Efficacy of 4-methylpyrazole for treatment of ethylene glycol intoxication in dogs

Abstract

Summary 4-Methylpyrazole (4-mp), an alcohol dehydrogenase inhibitor, was administered to dogs to treat ethylene glycol (eg) intoxication. Eleven dogs were given 10.6 g of eg/kg of body weight; 5 dogs were treated with 4-mp 5 hours after eg ingestion and 6 dogs were treated with 4-mp 8 hours after eg ingestion. 4-Methylpyrazole was administered iv as a 50-mg/dl solution in 50% polyethylene glycol: initial dose, 20 mg/kg; at 12 hours after initial dose, 15 mg/kg; at 24 hours after initial dose, 10 mg/kg; and at 30 hours after initial dose, 5 mg/kg. Physical, biochemical, hematologic, blood gas, serum and urine eg concentrations, and urinalysis findings were evaluated at 0, 1, 3, 6, 9, 12, 24, 48, 72 hours, and at 1 week and 2 weeks after eg ingestion. Dogs of both groups developed clinicopathologic signs associated with eg intoxication, including cns depression, hyperosmolality, high anion gap metabolic acidosis, polydipsia, polyuria, calcium oxalate monohydrate and dihydrate crystalluria, and isosthenuria. Fractional excretion of sodium was increased in all dogs between 1 and 9 hours after eg ingestion, but remained increased beyond 24 hours only in the 2 dogs treated at 8 hours after eg ingestion that developed acute renal failure. All dogs treated 5 hours after eg ingestion recovered without morphologic, biochemical, or clinical evidence of renal impairment. Of the 6 dogs treated 8 hours after eg ingestion, 2 developed acute renal failure. One of the dogs treated 8 hours after eg ingestion remained isosthenuric for 2 months, but did not manifest any other signs of renal impairment. Of the dogs treated 8 hours after eg ingestion, 3 recovered without morphologic, biochemical, or clinical evidence of renal impairment. Serum half-life of eg was prolonged in the dogs treated 8 hours after eg ingestion. Percentage of eg excreted unchanged was 84 ± 2% in the dogs treated 5 hours after eg ingestion, and was 40 ± 10% in the dogs treated 8 hours after eg ingestion. 4-Methylpyrazole was effective in preventing renal failure in all dogs given 10.6 g of eg/kg when treatment was initiated by 5 hours after eg ingestion, and in 4 of 6 dogs when treatment was initiated by 8 hours after eg ingestion.