Risk of thiazideinduced hyponatremia in patients with. The rationale for this adverse effect is that thiazideinduced hyponatremia may result in bone damage as sodium is a crucial element found extensively in skeletal bone that may play an important role in bone and sodium homeostasis 29r. Certain drugs eg, diuretics, antidepressants, 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. Owing to the very large number of patients prescribed thiazides, 8 thiazide induced hyponatremia tih is the most common cause of drug induced 9 hyponatremia requiring hospitalization 4,5. First described in 1957 by schwartz and associates,1 the syndrome of inappropriate secretion of antidiuretic hormone siadh has been recognized more frequently in recent years.
Two hundred twenty patients exposed to ongoing thiazide therapy were compared with 2393 patients who were not exposed. Thiazide induced hyponatremia is this weeks version of. The adjusted incidence rate of hyponatremia was 140 cases per personyears for patients treated with thiazides. 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 dose, and estimated glomerular filtration rate. Moreover, amiloride, which spares potassium, aggravates thiazideinduced hyponatremia as a consequence of potassium retention by exchanging it for sodium in the distal tubule. There are little data on the effect or safety of protein supplementation and also on whether a. Leung, md, aadam wright, phd, valeria pazo, md,a andrew karson, md,b david w. Thiazide diuretics are one of the most widely used and cost.
The silent epidemic of thiazideinduced hyponatremia mann. The risk factors for the development of thiazideassociated hyponatremia are shown in table 1. Knowing the pathophysiology of tdinduced hyponatremia in elderly htn. The rationale for this adverse effect is that thiazide induced hyponatremia may result in bone damage as sodium is a crucial element found extensively in skeletal bone that may play an important role in bone and sodium homeostasis 29r. Of these, the mechanism of thiazide induced hyponatremia tih is poorly understood. Patients with thiazideinduced hyponatremia had significantly lower body weight and lower plasma sodium and osmolality at baseline. Thiazideassociated hyponatremia, report of the hyponatremia. Medline abstracts for references 17 of diureticinduced. A total of,325 patients were included, of which 718 were on a thiazide diuretic at the time of enrollment, and an additional 2,738 were started on a thiazide diuretic during the study period. Aug 01, 2012 thiazide induced hyponatremia is predictable thiazide induced hyponatremia is predictable grossman, ehud.
Thus, sodium deficiency has been implicated as the major etiologic factor of hyponatremia induced by the combination of amiloride plus thiazide. Background thiazide, a firstline therapy for hypertension, lowers blood pressure, increases bone mineral density, and reduces the risk of fractures. Thiazide diureticcaused hyponatremia in the elderly. The importance of thiazideinduced hyponatremia tih is reemerging because thiazide diuretic prescription seems to be increasing after the guidelines recommending thiazides as firstline. 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. Thiazideinduced syndrome of inappropriate secretion of. Thiazides are a common cause of severe hyponatremia in hospitalized patients5 and are associated with high morbidity and mortality6, 7. Hence, tah occurs in a heterogeneous group of patients, and thiazides may not be directly responsible in all instances. Risk factors for thiazideinduced hyponatraemia qjm. In contrast, loop diuretics are implicated much less commonly7.
Hypertension affects more than 30% of the worlds adult population and thiazide and thiazidelike diuretics are amongst the most widely used. Overall, td induced hyponatremia is a significant clinical problem among elderly hypertensives which prohibits their use in a significant proportion at best and may have serious adverse outcomes if not recognized or treated in a worst case scenario. 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. The onset of thiazide induced hyponatremia may in some cases occur. Jun 30, 2010 virtually all cases of severe diuretic induced hyponatremia have been due to a thiazide type diuretic612. Dec 01, 2017 of these, the mechanism of thiazide induced hyponatremia tih is poorly understood. In the exposed group, 66 30% developed hyponatremia sodium. The onset of thiazideinduced hyponatremia may in some cases occur. Thiazideinduced hyponatremia is one of the main causes of decreased sodium levels in elderly individuals. The presence of neurologic signs is an indication for active sodium replacement.
Thiazide induced hyponatremia is one of the main causes of decreased sodium levels in elderly individuals. Managing drug induced hyponatraemia in adults spiros fourlanos, fellow in endocrinology, royal melbourne hospital, and peter greenberg, department of general medicine and department of diabetes and endocrinology, royal melbourne hospital, and university of melbourne department of medicine, royal melbourne hospital, melbourne synopsis. Thiazide diuretics work at the site of the distal tubule by inhibiting uptake of sodium and chloride. We read with interest the article of leung et al 1 evaluating the risk of diuretic induced hyponatremia in hypertensive patients. Virtually all cases of severe diuretic induced hyponatremia have been due to a thiazide type diuretic. Reports of bowel strictures associated with thiazide ingestion have been reported in the 1960s, although these patients were on a combination hctzpotassium product. Knowing the pathophysiology of td induced hyponatremia in elderly htn.
You have free access to this content the journal of clinical hypertension volume 10, issue 6, article first published online. Virtually all cases of severe diureticinduced hyponatremia have been due to a. However, hyponatremia, an adverse effect of thiazide, is associated with increased risk of osteoporosis and fractures. Thiazideinduced hyponatremia increased incidence in women and elderly patients pathogenesis unclear, but potential causes. Full text get a printable copy pdf file of the complete article 992k, or click on a page image below to browse page by page. 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. Clinical manifestations severity of symptoms depends on the degree and rate of rise in serum calcium gastrointestinal symptoms nausea, vomiting, constipation, abdominal pain, and rarely, pud or pancreatitis neuromuscular involvement altered mentation, impaired concentration, fatigue, lethargy, muscle weakness. Hyponatremia is a frequent and potentially lifethreatening adverse side effect of thiazide diuretics. Aalborg universitet thiazide diuretics and hyponatremia in. Phenotypic and pharmacogenetic evaluation of patients with.
However, some patients given thiazides develop thiazide induced hyponatremia tih 5. 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. Hydrochlorothiazide in intensive care unitacquired. Thiazideinduced hyponatremia associated with death or neurologic damage in outpatients. Our results show that symptoms from thiazideinduced hyponatremia primarily reflect osmotic water shift into brain cells rather than extracellular fluid volume depletion. Hyponatremia is an occasional but potentially fatal complication of diuretic therapy.
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. Thiazideinduced hyponatraemia is common and potentially life threatening. 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. Moreover, the higher prevalence of congestive heart failure and chronic kidney disease in the non thiazide exposed group would likely attenuate our ability to detect the risk of thiazide induced hyponatremia, and thus lead to an even more conservative estimate of true risk. It is currently unclear whether thiazide associated hyponatremia tah outweighs the protective effects of thiazide. Virtually all cases of severe diureticinduced hyponatremia have been due to a thiazidetype diuretic. Among the various causes of druginduced hyponatremia, thiazideinduced hyponatremia comprises a main cause, while loop diuretics only occasionally induce.
Thiazideassociated hyponatremia attenuates the fracture. 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. It is currently unclear whether thiazideassociated hyponatremia tah outweighs the protective effects of thiazide. Thiazides however have a significant side effect profile and are frequently insufficient. Thiazide diuretics may increase serum cholesterol and triglycerides, resulting in increased risk of cholesterol gallstone formation. There were a total of 522 patients who developed hyponatremia during the study period, of which 32. Medullary interstitium depend on nacl reabsorption to restore its hypertonicity. Virtually all cases of severe diureticinduced hyponatremia have been due to a thiazidetype diuretic612. There was a high frequency of neurologic manifestation of thiazide induced hyponatremia, whereas clinical dehydration was not a discernible feature.
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. Thiazideinduced hyponatremia is predictable thiazideinduced hyponatremia is predictable grossman, ehud. Thiazideinduced hyponatremia is predictable deepdyve. Tih occur in up to 15% of treated adults and is one of the most common causes of severe hyponatremia in adults. Jun 15, 2003 severe hyponatremia as a result of thiazide diuretic. Sodium plus potassium concentration in urine exceeds that in the plasma, which directly lowers plasma sodium concentration. Thiazide diuretics and hyponatremia in relation to osteoporosis kruse, christian doi link to publication from publisher. Pdf the importance of thiazideinduced hyponatremia tih is reemerging because thiazide diuretic prescription seems to be increasing after the. We read with interest the article of leung et al 1 evaluating the risk of diureticinduced hyponatremia in hypertensive patients. Hyponatremia is an uncommon, but serious, complication of diuretic therapy. Hyponatremia is one of the most common adverse reactions to thiazide diuretics. 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.
Thiazide induced hyponatremia is this weeks version of spooky sodium. Dec 09, 2019 thiazide diuretics may increase serum cholesterol and triglycerides, resulting in increased risk of cholesterol gallstone formation. In 1971, fichman et al4 reported 25 cases of diureticinduced all of the patients were taking thiazide diuretics hyponatremia that resembled classic siadh. A recent retrospective cohort study evaluated the effect of thiazideinduced hyponatremia on incidence of.
Severe hyponatremia as a result of thiazide diuretic. Druginduced hyponatraemia occurs in approximately 5% of outpatients and 15% of inpatients. Thiazide induced hyponatremia, a detailed phenotypic and. Hyponatraemia is the most frequent electrolyte disorder in clinical practice. Overall, tdinduced hyponatremia is a significant clinical problem among elderly hypertensives which prohibits their use in a significant proportion at best and may have serious adverse outcomes if not recognized or treated in a worst case scenario. Moreover, amiloride, which spares potassium, aggravates thiazide induced hyponatremia as a consequence of potassium retention by exchanging it for sodium in the distal tubule. Managing druginduced hyponatraemia in adults spiros fourlanos, fellow in endocrinology, royal melbourne hospital, and peter greenberg, department of general medicine and department of diabetes and endocrinology, royal melbourne hospital, and university of melbourne department of medicine, royal melbourne hospital, melbourne synopsis. Moreover, the higher prevalence of congestive heart failure and chronic kidney disease in the nonthiazideexposed group would likely attenuate our ability to detect the risk of thiazideinduced hyponatremia, and thus lead to an even more conservative estimate of true risk. A recent retrospective cohort study evaluated the effect of thiazide induced hyponatremia on incidence 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. A minority of patients develop thiazideinduced hyponatremia tih and this is. Clinical and molecular features of thiazideinduced hyponatremia. This observation is probably derived from the different nephronal sites of action of these two classes of diuretics.
Thiazide diuretics are associated with an increased risk of hyponatremia. Clinical and genetic factors associated with thiazideinduce. Most patients with hyponatraemia are diagnosed incidentally on routine blood tests. The management of overcorrection of hyponatremia is similar to the general approach to hyponatremia. The importance of thiazide induced hyponatremia tih is reemerging because thiazide diuretic prescription seems to be increasing after the guidelines recommending thiazides as firstline.
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