Credit goes to Eric for informing us about this case!

A 48yo M presents with acute onset encephalopathy. He has a distant history of alcohol abuse, and during the day of presentation he had complained about not being able to see. On presentation, his labs were notable for an anion gap of 35 with bicarb of 4, lactic acid of 11.9,  ABG of 6.56/52/336, and osm gap of 65. Volatile screen ultimately came back positive for methanol level of 145.56 mg/dL (yes this is very high). He was given bicarb pushes, fomepizole, and urgent dialyzed.

It turns out that he might have ingested Klean Strip denatured alcohol, which is 40-60% methanol!

Methanol Toxicity

Pathophysiology

• Toxic metabolite of methanol poisoning is formic acid, which is formed from formic acid after methanol is metabolized in the liver by alcohol dehydrogenase and aldehyde dehydrogenase
• Leads to retinal injury and eventual blindness (permanent)
• Formic acid can also cause ischemic or hemorrhagic injury to the basal ganglia, hence in methanol poisoning you might see changes around the area (putamen is part of the basal ganglia).
• Ingestion of 1g/kg is fatal, and toxicity has been reported in as little as one teaspoon
• Ethylene glycol, on the other hand, mainly causes renal damage. (Flank pain, hematuria, oliguria). Buzz words = calcium oxalate crystals in urine.

Presentation

• Visual blurring, central scotomata (black spot in center of vision), and blindness are suggestive of methanol poisoning.
• Eye exam might reveal: mydriasis, retinal edema, hyperemia of the optic disk
• Co-ingestion of ethanol can delay presentation of toxicity.
• Labs:
  • Profound AGMA, bicarb often < 8 mEqL
  • High serum lactate
  • Elevated plasma osmo gap
    • Calculated osmolality = 2 x [Na mmol/L] + [glucose mg/dL] / 18 + [BUN mg/dL] / 2.8 + [Ethanol/3.7]
    • OG = Measured osmo – calculated osmo
    • Nrl < 10
  • Typical agents that inc the osmolar gap:
    • Methanol
    • Ethylene Glycol
    • Diuretics (osmotic diuretics i.e. mannitol)
    • Isopropyl alcohol
    • Ethanol
  • Osmo gap takes Into account the quantity of uncharged molecules, hence it will only be elevated in presence of the parent alcohols.
  • In late presentation: most alcohols have been metabolized already into charged active metabolic, hence osmo gap is not very sensitive in late presentation.

Management

• ABC comes first.
• Sodium bicarb administration
  • Corrects systemic acidosis, which limits penetration of formic acid by converting it into negatively charged formate, which cannot cross cell membrane to cause damage.
    • Formic Acid <- -> H+  & Formate-, adding bicarb dec H+, hence driving the equilibrium equation to the right. See? College O-chem is still helpful.
  • HCO3 (mEq) required = 0.5 x weight (kg) x [24 – serum HCO3 (mEq/L)], and in general up front give 1-2 mEq/kg via IV bolus for any patients with pH < 7.3 followed by a sodium bicarb D5 gtt, at least 150-250cc/hr to correct acidosis
    • Goal of infusion is to keep pH above 7.35
  • Bicarb can be found in:
    • Most common: 8.4%, 1mEq/mL, 1Amp = 50mEq, you will see these in the crash cart, very helpful to familiarize yourself with setting the syringe up for injection in a code blue situation!
    • Gtt: 100-150 mEq/1000 mL in D5
    • Concentrated gtt: 1mEq/mL, might need pharmacy’s help in formulating this. You can only use this in the ICU!
    • PO tabs: Useful for CKD patients
• Inhibition of alcohol dehydrogenase in the liver
  • Fomepizole
    • 1st line
    • Loading: 15mg/kg, followed by 10mg/kg Q12hr, continue until blood pH is normalized and serum methanol is less than 20mg/dL
  • Ethanol: ADH has better affinity for ethanol, leading to competitive inhibition.
    • Difficult to dose, sedating effect, cannot be used in cirrhosis patients, pregnant patients.
• HD indicated if:
  • Severe acid-base derangements, or even high AGMA regardless of drug level
  • Severe levels of methanol
  • End organ damage
  • Interacts with fomepizole, hence if concurrent therapy, fomepizole should be dosed Q4H
• Co-factor therapy
  • All methanol patients treated with ADH inhibition should also receive:
    • Leucovorin 50mg IV (folinic acid) or folic acid Q6H
    • Thiamine also commonly administered due to unclear nutritional status.
• GI decontamination: Has no role whatsoever.