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Association of Therapies With Morbidity and Mortality

J. Carlos Ayus, MD; Allen I. Arieff, MD

JAMA. 1999;281:2299-2304.

Context  Chronic hyponatremia in postmenopausal women is a common clinical problem often viewed as benign. Fluid restriction is usually the recommended therapy, largely because the extent of morbidity is unknown and because it has been postulated that intravenous (IV) sodium chloride may cause brain damage.

Objective  To compare IV sodium chloride with fluid restriction in the treatment of postmenopausal women with chronic symptomatic hyponatremia.

Design  Nonrandomized prospective study.

Setting  Two university medical centers and affiliated community hospitals.

Patients  A total of 53 postmenopausal women with chronic symptomatic hyponatremia (chronic plasma sodium <130 mmol/L in the presence of central nervous system manifestations) treated consecutively from 1988-1997 and followed up for 1 year. The mean (SD) age of the patients was 62 (11) years.

Interventions  The therapeutic interventions were IV sodium chloride before respiratory insufficiency (n=17), IV sodium chloride after respiratory insufficiency (n=22), and fluid restriction only (n=14).

Main Outcome Measures  Morbidity and neurological outcome at 4 months or longer as assessed by cerebral performance category (CPC) in relation to the therapy, initial plasma sodium level, and rate of correction.

Results  Chronic symptomatic hyponatremia (mean [SD] sodium level 111 [12] mmol/L) was present for 5.2 [4.5] days. Death or major morbidity occurred in 44 (83%) of 53 patients, including 10 with orthopedic injury. Twelve patients had hypoxemia (PO₂=63 [25] mm Hg) and cerebral edema. Among patients who received IV sodium chloride before respiratory insufficiency, plasma sodium levels were increased by 22 (10) mmol/L in 35 hours and patients had a CPC of 1.0 (normal or slight disability). Among patients who received IV sodium chloride after respiratory insufficiency, plasma sodium levels were increased by 30 (6) mmol/L in 41 hours and patients had a CPC of 3.0 (1.2) (severe disability). Among patients who had fluid restriction only, plasma sodium levels were increased by 3 (2) mmol/L in 41 hours and patients had a CPC of 4.6 (0.7) (4=persistent vegetative state; 5=death). The outcomes did not correlate with either the initial plasma sodium level (r=0.05, P>.12) or the rate of correction (r=0.31, P>.10).

Conclusions  Chronic symptomatic hyponatremia in postmenopausal women can be associated with major morbidity and mortality. Therapy with IV sodium chloride was associated with significantly better outcomes than fluid restriction.

Author Affiliations: Department of Medicine, Baylor College of Medicine, Houston, Tex (Dr Ayus); and Department of Medicine, University of California School of Medicine, San Francisco (Dr Arieff).

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