A systematic review and meta‐analysis of thiazide‐induced hyponatraemia: time to reconsider electrolyte monitoring regimens after thiazide initiation?

Abstract

AimsHyponatraemia is one of the major adverse effects of thiazide and thiazide-like diuretics and the leading cause of drug-induced hyponatraemia requiring hospital admission. We sought to review and analyze all published cases of this important condition.MethodsOvid Medline, Embase, Web of Science and PubMed electronic databases were searched to identify all relevant articles published before October 2013. A proportions meta-analysis was undertaken.ResultsOne hundred and two articles were identified of which 49 were single patient case reports. Meta-analysis showed that mean age was 75 (95% CI 73, 77) years, 79% were women (95% CI 74, 82) and mean body mass index was 25 (95% CI 20, 30) kg m−2. Presentation with thiazide-induced hyponatraemia occurred a mean of 19 (95% CI 8, 30) days after starting treatment, with mean trough serum sodium concentration of 116 (95% CI 113, 120) mm and serum potassium of 3.3 (95% CI 3.0, 3.5) mm. Mean urinary sodium concentration was 64 mm (95% CI 47, 81). The most frequently reported drugs were hydrochlorothiazide, indapamide and bendroflumethiazide.ConclusionsPatients with thiazide-induced hyponatraemia were characterized by advanced age, female gender, inappropriate saliuresis and mild hypokalaemia. Low BMI was not found to be a significant risk factor, despite previous suggestions. The time from thiazide initiation to presentation with hyponatraemia suggests that the recommended practice of performing a single investigation of serum biochemistry 7–14 days after thiazide initiation may be insufficient or suboptimal. Further larger and more systematic studies of thiazide-induced hyponatraemia are required.

Thiazide-Associated Hyponatremia, Report of the Hyponatremia Registry: An Observational Multicenter International Study

“…Overall, 10% of TAH patients were neither subjected to thiazide withdrawal nor received any active hyponatremia therapy. Hyponatremia frequently appears months or even years after the initiation of a thiazide diuretic, presumably as a consequence of acute development of a concurrent disorder, such as gastroenteritis or worsening heart failure, that led to the perturbation of a formerly stable steady state in which dietary intake matched water and solute losses [9]. Under these circumstances, the ensuing deterioration of osmotic homeostasis is often severe and potentially life threatening [10,12].…”

“…Advanced age, female gender, and low body mass index have been identified as risk factors for hyponatremia in thiazide-treated patients [4,6,8]. Usually, hyponatremia ensues within days after the initiation of treatment and the average time from initiation to diagnosis was calculated to be 19 days in a recent meta-analysis [9], but onset can be delayed by months [10,11]. True TIH seems to be dose-independent and probably occurs only in a susceptible subpopulation of patients.…”

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“…Both hypokalemia and hyponatremia occurred consecutively in 07 patients (17.5%). Studies suggest that thiazide-induced hyponatremia occurs within 1 dayto a median time of one year of drug initiation 9,10 .…”

Should we switch from bendrofluazide to chlorthalidone as the initial treatment for hypertension? A review of the available medication

“…30 another review reported that when compared to other antihypertensive therapy, both thiazidelike and thiazide-type diuretics showed a similar number of adverse events in patients with comparable reductions in blood pressure. 4 …”