NYU Winthrop Hospital announced the results of a new, groundbreaking study that shows that frequent misdiagnoses involving sodium imbalances in hospital patients result in thirsty, sodium-depleted patients denied fluids that their bodies desperately need, leading to increases in morbidity and mortality. The study involves hyponatremia, a common disorder that occurs when the concentration of sodium in a person’s blood becomes abnormally low. The condition is sometimes brought to light when powerful athletes, such as marathon runners or football players, die suddenly after drinking too much water, also known as “water intoxication.” The new study and its revelations on misdiagnoses may revolutionize the worldwide medical protocol among all physicians who treat patients with hyponatremia. Results of the study were recently published in two scholarly journals, Frontiers in Medicine and The American Journal of the Medical Sciences.
Water intoxication is commonly diagnosed among hospital patients with lung disease, heart failure, and cancers, but many of those hospital patients actually have a different sodium-related condition, “cerebral salt wasting.” Treatment protocol for these two hyponatremia conditions is diametrically opposite: patients with salt wasting are depleted of salt and water and require administration of the same; patients with water intoxication (clinically known as syndrome of inappropriate ADH secretion, or SIADH) retain too much water and need fluid restriction.
“For decades, the medical community widely presumed—incorrectly—that cerebral salt wasting had to involve a brain injury,” said John K. Maesaka, MD, who led the study in the Division of Nephrology and Hypertension at NYU Winthrop Hospital. “The common perception is that cerebral salt wasting is an uncommon disease, so sodium issues were typically attributed to SIADH where fluid restriction is the treatment of choice. Our study showed that more than a third of these patients actually had cerebral salt wasting and were in dire need of hydration.”
An estimated 5 percent to 30 percent of all hospital inpatients worldwide have some form of hyponatremia. Misdiagnoses involving cerebral salt wasting are especially common, since the condition is typically thought to be tied to brain injury or disease, though the NYU Winthrop study turned this assumption on its head, finding the majority of patients with cerebral salt wasting actually had no neurological findings. In the absence of cerebral disease, these patients would have been misdiagnosed with SIADH and denied fluids that their bodies needed. Their conditions then deteriorate further, with clinicians chalking it up to the patient’s underlying disease, such as a cancer finally “getting to them.” The new study, which found that 34 percent of cases would typically have been misdiagnosed if standard protocol had been followed, is expected to result in lifesaving changes to that protocol.
Sodium is an electrolyte that helps regulate the amount of salt and water that exists outside of the cells. In the case of SIADH, serum sodium levels decrease and excess water in the body causes cells to swell, especially brain cells. This can lead to irritability, confusion, and an unsteady gait. When severe and acute, as sometimes seen in athletes or others drinking large volumes of water over a short period of time, it can cause seizures, coma and death. SIADH is easily treated with fluid restriction and medication.
“It is essential to differentiate these SIADH water-logged patients from dehydrated patients with cerebral salt wasting,” noted Dr. Maesaka. “Differentiating the two syndromes has been difficult because both present with identical biochemical testing and are associated with similar clinical diseases.”
The NYU Winthrop research was the first large study to rely on firm physiologic principles, developed over a 25-year period of testing, rather than existing algorithms fraught with inaccuracies and limitations. The study involved 62 hyponatremic patients over a two-year period. Hyponatremia is defined as a serum sodium <135mmol/L. Patients with congestive heart failure, cirrhosis of the liver, and advanced kidney failure were excluded from the study.
Of the 62 patients studied, 33 were determined to have excess water in their body—SIADH—and needed fluid restriction. Surprisingly, 24 patients were found to have cerebral salt wasting, yet 21 out of those 24 had no clinical evidence of cerebral disease. Without neurological findings of any brain injury, standard protocol would have called for these 21 patients to be treated as if they had SIADH and restricted of fluids when, in fact, renal abnormalities and salt wasting had already depleted their bodies of water. Fluid restricting patients with renal salt wasting might thus contribute to an increase in morbidity and mortality.
Added Dr. Maesaka, “This study supports our proposal to change the term ‘cerebral salt wasting’ to ‘renal salt wasting,’ because salt wasting is not necessarily accompanied by cerebral disease.” Dr. Maesaka has developed a diagnostic algorithm to differentiate between the two conditions—renal salt wasting and SIADH—with the algorithm largely based on the excretion of uric acid and response to saline infusion.
The NYU Winthrop Hospital study was co-authored by NYU Winthrop physicians Louis Imbriano, MD, and Nobuyuki Miyawaki, MD. Study results were published in The American Journal of the Medical Sciences under the title, “High Prevalence of Renal Salt Wasting Without Cerebral Disease as Cause of Hyponatremia in General Medical Wards,” and in Frontiers in Medicine under the title, “Determining Fractional Urate Excretion Rates in Hyponatremic Conditions and Improved Methods to Distinguish Cerebral/Renal Salt Wasting From the Syndrome of Inappropriate Secretion of Antidiuretic Hormone.”