Risk of Overcorrection in Rapid Intermittent Bolus vs Slow Continuous Infusion Therapies of Hypertonic Saline for Patients With Symptomatic Hyponatremia

Abstract

IMPORTANCEFew high-quality studies have clarified whether hypertonic saline is best administered as slow continuous infusion (SCI) therapy or rapid intermittent bolus (RIB) therapy for symptomatic severe hyponatremia.OBJECTIVE To compare the risk of overcorrection in RIB and SCI with hypertonic saline in patients with symptomatic hyponatremia. DESIGN, SETTING, AND PARTICIPANTS This prospective, investigator-initiated, multicenter, open-label, randomized clinical trial enrolled 178 patients older than 18 years with moderately severe to severe hyponatremia and glucose-corrected serum sodium (sNa) levels of 125 mmol/L or less. Recruitment took place from August 24, 2016, until August 21, 2019, across emergency departments and wards of 3 general hospitals in the Republic of Korea.INTERVENTIONS Either RIB or SCI of hypertonic saline, 3%, for 24 to 48 hours stratified by the severity of clinical symptoms. MAIN OUTCOME AND MEASURESThe primary outcome was overcorrection at any given period, defined as increase in the sNa level by greater than 12 or 18 mmol/L within 24 or 48 hours, respectively. Secondary and post hoc outcomes included efficacy and safety of the treatment approaches. The sNa concentrations were measured every 6 hours for 2 days. RESULTSThe 178 patients (mean [SD] age, 73.1 [12.2] years; 80 (44.9%) male; mean [SD] sNa concentrations, 118.2 [5.0] mmol/L) were randomly assigned to the RIB group (n = 87) or the SCI group (n = 91). Overcorrection occurred in 15 of 87 (17.2%) and 22 of 91 (24.2%) patients in the RIB and SCI groups, respectively (absolute risk difference, −6.9% [95% CI, −18.8% to 4.9%]; P = .26). The RIB group showed lower incidence of relowering treatment than the SCI group (36 of 87 [41.4%] vs 52 of 91 [57.1%] patients, respectively; absolute risk difference, −15.8% [95% CI, −30.3% to −1.3%]; P = .04; number needed to treat, 6.3). Groups did not differ in terms of efficacy in increasing sNa concentrations nor improving symptoms, but RIB, when compared with SCI, showed better efficacy in achieving target correction rate within 1 hour (intention-to-treat analysis: 28 of 87 (32.2%) vs 16 of 91 (17.6%) patients, respectively; absolute risk difference, 14.6% [95% CI, 2%-27.2%]; P = .02; number needed to treat, 6.8; per-protocol analysis: 21 of 72 (29.2%) vs 12 of 73 (16.4%) patients, respectively; absolute risk difference, 12.7% [95% CI, −0.8% to 26.2%]; P = .07). The statistical significance of the intention-to-treat and per-protocol analyses were similar for all outcomes except for achieving the target correction rate within 1 hour.CONCLUSIONS AND RELEVANCE This randomized clinical trial found that both RIB and SIC therapies of hypertonic saline for treating hyponatremia were effective and safe, with no difference in the overcorrection risk. However, RIB had a lower incidence of therapeutic relowering treatment and tended to have a better efficacy in achieving sNa within 1 hour than SCI. RIB could be suggested as the preferred treatment of symptomatic hyponatremia, which is consistent with the cu...

Treatment of symptomatic hyponatremia with hypertonic saline: a real-life observational study

“…Therefore, we believe that it may be better not to recommend an immediate second bolus of 150 mL 3%NaCl but instead rely on clinical presentation and decide about treatment intensification sometimes later. Neurologic outcome was also not different in the trial from Garrahy et al and in the SALSA trial although sodium increased faster in the bolus groups of both trials ( 14 , 15 ).…”

“…The recently published prospective multicentric randomized SALSA trial compared weight adjusted hypertonic saline bolus with a slow continuous hypertonic saline infusion in symptomatic hyponatremia. This study found that hypertonic boluses were superior in achieving the targeted increase in sNa without exposing patients to a higher overcorrection rates ( 15 ). Bolus therapy required less relowering interventions compared to the continuous infusion ( 15 ).…”

“…This study found that hypertonic boluses were superior in achieving the targeted increase in sNa without exposing patients to a higher overcorrection rates ( 15 ). Bolus therapy required less relowering interventions compared to the continuous infusion ( 15 ).…”

Optimal treatment with hypertonic saline in patients with symptomatic hyponatremia: a perspective from a randomized clinical trial (SALSA trial)

“…American and European guidelines have recommended administering hypertonic saline in small, fixed boluses based on low-quality evidence from small randomized trials and expert opinions [ 1 , 5 , 6 ]. Recently, efficacy and safety of rapid intermittent correction vs slow continuous correction with hypertonic saline in patients with symptomatic hyponatremia: a randomized clinical trial (SALSA trial) involving patients from three general hospitals in Korea from 2016 to 2019 has investigated the efficacy and safety of rapid intermittent bolus (RIB) compared with slow continuous infusion (SCI) with hypertonic saline [ 7 ]. This study aimed to introduce the results of the SALSA trial and discuss a bolus regimen of hypertonic saline as an optimal treatment in patients with symptomatic hyponatremia.…”

“…We recommend rapid intermittent bolus correction as shown in Fig. 1 [ 1 , 5 , 7 ]. First, patients should be classified into two groups based on severity of hyponatremia: moderately severe (nausea, headache, drowsiness, general weakness, and malaise) and severe (vomiting, stupor, seizure, and coma [Glasgow coma scale, ≤ 8]) symptomatic hyponatremia.…”