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Laura Potasso, Julie Refardt, Irina Chifu, Martin Fassnacht, Wiebke Kristin Fenske, and Mirjam Christ-Crain

Objective: Hyperkalemia has been reported upon different hypertonic saline infusion protocols. Since hypertonic saline test has recently been validated for the differential diagnosis of diabetes insipidus (DI), we aimed to investigate the course of plasma potassium during the test.

Design: We analyzed data of 90 healthy volunteers and 141 patients with polyuria-polydipsia syndrome (PPS) from two prospective studies evaluating the hypertonic saline test. Our primary outcome was the incidence rate of hypertonic saline induced hyperkalemia >5mmol/L.

Methods: Participants received a 250 ml bolus of 3% NaCl solution, followed by 0.15ml/min/kg body weight continuously infused targeting a plasma sodium level of 150mmol/L. Blood samples and clinical data were collected every 30 minutes.

Results: Of the 231 participants, 16% (n=37/231) developed hyperkalemia. The incidence of hyperkalemia was higher in healthy volunteers and in patients with primary polydipsia (25.6% (n=23/90) and 9.9% (n=14/141) respectively), and only occurred in 3.4% (n=2/59) of patients with diabetes insipidus. Hyperkalemia developed mostly at or after 90-minute test duration (81.1%, n= 30/37). Predictors of hyperkalemia (OR (95% CI)) were male sex (2.9 (1.2-7.4), p=0.02), a plasma potassium at baseline >3.9mmol/L (5.2, (1.8-17.3), p=0.004), normonatremia at 30-minute test duration (3.2 (1.2-9.5), p=0.03), and an increase in potassium levels already at 30-minute test duration as compared to baseline (4.5 (1.7-12.3), p=0.003). Hyperkalemia was transient and resolved spontaneously in all cases.

Conclusion: The hypertonic saline test can lead to hyperkalemia, especially in patients with primary polydipsia who experience a longer test duration. Monitoring potassium levels in these patients is recommended.