Formate kinetics in methanol poisoning.
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.
Emergency Medicine and Toxicology, Carolinas Medical Center, Charlotte, North Carolina 28232-2861, USA. rkerns@carolinashealthcare.org
William
W
Kerns
Christian
C
Tomaszewski
Kenneth
K
McMartin
Marsha
M
Ford
Jeffrey
J
Brent
D000328:Adult; D005260:Female; D005561:Formates / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008657:Metabolic Clearance Rate; D000432:Methanol / Q000378:metabolism / Q000506:poisoning*; D008875:Middle Aged; D006435:Renal Dialysis; D013406:Suicide, Attempted
D005561:Formates; C030544:formic acid; D000432:Methanol