as a solvent in paint products, windshield wiper fluid, and antifreeze.
Ethylene glycol is commonly used as antifreeze, and is found in polishes and detergents.
PATHOPHYSIOLOGY OF METHANOL
Methanol is metabolized in the liver by alcohol dehy-drogenase to the toxic compounds formaldehyde and then formic acid. In the presence of folate, formic acid is converted to carbon dioxide and water.
Methanol accumulation results in an elevated osmolal gap.
Formaldehyde accumulation in the retina causes edema and optic papillitis.
Formic acid accumulation results in a high anion gap metabolic acidosis.
Methanol is a potent GI mucosal irritant and causes pancreatitis and gastritis.
PATHOPHYSIOLOGY OF ETHYLENE GLYCOL
Ethylene glycol is metabolized in the liver by alcohol dehydrogenase to the toxic compound glycoaldehyde. This is further metabolized to glycolic acid, and then glyoxylic acid. The major pathway after this converts it to oxalic acid. In the presence of thiamine or pyridoxine, glyoxylic acid is converted to nontoxic metabolites.
Ethylene glycol accumulation results in a high osmolal gap, although toxicity can occur with a normal osmolal gap.
Acid metabolite accumulation eventually causes an anion gap metabolic acidosis.
Oxalic acid precipitates with calcium to form calcium oxalate crystals found in the urine and tissues.
CLINICAL FEATURES OF METHANOL POISONING
Symptoms may not appear for 12 to 24 hours after ingestion and may be delayed further if ethanol is consumed, as ethanol inhibits methanol metabolism.
Symptoms include altered mental status, visual disturbances (classically, feeling as if one is looking at a snowstorm), abdominal pain, nausea, and vomiting.
GI symptoms may be caused by direct mucosal irritation or pancreatitis.
Physical examination reveals varying degrees of CNS depression.
Funduscopic examination may reveal papilledema.
CLINICAL FEATURES OF ETHYLENE GLYCOL POISONING
Ethylene glycol poisoning often exhibits three distinct clinical phases:
In the first 12 hours, CNS effects predominate: patients appear intoxicated without the odor of ethanol on the breath.
Twelve to 24 hours after ingestion, cardiopulmo-nary effects predominate: tachycardia, tachypnea, and hypertension are common; congestive heart failure, acute respiratory distress syndrome, and circulatory collapse may develop.
Twenty-four to 72 hours after ingestion, renal effects predominate characterized by flank pain, costovertebral angle tenderness, and acute tubular necrosis with acute renal failure.
Hypocalcemia may result from precipitation of calcium oxalate into tissues and can cause tetany and ECG changes (prolonged QT interval).
DIAGNOSIS AND DIFFERENTIAL
Diagnosis is based on clinical presentation and laboratory findings. Serum methanol or ethylene glycol levels provide definitive diagnosis, although may not be readily available. Metabolic acidosis with elevated anion gap and an elevated osmolal gap are often present (although dependent on the time of ingestion, and potentially absent even with toxic levels) and can be useful diagnostic clues.
Other laboratory abnormalities include hypocalcemia, leukocytosis, and calcium oxalate crystals in the urine (ethylene glycol).
Ethylene glycol poisoning differs from methanol poisoning in that visual disturbances and funduscopic abnormalities are absent and calcium oxalate crystals are present in the urine.
Differential diagnosis includes other causes of an anion gap metabolic acidosis such as iron, salicylate, or isoniazid toxicity; diabetic or alcoholic ketoacido-sis; uremia; and lactic acidosis.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
General supportive measures are indicated, including support of the airway, breathing, and circulation, and the administration of glucose, thiamine, and naloxone in the undifferentiated patient with altered mental status.
Charcoal does not bind toxic alcohols and has no role in isolated methanol or ethylene glycol poisoning.
Specific treatment is directed toward preventing formation and removing toxic metabolites.
Both fomepizole and ethanol have a greater affinity for alcohol dehydrogenase than methanol or ethylene glycol and therefore block metabolism to toxic compounds. Indications for initiating metabolic blockade are listed in Table 106-1.
Administer fomepizole 15 milligrams/kg IV load over 30 minutes followed by 10 milligrams/kg every 12 hours. Fomepizole is a potent inhibitor of alcohol dehydrogenase with greater affinity and fewer side effects than ethanol.
If fomepizole is not available, or the patient allergic, use ethanol 800 milligrams/kg IV load, followed by a continuous infusion of 100 milligrams/kg/h in the average drinker and 150 milligrams/kg/h in the heavy drinker. The continuous infusion is adjusted to maintain blood ethanol levels of 100 to 150 milligrams/dL.
If necessary, oral therapy with commercial 80 proof liquor can be initiated with a loading dose of 1.5 to 2.0 mL/kg followed by a maintenance dose of 0.2 to 0.5 mL/kg/h. Alternatively, a load of 3 to 4 “shots” with maintenance of 1 to 2 “shots” per hour is a typical dose for a 70-kg patient.
Glucose levels are monitored during treatment with ethanol as hypoglycemia may occur, especially in children.
Dialysis eliminates both methanol and ethylene glycol and their toxic metabolites. Indications for dialysis are listed in Table 106-2.
Use of fomepizole or ethanol does not affect indications for dialysis. Both fomepizole and ethanol are removed by dialysis; therefore, dosing of fomepizole is increased to every 4 hours and the continuous infusion rate of ethanol is doubled initially and readjusted to maintain therapeutic serum levels. Serum ethanol levels should be checked every 1 to 2 hours.
Continue dialysis, fomepizole, or ethanol until the methanol or ethylene glycol level is less than 20 milligrams/dL and acidosis has resolved.
In methanol poisoning, folate 1 milligram/kg (up to 50 milligrams) IV should be given every 4 hours.
In ethylene glycol poisoning, pyridoxine 50 to 100 milligrams andthiamine 100 milligrams IV are administered every 6 hours for 2 days to drive the conversion of toxic to nontoxic metabolites.
Even asymptomatic individuals should be admitted for observation because of possible delayed onset of toxic symptoms.
TABLE 106-1 Indications for Metabolic Blockade I with Fomepizole or Ethanol
TABLE 106-2 Indications for Urgent Hemodialysis after Methanol or Ethylene Glycol Ingestion
For further reading in Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7th ed., see Chapter 179, “Alcohols,” by Jennifer C. Smith and Dan Quan.