Ethylene Glycol is a Primary Alcohol Which is Metabolized by Alcohol Dehydrogenase and Aldehyde Dehydrogenase to Carboxylic Acids (Namely, Glycolic Acid, Glyoxylic Acid, and Oxalic Acid): these carboxylic acids cause most of the toxic effects
Methanol
Methanol is a Primary Alcohol Which is Metabolized by Alcohol Dehydrogenase and Aldehyde Dehydrogenase to Carboxylic Acids (Namely, Formic Acid): these carboxylic acids cause most of the toxic effects
Isopropanol is a Secondary Alcohol Which is Metabolized by Alcohol Dehydrogenase Only to a Ketone (Namely, Acetone), Rather than to an Aldehyde: ketones cannot be oxidized to an aldehyde and therefore, only limited acidosis can result
Methanol Metabolism
Methanol is (Predominantly) Hepatically Metabolized by Alcohol Dehydrogenase to Formaldehyde, Then By Aldehyde Dehydrogenase to Formic Acid
Approximately 10% of methanol is renally excreted unchanged
Kinetics
Absence of Treatment: methanol elimination follows zero-order kinetics
Rate of Elimination: 8.5 mg/dL per hr
Treatment with Alcohol Dehydrogenase Inhibitor (Ethanol, Fomepizole): methanol elimination changes to first-order kinetics
Rate of Elimination: decreases (half-life increases to 48-54 hrs)
Elimination via renal and pulmonary routes increases
End-Organ Toxicity
General Comments
The metabolites which cause most of the toxicity associated with methanol are distributed in body water
Acidemia increases the central nervous system cellular penetration by formic acid
Formic acid is a highly-specific neurotoxin (often leaving other organs spared)
Central Nervous Depression Depression
Cerebral Edema
Retinal and Basal Gangliar Damage: due to formic acid
Believed to be mediated via disruption of mitochondrial function
Diagnosis
Arterial Blood Gas (ABG) (see Arterial Blood Gas, [[Arterial Blood Gas]])
Elevated Anion Gap Metabolic Acidosis (see Metabolic Acidosis-Elevated Anion Gap, [[Metabolic Acidosis-Elevated Anion Gap]]): anion gap is usually >20 (due to lactic acid and formic acid, therefore, may not be seen early in all cases)
Note: the serum osmolal gap estimates the molar quantity of uncharged molecules and consequently, increases only in the presence of the parent alcohol methanol
The toxic methanol metabolite (formic acid), exist primarily in a dissociated/charged form at physiologic pH: as these anions are accompanied by a cation (mostly sodium), they do not contribute to the serum osmolal gap since they are accounted for in the serum sodium term in the formula for the serum osmolal gap
Elevated Osmolal Gap (see Serum Osmolality, [[Serum Osmolality]])
Physiology: due to presence of the osmotically-active solute, methanol
Importantly, the serum osmolal gap estimates the molar quantity of uncharged molecules -> consequently, the osmolal gap is increased due to the presence of methanol itself
The toxic methanol metabolite, formic acid, exists primarily in a dissociated (charged) form at physiologic pH -> as this anion is accompanied by a cation (mostly sodium), it does not contribute to the serum osmolal gap since it is accounted for in the serum sodium term in the serum osmolal gap formula
Clinical: may produce a large osmolal gap (>20 mOsm/L)
Osmolal gap may occur with/without an anion gap metabolic acidosis
The absence of an osmolal gap does not exclude the presence of methanol
There are often discrepancies between the degree of osmolal gap and the severity of clinical manifestations
Mechanism: competes with both methanol and ethylene glycol for alcohol dehydrogenase (alcohol dehydrogenase enzyme has higher affinity for ethanol and becomes saturated at an ethanol level between 13-30 mg/dL), preventing formation of toxic metabolites
Administration: load with 10% ethanol at 10 mL/kg IV, then infuse 10% ethanol at 1.5 mL/kg/hr IV drip -> titrate to keep ethanol level between 100-200 mg/dl
Concomitant Hemodialysis and Ethanol Infusion: when hemodialysis is used with ethanol infusion, increase the ethanol drip rate to account for its loss with hemodialysis -> administer 3 mL/kg/hr IV drip instead
Monitor: monitor ethanol and methanol levels during therapy
Continue until methanol level is <6 mmol/L (20 mg/dL) and symptoms have resolved
May be useful (but is currently only approved for ethylene glycol intoxication)
Alkalinization
Decreases renal and optho toxicity in MeOH intoxication (possibly by decreasing the relative concentration of formic acid in central nervous system in presence of systemic acidosis)
Alkalinization of urine also facilitates formic acid excretion
