Question 19.2

List 3 drugs or poisons that, when taken as an overdose, result in both a raised osmolar gap and anion gap. List the major anion associated with each drug responsible for the rise in anion gap.

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College Answer

Drug                                            Anion
Ethanol                                   - Lactate
Methanol                                 - Formate or formic acid
Ethylene glycol                       - Glycolate / oxalate


Ethanol overindulgeance can indeed cause a lactic acidosis, but I would have chosen a different drug:

  • Toxicological causes of high anion and high osmolar gap
    • Methanol intoxication (the anion is formic acid)
    • Ethylene glycol intoxication (the anions are glycolic acid and oxalic acid)
    • Diethylene glycol intoxication (the anion is 2-hydroxyethoxyacetic acid, HEAA)
    • Propylene glycol intoxication (the anions are pyruvate, lactate and acetate)
    • Salicylate intoxication (the anions are salicylate and lactate)
    • Any toxin causing massive lactic acidosis, eg. isoniazid
  • Endocrine and metabolic causes of high anion and high osmolar gap
    • Lactic acidosis
    • Alcoholic or diabetic ketoacidosis
    • Acute kidney injury


Erstad, Brian L. "Osmolality and osmolarity: narrowing the terminology gap."Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy23.9 (2003): 1085-1086.

Gennari, F. John. "Current concepts. Serum osmolality. Uses and limitations."The New England journal of medicine 310.2 (1984): 102-105.

Hoffman, Robert S., et al. "Osmol gaps revisited: normal values and limitations."Clinical Toxicology 31.1 (1993): 81-93.

Dorwart, William V., and Leslie Chalmers. "Comparison of methods for calculating serum osmolality from chemical concentrations, and the prognostic value of such calculations." Clinical chemistry 21.2 (1975): 190-194.

Kraut, Jeffrey A., and Shelly Xiaolei Xing. "Approach to the evaluation of a patient with an increased serum osmolal gap and high-anion-gap metabolic acidosis." American Journal of Kidney Diseases 58.3 (2011): 480-484.