What is the significance of an increased osmolal (osmolar) gap?

From the Guidelines

The osmolar gap is a critical parameter in the diagnosis and management of ethylene glycol poisoning, and an osmol gap > 50 is a strong recommendation for extracorporeal treatment (ECTR) initiation, as suggested by the EXTRIP workgroup 1.

Calculation and Interpretation

The osmolar gap is calculated as the difference between measured serum osmolality and calculated serum osmolality, with a normal range typically between -10 and +10 mOsm/kg. To calculate it, first determine the calculated osmolality using the formula: 2 × [Na+] + [glucose]/18 + [BUN]/2.8 + [ethanol]/4.6 (if applicable), then subtract this value from the measured osmolality.

Clinical Significance

An elevated osmolar gap indicates the presence of unmeasured osmotically active substances in the serum, which commonly occurs in toxic alcohol ingestions (methanol, ethylene glycol, isopropyl alcohol), alcoholic ketoacidosis, lactic acidosis, or mannitol therapy. This measurement is particularly useful in emergency settings when toxic ingestion is suspected but not confirmed, as it can guide initial management before specific toxin levels return.

Management

The EXTRIP workgroup recommends ECTR initiation based on osmol gap values, with an osmol gap > 50 being a strong recommendation for ECTR initiation when fomepizole or ethanol is used as an antidote 1. The workgroup also suggests ECTR initiation when the osmol gap is 20-50, especially if there are severe clinical features such as coma, seizures, or acute kidney injury (AKI) 1.

Key Points

• The osmolar gap is a useful parameter in the diagnosis and management of ethylene glycol poisoning.
• An osmol gap > 50 is a strong recommendation for ECTR initiation.
• The EXTRIP workgroup provides guidelines for ECTR initiation based on osmol gap values and clinical features.
• ECTR should be individualized based on patient characteristics and clinical context, as suggested by the EXTRIP workgroup 1.

From the FDA Drug Label

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 osmolar gap is a factor to consider when deciding to start treatment with fomepizole injection, as an increased osmolar gap can indicate ethylene glycol or methanol ingestion 2.

From the Research

Definition and Causes of Osmolar Gap

• The osmolal gap is a measure of the difference between the measured and calculated osmolality of the blood [(3,4,5,6,7)].
• It can be elevated in various clinical scenarios, including:
  • Ingestion of toxic alcohols such as methanol, ethylene glycol, and isopropyl alcohol [(3,4,5,7)].
  • Renal failure [(4,5,7)].
  • Diabetic ketoacidosis [(5,7)].
  • Shock 5.
  • Multiple myeloma 4.
  • Alcoholic ketoacidosis 6.

Clinical Significance of Osmolar Gap

• An elevated osmolal gap can indicate the presence of toxic substances in the blood, which can cause metabolic acidosis and other complications [(3,5,7)].
• The osmolal gap can be used as a diagnostic tool to help identify the cause of high-anion-gap metabolic acidosis [(5,7)].
• A high osmolal gap associated with increased anion gap acidosis is said to be indicative of toxic alcohol poisoning, although this is not specific 6.

Treatment and Management

• Treatment of elevated osmolal gap depends on the underlying cause, but may include:
  • Hemodialysis to remove toxic substances from the blood [(3,4,7)].
  • Administration of fomepizole or ethanol to inhibit alcohol dehydrogenase [(3,7)].
  • Supportive care, such as correction of metabolic acidosis and management of renal failure [(3,7)].