Similar Risk of Hyponatremia Overcorrection With Bolus, Infusion Therapies

By Will Boggs MD

November 06, 2020

NEW YORK (Reuters Health) - Rapid intermittent bolus and slow continuous infusion therapies with hypertonic saline are associated with a similar risk of overcorrection of symptomatic hyponatremia, according to results from the SALSA randomized clinical trial.

"Both bolus and infusion regimens are safe and effective to correct symptomatic hyponatremia," Dr. Sejoong Kim of Seoul National University Bundang Hospital, in Seongnam, South Korea, told Reuters Health by email. "However, bolus regimens have a lower incidence of relowering therapy and a better efficacy within 1 hour after starting hyponatremic management."

Hypertonic saline effectively treats symptomatic hyponatremia, but overcorrection can result in permanent neurologic disability from osmotic demyelination syndrome (ODS). While most guidelines recommend administering hypertonic saline as small, fixed boluses, there is little high-quality evidence suggesting this is superior to slow continuous infusion (SCI) therapy.

Dr. Kim and colleagues from three general hospitals compared the efficacy and safety of rapid intermittent bolus (RIB) and SCI with hypertonic saline in their open label trial of 178 patients with symptomatic hyponatremia.

Overall, overcorrection occurred in 15 of 87 patients (17.2%) in the RIB group versus 22 of 91 patients (24.2%) in the SCI group, a nonsignificant difference, the researchers report in JAMA Internal Medicine.

The treatment groups did not differ significantly in symptoms at 24 and 48 hours after treatment initiation; first time to an increase of serum sodium 5 mmol/L or greater after treatment initiation; incidence of target correction rate; time from treatment initiation to achievement of serum sodium greater than 130 mmol/L; or length of hospital stay.

There were no events of ODS in either treatment group.

The incidence of relowering treatment was significantly lower in the RIB group (41.4%) than in the SCI group (57.1%), and the proportion of patients achieving target serum sodium levels within one hour was significantly higher in the RIB group (32.2% vs. 17.6%).

The RIB group had a higher cumulative amount of hypertonic saline administered within one and six hours, compared with the SCI group, but the cumulative amount of hypertonic saline administered within 24 and 48 hours did not differ between the groups.

"Bolus regimens are simple and less of a medical burden if medical staffs learn the protocols," Dr. Kim said. "We suggest that the bolus regimen is preferable to the primary physician, as well as to nephrologists."

"Until now, medical students and residents have been suffering to memorize several equations or formulas to correct hyponatremia," he said. "This study used an amazingly simple bolus regimen, one shot of 3% saline (2 mL/kg of body weight) every six hours. I hope that they will not use calculators to manage symptomatic hyponatremic patients."

Dr. Srijan Tandukar of the University of Pittsburgh Medical Center, in Pennsylvania, who recently reviewed the treatment of severe symptomatic hyponatremia, told Reuters Health by email, "There is no evidence to suggest that the rates of overcorrection of serum sodium level are any different in the rapid-infusion group as compared to the continuous-infusion group of hypertonic saline, although there is evidence that rapid infusion of hypertonic saline led to lower incidence of therapeutic relowering than continuous infusion."

"Hyponatremia is one of the commonest electrolyte disorders occurring in hospitalized patients, with serious consequences, such as cerebral edema, if not treated in a timely manner, and osmotic demyelination syndrome, if serum sodium is corrected rapidly," he said. "Use of hypertonic saline can prevent these adverse outcomes if used appropriately, but strict clinical vigilance during management is the cornerstone of successful hyponatremia treatment."

Dr. Richard H. Stearns of the University of Rochester School of Medicine and Dentistry, in New York, who has also reviewed the treatment of severe hyponatremia, told Reuters Health by email, "Hypertonic saline is effective when prompt correction is needed for severe or life-threatening symptoms. However, many clinicians avoid it, fearing excessive correction and ODS. Unfortunately, this study does little to resolve this dilemma: serious or life-threatening symptoms were mostly lacking and the risk of ODS was extremely low."

"Hopefully this trial will spawn future studies of patients with more severe symptoms and/or greater risk of ODS," he said.

SOURCE: JAMA Internal Medicine, online October 26, 2020.