The challenges of sodium measurements: indirect versus direct ion-selective method

in European Journal of Endocrinology
Correspondence should be addressed to M Christ-Crain; Email: mirjam.christ-crain@usb.ch

*(J Refardt and C O Sailer contributed equally to this work)

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Background

Diagnosis and treatment of dysnatremia is challenging and further complicated by the pitfalls of different sodium measurement methods. Routinely used sodium measurements are the indirect (plasma/serum) and direct (whole blood) ion-selective electrode (ISE) method, showing discrepant results especially in the setting of acute illness. Few clinicians are aware of the differences between the methods in clinically stable patients or healthy volunteers.

Methods

Data of 140 patients and 91 healthy volunteers undergoing osmotic stimulation with hypertonic saline infusion were analyzed. Sodium levels were measured simultaneously by indirect and direct ISE method before and at different time points during osmotic stimulation up to a sodium threshold of ≥150 mmol/L. The primary outcome was the difference in sodium levels between the indirect and direct ISE method.

Results

878 sodium measurements were analyzed. Mean (s.d.) sodium levels ranged from 141 mmol/L (2.9) to 151 mmol/L (2.1) by the indirect ISE compared to 140 mmol/L (3) to 149 mmol/L (2.8) by the direct ISE method. The interclass correlation coefficient between the two methods was 0.844 (95% CI: 0.823–0.863). On average, measurements by the indirect ISE were 1.9 mmol/L (95% CI limits: −3.2 to 6.9) higher than those by the direct ISE method (P < 0.001). The tendency of the indirect ISE method resulting in higher levels increased with increasing sodium levels.

Conclusion

Intra-individual sodium levels differ significantly between the indirect and direct ISE method also in the absence of acute illness. It is therefore crucial to adhere to the same method in critical situations to avoid false decisions due to measurement differences.

Downloadable materials

  • Supplementary Figure 1: Pearson&#x2019;s correlation coefficient between the indirect and the direct ISE measurement method at A) University Hospital Basel: R = 0.89 and B) University Hospital Wuerzburg: R = 0.8.
  • Supplementary Figure 2: Bland-Altman graph of difference in sodium measurements between the indirect and the direct ISE method in A) the University Hospital Basel and B) the University Hospital Wuerzburg. The middle line represents the average difference of A) 2 mmol/l and B) 2.6 mmol/l between the two methods. The two outer dotted lines represent the 95%-confidence interval limits of agreement (A) lower limit -2.2, upper interval limit 6.2, and B) lower limit -3.4, upper limit 8.5).

 

     European Society of Endocrinology

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Figures

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    Course of sodium levels during the hypertonic saline infusion test according to the indirect and direct ISE measurement methods. Mean and error bar are represented at different time points.

  • View in gallery

    Correlation between indirect and direct ion selective electrode method. The blue line represents the linear regression line between the two measurements. The black line represents the ideal correlation line. A full colour version of this figure is available at https://doi.org/10.1530/EJE-19-0101.

  • View in gallery

    Bland–Altman graph of difference in sodium measurements between the indirect and the direction selective electrode method. The middle line represents the mean difference of 1.9 mmol/L between the two methods. The two outer dotted lines represent the 95% confident interval limits of agreement (lower limit −3.2, upper limit 6.9).

  • View in gallery

    Difference in sodium levels between the indirect and direction selective electrode method according to nine randomly selected individual participants with at least six consecutive simultaneous sodium measurements. Every color represents one participant. Values above 0 represent sodium levels measured by indirect ISE being higher compared to the direct ISE method; values below 0 represent sodium levels measured by indirect ISE being lower compared to the direct ISE method.

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