FORMATE KINETICS IN METHANOL POISONING

Objective: We sought to describe the kinetics, dialysis clearance, & clinical markers of formate (FA), the toxic metabolite of methanol (MeOH). Methods: Data were obtained from a prospective, multicenter treatment protocol using fomepizole [+ or -] hemodialysis (HD) for MeOH poisoning. HD indications included: MeOH [is greater than] 50 mg/dl, pH [is less than] 7.1, refractory acidosis, or altered visual acuity. Blood samples were drawn for serial FA, MeOH, pH, & bicarbonate measurements. Plasma MeOH & FA were determined by gas chromatography. Elimination half-life ([t.sub.1/2]) was calculated as [t.sub.1/2] = 0.693/Kd, where Kd, the elimination rate constant, was determined from the slope of ln[FA] vs time. HD clearance was calculated using the relationship HD flow x [(inlet FA - outlet FA)/inlet FA]. Pearson correlation coefficients were determined for initial FA vs initial pH, serum bicarbonate, & anion gap (AG). Data were analyzed using SAS statistical software (p [is less than] 0.05 significant). Results: 11 patients (10 males) with mean age 39.9 years (range 19-61) were included. 7 patients underwent HD. The mean initial MeOH was 196.3 mg/dL (range 28-768) & FA, 11.0 mmol/L (range 0-34.8). Non-HD [t.sub.1/2] was 205 min [+ or -] 25 sd and HD [t.sub.1/2], 185 min [+ or -] 62.7 sd (NS by Student's t-test). Overall HD FA clearance was 223 mL/min [+ or -] 24.5 sd. Correlation coefficients were: pH vs FA [r.sup.2] = 0.929 (p [is less than] 0.05); bicarbonate vs FA [r.sup.2] = 0.804 (p [is less than] 0.05); & AG vs FA [r.sup.2] = 0.760 (p [is less than] 0.05). Conclusions: Even though HD clears FA, HD does not decrease the FA elimination [t.sub.1/2]. Low pH, low bicarbonate, and elevated AG correlate with FA presence.
Kerns W, Tomaszewski C, McMartin K, Ford M, Brent J, META Study Group. Carolinas Medical Center, Charlotte, NC; Louisiana State University, Shreveport, LA; and University of Colorado Health Sciences Center, [...]