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Background: Hyponatremia caused by SIADH is common in hospitalized patients, and most evidence for treatment comes from noncontrolled studies. This study aims to investigate the efficacy and safety of fluid restriction compared with furosemide, with or without NaCl supplementation, for treating SIADH.

Dr. Katherine Welter, Division of Hospital Medicine, Northwestern University, Chicago
Dr. Katherine Welter


Study design: Open-label randomized controlled trial.

Setting: Single center in Thailand.

Synopsis: There were 92 participants randomized to fluid restriction alone, fluid restriction and furosemide, or fluid restriction, furosemide, and NaCl supplementation. The authors assessed the primary outcome, change in sodium, at 4, 7, 14, and 28 days (baseline mean Na 125 mmol/L). By day 4, all groups had a significant increase in sodium (mean delta 5 mmol/L). The time to achieve a safe sodium level (Na less than 130 mmol/L) was not different among groups. Acute kidney injury was most common in patients who received furosemide and NaCl supplementation, compared with the fluid restriction and fluid restriction plus furosemide groups (32%, 10%, 17%, respectively; P = .07). Hypokalemia was also most common in the furosemide and NaCl group (42%, 13%, 23%, respectively; P = .01). Limitations include open-label study design, poor fluid restriction adherence (63% overall), and inflexible treatment regimens that excluded treatment with oral potassium.

Bottom line: In treatment of hyponatremia caused by SIADH, there was no benefit to adding furosemide with or without NaCl supplementation to fluid restriction. However, there was potential associated risk of acute kidney injury and hypokalemia.Citation: Krisanapan P et al. Efficacy of furosemide, oral sodium chloride, and fluid restriction for treatment of syndrome of inappropriate antidiuresis (SIADH): An open-label randomized controlled study (the EFFUSE-FLUID trial). Am J Kidney Dis. 2020 Aug;76(2):203-12. doi: 10.1053/j.ajkd.2019.11.012.

Dr. Welter is a hospitalist at Northwestern Memorial Hospital and instructor of medicine, Feinberg School of Medicine, both in Chicago.

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Background: Hyponatremia caused by SIADH is common in hospitalized patients, and most evidence for treatment comes from noncontrolled studies. This study aims to investigate the efficacy and safety of fluid restriction compared with furosemide, with or without NaCl supplementation, for treating SIADH.

Dr. Katherine Welter, Division of Hospital Medicine, Northwestern University, Chicago
Dr. Katherine Welter


Study design: Open-label randomized controlled trial.

Setting: Single center in Thailand.

Synopsis: There were 92 participants randomized to fluid restriction alone, fluid restriction and furosemide, or fluid restriction, furosemide, and NaCl supplementation. The authors assessed the primary outcome, change in sodium, at 4, 7, 14, and 28 days (baseline mean Na 125 mmol/L). By day 4, all groups had a significant increase in sodium (mean delta 5 mmol/L). The time to achieve a safe sodium level (Na less than 130 mmol/L) was not different among groups. Acute kidney injury was most common in patients who received furosemide and NaCl supplementation, compared with the fluid restriction and fluid restriction plus furosemide groups (32%, 10%, 17%, respectively; P = .07). Hypokalemia was also most common in the furosemide and NaCl group (42%, 13%, 23%, respectively; P = .01). Limitations include open-label study design, poor fluid restriction adherence (63% overall), and inflexible treatment regimens that excluded treatment with oral potassium.

Bottom line: In treatment of hyponatremia caused by SIADH, there was no benefit to adding furosemide with or without NaCl supplementation to fluid restriction. However, there was potential associated risk of acute kidney injury and hypokalemia.Citation: Krisanapan P et al. Efficacy of furosemide, oral sodium chloride, and fluid restriction for treatment of syndrome of inappropriate antidiuresis (SIADH): An open-label randomized controlled study (the EFFUSE-FLUID trial). Am J Kidney Dis. 2020 Aug;76(2):203-12. doi: 10.1053/j.ajkd.2019.11.012.

Dr. Welter is a hospitalist at Northwestern Memorial Hospital and instructor of medicine, Feinberg School of Medicine, both in Chicago.

Background: Hyponatremia caused by SIADH is common in hospitalized patients, and most evidence for treatment comes from noncontrolled studies. This study aims to investigate the efficacy and safety of fluid restriction compared with furosemide, with or without NaCl supplementation, for treating SIADH.

Dr. Katherine Welter, Division of Hospital Medicine, Northwestern University, Chicago
Dr. Katherine Welter


Study design: Open-label randomized controlled trial.

Setting: Single center in Thailand.

Synopsis: There were 92 participants randomized to fluid restriction alone, fluid restriction and furosemide, or fluid restriction, furosemide, and NaCl supplementation. The authors assessed the primary outcome, change in sodium, at 4, 7, 14, and 28 days (baseline mean Na 125 mmol/L). By day 4, all groups had a significant increase in sodium (mean delta 5 mmol/L). The time to achieve a safe sodium level (Na less than 130 mmol/L) was not different among groups. Acute kidney injury was most common in patients who received furosemide and NaCl supplementation, compared with the fluid restriction and fluid restriction plus furosemide groups (32%, 10%, 17%, respectively; P = .07). Hypokalemia was also most common in the furosemide and NaCl group (42%, 13%, 23%, respectively; P = .01). Limitations include open-label study design, poor fluid restriction adherence (63% overall), and inflexible treatment regimens that excluded treatment with oral potassium.

Bottom line: In treatment of hyponatremia caused by SIADH, there was no benefit to adding furosemide with or without NaCl supplementation to fluid restriction. However, there was potential associated risk of acute kidney injury and hypokalemia.Citation: Krisanapan P et al. Efficacy of furosemide, oral sodium chloride, and fluid restriction for treatment of syndrome of inappropriate antidiuresis (SIADH): An open-label randomized controlled study (the EFFUSE-FLUID trial). Am J Kidney Dis. 2020 Aug;76(2):203-12. doi: 10.1053/j.ajkd.2019.11.012.

Dr. Welter is a hospitalist at Northwestern Memorial Hospital and instructor of medicine, Feinberg School of Medicine, both in Chicago.

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