Review
Hyponatremia: Clinical Diagnosis and Management

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Abstract

Hyponatremia is a common clinical problem in hospitalized patients and nursing home residents. It also may occur in healthy athletes after endurance exercise. The majority of patients with hyponatremia are asymptomatic and do not require immediate correction of hyponatremia. Symptomatic hyponatremia is a medical emergency requiring rapid correction to prevent the worsening of brain edema. How fast we should increase the serum sodium levels depends on the onset of hyponatremia and still remains controversial. If the serum sodium levels are corrected too rapidly, patients may develop central pontine myelinolysis, but if they are corrected too slowly, patients may die of brain herniation. We review the epidemiology and mechanisms of hyponatremia, the sensitivity of women to hyponatremic injury, the adaptation and maladaptation of brain cells to hyponatremia and its correction, and the practical ways of managing hyponatremia. Because the majority of hyponatremia is caused by the non-osmotic release of vasopressin, the recent approval of the vasopressin receptor antagonist conivaptan for euvolemic hyponatremia may simplify hyponatremia management. However, physicians should be aware of the risk of rapid correction of hyponatremia, hypotension, and excessive fluid intake.

Section snippets

Physiology of Water Metabolism

The mechanisms involved in producing concentrated or dilute urine have been enumerated in great detail elsewhere,17 and we will review these mechanisms only briefly so as to provide a context for the clinical categorization of patients with hyponatremia. Humans with normal kidney function can produce urine with a solute concentration range from less than 100 mosm/L to more than 1000 mosm/L. This allows for a more than 10× range in urine volume and, by extension, fluid intake while preserving

Mechanisms of Hyponatremia

The clinical approach to hyponatremia (Figure 2) generally begins by excluding conditions in which the osmolarity is not reduced. In fact, because sodium is the predominant osmole in the extracellular fluid (ECF) compartment and serum, physicians consider hyponatremia to be essentially synonymous with a reduction in osmolarity. This rather casual association has led to the characterizations of all situations in which hyponatremia does not reflect hypo-osmolarity as “pseudohyponatremia.” This is

Sensitivity of Women to Hyponatremic Injury

Patients with hyponatremia may present with decreased levels of consciousness and even seizures. The severity of these symptoms and signs seems to be related to both the acuity and the severity of the hyponatremia.31 The gender and age of the afflicted individual also seems to be important.

In a landmark article in 1986, Arieff32 described 15 previously healthy women who developed acute hyponatremia (average SNa decreased to 108 mmol/L) after elective surgery. The outcomes in these patients were

Brain Osmoles and Hyponatremia

The brain is the organ that is most susceptible to the sudden decrease of SNa in the body because it is confined within the rigid skull. In the setting of EAH, symptoms such as nausea, vomiting, and confusion begin when SNa decreases to less than 129 mEq/L.15 If hyponatremia develops slowly over several days, brain cells are capable of adapting by releasing intracellular K and other solutes to maintain the cell volume. We have shown that in chronically hyponatremic rats, the decrease in brain

Therapy of Hyponatremia

The treatment of hyponatremia is determined by 3 major factors: severity of hyponatremia, that is, the presence or absence of severe central nervous system symptoms such as lethargy, delirium, seizure, and coma; onset of hyponatremia: acute (within 48 hours) or chronic (>48 hours); and volume status. Symptomatic hyponatremia, particularly if associated with hypoxia, is a medical emergency. An immediate increase in SNa level by 8 to 10 meq/L in 4 to 6 hours with hypertonic saline is recommended.

New Therapies for Hyponatremia

Recently, conivaptan, a V1A/V2-receptor antagonist, was approved for treating hospitalized patients with euvolemic hyponatremia. Because most hyponatremia is caused by the non-osmotic release of vasopressin, the availability of vasopressin antagonists is exciting and may change the management of hyponatremia completely. Ghali et al50 reported the efficacy and safety of 5-day oral conivaptan therapy (40 or 80 mg/day) for euvolemic or hypervolemic hyponatremia. In 1 day, SNa was increased by 4

Acknowledgments

The authors thank Carol Woods and Kathy Glockner for their excellent secretarial assistance. The authors would also like to acknowledge salary support from the National Institutes of Health (HL67963 and DK45666).

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    The authors received salary support from the National Institutes of Health (HL67963 and DK45666).

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