Plasma arginine vasopressin and atrial natriuretic peptide concentration in patients with hyponatremia at diagnosis and following treatment

BACKGROUND: Much evidence for arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) in the pathogenesis of hyponatremia in humans is based on single measurements. To study the roles of AVP and ANP in the pathogenesis and recovery of hyponatremia, sequential measurements of ANP and AVP were taken during treatment in a group of hyponatremic patients with different etiologies. METHODS: Consecutive adult patients with hyponatremia (serum Na <130 mmol/l) and healthy controls were studied. Volume status was determined by clinical and laboratory criteria. Plasma AVP and ANP, fractional sodium excretion, and urine osmolality were determined daily until serum Na was above 135 mmol/l or for at most 7 days. RESULTS: A total of 16 controls and 40 hyponatremic patients (12 normovolemic, 9 hypervolemic, and 19 hypovolemic) were studied. Patients' plasma AVP on the first day [1.0 (0.3-2.3) ng/l] and on the last day [1.1 (0.3-2.5) ng/l] of the study did not differ from that of controls [0.7 (0.5-1.0) ng/l]. Serum sodium concentration increased significantly in patients between the first and the last day. Patients had significantly lower ANP concentrations, both on the first day [25 (15-46) ng/l] and on the last day [29 (17-46) ng/l], than controls [41 (28-51) ng/l]. Plasma AVP was elevated relative to serum osmolality on the first day and to a lesser extent on the last day of the study. CONCLUSIONS: AVP is inappropriately high in a majority of hyponatremic patients. Plasma AVP and ANP concentrations do not change during treatment in hyponatremic patients despite a significant increase in serum osmolality. A low ANP concentration in clinically normovolemic and hypovolemic patients indicates volume depletion, which may lead to baroreceptor-stimulated AVP secretion.     

Post-operative hyponatremia in patients with pituitary adenoma: post-operative management with a uniform treatment protocol

This study is a retrospective analysis of hyponatremia after transsphenoidal surgery in patients with pituitary adenoma. We evaluated (i) the incidence of post-operative hyponatremia (serum Na levels ≤ 135 mEq/L) and the emergence of hyponatremic symptoms, and assessed (ii) the risk factors under a uniform protocol of i.v. infusion with steroid and electrolyte fluid. We examined 88 consecutive operated patients (female: 60; male: 28) with pituitary adenoma. Apart from reconfirming the effects of the purported risk factors, we focused on the degree of serum Na decline on post-operative hyponatremia. Although remained stable during early post-operative period (4 days after surgery), the serum Na levels subsequently decreased after post-operative day 4 in 81 of 88 cases (92.0%). Of 88 patients, 27 (30.7%) and 9 (10.2%) cases suffered from hyponatremia, and developed hyponatremic symptoms. Interestingly, the degree of serum Na levels decline (from pre-operative levels) indicated a useful independent risk factor for monitoring hyponatremic symptoms (p = 0.006) and the degree of decline tended to be greater in elder patients (> 60 years) (p = 0.0346). Serum Na levels should be monitored from, at least, post-operative day 7 to detect early development of hyponatremia. Special attention and recovery effort should be given to elder patients with marked serum Na level decline after surgery.     

Neurological manifestations and morbidity of hyponatremia: correlation with brain water and electrolytes.

1. An attempt was made to evaluate the pathophysiology of symptoms of hyponatremia as related to changes in brain water and electrolytes. Studies were carried out in 66 hyponatremic patients and 5 groups of experimental animals. 2. In hyponatremic patients, symptoms (depression of sensorium, seizures) correlated well with plasma Na+ (r = 0.64, p less than .001), but there was substantial overlap. In patients with acute hyponatremia, all were symptomatic and 50% died. Among patients with hyponatremia of at least 3 days duration, sympatomatic patients had plasma Na+ (115 +/- 1 mEq/L) which was significantly less (p less than .001) than that of asymptomatic patients (plasma Na+ = 122 +/- 1 mEq/L). Among symptomatic patients, mortality was 12% and 8% had seizures, while none of the asymptomatic patients died or had seizures. 3. Among 14 patients with acute (less than 12 hrs) hyponatremia, the mean plasma Na+ was 112 +/- 2 mEq/L. All such patients had some depression of sensorium and four had grand male seizures. Seven of these patients were treated with hypertonic (862 mM) NaCl, while four were treated only with fluid restriction. Of the seven patients treated with hypertonic NaCl, five survived, while three of four patients treated with fluid restriction died. There was no evidence of circulatory congestion or cerebral damage in the patients treated with hypertonic NaCl. 4. Among rabbits with acute (2-3 hours) hyponatremia (plasma Na+ = 119 +/- 1 mEq/L), all had grand mal seizures and 86% died. All such animals had cerebral edema (brain H2O content 17% above control value) but brain content of Na+, K+ and Cl- was normal. 5. Rabbits with 3 1/2 days of hyponatremia (plasma Na+ = 122 +/- 2 mEq/L) appeared to be asymptomatic, even though brain water content was 7% above normal (p less than .01). 6. Rabbits with 16 days of more severe hyponatremia (plasma Na+ = 99 +/- 3 mEq/L) were weak, anorexic, lethargic and unable to walk. Brain water content was 7% above normal, although brain osmolality (218 +/- 12 mOsm/kg H2O) was similar to plasma (215 +/- 8 mOsm/kg). Brain content of Na+, K+, Cl- and osmoles was 17 to 37% less than normal values, so that the brain established osmotic equilibrium with plasma primarily by means of a loss of electrolytes. 7. These studies suggest that in patients with hyponatremia, symptoms and morbidity are only grossly correlated with either magnitude or duration of hyponatremia. Symptoms appear to correlate best with the interplay between a net increase in brain water versus a loss oof brain electrolytes. However, even asymptomatic animals have subclinical brain edema when plasma Na+ is below 125 mEq/L, and such edema may cause permanent brain damage. Thus, many patients with similar levels of plasma Na+, particularly when they are symptomatic, should probably be treated with hypertonic NaCl infusions.     

Total paracentesis in cirrhotic patients with tense ascites and dilutional hyponatremia

OBJECTIVE: The safety of large-volume paracentesis with plasma expander infusion in ascitic cirrhotic patients with advanced liver disease, hyponatremia, or renal failure has not been elucidated. Our aim was to investigate the safety of total paracentesis in cirrhotic patients with ascites and severe hyponatremia. METHODS: Forty-five cirrhotic patients with tense ascites were treated with total paracentesis and infusion of plasma expanders. At inclusion, 20 patients showed severe hyponatremia (serum sodium <130 mEq/L). In the remaining 25 patients, serum sodium was >130 mEq/L (range, 133-146 mEq/L). RESULTS: Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were significantly higher in patients with hyponatremia (PRA: 19.7 +/- 5.8 ng/mL/h; PAC: 217 +/- 35 ng/dL) than in those patients without hyponatremia (PRA: 4.9 +/- 1.1 ng/mL/h; PAC: 95 +/- 31 ng/dL), indicating a more severe systemic hemodynamic deterioration. After paracentesis, PRA and PAC increased similarly in both groups of patients. Serum sodium levels remained unchanged after paracentesis in patients with hyponatremia (127 +/- 0.5 to 128 +/- 1.5 mEq/L) and decreased slightly in patients without hyponatremia (137 +/- 1 to 135 +/- 1 mEq/L; p < 0.005). The incidence of complications during the first hospitalization, the probability of readmission for complications of cirrhosis, and the probability of survival at 1 yr were similar in both groups of patients. CONCLUSIONS: These results indicate that therapeutic paracentesis is a safe treatment for tense ascites in cirrhotic patients with severe hyponatremia.     

Hyponatremia and arginine vasopressin secretion in patients with refractory hepatic ascites undergoing peritoneovenous shunting

Seven patients with persistent hyponatremia but normal or elevated serum arginine vasopressin levels and refractory ascites undergoing peritoneovenous shunting were studied in a Metabolic Unit on a 20 mEq sodium 1200 ml fluid-restricted diet to elucidate the mechanism of this response. The intravascular volume expansion after shunt implantation resulted in improvements in cardiac output, renal plasma flow and creatinine clearance (70.7 +/- 9.5 to 140.1 +/- 18.5 ml/min, p less than 0.005). There was an immediate diuresis (632 +/- 135 to 2450 +/- 323 ml/day, p less than 0.005) and natriuresis (3 +/- 1 to 25.9 +/- 10.6 mEq/24 h, p less than 0.05), and urine osmolality decreased significantly (622 +/- 91 to 251 +/- 76 mosmol/L, p less than 0.05) with a significant rise in serum sodium concentration by 72 hr (131 +/- 2 to 135 +/- 1.6 mEq/L, p less than 0.05) and serum osmolality. Serum arginine vasopressin levels remained elevated at 3.85 +/- 0.94 microU/ml, however, although a transient depression cannot be excluded. Subsequently, a small but significant decrease in serum arginine vasopressin levels to 3.04 +/- 0.65 microU/ml (p less than 0.05) was associated with a further rise in serum sodium levels above baseline values (138 +/- 1.4 mEq/L, p less than 0.01) and in serum osmolality. In conclusion, these results indicate that in this group of cirrhotic patients with refractory ascites, intrarenal factors, such as decreased delivery of filtrate to the distal nephron as well as elevated inappropriate levels of arginine vasopressin, are important in the pathogenesis of hyponatremia.     

Adaptation to sustained high plasma vasopressin in water and electrolyte homeostasis in the rat transgenic for the metallothionein-vasopressin fusion gene

Prolonged exposure of tissues to a receptor agonist often leads to adaptive changes that limit the subsequent responsiveness of the tissue to the same agonist. Recently, we have generated rats transgenic for the metallothionein I-human arginine vasopressin (AVP) fusion gene (Tg), which produced high plasma AVP with relatively preserved renal water excretion, suggesting that there might be adaptive mechanism(s) for maintaining water and electrolyte homeostasis against chronic AVP oversecretion from the earliest stage of life. In this study, to investigate whether down-regulation of AVP V2 receptor (V2R), which could possibly be caused by long-standing high plasma AVP, participates in this adaptive mechanism(s), non-peptidic V2R antagonist OPC31260 was administered to reverse the down-regulation, and water loading was performed after V2R antagonist treatment had been withdrawn. Additionally, to confirm the down-regulation, Northern blotting analysis for V2R mRNA was carried out. Tg rats showed slightly decreased urine volume and water intake with an equivalent plasma [Na(+)] level (Tg 140.4 +/- 0.6 mEq/l; control 139.3 +/- 0.6 mEq/l) under basal conditions. After water loading using a liquid diet containing zinc, which stimulates the promoter region in the transgene, the urine increase showed only limited suppression with a dramatically increased plasma AVP level and mild hyponatremia (135.8 +/- 1.8 mEq/l) in Tg rats. When diet containing OPC31260 had been provided for 4 days until the day before the start of water loading, antidiuresis and hyponatremia (125.4 +/- 1.mEq/l) were significantly potentiated. V2R mRNA expression in kidney was significantly less in Tg rats than in control rats under basal conditions, and this suppression was restored by OPC31260 treatment to levels comparable with those of control rats. These results suggest that long-standing high plasma AVP causes V2R down-regulation, and it may play an important role in the adaptive mechanism(s) for maintaining water and electrolyte homeostasis in chronically AVP-overexpressing rats.     

Chronic Idiopathic Hyponatremia in Older People Due to Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) Possibly Related to Aging

OBJECTIVE: To determine the prevalence of syndrome of inappropriate antidiuretic hormone secretion (SIADH) among older hyponatremic patients in a subacute geriatric facility, to identify patients with no apparent cause for the SIADH (idiopathic SIADH), and to determine their clinical characteristics. DESIGN: Prospective analysis of a cohort of older patients over a period of 3 months. SETTING: Two wards in a geriatric rehabilitation hospital. PARTICIPANTS: Patients aged 65 and older. MEASUREMENTS: All patients with hyponatremia (serum sodium <135 mmols/l) were clinically examined and relevant investigations were performed to determine the etiology of hyponatremia. Patients were observed for symptoms of hyponatremia. Hyponatremia was classified into possible SIADH and non-SIADH types. Patients with SIADH type hyponatremia were screened for possible causes. Past medical histories were obtained from the general practitioners. RESULTS: Of the 172 patients studied, 43 (25%) had hyponatremia. It was symptomatic in only four patients. Twenty-two (51%) had SIADH etiology. In nine (mean age 84 +/- 4), no cause for the SIADH was evident (presumed idiopathic SIADH) and in seven, hyponatremia (128-135 mmols/l) was chronic (12 to 72 months). Further reduction in serum sodium, which was symptomatic, was noted in two of these patients with the onset of pneumonia. CONCLUSION: Most older hyponatremic patients in a rehabilitation setting seem to have SIADH etiology. This study confirms the presence of a group of older individuals with chronic idiopathic hyponatremia in whom the underlying mechanism may be SIADH related to aging. Hyponatremia is modest in these patients and has little clinical significance. However, they may be at increased risk of developing symptomatic hyponatremia with intercurrent illnesses.     

Hyponatremia and/or hyperkalemia in patients treated with the standard dose of trimethoprim-sulfamethoxazole

OBJECTIVE: High-dose trimethoprim-sulfamethoxazole (TMP-SMX) is known to cause hyperkalemia by blocking amiloride-sensitive sodium (Na) channels in distal nephrons. The purpose of this study was to establish whether the standard dose of TMP-SMX could cause electrolyte disorders. METHODS AND PATIENTS: Serum Na, potassium (K) and creatinine (Cr) levels were examined retrospectively in 53 of 77 patients prescribed TMP-SMX, before and after taking the antibiotic combination. RESULTS: Electrolyte disorders (Na < 135 mEq/l and/or K > 5.0 mEq/l) were found in 14 of the 53 patients (26.4%) during TMP-SMX treatment. The average dose was 145.7 +/- 24.9 mg/day. The dose of TMP was significantly larger in patients with electrolyte disorders (267.7 +/- 84.2 mg vs. 101.9 +/- 9.38 mg, p = 0.0024). Electrolyte disorders were also seen in 9.1% and 22.2% of patients given the low dose (TMP < 80 mg) or standard dose (TMP 80-120 mg) of TMP-SMX, respectively. Electrolyte disorders were seen in 85.7% of patients with renal dysfunction (Cr > 1.2 mg/dl), compared with 17.5% of patients with normal renal function (p = 0.0008). Logistic regression analysis showed that the dose of TMP and the presence of renal dysfunction increased the incidence of electrolyte disorders with an odds ratio of 2.35 and 80.29, respectively. CONCLUSION: Electrolyte disorders, particularly hyperkalemia and hyponatremia can be detected in patients given TMP-SMX. These disorders are more frequent in patients given high doses, but can also be detected after low-dose administration. Renal dysfunction accelerates the incidence of electrolyte disorders induced by TMP-SMX.     

Efficacy and safety of oral conivaptan: a V1A/V2 vasopressin receptor antagonist, assessed in a randomized, placebo-controlled trial in patients with euvolemic or hypervolemic hyponatremia

CONTEXT: Hyponatremia [serum sodium concentration ([Na(+)]), <135 mEq/liter] is the most common fluid and electrolyte abnormality among hospitalized patients. It is frequently caused by the inappropriate release of arginine vasopressin. OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of oral conivaptan, a vasopressin V(1A)/V(2) receptor antagonist, in patients with euvolemic or hypervolemic hyponatremia. DESIGN: The study design was a 5-d placebo-controlled, randomized, double-blind study. SETTING: The study was performed at a hospital. Intervention: Oral conivaptan (40 or 80 mg/d) or placebo was given in two divided doses. PATIENTS: Seventy-four patients (average baseline serum [Na(+)], 115 to <130 mEq/liter) were studied. MAIN OUTCOME MEASURE: The main outcome measure was the change from baseline in serum [Na(+)] area under the curve. RESULTS: The least-squares mean change from baseline in the serum [Na(+)] area under the curve with conivaptan (40 and 80 mg/d) was 2.0-fold (P = 0.03) and 2.5-fold (P < 0.001) greater, respectively, than that with placebo. The median time to achieve a confirmed increase in serum [Na(+)] of 4 mEq/liter or more from baseline was 71.7 h for placebo, 27.5 h for 40 mg/d conivaptan (P = 0.044), and 12.1 h for 80 mg/d conivaptan (P = 0.002). The mean total times during which patients had a serum [Na(+)] level of 4 mEq/liter or more above baseline were 46.5, 69.8, and 88.8 h (P = 0.001), respectively. The least-squares mean change in serum [Na(+)] from baseline to end of treatment was 3.4 mEq/liter for placebo, 6.4 mEq/liter for 40 mg/d conivaptan, and 8.2 mEq/liter for 80 mg/d conivaptan (P = 0.002). A confirmed normal serum [Na(+)] (>/=135 mEq/liter) or increase of 6 mEq/liter or more was observed in 48% of patients given placebo, 71% given 40 mg/d conivaptan, and 82% given 80 mg/d conivaptan (P = 0.014). Headache, hypotension, nausea, constipation, and postural hypotension were the most common adverse events. CONCLUSION: Oral conivaptan (40 and 80 mg/d) was well tolerated and efficacious in correcting serum [Na(+)] in hyponatremia.     

Severe hyponatremia due to hypopituitarism with adrenal insufficiency: report on 28 cases

OBJECTIVE: Severe hyponatremia due to hypopituitarism and adrenal insufficiency can be life-threatening, and treatment with glucocorticoids is very effective once the diagnosis of the underlying disorder has been made. In our experience, the diagnosis of hypopituitarism in hyponatremic patients is often overlooked. METHODS: In a retrospective study we screened the files of 185 patients with severe hyponatremia (<130 mmol/l) that had been seen in one endocrinological unit of a university hospital between 1981 and 2001 in order to describe the clinical spectrum of patients with hyponatremia and hypopituitarism including secondary adrenal insufficiency. RESULTS: In 139 cases it was possible to clearly ascribe the patients to the pathophysiological groups of (i) primary sodium deficiency, (ii) edematous disorders, and (iii) normovolemic disorders including the "syndrome of inappropriate secretion of antidiuretic hormone" (SIADH). Twenty-eight patients with severe "normovolemic hyponatremia" (serum sodium: 116+/-7 mmol/l, mean+/-s.d.) had hypopituitarism and secondary adrenal insufficiency as shown by basal cortisol measurements and dynamic tests of adrenal function. In 25 cases of this group hypopituitarism (mostly due to empty sella, Sheehan's syndrome and pituitary tumors) had not been recognized previously, and in 12 cases recurrent hyponatremia during previous hospital admissions (up to four times) could be documented. The mean age of these patients (21 women, seven men) was 68 Years. The most frequently occurring clinical signs were missing or scanty pubic and axillary hair, pale and doughy skin, and small testicles in the men. Frequent symptoms like nausea and vomiting, confusion, disorientation, somnolence or coma were similar to those in 91 patients with SIADH. Basal serum cortisol levels in the acutely ill state ranged from 20 to 439 nmol/l (mean+/-s.d.: 157+/-123), while in 30 other severely hyponatremic patients it ranged from 274 to 1732 nmol/l (732+/-351 nmol/l). In most patients with hyponatremic hypopituitarism, plasma antidiuretic hormone levels were inappropriately high, probably due to a failure of endogenous cortisol to suppress the hormone in a stressful situation. All patients recovered after low-dose hydrocortisone substitution. Most patients had other pituitary hormone deficiencies and were appropriately substituted subsequently. CONCLUSIONS: Hypopituitarism including secondary adrenal insufficiency seems to be a frequently overlooked cause of severe hyponatremia. A high level of suspicion is the best way to recognize the underlying disorder. Treatment with hydrocortisone is very effective.     

Overexpression of vasopressin in the rat transgenic for the metallothionein-vasopressin fusion gene

Arginine vasopressin (AVP) is a major antidiuretic hormone, the overproduction of which causes diluting hyponatremia in humans and is called the syndrome of inappropriate antidiuresis (SIAD). To study physiological changes resulting from AVP overproduction and to develop an animal model of hyponatremia, the human AVP gene was expressed under the control of the metallothionein promoter in transgenic (Tg) rats. Analyses of AVP immunoreactivity (irAVP) in the tissues revealed that the transgene is expressed mainly in the central nervous system. Gel filtration showed that irAVP in the brain and plasma was properly processed AVP. AVP purified from the brains of both Tg and control rats also exerted equal bioactivity to generate cAMP in LLC-PK1 cells. The founder rats did not show any physical or anatomical abnormalities. Under basal conditions, Tg rats had high plasma AVP levels (Tg 13.8 +/- 2.5 pg/ml; control 2.7 +/- 1.2 pg/ml; n=6 in both groups; means +/- S.E.M.), decreased urine volume, and normal plasma [Na(+)]. Hypertonic saline injected i.p. did not affect AVP secretion in Tg rats. In response to a zinc-supplemented liquid diet, plasma AVP decreased in control rats, but increased in Tg rats (Tg 32.7 +/- 2.7 pg/ml; control 1.0+/-0.1 pg/ml; n=6), resulting in hyponatremia (Tg 135.2 +/- 2.5 mEq/l; control 140.8 +/- 0.4 mEq/l; n=6). To our knowledge, this is the first transgenic animal to show diluting hyponatremia. This transgenic rat may therefore provide a useful model in which to investigate various physiological alterations resulting from the oversecretion of AVP which involve SIAD, stress response, behavior, and blood pressure.     

Case of pulmonary aspergillosis associated with inappropriate antidiuretic hormone syndrome caused by voriconazole therapy]

A 75-year-old man presented with hemoptysis. Consolidation was identified in the left lower lobe around multiple bullae. He was found to have chronic necrotizing pulmonary aspergillosis based on a high titer of aspergillus antigen and positive antibody. He was treated with 400 mg/day voriconazole. However, liver dysfunction and hyponatremia developed at 21 days after beginning administration of voriconazole. Serum sodium levels were 122 mEq/l. but urinary sodium showed a high level of 135 mEq/l. The serum sodium level improved 10 days after voriconazole was discontinued. Serum levels of voriconazole on day 15 were high at 18 microg/ml (safe effective serum level: 1.5 to 4.5 microg/ml). An analysis of genetic polymorphism showed a mutation of cytochrome P450 (CYP2C19*2 G681A). We report the first case of a voriconazole-induced syndrome of inappropriate antidiuretic hormone caused by a polymorphism mutation of cytochrome P450.     

Hyponatremia in geriatric inhospital patients: effects on results of a comprehensive geriatric assessment

Objectives: To study whether geriatric patients with mild-to-moderate hyponatremia (≤131 mmol/l) reveal different outcomes in structured tests for functional and cognitive impairments, depression and malnutrition compared to normonatremic patients. Design: Single-center, retrospective case control study. Setting: The study was conducted in a Geriatric Evaluation and Management Unit of a Department for Geriatrics and Internal Medicine. Methods and Participants: We included 2,880 elderly patients (75.6% female, mean age 78.6 ± 6.98 years), consecutively admitted to the GEMU primarily or from another hospital or emergency department. Results were compared between a group of 129 patients with mild-to-moderate hyponatremia (118-131 mmol/l) and an age- and sex-matched control group of 129 patients with normal serum sodium values (>135 mmol/l). To assess functional and cognitive status, depression and malnutrition we used standardized tests of a geriatric assessment. Results: 16.7% (n = 477) of the total 2,880 patients were hyponatremic (≤135 mmol/l), 4.5% (n = 129) revealed moderate hyponatremia. Compared to the control group, these patients had significantly worse results in all tests of the Geriatric Assessment, including Activities of Daily Living, Mini Mental State Examination, Clock Completion Test, Geriatric Depression Score, Tinetti Mobility Test and the Timed Up&Go Test and the Mini Nutritional Assessment. Comorbidities were assessed by the Charlson Comorbidity Index and the Cumulative Illness Rating Scale with no significant difference between the two groups. The hyponatremic patients received significantly more medications than the normonatremic control group, but we could not find a significant difference with respect to the use of a distinct single drug therapy. Conclusion: We were able to demonstrate that geriatric patients with mild-to-moderate hyponatremia revealed a significantly worse outcome in all standardized tests of the geriatric assessment compared to a normonatremic control group. Serum sodium levels should therefore be considered when interpreting common tests of geriatric assessment.     

Mechanisms, risks, and new treatment options for hyponatremia

Hyponatremia is the most common electrolyte abnormality in hospitalized patients and is associated with increased mortality, morbidity, and longer hospital stays. Because patients with this disorder are often asymptomatic, hyponatremia is frequently undiagnosed and untreated. Serious neurologic complications may ensue when hyponatremia develops too rapidly or the serum sodium concentration ([Na(+)]) falls below 120 mEq/l. Hypotonic dilutional hyponatremia is the most common form of this disorder, which may present as euvolemic [e.g., due to failure to suppress secretion of arginine vasopressin (AVP)] or hypervolemic (due to edema-forming conditions such as heart failure). Hypovolemic hyponatremia is due to conditions promoting renal or extrarenal sodium loss. Because AVP, which is intimately involved in regulating osmolar homeostasis, is often elevated in patients with hypervolemic and euvolemic hyponatremia, treatments that directly target the effects of this hormone may provide a more predictable correction of serum [Na(+)] than those traditionally used. The AVP receptor antagonists (conivaptan, tolvaptan, lixivaptan, and satavaptan) are a new class of agents that have been shown to normalize serum [Na(+)] by promoting aquaresis - the electrolyte-sparing excretion of free water.     

Hyponatremia after transsphenoidal surgery for hypothalamo-pituitary tumors

Transient diabetes insipidus is a well-known complication after transsphenoidal surgery (TSS). On the other hand, transient hyponatremia has been reported as being a delayed complication of TSS. Transient hyponatremia has been attributed to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), but the details of hyponatremia have not been clarified. In the present study, we retrospectively reviewed 110 consecutive patients (39 males and 71 females, age 9-80 years) operated on transsphenoidally for pituitary and hypothalamic tumors. We investigated the frequency, time of onset, duration of hyponatremia after TSS, and analyzed possible factors associated with it. A postoperative sodium concentration <135 mEq/l was observed in 29 (26%) patients. Five patients were excluded from this study because their hyponatremia could be due to either overdose of desmopressin or SIADH for meningitis. Therefore, we investigated 24 (22%) patients with hyponatremia in this study. The sodium levels in the patients with hyponatremia ranged from 110 to 134, with a mean of 126.2 +/- 5.3 mEq/l. Hyponatremia was observed on average on postoperative day 9.5 +/- 2.4, the serum sodium levels normalized within 3.8 +/- 1.7 days. Hyponatremia occurred in patients with non-functioning pituitary adenoma (26%, 11/42), Rathke's cleft cyst (29%, 5/17), prolactinoma (31%, 4/13) and acromegaly (15%, 4/27). 18 patients (75%, 6/24) who developed hyponatremia had macrotumor (>10 mm), and 6 patients (25%, 6/24) had microtumor. The plasma arginine vasopressin (AVP) levels in the patients with hyponatremia ranged from 0.21 to 2.1, with a mean of 0.79 +/- 0.46 pg/ml, and the levels were inversely correlated with plasma osmolality (r = -0.80, p = 0.002). The urine to plasma osmolality ratios were >1. All the patients received appropriate hormonal replacement, including hydrocortisone. These data showed that postoperative hyponatremia after TSS was not rare, and the hyponatremia was mainly associated with SIADH. As the hyponatremia could be a life-threatening complication, all patients should be screened for serum electrolytes after TSS.     

Disturbances of fluid and electrolyte balance in patients with acute stroke

Serum sodium and potassium concentrations were measured in 196 patients with acute cerebral infarction and 56 with cerebral hemorrhage. All patients were admitted within 7 days of onset and the data within 2 weeks of admission were recorded. The incidences of hypernatremia (serum Na greater than or equal to 149 mEq/l), hyponatremia (less than or equal to 134 mEq/l), hyperkalemia (serum K greater than or equal to 4.8 mEq/l) and hypokalemia (less than or equal to 3.2 mEq/l) were higher in patients with hemorrhage (18, 7, 13 and 14%, respectively) than infarction (4.5, 4.5, 11 and 6%, respectively). The incidences of hypernatremia and hyponatremia in infarction were higher in those who had cortical lesions than in those who had lesions in the basal ganglia or infratentorium. In cerebral hemorrhage, the incidence of hypernatremia was the highest in those with brain stem lesion. Hypernatremia was found in 27% of large sized hematoma, being significantly higher than that of those with medium (16%) or small (1%) hematoma. A similar tendency was also observed in hyponatremia and hyperkalemia. In elderly patients, electrolyte disturbances were more common than in young or middle-aged patients. Renal insufficiency and diabetes mellitus were frequent complications in stroke patients with hypernatremia (42 and 32%, respectively), of which 57% died within one month of admission.     

急性心肌梗死低钠血症的预后价值

目的探讨急性心肌梗死(AMI)低钠血症的预后价值。方法对我院心内科CCU病房2003年1月至2004年12月670例资料完整的AMI患者进行了回顾性分析,根据患者入院后即刻、24、48h血清钠离子浓度最低值共分为三组:A组Na+≥135mmol/L;B组Na+120~135mmol/L;C组Na+≤120mmol/L。比较各组心肌酶、心肌梗死面积、心功能及住院病死率。结果(1)三组住院病死率分别为:A组7·6%(17/225),B组8·1%(34/421),C组33·3%(8/24),C组分别与A组和B组比较,差异具有统计学意义(P<0·05)。(2)三组肌酸激酶(CK),肌酸激酶同工酶(CK-MB)及心肌梗死面积(S)进行比较,C组分别与A组和B组比较差异有统计学意义(P<0·05)。(3)住院期间死亡59例,存活611例,存活组与死亡组血清钠离子浓度分别为(133·00±5·25)mmol/L和(122·00±7·25)mmol/L,两组比较差异有统计学意义(P<0·01)。(4)对AMI后30天住院期间死亡危险因素进行多因素logistic回归分析,血清钠离子浓度降低与AMI后30天住院期间病死率相关。并且30天住院期间病死率随着血清钠离子浓度降低而升高。结论低钠血症可能是AMI预后不良的标志之一。     

Postoperative hyponatremic encephalopathy in menstruant women.

OBJECTIVES: To determine factors associated with the development of encephalopathy and with its clinical course in patients with postoperative hyponatremia. SETTING: Consultation and referral services of two university medical centers and community hospitals. DESIGN: Case-control study (risk factors for encephalopathy) and cohort study (clinical course among patients with encephalopathy). PATIENTS: Case patients included 65 adults with postoperative hyponatremic encephalopathy; controls included 674 adult patients who had postoperative hyponatremia without encephalopathy and who were selected from 76,678 consecutive adult surgical inpatients. MEASUREMENTS: Age, gender, menstrual status, neurologic symptoms, time to development and degree of hyponatremia, arterial blood gas determinations, serum chemistries, morbidity and mortality. RESULTS: Case patients included 40 women (62%) and 25 men (38%) (P > 0.05); controls included 367 women (54%) and 307 men (46%) (P > 0.1). Of the 34 case patients who developed permanent brain damage or died, 33 (97%) were women (P < 0.001). Among the women with brain damage, 25 (76%) were menstruant (P < 0.001). The relative risk for death or permanent brain damage from hyponatremic encephalopathy in women compared with men was 28 (95% Cl, 5 to 141) and in menstruant women compared with postmenopausal women, 26 (Cl, 11 to 62). Arterial PO2 at diagnosis was significantly lower in female than in male case patients (34 +/- 5 compared with 91 +/- 3 mm Hg; P < 0.001). Further, of the 38 case patients who had respiratory arrest before the diagnosis of hyponatremic encephalopathy, 36 (95%) were women. Extent of or time to development of hyponatremia did not correlate with subsequent brain damage (P > 0.1). CONCLUSIONS: Women and men are equally likely to develop hyponatremia and hyponatremic encephalopathy after surgery. However, when hyponatremic encephalopathy develops, menstruant women are about 25 times more likely to die or have permanent brain damage compared with either men or postmenopausal women.     

Burden of sodium abnormalities in patients hospitalized for heart failure

Hyponatremia presumably is associated with adverse clinical outcomes in patients with congestive heart failure (CHF), but risk thresholds and economic burden are less studied. The authors analyzed 115,969 patients hospitalized for CHF and grouped them by serum sodium levels (severe hyponatremia, ≤130 mEq/L; hyponatremia, 131-135 mEq/L; normonatremia, 136-145 mEq/L; hypernatremia, >145 mEq/L). Univariable and multivariable analyses on the associated clinical and economic outcomes were performed. The most common abnormality was hyponatremia (15.9%), followed by severe hyponatremia (5.3%) and hypernatremia (3.2%). Hospital mortality was highest for severe hyponatremia (7.6%), followed by hypernatremia (6.7%) and hyponatremia (4.9%) (P<.0001). Compared with normonatremia, risk-adjusted mortality was highest for severe hyponatremia (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.59-1.99), followed by hypernatremia (OR, 1.55; 95% CI, 1.34-1.80) and hyponatremia (OR, 1.29; 95% CI, 1.19-1.40; all P<.0001). Risk-adjusted hospital prolongation was greater for each level of sodium abnormality than for normonatremia, ranging from 0.42 (CI, 0.26-0.60) days for hypernatremia to 1.28 (CI, 1.11-1.47) days for severe hyponatremia. Risk-adjusted attributable hospital cost increase was highest for severe hyponatremia ($1132; CI, $856-$1425; all (P<.0001). Sodium abnormalities were common in patients hospitalized for CHF. Adverse outcomes resulted not only from severe hyponatremia, but also from mild hyponatremia and hypernatremia.     

Urinary excretion of sodium and potassium in a screened cohort in Okinawa, Japan.

Information regarding daily intake of sodium (Na) is useful for both normotensive and hypertensive subjects. We measured urinary excretion of sodium (U-Na) and urinary excretion of potassium (U-K) to estimate daily salt intake in a cohort of health screening subjects in Okinawa, Japan. Urine samples were obtained from 2,411 subjects (1,554 men and 857 women) who were examined on a half-day dry-doc at the Okinawa General Health Maintenance Association (OGHMA). Four hundred and one subjects were examined twice, once between September and November in 1997, and once between September and November in 1998. The mean U-Na was 182 mEq/day for men and 176 mEq/day for women. The mean U-K was 54 mEq/day for men and 50 mEq/day for women. U-Na was higher in young men, and U-K was lower in young women. In both men and women, smokers had a significantly lower Na excretion compared to nonsmokers. Subjects treated for hypertension had a significantly lower Na excretion (173 mEq/day) compared to subjects not treated for hypertension (192 mEq/day). Our findings suggest that Na excretion in screened subjects in Okinawa is lower than the national average. Sodium excretion, however, was higher in young men than in elderly subjects, and K excretion was lower in young women than in elderly subjects. Both trends are disadvantageous for controlling hypertension.