Glycolate kinetics and hemodialysis clearance in ethylene glycol poisoning. META Study Group.

Abstract

Toxic manifestations following ethylene glycol exposure are due to accumulation of metabolites, particularly glycolate. We characterized glycolate elimination kinetics and dialysis properties in a series of ethylene glycol poisonings. Patients who ingested ethylene glycol and received fomepizole (4-methylpyrazole; 4-MP) +/- hemodialysis were prospectively evaluated. Serial blood samples for ethylene glycol, glycolate, pH, and bicarbonate were drawn to determine glycolate elimination rate, t1/2, and correlations between initial glycolate and initial markers of acidosis. Dialyzer inlet and outlet samples were obtained to measure hemodialysis glycolate clearance. Plasma ethylene glycol and glycolate were determined by gas chromatography. Ten patients, mean age 49 years (range 28-73 years), presented a mean of 10.5 hours (range 3.5-21.5 hours) after ethylene glycol ingestion. Mean initial ethylene glycol was 18.5 mmol/L (range 0.8-62.2 mmol/L) (115 mg/dL; range 5-386 mg/dL) and glycolate was 17.0 mmol/L (range 10.0-23.7 mmol/L). Nine of 10 underwent hemodialysis. Nonhemodialysis (n = 4) elimination rate was 1.08 +/- 0.67 mmol/L/h (mean +/- SD) and t1/2 was 626 +/- 474 minutes. Elimination t1/2 during hemodialysis (n = 8) was 155 +/- 42 minutes. Hemodialysis clearance (n = 5) was 170 +/- 23 mL/min with flow rates 250-400 mL/min. Pearson correlation coefficients were: anion gap vs glycolate r2 = 0.65 (p = 0.005), bicarbonate vs glycolate r2 = 0.10 (NS) and pH vs glycolate r2 = 0.06 (NS). Glycolate has a slow elimination rate and long half-life. Hemodialysis effectively clears glycolate. An increased anion gap correlates with the presence of glycolate. Hemodialysis is projected as useful for ethylene glycol-poisoned patients with anion gap acidosis and low ethylene glycol blood levels.