Mortality rates are lower in SIAD, than in hypervolaemic or hypovolaemic hyponatraemia: Results of a prospective observational study.

OBJECTIVE: Hyponatraemia is associated with increased mortality, but the mortality associated specifically with SIAD is not known. We hypothesized that mortality in SIAD was elevated, but that it was less than in hypervolaemic (HEN) or hypovolaemic (HON) hyponatraemia. DESIGN: Mortality rates are presented as risk ratios (RR),with 95% confidence intervals (CI), and compared to normonatraemic controls (NN). METHODS: Prospective, single centre, noninterventional study of all patients with hyponatraemia (≤130 mmol/L) admitted to hospital. RESULTS: A total of 1323 admissions with hyponatraemia were prospectively evaluated and 1136 contemporaneous NN controls. 431(32.6%) hyponatraemic patients had HON, 573(43.3%) had SIAD and 275(20.8%) patients had HEN. In patient mortality was higher in hyponatraemia than NN (9.1% vs 3.3%, P<.0001). The RRs for in-hospital mortality compared to NN were: SIAD, 1.76 (95% CI 1.08-2.8, P=.02), HON 2.77 (95% CI 1.8-4.3, P<.0001) and HEN, 4.9 (95% CI 3.2-7.4, P<.0001). The mortality rate was higher in HEN (RR 2.85; 95% CI 1.86-4.37, P<.0001) and in HON, (RR 1.6; 95% CI 1.04-2.52; P=.03), when compared to SIAD. The Charlson Comorbidity Index was lower in SIAD than in eunatraemic patients (P<.0001). 9/121(7.4%) patients died with plasma sodium <125 mmol/L and 4(3.3%) with plasma sodium <120 mmol/L. However, 69/121(57%) patients died with a plasma sodium above 133 mmol/L. CONCLUSIONS: We confirmed higher all-cause mortality in hyponatraemia than in NN. Mortality was higher in SIAD than in normonatraemia and was not explained on the basis of co-morbidities. Mortality was higher in HON and HEN than in SIAD. Mortality rates reported for all-cause hyponatraemia in the medical literature are not applicable to SIAD.

Cerebral Salt Wasting Is the Most Common Cause of Hyponatremia in Stroke.

OBJECTIVE: The study aimed to evaluate the frequency, severity, and causes of hyponatremia in stroke and its influence on outcome. MATERIALS AND METHODS: Consecutive computed tomography- or magnetic resonance imaging-proven stroke patients within 7 days of stroke were included. Severity of stroke was assessed using the National Institute of Health Stroke Scale and consciousness using the Glasgow Coma Scale. Hyponatremia was defined if 2 consecutive serum sodium levels were <135 mEq/L and hypernatremia if >145 mEq/L. Causes of hyponatremia, such as cerebral salt wasting (CSW) and syndrome of inappropriate secretion of antidiuretic hormone (SIADH), were based on predefined criteria. Patients with CSW were managed by salt supplementation and normal saline, and fludrocortisone was used in refractory cases. In SIADH, fluid was restricted. Outcome on discharge was defined using the modified Rankin Scale (mRS). RESULTS: One hundred patients with stroke were included: 47% had ischemic stroke and 53% had intracerebral hemorrhage. Forty-three percent of the patients had hyponatremia, 6% had hypernatremia, and 4% had both. Hyponatremia was due to CSW in 19 (44.2%), SIADH in 3 (7%), miscellaneous causes in 14 (32.6%), and indeterminate in 7 (16.3%) patients. Duration of hospitalization was the independent predictor of hyponatremia and CSW. Fourteen patients died, whereas 15 had good outcome (mRS score of ≤2) and 71 had poor outcome (mRS score of 3-5). Hypernatremia was associated with high mortality compared with eunatremia and hyponatremia. CONCLUSION: Hyponatremia occurred in 43% of stroke patients. CSW was the most common cause of hyponatremia. Hyponatremia, however, was not related to death or disability.

Malignancy associated SIADH: Characterization and clinical implications.

PURPOSE: To determine the distribution of etiologies for the syndrome of inappropriate antidiuretic hormone secretion (SIADH) in hospitalized patients with active malignancies and to characterize them according to the different etiologies. METHODS: A single center retrospective study including all patients with active malignancies diagnosed with SIADH in a large community hospital and tertiary center between 1 January 2007 and 1 January 2013. Two physicians reviewed every patient's medical file for predetermined relevant clinical data. RESULTS: The study cohort included 204 patients. 74.4% of those with solid tumors had metastatic disease. Most patients (149, 73%) had malignancy associated SIADH, while 55 (27%) had SIADH due to other etiologies. All of the major malignancy types were implicated in SIADH. Patients with breast cancer without lung or brain involvement were significantly less likely to be diagnosed with malignancy associated SIADH compared with other malignancies [Odds ratio (OR) 0.031, 95% CI 0.003-0.25, p < 0.001]. Patients with malignancy associated SIADH had lower serum sodium concentrations on short-term follow-up (p = 0.024) and significantly shorter median survival (58 vs. 910 days, p < 0.001). Short-term hyponatremia correction was associated with better survival. CONCLUSIONS: SIADH is associated with most malignancy types. Physicians caring for patients with breast cancer without lung or brain involvement diagnosed with SIADH without an obvious etiology should consider obtaining lung and brain imaging to rule out undiagnosed metastatic spread. Patients with malignancy associated SIADH have considerably worse outcomes compared to cancer patient with SIADH due to other etiologies. Short-term sodium concentration can be used as a prognostic marker for these patients.

The syndrome of inappropriate antidiuretic hormone secretion: Distribution and characterization according to etiologies.

PURPOSE: To determine the distribution of etiologies for the syndrome of inappropriate antidiuretic hormone secretion (SIADH) in hospitalized patients and to characterize patients according to the different etiologies. METHODS: A single-center retrospective study including all patients diagnosed with SIADH in a large community hospital and tertiary center between 1.1.2007 and 1.1.2013. Two physicians reviewed every patient's medical file for predetermined relevant clinical data. RESULTS: The study cohort included 555 patients. The most common etiologies were malignancies and medication-induced SIADH, followed by idiopathic SIADH, pulmonary infections, pain and nausea, and central nervous system (CNS) disorders. Subgroup analysis according to etiology showed that CNS disorders were associated with more severe episodes of SIADH. Patients with idiopathic SIADH were older than patients with a specific diagnosis, had a lower urine osmolality, and required less treatment with hypertonic saline. Long-term survival was determined primarily by SIADH etiology rather than hyponatremia severity, with hazard ratios for death of up to 7.31 (95% CI 4.93-10.82, p<0.001) for patients with malignancy-associated SIADH as compared to patients with idiopathic SIADH. Hyponatremia grade at short-term follow-up was also predictive for long-term survival (HR 1.42 per grade, 95% CI 1.21-1.66, p<0.001). CONCLUSIONS: Patients with SIADH have different characteristics and a different prognosis according to SIADH etiology. Serum sodium concentration at short-term follow-up is predictive of long-term survival. These findings might have diagnostic and treatment-related implications.

The syndrome of inappropriate antidiuresis is associated with excess long-term mortality: a retrospective cohort analyses.

INTRODUCTION: The syndrome of inappropriate antidiuresis (SIAD) is the commonest cause of euvolaemic hyponatraemia in patients admitted to hospital. The mortality after discharge from hospital has not been previously studied in patients with SIAD. AIMS: To compare mortality in patients with SIAD and those with kidney injury (KI). To identify underlying diagnoses associated with deaths due to SIAD. METHODS: Single-centre retrospective cohort analyses of 804 patients with severe hyponatraemia over a 3-year period. Five-year survival data in patients with SIAD and those with KI were compared. The underlying diagnoses that contributed to SIAD in this cohort were analysed using ICD-10 codes. RESULTS: 202 patients had SIAD using biochemical cut-off parameters; 248 patients had KI. Patient with KI had a statistically significant (log-rank p<0.0001) shorter median survival time (2.24 months (95% CI 1.3 to 4.3)) compared with those with SIAD (31.0 months (95% CI 21.6 to 54.8)). 53.8% (n=78) of patients with hyponatraemia due to SIAD died within the first year after admission; the corresponding figure for those presenting with KI was 74.1% (n=166). Five years after admission, 80.8% (n=117) of those with SIAD had died; the corresponding figure for those with KI was 88.4% (n=200). In those patients with SIAD that died within the first year, malignancy appeared to be the most common cause (25.4%) followed by infection (23.8%). CONCLUSIONS: Severe hyponatraemia in SIAD carries a high mortality after discharge, and although this seems often to be attributable to the underlying cause, the extent to which treatment with V2-recptor antagonists may help to correct the hyponatraemia associated with SIAD and influence the medium-to-long-term outcome in such patients is worthy of further study.

[Hyponatremia : The water-intolerant patient]. / Hyponatriämie : Der "wasserintolerante" Patient.

Hyponatremia due to intolerance to water is a frequent clinical condition and associated with increased mortality. Besides the well known neurological symptoms, gait disturbances, falls, fractures and osteoporosis have also been described recently in patients with chronic hyponatremia. Acute hyponatremia is a more dramatic situation and needs rapid action when severe neurological symptoms are present. Hypertonic saline is recommended to treat this condition until relief of severe symptoms. The causes of hyponatremia have to be carefully examined. Especially diuretics, antidepressants and endocrine causes, e.g. hypothyroidism, hypocortisolism and hypoaldosteronism should be excluded by examination of the patient history, clinical examination and by laboratory tests. Patients should be classified as being euvolemic, hypovolemic or hypervolemic. Whereas acute hyponatremia with severe symptom should be treated with hypertonic saline, euvolemic hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) with mild and moderate symptoms can now be treated with tolvaptan, a selective V(2)-vasopressin antagonist. Oral tolvaptan has been shown to be an effective and potent aquaretic to treat hyponatremia caused by SIADH as evidenced by a simultaneous increase in serum sodium and a decrease in urine osmolality. The condition of patients with mild or moderate hyponatremia is also improved. Side effects associated with tolvaptan include increased thirst, dry mouth, polyuria and hypernatremia. Rapid increases in serum sodium should be avoided by close monitoring in a hospital setting.

Impact of hyponatremia and the syndrome of inappropriate antidiuresis on mortality in elderly patients with aspiration pneumonia.

BACKGROUND: Hyponatremia is associated with pneumonia, and aspiration pneumonia is common in the elderly, however, there has been no study of hyponatremia in this population. OBJECTIVE: To determine the impact of hyponatremia on mortality in elderly patients with aspiration pneumonia, while focusing on the comparison between those with and without the syndrome of inappropriate antidiuresis (SIAD). DESIGN: Retrospective review of existing database and medical records. SETTING: A community teaching hospital in Japan. PATIENTS: Two hundred and twenty-one elderly patients hospitalized with aspiration pneumonia. MEASUREMENTS: Multivariate logistical regression models were used to compare 30-day and in-hospital mortality, in patients with hyponatremia of various severities and etiologies, with that in patients with normal serum sodium concentrations. RESULTS: Sixty-five (29%) of 221 patients had hyponatremia. Of these 62 (95%) had hypotonic hyponatremia, which were further assessed as having hypovolemic (39 [63%]), hypervolemic (3 [5%]), and euvolemic (20 [32%]) hyponatremia. Of the 20 euvolemic patients, 14 (70%) had SIAD. Both moderate and severe hypotonic hyponatremia were significantly associated with increased in-hospital mortality (odds ratio [OR] 6.05, 95% confidence interval [CI] 1.46-25.0, and OR 5.65, 95% CI 1.14-28.1, respectively). Hyponatremia due to SIAD was significantly associated with both increased 30-day mortality (OR 7.40, 95% CI 1.73-31.7) and increased in-hospital mortality (OR 22.3, 95% CI 4.26-117). In contrast, hypovolemic hyponatremia was not significantly associated with increased mortality. CONCLUSIONS: Hyponatremia due to SIAD was strongly associated with increased mortality in elderly patients with aspiration pneumonia, whereas hypovolemic hyponatremia was not associated with increased mortality.

[Is hyponatremia a prognostic marker of survival for lung cancer?]. / Ist die Hyponatriämie (HN) ein Prognosefaktor für das Gesamtüberleben der Patienten mit Lungenkarzinom?

Hyponatremia is frequently observed on the basis of syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH) in patients suffering from lung cancer. This electrolyte imbalance is associated with higher mortality and morbidity. If hyponatremia influences survival of lung cancer remains controversial. In the current study we retrospectively analysed if survival is directly impacted by hyponatremia and evaluated if hyponatremia is a prognostic marker for lung cancer.

Treatment of hypervolemic or euvolemic hyponatremia associated with heart failure, cirrhosis, or the syndrome of inappropriate antidiuretic hormone with tolvaptan: a clinical review.

BACKGROUND: Tolvaptan is an oral nonpeptide selective vasopressin V(2)-receptor antagonist indicated for the treatment of clinically relevant hypervolemic or euvolemic hyponatremia associated with heart failure, cirrhosis, or syndrome of inappropriate antidiuretic hormone. OBJECTIVE: The objective of this article was to review the pharmacology, efficacy, and tolerability of tolvaptan in the treatment of hypervolemic or euvolemic hyponatremia, heart failure, and autosomal dominant polycystic kidney disease (ADPKD). METHODS: Articles were identified using MEDLINE (1966-February 28, 2010) and EMBASE (1947-February 28, 2010). Abstracts and proceedings from the annual meetings (2007-2009) of the American Heart Association, the European Society of Cardiology, and the American Society of Nephrology were searched to identify additional relevant publications. Searches were conducted using the terms tolvaptan, vasopressin antagonist, heart failure, polycystic kidney disease, hyponatremia, drug interaction, pharmacokinetics, and pharmacology. The reference lists of the identified publications were reviewed for additional references. All clinical trials that assessed the use of tolvaptan in the management of hypervolemic/euvolemic hyponatremia or heart failure in humans were included, regardless of study design. RESULTS: A total of 9 trials were identified. For the treatment of hyponatremia, tolvaptan was associated with significantly increased serum sodium concentrations compared with placebo on treatment days 4 (3.62 [2.68] vs 0.25 [2.08] mmol/L, respectively; P < 0.001) and 30 (6.22 [4.10] vs 1.66 [3.59] mmol/L; P < 0.001). In the clinical trials in patients with heart failure, tolvaptan at doses of 30, 60, and 90 mg/d was associated with mean weight changes of -1.80, -2.10, and -2.05 kg, respectively, versus -0.60 kg with placebo (P = 0.002, P = 0.002, and P = 0.009). Trials of tolvaptan in humans with ADPKD are ongoing. Overall, mortality rates were not significantly altered with tolvaptan compared with placebo (25.9% vs 26.3%). The most commonly reported adverse events associated with tolvaptan in clinical trials were dry mouth (4.2%-23.0%), thirst (7.7%-40.3%), and polyuria (0.6%-31.7%), all consistent with the mechanism of action of the drug. CONCLUSION: Based on findings from clinical trials to date, tolvaptan is effective for the correction of hyponatremia but has not been associated with significant improvements in mortality in patients with heart failure compared with placebo, and its utility in the treatment of ADPKD in humans remains to be determined.

A comparative study of the syndrome of inappropriate antidiuretic hormone secretion in community-dwelling patients and nursing home residents.

BACKGROUND AND AIMS: Limited data exist about the clinical characteristics of the syndrome of inappropriate antidiuretic hormone secretion (SIADHS) in hospitalized elderly. Moreover, there may be differences regarding this syndrome between populations, depending on the referral source to hospitals. The objectives of the study were to determine the etiology, clinical characteristics and hospital outcome in a sample of elderly hospitalized patients with SIADHS, and to compare community-dwelling patients (CDP) with nursing home residents (NHR). METHODS: This retrospective chart analysis was conducted in a university affiliated referral hospital. The participants were consecutive elderly patients, admitted with hyponatremia (< 135 mmol/L), and ultimately diagnosed as having SIADHS. We examined patient demographics, medical history, clinical presentation, laboratory and imaging studies, and hospital outcome. RESULTS: Of the 179 patients presenting with hyponatremia, 79 patients (44%) fulfilled the criteria for SIADHS; 73% of these patients were CDP and 27% were NHR (mean ages, 74.4 +/- 6.9 and 75.7 +/- 7.2 years, respectively). Most CDP complained of weakness and dizziness, while NHP presented with confusion, seizures and vomiting. Mean sodium levels and mean plasma osmolality values were similar in both groups, however, the number of patients with sodium levels < or = 121 mmol/L was significantly higher among NHR. The leading causes of SIADHS in both groups were medications, idiopathic form, and concurrent malignancies. In patients older than 81 years, idiopathic (50%) and drug-induced (20%) SIADHS were more frequent, compared with younger age groups. The overall in-hospital mortality rate was significantly higher in NHR as compared with CDP (p = 0.014), yet, it was similar in both groups once only patients with sodium levels of 121 mmo/L or lower were considered. CONCLUSIONS: While leading causes of SIADHS in community and nursing home residents are similar, there are marked differences in clinical presentation and outcome. This knowledge should help in identifying high-risk patients and taking appropriate measures.

Inappropriate secretion of antidiuretic hormone in acute bacterial meningitis.

Sixty children aged from 1 month to 12 years (mean (SD) 3.18 (3.49) years) with acute bacterial meningitis were studied for the incidence, clinical manifestations and outcome of the inappropriate secretion of antidiuretic hormone syndrome (SIADH). Serum sodium levels and osmolality of serum and urine were estimated on admission and on days 3 and 10. SIADH was diagnosed in 22 out of 60 cases (36.7%) on admission and in six of 48 cases (12.5%) on day 3. Hyponatraemia without SIADH, attributed to vomiting and fever, was detected in seven cases (11.7%). Serum sodium levels returned to normal within 48 hours in these cases. Serum osmolality and sodium levels took longer to return to normal values in patients with SIADH. However, none of the cases showed any evidence of SIADH on the 10th day. A significant correlation with SIADH was observed in cases with evidence of severe meningeal inflammation (p < 0.001). The incidence of SIADH was highest with Streptococcus pneumoniae (75%), followed by Haemophilus influenzae (57.1%). Overall mortality was 26.7%, and mortality was significantly higher (p < 0.001) in cases with SIADH, all of whom died during the 1st 72 hours. Ten out of 22 cases (45.4%) with SIADH who survived beyond the 1st 72 hours had an uneventful course even though all of them had biochemical evidence of SIADH on the 3rd day. Mortality was quite high also in children with severe malnutrition (75%) and in those with S. pneumoniae as the aetiological organism (75%).

[Prognosis and treatment of symptomatic hyponatremia--a study of 28 intensive care cases]. / Prognos och terapi vid symtomatisk hyponatremi--en studie av 28 intensivvårdsfall.

In symptomatic cases of hyponatraemia, where the serum sodium concentration is less than 115 mmol/l, prognosis has hitherto been considered to be poor, and mortality rates of 50 per cent have been reported. The management of this condition is controversial, particularly concerning the optimal rate of correction, correlations having been reported between the occurrence of central pontine myelinolysis and both over-correction and too rapid correction. During the 3-year duration of the study reported in the article, of 28 cases with a mean sodium concentration of 106 mmol/l, the outcome was fatal in only one case. In both of the only two cases of acute hyponatraemia (i.e., developing within 24 hours), correction had been rapid (mean rate 2.6 mmol/l per hour). In the remaining 26 cases correction of chronic hyponatraemia was slower (mean rate 0.6 mmol/l per hour), adjustment to a slightly hyponatraemic level having been achieved with isotonic saline (N = 25) or water restriction (N = 1). The findings in the study suggest that, provided that the rate of correction is not too rapid, the prognosis in cases of severe symptomatic hyponatraemia is more favourable than previously reported.

A retrospective study of thirty-two patients with small-cell bronchogenic carcinoma and inappropriate secretion of antidiuretic hormone.

Thirty-two patients with inappropriate secretion of antidiuretic hormone (ADH) complicating small-cell carcinoma of the bronchus were identified from a total of 226 patients with small-cell carcinoma of the bronchus treated at the Christie Hospital, Manchester, between 1978 and 1984. Basic data were collected from patients' files concerning the extent of the tumour, symptoms of inappopriate secretion of antidiuretic hormone, biochemical findings, treatment, the course of the inappropriate secretion of ADH and that of the underlying tumour. The data were then analysed and compared with results of previous studies. The response of the inappropriate secretion of ADH to treatment was found to be a significant prognostic factor. Further data were collected to determine the reason for this but it was difficult to drawn any firm conclusions.