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Ethylene Glycol Intoxication 7/11/10 PY Mindmaps - relatively non-toxic -> metabolites extremely toxic (glycolate) - rate limiting step = alcohol dehydrogenase activity - accumulation of glycolate -> direct cellular toxicity CLINICAL FEATURES - drunk: automotive antifreeze, solvent, polish, paints, cosmetics, brake fluid, car wash fluid. - 30 minutes -> 12 hours post ingestion:excitement, confusion, disorientation -> ataxia, lethargy, stupor, coma, nausea/vomiting, myoclonus, seizures, cranial nerve deficits: nystagmus, ophthalmoplegia, facial palsy, dysarthria, dysphagia - 12 – 24 hours: progressive cardiorespiratory failure - 24 – 72 hours: renal failure from ATN - toxic dose = 1.5mL/kg of 95% ethylene glycol INVESTIGATIONS - ethylene glycol level - severe metabolic acidosis (high anion gap) from glycolic acid accumulation - very high lactate (artefactual as there is high cross reactivity between lactate and glycolate in laboratory analysis) -> high lactate with oxidase method, less high with lactate dehydrogenase method - high osmolar gap - calcium oxalate crystalluria (oxalate produced by ethylene glycol metabolism chelates Ca2+ -> formation of crystals) + hypocalcaemia - fluorescence of urine on exposure to UV light (automotive antifreeze solutions have this to identify cooling system leaks) MANAGEMENT - goal = blockade of alcohol dehydrogenase -> so ethylene glycol isn’t converted to glycolate - decrease absorption: no techniques really effective - decrease production of toxic metabolites: ethanol or 4-methylpyrazole (not easily available in Australiasia) -> ethanol dose (IV): 10% solution in D5W as a 40% solution, loading dose 7.5mL/kg -> 1-2mL/kg/hr -> ethanol dose (PO): quarter the above dose -> dose in CRRT: double IV dose -> maintain ethanol level @ 25-40mmol/L - haemodialysis thamine 100mg IV Q6 hrly – theoretical benefit to increase elimination pyridoxine (vitamin B6) 50mg IV Q6hrly – theoretical benefit to increase elimination don’t replace Ca2+ unless low enough to cause manifestations Jeremy Fernando (2011)