A loop diuretic is much less likely to induce this problem unless the diuretic has induced volume depletion 8 or water intake is very high since. Hyponatremia associated with diuretic use can be clinically difficult to differentiate from the syndrome of inappropriate antidiuretic hormone secretion siadh. Hyponatremia is an uncommon, but serious, complication of diuretic therapy. Virtually all cases of severe diureticinduced hyponatremia have been due to a thiazidetype diuretic 6 12. Thiazideinduced hyponatraemia is associated with increased. Usually this electrolyte disorder develops insidiously, the degree of hyponatremia is modest, the patient is asymptomatic, and it improves after cessation of treatment. A total of 40 consecutive patients with tdinduced hyponatremia over the period of 1218 months will be recruited for this study from the renal htn clinic at the ottawa hospital. With increasing polypharmacy and an ageing population, the prevalence of druginduced hyponatraemia is likely to increase. Virtually all cases of severe diuretic induced hyponatremia have been due to a thiazide type diuretic 17.
Department of internal medicine, school of medicine, university of ioannina, ioannina, greece. A minority of patients develop thiazideinduced hyponatremia tih and this is. To determine whether a singledose of thiazide administered to patients with previous thiazideinduced hyponatremia will cause hyponatremia and, if so, to analyze its pathogenesis. A decrement in the serunm concentration of sodium is a common complication of diuretic therapy. Thiazide induced hyponatremia is this weeks version of spooky sodium. Hyponatremia is one of the most common adverse reactions to thiazide diuretics. Eleven patients with thiazide induced kaluril hydrochlorothiazide, 50 mg. Thiazideassociated hyponatremia is observed mainly in patients with cer.
Severe hyponatremia associated with the use o f angiotensin. Clinical studies thiazideinduced hyponatremia associated with death or neurologic damage in outpatients nasim ashraf, m. Severe hyponatremia as a result of thiazide diuretic. Thiazide induced hyponatremia, a detailed phenotypic and. Thiazideinduced hyponatremia is a common complication following thiazide treatment. Thiazide associated hyponatremia is observed mainly in patients with cer. Jun 15, 2003 thiazide diuretics work at the site of the distal tubule by inhibiting uptake of sodium and chloride. Hyponatremia is often found in the early stages of diuretic therapy17,18. Of these, 118 met criteria for true thiazideinduced hyponatremia tih. Thiazideinduced hyponatremia is one of the main causes of decreased sodium levels in elderly individuals.
W risk of thiazideinduced hyponatremia in patients with hypertension. Weiss, md, college of medicine, university of arizona hypokalemia is one of the most common electrolyte disorders seen in both outpatient practice and inpatient care. The risk of thiazideinduced hyponatremia persists even up to 10 years of treatment. Diuretics are a common cause of hyponatremia, as first was reported almost 50 years ago. Thiazides increased hyponatremia, but not hospitalizations. Leung et al risk of thiazideinduced hyponatremia 1065.
Tih occur in up to 15% of treated adults and is one of the most common causes of severe hyponatremia in adults. Thiazideinduced hyponatremia is predictable american journal of. Prospective controlled study comparing patients with previous thiazideinduced hyponatremia with two control groups. Carlos ayus, md, in the july issue of the archives. Severe symptomatic hyponatremia in elderly outpatients. Hydrochlorothiazide is a cheap and effective antihypertensive agent but may cause hyponatremia. Thiazide diuretics were first introduced in 1957 and soon became recognized as a cause of hyponatremia. Clinical studies thiazide induced hyponatremia associated with death or neurologic damage in outpatients nasim ashraf, m. Trimethoprimassociated hyponatremia american journal of. Thiazides induced hyponatremia is usually chronic and should be corrected slowly as risk of ods is high. Rapid average correction of hyponatremia and a relatively high total correction over 20 meql in the first 24 h were significantly associated with higher mortality or demyelinating syndrome. Additional risk factors associated with symptomatic. Jci phenotypic and pharmacogenetic evaluation of patients. Since then, many others have come to the same conclusion that thiazide diuretics will sporadically induce hyponatremia, even with a short duration of medical administration.
The importance of thiazideinduced hyponatremia tih is reemerging because thiazide diuretic prescription seems to be increasing after the guidelines recommending thiazides as firstline treatment of essential hypertension have been introduced. Women have a more than 3 times higher risk to be hospitalized due to diuretic induced hyponatremia than men. Severe and symptomatic hyponatremia requires urgent management, usually requiring infusion of normal or hypertonic saline. Among the various causes of druginduced hyponatremia, thiazideinduced hyponatremia comprises a main cause, while loop diuretics only occasionally induce. While cases of thiazideinduced hyponatremia are well documented, this severity of. Apr 10, 2018 hypertension affects more than 30% of the worlds adult population and thiazide and thiazidelike diuretics are amongst the most widely used, effective, and least costly treatments available, with allcause mortality benefits equivalent to angiotensinconverting enzyme inhibitors or calcium channel antagonists. The number needed to harm to result in one excess case of hyponatremia in 5 years is approximately 15. Hyponatraemia is the most frequent electrolyte disorder in clinical practice.
There were a total of 522 patients who developed hyponatremia during the study period, of which 32. Apr 17, 2012 leung aa, wright a, pazo v, karson a, bates dw. Hence, tah occurs in a heterogeneous group of patients, and thiazides may not be directly responsible in all instances. We report a case of a 28yearold man with hiv human immunodeficiency virus and pneumocystis pneumonia who developed hyponatremia while receiving trimethoprimsulfamethoxazole tmpsmx. In contrast, loop diuretics are implicated much less commonly 7. To find the cause, it may be helpful to assess the fluid status and plasma osmonality of the patient. Even though several risk factors for hydrochlorothiazideinduced hyponatremia have been reported, this study aimed to evaluate additional risk factors for hydrochlorothiazideinduced hyponatremia in hypertensive patients. The importance of thiazide induced hyponatremia tih is reemerging because thiazide diuretic prescription seems to be increasing after the guidelines recommending thiazides as firstline treatment of essential hypertension have been introduced.
However, there have not been many studies done regarding cases where patients under such regimens showed severe hyponatremia, even when the amount of thiazide included was low. Because, on average, the elderly take more medications, as our population ages the incidence of druginduced hyponatremia will likely increase. Women have a more than 3 times higher risk to be hospitalized due to diureticinduced hyponatremia than men. Most patients with druginduced hyponatraemia are asymptomatic and the.
Patients with thiazideinduced hyponatremia are usually or antidepressant drugs such as fluoxetine may also produce siadh in a few patients. Reproducibility by single dose rechallenge and an analysis of pathogenesis. Risk factors for thiazideinduced hyponatraemia qjm. However, taking into consideration that thiazides may aggravate the hyponatremia induced by siadh, an evaluation is a prudent ap. Thiazideassociated hyponatremia, report of the hyponatremia. Interestingly tih is reproducible with drug rechallenge in some patients the hyponatremia can be induced with a single dose in susceptible patients. Thiazide diureticinduced hyponatremia is an important adverse effect, with significant clinical impact, such as delirium and falls, and limits the use of these potent antihypertensive agents. Get a printable copy pdf file of the complete article 992k, or click on a page. Clinical and genetic factors associated with thiazideinduced.
Because, on average, the elderly take more medications, as our population ages the incidence of drug induced hyponatremia will likely increase. Patients with thiazideinduced hyponatremia are at high risk for a recurrence and should not be rechallenged with a thiazide. Thiazide diuretics are among the most widely used treatments for hypertension, but thiazide induced hyponatremia tih, a clinically significant adverse effect, is poorly understood. Considerable attention is paid to the problem of thiazide.
Diureticinducedn hyponatremia jama internal medicine. Mineralocorticoid deficiency associated hyponatremia is chronic and responsds to 0. Eleven patients with thiazideinduced kaluril hydrochlorothiazide, 50 mg. Severe hyponatremia associated with the use of angiotensin ii. Clinical and molecular features of thiazideinduced hyponatremia. It is common in older adults, and increasing age is associated with a marked increase in the incidence of. Although drugs are a common cause of hyponatremia, other causes should be considered. Risk of thiazideinduced hyponatremia in patients with hypertension. Thiazide diuretic induced hyponatremia is an important adverse effect, with significant clinical impact, such as delirium and falls, and limits the use of these potent antihypertensive agents. Severe thiazideinduced hyponatraemia during treatment with. The hazard ratio for thiazideassociated hyponatremia varied from 2.
Pdf the importance of thiazideinduced hyponatremia tih is reemerging because thiazide diuretic prescription seems to be increasing after the. The onset of thiazide induced hyponatremia may in some cases occur. Thiazideinduced hyponatremia in the postoperative total. Thiazide diuretics are among the most widely used treatments for hypertension, but thiazideinduced hyponatremia tih, a clinically significant adverse effect, is poorly understood. Hyponatremia is usually induced within 2 weeks of starting the thiazide diuretic, but it can occur any time during thiazide therapy when subsequent contributory factors are complicated, such as. Hyponatremia and thiazides, journal of clinical hypertension. Thiazide diuretics are associated with markedly impaired free water excretion at low adh and aqp2 in elderly patients. Prospective controlled study comparing patients with previous thiazide induced hyponatremia with two control groups. There are little data on the effect or safety of protein supplementation and also on whether a trial of this is feasible.
This observation is probably derived from the different nephronal sites of action of these two classes of diuretics. Sep 26, 2007 although drugs are a common cause of hyponatremia, other causes should be considered. Dec 01, 2017 of these, the mechanism of thiazide induced hyponatremia tih is poorly understood. Hyponatremia is a recognized complication of treatment with thiazide diuretics, particularly in patients older than 70 years. This clinic has about patients with hypertension, and tds. Diureticinduced hyponatremia jama internal medicine jama. Drug induced hyponatraemia is commonly associated with diuretics, selective serotonin reuptake inhibitors and antiepileptics. A loop diuretic is much less likely to induce this problem unless the diuretic has induced volume depletion 8 or water intake is very high since loop diuretics partially impair urinary diluting capacity. Son francisco, california from the nephrology section, department of medicine, veterans administration medical center and the university of california school of medicine, san francisco, california. The silent epidemic of thiazideinduced hyponatremia mann. Thiazideinduced hyponatremia associated with death or.
The higher water intake and lower urea excretion in patients points to an important role for polydipsia and ureamediated water excretion in the pathogenesis of thiazide induced hyponatraemia. I cannot agree with the treatment regimen for diureticinduced hyponatremia advocated in the editorial by j. Most patients with drug induced hyponatraemia are asymptomatic and the. Hyponatremia is a recognized complication of treatment with thiazide. Thiazides are very commonly used for the treatment. Thiazide induced hyponatremia is one of the main causes of decreased sodium levels in elderly individuals. Thiazideinduced hyponatremia associated with death or neurologic damage in outpatients. Our results show that symptoms from thiazideinduced hyponatremia primarily. Hyponatremia is usually induced within 2 weeks of starting the thiazide diuretic, but it can occur any time during thiazide therapy when subsequent contributory factors are complicated, such as reduction of renal function with aging, ingestion of other drugs that affect free water clearance, or changes in water or sodium intake. Risk was greater in women than men, was greater at higher diuretic dose, and was greater in patients with low bmi. Jun 30, 2010 hyponatremia is usually induced within 2 weeks of starting the thiazide diuretic, but it can occur any time during thiazide therapy when subsequent contributory factors are complicated, such as reduction of renal function with aging, ingestion of other drugs that affect free water clearance, or changes in water or sodium intake. The hyponatremia developed within 14 days in most of the patients receiving thiazides but in none of the patients who were treated with furosemide. Hyponatremia is an occasional but potentially fatal complication of diuretic therapy.
Thiazide diureticcaused hyponatremia in the elderly. The presence of neurologic signs is an indication for active sodium replacement. In the present study, we analyzed differences in thiazideassociated hyponatremia between men and women and between different categories of age, body mass index bmi, daily. Thiazide diuretics are one of the most widely used and cost. Of these, the mechanism of thiazide induced hyponatremia tih is poorly understood. Thiazide induced hyponatremia is this weeks version of. Risk of thiazide induced hyponatremia in patients with hypertension. Nov 15, 2018 hyponatremia is an occasional but potentially fatal complication of diuretic therapy.
With increasing polypharmacy and an ageing population, the prevalence of drug induced hyponatraemia is likely to increase. Certain drugs eg, diuretics, antidepressants, and antiepileptics. For these reasons, fixeddose arb thiazide combination antihypertensive drugs have been widely used for the treatment of hypertension. Thiazides are very commonly used for the treatment of hypertension and are recommended by the seventh report of the joint national committee on prevention, detection, evaluation and treatment of high blood pressure jnc 7 as first. In the present study, we analyzed differences in thiazide associated hyponatremia between men and women and between different categories of age, body mass index bmi, daily thiazide dose, and estimated glomerular filtration rate. Thiazide diuretics work at the site of the distal tubule by inhibiting uptake of sodium and chloride. The thiazide drug class was discovered and developed at merck and co.
The onset of thiazideinduced hyponatremia may in some cases occur. Hypertension affects more than 30% of the worlds adult population and thiazide and thiazidelike diuretics are amongst the most widely used, effective, and least costly treatments available, with allcause mortality benefits equivalent to angiotensinconverting enzyme inhibitors or calcium channel antagonists. Druginduced hyponatraemia is commonly associated with diuretics, selective serotonin reuptake inhibitors and antiepileptics. Hypertension affects more than 30% of the worlds adult population and thiazide and thiazidelike diuretics are amongst the most widely used. While cases of thiazide induced hyponatremia are well documented, this severity of. The higher water intake and lower urea excretion in patients points to an important role for polydipsia and ureamediated water excretion in the. Thiazides however have a significant side effect profile and are frequently insufficient. You have free access to this content the journal of clinical hypertension volume 10, issue 6, article first published online. For these reasons, fixeddose arbthiazide combination antihypertensive drugs have been widely used for the treatment of hypertension. Here, we have studied the phenotypic and genetic characteristics of patients hospitalized with tih. There are little data on the effect or safety of protein supplementation and also on whether a. The risk factors for the development of thiazideassociated hyponatremia are shown in table 1. Risk of thiazideinduced hyponatremia in patients with.
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