title: A systematic review and meta-analysis of thiazide-induced hyponatraemia: time to reconsider electrolyte monitoring regimens after thiazide initiation?
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Therapeutics and Molecular Medicine, University of Nottingham, Nottingham, NG7 2UH, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Barber
authors.forename: Tricia M
authors.initials: TM
authors.lastname: McKeever
authors.forename: Sarah E
authors.initials: SE
authors.lastname: McDowell
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Clayton
authors.forename: Robin E
authors.initials: RE
authors.lastname: Ferner
authors.forename: Richard D
authors.initials: RD
authors.lastname: Gordon
authors.forename: Michael
authors.initials: M
authors.lastname: Stowasser
authors.forename: Kevin M
authors.initials: KM
authors.lastname: O'Shaughnessy
authors.forename: Ian P
authors.initials: IP
authors.lastname: Hall
authors.forename: Mark
authors.initials: M
authors.lastname: Glover
mesh_terms: D000367:Age Factors; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007010:Hyponatremia / Q000139:chemically induced* / Q000453:epidemiology / Q000652:urine; D008297:Male; D012737:Sex Factors; D049993:Sodium Chloride Symporter Inhibitors / Q000009:adverse effects*
chemical_list: D049993:Sodium Chloride Symporter Inhibitors
keywords: hypokalaemia; hypokalemia; hyponatraemia; hyponatremia; thiazide; thiazide-like