Pseudohyponatremia in a Hyperglycemic Emergency
A 58-year-old man with type 2 diabetes is admitted with confusion and a glucose of 41.6 mmol/L (750 mg/dL). The chemistry analyzer reports sodium 118 mmol/L by indirect ion-selective electrode (ISE) on a diluted, lipemic sample; triglycerides are 24 mmol/L (2,120 mg/dL), total protein 82 g/L, and the lipemic index is 4+. Measured osmolality by freezing-point depression is 331 mOsm/kg; urea is 9.0 mmol/L. The clinician requests 3% saline for severe hyponatremia. A repeat sodium on whole blood using a direct ISE point-of-care device is 139 mmol/L. The patient's sodium was 137 mmol/L two weeks ago. The laboratory scientist must decide whether 118 mmol/L is real, calculate expected osmolality and the osmolal gap, and advise on reporting and immediate treatment. No hemolysis or icterus is present.
1. Calculate the expected osmolality from the direct ISE sodium and the osmolal gap. What do the gap and the two sodium values indicate?
Read the worked answer
Expected osmolality = 2 × Na + glucose + urea (all in mmol/L). Using the direct ISE sodium: 2 × 139 = 278; 278 + 41.6 + 9.0 = 328.6 mOsm/kg. Measured osmolality is 331, so the osmolal gap is 331 − 328.6 = 2.4 mOsm/kg, which is within the usual reference of less than 10. Using the indirect ISE sodium of 118 gives 236 + 41.6 + 9.0 = 286.6 and a gap of 44.4, an implausible value that signals an artefact. The indirect ISE dilutes the sample and reports sodium per total plasma volume; with triglycerides of 24 mmol/L, plasma water is displaced, so the result is falsely low - pseudohyponatremia. The direct ISE measures sodium activity in undiluted whole blood and gives 139 mmol/L. Therefore the 118 mmol/L is not true hyponatremia; the patient is hyperosmolar because of glucose.
2. The clinician wants a glucose-corrected sodium. Calculate it using 1.6 mmol/L per 100 mg/dL of glucose above 100 mg/dL. Does this explain the 118 mmol/L, and what is the patient's tonicity?
Read the worked answer
Glucose is 750 mg/dL, which is 650 mg/dL above 100. 650/100 = 6.5; 6.5 × 1.6 = 10.4 mmol/L. Corrected sodium = 118 + 10.4 = 128.4 mmol/L. Even this correction does not reach 139 mmol/L: the glucose effect explains only about 10 mmol/L, and the remaining roughly 11 mmol/L is the lipid-related analytical artefact. Some sources use 2.4 mmol/L per 100 mg/dL in marked hyperglycemia, which would give 133.6 mmol/L, still below 139. With the direct sodium of 139, effective osmolality is approximately 2 × 139 + 41.6 = 319.6 mOsm/kg (urea crosses membranes and does not contribute to tonicity), confirming hypertonicity. Three percent saline is contraindicated because it would worsen hyperosmolality. Treat the hyperglycemic emergency with isotonic fluids, insulin, potassium replacement, and frequent osmolality and neurologic monitoring, with a controlled decline in glucose.
3. What should be reported, and what analytical and reporting corrective actions are needed?
Read the worked answer
Report the direct ISE sodium of 139 mmol/L as the clinically valid result, with a comment that the indirect ISE sodium is invalid because of marked lipemia (triglycerides 24 mmol/L) and that the sample was analyzed by direct ISE or after ultracentrifugation. Notify the clinician urgently so the 3% saline order is cancelled. Do not release 118 mmol/L as a final result; if the LIS auto-verifies, suppress auto-verification or append an interpretive comment and a lipemic-index flag. Repeat on a fresh sample once triglycerides clear and monitor sodium with a direct ISE method. Analytically, review the indirect ISE dilution protocol, validate direct ISE or ultracentrifugation for lipemic samples, and document the event as an analytical interference with pre-analytical contributors. Report measured osmolality and the osmolal gap to support interpretation.