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Prevalence of Clinically Significant Differences in Sodium Measurements Due to Abnormal Protein Concentrations Using
Waddah Katrangi1, Nikola A Baumann1, Ryan C Nett1
1Mayo Clinic, Department of Laboratory Medicine and Pathology, Rochester, MN.
Insights
High serum total protein can falsely lower indirect ISE sodium measurements, leading to pseudohyponatremia. This study quantizes this effect and highlights the need for clinical decision support to detect such discrepancies.
Area of Science:
- Clinical Chemistry
- Laboratory Medicine
- Analytical Chemistry
Background:
- Indirect ion-selective electrode (ISE) is standard for serum sodium measurement in clinical labs.
- Electrolyte exclusion effect can cause pseudohyponatremia, particularly with hyperproteinemia, impacting patient management.
- Understanding the relationship between total protein (TP) and sodium measurement errors is crucial.
Purpose of the Study:
- To establish the relationship between serum total protein (TP) concentration and the magnitude of the electrolyte exclusion effect on indirect ISE-measured sodium.
- To estimate the frequency of TP concentrations impacting indirect ISE sodium measurements.
- To determine the effectiveness of clinical decision support rules for detecting pseudohyponatremia.
Main Methods:
- Analyzed residual serum specimens (n=112) comparing indirect ISE (Cobas 8000) and direct ISE (ABL 825) sodium measurements.
- Calculated the difference in sodium concentration (Δ[Na+]) between the two methods.
- Stratified retrospective TP results and quantified sodium and TP co-ordering rates.
Main Results:
- A strong inverse relationship (R=-0.883) was found between Δ[Na+] and TP concentration.
- When TP >7.9 g/dL, the average Δ[Na+] was -6.1 mmol/L, with 69% of samples showing differences ≥4.0 mmol/L.
- Hypoproteinemia was prevalent in ICU patients (81%), and only 10.9% of sodium orders included TP testing.
Conclusions:
- Increased TP concentrations significantly impact indirect sodium measurements via the electrolyte exclusion effect.
- Abnormal TP concentrations are common, yet sodium and TP are infrequently ordered together.
- Healthcare systems must recognize the limitations of indirect ISE sodium methods and consider implementing decision support tools.
Background:
Indirect ion-selective electrode (ISE) is the primary method used to measure sodium in automated clinical laboratories and is susceptible to the electrolyte exclusion effect. Pseudohyponatremia due to hyperproteinemia can affect patient management. The aims of this study were to (a) establish the relationship between serum total protein (TP) concentration and the magnitude of the electrolyte exclusion effect on indirect ISE-measured sodium values (b) estimate the frequency at which TP concentrations outside the reference interval may impact indirect-ISE measured sodium values, and (c) determine whether clinical decision support (middleware) rules in the laboratory would be effective for detecting cases of pseudohyponatremia.
Methods:
Residual waste serum specimens from physician-ordered TP testing were collected (n = 112). Sodium concentration was measured using indirect ISE (Cobas 8000, Roche Diagnostics) and direct ISE (ABL 825, Radiometer) methods. The difference in sodium concentration (Δ[Na+]) was calculated as follows: ([Na+]indirect-ISE - [Na+]direct-ISE). Retrospective TP results reported from July 31, 2013, to September 24, 2014, were stratified by ordering location and sodium and TP co-ordering rates were quantified.
Results:
Δ[Na+] was inversely proportional to TP concentration (y = -1.29x + 8.6, R = -0.883). The average difference (SD, range) was -6.1(3.4, -16-0) mmol/L when TP >7.9 g/dL (>79g/L), with 69% of samples demonstrating differences ≥4.0 mmol/L. A majority of intensive care unit patients (81%) were hypoproteinemic (<6.3 g/dL, <63g/L). Only 10.9% of sodium test orders include an order for TP on the same collection.
Conclusions:
Indirect sodium measurement is impacted when TP concentrations are increased. TP concentration outside the reference interval is prevalent and sodium is usually not ordered with TP. Health systems need to be aware of the limitations of their indirect-ISE method for sodium measurement.
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