Formate Kinetics in Methanol Poisoning

Abstract

Objective: We sought to describe the kinetics, dialysis clearance, and laboratory markers of formate (FA), the toxic metabolite of methanol (meOH). Methods: Data were obtained from a prospective, multicenter study of fomepizole±dialysis for methanol poisoning. Inclusion criteria confirmed methanol exposure or suspicion of exposure plus either acidemia or abnormal osmolar gap. Dialysis indications were [meOH]>50 mg/dL, pH<7.1, refractory acidosis, or visual toxicity. Serial plasma formate, methanol, pH, and electrolyte measurements were made. Formate was determined by gas chromatography. Endogenous and dialysis elimination half-lives were calculated as t_1/2=0.693/Ke, with Ke (elimination constant) derived from the slope of log (FA) vs. time. Half-lives were compared with an unpaired Student's t-test. Dialysis clearance was calculated using the Fick Principle. Pearson correlation analysis compared initial formate with initial pH, serum bicarbonate, and anion gap. Results: Eleven patients were treated in the study. Eight had detectable formate with mean [FA] of 15.1 mmol/L (range 0.5–34.8). Endogenous elimination half-life was 205±90 minutes. Elimination half-life during dialysis (n=5) was 150±37 minutes, which was not different (t=0.22; NS). The overall dialysis formate clearance rate was 223±25 mL/min. Correlation coefficients were: pH vs. formate r²=0.93; bicarbonate vs. formate r²=0.81; and anion gap vs. formate r²=0.76 (all p<0.05). Conclusions: Although dialysis clears formate, it did not significantly enhance endogenous elimination in our series of patients. Low pH, low bicarbonate, and elevated anion gap correlate independently with formate presence.

Keywords :

• Formate
• Methanol
• Kinetics
• Hemodialysis
• Clearance
• Acidemia