What is the evidence behind the use of hypertonic saline (HS) in the management of heart failure (HF)?

Evidence for Hypertonic Saline Use in Heart Failure

Summary of Evidence

Hypertonic saline in combination with loop diuretics may enhance diuresis and improve clinical outcomes in patients with refractory heart failure, particularly those with hyponatremia, though this approach is not currently included in major heart failure guidelines.

Mechanism of Action

• Hypertonic saline (HS) works primarily through osmotic fluid shifts from the intracellular to the interstitial and intravascular spaces, with sodium having a reflection coefficient of 1 across cell membranes 1
• HS can increase intravascular volume by up to four times the infused volume within minutes of administration, providing more effective plasma volume expansion than isotonic crystalloids 1
• When combined with loop diuretics, HS appears to enhance diuretic effect by improving renal perfusion and overcoming diuretic resistance 2

Clinical Evidence in Heart Failure

• Recent studies show that combining hypertonic saline with high-dose furosemide can enhance diuresis in patients with refractory heart failure 3, 2
• The combination therapy has demonstrated improvements in:
  • Increased urine output (14-18% improvement)
  • Enhanced sodium excretion (16-29% improvement)
  • Improved urinary osmolality (20-45% improvement)
  • Better furosemide delivery to the kidneys (27-36% improvement) 2
• Case reports suggest that correction of hyponatremia using hypertonic saline in combination with furosemide can dramatically increase urinary volume and improve cardiac output in patients with refractory heart failure 3

Current Research

• The SALT-HF trial is currently evaluating the efficacy and safety of hypertonic saline therapy in ambulatory heart failure patients 4
• This multicenter, double-blinded, randomized study is examining whether a 1-hour infusion of IV furosemide plus hypertonic saline (2.6-3.4% NaCl) improves diuresis and decongestion compared to furosemide alone 4
• Preliminary case series suggest that hypertonic saline with furosemide may provide faster decongestion without significant adverse effects or worsening renal function in refractory acute decompensated heart failure 5

Guidelines and Recommendations

• Current ACC/AHA heart failure guidelines do not specifically mention hypertonic saline as a recommended therapy for heart failure management 1
• For patients with diuresis inadequate to relieve congestion, guidelines recommend:
  1. Higher doses of loop diuretics
  2. Addition of a second diuretic (such as metolazone, spironolactone, or IV chlorothiazide)
  3. Continuous infusion of a loop diuretic 1
• For patients with advanced heart failure and hyponatremia, the benefit of fluid restriction to reduce congestive symptoms is uncertain (Class 2b, Level of Evidence C-LD) 1

Practical Considerations and Cautions

• Hypertonic saline should be used cautiously in patients with heart failure as it can potentially worsen fluid overload if not properly balanced with effective diuresis 1
• Monitoring is essential during hypertonic saline administration:
  • Vital signs, especially blood pressure
  • Urine output
  • Daily weights
  • Serum electrolytes, particularly sodium
  • Renal function 6, 7
• The optimal concentration of hypertonic saline for heart failure management is not standardized, with studies using concentrations ranging from 2.6-3.4% 4 to 7.5% 1

Conclusion

While emerging evidence suggests potential benefits of hypertonic saline in combination with loop diuretics for refractory heart failure, particularly in patients with hyponatremia, this approach is not yet incorporated into major heart failure guidelines. The ongoing SALT-HF trial may provide more definitive evidence regarding the efficacy and safety of this treatment strategy in ambulatory heart failure patients.