Putting the freeze on antifreeze
Written by Curtis Elko, PharmD, CSPI at the Washington Poison Center
TL;DR
- “Antifreeze” is a common term for alcohols and glycols, including methanol (MeOH), ethylene glycol (EG), and diethylene glycol (DEG). These compounds can cause severe toxicity, including acidosis, liver or kidney failure, and neurologic damage, which can lead to permanent injury or death.
- Early recognition and intervention are the cornerstones for preventing illness. While each of these compounds have their own toxicity, their metabolites are what lead to morbidity and mortality. Blocking metabolic conversion with ethanol or fomepizole (4MP) provides the best chance for a positive outcome. Enhanced elimination by dialysis may rescue an already sickened patient.
- Poison centers can help practitioners identify the patient at-risk who will benefit from these life-saving measures and avoid the consequences of these life-threatening exposures.
Background
Toxic alcohol poisoning is nothing new. During Prohibition in the 1920’s– 1930’s, ethanol (drinking alcohol) was contaminated with methanol. In 1938, a sulfanilamide elixir was “sweetened” with diethylene glycol. Throughout the early 20th century, people drank ethylene glycol products meant for cooling internal combustion engines. Today, methanol (MeOH), diethylene glycol (DEG), and ethylene glycol (EG) are still used in “antifreeze” products and continue to be implicated in poisonings and fatalities.
Historically, toxic alcohol poisoned patients were managed with sodium bicarbonate (for acidosis) and with supportive care until recovery or death. However, recovery was often partial, with MeOH and EG causing neural damage and renal failure, respectively. By the late 1940’s to early 1950’s, medical practice came to recognize that toxicity is prevented or limited by the co-administration of ethanol, an inhibitor of the ADH enzyme. Providers have now largely replaced ethanol with fomepizole (4-methylpyrazole, 4-MP) as the ADH-blocker of choice. DEG toxicity is also managed with this antidote.
Pathophysiology
The enzymes responsible for the transformation from a “safe” to “toxic” alcohol or glycol are primarily Alcohol dehydrogenase and Aldehyde Dehydrogenase (ADH). Unlike ethanol and isopropyl alcohol, MeOH/EG/DEG produce less CNS depression and cause more metabolic toxicity — the earliest finding may be the presence of an osmol gap created by the parent compound. As ADH metabolism commences, accumulation of toxic acid metabolites results in an anion gap metabolic acidosis that becomes progressively severe. Later in the course, optic nerve damage by MeOH or renal dysfunction by EG and DEG emerges. Hypotension, dysrhythmias, coma, and seizures signal a poor prognosis. Alternatively, with early recognition and treatment, patients may resolve with few consequences.
Diagnostic Testing
Obtain these specimens simultaneously for correct interpretation
- Blood gas (venous draw acceptable) → pH and bicarbonate assessment of metabolic acidosis
- Complete Metabolic Panel → anion gap, sodium, BUN, and glucose
- Measured serum osmolarity and osmol gap calculation → increased osmol gap suggests presence of unmeasured glycols/alcohols
- Quantitative ETOH, MeOH, isopropyl alcohol, acetone and EG levels → other alcohols or glycols usually unavailable
Contact the poison center (1–800–222–1222) for laboratory interpretation guidance and therapeutic intervention recommendations.
Treatment
Documenting exposure history and laboratory testing are crucial for managing MeOH/EG/DEG toxicity. Once recognized, management may involve early gastrointestinal decontamination, serial laboratory evaluation, ADH metabolism blockade, and, if necessary, hemodialysis.
Following blood draws, administer 4-MP and consider hemodialysis. If alcohol/glycol levels are negative, then ADH-blocking is usually discontinued.
Pitfalls
Do not be misled by low EG or MeOH levels accompanied by an anion gap metabolic acidosis. This late presentation where the parent compound is already transformed to toxic metabolites is usually managed with 4-MP and hemodialysis until the glycol/alcohol level is < 20 mg/dL and the acidosis is resolved.
In alcoholic/diabetic/starvation ketoacidosis, the appropriate treatment for restoring normal glucose metabolism can quickly eliminate the acid/base abnormalities. When patients are not responding or worsening, and have persistent acidosis, consider the addition of 4-MP or dialysis until the problem is resolved.
Contact the poison center early to save valuable time, avoid costly mistakes, and put the freeze on antifreeze!
