-Alcohols that are metabolized to organic acids – methanol, ethylene glycol, diethylene glycol
-Even a mouthful in a child can be a toxic ingestion
Methanol: Windshield washer, printer/copier fluid, paint thinner, sterno fuel, fuel for RC cars, perfumes, “denatured” alcohol
- Metabolized formaldehyde>formic acid – acidosis and retina/optic nerve damage
- Intoxicated + blurry/snowfield vision ->mitochondrial poison ->seizure, coma, death
- Can have significant level without clinical signs of intoxication
- Can cause a false positive breath ethanol – should get blood ethanol if concern
- Putamenal and basal ganglia hyperintensity on HCT
Ethylene glycol: Antifreeze/engine coolant
- Glycolic acid>oxalate crystals – acidosis and renal/CNS damage
- Hypocalcemia d/t precipitation w/ oxalate
Diethylene glycol: Brake fluid/wheel cleanter
- Diglycolic acid
- Less well understood, causes renal, hepatic, CNS injury
Isopropyl alcohol: Rubbing alcohol
- Not actual toxic alcohol
- Ketosis w/o acidosis
Propylene glycol: Antifreeze, Medication diluent (lorazepam, diazepam, phenobarb, phenytoin, nitroglycerin, Bactrim)
- Metabolized to lactate
- Usually metabolized normally but can cause AGMA in liver disease or large amounts
Presentation
-All cause intoxication
-Pattern w/ metabolism over time: absent to worsening AGMA + elevated to resolving osm gap
-Need to consider in all bad gap acidosis
-Osmolar gap – not very sensitive or specific – cannot use as a rule out test but can essentially rule in
- Normal osm gap range is broad: -14 – +10
- Typically quoted normal gap is <10
- Osm gap >30 is fairly specific
- Serum Osmolality (US) = (2 * (Na) + (BUN / 2.8) + (glucose / 18) + (ethanol/4.6)
- Need to use mg/dl for BUN, glucose and ethanol – e.g. 0.08 instead of 80 for ethanol
- Serial chems and osm gap calculations can help clarify – e.g worsening AGMA with decreasing osm gap
-Send toxic alcohol levels if concerned – turnaround dependent on location
-Substantial limitations to checking for urine CaOx crystals or florescence as adjunctive tests – neither or sensitive or specific
Treatment
Treatment threshold > 20 mg/dl regardless of symptoms
-If ethanol ≥ 0.1 mg/dl then will be preferentially metabolized before toxic alcohol and there is there is some time before needing to start treatment
Metabolic treatment:
- Fomepizole – load then q 12h dosing while in treatment range (expensive)
- Ethanol – target > 0.1 mg/dl
- Loading dose 600-800 mg/kg
- Then maintenance drip
- Doesn’t fix acidosis or damage from metabolites that are already present
Dialysis – all are dialyzable
- Some recommend empiric dialysis at levels > 50 mg/dl
- Absolute: Cardiac arrest, renal failure, severe acidosis
- Relative: Level >50, vision changes, mild acidosis, very high levels
- May also be cheaper/safer/better than prolonged MICU admission for standard tx of overdose w/ high levels
Adjunctive treatment:
- Methanol: Folic acid (protects optic nerve, important), NaHCO3 (shunts formic acid, not good data, more theoretical benefit)
- Ethylene glycol: Thiamine, Pyridoxine, Magnesium (Encourage alternate metabolic pathways)