Risk factors for thiazide-induced hyponatraemia.

BACKGROUND Thiazide-induced hyponatraemia is common and potentially life threatening. In the absence of well-defined risk factors for this complication, guidelines for prescribing cannot be established. AIM To examine whether a subgroup of patients is particularly susceptible to this complication. DESIGN Retrospective case-control study. METHODS We defined and recruited cases of symptomatic hyponatraemia that necessitated hospitalization from January 1996 to April 2002. Controls were selected from 8420 patients being prescribed thiazides and seen at the same institution during that period of time. RESULTS There were 223 cases and 216 controls, with a median 115 days thiazide use. Cases were older than controls (76 +/- 9 vs. 66 +/- 13 years, p < 0.001) and lighter (52.3 +/- 10.3 vs. 63.4 +/- 3 kg, p < 0.001). By univariate analysis, serum potassium level, use of indapamide, elderly home institutionalization and physical immobility were risk factors for thiazide-induced hyponatraemia, but gender, duration of thiazide use, concomitant therapy with loop diuretics, angiotensin-converting enzyme inhibitors or non-steroidal anti-inflammatory drugs, and renal function were not. By stepwise logistic regression analysis, patient age, body weight and serum potassium were the only independent predictive factors. Each 10-year increment of age was associated with a two-fold increase in risk (hazards ratio 2.14, 95%CI 1.59-2.88). For a 5 kg increment in mass, there was a 27% decrease in odds ratio (odds ratio 0.77, 95%CI 0.68-0.87). One SD increase in serum potassium (0.84 mmol/l) was associated with a 63% decrease in risk (odds ratio 0.37, 95%CI 0.27-0.50; p < 0.0001). DISCUSSION Hyponatraemia is a common problem after thiazide therapy. Extra caution and close monitoring are warranted when prescribing thiazides for elderly patients with low body mass.

[1]  Y. Friedlander,et al.  Diuretic-induced severe hyponatremia. Review and analysis of 129 reported patients. , 1993, Chest.

[2]  G. Rai,et al.  A study of plasma sodium levels in elderly people taking amiloride or triamterene in combination with hydrochlorothiazide. , 1993, Postgraduate medical journal.

[3]  A. Salvetti,et al.  Long-term effects of indapamide: final results of a two-year Italian multicenter study in systemic hypertension. , 1990, The American journal of cardiology.

[4]  J. Critchley,et al.  Sodium and potassium intakes and blood pressure in Chinese adults in Hong Kong: A comparison with southern China. , 1998, Asia Pacific journal of clinical nutrition.

[5]  D. Webb,et al.  Severe thiazide-induced hyponatraemia during treatment with enalapril. , 1987, Postgraduate medical journal.

[6]  S. Shapiro,et al.  Epidemiological assessment of drug-induced disease , 2000, The Lancet.

[7]  R. Schrier Diseases of the Kidney and Urinary Tract , 2001 .

[8]  J. Critchley,et al.  Use of indapamide in hospital and community clinics and its effect on plasma potassium in Chinese patients , 1998, Journal of clinical pharmacy and therapeutics.

[9]  R. Kennedy,et al.  Profound hyponatremia resulting from a thiazide-induced decrease in urinary diluting capacity in a patient with primary polydipsia. , 1970, The New England journal of medicine.

[10]  J. Grünfeld,et al.  Advances in Nephrology , 1999 .

[11]  G. McKillop,et al.  Dilutional hyponatraemia due to hydrochlorothiazide plus amiloride (Moduretic®): not to be mistaken for the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) , 1988, The British journal of clinical practice.

[12]  O. Ashouri Severe diuretic-induced hyponatremia in the elderly. A series of eight patients. , 1986, Archives of internal medicine.

[13]  M. Sonnenblick,et al.  Thiazide-induced hyponatremia and vasopressin release. , 1989, Annals of internal medicine.

[14]  E Cogan,et al.  Clinical aspects and pathophysiology of diuretic-induced hyponatremia. , 1984, Advances in nephrology from the Necker Hospital.

[15]  T. Mathew,et al.  Hyponatraemia due to the combination of hydrochlorothiazide and amiloride (Moduretic): Australian spontaneous reports 1977‐1988 , 1990, The Medical journal of Australia.

[16]  S. Massry,et al.  NEUROLOGICAL MANIFESTATIONS AND MORBIDITY OF HYPONATREMIA: CORRELATION WITH BRAIN WATER AND ELECTROLYTES , 1976, Medicine.

[17]  H. Halkin,et al.  Thiazide-induced hyponatremia. Reproducibility by single dose rechallenge and an analysis of pathogenesis. , 1989, Annals of internal medicine.

[18]  B. Davis,et al.  Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). , 2002, JAMA.

[19]  W. Hoefnagels,et al.  Prescription patterns of diuretics in Dutch community-dwelling elderly patients. , 1998, British journal of clinical pharmacology.

[20]  Gerhard Giebisch,et al.  The Kidney: Physiology and Pathophysiology , 1992 .

[21]  A. Schömig,et al.  Role of diuretics, hormonal derangements, and clinical setting of hyponatremia in medical patients , 1988, Klinische Wochenschrift.

[22]  J. Denham,et al.  Hyponatremia induced by thiazide-like diuretics in the elderly. , 1984, Southern medical journal.

[23]  Johnson Je,et al.  Thiazide-induced hyponatremia. , 1983 .

[24]  M. Maxwell,et al.  Maxwell & Kleeman's clinical disorders of fluid and electrolyte metabolism , 1994 .

[25]  C. Pinnock Hyponatraemia associated with hydrochlorothiazide treatment. , 1978, British medical journal.

[26]  A. Spital Diuretic-Induced Hyponatremia , 1999, American Journal of Nephrology.

[27]  T. Chan Indapamide-Induced Severe Hyponatremia and Hypokalemia , 1995, The Annals of pharmacotherapy.

[28]  C. Kleeman,et al.  Diuretic-induced hyponatremia. , 1971, Annals of internal medicine.

[29]  T. Lam,et al.  Dietary intake and practices in the Hong Kong Chinese population. , 1998, Journal of epidemiology and community health.

[30]  P. Cohen,et al.  Diuretic-induced hyponatremia and sustained antidiuresis. , 1962, The American journal of medicine.

[31]  R. Buist,et al.  A Survey of the Practice of Regional Anaesthesia , 1990, Journal of the Royal Society of Medicine.

[32]  J. Ménard,et al.  Summary of 1993 World Health Organisation-International Society of Hypertension guidelines for the management of mild hypertension. Subcommittee of WHO/ISH Mild Hypertension Liaison committee. , 1993, BMJ.

[33]  R. DeFronzo,et al.  Fluid, electrolyte, and acid-base disorders , 1995 .

[34]  L. Ridsdale,et al.  Continuing medical education at a university—evaluation of an MSc programme in general practice , 1990, Journal of the Royal Society of Medicine.

[35]  Lippincott Williams Wilkins,et al.  1993 guidelines for the management of mild hypertension. Memorandum from a World Health Organization/International Society of Hypertension meeting. Guidelines Subcommittee of the WHO/ISH Mild Hypertension Liaison Committee. , 1993, Hypertension.

[36]  F. Epstein,et al.  Increased susceptibility to thiazide-induced hyponatremia in the elderly. , 1994, Journal of the American Society of Nephrology : JASN.

[37]  I. Edelman,et al.  Interrelations between serum sodium concentration, serum osmolarity and total exchangeable sodium, total exchangeable potassium and total body water. , 1958, The Journal of clinical investigation.

[38]  M. Cesari,et al.  Trends in antihypertensive drugs in the elderly: the decline of thiazides , 2001, Journal of Human Hypertension.

[39]  S. van Assen,et al.  Severe hyponatraemia in an amiloride/hydrochlorothiazide-treated patient. , 1999, The Netherlands journal of medicine.

[40]  R. Locksley,et al.  Thiazide-induced hyponatremia associated with death or neurologic damage in outpatients. , 1981, The American journal of medicine.

[41]  Lawrence J Appel,et al.  The verdict from ALLHAT--thiazide diuretics are the preferred initial therapy for hypertension. , 2002, JAMA.

[42]  B. Rose New approach to disturbances in the plasma sodium concentration. , 1986, The American journal of medicine.

[43]  C. Roberts,et al.  Hyponatraemia: adverse effect of diuretic treatment. , 1977, British medical journal.

[44]  C. Bulpitt,et al.  Management guidelines in essential hypertension: report of the second working party of the British Hypertension Society. , 1993, BMJ.

[45]  M. Bailey,et al.  HLA-B12 as a genetic marker for vesicoureteric reflux? , 1978, British medical journal.

[46]  Y. Sharabi,et al.  Diuretic induced hyponatraemia in elderly hypertensive women , 2002, Journal of Human Hypertension.

[47]  A. Greenberg Original articleDiuretic Complications , 2000 .

[48]  D. Mitchell,et al.  Severe hyponatraemia in hospital inpatients. , 1978, British medical journal.

[49]  W. Elliott,et al.  A Double‐Blind, Randomized, Placebo‐Controlled Comparison of the Metabolic Effects of Low‐Dose Hydrochlorothiazide and Indapamide , 1991, Journal of clinical pharmacology.

[50]  R. Brown,et al.  Role of renal prostaglandins during antidiuresis and water diuresis in man. , 1982, Kidney international.

[51]  M. Field,et al.  Complications of thiazide diuretic therapy: an update , 1986, The Medical journal of Australia.

[52]  S. Husby,et al.  Hyponatraemia due to a thiazide diuretic. A case report. , 2009, Acta medica Scandinavica.