Diuretic-induced Hyponatremia Research Articles

Women on diuretics have a higher risk of hospital admission because of hyponatremia than men.

Recent studies suggest that women are more susceptible to diuretic-induced hyponatremia resulting in hospital admission than men. The aim of this study was to confirm whether these sex differences in hyponatremia-related hospital admissions in diuretic users remain after adjusting for several confounding variables such as age, dose, and concurrent medication. In a case-control design nested in diuretic users, cases of hyponatremia associated hospital admissions between 2005 and 2017 were identified from the PHARMO Data Network. Cases were 1:10 matched to diuretic users as controls. Odds ratios (OR) with 95%CIs were calculated for women versus men and adjusted for potential confounders (age, number of diuretics, other hyponatremia-inducing drugs, chronic disease score) using unconditional logistic regression analysis. A subgroup analysis was performed for specific diuretic groups (thiazides, loop diuretics and aldosterone antagonists). Women had a statistically significantly higher risk of a hospital admission associated with hyponatremia than men while using diuretics (OR 1.86, 95%CI 1.64-2.11). Adjusting for the potential confounders resulted in an increased risk for women compared to men (ORadj 2.65, 95% CI 2.31-3.04). This higher risk in women was also seen in the three subgroup analyses after adjustment. Our findings show a higher risk of hyponatremia-related hospital admission in women than men while using diuretics. Further research is needed to understand the underlying mechanism of this sex difference to be able to provide sex-specific recommendations.

The Combined Use of Fractional Urate and Potassium Excretion in the Diagnosis of Diuretic-Induced Hyponatremia.

IntroductionThiazide and loop-diuretics are among the most widely used drugs in the therapy of hypertension and chronic heart failure. Furthermore, hyponatremia is the most prevalent electrolyte imbalance affecting up to 25-30% of hospitalized patients while syndrome of inappropriate antidiuresis (SIAD) is involving approximately 35% of hyponatraemic inpatients. Clinical and laboratoristic algorithms support the differential diagnosis of hypotonic hyponatremia in actual guidelines of SIAD, but a potential bias is represented by the misleading clinical assessment of the extracellular volume status in diuretic-treated patients where the necessity of withdrawal of the therapy is mandatory. We investigated the role of fractional uric acid and potassium excretion (FEUA and FEK) in the differential diagnosis of hypotonic hyponatremia in SIAD and diuretic-treated patients.MethodsThirty-six SIAD, 30 thiazide-induced hyponatremia (TIH), and 32 diuretic-induced hyponatremia (DIH) patients were investigated calculating FEUA and FEK values in receiver operating characteristic (ROC) curve analysis to improve the diagnostic approach of hypotonic hyponatremia.ResultsThe combination of the two investigated markers showed different significative results generating patterns useful to discriminate among the three different hyponatremic groups.ConclusionThe fractional uric acid and potassium excretion could be considered as new markers in the diagnostic approach of hyponatremic diuretic-treated patients where classical algorithms could fail.

The Role of Fractional Excretion of Uric Acid in the Differential Diagnosis of Hypotonic Hyponatraemia in Patients with Diuretic Therapy.

Hyponatraemia is the most common electrolyte imbalance found in hospital population and worldwide thiazide and loop-diuretics are among the most widely used drugs. Syndrome of inappropriate antidiuresis diagnosis (SIAD) is complicated in the presence of diuretic therapy due to the misleading clinical assessment of the extracellular volume status, and in order to make SIAD diagnosis it is often necessary to withdraw diuretic therapy. Our study aimed to investigate the diagnostic role of these alternative markers of volume status, serum uric acid (sUA) and fractional excretion of uric acid (FEUA), in hyponatraemic patients treated with different diuretic drugs. Eighty-nine patients were enrolled with the diagnosis of SIAD, diuretic-induced hyponatremia (DIH, treated with furosemide and potassium canrenoate) or thiazide-induced hyponatremia (TIH, treated with hydrochlorothiazide, metolazone or indapamide) and investigated with receiver operating characteristic analysis and a sensitivity test. Our results show that FEUA discriminated better than sUA between SIAD and DIH patients (area under curve 0.96, <0.001 vs. 0.88, <0.001) while it was a poor marker to discriminate between SIAD and TIH (0.65, NS vs. 0.67, NS). In conclusions, FEUA is an excellent marker to discriminate SIAD vs. sodium depleted patients treated with furosemide and/or potassium canrenoate while the diuretic withdrawal, beyond obtaining a serum Na normalization, is still mandatory for differential diagnosis of sodium depleted patients affected by thiazide-induced hyponatraemia.

Abstract P187: Incidence and Predictors of Diuretic-Induced Hyponatremia

Hyponatremia is a common adverse effect of diuretic use. The purpose of this study was to determine the incidence of Diuretic-induced hyponatremia (DIH) (serum sodium &lt;133mEq/L) caused by commonly used diuretics for treatment of hypertension, specifically, chlorthalidone, hydrochlorothiazide and spironolactone. Electronic health records of outpatients seen at UAB over the last 3 years were reviewed. Inclusion criteria included treatment with one or more of the above mentioned diuretics and having normal sodium levels before and after the hyponatremic episode. Exclusion criteria included heart failure, liver cirrhosis, adrenal insufficiency or an estimated glomerular filtration rate (eGFR) of &lt; 30 mL/min/1.73 m2. The cohort constituted of 270 patients. Based on the total number of prescriptions for each medication, the incidence of DIH was 3.6% for chlorthalidone (48 out of 1322), 3% for spironolactone (35 out of 1159), 1.7% for hydrochlorothiazide (178 out of 10660), while 9 developed hyponatremia on 2 diuretics. Only 57 patients normalized sodium levels after discontinuation of the diuretic, while 213 had normalization of sodium levels despite continuation of the diuretic. Individuals whose sodium levels returned to normal after the diuretic was stopped had lower sodium levels during the hyponatremic episode compared to those who continued the diuretic (129.3±3.9 vs. 130.4±2.0, p=0.002). Older age, Caucasian race, lower baseline sodium levels and lower eGFR values were all risk factors for developing DIH. In this retrospective study, 79% of the patients who developed hyponatremia on diuretics had normalization of serum sodium levels without stopping the diuretic.

Influence of Outdoor Temperature and Relative Humidity on Incidence and Etiology of Hyponatremia.

Hyponatremia is the most common electrolyte disturbance in hospitalized patients. Known risk factors are heart or renal failure, excessive drinking, or the use of diuretics. The incidence of hyponatremia may also be influenced by climate. Analyzing the influence of outdoor temperature and relative humidity on the incidence and etiology of hyponatremia. Cohort A: cross-sectional study from January 2011 to December 2016. Cohort B: prospective observational study from June 2011 to August 2013. Emergency departments of two tertiary centers. Cohort A: patients with plasma sodium ≤145 mmol/L (n = 222,217). Cohort B: consecutive patients (n = 294) with profound hyponatremia (plasma sodium ≤125 mmol/L). The effects of outdoor temperature and relative humidity on the incidence of mild (sodium 126 to 134 mmol/L) and profound hyponatremia (sodium ≤125 mmol/L) were investigated via logistic regression models. The effects of outdoor temperature and relative humidity on hyponatremia etiology were evaluated. In cohort A, 9.9% had mild and 1.08% had profound hyponatremia. Outdoor temperature was significantly associated with the incidence of profound but not mild hyponatremia (P < 0.01, P = 0.3). Relative humidity was not associated with the incidence of hyponatremia. In cohort B, diuretic-induced hyponatremia occurred more frequently with higher outdoor temperatures, whereas other etiologies showed no clear variation with outdoor temperature or relative humidity. Higher outdoor temperature, but not relative humidity, seems to be associated with the incidence of profound hyponatremia. Our data suggest that diuretics should be used with caution during hot weather.

Thiazide diuretic-caused hyponatremia in the elderly hypertensive: will a bottle of Nepro a day keep hyponatremia and the doctor away? Study protocol for a proof-of-concept feasibility trial

BackgroundHypertension is the most common modifiable risk factor for cardiovascular disease, with an increasing prevalence with age, but with easily available medications to control it. Adverse effects of these medications do limit their use, in particular hyponatremia due to thiazide and thiazide-like diuretics. This is more common in the elderly patients due to a combination of inadequate protein intake and impaired urinary dilution capability, made worse by additional thiazide use. Limiting free water intake and increasing protein intake are often not successful resulting in thiazide avoidance. Daily protein supplement is a potential option in this clinical scenario. We describe the protocol for a feasibility study to explore this option.MethodsThis is a single-arm, prospective, open-label proof-of-concept trial, including elderly patients with thiazide diuretic-induced hyponatremia. Forty patients will be enrolled and receive a bottle of a protein supplement daily, providing 120 mmol of solutes and permitting an extra 163 mL free water loss, for 4 weeks. The main outcome measures will be (1) feasibility for enrollment, (2) safety of the intervention, and (3) potential efficacy of the intervention in improving hyponatremia. Secondary outcome measures will include changes in urine osmolality, body weight, and urea measurements.DiscussionThiazide 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. There are little data on the effect or safety of protein supplementation and also on whether a trial of this is feasible. The results of this proof-of-concept feasibility trial will help plan and execute a larger definitive trial to test protein supplementation as an effective strategy in this condition.Trial registrationThe trial is registered with Clinical trials, registration identifier: NCT02614807.

Reference Change Values for Sodium Are Ignored by the American and European Treatment Guidelines for Hyponatremia

Updated revised expert panel recommendations on the evaluation and treatment of hyponatremia were published in the United States in 2013 (1). In 2014, a separate set of guidelines were issued by a group representing the European Society of Intensive Care Medicine, the European Society of Endocrinology, and the European Renal Association–European Dialysis and Transplant Association represented by European Renal Best Practice (2). The recommended rates of correction of chronic hyponatremia from the US group are 4–8 mmol/L per day for patients at low risk of osmotic demyelinating syndrome (ODS)4 and 4–6 mmol/L per day if that risk is high. The limits not to exceed are 8 mmol/L in any 24-h period when the ODS risk is high, and when the ODS risk is low, 10–12 mmol/L in any 24-h period and 18 mmol/L in any 48-h period. If 8 mmol/L is exceeded in a 24-h period, there should be no active therapeutic intervention for the next 24 h (1). Regarding frequency of sodium analysis, serum sodium should be measured at 4- to 6-h intervals until mildly hyponatremic concentrations ≥125 mmol/L have been reached. The section on counteracting overcorrection of chronic hyponatremia by >6–8 mmol/L in the first 24 h of therapy discusses the uses of 2–4 μg desmopressin with repeated 3-mL/kg infusions of 5% dextrose in water administered over 1 h combined with the measurement of serum sodium after each infusion, i.e., hourly until the therapeutic target for the patient has been reached when the starting serum sodium is <120 mmol/L. When using vasopressin receptor antagonists (vaptans) and when treating diuretic-induced hyponatremia, measurements of serum sodium are set at a 6- to 8-h minimum until a stable sodium value >125 mmol/L has been reached. When diuretics have caused hyponatremia-induced seizures, hypertonic saline is recommended to raise the …

Diuretic-induced hyponatremia and osteoporotic fractures in patients admitted to the emergency department

ObjectiveHyponatremia is a complication of diuretic treatment and has been recently identified as a novel factor associated with osteoporosis and fractures. The impact of diuretic-associated electrolyte disorders on osteoporotic fractures (OF) has rarely been studied systematically. Design and settingWe conducted a study in patients presenting to the emergency department at the University Hospital Bern. In this retrospective case series analysis of prospectively gathered data, over a 2-year period we identified 10,823 adult (≥50 years) outpatients with a measured baseline serum sodium, at admission to the hospital. OF patients were compared to a control group without fractures using standard statistical methods. ResultsFour hundred and eighty (5%) patients had 547 OF. The OF group had a higher mean age (73 vs. 68 years, p<0.0001), smaller proportion of men (37% vs. 58%, p<0.0001), higher hospitalisation rate (83% vs. 62%, p<0.0001) and longer hospital stay (8 vs. 6 days, p<0.0001). Any diuretic agent (p<0.0001), loop diurietics (p=0.02), spironolactone (p=0.02) and amiloride (p<0.01) were used significantly more in OF patients, but not thiazides (p=0.68). The prevalence of hyponatremia increased significantly (p<0.0001) with the number of diuretics taken. Advanced age (odds ratio [OR] 1.04, p<0.0001), hyponatremia (OR 1.46, p=0.011) higher serum creatinine (OR 1.53, p=0.0001), furosemide use alone (OR 1.40, p=0.01) and co-treatment with amiloride (OR 2.22, p=0.02) were associated with a higher risk for OF. ConclusionsThis study highlights the clinical association of hyponatremia during the use of certain diuretics (i.e. furosemide or in combination, i.e. amiloride) with an increased risk of osteoporosis associated fractures. Although evidence-based data is currently lacking a pragmatic approach concerning hyponatremia monitoring and correction appears reasonable in selected groups of patients.

Successful treatment with tolvaptan to control blood volume and hyponatremia in a chronic kidney disease patient.

We report a case of successful treatment with tolvaptan (15mg/day) in a 73-year-old female patient with chronic kidney disease (CKD) stage 5 due to diabetic nephropathy and renal sclerosis for volume control and loop diuretic-induced hyponatremia. Her creatinine clearance has remained at 7-10ml/min for the last 6months. She was treated by dietary and drug therapy, namely, antihypertensives (nifedipine: 40mg/day, olmesartan: 20mg/day) and loop diuretics (azosemide: 40-120mg/day), for CKD and concomitant diseases of hypertension and diabetic mellitus. She developed loop diuretic-induced hyponatremia (120mmol/l) by increased sodium excretion, but the diuretic was required for the control of volume overload. Hence, azosemide was suspended and tolvaptan (15mg/day) was administered. After tolvaptan treatment, the plasma sodium level gradually increased to a normal level (135-140mmol/l) and volume overload was improved. Urine volume was maintained at about 1000ml/day with low sodium excretion (<40mmol/day) and increased free water clearance. These results suggest that tolvaptan may be effective for volume control and diuretic-induced hyponatremia in CKD patients.

Corrigendum to "Hwang KS, Kim GH: Thiazide-induced Hyponatremia. Electrolyte Blood Press 8:51-57, 2010"

In several sections of our review paper, cited in the title, we have found some errors in quotation of sentences from the Dr. Aaron Spital's review article entitled published in American Journal of Nephrology 19:447-452, 1999. Quotation marks were missed, and we should have specifically acknowledged the source of our statements. In Introduction (p. 51), first detailed description of diuretic-induced hyponatremia was published over 35 years ago4). Since that time, numerous additional cases have been 14. Spital A: Diuretic-induced hyponatremia. Am J Nephrol 19:447-452, 1999 In Clinical characteristics of TIH(p. 53), One of the most remarkable features of TIH is the rapidity with which it can occur. In susceptible individuals, the serum sodium may fall within hours of administration8), and severe hyponatremia can develop within less than 2 days7,14). In most reported cases (50% to 90%) the duration of thiazide use was less than 2 weeks7,8,14,22) 14. Spital A: Diuretic-induced hyponatremia. Am J Nephrol 19:447-452, 1999 In Pathogenesis of TIH(p. 54), Friedman et al.8) showed that within 6 h of ingesting a single hydrochlorothiazide-amiloride tablet, previously affected patients had a small rise in urine osmolality and a fall in serum sodium of 5.5mmol/L in association with a small gain in weight; controls had only a slight fall in serum sodium, and their mean weight fell. Although water intake was not measured, the authors suggested that thiazides might cause polydipsia which, when combined with the renal effects, results in expansion of total body water and development of 14. Spital A: Diuretic-induced hyponatremia. Am J Nephrol 19:447-452, 1999 In Pathogenesis of TIH(p. 54), While thiazide diuretics do not inhibit concentrating ability, they do impair diluting ability in several ways15,26,34). As mentioned above, they inhibit electrolyte transport at the cortical diluting sites, thereby raising the minimum urinary osmolality34-36). Diuretics may also reduce glomerular filtration rate and enhance reabsorption of Na+ and water in the proximal nephron, diminishing fluid delivery to the distal diluting sites35). 14. Spital A: Diureticinduced hyponatremia. Am J Nephrol 19:447-452, 1999 In Pathogenesis of TIH(p. 54), There is much evidence that patients with TIH are electrolyte-deficient. First, virtually all relevant studies have found that during the development of TIH, sodium balance is negative4,6,10) Second, once diuretics are withdrawn, urinary sodium excretion falls to very low levels4,10). Third, many of these patients are hypokalemic4,6,10). Fichman et al.10) emphasized the importance of potassium depletion in TIH. The great majority of their 25 patients were hypokalemic, and hyponatremia was corrected in 4 of them by potassium repletion despite continued diuretic use and sodium restriction. These investigators argued that potassium depletion predisposes the patients to hyponatremia because the serum sodium concentration is dependent upon the ratio of the sum of exchangeable sodium and potassium to total body water. They also speculated that potassium depletion might cause a shift of sodium into the intracellular space, thereby further compromising the extracellular volume and stimulating vasopressin release 14. Spital A: Diuretic-induced hyponatremia. Am J Nephrol 19: 447-452, 1999

Copeptin in the Differential Diagnosis of Hyponatremia

Treatment of patients with hyponatremia varies widely; thus, convenient diagnostic parameters are needed to guide the correct treatment strategy. This study was designed to evaluate the diagnostic potential of copeptin, the C-terminal part of provasopressin, as a new marker in the differential diagnosis of hyponatremia. In this prospective observational study, 106 consecutive hyponatremic patients were classified based on their history, clinical evaluation, and laboratory tests. In patients and 32 healthy control subjects, plasma copeptin concentration and standard biochemical parameters were tested for their utility of diagnosing the syndrome of inappropriate antidiuresis (SIAD). Four patients (4%) were diagnosed as primary polydipsia, nine (8%) as diuretic-induced hyponatremia, 42 (40%) as SIAD, 29 (27%) as hypovolemic hyponatremia, and 22 patients (21%) as hypervolemic hyponatremia. In controls, a close correlation between plasma copeptin and serum sodium (r(2) = 0.62, P < 0.001) or urine osmolality (r(2) = 0.39, P = 0.001) was observed. Plasma copeptin levels were significantly higher in patients with hypo- and hypervolemic hyponatremia compared with SIAD (P < 0.005, respectively) and primary polydipsia (P < 0.001). The copeptin to U-Na ratio differentiated accurately between volume-depleted and normovolemic disorders (area under the receiver-operating characteristic curve 0.88, 95% confidence interval 0.81-0.95; P < 0.001), resulting in a sensitivity and specificity of 85 and 87% if a cutoff value of 30 pmol/mmol was used. The combined information of plasma copeptin less than 3 pmol/liter and urine osmolality less than 200 mOsm/kg ensured primary polydipsia in 100% of suspected patients. Copeptin measurement reliably identifies patients with primary polydipsia but has limited utility in the differential diagnosis of other hyponatremic disorders. In contrast, the copeptin to U-Na ratio is superior to the reference standard in discriminating volume-depleted from normovolemic hyponatremic disorders.

Copeptin in the differential diagnosis of hyponatremia

Background: Treatment of patients with hyponatremia varies widely; thus, convenient diagnostic parameters are needed to guide the correct treatment strategy. This study was designed to evaluate the diagnostic potential of copeptin, the C-terminal part of provasopressin, as a new marker in the differential diagnosis of hyponatremia. Methods: In this prospective observational study, 106 consecutive hyponatremic patients were classified based on their history, clinical evaluation, and laboratory tests. In patients and 32 healthy control subjects, plasma copeptin concentration and standard biochemical parameters were tested for their utility of diagnosing the syndrome of inappropriate antidiuresis (SIAD). Results: Four patients (4%) were diagnosed as primary polydipsia, nine (8%) as diuretic-induced hyponatremia, 42 (40%) as SIAD, 29 (27%) as hypovolemic hyponatremia, and 22 patients (21%) as hypervolemic hyponatremia. In controls, a close correlation between plasma copeptin and serum sodium (r2 = 0.62, P < 0...

Electrolyte Disturbances in Patients with Hyponatremia

Electrolyte abnormalities are frequently observed in patients with hyponatremia. The aim of this study was to determine the incidence of various electrolyte abnormalities encountered in hyponatremic patients admitted to an internal medicine clinic, as well as to investigate the possible pathogenetic mechanisms responsible for these abnormalities. We prospectively studied 204 adult patients who either on admission to our clinic or during their hospitalization were found to have hyponatremia. Ninety-two patients (45.5%) had at least one additional electrolyte abnormality. Hypophosphatemia was the most frequent electrolyte disorder observed (35 patients, 17%). Hypokalemia was seen in 32 patients (15.8%), hypomagnesemia in 31 patients (15.2%) and hyperkalemia in 12 patients (5.9%). Moreover, 5 patients (2.5%) had hyperphosphatemia, 4 patients (1.9%) exhibited hypermagnesemia, 3 patients (1.4%) had hypercalcemia, and 6 patients (2.9%) had true hypocalcemia. There were no statistically significant differences regarding the incidence of these electrolyte abnormalities (as a whole) between the main subgroups of hyponatremic patients (diuretic-induced, syndrome of inappropriate antidiuretic hormone, hypovolemia-induced and edematous state-related). However, hypokalemia and hypomagnesemia were more frequently observed in patients with diuretic-induced hyponatremia, while hyperkalemia was more frequently seen in edematous state-related hyponatremia. Additional electrolyte abnormalities are frequently encountered in patients with hyponatremia of any origin admitted to an internal medicine clinic.

Uric Acid Homeostasis in the Evaluation of Diuretic-Induced Hyponatremia

BackgroundDiuretics are one of the most common causes of severe hyponatremia. The responsible pathogenetic mechanisms remain unclear. Serum uric acid concentration has been proposed as an index of differentiating between...

Hyponatremia: Management Errors

Rapid correction of hyponatremia is frequently associated with increased morbidity and mortality. Therefore, it is important to estimate the proper volume and type of infusate required to increase the serum sodium concentration predictably. The major common management errors during the treatment of hyponatremia are inadequate investigation, treatment with fluid restriction for diuretic-induced hyponatremia and treatment with fluid restriction plus intravenous isotonic saline simultaneously. We present two cases of management errors. One is about the problem of rapid correction of hyponatremia in a patient with sepsis and acute renal failure during continuous renal replacement therapy in the intensive care unit. The other is the case of hypothyroidism in which hyponatremia was aggravated by intravenous infusion of dextrose water and isotonic saline infusion was erroneously used to increase serum sodium concentration.

Acid-base and electrolyte abnormalities observed in patients receiving cardiovascular drugs.

Cardiovascular drugs can cause a variety of acid-base and electrolyte abnormalities that need to be considered when clinicians manage the large number of patients who receive these agents. Diuretic-induced metabolic alkalosis is the most common acid-base disorder observed and is associated with hypokalemia. Drug-induced hyperkalemia is the most important cause of increased potassium levels in everyday clinical practice. Multifactorial-origin diuretic-induced hyponatremia is mostly due to thiazides and should be carefully managed. This review focuses on the pathogenetic mechanisms as well as on the treatment of these metabolic derangements that are commonly encountered in patients who receive cardiovascular drugs.

Defective post-diuretic antinatriuresis in the aging kidney: a possible explanation for thiazide-induced hyponatremia in the elderly

Objective: To test the susceptibility to diuretic-induced hyponatremia in the elderly (subjects over the age of 75). Design: To investigate the renal effect of a single oral-dose of furosemide or hydrochlorothiazide (HCTZ) in subjects under usual diet and activity conditions. The two drugs were given one week apart. Patients: 13 healthy elderly individuals (82.6 ± 5.8 years) vs. 6 healthy young individuals (26.2 ± 0.7 years). Main results: Following this acute oral test, no variations in plasma sodium levels were observed in either group. Two findings were clinically relevant in the aged: the absence of reduced Na excretion after the furosemide effect had worn off (defective ‘braking phenomenon’), and a persistent urinary hypertonicity (negative ‘effective water clearance’) after HCTZ. This renal behavior could explain the tendency to hyponatremia in the elderly and may be a normal feature of the aging kidney. Furthermore, we suggest that a less adaptive distal tubule could be the main factor altering electrolyte and water renal handling as the kidney ages. Conclusions: The absence of reduced Na excretion after the initial increase due to the diuretics, and the long lasting effect of HCTZ could explain the frequently observed susceptibility to diuretic-induced hyponatremia in elderly people, and justify a preventive limitation of liquid intake, together with a careful prescription of thiazide, taking into account this possible side-effect.

Diuretic-induced Severe Hyponatremia: Review and Analysis of 129 Reported Patients

Thiazides were responsible for severe diuretic-induced hyponatremia (serum sodium level < 115 mEq/L) in 94 percent of 129 cases reported in the literature between 1962 and 1990. The hyponatremia developed within 14 days in most of the patients receiving thiazides but in none of the patients who were treated with furosemide. Diuretic-induced hyponatremia was four times more common in women than in men. Advanced age was not associated with a higher tendency for hyponatremia. In the majority of the patients who received thiazides, excess antidiuretic hormone activity, hypokalemia, and excess water intake were accompanying findings which, singly or together, appeared to contribute to the development of hyponatremia. In 12 patients, mortality was directly related to hyponatremia. Rapid average correction of hyponatremia and a relatively high total correction (over 20 mEq/L) in the first 24 h were significantly associated with higher mortality or demyelinating syndrome. The presence of neurologic signs is an indication for active sodium replacement. The onset of thiazide-induced hyponatremia may in some cases occur within 1 day and therefore needs to be corrected rapidly, but within a total elevation of 20 mEq/L in the first 24 h. Where the onset is judged to have been slow (over several days), the level should be corrected at a slow rate, up to a total of 12 to 15 mEq/L in 24 h.

Diuretic-Induced Hyponatremia

<h3>To the Editor.</h3> —I cannot agree with the treatment regimen for diureticinduced hyponatremia advocated in the editorial by J. Carlos Ayus, MD, in the July issue of theArchives.¹While the recommended treatment with hypertonic saline is<i>usually</i>innocuous,¹some patients will be seriously and unnecessarily harmed by it.²When thiazide-induced hyponatremia is treated with large volumes of saline and withdrawal of the diuretic (thereby eliminating both the hypovolemic stimulus for antidiuretic hormone release and the renal diluting defect¹), the urinary excretion of free water may accelerate, increasing the serum sodium concentration more rapidly than intended—sometimes with disastrous results.^1-3Some hyponatremic patients, both alcoholic and nonalcoholic, have developed central pontine myelinolysis after receiving this recommended treatment.² Is potentially dangerous treatment with hypertonic saline<i>necessary</i>in patients with very low serum sodium concentrations? The editorial cites the "well-documented morbidity and mortality" when severe hyponatremia is

Diuretic-Induced Hyponatremia-Reply

—There seems to be some contradiction in Dr Sterns' letter. Although he starts by disagreeing with my approach in the treatment of diuretic-induced hyponatremia, he recommends, in the last paragraph of his letter, if the patient presents with either seizures or deep coma, it is reasonable to administer enough hypertonic saline to improve these symptoms. This is the exact therapeutic approach that I have advocated since my initial article on this subject in 1982, 1 and I am glad to see that Dr Sterns also thinks that these patients should be treated rapidly with hypertonic saline to correct the neurologic symptomatology! In our experience, these neurologic symptoms usually subside when the serum sodium concentration is raised to 120 to 125 mEq/L (120 to 125 mmol/L). After this, the patient needs to be closely monitored for several days to avoid overcorrection. In spite of Dr Sterns' recommendation of administering hypertonic saline