Toxic Alcohols

Key Points: 
1. ALL alcohols are more or less intoxicating based on number of carbon atoms (most: isopropyl alcohol and ethylene glycol; least is methanol)

2. Toxic Alcohols are toxic because of their TOXIC Metabolites

In general, the parent compound (alcohol) is not directly tissue toxic; the metabolites (aldehydes and especially the acids) made from the actions of alcholol and acetaldehyde dehyrdogenase are the major problem. For example, in ethylene glycol poisoning, the metabolites glycolate, glycoxylate, and oxalate cause acidosis and multiple organ failure. This process, as with all metabolic reactions, takes time and PATIENTS DO NOT BECOME ILL RIGHT AWAY. In many cases, it can take 12-24 hours for acidosis and organ failure to occur.


3. Therefore, the key to management of toxic alcohols is PREVENTION of metabolite formation until the parent compounds can be excreted or dialyzed.





4. Diagnostic Testing and the 2 Gaps: The extent of exposure to the PARENT compounds can be approximated by the osmolar gap; extent of acidosis due to the METABOLITES can be calculated by the anion gap. 

Gaps “cross over” one another (see diagram)below. This means that the osmolar gap is usually normal by the time a WIDE ANION GAP is notable.

Here is the OSMolar Gap formula: 

2 (Na) + (glucose/18) + (BUN/2.8) + (toxic alcohol level x 10 /molecular weight of the alcohol).


You can factor in the contribution of ethanol and other alcohols by using the following values for the molecular weight of the alcohols: EtOH: 46; MeOH: 32; EG: 64; Isopropyl Alcohol: 56

Example: An ethanol level of 46 gives you 10 osms; an EG level of 64 also gives you 10 osms. 

The OSM GAP is not that helpful for several reasons:

A. The measurement of osmolarity must be done at the same time as the initial electrolytes-- in other words, as soon as the ingestion is suspected. By the time the acidosis is manifest, the osm gap will be closed (see above).

B. Even when done on time, the osm gap is a poor test to begin with. That's because, unlike an anion gap, there is a wide variability of normal values.  The "Normal" Osm Gap in a population can vary from -5 to 14. So if you get an osm gap of 10, this could be normal, or it could represent an EG level correlating with 64mg/dL-- this is high enough to be toxic!!  

Bottom line: The osm gap helps to rule in a toxic alcohol ingestion when it is VERY positive, but it doesn't necessarily rule OUT toxic exposure when it is negative. 

Ethanol ingestion in children results in HYPOGLYCEMIA (low hepatic glycogen reserves, gluconeogenesis stops when there is a lot of NADH/NAD+ due to activity of alcohol dehydrogenase)




All toxic alcohols can cause intoxication, sedation and hypotension. Acidosis (except isopropanol) can be severe, but delayed up to 30 hours after ingestion. This is especially true if ethanol is coingested because it prevents formation of the acidic metabolites.




Methanol: winshield wiper fluids; industrial solvents; formalin (=methanol and formaldehyde); causes optic nerve toxicity due to FORMIC ACID toxicity; hemorrhagic infarcts of the basal ganglia; hemorrhagic pancreatitis is also a well-described complication. See images below of optic nerve edema and basal ganglia infarcts following methanol poisoning (from www.nature.com)

Ethylene glycol: antifreeze ingestions; severe multiorgan failure and edema due to deposition of OXALIC ACID crystals (calcium-oxalate crystals); can see these in the urine as needles or envelope-shaped crystals); fluorescent urine and oral cavity due to the presence of fluorescein in the antifreeze; cerebral edema with CN 6 palsy, pericarditis, rhabdomyolysis.Below is a picture of calcium oxalate crystals in the urine, which are highly specific for ethylene glycol poisoning and sometimes the first clue to the diagnosis.

Isopropanyl alcohol: rubbing alcohols. Converted to acetone and exhaled; no acidosis, only KETOSIS. Acetone breath. Very intoxicating and causes hemorrhagic pancreatitis.

Propylene glycol: newer antifreezes (safer than EG, see below). Converted to lactate in the liver, with resulting lactic acidosis and, occasionally, renal failure. Also used as a diluent in IV meds like phenytoin, lorazepam...may cause lactic acidosis in prolonged infusions (ICU patients on drips for more than 36 hrs).

Diethylene glycol: Severe renal failure and multiorgan failure when used as a diluent in medications. Epidemics in Haiti, India, lots of other places. In 1937, epidemic poisoning due from DEG in a sulfanilimide antibiotic solution in the USA (aka the "Sulfanilimide Disaster") led to the formation of FDA.

Treatment Considerations

General Treatment: Support Airway and BP; Multivitamins to help shunt metabolism away from toxic compounds (use folate for methanol; thiamine, magnesium, and pyridoxine for ethylene glycol). Rule out AKA with serum ketoacid levels. Use bicarb to maintain physiologic pH.

Specific therapy: BLOCK conversion to toxic compounds via Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase enzymes.
i. This was traditionally done with IV or PO ethanol—a competitive inhibitor of ADH. Titrate to keep a BAL of 100 mg/dL, which is sometimes challenging in the hemodynamically unstable (and withdrawing) alcoholic....these infusions invariably require ICU admission. Watch for hypotension and hypoglycemia, esp in kids.

ii. The New Antidote: Fomepizole—a direct inhibitor of ADH. This is more expensive, but easy to dose and does not require titration; causes no hypotension, transaminitis, or hypoglycemia. Use a loading dose of 20 mg/kg then BID dose of 10 mg/kg for 4 doses, then BID dose of 15 mg/kg until toxic alcohol level is below 20 mg/dL. Redose immediately after dialysis. Many published reports of low to no toxic sympoms when fomepizole is