High doses of the diuretics furosemide and spironolactone, or concomitant use of these drugs regardless of dose, appear to be an important cause of hyponatremia in patients hospitalized with heart failure (HF), according to investigators.

Ivan Velat, MD, of the University Hospital Center Split in Croatia, and colleagues conducted an observational prospective cohort study that included 565 patients with HF. Of these, 183 (32.4%) had hyponatremia, defined as serum sodium levels below 136 mmol/L. On multivariate analysis, after accounting for diuretic doses, furosemide doses of 250 to 500 mg and spironolactone doses of 50 to 100 mg were independently associated with approximately 14% and 20% increased odds of hyponatremia, respectively (P =.009 and P = .0003, respectively). The investigators reported these findings in BMC Pharmacology and Toxicology. Concomitant use of furosemide and spironolactone was independently associated with an approximately 11% increased odds of hyponatremia (P =.04).

The study found no significant association between hydrochlorothiazide and hyponatremia.

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In addition, on multivariate analysis, each 10-year increase in age, alcohol consumption, and the presence of diabetes mellitus were independently associated with 11% increased odds of hyponatremia (P =.03, P =.03, and P =.04, respectively).

Prior to hospitalization, 64.5% of the hyponatremia group and 58.4% of the non-hyponatremia group received furosemide; 24.6% of the hyponatremia group and 14.7% of the non-hyponatremia group received spironolactone. In addition, 23% of the patients with hyponatremia received furosemide and spironolactone concurrently compared with 13.1% of patients without hyponatremia.


Velat I, Bušić Ž, Jurić Paić M, Čulić V. Furosemide and spironolactone doses and hyponatremia in patients with heart failure. BMC Pharmacol Toxicol. 2020;21(1):57. doi:10.1186/s40360-020-00431-4