Thiazide diuretics up risk of electrolyte disorders, syncope, falls

Use of thiazide is independently associated with electrolyte disorders, such as hyponatraemia and hypokalaemia, and the effect appears to be dose-dependent and highly variable depending on the type of substance, a study has found.

In addition, syncope and falls are more common among patients taking thiazides. These drugs independently predict such complications even after correcting for age and the presence of hyponatraemia and hypokalaemia.

“Especially in patients who are elderly, female, and prone to falls, the use of thiazide diuretics should be thoroughly questioned,” the researchers said.

This cross-sectional analysis included all patients with measurements of serum sodium and potassium admitted to an interdisciplinary emergency department in Switzerland between 1 January 2017 and 31 December 2018. The researchers analysed data on serum electrolytes and creatinine for dysnatraemias, dyskalaemias, and acute kidney injury. They also performed chart reviews to screen for syncope or falls.

Of the patients, 1,604 (7.9 percent) used thiazides. Acute kidney injury occurred more frequently in thiazide users than nonusers (22.1 percent vs 7 percent; p<0.0001). Likewise, hyponatraemia (22.1 percent vs 9.8 percent; p<0.0001) and hypokalaemia (19 percent vs 11 percent; p<0.0001) were more common with thiazides. [Am J Med 2021;134:1148-1154]

“The high prevalence of hyponatremia and hypokalemia in the present collective of patients taking thiazide diuretics stands in line with previous studies on the issue,” the researchers said. [BMC Med 2013;11:83; Am J Med 2011;124:1064-1072]

A recent review showed that the mechanisms leading to hyponatraemia in patients taking thiazides are “complex and not completely understood.” Other studies described genetic predispositions for thiazide-associated hyponatraemia. [J Clin Invest 2017;127:3367-3374; Medicine (Baltimore) 2015;94:e1422; Am J Kidney Dis 2020;75:256-264]

On the other hand, significant potassium losses resulting from thiazide use partially explained hypokalaemia, although many patients had concomitant medication that inhibited the renin-angiotensin-aldosterone system. Genetic predisposing factors were also identified for hypokalaemia. [Ann Intern Med 1971;75:853-863; Hypertens Res 2014;37:759-764]

Thiazide use, along with higher age and female sex, independently predicted hyponatraemia and hypokalaemia. A dose-dependent effect was observed for these electrolyte disorders. A variance in risk also existed depending on the type of thiazides, with chlorthalidone bearing the highest and hydrochlorothiazide the lowest risk.

In addition, more episodes of syncope and falls occurred among patients taking thiazide diuretics. Slight hypovolaemia was possible, potentially resulting in orthostatic hypotension and gait disturbances, predisposing both syncope and falls, which could be worsened by hyponatraemia.

“Our findings imply an unfavourable effect of thiazide medication in elderly patients: This specific group is more prone to developing electrolyte disorders when taking thiazide diuretics and, in turn, is again more prone to syncope and falls with thiazides as supported by our current findings,” the researchers said. [J Am Soc Nephrol 1994;5:1106-1111; J Geriatric Cardiol 2016;13:175-182]

“Together with the comparably recent findings of hyponatraemia-induced osteoporosis, a more careful approach to prescribing thiazides in this vulnerable patient collective is wise,” they added.