Toxicology

metabolized.

As the osmolar gap declines, the anion gap will rise, resulting in a significant metabolic acidosis.

Calculations:

Osmolar gap (OG):

Measured osmolality - calculated osmolality (normal OG less than 10)

ii.

Calculated osmolality:

(sodium x 2) + (glucose/18) + (BUN/2.8)

iii.

Calculated osmolality with ethanol ingestion:

(sodium x 2) + (glucose/18) + (BUN/2.8) + (ethanol/4.6)

iv.

Calculated osmolality with methanol ingestion:

(sodium x 2) + (glucose/18) + (BUN/2.8) + (methanol/3.2)

Calculated osmolality with ethylene glycol ingestion:

(sodium x 2) + (glucose/18) + (BUN/2.8) + (ethylene glycol/6.2)

vi.

Anion gap (AG; normal 8-12 mEq/L):

Na − (Cl + HCO3)

Methanol and ethylene glycol serum concentrations may be monitored to determine severity and to

guide therapy in conjunction with an anion gap metabolic acidosis. Often, the ability to obtain these

serum concentrations is not readily available and may take several hours to perform; therefore, therapy

should not be delayed for lab results.

Treatment is focused on blocking the toxic alcohol metabolism and allowing it to be excreted unchanged

in the urine. Treatment is recommended when serum methanol or ethylene glycol concentrations

exceed 20 mg/dL, the patient has a documented history of ingestion, there is a high clinical suspicion of

ingestion combined with an osmolal gap >10 mOsm/kg, or there is a presence of an anion gap metabolic

acidosis of unknown etiology.

Fomepizole is the preferred antidote because of its predictable response, ease of dosing, and lack of

contraindications to use.

Mechanism of action is competitive inhibition of alcohol dehydrogenase.

Dosing is a 15-mg/kg intravenous bolus (as a loading dose); then 10 mg/kg every 12 hours for four

doses; then 15 mg/kg every 12 hours until methanol/ethylene glycol concentrations are less than

20 mg/dL.

After 48 hours, fomepizole induces its own metabolism, requiring dosage increases.

Therapy is discontinued when methanol/ethylene glycol concentrations are less than 20 mg/dL. If

the patient is still symptomatic with a normal pH, further workup is warranted, and hemodialysis

may be indicated.

Hemodialysis increases the clearance of fomepizole; therefore, doses must be administered every 4

hours during hemodialysis. Continuous renal replacement therapy has also been found to increase

the clearance of fomepizole, and although guidance regarding dosing adjustments is limited and

requires further investigation, current data suggest reducing the maintenance dose by half as

compared with hemodialysis (Clin Toxicol. 2022;60(4):451-457).

Adverse effects may include headache, nausea, dizziness, abdominal pain, hypotension, and

bradycardia.