Objective: Measurement of hypertonic saline-stimulated copeptin has recently been described for the differentiation of polyuria-polydipsia syndrome. This study aims to determine the copeptin response to intravenous 3% hypertonic saline, including evaluation of adverse effects, in a local cohort of healthy adults >18 years in Australia.
Design: Prospective clinical study
Methods: Twenty healthy volunteers (10 males and 10 females) were recruited. Participants underwent infusion of 3% hypertonic saline via a previously described standardised protocol (1,2), until the plasma sodium was ≥150 mmol/L, with measurement of plasma copeptin.
Results: Median peak sodium was 152 mmol/L (range 150 - 155) with osmolality 316 mmol/kg (range 306 - 320). Mean volume of hypertonic saline infused to reach target sodium ≥150 mmol/L was 1645 mL (range 1230 - 2220 mL). Median rate of plasma sodium rise was 5.6 mmol/L/hour (range 4.0 - 8.7 mmol/L/hour). Hypertonic saline-stimulated copeptin was normally distributed with mean of 48.0 pmol/L (median 29.1 pmol/L; range 9.6 - 167.4). Overall median symptom burden was 6/10 (range 3/10-9/10). Copeptin was significantly higher for those who experienced nausea and/or vomiting (n=13) (median 39.0 pmol/L; IQR 32.5, 90; range 25.0 - 67.4), compared to those participants who did not experience either (median 20.0 pmol/L; IQR 13.0 - 31.0; range 10.0 - 33.0) (p = 0.001). There were no serious adverse events.
Conclusions: Hypertonic saline-stimulated copeptin measurements were similar in our population compared to previously reported reference intervals in healthy volunteers (1). There is a wide range of stimulated copeptin measurements in the healthy population. Nausea and vomiting are common adverse effects and are associated with a significantly enhanced copeptin response. Significant nausea and/or vomiting could lead to possible false negative hypertonic saline-stimulated copeptin results in patients with central DI.