Chapter 104. Alcohols

All alcohols are potentially toxic and cause clinical inebriation and an anion gap metabolic acidosis. Ethanol and isopropanol are the most commonly ingested alcohols and cause direct toxicity, while methanol and ethylene glycol cause toxicity as a result of conversion to toxic metabolites.

Although acute ethanol intoxication may cause death directly from respiratory depression, morbidity and mortality are usually related to trauma from impaired cognitive function. On an average, nondrinkers eliminate ethanol from the bloodstream at a rate of 15 to 20 milligrams/dL/h and chronic drinkers at about 30 milligrams/dL/h.

Clinical Features

Signs and symptoms of ethanol intoxication include slurred speech, disinhibited behavior, central nervous system (CNS) depression, and altered coordination. Manifestations of serious head injury or hypoglycemia may be identical to, or clouded by, ethanol intoxication. Nystagmus and a characteristic odor of ethanol may be observed.

Diagnosis and Differential

Check a bedside glucose in all patients with altered mental status. Serum ethanol levels will confirm ethanol intoxication but are not required for mild to moderate intoxication. Consider comorbid disease or injury in the inebriated patient and obtain additional labs as indicated: electrolytes may demonstrate an anion gap acidosis; liver enzymes may reveal hepatic damage; a urine toxicology screen may reveal coingestion of other drugs of abuse. Obtain imaging as indicated by external signs of trauma in the inebriated patient.

Emergency Department Care and Disposition

1. The mainstay of treatment is observation. A careful physical examination should be performed to evaluate for complicating injury or illness.

2. Treat hypoglycemia with IV dextrose. Thiamine 100 milligrams IV or IM may be given concurrently if Wernicke encephalopathy is suspected.

3. Consider secondary causes of deterioration or lack of improvement during observation and manage accordingly.

4. Discharge the patient once sober enough to pose no threat to self or others.

Isopropanol is commonly found in rubbing alcohol, solvents, skin and hair products, paint thinners, and antifreeze. Acetone is the principle toxic metabolite.

Clinical Features

Clinically, isopropanol intoxication is similar to that of ethanol but lasts longer with deeper CNS depression. The smell of rubbing alcohol or the fruity odor of ketones may be noted on the patient's breath. Severe poisoning presents as coma, respiratory depression, and hypotension. Hemorrhagic gastritis is common and causes nausea, vomiting, abdominal pain, and upper gastrointestinal bleeding.

Diagnosis and Differential

Check a bedside glucose in all patients with altered mental status. Classic isopropanol toxicity is associated with an elevated osmolal gap, ketonemia and ketonuria, without acidosis. In the setting of upper GI bleeding, coagulation studies, a CBC, and a type and screen should be obtained. When available, a serum isopropanol and acetone level confirm the diagnosis.

Emergency Department Care and Disposition

1. Treat hypotension with aggressive infusion of IV crystalloids though persistent hypotension may require vasopressors. Treat significant bleeding from hemorrhagic gastritis with transfusion of packed red blood cells and plasma as indicated.

2. Do not administer metabolic blockade with Fomepizole or ethanol since acetone, the metabolite of isopropanol, is no more toxic than the parent compound.

3. Hemodialysis is indicated for refractory hypotension or an isopropanol level >400 milligrams/dL. Hemodialysis removes both isopropanol and acetone.

4. Patients with prolonged CNS depression require admission. Those who are asymptomatic after 6 to 8 hours of observation can be discharged or referred for psychiatric evaluation if indicated.

5. Charcoal does not bind alcohols, and is useful only if there is coingestion of an absorbable substance.

Methanol is a common solvent in paint products, windshield washing fluid, and antifreeze. Ethylene glycol is found in coolants, polishes, and detergents. Toxicity from these alcohols results from the formation of toxic metabolites, which produce a significant anion gap metabolic acidosis. Methanol leads to the formation of toxic formaldehyde and formic acid, while ethylene glycol is metabolized into the toxic compounds glycolic and glyoxylic acid.

Clinical Features

Symptoms of methanol toxicity may not appear for 12 to 24 hours after ingestion until toxic metabolites accumulate. Time to symptom onset may be longer if ethanol is consumed, as ethanol inhibits methanol metabolism. Signs and symptoms include CNS depression, visual disturbances (classically, a complaint of looking at a snowstorm), abdominal pain, nausea, and vomiting. The gastrointestinal symptoms may be due to mucosal irritation or pancreatitis. Funduscopic examination may reveal retinal edema or hyperemia of the optic disk.

Ethylene glycol poisoning often exhibits three distinct clinical phases after ingestion. First, within 12 hours, CNS effects predominate: the patient appears intoxicated without the odor of ethanol on the breath. Second, 12 to 24 hours after ingestion, cardiopulmonary effects predominate: elevated heart rate, respiratory rate, and blood pressure are common. Congestive heart failure, respiratory distress syndrome, and circulatory collapse may develop. Third, 24 to 72 hours after ingestion, renal effects predominate which are 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 leading to tetany and typical ECG changes.

Diagnosis and Differential

The diagnosis is based on clinical presentation and laboratory findings of an anion gap metabolic acidosis (which may take hours to develop) with elevated levels of methanol or ethylene glycol. An elevated osmolal gap is present and useful when immediate methanol or ethylene glycol testing is not available. Basic laboratory investigations include a bedside glucose, CBC, BMP, arterial blood gas, urinalysis, and methanol or ethylene glycol level. 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.

The differential diagnosis includes other causes of an anion gap metabolic acidosis such as salicylate or isoniazid toxicity, diabetic ketoacidosis, alcoholic ketoacidosis, uremia, and lactic acidosis.

Emergency Department Care and Disposition

Treatment is based on metabolic blockade and removing toxic metabolites from the body. Both fomepizole and ethanol have a greater affinity for alcohol dehydrogenase than methanol and ethylene glycol. Indications for metabolic blockade are listed in Table 104-1.

1. Administer fomepizole 15 milligrams/kilogram IV load followed by 10 mg/kilogram 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 is allergic, use ethanol 800 milligrams/kilogram IV load, followed by a continuous infusion of 100 milligrams/kilogram/h in the average drinker and 150 milligrams/kilogram/h in the heavy drinker. Adjust the infusion accordingly to maintain a blood ethanol level at 100 to 150 milligrams/dL. If resources are limited, oral therapy with commercial 80 proof liquor can be initiated. A load of 3 to 4 oz with maintenance of 1 to 2 oz/h is a typical dose for a 70 kilograms patient.

2. Monitor serum glucose during treatment with ethanol as hypoglycemia may be induced, especially in children. Treat hypoglycemia with 1 mL/kg 50% dextrose in water in adults and 4 mL/kg 10% dextrose in water in children.

3. Dialysis eliminates both methanol and ethylene glycol and their toxic metabolites. Indications are listed in Table 104-2. Fomepizole or ethanol treatment do not alter the indications for dialysis; however, both fomepizole and ethanol are dialyzed and, therefore, increase the dosing interval of fomepizole to every 4 hours. Double the infusion rate of ethanol during dialysis and adjust accordingly to maintain the level at 100 to150 milligrams/dL.

4. Continue dialysis, fomepizole, or ethanol treatment until the methanol or ethylene glycol level is <20 milligrams/dL and the metabolic acidosis has resolved.

5. In methanol poisoning, administer folate 50 milligrams IV. In ethylene glycol poisoning, administer pyridoxine 100 milligrams IV and thiamine 100 milligrams IV.

6. Administer sodium bicarbonate 1 to 2 mEq/kg and titrated to maintain a normal pH in methanol toxicity to increase renal excretion of formic acid.

7. Treat documented and symptomatic hypocalcemia in ethylene glycol toxicity with calcium gluconate or calcium chloride.

8. Consult a medical toxicologist or regional poison control center to aid in the management of symptomatic methanol or ethylene glycol ingestion.

9. Patients with suspected ethylene glycol ingestion who are asymptomatic after 6 hours with no ethanol detected and no osmolar gap or metabolic acidosis may be safely discharged. Since methanol toxicity and coingestion of ethanol may result in delayed symptoms, these patients should be observed for a minimum of 12 hours. Patients with significant signs and symptoms should be admitted to an intensive care unit.