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

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 h...

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Main Authors: Annelie Barrueta Tenhunen, Anders Larsson, Olav Rooyackers, Miklos Lipcsey, Michael Marks-Hultström
Format: Article
Language:English
Published: SpringerOpen 2025-08-01
Series:Intensive Care Medicine Experimental
Subjects:
Online Access:https://doi.org/10.1186/s40635-025-00800-5
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author Annelie Barrueta Tenhunen
Anders Larsson
Olav Rooyackers
Miklos Lipcsey
Michael Marks-Hultström
author_facet Annelie Barrueta Tenhunen
Anders Larsson
Olav Rooyackers
Miklos Lipcsey
Michael Marks-Hultström
author_sort Annelie Barrueta Tenhunen
collection DOAJ
description 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
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spelling doaj-art-4f3be05fca824dc882cfd24bad4f46012025-08-24T11:03:51ZengSpringerOpenIntensive Care Medicine Experimental2197-425X2025-08-0113111110.1186/s40635-025-00800-5Free water improves sodium mobilization in furosemide treated pigs after a hyperosmotic sodium loadAnnelie Barrueta Tenhunen0Anders Larsson1Olav Rooyackers2Miklos Lipcsey3Michael Marks-Hultström4Anaesthesiology and Intensive Care Medicine, Department of Surgical Sciences, Uppsala UniversityClinical Chemistry, Department of Medical Sciences, Uppsala UniversityDivision of Anesthesiology and Intensive Care, Department of Clinical Science, Intervention and Technology, Karolinska InstituteAnaesthesiology and Intensive Care Medicine, Department of Surgical Sciences, Uppsala UniversityAnaesthesiology and Intensive Care Medicine, Department of Surgical Sciences, Uppsala UniversityAbstract 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 Abstracthttps://doi.org/10.1186/s40635-025-00800-5Fluid managementHypernatremiaKidney functionSodium excretion
spellingShingle Annelie Barrueta Tenhunen
Anders Larsson
Olav Rooyackers
Miklos Lipcsey
Michael Marks-Hultström
Free water improves sodium mobilization in furosemide treated pigs after a hyperosmotic sodium load
Intensive Care Medicine Experimental
Fluid management
Hypernatremia
Kidney function
Sodium excretion
title Free water improves sodium mobilization in furosemide treated pigs after a hyperosmotic sodium load
title_full Free water improves sodium mobilization in furosemide treated pigs after a hyperosmotic sodium load
title_fullStr Free water improves sodium mobilization in furosemide treated pigs after a hyperosmotic sodium load
title_full_unstemmed Free water improves sodium mobilization in furosemide treated pigs after a hyperosmotic sodium load
title_short Free water improves sodium mobilization in furosemide treated pigs after a hyperosmotic sodium load
title_sort free water improves sodium mobilization in furosemide treated pigs after a hyperosmotic sodium load
topic Fluid management
Hypernatremia
Kidney function
Sodium excretion
url https://doi.org/10.1186/s40635-025-00800-5
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