Clinical research study
Utility and Limitations of the Traditional Diagnostic Approach to Hyponatremia: A Diagnostic Study

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Abstract

Background

The differential diagnosis of hyponatremia is often challenging because of its association with multiple underlying pathophysiological mechanisms, diseases, and treatment options. Several algorithms are available to guide the diagnostic approach to hyponatremia, but their diagnostic and clinical utility has never been evaluated. We aimed to assess in detail the diagnostic utility as well as the limitations of the existing approaches to hyponatremia.

Methods

Each of the 121 consecutive subjects presenting with hyponatremia (serum sodium <130 mmoL/L) underwent 3 different and independent diagnostic and therapeutic approaches: inexperienced doctor applying an established Algorithm, intensive care senior physicians acting as Senior Physician, and senior endocrinologist serving as Reference Standard.

Results

The overall diagnostic agreement between Algorithm and Reference Standard was 71% (respective Cohen's kappa and delta values were 0.64 and 0.70), the overall diagnostic agreement between Senior Physician and Reference Standard was 32% (0.20 and 0.19, respectively). Regarding the therapeutic consequences, the diagnostic accuracy of the Algorithm was 86% (0.70 and 0.72, respectively) and of the Senior Physician was 48% (0.01 and 0.04, respectively). In retrospect, by disregarding the patient's extracellular fluid volume and assessing the effective arterial blood volume by determination of the fractional urate excretion, the Algorithm improved its diagnostic accuracy to 95%.

Conclusion

Although the Algorithm performed reasonably well, several shortcomings became apparent, rendering it difficult to apply the Algorithm without reservation. Whether some modifications may enhance its diagnostic accuracy and simplify the management of hyponatremia needs to be determined.

Section snippets

Study Design and Population

All patients with serum sodium concentration <130 mmoL/L and serum osmolality <280 mosm/kg at admission to the University Hospital of Würzburg were consecutively enrolled in this diagnostic study between April and November 2007 (n = 121). Patients aged <18 years were not eligible. Study design, conduct, and reporting followed the criteria proposed by the “Standards for the Reporting of Diagnostic Accuracy Studies” initiative.7 The study was approved by the Ethical Committee of the University of

Baseline Characteristics

In total, 121 hyponatremic patients (53 male, 68 female) were enrolled. Fifteen patients exhibited severe hyponatremia (serum sodium <115 mmol/L; 12.4%) and 62 patients moderate hyponatremia (<125 mmol/L; 51.2%). The mean age was 64 years (range 22-91 years). The causes of hyponatremia according to the Reference Standard were as follows: primary polydipsia 4%, hypervolemia 20%, hypovolemia 32%, SIADH 35%, diuretic-induced 7%, and adrenal insufficiency 2%. In 10 patients (8%), severe or moderate

Discussion

For a classification to be useful, it must guide the clinician to arrive at the correct diagnosis in due course in order to commence the appropriate therapy. In this study, we analyzed the diagnostic accuracy of a given diagnostic algorithm to hyponatremia, originating from 2 approaches published by Schrier8 and Verbalis9 with minor modifications. To the best of our knowledge, this is the first analysis carried out in consecutive hyponatremic subjects within a real-world setting.

Surprisingly,

Conclusion

In conclusion, we demonstrated for the first time the utility of an established hyponatremia algorithm in a real-world clinical setting. Strict adherence to the existing algorithm by a young physician yielded a higher diagnostic accuracy compared with the diagnostic performance of a senior physician.

However, the algorithm revealed several shortcomings, making it difficult to apply in clinical practice. Whether the proposed modifications to this algorithm may enhance its diagnostic accuracy and

References (16)

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Funding: None.

Conflict of Interest: The authors have no conflicts to disclose.

Authorship: All authors had access to the data and played a role in writing this manuscript.

Both authors contributed equally.

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