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

AKA: THE “SALSA” TRIAL

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

PICO:

Population:

• 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

Intervention:

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

Excerpt from supplemental data within manuscript

Comparator:

• Weight and symptom severity based hypertonic saline infusion

Excerpt from supplemental data within manuscript

Outcome:

• 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.

Reference:

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