Hyponatremia authority Juan Carlos Ayus, MD, FACP, FASN, receives calls all the time from fellow nephrologists who have questions about the proper diagnosis and treatment of this condition. 

Dr. Ayus, who is Director of Clinical Research at Renal Consultants of Houston, is concerned that many practitioners are not aware of the standard of care for hyponatremia—a standard he helped create.


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How prevalent is hyponatremia?

Dr. Ayus: Probably up to 5% of patients admitted to the hospital for any reason have hyponatremia.

What are the most common causes?

Dr. Ayus: That depends. One group of people comes to the hospital with hyponatremia; another group develops it during the hospital stay. Hyponatremia in the hospital population is mostly a disease of people over age 65. They take many medications. Diuretics, especially thiazide, will make people prone to hyponatremia. Antidepressants, antiepileptics, and proton pump inhibitors have been associated with hyponatremia as well. Drugs that are used in cancer, especially cisplatin and cyclophosphamide, can also cause hyponatremia.

This means that when a person with hyponatremia is admitted to the hospital, the first thing the clinician should do is review all the medications the patient is taking and remove any medications that are linked with the possibility of hyponatremia.

Does the patient present with any specific complaints that would indicate hyponatremia?

Dr. Ayus: Remember, the diagnosis of hyponatremia is made by a lab test. You can’t look at somebody and say, “You have hyponatremia.” You can suspect that by the history and by the neurologic findings, but you have to confirm that with a laboratory test.

In the past, our group and others emphasized that the neurologic manifestations were the prominent factor in the presentation of hyponatremia. When serum sodium is lowered and the brain begins to swell, the brain can only expand to a limited extent because it is confined within the rigid skull. When expansion exceeds 5% of the volume of the brain, the person begins to have symptoms. This neurologic symptomatology, hyponatremic encephalopathy, is a constellation of symptoms ranging from nausea, vomiting, and headache, to convulsions, coma, respiratory arrest, and death. (Am J Physiol Renal Physiol 2008, 295:F619-F624)

These neurologic symptoms continue to be important, but now we know that hyponatremia in its chronic form can produce gait abnormalities similar to being intoxicated. Correcting the hyponatremia reverses the gait abnormality.

Also, animal studies suggest that chronic hyponatremia can produce osteoporosis. So now you have a double disadvantage: You have hyponatremia, which can produce weakness of the bones, and you can have chronic hyponatremia, which can cause gait abnormalities. When you combine them they can result in fractures and significant morbidity and mortality. (JAMA 1999; 281:2299-2304; Clin J Am Soc Nephrol 2010;15:167-178)

What misconceptions does the medical community have regarding hyponatremia?

Dr. Ayus: One basic misconception is that severe hyponatremic encephalopathy can occur in the absence of seizures. Example: A young female has had an appendectomy and now is receiving hypotonic fluids with a low concentration of sodium. In 48 hours she presents with nausea, vomiting, and headache. Hyponatremic encephalopathy is not considered, and she goes into respiratory arrest and dies with a sodium level of 119 or 120 mEq/L. The autopsy reveals massive brain edema and uncal herniation. This patient needed emergent treatment with hypertonic saline. (Ann Intern Med 1992;117:891-897)

Another misconception is that 0.9% sodium chloride is not associated with overcorrection of hyponatremia.  For example, an elderly female with chronic hyponatremia goes to the hospital, not overtly symptomatic but symptomatic nonetheless, with a sodium level of 115 mEq/L. She is treated with a continuous 0.9% sodium chloride and the sodium goes to 140 mEq/L in 48 hours, and she ends up with brain damage with evidence of demyelination. (N Engl J Med 1997;317:1190-1195)

The problem many nephrologists face is distinguishing patients with acute symptomatic hyponatremia that need urgent treatment with 3% hypertonic saline, from patients with chronic minimally symptomatic hyponatremia who are at risk for a spontaneous overcorrection that can result in brain damage. Appropriate treatment will not produce brain damage; inappropriate treatment will.

Our [research] group agrees with others that the patient with neurologic symptoms needs to be treated with hypertonic saline—basically, 3% hypertonic saline. We are now proposing a safer way, based on our experience with exercise-associated hyponatremia, such as hyponatremia that develops after running a marathon. 

At the end of the run the person may have respiratory complications like pulmonary edema, but the pulmonary edema is not because the heart is failing; it is the result of increased pressure in the brain secondary to cerebral edema. [Noncardiogenic pulmonary edema in hyponatremic encephalopathy is also referred to as Ayus-Arieff syndrome (Pediatr Nephrol 2010;25:1225-1238)—Eds] That syndrome is treated with intermittent boluses of hypertonic saline rather than a slow continuous infusion. When you resolve the cerebral edema, the pulmonary edema resolves. (Ann Intern Med 2000;132:711-714)

What is the safer treatment you recommend?

Dr. Ayus: We recommend 100 cc IV bolus of hypertonic saline for the treatment of symptomatic hyponatremia [N Engl J Med 2005;353:427-428]. This can be given over a 10-minute period and can be repeated once or twice. This treatment produces small but rapid increases in serum sodium.

It is not associated with any complications such as overcorrection, and at the same time it immediately establishes a gradient for removing water from the brain. It’s the safest way to avoid overcorrection and the brain damage secondary to inappropriate treatment. Nephrologists in general do not use this as the standard of care at the moment, but I believe it will become the standard.