Toxic Alcohols

The Compounds

Pathophysiology

Ethylene Glycol

Methanol

Isopropanol

Assessment

Key Points

References

About This Document

The Compounds:

· Ethylene glycol

· Methanol

· Isopropanol

Pathophysiology:

· All cause inebriation with mental status changes. None are toxic until metabolized.

· All cause a serum osmolar gap soon after ingestion, which helps with early identification.

· With metabolism, the osmolar gap decreases, and, with ethylene glycol and methanol, a metabolic acidosis develops [Figure 1].

· The acidosis is the cause of the end-organ damage recognized as the specific pattern of injury associated with each of these toxins.

· These toxic alcohols follow a common metabolic pathway via the enzyme alcohol dehydrogenase (ADH). Substrate substitution using ethanol will furnish a preferred metabolic pathway and help prevent development of acidosis and toxic metabolites. Co-injestion of alcohol is, therefore, protective.

· Enzyme blocking agents such a fomepizole can be protective.

· The time of ingestion and the half-life of the alcohol ingested will direct us to the segment of the graph we should use for individual cases for ethylene glycol and methanol [Figure 1].

· Often, more than 1 set of laboratory values obtained several hours apart are required to determine the degree of toxicity in an individual patient.

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Figure 1:

Figure 2:

Ethylene glycol:

Metabolic features:

• Ethylene glycol is found mostly in coolant mixtures, such as radiator antifreeze.
• Sweet tasting - animals and young children might consume considerable amounts of this poison.
• Short half-life of approximately 3 hours, so initial and 6-hour serum electrolytes and serum osmolality are sufficient to rule out serious toxicity.
• Alcohol dehydrogenase metabolizes ethylene glycol to glycoaldehyde, then aldehyde dehydrogenase further metabolizes glycoaldehyde into glycolic acid. The glycolic acid is then further metabolized into glyoxylic acid and finally into either glutamate or -ketoadipic acid or very toxic oxalate metabolites.
• A vitamin such as folic acid reduces the production of oxalate. If oxalate is formed, calcium oxalate is then also formed and deposited in the renal cortex and other tissues—the result is end-organ damage.

Toxicity follows a 3-phased pattern:

• In the first 12 hours postingestion, the patient will be inebriated, have some nausea and vomiting, and be somnolent. A few patients will be comatose.
• In the second phase, between 12 and 24 hours postingestion, symptoms include tachycardia, pulmonary edema, and hypocalcemia. The QTc interval can be prolonged via effects on calcium.
• The third and last phase consists of acute tubular necrosis and renal failure, and begins 24 hours post ingestion.

Ancillary evaluations:

· Urinalysis for calcium oxalate crystals.

· Wood lamp (UV light) examination of the urine, as almost all radiator fluids have fluorescein added to facilitate the detection of leaks. Fluorescein in the urine is contributory; however, a negative UV light test does not rule out ethylene glycol ingestion.

Management:

· Supportive care

· Consider folic acid

· ADH blockade with ethanol or fomepizole.

· Bicarbonate will limit penetration of toxic alcohols into end organs.

· Dialysis if necessary

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Methanol:

Metabolic features:

· Methanol is found in industrial solvents, paints and varnishes, windshield-washer fluid, Sterno fuel, and, sometimes, moonshine.

· It can be ingested unintentionally in alcoholic beverages or intentionally in solvent form. Intentional methanol ingestions are cause for serious concern.

· Methanol has a much longer half-life than the other toxic alcohols, approximately 8 hours, so serum electrolytes and levels must be repeated at far wider intervals than for ethylene glycol.

· Methanol is rapidly absorbed after ingestion and metabolized to formaldehyde by ADH.

· Methanol levels peak at 30 to 90 minutes postingestion. These correlate poorly with the degree of toxicity and we recommend formic acid levels. Then aldehyde dehydrogenase rapidly metabolizes the formaldehyde into formic acid, a very toxic metabolite.

· The formate accumulates in the body resulting in a metabolic acidosis, in addition to neurologic and ophthalmologic manifestations. In the presence of folate, the formic acid is reduced to carbon dioxide and water.

Toxicity also consists of 3 phases:

• Initially, there is inebriation.
• After a 12- to 24-hour lag postingestion, toxic manifestations begin to develop.
• Following the second phase, severe metabolic acidosis, visual disturbance, including the appearance of blurred vision and flashing lights, and neurologic manifestations, such as Parkinson-like syndrome, might be present.

Management:

· Supportive care

· Consider folic acid

· ADH blockade with ethanol or fomepizole.

· Bicarbonate will limit penetration of toxic alcohols into end organs.

· Dialysis if necessary

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Isopropanol:

Metabolic features:

· Isopropanol is found in rubbing alcohol (70%), some cleaning products, and many personal hygiene products.

· This alcohol produces an intense inebriation and more severe respiratory and neurologic depression than the other 2 toxic alcohols. Gastritis is also a frequent clinical finding in isopropanol poisonings.

· It causes an elevated osmolal gap without and elevated anion gap. It is not associated with the end organ toxicity of the other 2 toxic alcohols.

· Isopropanol is readily absorbed through the gastrointestinal tract and, unlike the other alcohols, toxicity can result from excessive dermal exposure.

· GI decontamination is not helpful, as it is rapidly absorbed. Approximately 30% of isopropanol is excreted unchanged through the kidney, while ADH metabolizes the other 70% into acetone, which is excreted through the lungs or the kidneys.

· A hallmark of ingestion is marked ketonuria and ketonemia in absence of acidosis.

Management:

· Supportive care.

· Special attention should be given to airway management owing to the degree of coma and respiratory depression coupled with severe gastritis. Intubation may be necessary.

· In severely symptomatic patients with cardiac manifestations, fluids and pressors should be considered, however management is usually supportive.

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Assessment of patient

History

• route of ingestion and source (physicians should make every attempt to obtain container in order to have access to accurate information about the contents of the ingestant),
• circumstances and intent,
• quantity ingested, and
• known or possible co-ingestants, most specifically ethanol.

Physical examination

• skin,
• neurologic,
• cardiorespiratory, and
• abdominal examinations.

· Laboratory evaluation

• complete blood count,
• serum electrolytes,
• serum osmolality,
• acetaminophen and acetylsalicylic acid levels
• glucose level
• ethanol and toxic alcohol levels.
• β-human chorionic gonadotropin test in female patients of childbearing age.
• ECG
• creatinine, calcium
• calculation of anion gap and osmolar gap [Figure 2].

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Key Points:

• Part of the differential in coma (all 3) or metabolic acidosis (propylene glycol and methanol).
• Take a history in order to rule out co-ingestants.
• Calculate and carefully interpret anion and osmolar gaps [Figure 2].
• Two sets of blood tests taken several hours apart are required.
• Use alcohol dehydrogenase blockade with fomepizole or ethanol for management.
• Be prepared for good supportive care including airway.

· Dialysis is indicated if a patient is comatose, has severe metabolic acidosis, or has large intentional ingestion.

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References:

1. LeBlanc C, Murphy N. Shoud I stay or should I go? Toxic alcohol case in the emergency department. Canadian Family Physician 2009; 55: 46-49.
2. Sivilotti MLA. Isopropyl alcohol intoxication. In: UpToDate, Rose, BD (Ed), UpToDate, Waltham, MA, 2008.
3. Sivilotti MLA. Methanol and ethylene glycol intoxication. In: UpToDate, Rose, BD (Ed), UpToDate, Waltham, MA, 2008.

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