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Prevalence and Impact of Hyponatremia in Patients With Coronavirus Disease 2019 in New York City.
Frontera, JA, Valdes, E, Huang, J, Lewis, A, Lord, AS, Zhou, T, Kahn, DE, Melmed, K, Czeisler, BM, Yaghi, S, et al
Critical care medicine. 2020;(12):e1211-e1217
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Abstract
OBJECTIVES Hyponatremia occurs in up to 30% of patients with pneumonia and is associated with increased morbidity and mortality. The prevalence of hyponatremia associated with coronavirus disease 2019 and the impact on outcome is unknown. We aimed to identify the prevalence, predictors, and impact on outcome of mild, moderate, and severe admission hyponatremia compared with normonatremia among coronavirus disease 2019 patients. DESIGN Retrospective, multicenter, observational cohort study. SETTING Four New York City hospitals that are part of the same health network. PATIENTS Hospitalized, laboratory-confirmed adult coronavirus disease 2019 patients admitted between March 1, 2020, and May 13, 2020. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Hyponatremia was categorized as mild (sodium: 130-134 mmol/L), moderate (sodium: 121-129 mmol/L), or severe (sodium: ≤ 120 mmol/L) versus normonatremia (135-145 mmol/L). The primary outcome was the association of increasing severity of hyponatremia and in-hospital mortality assessed using multivariable logistic regression analysis. Secondary outcomes included encephalopathy, acute renal failure, mechanical ventilation, and discharge home compared across sodium levels using Kruskal-Wallis and chi-square tests. In exploratory analysis, the association of sodium levels and interleukin-6 levels (which has been linked to nonosmotic release of vasopressin) was assessed. Among 4,645 patient encounters, hyponatremia (sodium < 135 mmol/L) occurred in 1,373 (30%) and 374 of 1,373 (27%) required invasive mechanical ventilation. Mild, moderate, and severe hyponatremia occurred in 1,032 (22%), 305 (7%), and 36 (1%) patients, respectively. Each level of worsening hyponatremia conferred 43% increased odds of in-hospital death after adjusting for age, gender, race, body mass index, past medical history, admission laboratory abnormalities, admission Sequential Organ Failure Assessment score, renal failure, encephalopathy, and mechanical ventilation (adjusted odds ratio, 1.43; 95% CI, 1.08-1.88; p = 0.012). Increasing severity of hyponatremia was associated with encephalopathy, mechanical ventilation, and decreased probability of discharge home (all p < 0.001). Higher interleukin-6 levels correlated with lower sodium levels (p = 0.017). CONCLUSIONS Hyponatremia occurred in nearly a third of coronavirus disease 2019 patients, was an independent predictor of in-hospital mortality, and was associated with increased risk of encephalopathy and mechanical ventilation.
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Hyponatremia is associated with occurrence of atrial fibrillation in outpatients with heart failure and reduced ejection fraction.
Cavusoglu, Y, Kaya, H, Eraslan, S, Yilmaz, MB
Hellenic journal of cardiology : HJC = Hellenike kardiologike epitheorese. 2019;(2):117-121
Abstract
OBJECTIVES Hyponatremia and atrial fibrillation (AF) have been established as strong predictors for worse clinical outcomes in patients with heart failure (HF). However, little is known about hyponatremia in relation to the occurrence of AF. This study aims to investigate the possible relationship between hyponatremia and AF in patients with chronic HF and reduced ejection fraction (HFrEF). METHODS Turkish research team-HF (TREAT-HF) is a network that has been undertaking multicenter, observational cohort studies on HF. A total of 880 patients who had plasma sodium measurement in TREAT-HF data set were included in this study. Hyponatremia was defined as a plasma sodium level of ≤135 mmol/L. The patients were classified into hyponatremia (n=213) or normonatremia (n=667) based on the sodium level. RESULTS The rate of AF was found to be 33.3% in patients with hyponatremia and 18.8% in patients with normonatremia (p<0.001). Univariate analysis demonstrated an association between hyponatremia and AF. Furthermore, in multivariate logistic regression model, hyponatremia was also found to be significantly and independently associated with the occurrence of AF (odds ratio [OR]=2.457, 95% confidence interval [CI]=1.586-3.806, p<0.001) in addition to other well-known risk factors for AF. CONCLUSION The results of this study showed that AF was more prevalent in outpatients with HFrEF and hyponatremia than in those with HFrEF and normonatremia. These results also suggest that hyponatremia is independently associated with the occurrence of AF.
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EARLY-ESLI study: Long-term experience with eslicarbazepine acetate after first monotherapy failure.
Villanueva, V, Bermejo, P, Montoya, J, Toledo, M, Gómez-Ibáñez, A, Garcés, M, Vilella, L, López-González, FJ, Rodriguez-Osorio, X, Campos, D, et al
Acta neurologica Scandinavica. 2017;(3):254-264
Abstract
PURPOSE Evaluate real-life experience with eslicarbazepine acetate (ESL) after first monotherapy failure in a large series of patients with focal epilepsy. METHOD Multicentre, retrospective, 1-year, observational study in patients older than 18 years, with focal epilepsy, who had failed first antiepileptic drug monotherapy and who received ESL. Data from clinical records were analysed at baseline, 3, 6 and 12 months to assess effectiveness and tolerability. RESULTS Eslicarbazepine acetate was initiated in 253 patients. The 1-year retention rate was 92.9%, and the final median dose of ESL was 800 mg. At 12 months, 62.3% of patients had been seizure free for 6 months; 37.3% had been seizure free for 1 year. During follow-up, 31.6% of the patients reported ESL-related adverse events (AEs), most commonly somnolence (8.7%) and dizziness (5.1%), and 3.6% discontinued due to AEs. Hyponatraemia was observed in seven patients (2.8%). After starting ESL, 137 patients (54.2%) withdrew the prior monotherapy and converted to ESL monotherapy; 75.9% were seizure free, 87.6% were responders, 4.4% worsened, and 23.4% reported ESL-related AEs. CONCLUSION Use of ESL after first monotherapy failure was associated with an optimal seizure control and tolerability profile. Over half of patients were converted to ESL monotherapy during follow-up.
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Evaluation of copeptin and commonly used laboratory parameters for the differential diagnosis of profound hyponatraemia in hospitalized patients: 'The Co-MED Study'.
Nigro, N, Winzeler, B, Suter-Widmer, I, Schuetz, P, Arici, B, Bally, M, Blum, CA, Nickel, CH, Bingisser, R, Bock, A, et al
Clinical endocrinology. 2017;(3):456-462
Abstract
OBJECTIVE Hyponatraemia is common and its differential diagnosis is challenging. Commonly used diagnostic algorithms have limited diagnostic accuracy. Copeptin, the c-terminal portion of the precursor peptide of arginine vasopressin might help in the differential diagnosis of hyponatraemia. DESIGN Prospective multicentre observational study. PATIENTS/METHODS A total of 298 patients admitted with profound hypoosmolar hyponatraemia (Na < 125 mmol/l) were evaluated. Three experts uninvolved in the patients' care determined the aetiology of hyponatraemia after standardized diagnostic evaluation. RESULTS Hyponatraemia differential diagnoses were as follows: syndrome of inappropriate antidiuresis (SIAD), 106 patients (35·6%); 'diuretic-induced', 72 (24·2%); 'hypovolaemic', 59 (19·8%); 'hypervolaemic', 33 (11·1%); primary polydipsia (PP), 24 (8·1%); and cortisol deficiency, 4 (1·3%). Copeptin levels <3·9 pmol/l identified patients with PP with high specificity (91%). Further, copeptin levels >84 pmol/l were highly predictive for hypovolaemic hyponatraemia (specificity: 90%). Urinary sodium levels and copeptin/urinary sodium ratio in patients with SIAD were higher and lower as compared to other hyponatraemia aetiologies (P < 0·0001). However, the specificity to identify SIAD was moderate for both parameters (31% and 61%). Fractional uric acid excretion (FEUA ) and fractional urea excretion (FEurea ) were higher in patients with SIAD compared to other hyponatraemia aetiologies (both P < 0·0001). FEurea values >55% and FEUA values >12% had a specificity of 96% and 77% to detect patients with SIAD. These results remained similar after excluding patients taking diuretics. CONCLUSIONS Overall, there is only limited diagnostic utility of copeptin in the differential diagnosis of profound hyponatraemia. Very low copeptin levels are seen in patients with PP and highest copeptin levels in hypovolaemic hyponatraemia. To discriminate between SIAD and other hyponatraemia aetiologies, FEurea and FEUA levels are valuable irrespective of diuretics use.
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Dose comparison of conivaptan (Vaprisol®) in patients with euvolemic or hypervolemic hyponatremia--efficacy, safety, and pharmacokinetics.
Palmer, BF, Rock, AD, Woodward, EJ
Drug design, development and therapy. 2016;:339-51
Abstract
PURPOSE This study aimed to evaluate the efficacy, safety, and pharmacokinetics of 20 and 40 mg/day conivaptan (Vaprisol®) in patients with hypervolemic or euvolemic hyponatremia. METHODS Hyponatremic patients - serum sodium (sNa) ≤130 mEq/L - received either 20 or 40 mg/day of conivaptan for 4 days, following an initial 20 mg loading dose. Efficacy was evaluated by the magnitude and extent of change in sNa. Safety was evaluated by the incidence of adverse events, changes in vital signs and laboratory parameters, rate of sNa correction, and frequency of infusion-site reactions. Pharmacokinetic parameters were also measured. RESULTS A total of 37 patients received 20 mg/day and 214 patients received 40 mg/day conivaptan. Baseline-adjusted sNa-area under the concentration-time curve increased by an average of 753.8±499.9 mEq·hr/L (20 mg/day) and 689.2±417.3 mEq·hr/L (40 mg/day) over the course of the 4-day treatment period. The majority of patients in both treatment groups achieved a 4 mEq/L increase in sNa over baseline in ~24 hours (82.5%). Average increase in sNa after 4 days was ~10 mEq/L, varying with dosage level and baseline volume status. Treatment success (normal sNa or increase of ≥6 mEq/L) was attained by 70.3% of patients in the 20 mg/day group and 72.0% in the 40 mg/day group. CONCLUSION Both 20 and 40 mg/day doses of conivaptan are efficacious in increasing sNa over 4 days of treatment with no observed increase in the frequency of adverse events or specific infusion-site reactions using the higher dose. The pharmacokinetic parameters of both doses were similar to what has been reported previously, exhibiting greater-than-dose-proportional plasma concentrations.
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Prognostic Significance of Hyponatremia in Acute Intracerebral Hemorrhage: Pooled Analysis of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial Studies.
Carcel, C, Sato, S, Zheng, D, Heeley, E, Arima, H, Yang, J, Wu, G, Chen, G, Zhang, S, Delcourt, C, et al
Critical care medicine. 2016;(7):1388-94
Abstract
OBJECTIVES To determine the association of hyponatremia at presentation with clinical and imaging outcomes in patients with acute intracerebral hemorrhage. DESIGN Retrospective pooled analysis of prospectively collected data from 3,243 participants of the pilot and main phases of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials 1 and 2 (international, multicenter, open, blinded endpoint, randomized controlled trials designed to assess the effects of early intensive blood pressure lowering in patients with acute intracerebral hemorrhage). SETTING Clinical hospital sites in 21 countries. PATIENTS Patients with predominantly mild-moderate severity of spontaneous intracerebral hemorrhage within 6 hours of onset and elevated systolic blood pressure (150-220 mm Hg) were included in the study. INTERVENTIONS Patients were assigned to receive intensive (target systolic blood pressure, < 140 mm Hg within 1 hr) or guideline-recommended (target systolic blood pressure, < 180 mm Hg) blood pressure-lowering therapy. MEASUREMENTS AND MAIN RESULTS Presentation hyponatremia was defined as serum sodium less than 135 mEq/L. The primary outcome was death at 90 days. Multivariable logistic regression was used to assess the association of hyponatremia with important clinical events. Of 3,002 patients with available data, 349 (12%) had hyponatremia. Hyponatremia was associated with death (18% vs 11%; multivariable-adjusted odds ratio, 1.81; 95% CI, 1.28-2.57; p < 0.001) and larger baseline intracerebral hemorrhage volume (multivariable adjusted, p = 0.046) but not with baseline perihematomal edema volume nor with growth of intracerebral hemorrhage or perihematomal edema during the initial 24 hours. CONCLUSIONS Hyponatremia at presentation is associated with increased mortality in patients with predominantly deep and modest volume intracerebral hemorrhage through mechanisms that seem independent of growth in intracerebral hemorrhage or perihematomal edema.
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Oral tolvaptan is safe and effective in chronic hyponatremia.
Berl, T, Quittnat-Pelletier, F, Verbalis, JG, Schrier, RW, Bichet, DG, Ouyang, J, Czerwiec, FS, ,
Journal of the American Society of Nephrology : JASN. 2010;(4):705-12
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Abstract
Vasopressin antagonists increase the serum sodium concentration in patients who have euvolemia and hypervolemia with hyponatremia in the short term (≤30 days), but their safety and efficacy with longer term administration is unknown. SALTWATER was a multicenter, open-label extension of the Study of Ascending Levels of Tolvaptan in Hyponatremia (SALT-1 and SALT-2). In total, 111 patients with hyponatremia received oral tolvaptan for a mean follow-up of 701 days, providing 77,369 patient-days of exposure. All patients had hyponatremia at randomization in SALT-1 and SALT-2, and 85% continued to have hyponatremia at entry in SALTWATER. The most common adverse effects attributed to tolvaptan were pollakiuria, thirst, fatigue, dry mouth, polydipsia, and polyuria. Six drug-related adverse effects led to study discontinuation. The increase in serum sodium exceeded the desired 1 mmol/L per h at initiation in five patients. Hypernatremia (>145 mmol/L) led to discontinuation in one patient. Mean serum sodium increased from 130.8 mmol/L at baseline to >135 mmol/L throughout the observation period (P < 0.001 versus baseline at most points). Responses were comparable between patients with euvolemia and those with heart failure but more modest in patients with cirrhosis. In conclusion, prolonged administration of tolvaptan maintains an increased serum sodium with an acceptable margin of safety.