Narrative Review
Hyponatremia and Mortality: Moving Beyond Associations

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Acute hyponatremia can cause death if cerebral edema is not treated promptly. Conversely, if chronic hyponatremia is corrected too rapidly, osmotic demyelination may ensue, which also potentially is lethal. However, these severe complications of hyponatremia are relatively uncommon and often preventable. More commonly, hyponatremia predicts mortality in patients with advanced heart failure or liver cirrhosis. In these conditions, it generally is assumed that hyponatremia reflects the severity of the underlying disease rather than contributing directly to mortality. The same assumption holds for the recently reported associations between hyponatremia and mortality in patients with pulmonary embolism, pulmonary hypertension, pneumonia, and myocardial infarction. However, recent data suggest that chronic and mild hyponatremia in the general population also are associated with mortality. In addition, hyponatremia has been associated with mortality in long-term hemodialysis patients without residual function in whom the underlying disease cannot be responsible for hyponatremia. These new data raise the question of whether hyponatremia by itself can contribute to mortality or it remains a surrogate marker for other unknown risk factors. We review hyponatremia and mortality and explore the possibility that hyponatremia perturbs normal physiology in the absence of cerebral edema or osmotic demyelination.

Section snippets

Complications of Hyponatremia

In a single issue in June 1986, the New England Journal of Medicine published 2 seminal articles on the complications of hyponatremia.6, 7 The study by Arieff6 reported the development of acute hyponatremia after elective surgery in 15 previously healthy women. Their average serum sodium level decreased from 138 to 108 mEq/L and was accompanied by grand mal seizures and respiratory arrest. Four women died and 9 were left in a persistent vegetative state. In most of these women, acute

Hospitalized Patients

Over the years, several studies have reported the outcome of hospitalized patients with hyponatremia (Table 1). In 1976, Arieff et al20 were some of the first to do so; the authors systematically studied the neurologic complications of hyponatremia in a selected cohort of 66 patients. They found that patients with acute hyponatremia were symptomatic significantly more often than those with chronic hyponatremia and that they had a mortality rate of 50%. Some patients with chronic hyponatremia

Possible Mechanisms of the Hyponatremia-Mortality Association

Previously, we proposed 3 possible scenarios to explain the association between hyponatremia and mortality (Fig 2).33 First, acute hyponatremia can contribute directly to mortality when there is progressive cerebral edema without timely intervention. Although it remains extremely important to recognize and treat this entity, as noted, it is unlikely to explain the overall association between hyponatremia and mortality. In the second scenario, hyponatremia is merely a surrogate marker for the

Conclusion

Hyponatremia increasingly is being recognized as an independent predictor of mortality. Prospective studies are necessary to determine whether hyponatremia in itself contributes to mortality and whether correcting hyponatremia improves outcomes. Mechanistically, the effects of hyponatremia on organs other than the brain should be a focus of research (Box 1). Until such studies are available, the presence of hyponatremia should be regarded as a risk factor for adverse outcomes and patients

Acknowledgements

Support: None.

Financial Disclosure: The authors declare that they have no relevant financial interests.

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    Originally published online January 7, 2013.

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