From the Guidelines
In patients presenting with ethylene glycol poisoning, we recommend extracorporeal treatment (ECTR) if the osmol gap is > 50, as this is associated with a high risk of adverse outcomes and mortality. The osmolar gap is calculated as measured osmolality − calculated osmolarity, in SI units and adjusted for ethanol, and is used as a surrogate to predict the ethylene glycol concentration when assays are not readily available 1.
Key Considerations
- The osmol gap is a poor screening test for ethylene glycol ingestion at low values, but correlates linearly with ethylene glycol concentration at high levels 1.
- An osmol gap > 50 is a reasonable criterion for initiating ECTR, especially if there is a confirmed history of ethylene glycol ingestion 1.
- If no antidote is available, an osmol gap > 10, in the context of ethylene glycol exposure, is also a reasonable criterion for hemodialysis 1.
Calculation and Interpretation
- The calculated osmolality is determined using the formula: 2 × [Na+] + [glucose]/18 + [BUN]/2.8 + [ethanol]/4.6 (if applicable) 1.
- The osmolar gap is then calculated by subtracting the calculated osmolality from the measured osmolality obtained from laboratory testing.
- An elevated osmolar gap (>10 mOsm/kg) suggests the presence of unmeasured osmotically active substances in the blood, which commonly occurs in toxic alcohol ingestions, including ethylene glycol poisoning 1.
Clinical Decision-Making
- The osmolar gap should be interpreted alongside clinical presentation and other laboratory values, as it may be normal early in toxic alcohol ingestion before significant metabolism occurs or in cases where the toxin has already been metabolized 1.
- In patients presenting with ethylene glycol poisoning, we suggest ECTR if the osmol gap is 20-50, as this is associated with a moderate risk of adverse outcomes 1.
- The decision to initiate ECTR should be individualized, taking into account the patient's clinical presentation, laboratory values, and the availability of antidotes 1.
From the Research
Osmolar Gap
- The osmolar gap is a useful diagnostic tool in clinical practice, particularly in the differential diagnosis of patients presenting with possible drug or substance overdose, as well as in comatose hospitalized patients 2.
- An increased serum osmolal gap can be an important clue to exposure to toxic alcohols, such as methanol, ethylene glycol, diethylene glycol, propylene glycol, or isopropanol 3.
- However, other disorders, including diabetic or alcoholic ketoacidosis, acute kidney injury, chronic kidney disease, and lactic acidosis, can also cause high-anion-gap metabolic acidosis associated with an increased serum osmolal gap 3.
Calculation and Interpretation
- The calculation of osmolal gap is crucial in the differential diagnosis of many patients, and the best formula used for the calculation of osmolal gap should be employed 2.
- An osmolar gap >10 mosm/kg is considered significant, and this can be observed in critically ill patients with true hyponatremia, particularly in those with severe organ dysfunctions 4.
Clinical Applications
- Fomepizole, an anti-metabolite therapy, is used to diminish the toxicity from methanol or ethylene glycol, and its elimination kinetics have been well described in healthy human subjects and poisoned patients 5, 6.
- The use of fomepizole has been shown to be efficacious and well tolerated in pediatric patients with ethylene glycol poisoning, and hemodialysis may not be necessary in most cases if treated with fomepizole 5.
- The osmolar gap can be useful in monitoring the effectiveness of treatment, as a decrease in plasma osmolar gap has been observed during correction of hyponatremia in patients with an increased osmolar gap 4.