Free water improves sodium mobilization in furosemide treated pigs after a hyperosmotic sodium load

Abstract

Abstract Background Hypernatremia, a common electrolyte disorder in critically ill patients, induces a hyperosmotic state linked to increased mortality and metabolic stress. While loop diuretics such as furosemide are used for fluid management, their main effect is water excretion, often worsening hypernatremia. This study aimed to determine whether free water infusion enhances sodium excretion when combined with furosemide after a sodium chloride bolus. We also hypothesized that hyperosmolar hypernatremia stimulates protein degradation and urea synthesis. Results Fourteen pigs (seven per group) received a sodium chloride bolus to induce hypernatremia (plasma Na⁺ > 150 mmol/L). One group received furosemide alone, while the other received furosemide plus free water to maintain normo-osmolality. Renal and metabolic parameters were analyzed over five hours. Free water infusion significantly lowered plasma sodium levels (134 ± 4 vs. 150 ± 4 mmol/L, p = 1.2e−14) and increased total sodium excretion (99 ± 20 vs. 70 ± 18 mmol, p = 0.00056) and urine output (1860 ± 220 vs. 1200 ± 160 mL, p = 2.47e-05). Fractional sodium excretion was higher with free water (5.3 ± 1.1% vs. 3.5 ± 2.2%, p = 0.012). Plasma glutamine was elevated in the no-water group (1305 ± 209 vs. 1084 ± 110 µmol/L, p = 0.029), indicating greater metabolic stress. Conclusions These results suggest that free water infusion enhances sodium clearance and reduces hypernatremia-induced metabolic alterations, supporting its potential role in fluid management strategies. Graphical Abstract

Keywords

• Fluid management
• Hypernatremia
• Kidney function
• Sodium excretion