Effect of hyponatremia (<135 mEq/L) on outcome in patients with non-ST-elevation acute coronary syndrome

Hyponatremia is associated with adverse outcomes in patients with heart failure and ST-elevation myocardial infarction (STEMI). We evaluated the effect of hyponatremia on outcomes in patients with suspected acute coronary syndrome and non-STEMI. All patients had a sodium level determined at time of admission, at 24 and 48 hours, and at discharge. Of 1,478 patients, 341 (23.1%) were hyponatremic (sodium <135 mEq/L) on presentation. Patients who had hyponatremia on admission were significantly more likely to die or have recurrent myocardial infarction in the next 30 days (odds ratio 1.98, 95% confidence interval 1.35 to 2.89, p <0.001). This relation persisted after adjusting for factors such as age, left ventricular ejection fraction, use of diuretics before admission, hypotension on presentation, anemia, chronic renal insufficiency, pulmonary edema, and high troponin levels (odds ratio 1.7, 95% confidence interval 1.1 to 2.5, p = 0.01). In conclusion, hyponatremia on admission is associated with 30-day adverse outcome in patients presenting with suspected acute coronary syndrome/non-STEMI.     

Risk factors for symptomatic hyponatraemia: the role of pre-existing asymptomatic hyponatraemia

Background: Hyponatraemia is associated with substantial morbidity and mortality. Identification of the risk factors associated with the development of symptomatic hyponatraemia is important in determining preventive strategies. Methods: A retrospective analysis of the risks factors associated with the development of severe, symptomatic hyponatraemia requiring hospital admission over the past 3 years at our institution was carried out. Results: Forty‐seven patients (26 women, 21 men) with a hospital admission serum sodium <134 mmol/L were identified. Of these patients, 31 (65.9%) had associated changes in the mental status that improved with the treatment of the hyponatraemia suggesting causality. The average admission sodium level of this cohort was 118.8 mmol/L. Symptomatic hyponatraemia was associated with volume depletion (32.6%), congestive heart failure (26%), syndrome of inappropriate antidiuretic hormone (26%), thiazide diuretic use (26%) and selective serotonin re‐uptake inhibitor use (26%). In 21.7% of cases, the cause was multifactorial (congestive heart failure, syndrome of inappropriate antidiuretic hormone or medication use with volume depletion). In 11% of cases, patients were taking both thiazide diuretics and serotonin re‐uptake inhibitors. Most importantly, 70.9% of all patients admitted with symptomatic hyponatraemia had pre‐existing hyponatraemia that was untreated and believed to be asymptomatic (P < 0.05). This was the most common risk factor identified. We next investigated the prevalence of presumed asymptomatic hyponatraemia in the outpatient setting. Out of 27 496 patients analysed, 14% had serum sodium levels less than or equal to 134 mEq/L and 4% had values less than 130 mEq/L. Conclusion: Pre‐existing asymptomatic hyponatraemia is a common finding and is associated with a high risk for the development of worsening hyponatraemia with altered mental status.     

A Case of Flecainide-Induced Hyponatremia

We present a case of flecainide-induced hyponatremia in a 67-year-old woman who was treated for paroxysmal atrial tachycardia. She developed dizziness after starting flecainide and was found to be hyponatremic with a sodium level of 122 mmol/L (decreased from 136 mmol/L). Work-up failed to reveal other causes of hyponatremia. She was not on diuretics, laxatives, or herbal medications. After discontinuation of flecainide, her symptoms and sodium levels improved. Hyponatremia is a previously unrecognized entity as an adverse effect of flecainide. We will discuss the clinical presentation, lab findings, and a possible explanation for this patient's unusual reaction to flecainide.     

Terlipressin-induced hyponatremic encephalopathy in a noncirrhotic patient

Terlipressin, an analogue of vasopressin, is frequently used for the management of esophageal varices bleeding and hepatorenal syndrome. Terlipressin therapy in portal hypertensive patients is frequently associated with hyponatremia, but is rarely accompanied with serious neurological manifestations. A 39-year-old female with pancreatic neuroendocrine tumor, liver metastasis, main portal vein thrombosis, and a history of esophageal varices presented to the emergency room because of hematemesis. Terlipressin was given with a loading dose of 2 mg followed by 1 mg every 6 hours. After a total of 6 mg terlipressin injection, she suffered from acute delirium. Pertinent examinations showed there was no gross brain lesion by computed tomography, whereas her serum sodium level dropped from baseline (136 mmol/L) to 116 mmol/L with a serum osmolality of 256 mOsm/kg. At that time, urine sodium and urine osmolality were 142 mmol/L and 488 mOsm/kg, respectively. Under the tentative diagnosis of terlipressin-induced hyponatremic encephalopathy, terlipressin was withheld and hypertonic saline infusion was given. Within 12 hours, her serum sodium level recovered to 130 mmol/L and she gradually regained her cognitive functions. Although symptomatic hyponatremic encephalopathy is a rare complication of terlipressin treatment, close monitoring of serum electrolyte level is warranted in patients receiving terlipressin.     

Refractory ascites and dilutional hyponatremia: current management and new aquaretics

Ascites is the most common complication of cirrhosis and is associated with 50% mortality at 2 years if patients do not receive orthotopic liver transplantation. Recently the International Ascites Club defined ascites into three groups: In grade I ascites fluid is detected only by ultrasound; in grade II, ascites is moderate with symmetrical distention of the abdomen; and in Grade 3 ascites is large or tense with marked abdominal distention. About 10% of patients with ascites are refractory to treatment with diuretics. In refractory ascites, patients do not respond to highest doses of diuretics (spironolactone 400 mg/day and furosemide 160 mg/ day) or develop side effects (hyperkalemia, hyponatremia, hepatic encephalopathy, or renal failure) that prohibit their use. Patients may be treated either by repeated large volume paracentesis plus albumin or transjugular intrahepatic portosystemic shunts (TIPS). Dilutional hyponatremia in cirrhotic patients is defined as serum sodium < or = 130 mEq/L in the presence of an expanded extracellular fluid volume, as indicated by the presence of ascites and/or edema. This complication of cirrhotic patients with ascites has recently gained attention given that several reports indicate that when serum sodium concentration is combined with the Model for End-Stage liver disease (MELD) it improves the prognostic accuracy of MELD score in patients awaiting orthotopic liver transplant (OLT). The first step in the management of dilutional hyponatremia is fluid restriction and discontinuation of diuretics. Water restriction at 1,000 mL/day helps prevent the progressive decrease in serum sodium concentration but usually does not correct hyponatremia in most cases. Actually are developing drugs that are active orally and act by selectively antagonizing the specific receptors (V2 receptor) of arginine vasopressin. These agents act in the distal collecting ducts of the kidneys, by increasing solute free water excretion and, thus, improving serum sodium concentration in hyponatremic patients.     

Value of fractional uric acid excretion in differential diagnosis of hyponatremic patients on diuretics

BACKGROUND: The syndrome of inappropriate antidiuresis (SIAD) is the most frequent cause of hyponatremia. Its diagnosis requires decreased serum osmolality, inappropriately diluted urine (e.g. >100 mOsm/kg), clinical euvolemia, and a urinary sodium (Na) excretion (U-Na) more than 30 mmol/liter. However, in hyponatremic patients taking diuretics, this definition is unreliable due to the natriuretic effect of diuretics. Here, we examined the diagnostic potential of alternative laboratory measurements to diagnose SIAD, regardless of the use of diuretics. METHODS: A total of 86 consecutive hyponatremic patients (serum Na <130 mmol/liter) was classified based on their history, clinical evaluation, osmolality, and saline response to isotonic saline into a SIAD and a non-SIAD group. U-Na, serum urate concentration, and fractional excretion (FE) of Na, urea, and uric acid (UA) were measured in all subjects. The accuracy to diagnose SIAD was assessed using receiver operating characteristic analysis. RESULTS: A total of 31 patients (36%) had a diagnosis of SIAD, and 55 (64%) were classified as non-SIAD. There were 57 patients (68%) who were on diuretics (15 in the SIAD group, 42 in the non-SIAD group). In the absence of diuretic therapy, SIAD was accurately diagnosed using U-Na (area under the receiver operating characteristic curve 0.96; 0.92-1.02). However, in patients on diuretics, the diagnosis was unreliable (area under the curve 0.85; 0.73-0.97). There, FE-UA performed best compared with all other markers tested (area under the curve 0.96; 0.92-1.12), resulting in a positive predictive value of 100% if a cutoff value of 12% was used. CONCLUSION: FE-UA allows the diagnosis of SIAD with excellent specificity. Combining the information on U-Na and FE-UA leads to a very high diagnostic accuracy in hyponatremic patients with and without diuretic treatment.     

Hyponatremia in cirrhosis: Results of a patient population survey

Low serum sodium concentration is an independent predictor of mortality in patients with cirrhosis, but its prevalence and clinical significance is unclear. To evaluate prospectively the prevalence of low serum sodium concentration and the association between serum sodium levels and severity of ascites and complications of cirrhosis, prospective data were collected on 997 consecutive patients from 28 centers in Europe, North and South America, and Asia for a period of 28 days. The prevalence of low serum sodium concentration as defined by a serum sodium concentration < or =135 mmol/L, < or =130 mmol/L, < or =125 mmol/L, and < or =120 mmol/L was 49.4%, 21.6%, 5.7%, and 1.2%, respectively. The prevalence of low serum sodium levels (<135 mmol/L) was high in both inpatients and outpatients (57% and 40%, respectively). The existence of serum sodium <135 mmol/L was associated with severe ascites, as indicated by high prevalence of refractory ascites, large fluid accumulation rate, frequent use of large-volume paracentesis, and impaired renal function, compared with normal serum sodium levels. Moreover, low serum sodium levels were also associated with greater frequency of hepatic encephalopathy, spontaneous bacterial peritonitis, and hepatorenal syndrome, but not gastrointestinal bleeding. Patients with serum sodium <130 mmol/L had the greatest frequency of these complications, but the frequency was also increased in patients with mild reduction in serum sodium levels (131-135 mmol/L). In conclusion, low serum sodium levels in cirrhosis are associated with severe ascites and high frequency of hepatic encephalopathy, spontaneous bacterial peritonitis, and hepatorenal syndrome.     

Hyponatremia, cerebral edema, and noncardiogenic pulmonary edema in marathon runners

BACKGROUND: Noncardiogenic pulmonary edema is often associated with increased intracranial pressure and can be the initial manifestation of hyponatremic encephalopathy. Marathon runners tend to develop conditions that lead to hyponatremia. OBJECTIVE: To describe the development and treatment of noncardiogenic pulmonary edema in marathon runners that was associated with hyponatremic encephalopathy. DESIGN: Case series. SETTING: One university hospital and two community hospitals. PATIENTS: Seven healthy marathon runners who had a history of nonsteroidal anti-inflammatory drug use. The runners collapsed after competing in a marathon and were hospitalized with pulmonary edema. MEASUREMENTS: Plasma sodium levels, chest radiograph, electrocardiogram, cardiac enzyme levels, and magnetic resonance imaging or computed tomographic scans of the brain. RESULTS: Patients had nausea, emesis, and obtundation. The mean (+/-SD) plasma sodium level was 121 +/- 3 mmol/L, and oxygen saturation was less than 70%. Electrocardiograms and echocardiograms were normal. Chest radiographs showed pulmonary edema with a normal heart. Creatine phosphokinase-MB bands, troponin levels, and pulmonary wedge pressure were not elevated. Scanning of the brain showed cerebral edema. All patients were intubated and mechanically ventilated. Treatment with intravenous NaCl, 514 mmol/L, increased plasma sodium levels by 10 mmol/L in 12 hours. Pulmonary and cerebral edema resolved as the sodium level increased. One patient had unsuspected hyponatremic encephalopathy and died of cardiopulmonary arrest caused by brainstem herniation. All six treated patients recovered and were well after 1 year of follow-up. CONCLUSIONS: In healthy marathon runners, noncardiogenic pulmonary edema can be associated with hyponatremic encephalopathy. The condition may be fatal if undiagnosed and can be successfully treated with hypertonic NaCl.     

Dysregulation of atrial natriuretic factor in hypertension-prone man

To evaluate the hypothesis of an atrial natriuretic factor (ANF) deficiency in hypertension-prone humans, we investigated plasma ANF and other variables in 116 white offspring of normotensive parents (ONorm) or essential hypertensive parents (OHyp). Ten ONorm and 10 OHyp, all men matched for age and body habitus, were studied after 4 days of low (70 mmol/day) and high (350 mmol/day) dietary sodium intake. After mild sodium restriction, plasma ANF did not differ between ONorm and OHyp (9.7 +/- 0.7 vs. 9.0 +/- 1.3 fmol/L). On high sodium intake, plasma ANF increased in ONorm, but not in OHyp (to 18.3 +/- 1.7 vs. 11.7 +/- 1.7 fmol/L; P less than 0.001). On the other hand, acute responses of plasma immunoreactive ANF (irANF) to saline loading or a norepinephrine-induced rise in blood pressure did not differ significantly between 8 ONorm and 8 OHyp. Fifty-one additional ONorm and 45 OHyp were evaluated during liberal sodium intake. Groups were further subdivided according to whether 24-h urinary sodium excretion was 91 mmol/m2 or less (modest salt intake) or more than 91 mmol/m2 (high salt intake). Twenty-four-hour urinary sodium was similar in the 26 ONorm and 21 OHyp on a modest salt intake (121 +/- 6 vs. 116 +/- 9 mmol) and in the 25 ONorm and the 24 OHyp on a high salt intake (226 +/- 10 vs. 221 +/- 9 mmol). However, compared with ONorm, plasma irANF in OHyp was slightly lower on modest sodium intake (7.7 +/- 0.7 vs. 5.3 +/- 0.7 fmol/L; P less than 0.05) and markedly reduced on high sodium intake (15.0 +/- 1.3 vs. 8.0 +/- 1.3 fmol/L; P less than 0.001). Moreover, the slope of the relationship between plasma irANF and 24-h urinary sodium was flatter in OHyp than in ONorm (z test = 2.4). We postulate a new endocrine syndrome characterized by a relative plasma ANF deficiency during high sodium intake in some hypertension-prone humans. This functional defect becomes apparent during chronic, rather than acute, stimulation of ANF release. It occurs as a familial disturbance and may potentially predispose to the development of hypertension.     

The value of serum magnesium determination in hypertensive patients receiving diuretics

Some clinicians contend that hypomagnesemia is a common problem in patients receiving diuretic therapy and that routine serum magnesium determinations may be indicated in such patients. We determined serum magnesium (Mg++) levels in 354 patients with uncomplicated hypertension. No significant difference was observed in the mean Mg++ between the 245 diuretic-treated patients and the 109 patients not receiving diuretics, 0.965 vs 0.97 mmol/L (1.93 vs 1.94 mEq/L). When analyzed by type of diuretic, there were statistically significant differences in the mean serum Mg++ concentrations between those receiving thiazides, 0.94 mmol/L (1.87 mEq/L); those receiving no diuretics, 0.97 mmol/L (1.94 mEq/L); and those receiving triamterene-containing diuretics, 1.01 mmol/L (2.01 mEq/L). These absolute differences, however, were clinically quite small, and hypomagnesemia was uncommon. Neither patient age, the duration of diuretic use, nor the serum potassium level correlated with Mg++. With respect to dose, those receiving 100 mg/d of hydrochlorothiazide had the lowest Mg++ concentrations and the greatest prevalence of hypomagnesemia (12%), defined as Mg++ less than 0.75 mmol/L (1.5 mEq/L). Serum Mg++ need not routinely be determined in patients with uncomplicated hypertension who are receiving triamterene-containing diuretics or low-dose (50 mg/d or less) hydrochlorothiazide.     

Frequency of hypomagnesemia in hospitalized patients receiving digitalis

We examined the frequency of hypokalemia and hypomagnesemia in patients receiving digitalis. Serum sodium, magnesium, and potassium levels were determined in 136 serum samples sent to the laboratory for digoxin assay. Hyponatremia (less than or equal to 130 mEq/L) occurred most frequently (21%), followed by hypomagnesemia (less than or equal to 1.25 mEq/L) in 19%, hypokalemia (less than or equal to 3.5 mEq/L) in 9%, and hypermagnesemia (greater than or equal to 2.25 mEq/L) in 7%. The twofold frequency of hypomagnesemia (19%) contrasted with hypokalemia (9%) indicates that clinicians are more attuned to avoiding hypokalemia than hypomagnesemia in patients receiving digitalis. Because hypokalemia and/or hypomagnesemia may contribute to the toxic effects of digitalis, our observation suggests that hypomagnesemia may be a more frequent contributor than hypokalemia to induction of toxic reactions to digitalis. Routine serum magnesium determination in patients receiving digitalis, who often are also receiving potent diuretics, may assist in identifying additional patients at risk for the toxic effects of digitalis.     

Severe hypophosphatemia in hospitalized patients

Severe hypophosphatemia (serum phosphorus less than or equal to 0.48 mmol/L [less than or equal to 1.5 mg/dL]) was found in 120 patients admitted to a major university hospital, during a period of 16 months. Fifty-one patients (42.5%) developed hypophosphatemia postoperatively. Medications known to precipitate hypophosphatemia were a causative factor in 82% of the patients, with glucose administered intravenously, antacids, diuretics, and steroids being the most common agents associated with profound hypophosphatemia. Gram-negative septicemia was observed in 16 patients, and it was the second most common cause of severe hypophosphatemia. The mortality rate was 20% in patients with a serum phosphorus concentration between 0.36 and 0.48 mmol/L (1.1 and 1.5 mg/dL) (group A) and 30% in patients with a serum phosphorus concentration of less than or equal to 0.32 mmol/L (less than or equal to 1.0 mg/dL) (group B). The cause of death and its temporal association with the lowest observed values of phosphorus concentration indicate that severe hypophosphatemia might be a contributory factor to mortality. Our data indicate that severe hypophosphatemia in hospitalized patients is the result of a combination of factors. Surgery, followed by a period of fasting with intravenous administration of glucose, and gram-negative septicemia are the most common causes.     

Metabolic alkalosis contributes to acute hypercapnic respiratory failure in adult cystic fibrosis

BACKGROUND: and study objectives: Patients with end-stage cystic fibrosis (CF) develop respiratory failure and hypercapnia. In contrast to COPD patients, altered electrolyte transport and malnutrition in CF patients may predispose them to metabolic alkalosis and, therefore, may contribute to hypercapnia. The aim of this study was to determine the prevalence of metabolic alkalosis in adults with hypercapnic respiratory failure in the setting of acute exacerbations of CF compared with COPD. DESIGN: Levels of arterial blood gases, plasma electrolytes, and serum albumin from 14 consecutive hypercapnic CF patients who had been admitted to the hospital with a respiratory exacerbation were compared with 49 consecutive hypercapnic patients with exacerbations of COPD. Hypercapnia was defined as a PaCO(2) of > or = 45 mm Hg. RESULTS: Despite similar PaCO(2) values, patients in the CF group were significantly more alkalotic than were those in the COPD group (mean [+/- SD] pH, 7.43 +/- 0.03 vs 7.37 +/- 0.05, respectively; p < 0.01). A mixed respiratory acidosis and metabolic alkalosis was evident in 71% of CF patients and 22% of COPD patients (p < 0.01). The mean concentrations of plasma chloride (95.1 +/- 4.9 vs 99.8 +/- 5.2 mmol/L, respectively; p < 0.01) and sodium (136.5 +/- 2.8 vs 140.4 +/- 4.5 mmol/L, respectively; p < 0.01) were significantly lower in the CF group, and the levels of serum albumin were significantly reduced (27.4 +/- 5.8 vs 33.7 +/- 4.8 mmol/L, respectively; p < 0.01). CONCLUSION: Metabolic alkalosis contributes to hypercapnic respiratory failure in adults with acute exacerbations of CF. This acid-base disturbance occurs in conjunction with reduced total body salt levels and hypoalbuminemia.     

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.     

Repeated paracentesis and i.v. albumin infusion to treat 'tense' ascites in cirrhotic patients. A safe alternative therapy

To investigate the usefulness of paracentesis as an alternative treatment for ascites, 41 cirrhotic patients with 'tense' ascites were randomly assigned to treatment with either repeated paracenteses plus i.v. albumin infusion (n = 20) or diuretics (n = 21). Satisfactory mobilization of ascites was obtained with paracentesis in all but one case and with diuretics in all but two cases. Ascites disappeared within 3 or 4 days with paracentesis, but only after 15 days with diuretics. The rate of reaccumulation of ascites following paracentesis, without diuretic administration, exceeded 300 g/day in only 5 patients. The incidence of complications and the mortality rate were similar in both groups of patients during hospital stay and during follow-up. This was corroborated by the evidence that no negative changes were induced in clinical and laboratory parameters of hemodynamic, hepatic and renal function after evacuation of the ascites. These results confirm that repeated paracenteses combined with human albumin replacement are safe and effective for treating 'tense' ascites, and more rapid than traditional diuretic therapy.     

Short-Term Course of Corticosteroids in the Treatment of Resistant Ascites Complicating Schistosomal Liver Disease

The aim of this work was to evaluate the effect of short-term corticosteroids in resistant ascites complicating schistosomal liver disease after 4 wk or more on standard treatment. Thirty-seven patients were randomly allocated to two groups: Group I (18 patients) was put on 40 mg furosemide and 200 mg spironolactone, in addition to a 15-day, tapering dose of prednisone (15, 10, 5 mg). Group II (19) patients received the same diuretics without steroids, and served as controls. At the end of a 2-wk course of therapy, the mean variations were as follows: body weight in patients in Group I ("cases") decreased by 9.8 kg, compared with 4.3 kg in controls; abdominal girth decreased by 7.4 cm in cases, compared with 3.6 cm in controls; urine output increased by 635.9 ml in cases, compared with 364.6 ml in controls; urinary sodium excretion increased by 16.5 mEq/day in cases, compared with 4.1 mEq/day in controls. These differences between cases and controls were found to be statistically significant (p less than 0.01). On the other hand, there were insignificant differences as regards decrease in blood urea (3.2 g/dl for cases and 2.7 g/dl for controls), decrease in serum creatinine (0.2 mg/dl for both cases and controls), increase in serum albumin (0.3 g/dl in cases and 0.2 g/dl in controls), increase in serum sodium (3.2 mEq/L in cases and 2.7 mEq/L in controls), and increase in serum potassium (0.2 mEq/L in cases and 0.4 mEq/L in controls). We conclude that a short-term course of corticosteroids in conjunction with standard diuretics has proved to be an effective, safe, and economical modality to relieve resistant hepatic ascites. It can be considered a temporary alternative to paracentesis with albumin infusion.     

The pressor effect of sodium-volume expansion is calcium mediated.

To investigate the calcium dependence of salt-induced hypertension we concurrently measured blood pressure and serum ionized calcium in conscious normotensive female dogs undergoing five infusions: 1) sodium chloride (0.9%) 2) calcium chloride (10 mg/kg), 3) combined sodium chloride and calcium chloride, 4) nicardipine (1 micrograms/kg/min), and 5) combined sodium chloride and calcium chloride in the presence of nicardipine. While saline and calcium chloride infusions individually did not affect blood pressure, saline combined with calcium chloride significantly and consistently raised mean arterial pressure (MAP) (delta MAP = 7 +/- 2 mm Hg, P less than .001 v baseline). Serum ionized calcium (Caio) levels increased within the normal range with the infusion of calcium alone (1.32 +/- 0.03 to 1.48 +/- 0.01 mmol/L, P less than .005). Extracellular Caio rose less with the combined NaCl-CaCl2 infusion (delta Caio 0.10 +/- 0.01 v 0.16 +/- 0.02 mmol/L, P less than .02). The difference in calcium elevations could not be attributed to volume expansion alone, since saline infusion itself did not affect serum ionized calcium (1.32 +/- 0.3 to 1.31 +/- 0.01 mmol/L, P = NS). Furthermore, nicardipine prevented the pressor effect of the combined saline-calcium infusion. (delta MAP = -2 +/- 3 v 7 +/- 2 mm Hg, P less than .001), and restored the rise in extracellular Caio to that seen with the nonpressor calcium infusion (delta Caio 0.15 +/- 0.01 mmol/L v 0.16 +/- 0.02 mmol/L, P = NS). Altogether, these data demonstrate that the rise in blood pressure and ionized calcium following an acute infusion of sodium and calcium chloride are interdependent.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Hyponatremia as the presenting manifestation of Sheehan's syndrome in elderly patients

BACKGROUND AND AIMS: Hyponatremia is not a disease in itself, but a manifestation of a variety of disorders and side-effects of diuretics; alternatively, it may be the only manifestation of hypopituitarism or hypothyroidism. In our experience, diagnosis of hypopituitarism in hyponatremic patients is often overlooked, especially in the elderly. METHODS: We report here data from five elderly multiparous women (mean age 69 yr; range 62-78 yr) with a past history of complicated delivery, in whom initial symptoms were due to hyponatremia (serum sodium less than 128 mEq/L) who went undiagnosed and untreated for a long time (up to 42 years) after the initial event. RESULTS: Initial hormonal levels indicated hypopituitarism, and magnetic resonance imaging led to diagnosis of empty sella in all patients, so that they were diagnosed as suffering from Sheehan's syndrome (SS). The occurrence of sodium and water disorders associated with SS depends on the degree of pituitary damage, time of onset since the initial pituitary insult, and concurrent medical conditions which also play a role in sodium and water balance. In these patients, clinical condition and hyponatremia improved rapidly after glucocorticoid substitution. L-thyroxine was appropriately substituted subsequently. CONCLUSIONS: We suggest that, especially in elderly patients, much more attention should be paid to patients' past history. Early recognition of severe hyponatremia due to hypopituitarism with adrenal insufficiency is critical, and treatment with hydrocortisone results in safe and improved quality of life.     

Arzneimittelassoziierte St?rungen des S?ure-Basen-Haushalts

Renal elimination of drugs and/or their metabolites may interact with different parts of the renal tubule system resulting in drug-induced acid-base disorders. Drug withdrawal or dose adjustment is the consequence. Antibiotic-related changes include many different acid-base disorders. Penicillin might cause hypokalemia, metabolic alkalosis or high-anion metabolic acidosis, aminoglycosides and tetracyclines are associated with Fanconi syndrome. Gentamicin may cause hypokalemic metabolic alkalosis together with hypomagnesemia and hypokalemia. Treatment with loop diuretics might result in hypochloremic metabolic acidosis nowadays termed chloride-depletion alkalosis for pathophysiological reasons. Using potassium-sparing diuretics, a mild hyperchloremic metabolic acidosis along with hyperkalemia has been reported. The incidence of calcium-alkali syndrome classified by the trias hypercalcemia, metabolic alkalosis and renal failure with polyuria is increasing due to the widespread use of vitamin D and calcium supplementation. Severe metabolic acidosis is associated with propofol use (propofol-related syndrome) as well as drug use containing propylene glycol (e.g. diazepam).