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

Barber, Jennifer; McKeever, Tricia M.; McDowell, Sarah E.; Clayton, Jennifer A.; Ferner, Robin E.; Gordon, Richard D.; Stowasser, Michael; O'Shaughnessy, Kevin M.; Hall, Ian P.; Glover, Mark

Abstract

Aims: Hyponatraemia 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.

Methods: Ovid 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.

Results: One 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.

Conclusions: Patients 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.

Citation

Barber, J., McKeever, T. M., McDowell, S. E., Clayton, J. A., Ferner, R. E., Gordon, R. D., …Glover, M. (2015). A systematic review and meta-analysis of thiazide-induced hyponatraemia: time to reconsider electrolyte monitoring regimens after thiazide initiation?. British Journal of Clinical Pharmacology, 79(4), https://doi.org/10.1111/bcp.12499

• Journal Article Type: Article
• Publication Date: Apr 1, 2015
• Deposit Date: Feb 3, 2016
• Publicly Available Date: Feb 3, 2016
• Journal: British Journal of Clinical Pharmacology
• Print ISSN: 0306-5251
• Electronic ISSN: 1365-2125
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 79
• Issue: 4
• DOI: https://doi.org/10.1111/bcp.12499
• Keywords: hypokalaemia; hypokalemia; hyponatraemia; hyponatremia; thiazide; thiazide-like
• Public URL: https://nottingham-repository.worktribe.com/output/984114
• Publisher URL: http://onlinelibrary.wiley.com/doi/10.1111/bcp.12499/abstract