Formate kinetics in methanol poisoning

William Kerns, Christian Tomaszewski, Kenneth McMartin, Marsha Ford, Jeffrey Brent, G. Bogdan, R. Dart, K. Heard, L. Kokan, K. Kulig, S. Phillips, M. Wells, J. Akhtar, N. Ahsan, K. Burkhart, J. Donovan, H. Zimmerman, S. Curry, K. Wallace, C. AaronM. Burns, C. Graudins, S. Hartigan, C. Hantsch, D. Seger, R. Berlin, D. Douglas, S. White, M. Kirk, J. Hollander, C. McKay, P. Wax

Research output: Contribution to journalArticle

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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 t1/2 = 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.

Original languageEnglish (US)
Pages (from-to)137-143
Number of pages7
JournalJournal of Toxicology - Clinical Toxicology
Volume40
Issue number2
DOIs
StatePublished - 2002

Fingerprint

formic acid
Poisoning
Methanol
Dialysis
Kinetics
Acid-Base Equilibrium
Bicarbonates
Half-Life

Keywords

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

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Kerns, W., Tomaszewski, C., McMartin, K., Ford, M., Brent, J., Bogdan, G., ... Wax, P. (2002). Formate kinetics in methanol poisoning. Journal of Toxicology - Clinical Toxicology, 40(2), 137-143. https://doi.org/10.1081/CLT-120004401

Formate kinetics in methanol poisoning. / Kerns, William; Tomaszewski, Christian; McMartin, Kenneth; Ford, Marsha; Brent, Jeffrey; Bogdan, G.; Dart, R.; Heard, K.; Kokan, L.; Kulig, K.; Phillips, S.; Wells, M.; Akhtar, J.; Ahsan, N.; Burkhart, K.; Donovan, J.; Zimmerman, H.; Curry, S.; Wallace, K.; Aaron, C.; Burns, M.; Graudins, C.; Hartigan, S.; Hantsch, C.; Seger, D.; Berlin, R.; Douglas, D.; White, S.; Kirk, M.; Hollander, J.; McKay, C.; Wax, P.

In: Journal of Toxicology - Clinical Toxicology, Vol. 40, No. 2, 2002, p. 137-143.

Research output: Contribution to journalArticle

Kerns, W, Tomaszewski, C, McMartin, K, Ford, M, Brent, J, Bogdan, G, Dart, R, Heard, K, Kokan, L, Kulig, K, Phillips, S, Wells, M, Akhtar, J, Ahsan, N, Burkhart, K, Donovan, J, Zimmerman, H, Curry, S, Wallace, K, Aaron, C, Burns, M, Graudins, C, Hartigan, S, Hantsch, C, Seger, D, Berlin, R, Douglas, D, White, S, Kirk, M, Hollander, J, McKay, C & Wax, P 2002, 'Formate kinetics in methanol poisoning', Journal of Toxicology - Clinical Toxicology, vol. 40, no. 2, pp. 137-143. https://doi.org/10.1081/CLT-120004401
Kerns W, Tomaszewski C, McMartin K, Ford M, Brent J, Bogdan G et al. Formate kinetics in methanol poisoning. Journal of Toxicology - Clinical Toxicology. 2002;40(2):137-143. https://doi.org/10.1081/CLT-120004401
Kerns, William ; Tomaszewski, Christian ; McMartin, Kenneth ; Ford, Marsha ; Brent, Jeffrey ; Bogdan, G. ; Dart, R. ; Heard, K. ; Kokan, L. ; Kulig, K. ; Phillips, S. ; Wells, M. ; Akhtar, J. ; Ahsan, N. ; Burkhart, K. ; Donovan, J. ; Zimmerman, H. ; Curry, S. ; Wallace, K. ; Aaron, C. ; Burns, M. ; Graudins, C. ; Hartigan, S. ; Hantsch, C. ; Seger, D. ; Berlin, R. ; Douglas, D. ; White, S. ; Kirk, M. ; Hollander, J. ; McKay, C. ; Wax, P. / Formate kinetics in methanol poisoning. In: Journal of Toxicology - Clinical Toxicology. 2002 ; Vol. 40, No. 2. pp. 137-143.
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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 t1/2 = 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.",
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T1 - Formate kinetics in methanol poisoning

AU - Kerns, William

AU - Tomaszewski, Christian

AU - McMartin, Kenneth

AU - Ford, Marsha

AU - Brent, Jeffrey

AU - Bogdan, G.

AU - Dart, R.

AU - Heard, K.

AU - Kokan, L.

AU - Kulig, K.

AU - Phillips, S.

AU - Wells, M.

AU - Akhtar, J.

AU - Ahsan, N.

AU - Burkhart, K.

AU - Donovan, J.

AU - Zimmerman, H.

AU - Curry, S.

AU - Wallace, K.

AU - Aaron, C.

AU - Burns, M.

AU - Graudins, C.

AU - Hartigan, S.

AU - Hantsch, C.

AU - Seger, D.

AU - Berlin, R.

AU - Douglas, D.

AU - White, S.

AU - Kirk, M.

AU - Hollander, J.

AU - McKay, C.

AU - Wax, P.

PY - 2002

Y1 - 2002

N2 - 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 t1/2 = 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.

AB - 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 t1/2 = 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.

KW - Acidemia

KW - Clearance

KW - Formate

KW - Hemodialysis

KW - Kinetics

KW - Methanol

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