New European Hyponatremia Guidelines Released

Recently released guidelines seek to provide clarity to the management of hyponatremia by outlining an evidence-based, patient-centered approach to diagnosis and treatment.

Despite being a commonly encountered condition across a range of patients and settings (it can occur in up to 30% of hospitalized patients), approaches to hyponatremia management tend to vary from institution to institution. According to “Clinical Practice Guideline on Diagnosis and Treatment of Hyponatraemia,” created by the Hyponatraemia Guideline Development Group and published in the European Journal of Endocrinology, this is due to the fact that “previous guidance has often been based on experience or practice, without a systematic approach to evaluation and lacking a clear, patient-centered focus.” Effective management of hyponatremia in the “front line” practice setting requires “clear, concise and practical advice” that does not rely on “complex diagnostic algorithms and time-consuming investigations.”

To remedy this, the European Society of Intensive Care Medicine (ESICM), the European Society of Endocrinology (ESE), and the European Renal Association—European Dialysis and Transplant Association (ERA–EDTA) developed this new guidance on the diagnostic approach and treatment of hyponatremia, defined as a serum sodium concentration of less than 135 mmol/L.

The guidelines specifically cover only the management of hyponatremia in adult patients, as the guideline group “judged that hyponatraemia in children represented a specific area of expertise.”

In the interest of providing consistent and clear classification of hyponatremia that is “directly relevant for patient management,” the authors provided definitions of hyponatremia based on three factors: serum sodium concentration, duration of disease, and symptoms.

They defined mild hyponatremia as serum sodium concentration between 130 and 135 mmol/l, moderate hyponatremia as serum sodium concentration between 125 and 129 mmol/l, and “profound” hyponatremia as serum sodium concentration <125 mmol/l.

Acute hyponatremia was defined as hyponatremia that has been documented to exist for less than 48 hours; chronic hyponatremia was defined as documented disease existing for more than 48 hours. “Moderately symptomatic” hyponatremia was deemed to be “any biochemical degree of hyponatraemia in the presence of moderately severe symptoms of hyponatraemia,” whereas “severely symptomatic” hyponatremia was defined as “any biochemical degree of hyponatraemia in the presence of severe symptoms of hyponatraemia.”

Distinguishing between chronic and acute hyponatremia is of critical importance because it allows clinicians to assess whether a patient is at a greater risk of immediate brain edema than of osmotic demyelination. The authors wrote that unfortunately too often in clinical practice this distinction “is often unclear, particularly for patients presenting to the emergency room. It is often unknown when the serum sodium concentration has started decreasing.”

The authors also cautioned that the differential diagnosis of hyponatremia is difficult and emphasized that “the different classifications of hyponatraemia are not mutually exclusive and that classification should always occur with the clinical condition and the possibility of combined causes of hyponatraemia in mind.”

Before determining the course of treatment, clinicians should confirm whether the patient has hypotonic or non-hypotonic hyponatraemia (this is covered in depth in the guideline), test for hyperglycemic hyponatremia, and identify the underlying cause of the patient’s hyponatremia.

The guidelines recommend determining the underlying cause of hyponatremia by measuring urine osmolality and urine sodium using spot urine samples. Urine osmolality of <100 mOsm/kg usually indicates relative excess water intake as the underlying cause of the condition. Patients with urine osmolality of >100 mOsm/kg should be measured for urine sodium. Low urine sodium concentration (≤30 mmol/l) indicates low effective arterial volume as the cause of the hyponatremia. Urine sodium concentration >30 mmol/l should prompt clinicians to assess the patient for extracellular fluid status and use of diuretics.

The section of the guidelines on treatment includes recommendations for treating hyponatremia with severe symptoms regardless of whether it is acute or chronic (with an emphasis on prompt infusion of 3% hypertonic saline and close monitoring of serum sodium concentrations during the first 24 hours of treatment especially) and moderately severe symptoms (infusion of 3% hypertonic saline, aiming for a 5 mmol/l per 24-hour increase in serum sodium concentration while limiting the increase to 10 mmol/l in the first 24  hours and 8 mmol/l during every 24  hours thereafter).

For patients with expanded cellular fluid, the guidelines recommend fluid restriction, and recommend against the use of vasopressin receptor antagonists and demeclocycline. For patients with syndrome of inappropriate antidiuresis (SIAD), the guidelines recommend fluid restriction as first-line treatment for moderate or profound hyponatremia, followed by increasing solute intake with 0.25—0.50 g/kg per day of urea or a combination of low-dose loop diuretics and oral sodium chloride. The guidelines recommend against lithium or demeclocycline, as well as the use of vasopressin receptor antagonists in moderate hyponatremia.

For patients with reduced circulating volume, the guidelines recommend IV infusion of 0.9% saline or a balanced crystalloid solution at 0.5—1.0 ml/kg per hour to restore volume. In patients with hemodynamic instability, the guidelines note that “the need for rapid fluid resuscitation overrides the risk” of overcorrection.

The guidelines recommend prompt intervention in cases of overcorrection of serum sodium concentration (>10 mmol/l during the first 24  hours or >8 mmol/l in any 24 -hour period thereafter), including stopping treatment and consulting with a specialist about initiating infusion of 10 ml/kg body weight of electrolyte-free water and/or IV desmopressin 2 μg.