52 in 52 – #2: The SALSA Trial

Welcome back to the “52 in 52” series. This collection of posts features recently published must-know articles. Our second post looks at the SALSA trial.

Authors: Sarah Mongold, MD (Chief Resident, Emergency Medicine Physician, San Antonio, TX); Brannon Inman (Chief Resident, Emergency Medicine Physician, San Antonio, TX) // Reviewed by: Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

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


Let’s Cha-Cha into this one (I’m sorry I had to).


Clinical question:

What is the risk of overcorrection of hyponatremia using hypertonic saline (3%) as rapid intermittent bolus (RIB) versus slow continuous infusion (SCI)?


Study design:

  • Prospective, multicenter, investigator initiated open label (not blinded) randomized clinical trial
  • Serum sodium measured every 6 hours for 2 days
  • Hypertonic saline administered for 24-48 hours




  • Included moderately severe to severe symptomatic hyponatremic patients > 18 years with glucose corrected sodium below 125 mmol/L
  • Severe symptoms included vomiting, stupor, seizure, and coma (GCS ≤8)
  • Performed in 3 general hospitals in the Republic of Korea
  • Patients were excluded if they had:
    • primary polydipsia (urine osmolality ≤100 mOsm/kg)
    • were pregnant or breastfeeding
    • anuria
    • arterial hypotension (systolic blood pressure <90 mm Hg and mean arterial pressure <70 mm Hg)
    • liver disease (defined as transaminase levels >3 times the upper limit of normal, known decompensated liver cirrhosis with ascites or diuretic use, hepatic encephalopathy, and varices)
    • uncontrolled diabetes (A1C >9%)
    • history of cardiac surgery, acute myocardial infarction, sustained ventricular tachycardia, ventricular fibrillation, acute coronary syndrome
    • cerebral trauma, and increased intracranial pressure within 3 months prior to randomization
  • 178 patients randomized, mean age 73.1 years, mean serum sodium 118.2 mmol/L



  • 2 cc/kg 3% NaCl serial measurements and repeat dosing vs. observation vs. therapeutic relowering

Excerpt from supplemental data within manuscript



  • Weight and symptom severity based hypertonic saline infusion

Excerpt from supplemental data within manuscript



  • Primary outcome was over correction, defined as increase in serum sodium of 12 mmol/L in 24 hours or 18 mmol/L in 48 hours
  • Overcorrection occurred in 17% of RIB and 24 % of SCI (not statistically significant, P=0.26)
  • Therapeutic relowering more common in SCI (41% in RIB, 57% in SCI, P=0.04)
  • RIB demonstrated better efficacy in achieving target correction rate within 1 hour versus SCI
    • Intention to treat analysis: RIB 32.3%, SCI 17.6%, absolute risk difference 14.6% (95% CI 2% – 27.2%), NNT 6.8
    • Per protocol analysis: RIB 29.2%, SCI 16.4%, absolute risk difference 12.7% (95% CI -0.8% to 26.2%)

Take away:

  • No difference in achieving correction goal at 48 hours. Trend toward over correction in SCI (P=0.26). Relowering more common in SCI group (P=0.04).
  • Rates of achieving target correction in 1st hour higher in the RIB group.
  • This study asks an important clinical question and is the first prospective RCT evaluating RIB and SCI.
  • Groups were similar at baseline.
  • Unfortunately, the outcomes are not patient centered, and the 95% CIs were wide for overcorrection incidence.
  • A significant number of patients were excluded because of protocol violations, and the exclusion criteria are complicated.


My take:

  • I find RIB more feasible in the stressful environment of the ED, and it achieved target correction rate in the 1st hour at higher rates compared to SCI. When I think management of symptomatic hyponatremia is needed in the ED, I will be doing RIB.
  • However, both RIB and SCIR therapy were safe and effective, and further RCTs are needed evaluating this question.



  1. Baek SH, Jo YH, Ahn S, et al. Risk of Overcorrection in Rapid Intermittent Bolus vs Slow Continuous Infusion Therapies of Hypertonic Saline for Patients With Symptomatic Hyponatremia: The SALSA Randomized Clinical Trial. JAMA Intern Med. 2021;181(1):81-92. doi:10.1001/jamainternmed.2020.5519


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