Rapid correction of severe hyponatremia with intravenous hypertonic saline solution

Severe hyponatremia with hypoosmolality carries a high morbidity and mortality and constitutes a life-threatening emergency. We report seven cases of severe hyponatremia (serum sodium concentration 99.7 ± 3.0 meq/liter) (mean ± SEM) with hypoosmolality (212 ± 8 mOsm/kg water) that presented with severe neurologic complications. Serum sodium concentration was corrected in 13.3 ± 2.2 hours to mildly hyponatremic levels (serum sodium concentration 128.3 ± 1.6 meq/liter). The rate of correction of serum sodium concentration was 2.4 ± 0.5 meq/liter/hr. This was achieved by the intravenous administration of 3 percent hypertonic saline solution (687 ± 43 meq sodium chloride) and furosemide or by hemodialysis where indicated. No complications occurred from treatment and all of our patients recovered without neurologic sequelae. Early diagnosis and rapid correction of serum sodium concentration appear to reduce the significant morbidity and mortality of severe hyponatremia.     

Idiopathic, sustained, inappropriate secretion of ADH with associated hypertension and thirst.

A 15 year old girl presented with excessive thirst and hypertension (170/110 mm Hg). Biochemical investigations revealed serum sodium 118 meq/liter, serum osmolality 238 mosmol/liter, urine sodium 90 meq/liter, urine osmolality 700 mosmol/liter, persistenly elevated serum antidiuretic hormone (ADH) levels (5.8 to 11.9 pg/ml) and no obvious cause for the hypertension. The hypertension is, at least in part, volume-related, diminishing with fluid restriction. Features of gross water intoxication (e.g., confusion, coma) have not occurred. The etiology of the inappropriate secretion of ADH is not obvious but is not thought to be due to "resetting of osmoreceptors" as evidenced by failure to maximally dilute urine following a water load test and persistently elevated serum ADH levels. A similar patient described by Epstein and associates in 1962 is presently well with persistent features of inappropriate secretion of ADH.     

Outpatient conversion of treatment to potassium-sparing diuretics

Thiazide diuretics frequently cause a decrease in serum potassium levels. In this study, 34 percent of patients taking hydrochlorothiazide had serum potassium levels below 3.5 meq/liter. The response of the serum potassium level was studied after treatment in 56 patients was switched from 50 mg of hydrochlorothiazide daily to either two capsules of hydrochlorothiazide/triampterene (Dyazide), or one tablet of hydrochlorothiazide/amiloride (Moduretic) daily, over nine to 15 months. The 24 patients whose treatment was changed to Dyazide had a rise in serum potassium levels from a mean of 3.56 meq/liter to 4.17 meq/liter in two to three weeks. The 32 patients whose treatment was changed to Moduretic had a rise in serum potassium levels from a mean of 3.76 meq/liter to 4.14 meq/liter in two to three weeks. The resultant rise in potassium levels was stable throughout the follow-up period in both groups. Patient acceptance of this change was excellent.     

Clinical assessment of extracellular fluid volume in hyponatremia

Assessment of the status of extracellular fluid volume is important in evaluating the cause and selecting appropriate therapy for hyponatremic disorders. Since the sensitivity and specificity of clinical assessment of extracellular fluid volume status in hyponatremic states remain unknown, 58 non-edematous patients with serum sodium less than 130 meq/liter were prospectively evaluated. Patients were judged to be either normovolemic (no response of serum sodium to saline infusion) or hypovolemic (saline infusion significantly corrected hyponatremia). Hypovolemic patients had significantly higher plasma renin activity (5.0 +/- 1.5 versus 2.5 +/- 0.5 ng/ml per three hours, p less than 0.05) and norepinephrine (1,054 +/- 252 versus 519 +/- 55 pg/ml, p less than 0.05) concentrations than did normovolemic patients. Clinical assessment correctly identified only 47 percent of hypovolemic patients and 48 percent of normovolemic patients. Thus, clinical assessment was of limited sensitivity and specificity in identifying extracellular fluid volume status in these hyponatremic patients. However, the concentration of sodium in a spot urine sample clearly separated hypovolemic (mean UNa = 18.4 +/- 3.1 meq/liter) from normovolemic (mean UNa = 72 +/- 3.7 meq/liter, p less than 0.001) hyponatremic patients.     

Captopril-induced hyponatremia with irreversible neurologic damage

A 61-year-old Chinese-American man with a history of congestive heart failure and hypertension was admitted to the San Francisco Veterans Administration Hospital with confusion, cortical blindness, and generalized flaccidity. Serum sodium level on admission was 114 meq/liter. Administration of captopril had been begun for afterload reduction two weeks before admission with a concomitant fall in serum sodium level from 137 meq/liter to 126 meq/liter in one week. A history of marked thirst with consumption of large volumes of water was reported for over one week prior to hospitalization. Despite correction of the hyponatremia within 24 hours at a rate of 0.9 meq/liter per hour, the patient remained semi-comatose and died four days later with a gastrointestinal bleed. It is suggested that the thirst phenomenon and hyponatremia were caused by the introduction of captopril. This lead to irreversible neurologic damage and death, despite the correction of the serum sodium level.     

Hyponatremia with consciousness disturbance caused by omeprazole administration

Summary A 68-year-old man developed severe consciousness disturbance after daily administration of 20 mg omeprazole for four days for the treatment of bleeding gastric ulcer. Systemic investigation revealed severe hyponatremia (111 meq/liter). Consciousness did not become clear until his sodium intake was increased to 480 meq/day, and his serum sodium concentrations reached 130 meq/liter. After the discontinuation of omeprazole, his serum sodium levels returned to the normal range with only minimum supplementation of sodium in the form of dietary sodium chloride intake of 10 g/day. Although the mechanism of hyponatremia induced by omeprazole is not clear, an excessive loss of urinary sodium appears to be more likely than water retention with an increase in fluid intake. The literature was also reviewed.     

Changing concep in treatment of severe symptomatic hyponatremia. Rapid correction and possible relation to central pontine myelinolysis

Severe symptomatic hyponatremia (serum sodium level below 120 meq/liter) is often a life-threatening emergency that can result in permanent neurologic damage or death if left untreated. Early recognition and rapid correction to mildly hyponatremic levels by the administration of hypertonic saline are important in order to reduce the potential mortality and morbidity. If the serum sodium level is more than 105 meq/liter, it can be corrected to a value of 125 to 130 meq/liter. However, if the serum sodium level is less than 105 meq/ liter, it may be safe to raise the value by only 20 meq/ liter. Care should be taken to avoid acute correction to normonatremia or hypernatremia. Moreover, it is also of equal importance to avoid development of hypernatremia in the subsequent days following the correction to mild hyponatremia.     

Regulation of urinary prostaglandins in Bartter's syndrome.

Enhanced prostaglandin production, possibly stimulated by hypokalemia, may mediate the manifestations of Bartter's syndrome. To investigate the cause of increased urinary prostaglandin excretion, we measured urinary immunoreactive prostaglandin E (iPGE) during the oral administration of potassium and the parenteral administration of magnesium, and during water restriction and oral water loading in two subjects with Bartter's syndrome. In one patient (Case 1), iPGE was 0.91 μg/day (normal 0.50 ± 0.20 μg/day, SD). Following the administration of indomethacin, 200 mg/day, iPGE, plasma renin activity (PRA), plasma aldosterone and angiotensin pressor sensitivity returned to normal but serum potassium did not. The oral administration of potassium citrate, acetate, bicarbonate, (Potassium Triplex), 240 meq/day for four days, increased iPGE to 2:3 μg/day and PRA from 47 to 73 ng/ml/hour (normal 1 to 3 ng/ml/hour). In the second patient (Case 2), iPGE was 1.4 μg/day. Therapy with ibuprofen, 1,600 mg/day, and indomethacin, 200 mg/day, again resulted in the return of iPGE, PRA, plasma aldosterone and angiotensin pressor sensitivity to normal, but serum potassium increased only transiently from 2.1 to 3.1 meq/liter. The oral administration of potassium chloride, 240 meq/day for four days, increased potassium to 3.0 meq/liter and increased iPGE to 8.0 μg/day. The administration of potassium triplex, 240 meq/day for four more days, further increased potassium to 3.4 meq/liter and iPGE to 9.3 μg/day, and PRA increased from 7.1 to 13.8 ng/ml/hour. This patient (Case 2) was hypomagnesemic (1.0 meq/liter, normal 1.5 to 2.4 meq/liter), and the intravenous administration of magnesium transiently increased iPGE by 15-fold. Following water restriction iPGE returned to normal (0.35 μg/day), and water loading increased iPGE to 3.0 μg/day, but neither maneuver altered PRA, aldosterone or serum electrolytes. The findings that potassium administration failed to reduce iPGE excretion and that water restriction renormalized iPGE excretion suggest that hypokalemia is not the primary stimulus to prostaglandin excretion.     

Severe symptomatic hyponatremia in elderly outpatients: the role of thiazide therapy and stress

Severe symptomatic hyponatremia (serum sodium level 112 +/- 5.5 mEq/l) was encountered in six elderly outpatients within four days of the onset of thiazide therapy. Associated polydipsia was present in two of these patients, but the thiazides alone appeared responsible in the others. In three other elderly outpatients, severe hyponatremia (serum sodium level 112 +/- 5.25 mEq/l) developed after the acute emotional stress of relocation from their place of abode to a nursing home or hospital. Recurrent episodes of hyponatremia occurred in two patients following reinstitution of diuretic therapy, and, in two other patients, was precipitated by thiazides and stress on different occasions. Severe neurologic manifestations occurred in all patients and were mostly attributed to atherosclerotic dementia or stroke. Two patients died with severe hyponatremia, although all patients in whom cessation of thiazide therapy and water restriction were instituted promptly recovered without permanent sequelae.     

Thiazide-induced hyponatremia. Reproducibility by single dose rechallenge and an analysis of pathogenesis

STUDY OBJECTIVE: To determine whether a single-dose of thiazide administered to patients with previous thiazide-induced hyponatremia will cause hyponatremia and, if so, to analyze its pathogenesis. DESIGN: Prospective controlled study comparing patients with previous thiazide-induced hyponatremia with two control groups. PATIENTS AND CONTROLS: Eleven patients with thiazide-induced (Kaluril [hydrochlorothiazide, 50 mg; amiloride, 5 mg]) hyponatremia of less than 130 mmol/L at least 1 week before the study. Two groups of controls: 10 young healthy volunteers and 11 elderly hypertensive patients previously treated uneventfully with thiazide. INTERVENTIONS: Administration of a single dose of hydrochlorothiazide, 50 mg, and amiloride, 5 mg. MEASUREMENTS: Blood pressure, pulse rate, body weight, serum urea, creatinine, sodium, potassium, magnesium, osmolality, plasma antidiuretic hormone, renin, aldosterone and also urinary sodium, potassium, osmolality, and cyclic adenosine monophosphate (cAMP) before and 6 to 8, 12, and 24 hours after drug administration. RESULTS: Within 6 to 8 hours serum sodium decreased in patients, young controls, and elderly controls by 5.5 +/- 1.1 (mean +/- SE), 1.2 +/- 0.4, and 1.8 +/- 0.9 mmol/L, respectively (Py less than 0.001 [patients versus young controls], Pe = 0.017 [patients versus elderly controls]). Serum osmolality decreased in patients, young controls, and elderly controls by 14.9 +/- 2.6, 2.8 +/- 1.6, and 6.6 +/- 1.5 mmol/kg, respectively (Py less than 0.001, Pe = 0.012). All patients and only one control subject reached osmolality of less than 280 mmol/kg. At 6 to 8 hours all patients gained weight (0.85 +/- 0.13 kg) whereas young and elderly controls lost weight (0.47 +/- 0.23 and 0.45 +/- 0.2 kg, respectively) (Py much less than 0.001, Pe much less than 0.001). Patients' responses to the drug did not differ from both control groups regarding sodium and potassium urinary excretion, osmolar and free water clearance, and antidiuretic hormone blood levels. Water restriction in one patient attenuated serum sodium reduction. CONCLUSIONS: Use of a single-dose of a thiazide diuretic may predict the development of hyponatremia. Increased body weight apparently due to polydipsia may play a major role in the pathogenesis of thiazide-induced hyponatremia.     

Therapeutic effects of tolvaptan, a potent, selective nonpeptide vasopressin V2 receptor antagonist, in rats with acute and chronic severe hyponatremia

The therapeutic efficacy of tolvaptan (OPC-41061), a potent, selective nonpeptide vasopressin V(2) receptor antagonist, on acute and chronic severe hyponatremia was assessed in rats. Experiments were designed to demonstrate the efficacy of tolvaptan reducing mortality in an acute model, and controlling the extent of serum sodium elevation without causing abnormal animal behavior suggesting neurological symptoms in a chronic model. In the acute model, rats developed rapidly progressive, severe hyponatremia by continuous sc infusion of [deamino-Cys(1), D-Arg(8)]-vasopressin (10 ng/h) and forced water-loading (additional 10% initial body weight per day). By d 6, untreated rats had a 47% mortality rate. However, rats treated with repeated oral administrations of tolvaptan (1, 3, and 10 mg/kg) produced dose-dependent aquaresis (i.e. urine volume increased and urine osmolality decreased) that resulted in a gradual increase in plasma sodium concentration. Consequently, tolvaptan treatment reduced mortality and, at higher doses, resulted in no observed deaths. In the gradual model, rats receiving a continuous sc infusion of [deamino-Cys(1), D-Arg(8)]-vasopressin (1 ng/h) combined with a liquid diet were induced to stable, severe hyponatremia (approximately 110 mEq/liter), which lead to increased organ weight and water content. Rats receiving dose titrations of tolvaptan (0.25, 0.5, 1, 2, 4, and 8 mg/kg) increased plasma sodium to healthy levels without causing abnormal animal behavior suggesting neurological symptoms or death, improved hyponatremia-driven increases in wet weight and water content in the organs. Thus, in animal models, analogous to the hyponatremia forms seen in humans, tolvaptan presents exciting therapeutic implications in the management of patients with severe hyponatremia.     

Treatment of the syndrome of inappropriate secretion of antidiuretic hormone by urea

Recent data have shown the role of urea in the urinary concentrating mechanism. We studied the effects of exogenous urea administration in hyponatremia associated with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). In 20 patients with SIADH, we observed a positive correlation between serum sodium and blood urea levels (r = 0.65; p < 0.01). In one patient with an oat cell carcinoma and SIADH-induced hyponatremia, we observed the same positive correlation (r = 0.80; p < 0.01) but also a negative one between the excreted fraction of filtered sodium and urinary urea (r = -0.67; p < 0.001). The short-term administration of low doses of urea (4 to 10 g) resulted in correcting the “salt-losing” tendency of this patient. Longer term administration of high doses of urea (30 g/day) was attempted with the same patient as well as with a healthy volunteer subject with Pitressin^®-induced SIADH. In both patients, urea treatment lowered urinary sodium excretion as long as hyponatremia was significant (< 130 meq/liter). Urea treatment also induced a persistent osmotic diuresis, allowing a normal daily intake of water despite SIADH. This was clearly shown during the long-term treatment of a third patient with SIADH who was taking 30 g urea/day during 11 weeks.It is concluded that urea is a good alternative in the treatment of patients with SIADH who present with persistent hyponatremia despite the restriction of water intake.     

Mechanism of antihypertensive effect of thiazide diuretics

Hemodynamic studies were carried out before and during 8 weeks of treatment with hydrochlorothiazide 50 mg. twice daily in 11 hypertensive patients. Forty-eight hours after beginning treatment there was a significant reduction in blood pressure, cardiac output, plasma volume, and extracellular fluid volume (thiocyanate space) while total peripheral resistance increased. After 6 and 8 weeks of treatment, the blood pressure and the plasma and extracellular volumes remained reduced. However, total peripheral resistance fell while cardiac output rose to control levels. These results were consistent with the “reverse autoregulation” theory of the action of the thiazides as proposed by Tobian. The present findings as well as other clinical and experimental evidence discussed below makes it appear unlikely that the thiazides have an important direct vasodilator effect.     

Pharmacodynamic effects of a nonpeptide antidiuretic hormone V2 antagonist in cirrhotic patients with ascites

Water retention and dilutional hyponatremia, mainly attributable to an impairment of free water excretion and increased vasopressin activity, are well-documented complications in cirrhotic patients with ascites. VPA-985 is a selective, nonpeptide, orally active, vasopressin-2-receptor antagonist. The aim of this study was to determine the pharmacodynamics, safety, and pharmacokinetics of ascending single doses (25, 50, 100, 200, and 300 mg) in cirrhotic patients with ascites in a randomized, double-blind, placebo-controlled trial. Each dose level was studied in 5 patients (4 active and 1 placebo). After an overnight fast and fluid restriction (continued for 4 hours after dose administration), all patients were given placebo on baseline day and an oral suspension of VPA or placebo on the following day. VPA produced a significant dose-related increase in daily urine output (1,454 +/- 858 mL to 4,568 +/- 4,385 mL with VPA 300 mg) and a dose-related decrease in urine osmolality. The free water clearance reached greater than 3 mL/min for doses 100 mg or greater. Simultaneously, significant increases in serum osmolality, sodium, and vasopressin levels were found. There was a significant increase in sodium urine excretion. VPA was rapidly absorbed and maximum serum concentrations were achieved within 1 hour after administration. Elimination half-life ranged from 9.0 hours after 100 mg to 22.6 hours after 200 mg. In conclusion, VPA induced a dose-related aquaretic response, suggesting a therapeutic potential in managing water retention in patients with liver cirrhosis with ascites.     

The role of the prostaglandin system in the regulation of renal function in normal women

The role of prostaglandins in the regulation of renal function was studied in seven healthy female volunteers taking a constant metabolic diet containing 59 meq of sodium and about 50 meq of potassium daily. Each subject underwent two renal clearance studies, during which vasopressin (priming dose, 200 mU; "sustainer," 200 mU/hour at 1 ml/min) was infused intravenously. The first clearance study served as the control; indomethacin (2 mg/kg/day) was given for seven days before the second clearance study to inhibit prostaglandin synthesis. Food and fluid were withheld for 12 hours before the studies. Urine was collected through an indwelling bladder catheter at 30 minute intervals. Glomerular filtration rate was estimated from inulin clearance and renal blood flow from para-aminohippurate (PAH) clearance. Indomethacin was associated with a significant increase in maximal urinary osmolality from 826 +/- 47 mosmol/kg H2) to 920 +/- 32 mosmol/kg H2O (P < 0.01). Minimal "free water" clearance was -1.40 +/- 0.02 ml/min before and -1.63 +/- 0.04 ml/min (P < 0.01) after the administration of indomethacin. Indomethacin did not affect urine flow, urinary sodium or potassium excretion, glomerular filtration rate or renal plasma flow. In addition, indomethacin did not affect the urinary excretion of cyclic adenosine monophosphate (AMP). Plasma arginine-vasopressin, measured in two subjects by radioimmunoassay, did not change with blockade of prostaglandin synthesis. It appears that prostaglandins antagonize the hydro-osmotic effect of antidiuretic hormone by an intrarenal mechanism, independent of changes in renal hemodynamics or cation excretion. This mechanism is probably mediated by an alteration in the water permeability of the collecting ducts. Since urinary cyclic AMP did not change during blockade of prostaglandin synthesis, whereas urinary osmolality increased, a change of vasopressin-dependent cyclic AMP production in the kidney was probably not reflected in urinary cyclic AMP.     

Role of prostaglandins in the pathogenesis of Bartter's syndrome

Increased renal prostaglandins activated by β-catecholamines could produce renal tubular sodium wasting and angiotensin pressor resistance observed in Bartter's syndrome. We therefore measured plasma renin activity (PRA), aldosterone and prostaglandin A (PGA) by radioimmunoassay, and body composition by isotope dilution prior to and following β-adrenergic blockade with propranolol (200 mg/day for 4 days) and prostaglandin synthesis inhibition by indomethacin (200 mg/day for 4 days) in a patient with Bartter's syndrome on a 250 meq sodium diet. After the administration of propranolol, body weight increased 3 kg, daily urine sodium decreased within 24 hours from 230 to 64 meq, and urine potassium from 102 to 45 meq, but PRA and the aldosterone level remained elevated. With the administration of indomethacin, body weight increased 5 kg, daily urinary sodium decreased within 24 hours to 11 meq and urine potassium to 16 meq, PRA (normal < 3 ng/100 ml/hour) decreased from 55 to 4.3 ng/ml/hour, plasma aldosterone (normal < 8 ng/100 ml) from 74.1 to 3.6 ng/100 ml, and whole blood PGA (normal 546 ± 307 pg/ml) decreased from 1,390 and 945 to 86 pg/ml. After the administration of propranolol or indomethacin, exchangeable sodium total body water, extracellular volume and plasma volume all increased from less than to greater than predicted, and pressor resistance to angiotensin was normalized. These results suggest that Bartter's syndrome results from β-adrenergic and prostaglandin-mediated proximal tubular rejection of sodium leading to increased distal sodium-potassium exchange.     

Low sweat electrolytes in a patient with cystic fibrosis

A patient with the clinical syndrome of cystic fibrosis characterized by chronic pulmonary disease, infection with mucoid Pseudomonas aeruginosa, sinusitis, nasal polyposis, abnormal pancreatic bicarbonate response to secretin stimulation, but normal levels of trypsin and chymotrypsin in the duodenal drainage, and a sibling with autopsy-documented cystic fibrosis, is described. Sweat chloride ranged from 20 to 44 meq/liter and sweat sodium from 36 to 55 meq/liter. Immunoglobulin deficiency, α₁-antitrypsin deficiency, tuberculosis and abnormalities of ciliary ultrastructure were excluded. Review of sweat electrolytes in 213 patients with cystic fibrosis revealed that patients with normal pancreatic enzyme release have significantly lower sweat sodium and chloride concentrations (p <0.0005) than do patients with pancreatic insufficiency.Chronic pulmonary disease, pancreatic insufficiency and elevated levels of sweat electrolytes comprise the classic diagnostic triad for cystic fibrosis. The expression of these features may be variable, but the sweat test remains the cardinal laboratory confirmation of the diagnosis. Over 98 percent of patients with cystic fibrosis have sweat chloride values greater than 60 meq/liter, 1 to 2 percent between 50 and 60 meq/liter, and only about one in 1,000, like our patient, less than 50 meq/liter. Patients with cystic fibrosis with borderline sweat chloride values frequently have chronic pulmonary disease but intact pancreatic enzyme release. In such patients, family history, ancillary clinical features and systematic exclusion of other syndromes assume special diagnostic importance.     

Relation between serum sodium concentration and the hemodynamic and clinical responses to converting enzyme inhibition with captopril in severe heart failure

The relation between pretreatment serum sodium concentration and the early and late effects of captopril was examined in 77 consecutive patients with severe chronic heart failure, in whom cardiac catheterization was performed during initiation of treatment and after 2 to 8 weeks. Two groups of patients were defined: 37 patients had hyponatremia (serum sodium less than 135 mEq/liter, group A) and 40 patients had a normal serum sodium concentration (greater than or equal to 135 mEq/liter, group B). With first doses of captopril, patients in group A showed more marked hemodynamic responses than did patients in group B (p less than 0.02). The changes in mean arterial pressure and left ventricular filling pressure seen with first doses of the drug varied linearly and inversely with the pretreatment serum sodium concentration (r = -0.58 and r = -0.53, respectively); this was likely related to the finding that, before administration of captopril, the serum sodium concentration varied linearly and inversely with the logarithm of the plasma renin activity (r = -0.78). However, the pretreatment serum sodium concentration did not predict the long-term hemodynamic or clinical responses to converting enzyme inhibition. Symptomatic hypotension occurred early in the course of therapy (within 24 hours of initiating captopril therapy) in 9 (12%) of the 77 patients; 8 of these 9 had severe hyponatremia (serum sodium less than 130 mEq/liter) and comprised 53% of the 15 patients in our study with such low serum sodium concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thiazide–associated hyponatremia in the elderly: what the clinician needs to know

Thiazide-induced hyponatremia is one of the main causes of decreased sodium levels in elderly individuals. This review presents the current evidence regarding the thiazide-associated hyponatremia. Thiazide-associated hyponatremia is observed mainly in patients with certain risk factors such as those receiving large doses of thiazides, having much comorbidity, such as heart failure, liver disease or malig-nancy, and taking several medications, such as non-steroidal anti-inflammatory drugs, selective serotonin re-uptake inhibitors or tricyclic antidepressants. Sodium concentration should be monitored in patients with risk factors for developing thiazide-associated hyponatremia and clinicians should measure promptly serum sodium levels in patients with neurologic signs indicating reduced sodium levels. The clini-cal and biochemical profile of patients with thiazide-associated hyponatremia may be that of extracellular volume depletion or the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The investigation of possible thiazide-associated hyponatremia includes the exclusion of other causes of decreased sodium levels and the identification of the characteristics of hyponatremia due to thiazides (ex-tracellular volume depletion-related or SIADH-like). Treatment should be carefully monitored to avoid serious neurologic complications due to overcorrection. Clinicians should discourage prescribing thiazides in patients with a history of diuretic-associated hyponatremia and should prefer low doses of thiazides in patients with risk factors for developing thiazide-associated hyponatremia.     

Hyponatremia in patients treated with lorcainide, a new antiarrhythmic drug

The effects of lorcainide, a new antiarrhythmic drug, on serum electrolytes and osmolality are described in a series of 33 patients with organic heart disease and complex ventricular arrhythmias treated with lorcainide. In eight patients, a mean decrease in serum Na+ of 8.25 +/- 3.2 mEq/L was observed after a single 200 mg intravenous dose of lorcainide. Sixteen of 33 patients developed significant hyponatremia and hypoosmolality during oral treatment with lorcainide. In all except two patients, serum Na+ returned to normal values within 3 to 12 months of continued lorcainide therapy. Low serum Na+ and hypoosmolality in the absence of volume depletion, clinically manifest edema, and unaltered renal, adrenal, cardiac, or thyroid function suggest that this antiarrhythmic drug produced the syndrome of inappropriate antidiuretic hormone secretion (SIADH). SIADH appeared to be transient and asymptomatic in our patients. One patient developed severe hyponatremia with serum Na+ of 108 mEq/L when hydrochlorothiazide was given to control hypertension. It is concluded that SIADH is an important side effect of lorcainide therapy. We recommend that serum Na+ be carefully monitored in patients started on lorcainide therapy, and extreme caution should be exercised in prescribing diuretics to patients with persistent hyponatremia.