Observational study of biochemical volume biomarker levels in response to a standardized intravenous isotonic saline infusion in patients with hyponatremia.

Hyponatremia (low plasma sodium concentration) is a common electrolyte disorder among hospitalized patients that can lead to complications such as gait instability, falls and mental changes. Both hyponatremia itself and overly rapid correction of hyponatremia may lead to brain damage.

There are several underlying causes of hyponatremia that require different treatment strategies. Specifically, hypovolemia is treated with fluid infusion while other common causes such as the syndrome of inappropriate diuresis (SIAD) and hypervolemic conditions need fluid restriction. In clinical practice, it can be challenging to identify the main cause of hyponatremia due to overlapping diagnosis and unreliable diagnostic tools, typically leading to a timely trial and error approach to therapy.

A saline infusion test (SIT) is often used to diagnose hypovolemic hyponatremia. To our knowledge, the test has never been validated, but relies on the rationale that the sodium concentration will increase more with saline infusion in hypovolemia than in other causes of hyponatremia. Typically, one liter of isotonic saline is infused intravenously and an arbitrarily set cut-off for sodium increase is used to indicate hypovolemia. As the response of sodium depends on several factors that affects the renal free water excretion capacity, this measure may not be the most accurate nor the most efficient. Another, more direct, approach could be to measure the change in biochemical markers of circulating volume in response to the volume expansion that comes with saline infusion. We will measure several different biomarkers before, during and after a standardized isotonic saline infusion in patients hospitalized with hyponatremia. Based on the results, we hope to develop a more precise tool for the differential diagnosis of hyponatremia.

Inclusion Criteria:

• Plasma sodium 120-130 mmol/L
• Effective osmolality (2 x plasma sodium + plasma glucose) < 275 milliosmol/L
• Age > 18 years

Exclusion Criteria:

• Intensive care unit (ICU) admission
• Adequate sodium correction rate: > 4 mmol/L last 24 hours
• Primary polydipsia: urine osmolality < 100 mOsm/L
• Hypertonic saline therapy
• Adrenal insufficiency
• Severe heart failure: ejection fraction < 35 % or clinical suspicion of decompensated heart failure
• Ascites grade 3 (marked abdominal distention and discomfort)
• Chronic renal failure stage 4 or 5: estimated glomerular filtration rate < 30
• Failure to submit informed consent

Patients admitted to hospital with hyponatremia.