Current management of ethylene glycol poisoning.
Ethylene glycol, a common antifreeze, coolant and industrial solvent, is responsible for many instances of accidental and intentional poisoning annually. Following ingestion, ethylene glycol is first hepatically metabolised to glycoaldehyde by alcohol dehydrogenase. Glycoaldehyde is then oxidised to glycolic acid, glyoxylic acid and finally oxalic acid. While ethylene glycol itself causes intoxication, the accumulation of toxic metabolites is responsible for the potentially fatal acidosis and renal failure, which characterises ethylene glycol poisoning. Treatment of ethylene glycol poisoning consists of emergent stabilisation, correction of metabolic acidosis, inhibition of further metabolism and enhancing elimination of both unmetabolised parent compound and its metabolites. The prevention of ethylene glycol metabolism is accomplished by the use of antidotes that inhibit alcohol dehydrogenase. Historically, this has been done with intoxicating doses of ethanol. At a sufficiently high concentration, ethanol saturates alcohol dehydrogenase, preventing it from acting on ethylene glycol, thus allowing the latter to be excreted unchanged by the kidneys. However, ethanol therapy is complicated by its own inherent toxicity, and the need to carefully monitor serum ethanol concentrations and adjust the rate of administration. A recent alternative to ethanol therapy is fomepizole, or 4-methylpyrazole. Like ethanol, fomepizole inhibits alcohol dehydrogenase; however it does so without producing serious adverse effects. Unlike ethanol, fomepizole is metabolised in a predictable manner, allowing for the use of a standard, validated administration regimen. Fomepizole therapy eliminates the need for the haemodialysis that is required in selected patients who are non-acidotic and have adequate renal function.
Brent
J
J
Division of Emergency Medicine, University of Colorado Health Sciences Center, Denver, USA. jeffrey.brent@uchsc.edu
D000931:Antidotes / Q000627:therapeutic use*; D000431:Ethanol / Q000627:therapeutic use; D019855:Ethylene Glycol / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics / Q000506:poisoning; D000077604:Fomepizole; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption; D011041:Poisoning / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism / Q000503:physiopathology; D011720:Pyrazoles / Q000627:therapeutic use*
D000931:Antidotes; D011720:Pyrazoles; D000431:Ethanol; D000077604:Fomepizole; D019855:Ethylene Glycol