Hyponatremia affects nearly 2% of the general population and up to 60% of hospitalized patients, according to data from the National Health and Nutrition Examination Survey for 1999 to 2004. That makes it the most common electrolyte disorder that hospitalists manage, yet it still often goes untreated or undertreated.
In one multicenter study of 762 inpatients with heart failure who were hyponatremic on admission, only 19% had serum sodium concentrations of at least 135 mEq/L at discharge.
Findings like these—published online Aug. 3, 2017, by the Journal of the American Heart Association—are particularly concerning given emerging evidence about the implications of hyponatremia. “It is known that inpatients with hyponatremia have increased morbidity and mortality in general, along with increased overall hospital costs and readmission rates,” said Melinda J. Johnson, MD, FACP, a hospitalist and clinical professor of internal medicine at the University of Iowa Carver College of Medicine in Iowa City.
Chronic hyponatremia has been linked to balance problems and increased risk of falls and fractures, she noted. As yet, it's unclear if these associations are causal—hyponatremia tends to denote poor overall health and is linked to several comorbidities. But she recommends taking hyponatremia seriously, starting with a hard look at potential underlying causes.
“The history is the most important aspect for diagnosing and treating hyponatremia,” she said. “In the history of present illness, ask about diarrhea, vomiting, low protein intake, diuretic use, and high fluid intake. In the past medical history, look for HIV, cirrhosis, heart failure, central nervous system disease, pulmonary disease, malignancy, and recent surgery.” Alcohol and ecstasy use are relevant factors in the social history, while thiazides and selective serotonin reuptake inhibitors can cause drug-induced hyponatremia, which is often overlooked, she and other experts noted.
Rate of correction
Besides seeking an underlying cause, hospitalists should determine how long a patient has been hyponatremic to guide treatment. “The rate of drop in sodium leading to hyponatremia is much more important than the actual absolute serum sodium value,” Dr. Johnson said. “Acute and hyperacute hyponatremia should be treated rapidly, but chronic hyponatremia should not. Above all, the history of hyponatremia and the patient's most recent previous serum sodium level are essential to know.”
Acute hyponatremia—defined as having started within 48 hours—merits rapid correction with hypertonic saline to prevent brain herniation, according to a joint guideline issued by European societies in 2014. But hyponatremia among inpatients is usually subacute or chronic and should be corrected gradually to avoid causing osmotic demyelination syndrome, experts emphasized.
Alcoholism, liver disease, malnutrition, and hypokalemia increase the risk of osmotic demyelination and therefore patients with any of these conditions require particular caution, Dr. Johnson said. Overly rapid correction of chronic hyponatremia is one of the most common errors she sees in hospital settings, she added.
To be safe, assume a case of hyponatremia is chronic unless it developed under observation, said Arthur Greenberg, MD, a nephrologist and professor emeritus of medicine at Duke University School of Medicine in Durham, N.C. For example, if a patient was known to have a normal serum sodium concentration two days previously but now has a very low reading, that would indicate an acute problem, he said. “If you don't have that evidence, you have to assume hyponatremia is chronic.”
The appropriate correction rate of serum sodium has been an area of debate, particularly for chronic hyponatremia, said Satyen S. Nichani, MD, ACP Member, clinical assistant professor of internal medicine at the University of Michigan Medical School in Ann Arbor. “An increase in serum sodium of 10 to 12 [mEq] per L per day is thought to be appropriate by some, while others feel that a lower goal rate of 6 to 8 mEq per L per day is safer to minimize the risk of osmotic demyelination,” he said.
All three experts favored the slower approach. The worst symptoms of acute hyponatremia, such as seizure and obtundation, can usually be corrected by rapidly correcting serum sodium concentration by only 4 to 6 mEq/L, Dr. Johnson noted. “The risk of osmotic demyelination increases after the rate of correction exceeds 12 [mEq] per L per day,” Dr. Nichani added. “Therefore, hospitalists should aim for a maximal increase of 8 [mEq] per L in the first 24 hours, particularly when the risk of osmotic demyelination is high.”
It's also vital to differentiate treatment goals from limits when correcting serum sodium concentration, Dr. Greenberg said. “Keep in mind that the goal for treatment on any given day is very modest—6 to 8 mEq per L in any 24-hour period for a patient who is not at risk of osmotic demyelination syndrome, or 4 to 6 mEq per L for someone who is at increased risk of osmotic demyelination syndrome.”
For the limits of correction, he recommends 8 mmol/L in any 24-hour period for patients at high risk of osmotic demyelination and, for patients at normal risk, 10-12 mmol/L in 24 hours and 18 mmol/L in 48 hours.
These goals and limits were endorsed in a set of expert panel recommendations, published as a supplement to the American Journal of Medicine in 2013. The recommendations cited a lack of evidence that increasing serum sodium levels by more than 6 mEq/L in 24 hours improves outcomes. The authors shared a handy mnemonic: “Six a day makes sense for safety; so [correct by] six in six hours for severe sx's and stop.”
For all patients, Dr. Johnson advised that physicians avoid correcting hyponatremia by more than 8 mEq/L in 24 hours, and keep in mind that giving potassium for hypokalemia can increase serum sodium concentration. “Patients must be monitored accordingly,” he said.
Also be wary of relying too heavily on formulas that predict changes in serum sodium concentration as a function of dose-infused hypertonic saline, Dr. Greenberg said. “They are not precise and tend to under-predict the increase. Regard them as approximations. If you give hypertonic saline, expect the response to be unpredictable.”
Given the vagaries of scheduled blood draws and laboratory reporting, he advises monitoring serum sodium concentration every two hours in order to be sure to have a new result in hand at least every four hours when hypertonic saline is administered or if patients are at risk of a rapid rise in serum sodium concentration because of spontaneous water diuresis.
Examples of the latter include patients with water intoxication, beer potomania, volume depletion, thiazide use, or hyponatremia resulting from a low-solute diet. “Without frequent monitoring, hours can pass with an uncontrolled and unmonitored sodium rise,” Dr. Greenberg said. “You don't want patients going from 105 to 131 [mEq per L] on the floor in the course of a day.”
The risk of osmotic demyelination syndrome due to rapid correction tends to decrease over subsequent days of treatment, as patients' serum sodium levels gradually increase. At that point, serum sodium concentration can be measured less frequently, such as twice daily, experts said.
Syndrome of inappropriate antidiuretic hormone secretion
Syndrome of inappropriate antidiuretic hormone secretion (SIADH), the most frequent cause of chronic, euvolemic hyponatremia, is another area where experts noted room for improvement. “Differentiating SIADH from dehydration is a common dilemma that requires clinicians to base their diagnosis on their judgment of the patient's volume status,” said Dr. Nichani. “The accuracy of the physical signs of hyponatremia varies considerably, making it difficult to distinguish mild hypovolemia from euvolemia on clinical grounds alone.”
Dr. Johnson agreed, noting that many hospitalists diagnose SIADH without completing a proper work-up. “Urine osmolality, plasma osmolality, and urine sodium are the cardinal studies,” she said. “If those studies are all consistent with SIADH, creatinine, thyroid function, and cortisol help completely rule out other etiologies.”
That diagnostic workup is important because isotonic (0.9%) saline therapy is ineffective for treating hyponatremia associated with SIADH, as the 2013 expert panel recommendations note. However, treating SIADH with isotonic saline can cause a transient rise in serum sodium concentration, reinforcing the mistaken conclusion that the patient was hypovolemic, said Cynthia A. Korzelius, MD, a coauthor of the recommendations and assistant chief of adult inpatient medicine at Newton-Wellesley Hospital in Newton, Mass.
Normal saline causes an initial increase in serum sodium concentration because it is hypertonic to the serum of patients with hyponatremia, she explained. But in euvolemic patients with SIADH, “the infused sodium and chloride will be excreted in a volume of urine that is less than the volume infused, leading to the retention of free water. The more concentrated the urine, the more free water will be retained.”
Fluid restriction is a common first-line treatment for SIADH. However, hospitalists often follow a “one-size-fits-all” approach, which can undermine efficacy, Dr. Korzelius said.
“It's common to see a patient prescribed a 1,000- or even a 1,500-cc daily fluid restriction when rational evaluation of urine electrolytes and estimate of free water clearance would predict worsening hyponatremia,” she explained. “In some cases, patients report that they are already drinking even less than the prescribed amount, so this volume would not even be a restriction, per se.”
A more thoughtful approach incorporates the patient's urinary findings by adding the urine sodium and urine potassium concentrations, she advised. “If the sum is greater than the serum sodium concentration, then the patient has negative free water clearance and will need very stringent fluid restriction. A restriction of 1 liter or 1.5 liters will be inadequate.”
Patients and families might worry that fluid restriction will cause dehydration, Dr. Korzelius said. “Stressing that hypo-osmolar hyponatremia is a condition of too much water—or water intoxication—may help patients and families accept that water restriction is appropriate.” Finally, consider other strategies to help enhance free water clearance, including loop diuretics, salt tablets, a high-protein diet, and oral urea therapy, she advised.