• Shyam Murali

Deep Dive into Toxic Alcohols - Michael McCrea, MD

Dr. Michael McCrea, our Associate Program Director, recently gave us a lecture about toxic alcohols. Here are the learning pearls from that lecture:

Causes of elevated anion gap metabolic acidosis (image taken from Wikipedia.org)

The first thing to learn with respect to toxic alcohols are the:

Gaps

  1. Anion Gap = [Na] - ([Cl] + [HCO3]), Normal </= 12 Causes of elevated anion gap: "CAT MUDPILES". Among these are both methanol and ethylene glycol (note: ethanol and isopropyl alcohol themselves do not elevate the anion gap)

  2. Osmolar Gap = Measured osmolarity - Calculated osmolarity, Normal </=12 Calculated osmolarity = 2[Na] + [Glucose]/18 + [BUN]/2.8, Normal 285-295 Causes of elevated osmolar gap: "ME DIE" mnemonic Tip: multiply the osmolar gap by the conversion factor* to estimate the amount of toxic alcohol in mg/dL

*Conversion factors for various alcohols (image taken from Cancer Therapy Advisor)

The anion gap and osmolar gap can give you valuable information about what substance has been ingested, and roughly how much.

Methanol

  • Sources: windshield washer fluid, solvents, sterno cooking fuel, moonshine, pesticide

  • Toxic metabolite, Formic Acid, causes symptoms

  • Elevated anion gap AND osmolar gap

  • Symptoms: inebriation, blindness (directly toxic to the optic disc and optic nerve), "snowstorm" vision. Basal ganglia hemorrhages.

  • Toxic level is >20mg/dL

  • Treatment: - Folate: cofactor for formic acid metabolism. Goal is to get rid of the toxic metabolite quickly. - Give 1-2mEq/kg of Sodium Bicarbonate if pH<7.3 - Ethanol: oral or IV to achieve ethanol level of 100-150mg/dL • Oral: 0.8mg/kg 20% EtOH solution in diluted orange juice, then 80mg/kg/hr • IV: 10mL/kg 10% EtOH solution in D5W over 60 minutes, then 1mL/kg/hr of 10% EtOH solution (titrate to serum ethanol levels) - Fomepizole: 8000x affinity for alcohol dehydrogenase • IV: 15mg/kg, then 10mg/kg every 12 hours for 4 doses, then 15mg/kg every 12 hours

  • Indications for dialysis: - Intractable acidosis - Acute renal failure - ANY visual symptoms - Methanol >50mg/dL


Ethylene Glycol

  • Sources: radiator antifreeze

  • Toxic metabolites: - Glycolic Acid: exerts its toxicity through oxalic acid - Glyoxylic Acid: exerts its toxicity through oxalic acid - Oxalic Acid: causes hypocalcemia and QTc prolongation; binds with calcium to form calcium oxalate crystals that precipitate in the kidneys causing renal failure

  • Elevated anion gap AND osmolar gap

  • Symptoms: inebriation, neurologic effects (coma, seizures, cranial nerve deficits), cardiovascular effects (tachycardia, hyperventilation, ARDS, heart failure), oliguria, flank pain

  • Toxic level is >20mg/dL

  • Treatment: - Thiamine: 100mg IV daily until symptoms or acidosis resolves; facilitates breakdown of toxic metabolite - Pyridoxine (Vitamin B6): 10-25mg IV daily; facilitates breakdown of toxic metabolite - Sodium bicarbonate, Ethanol, and Fomepizole as above

  • Indications for dialysis (similar to methanol above): - Intractable acidosis - Acute renal failure - ANY visual symptoms - Ethylene glycol >50mg/dL

Extra Pearls

  • Common elements for both methanol and ethylene glycol: - Elevated anion gap - Elevated osmolar gap - Toxic level is >20mg/dL - Dialysis level is >50mg/dL, other dialysis indications are similar

  • Buzz words: - Methanol: formic acid; blindness or "snowstorm" vision; treat with folate and ethanol or fomepizole, +/-Sodium bicarb - Ethylene glycol: antifreeze; oxalic acid, glyoxylic acid, glycolic acid; treat with thiamine, pyridoxine, and ethanol or fomepizole, +/-Sodium bicarb

  • FOUR things give elevated anion gap AND elevated osmolar gap - Methanol - Ethylene Glycol - Alcoholic ketoacidosis if ethanol is still high - Diabetic ketoacidosis if glucose is very high


References and other resources to check out:

  1. Episode 43 - Alcohols by Lauren Westafer and Jeremy Faust on FOAMCast.org

  2. Toxic Alcohol Ingestion by Edward Burns on Life in the Fast Lane

  3. Methanol Toxicology and Ethylene Glycol Toxicology on EBM Consult

  4. Hassanian-Moghaddam H, Zamani N. A Brief Review on Toxic Alcohols. Iranian Journal of Kidney Diseases. 2016;10:344-50.

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