Hyponatremia is a recognized complication of treatment with thiazide diuretics. Previous experiments have suggested a direct effect of thiazide diuretics on the plasma membrane expression of aquaporin aqp2 methods. 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. 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. In the absence of welldefined risk factors for this complication, guidelines for prescribing cannot be established. Although they ascribe the pathogenesis of thiazideinduced hyponatremia to excess drinking, they did not monitor water intake. Clinical studies thiazideinduced hyponatremia associated with death or neurologic damage in outpatients nasim ashraf, m. Thiazideinduced hyponatremia in the postoperative total joint replacement patient joel w malin, md.
Prospective controlled study comparing patients with previous thiazide induced hyponatremia with two control groups. Patients with thiazideinduced hyponatremia are usually or antidepressant drugs such as fluoxetine may also produce siadh in a few patients. 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 onset of thiazide induced hyponatremia may in some cases occur. Most patients with drug induced hyponatraemia are asymptomatic and the. When both dehydration and hyponatremia are documented, query the provider if the relationship between the dehydration and hyponatremia can be linked or be further specified.
Thiazideinduced hyponatremia is one of the main causes of decreased sodium levels in elderly individuals. It is currently unclear whether thiazideassociated hyponatremia tah outweighs the protective effects of thiazide. Thiazide diuretics inhibit the thiazide sensitive sodium chloride cotransporter ncc in the distal convoluted tubule dct of the kidney 3 and are among the most widely used class of medicines in the management of hypertension 4. The mechanism of thiazideinduced hyponatraemia is incompletely understood. Avoidance of neurologic injury requires a clear understanding of why the serum sodium na concentration falls and why it rises, how the brain responds to a changing serum na concentration, and what the goals of therapy should be. However, hyponatremia, an adverse effect of thiazide, is associated with increased risk of osteoporosis and fractures. Thiazide induced hyponatremia is one of the main causes of decreased sodium levels in elderly individuals. However, some patients given thiazides develop thiazide induced hyponatremia tih 5. With respect to the mechanisms of this hyponatremia, metolazone, a thiazide, was shown to turn a positive freewater clearance into a negative one 78 x 78 ashraf, n. To find the cause, it may be helpful to assess the fluid status and plasma osmonality of the patient. 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. Most patients with druginduced hyponatraemia are asymptomatic and the. Diureticinduced hyponatremia jama internal medicine.
Although one might expect thiazideinduced hyponatremia to be due to hypovolemia secondary to saliuresis, this is not the case. Hyponatraemia is the most frequent electrolyte disorder in clinical practice. It is also surprising that the free water clearance was not more significantly reduced in the patients, an expected accompaniment when serum sodium is diluted. Clinical characteristics of diuretic induced hypokalemia the clinical characteristics of the abnormality in potassium. Thiazide induced hyponatraemia is common and potentially life threatening. Profound hyponatremia resulting from a thiazide induced decrease in urinary diluting capacity in a patient with primary polydipsia. The onset of thiazideinduced hyponatremia may in some cases occur. Virtually all cases of severe diureticinduced hyponatremia have been due to a thiazidetype diuretic 17. As examples, carbamazepine and fluoxetine can produce hyponatremia with an siadhlike. The silent epidemic of thiazidea induced hyponatremia.
Diureticinduced hyponatraemia in elderly hypertensive. While we confirmed an early risk of thiazide induced hyponatremia within the first quarter year of treatment, we further found that the risk of hyponatremia continued for even up to 10 years. Nov 15, 20 thiazide induced hyponatremia occurs most frequently in elderly woman and usually develops within 2 weeks of therapy initiation. In a cohort of 109 tih patients, those with severe tih displayed an extended phenotype of intravascular volume expansion, increased free water reabsorption, urinary prostaglandin e2 excretion, and reduced.
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 is an occasional but potentially fatal complication of diuretic therapy. Of the 26, 11 had plasma potassium levels less than 3. Drug induced hyponatraemia is commonly associated with diuretics, selective serotonin reuptake inhibitors and antiepileptics. The importance of thiazideinduced hyponatremia tih is reemerging because thiazide diuretic prescription seems to be increasing after the guidelines. Of these, 118 met criteria for true thiazideinduced hyponatremia tih. Eleven patients with thiazide induced kaluril hydrochlorothiazide, 50 mg. The thiazide may be directly responsible box 1, termed thiazideinduced hyponatremia by the hyponatremiaregistry,whichencompassesmorethan5,000 patients with serum sodium levels.
Diureticinduced hyponatremia annals of internal medicine. Risk factors for thiazideassociated hyponatremia include age, female sex, and possibly low body mass. With increasing polypharmacy and an ageing population, the prevalence of drug induced hyponatraemia is likely to increase. Hyponatremia can complicate thiazide use in a minority of susceptible individuals and can result in.
The presence of neurologic signs is an indication for active sodium replacement. Thiazideinduced hyponatremia associated with death or. Studies of the antidiuresis induced by natrichloruretic drugs in rampant diabetes insipidus. The importance of thiazideinduced hyponatremia tih is reemerging because thiazide diuretic prescription seems to be increasing after the guidelines recommending thiazides as firstline. Thiazide diuretics are among the most widely used treatments for hypertension, but thiazideinduced hyponatremia tih, a clinically significant adverse effect, is poorly understood. Thiazideassociated hyponatremia is observed mainly in patients with cer. Thiazide associated hyponatremia is observed mainly in patients with cer. Severe diureticinduced hyponatremia in the elderly. Severe and symptomatic hyponatremia requires urgent management, usually requiring infusion of normal or hypertonic saline. Although they ascribe the pathogenesis of thiazide induced hyponatremia to excess drinking, they did not monitor water intake.
Because, on average, the elderly take more medications, as our population ages the incidence of drug induced hyponatremia will likely increase. Jun 15, 2003 thiazide diuretics work at the site of the distal tubule by inhibiting uptake of sodium and chloride. Interestingly tih is reproducible with drug rechallenge in some patients the hyponatremia can be induced with a single dose in susceptible patients. In our study, among those that developed hyponatremia with thiazides, the median time to event was 1.
Tih occur in up to 15% of treated adults and is one of the most common causes of severe hyponatremia in adults. Mar 01, 2015 hyponatremia is a common electrolyte disorder defined as a serum sodium level of less than 5 meq per l. Jci phenotypic and pharmacogenetic evaluation of 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. Nov 15, 2018 virtually all cases of severe diuretic induced hyponatremia have been due to a thiazide type diuretic. Thiazide induced hyponatremia in the postoperative total joint replacement patient joel w malin, md.
The association between thiazide exposure and hyponatremia defined as sodium level 5. Reporting dehydration with hypernatremia or hyponatremia requires two codes. Clinicians should be aware for neurologic signs indicating decreased sodium levels and should monitor sodium concentration in patients with risk factors for thiazideassociated hyponatremia. Thiazide diuretics inhibit the thiazidesensitive sodium chloride cotransporter ncc in the distal convoluted tubule dct of the kidney 3 and are among the most widely used class of medicines in the management of hypertension 4. Clinical presentation the clinical manifestations of tih are similar to those due to other causes of hyponatraemia and vary from mild fatigue or. Prospective controlled study comparing patients with previous thiazideinduced hyponatremia with two control groups. Thiazideinduced hyponatremia is predictable the american. Clinical and molecular features of thiazideinduced. With increasing polypharmacy and an ageing population, the prevalence of druginduced hyponatraemia is likely to increase. Clinical and molecular features of thiazideinduced hyponatremia.
Dec 01, 2017 of these, the mechanism of thiazide induced hyponatremia tih is poorly understood. Background thiazide, a firstline therapy for hypertension, lowers blood pressure, increases bone mineral density, and reduces the risk of fractures. Thiazideassociated hyponatremia, report of the hyponatremia. Diuretic induced hyponatremia in hypertensive patients. Thiazideinduced hyponatremia is frequent in elderly individuals. 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.
Among the various causes of druginduced hyponatremia, thiazideinduced hyponatremia comprises a main cause, while loop diuretics only occasionally induce. Thiazideinduced hyponatremia in the postoperative total. The thiazide may be directly responsible, termed thiazideinduced hyponatremia by the hyponatremia registry, which encompasses more than 5,000 patients with serum sodium levels. Thiazide induced hyponatremia associated with death or neurologic damage in outpatients. Thiazide diuretics are among the most widely used treatments for hypertension, but thiazide induced hyponatremia tih, a clinically significant adverse effect, is poorly understood. While cases of thiazide induced hyponatremia are well documented, this severity of.
Risk of thiazideinduced hyponatremia in patients with. When a euvolemic patient receiving a thiazide manifests hyponatremia, it should be termed thiazideassociated hyponatremia tah. Sep 26, 2007 although drugs are a common cause of hyponatremia, other causes should be considered. Among the 26 with reversible thiazideinduced hyponatraemia, there were 10 with plasma sodium levels in the range 101109 mmoll. Druginduced hyponatraemia is commonly associated with diuretics, selective serotonin reuptake inhibitors and antiepileptics.
A minority of patients develop thiazideinduced hyponatremia tih and this is. We examined the effects of a single reexposure to hydrochlorothiazide. It is currently unclear whether thiazide associated hyponatremia tah outweighs the protective effects of thiazide. Treatment of severe hyponatremia kidney international.
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. Hyponatraemia is a common, potentially lifethreatening, complication of thiazide diuretics. Risk factors for thiazideinduced hyponatremia request pdf. What, if any, role a direct effect of diuretics on potassium secretion might play in vivo has not been examined. Risk factors for thiazideinduced hyponatraemia qjm.
A 4 to 6 meql increase in serum na concentration is sufficient to treat lifethreatening cerebral edema caused by. Thiazide induced hyponatremia, a detailed phenotypic and. Increased susceptibility to thiazideinduced hyponatremia jasn. Certain drugs eg, diuretics, antidepressants, and antiepileptics. Milder, asymptomatic, thiazide induced hyponatremia requires steps to man. Hypertension affects more than 30% of the worlds adult population and thiazide and thiazidelike diuretics are amongst the most widely used. Thiazideinduced hyponatremia and vasopressin release. 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. Severe hyponatremia as a result of thiazide diuretic. Mark glover, division of therapeutics and molecular medicine, university of nottingham, nottingham, united kingdom.
Treatment involves discontinuing thiazide diuretic therapy. A genetic susceptibility has recently been uncovered. Treatment of severe hyponatremia american society of. Hyponatremia can complicate thiazide use in a minority of susceptible individuals and can result in significant morbidity and even mortality. Admit due to thiazideinduced hyponatremia, sodium level, patient compliant with regimen. The risk factors for the development of thiazideassociated hyponatremia are shown in table 1. Eleven patients with thiazideinduced kaluril hydrochlorothiazide, 50 mg. Hyponatremia is a recognized complication of treatment with thiazide diuretics, particularly in patients older than 70 years. We read with interest the report of friedman and colleagues 1 on thiazide induced hyponatremia.
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