Formate kinetics in methanol poisoning

被引:53
作者
Kerns, W
Tomaszewski, C
McMartin, K
Ford, M
Brent, J
机构
[1] Louisiana State Univ, Med Ctr, Shreveport, LA 71105 USA
[2] Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA
[3] Toxicol Associates, Denver, CO USA
[4] Carolinas Med Ctr, Charlotte, NC 28232 USA
来源
JOURNAL OF TOXICOLOGY-CLINICAL TOXICOLOGY | 2002年 / 40卷 / 02期
关键词
formate; methanol; kinetics; hemodialysis; clearance; acidemia;
D O I
10.1081/CLT-120004401
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
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 hurl 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 r(2) = 0.93; bicarbonate vs. formate r(2) = 0.81; and anion gap vs. formate r(2) = 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.
引用
收藏
页码:137 / 143
页数:7
相关论文
共 19 条
[1]   GAS-CHROMATOGRAPHIC HEADSPACE ASSAY OF FORMIC-ACID AS METHYL FORMATE IN BIOLOGIC FLUIDS - POTENTIAL APPLICATION TO METHANOL POISONING [J].
ABOLIN, C ;
MCRAE, JD ;
TOZER, TN ;
TAKKI, S .
BIOCHEMICAL MEDICINE, 1980, 23 (02) :209-218
[2]   SIMULTANEOUS DETERMINATION OF LOWER ALCOHOLS ACETONE AND ACETALDEHYDE IN BLOOD BY GAS CHROMATOGRAPHY [J].
BAKER, RN ;
ALENTY, AL ;
ZACK, JF .
JOURNAL OF CHROMATOGRAPHIC SCIENCE, 1969, 7 (05) :312-&
[3]   EXPERIMENTAL METHANOL TOXICITY IN PRIMATE - ANALYSIS OF METABOLIC-ACIDOSIS [J].
CLAY, KL ;
MURPHY, RC ;
WATKINS, WD .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1975, 34 (01) :49-61
[4]   GAS-CHROMATOGRAPHIC ANALYSIS OF METHYL FORMATE AND APPLICATION IN METHANOL POISONING CASES [J].
FRASER, AD ;
MACNEIL, W .
JOURNAL OF ANALYTICAL TOXICOLOGY, 1989, 13 (02) :73-76
[5]   METHANOL AND FORMATE KINETICS IN LATE DIAGNOSED METHANOL INTOXICATION [J].
JACOBSEN, D ;
WEBB, R ;
COLLINS, TD ;
MCMARTIN, KE .
MEDICAL TOXICOLOGY AND ADVERSE DRUG EXPERIENCE, 1988, 3 (05) :418-423
[6]   4-methylpyrazole (4-MP) is effectively removed by haemodialysis in the pig model [J].
Jacobsen, D ;
Ostensen, J ;
Bredesen, L ;
Ullstein, E ;
McMartin, K .
HUMAN & EXPERIMENTAL TOXICOLOGY, 1996, 15 (06) :494-496
[7]  
JACOBSON JW, 1983, MENT RETARD, V21, P1
[8]   METHANOL AND FORMIC-ACID TOXICITY - BIOCHEMICAL-MECHANISMS [J].
LIESIVUORI, J ;
SAVOLAINEN, H .
PHARMACOLOGY & TOXICOLOGY, 1991, 69 (03) :157-163
[9]  
MCMARTIN KE, 1977, J PHARMACOL EXP THER, V201, P564
[10]   METHANOL POISONING .1. ROLE OF FORMIC-ACID IN DEVELOPMENT OF METABOLIC-ACIDOSIS IN MONKEY AND REVERSAL BY 4-METHYLPYRAZOLE [J].
MCMARTIN, KE ;
MAKAR, AB ;
MARTIN, G ;
PALESE, M ;
TEPHLY, TR .
BIOCHEMICAL MEDICINE, 1975, 13 (04) :319-333