From the Guidelines
An elevated anion gap metabolic acidosis, with an anion gap greater than 27 mmol/L, is the key lab value suggesting toxic alcohol ingestion, particularly ethylene glycol poisoning, as indicated by the most recent study 1. This occurs because toxic alcohols like methanol, ethylene glycol, and isopropanol are metabolized to acidic compounds that increase the anion gap. Other supportive findings include:
- an osmolal gap greater than 10 mOsm/kg, which appears early in the ingestion before metabolism occurs
- a plasma ethylene glycol concentration greater than 50 mmol/L
- a plasma glycolate concentration greater than 12 mmol/L As the parent alcohol is metabolized, the osmolal gap decreases while the anion gap increases. Additional laboratory clues include:
- hypocalcemia
- oxalate crystals in urine (with ethylene glycol)
- visual disturbances (with methanol)
- ketosis without significant hyperglycemia (with isopropanol) Prompt recognition of these laboratory abnormalities is crucial as toxic alcohol ingestions require immediate treatment with fomepizole or ethanol to block alcohol dehydrogenase, along with hemodialysis in severe cases to remove the toxic alcohol and its metabolites before life-threatening complications develop, as recommended by the most recent guidelines 1. It is also important to note that the osmol gap can be used as a surrogate to predict the EG concentration, especially at high EG concentrations, despite its limitations as a screening test 1. The decision to initiate extracorporeal treatment should be based on individualized assessment of the patient's condition, taking into account the presence of clinical indications such as coma, seizures, or kidney impairment, as well as the availability of antidotes and the potential risks and benefits of treatment 1.
From the FDA Drug Label
The diagnosis of these poisonings may be difficult because ethylene glycol and methanol concentrations diminish in the blood as they are metabolized to their respective metabolites Hence, both ethylene glycol and methanol concentrations and acid base balance, as determined by serum electrolyte (anion gap) and/or arterial blood gas analysis, should be frequently monitored and used to guide treatment Treatment with Fomepizole Injection Begin fomepizole injection treatment immediately upon suspicion of ethylene glycol or methanol ingestion based on patient history and/or anion gap metabolic acidosis, increased osmolar gap, visual disturbances, or oxalate crystals in the urine, OR a documented serum ethylene glycol or methanol concentration greater than 20 mg/dL
The lab value that suggests ingestion of a toxic alcohol is an increased anion gap or osmolar gap, as well as the presence of oxalate crystals in the urine. Additionally, a documented serum ethylene glycol or methanol concentration greater than 20 mg/dL is also indicative of toxic alcohol ingestion 2.
From the Research
Lab Values Indicative of Toxic Alcohol Ingestion
- A high anion gap (AG) metabolic acidosis is typically present in cases of toxic alcohol ingestion 3, 4, 5
- An elevated osmolar gap (OG) is also a common finding in toxic alcohol ingestion 3, 4, 6, 5
- Normal anion gap metabolic acidosis with a high OG can occur in early ingestions of toxic alcohols 3
- Lactic acidosis can be present, but false elevation of lactate can occur with ethylene glycol ingestion due to cross-reaction with L-lactate oxidase in the analyzer 3
- The combination of lactic acidosis, high OG, and normal AG should raise suspicion for toxic alcohol ingestion 3
Specific Lab Values
- Osmolal gap >20 mOsm/kg is usually caused by ingestion of methanol, ethylene glycol, isopropanol, propylene glycol, diethylene glycol, or organic solvents such as acetone 6
- An osmolal gap of 170 was reported in a case of combined toxic alcohols ingestion 3
- A median osmolal gap of 119 +/- 47 mOsm/l was reported in cases of life-threatening alcohol intoxication 4
- An extremely elevated osmolal gap of 91 mOsm/kg was reported in a case of severe ethanol intoxication 6
Limitations and Considerations
- The increase in serum osmolal gap and metabolic acidosis can occur either together or alone depending on several factors, including baseline serum osmolal gap, molecular weight of the alcohol, and stage of metabolism of the alcohol 5
- Other disorders, such as diabetic or alcoholic ketoacidosis, acute kidney injury, chronic kidney disease, and lactic acidosis, can cause high-anion-gap metabolic acidosis associated with an increased serum osmolal gap 5, 7