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Preventing pseudohyponatremia: Intralipid®-based lipemia cutoffs for sodium are inappropriate
Christopher D Koch1, Michael A Vera1, Jasmine Messina1
1Departments of Laboratory, Yale School of Medicine, New Haven, CT, United States.
Insights
Pseudohyponatremia, an artifactual low sodium result, is often caused by inaccurate lipemia interference detection. Using endogenous hyperlipidemic samples, not Intralipid®, is crucial for accurate sodium measurements in clinical labs.
Area of Science:
- Clinical Chemistry
- Laboratory Medicine
- Diagnostic Accuracy
Background:
- Pseudohyponatremia results from artifactual low plasma sodium in samples with high lipids/proteins using indirect ion-selective electrode (ISE) methods.
- Intralipid®-based lipemia cutoffs may be inadequate for detecting lipid interference in human samples, contributing to pseudohyponatremia.
Purpose of the Study:
- To evaluate the accuracy of Intralipid® in simulating lipemic interference compared to endogenous hyperlipidemic samples.
- To determine an appropriate lipemia cutoff for reliable sodium measurement in clinical laboratories.
Main Methods:
- Compared sodium measurements from indirect ISE and direct ISE methods using pooled, Intralipid®-spiked samples and 31 endogenous hyperlipidemic samples.
- Measured triglycerides, lipemic index (L-index), and sodium concentrations on Roche Cobas® 8000 and Radiometer® ABL835 Flex analyzers.
- Re-analyzed ultracentrifuged endogenous samples using indirect ISE to assess lipid interference.
Main Results:
- Intralipid® did not accurately emulate lipemic interference, showing no effect up to L-index 2000.
- Endogenous hyperlipidemic samples showed significant sodium deviations (≥4 mmol/l) at L-index ≥700.
- A strong positive correlation was observed between L-index and the extent of pseudohyponatremia.
Conclusions:
- Clinical laboratories should lower the lipemia tolerance cutoff from L-index 2000 to 700 for Roche Cobas 8000®.
- Recommend reflex testing via direct ISE when L-index exceeds 700.
- Manufacturers and labs should validate lipid interference using hyperlipidemic human samples, not Intralipid®.
Background:
Pseudohyponatremia describes an artifactual decrease in plasma sodium result in samples with high proteins and/or lipids when measured by an indirect ion-selective electrode (ISE) method. We suspected that Intralipid®-based lipemia cutoffs are inappropriate for detecting interfering lipids in human samples and a major contributing factor to the existence of pseudohyponatremia.
Methods:
We evaluated 2 approaches to derive a lipemia cutoff for sodium, one in which patient plasma samples were pooled and spiked to simulate hyperlipidemia using Intralipid® (commonly used approach by in-vitro diagnostics manufacturers), and another in which endogenous hyperlipidemic samples (n = 31) were measured by methods not affected by hyperlipidemia (i.e., direct ISE and post-ultracentrifugation indirect ISE). Triglycerides, lipemic index (L-index) and indirect ISE sodium concentrations of samples were measured on Roche Cobas® 8000 and direct ISE on Radiometer® ABL835 Flex analyzers. Endogenous hyperlipidemic samples were also ultracentrifuged on Beckman Coulter® Airfuge to clear excess lipids and re-analyzed for sodium by indirect ISE.
Results:
We discovered that Intralipid® is not an accurate emulation of the lipemic interference seen in pseudohyponatremia because it showed no effect up to the maximum level of lipemia tested (L-index = 2000). By contrast, endogenous hyperlipidemic samples demonstrated significant deviations in sodium concentration (≥4 mmol/l) when L-index approached or exceeded 700, and a strong positive correlation between L-index and the difference between the indirect and direct methods (i.e., extent of pseudohyponatremia).
Conclusions:
Clinical laboratories should lower their tolerance for lipemia from the currently recommended L-index cutoff of 2000 on Roche Cobas 8000®. We recommend reflexing to direct ISE when L-index exceeds 700. Manufacturers and laboratories with other indirect ISE methods should evaluate the effect of lipid interference on their method using hyperlipidemic human samples not Intralipid®.
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