Management of hyponatremia: Providing treatment and avoiding harm

Author and Disclosure Information

ABSTRACTHyponatremia, in its most severe form, requires urgent infusion of hypertonic saline to correct cerebral edema. However, overly rapid correction of chronic hyponatremia can cause osmotic demyelination syndrome. The authors review the treatment of hyponatremia in order to provide clinicians with a sound approach in a variety of settings in which severity, symptoms, and underlying disease states influence therapy. Also discussed is the current role of vasopressin antagonists in treatment.


  • Some hyponatremic patients present with acute, life-threatening cerebral edema due to severe hyponatremia. In others, the hyponatremia may be chronic and less severe, causing relatively few symptoms, but representing an important, independent marker of poor prognosis due to an underlying disease (eg, heart failure).
  • Even patients with chronic, less severe hyponatremia may have subtle symptoms of neurocognitive dysfunction and a higher risk of bone fractures.
  • Overly rapid correction of chronic hyponatremia or undercorrection of acute symptomatic hyponatremia can lead to serious neurologic injury.
  • Treatment strategies vary depending on the extracellular fluid volume status and the cause of hyponatremia.
  • Vasopressin antagonists (“vaptans”), a new class of aquaretic agents, specifically target the mechanism driving hyponatremia in some patients.



Hyponatremia, defined as a serum sodium concentration below 135 mmol/L, is one of the most frequently encountered electrolyte disorders. In 1981, Flear et al1 reported that 15% of their hospitalized patients had plasma sodium concentrations lower than 134 mmol/L, the cutoff they were using at that time.

Hyponatremia is sometimes merely a laboratory artifact or a result of improper blood collection. If real, it can be due to excessive water intake or, most often, the inability of the kidney to excrete water coupled with continued water intake. Patients with significant underlying cardiac, hepatic, or renal dysfunction are at greatest risk of developing hyponatremia, secondary to the nonosmotic release of antidiuretic hormone (ADH). Others at risk include postoperative patients (especially menstruating women), older patients on thiazide diuretics, patients with malignant or psychiatric illness, and endurance athletes.

In this article, we review the treatment of acute and chronic hyponatremia, emphasizing the importance of basing the therapy on the severity of symptoms and taking care not to raise the serum sodium level too rapidly, which can cause neurologic dysfunction.

Guidelines for managing hyponatremia2 are based mostly on retrospective studies and expert opinion, since few prospective studies have been done. Despite the paucity of evidence-based recommendations, we will attempt to incorporate findings from important human and animal studies and consensus guidelines from expert panels. We will focus initially on the critical diagnostic considerations necessary to initiate treatment.


Subsequent sections will address therapeutic approaches in two clinical settings:

Symptomatic hyponatremia, ie, with severe signs or symptoms of cerebral edema—a medical emergency; and

Asymptomatic hyponatremia, ie, without serious signs or symptoms of cerebral edema.


The treatment of hyponatremia begins by confirming a truly hypo-osmolar state, assessing its clinical significance, and determining its cause (Table 1).

The clinical and laboratory evaluations form the foundation of a proper approach to any patient with hyponatremia. The rationale behind making several important diagnostic distinctions will be discussed here briefly and then expanded on in the remaining text. The reader is referred to another review on the diagnostic evaluation of hyponatremia.3

Confirm that the patient truly has hypo-osmolar hyponatremia

The serum osmolality should be measured to confirm that it is low (ie, < 275 mOsm/kg). In addition, the arterial serum sodium concentration can be measured using a blood gas device if pseudohyponatremia (see below) is suspected. This method uses direct potentiometry and bypasses the dilutional step in the processing of venous samples.4

Rationale. The clinical consequences of hyponatremia are due to water moving from hypo-osmolar extracellular fluid into the relatively hyperosmolar interior of the cell. This water movement can cause progressive cerebral edema, resulting in a spectrum of signs and symptoms from headache and ataxia to seizures and coma. But significant fluid shifts and cerebral edema occur only if the extracellular fluid is hypo-osmolar relative to the intracellular fluid.

In fact, hyponatremia can occur in several situations in which the extracellular fluid is not hypo-osmolar. An increase in effective plasma osmoles (substances in the extracellular fluid that do not readily move across the plasma membrane) can cause water to move out of cells, resulting in translocational hyponatremia. This may be seen in hyperglycemia or when mannitol or contrast dye has been given. In these situations, the plasma is either isotonic or even hypertonic to the intracellular fluid, resulting in no movement of water into the cells and therefore no clinical consequences relating to the hyponatremia. Importantly, no therapy is required for the hyponatremia.

Other situations in which hyponatremia is present but not associated with true hypotonicity include states of excess protein or lipid in the blood (pseudohyponatremia). Also, if an infusion of hypotonic fluid is running, clinicians must be sure that blood samples are not drawn proximally in the same vein.

Are there significant signs or symptoms of cerebral edema?

Hyponatremia can cause brain swelling within the confined space of the skull as water shifts from the extracellular fluid into the cells. Depending on underlying risk factors (Table 2)5 and the severity and duration of hyponatremia (see below), this may result in signs or symptoms of cerebral edema, including visual changes, focal neurologic changes, encephalopathy, respiratory depression, and seizures. Ultimately, brain herniation can occur.

Patients need to be assessed quickly because those with serious neurologic signs or symptoms thought to be related to hyponatremia require urgent treatment with hypertonic saline to increase the serum sodium concentration, regardless of the underlying volume status, the cause of hyponatremia, or the time of onset.


Next Article: