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:

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

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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.


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.


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.


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.

Supplementary 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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