Increase In Serum Sodium Concentration Research Articles

Safety and Efficacy of Vaptans in the Treatment of Hyponatremia from Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH): A Systematic Review and Meta-Analysis.

The utilization of vasopressin receptor antagonists, known as vaptans, in the management of hyponatremia among patients afflicted with the syndrome of inappropriate antidiuretic hormone (SIADH) remains a contentious subject. This meta-analysis aimed to evaluate the safety and efficacy of vaptans for treating chronic hyponatremia in adult SIADH patients. Clinical trials and observational studies were identified by a systematic search using MEDLINE, EMBASE, and Cochrane Database from inception through September 2022. The inclusion criteria were the studies that reported vaptans' safety or efficacy outcomes compared to placebo or standard therapies. The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD 42022357307). Five studies were identified, comprising three RCTs and two cohort studies, enrolling a total of 1840 participants. Regarding short-term efficacy on days 4-5, vaptans exhibited a significant increase in serum sodium concentration from the baseline in comparison to the control group, with a weighted mean difference of 4.77 mmol/L (95% CI, 3.57, 5.96; I2 = 34%). In terms of safety outcomes, the pooled incidence rates of overcorrection were 13.1% (95% CI 4.3, 33.6; I2 = 92%) in the vaptans group and 3.3% (95% CI 1.6, 6.6; I2 = 27%) in the control group. Despite the higher correction rate linked to vaptans, with an OR of 5.72 (95% CI 3.38, 9.70; I2 = 0%), no cases of osmotic demyelination syndrome were observed. Our meta-analysis comprehensively summarizes the efficacy and effect size of vaptans in managing SIADH. While vaptans effectively raise the serum sodium concentration compared to placebo/fluid restriction, clinicians should exercise caution regarding the potential for overcorrection.

Impact of Dapagliflozin Treatment on Serum Sodium Concentrations in Acute Heart Failure

Introduction: The dynamics of serum sodium are important in acute heart failure (AHF), and hyponatremia is associated with a poor prognosis. The effect of sodium-glucose cotransporter type 2 inhibitors (SGLT2i) on serum sodium concentrations in AHF is unknown. Methods: In a single-centre, controlled, randomized study, patients were prescribed dapagliflozin in addition to standard treatment during the first 24 h of hospitalization versus standard treatments. The pre-specified outcome was an absolute change in plasma sodium concentrations between randomization (first 24 h after admission) and discharge. The secondary outcomes were an absolute change in serum sodium concentrations within 48 h of randomization and the persistence of hyponatremia. Results: The sample comprised 285 patients (53% males; average age 73.26 ± 13 years); 140 of these were randomized to the dapagliflozin group. The average ejection fraction was 46 ± 14%; 155 patients (54%) had ischaemic heart failure; and 35% had diabetes mellitus. Median N-terminal pro b-type natriuretic peptide was 4,225 [2,120; 9,105] pg/mL. The average estimated glomerular filtration rate was 53.9 ± 17.2 mL/min. Hospital mortality was 6.7%. At randomization, serum sodium concentrations were 139.8 ± 4.32 mmol/L in the dapagliflozin group versus 140.85 ± 4.04 mmol/L in the control group; p = 0.048. 48 h later, there was an increase in serum sodium in the dapagliflozin group (2 [−2; 4] mmol/L), as compared to the control group (−1 [−3.75; 2]); p < 0.001. This was accompanied by equilibration of the sodium levels between the groups (141.08 ± 4.08 mmol/L in the dapagliflozin group vs. 140.05 ± 4.82 mmol/L in the control group; p = 0.096). At the time of discharge, there was no difference in serum sodium concentrations (140.98 ± 4.77 mmol/L vs. 139.86 ± 4.45 mmol/L; p = 0.082). The increase in serum sodium concentrations during the period of observation [randomization; discharge] was small but statistically significant in the dapagliflozin group (1 [−3; 3.75] mmol/L vs. −2 [−4.5; 2] mmol/L; p = 0.015). Of 36 patients (21 in the dapagliflozin group and 15 in the control group) with baseline hyponatraemia, this persisted in 6 (16.6%) in the dapagliflozin group and in 11 (73.3%) in the control group (p = 0.008). Conclusion: The use of dapagliflozin in AHF is associated with a tendency to the increase in serum sodium concentrations and lesser persistence of hyponatremia. This effect occurred within the first 48 h and persisted until discharge. The impact of dapagliflozin on serum sodium was more pronounced in patients with hyponatremia at randomization.

Tolvaptan for the treatment of the syndrome of inappropriate antidiuresis (SIAD).

The syndrome of inappropriate antidiuresis (SIAD), the commonest cause of hyponatraemia, is associated with significant morbidity and mortality. Tolvaptan, an oral vasopressin V2-receptor antagonist, leads through aquaresis to an increase in serum sodium concentration and is the only medication licenced in Europe for the treatment of euvolaemic hyponatraemia. Randomised controlled trials have shown that tolvaptan is highly efficacious in correcting SIAD-related hyponatraemia. Real-world data have confirmed the marked efficacy of tolvaptan, but they have also reported a high risk of overly rapid sodium increase in patients with a very low baseline serum sodium. The lower the baseline serum sodium, the higher the tolvaptan-induced correction rate occurs. Therefore, a lower starting tolvaptan dose of 7.5 mg has been evaluated in small cohort studies, demonstrating its efficacy, but it still remains unclear as to whether it can reduce the risk of overcorrection. Most international guidelines, except for the European ones, recommend tolvaptan as second-line treatment for SIAD after fluid restriction. However, the risk of unduly rapid sodium correction in combination with its high cost have limited its routine use. Prospective controlled studies are warranted to evaluate whether tolvaptan-related sodium increase can improve patient-related clinical outcomes, such as mortality and length of hospital stay in the acute setting or neurocognitive symptoms and quality of life in the chronic setting. In addition, the potential role of a low tolvaptan starting dose needs to be further explored. Until then, tolvaptan should mainly be used as second-line treatment for SIAD, especially when there is a clinical need for prompt restoration of normonatraemia. Tolvaptan should be used with specialist input according to a structured clinical pathway, including rigorous monitoring of electrolyte and fluid balance and, if needed, implementation of appropriate measures to prevent, or when necessary reverse, overly rapid hyponatraemia correction.

Poređenje efekta manitola i 3% hipertoničnog rastvora natrijum hlodira na intrakranijalnu relaksaciju tokom elektivne supratentorijalne kraniotomije - neurohirurška anestezija

Introduction: Brain relaxation is essential in anesthesia for intracranial surgery; it has been considered a neuroprotective measure as it can reduce surgical compression, local hypoperfusion, cerebral ischemia, and blood loss. To ease surgical tumor removal, measures are taken to reduce brain swelling, often referred to as brain relaxation. In the present study, we aimed to compare the effects of 20% mannitol and 3% hypertonic saline (HS) on brain relaxation during supratentorial craniotomy. Fluid input, urine output, arterial blood gases and serum sodium concentration were also measured. Methods: We conducted a prospective, randomized, double blind controlled trial. Sixty patients, ages 18 to 50, belonging to American Society of Anesthesiologist (ASA) physical status (II-IV), posted for craniotomy were divided into two equal groups in a double-blinded selection by using computer-generated random numbers (Thirty patients in each group). The surgeon and anesthesiologist were unaware of the identity of the study agents. Each patient was administered 150 ml of either 20% mannitol (Group M) or 3% HTS over 20 minutes (min) (Group H) after skin incision. The neurosurgeon assessed the brain conditions on a four-point scale as "Perfectly relaxed," "Satisfactory relaxed," "Firm brain," or "Bulging brain," immediately after opening the dura mater. Results: Intraoperative brain relaxation was comparable between the two groups. Brain relaxation observed in Group M (perfectly relaxed/satisfactory relaxed/firm brain/bulging brain, n = 8/13/5/4) was similar to that observed in Group H (perfectly relaxed/satisfactory relaxed/firm brain/bulging brain, n = 7/13/8/2; P= 0.77). Urine output was significantly higher in the mannitol group (P &lt;0.05). Administration of HTS was associated with a transient increase in serum sodium concentrations, which was statistically significant but returned to normal within 48 h (P &lt; 0.05). There were no significant differences in fluid input and arterial blood pressure during surgery in between two groups. Conclusion: Our results suggested that hypertonic saline and mannitol both had a similar effect on brain relaxation during elective supratentorial craniotomy.

Relationship between high fructose corn syrup sweetened drinks, diet soft drinks, and serum sodium: NHANES 2003–2006

BackgroundConsumption of high fructose corn syrup sweetened drinks and diet soft drinks has increased in the United States. However, the relationship between the intake of high fructose corn syrup sweetened drinks and diet soft drinks, and serum sodium has been scarcely studied. Our objective is to evaluate the relation between intake of high fructose corn syrup sweetened drinks and diet soft drinks, and serum sodium, and explore the possible effect modifiers in a nationally representative sample of adults from the United States.MethodsWe conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey 2003–2006. The study participants included 6989 adults aged ≥18 years. Using survey-weighted generalized linear regression analyses, we investigated the relationship between high fructose corn syrup sweetened drink, diet soft drink consumption, and serum sodium. Consumption of high fructose corn syrup sweetened drinks and diet soft drinks was evaluated through a food-frequency questionnaire.ResultsSerum sodium levels increased as high fructose corn syrup sweetened drink intake increased. Serum sodium levels were higher in participants in the highest high fructose corn syrup sweetened drink consumption quantile, compared with those in the lowest high fructose corn syrup sweetened drink intake quantile (p = 0.020). The multivariate betas for serum sodium, according to the corresponding high fructose corn syrup sweetened drink intake quantiles, were 0.16, 0.19, and 0.21, respectively (P for trend = 0.051). We found no relationship between diet soft drink consumption and serum sodium after adjustment of confounding. (multivariate P > 0.05).ConclusionThere was a a step-wise increase in serum sodium concentration with increasing consumption of HFCS sweetened beverages. Even moderate HFCS sweetened soft drink intake was associated with an elevated serum sodium level - a risk factor for hypertension.

Incidence and risk factors of overcorrection in patients presenting with severe hyponatremia to the emergency department.

Hyponatremia is one of the most common electrolyte abnormalities. Overcorrection of severe hyponatremia can result in serious neurological complications such as osmotic demyelination syndrome, but the incidence and risk factors of overcorrection and osmotic demyelination have not been thoroughly investigated. This is a single-center retrospective cohort study of 50 patients admitted through the emergency department with initial serum sodium (serum Na) < 125mEq/L between January 2015 and December 2017. Incidence and risk factors of overcorrection and osmotic demyelination were examined. Overcorrection was defined as an increase in serum sodium concentration > 10mEq/L at 24h and/or > 18mEq/L at 48h, respectively. Six patients (12%) and one patient (2%) had overcorrection at 24h and 48h, respectively. A total of 5 (10%) patients had a brain MRI completed after overcorrection, and no patient showed radiologic evidence of osmotic demyelination. Symptomatic hyponatremia at presentation and 3% saline use were associated with the risk of overcorrection in univariable analysis (p < 0.001; p = 0.006, respectively). Among patients admitted with severe hyponatremia, overcorrection occurred in 14%. Symptomatic hyponatremia at presentation and 3% saline use were associated with the risk of overcorrection.

Changes in Factors Regulating Serum Sodium Homeostasis During Two Ultra-Endurance Mountain Races of Different Distances: 69km vs. 121km.

Overdrinking and non-osmotic arginine vasopressin release are the main risk factors for exercise-associated hyponatremia (EAH) in ultra-marathon events. However, particularly during ultra-marathon running in mountainous regions, eccentric exercise and hypoxia, which have been shown to modulate inflammation, hormones regulating fluid homeostasis (hypoxia), and oxidative stress, could contribute to serum sodium changes in a dose-dependent manner. To the best of our knowledge, the contribution of these factors, the extent of which depends on the duration and geographical location of the race, has not been well studied. Twelve male participants (11 finishers) of the short (69km, 4,260m elevation-gain) and 15 male participants (seven finishers) of the long (121km, 7,554m elevation-gain) single-stage Südtirol Ultra Sky-Race took part in this observational field study. Venous blood was drawn immediately before and after the race. Analyses included serum sodium concentration, copeptin (a stable marker for vasopressin), markers of inflammation, muscle damage and oxidative stress. Heart rate was measured during the race and race time was obtained from the race office. During the short and the long competition two and one finishers, respectively showed serum sodium concentrations >145mmol/L. During the long competition, one athlete showed serum sodium concentrations <135mmol/L. Only during the short competition percent changes in serum sodium concentrations of the finishers were related to percent changes in body mass (r=−0.812, p=0.002), total time (r=−0.608, p=0.047) and training impulse (TRIMP) (r=−0.653, p=0.030). Data show a curvilinear (quadratic) relationship between percent changes in serum sodium concentration and body mass with race time when including all runners (short, long, finishers and non-finishers). The observed prevalence of hypo- and hypernatremia is comparable to literature reports, as is the relationship between serum sodium changes and race time, race intensity and body mass changes of the finishers of the short race. The curvilinear relationship indicates that there might be a turning point of changes in serum sodium and body mass changes after a race time of approximately 20h. Since the turning point is represented mainly by non-finishers, regardless of race duration slight decrease in body mass and a slight increase in serum sodium concentration should be targeted to complete the race. Drinking to the dictate of thirst seems an adequate approach to achieve this goal.

Sodium Levels Predict Disability at Discharge in Guillain-Barré Syndrome: A Retrospective Cohort Study.

Guillain-Barré syndrome (GBS) is an inflammatory polyradiculopathy with potentially severe complications. Clinical tools for risk stratification have been developed, but no definitive prognostic biomarker has been reported. Hyponatremia is frequent in GBS patients, but the impact of serum sodium levels on clinical outcomes is still ill-defined. In this retrospective cohort study, we included all adult patients diagnosed with GBS spectrum disorders at our center from January 2010 to July 2020. Disability at discharge was assessed with the GBS Disability Score (GDS), and all clinical and laboratory data was retrieved from medical charts. Thirty (58.8%) of the 51 subjects included in the study were discharged with severe residual disability (GDS ≥ 3). After accounting for relevant confounders, the odds of experiencing severe disability decreased by 27% (p = 0.027) for each unitary increase in serum sodium concentration. Thirteen (25.5%) patients were diagnosed with mild to moderate hyponatremia; the use of intravenous immune globulin (IVIG) independently increased the odds of developing hyponatremia. In conclusion, we found a significant, independent association between baseline serum sodium levels and severe disability at discharge in GBS patients. In our cohort, hyponatremia was more frequently observed after treatment with IVIG, suggesting dilutional pseudohyponatremia as a probable cause.

A Comparison of Hypertonic Saline and Mannitol on Intraoperative Brain Relaxation in Patients with Raised Intracranial Pressure during Supratentorial Tumors Resection: A Randomized Control Trial

Hyperosmotic agents are used to decrease intracranial pressure (ICP). We aim to compare the effect of euvolemic solutions of 3% hypertonic saline (HTS) and 20% mannitol on intraoperative brain relaxation in patients with clinical or radiological evidence of raised ICP undergoing surgery for supratentorial tumors. A. Intraoperative brain relaxation was comparable between the two groups. There was a statistically significant difference in the mean arterial pressures (MAPs) between the two groups after one minutes (min) with a greater degree of decrease in blood pressure recorded in the mannitol group (P = 0.041). MAP with mannitol was significantly lower than the preinduction value after 75 min of administration of drug (P = 0.003). Urine output was significantly higher in the mannitol group (P = 0.00). Administration of HTS was associated with a transient increase in serum sodium concentrations, which was statistically significant but returned to normal within 48 h (P < 0.001). Both mannitol and HTS provided adequate intraoperative brain relaxation. On the contrary, there was no statistically significant fall in blood pressure with HTS. Thus, we advocate the use of HTS over mannitol as it maintains better hemodynamic stability.

Rehabilitation of anterior pituitary dysfunction combined with extrapontine myelinolysis: A case report

BACKGROUNDExtramedullary myelinolysis is a rare demyelinating disease, often caused by rapid increases in serum sodium concentration in patients with hyponatremia. Clinical manifestations are neuropsychiatric symptoms, limb weakness, and dysarthria. Because of its poor prognosis and high disability rate, it poses a huge burden on the global economy, societies, and families. This article reports rehabilitation in a patient with pituitary dysfunction combined with extramedullary myelinolysis.CASE SUMMARYA 27-year-old Chinese man developed anorexia, vomiting, and limb weakness and was diagnosed with pituitary insufficiency. He had low serum sodium, slow movement, muscle weakness, and muscle tone abnormalities after sodium supplementation, involuntary limb shaking, ataxia, and dysarthria. According to the symptoms and signs and imaging reports, he was diagnosed with extramedullary myelinolysis. After treatment with hormone therapy and neurotrophic drugs, motor and speech function did not improve, so he was treated in the rehabilitation department for 4 wk. The patient’s physical status was improved substantially during his stay at the rehabilitation department.CONCLUSIONPatients with extramedullary myelinolysis who actively participate in rehabilitation intervention can significantly improve their activities of daily living.

P4544Impact of hyponatremia improvement on one-year outcomes in patients with acute decompensated heart failure

Abstract Background Impact of hyponatremia improvement on prognosis in patients with acute decompensated heart failure (ADHF) remains unclear. Methods Patients hospitalized for ADHF at 19 hospitals in Japan were enrolled between October 2014 and March 2016. Hyponatremia was defined as serum sodium concentration less than 135 mmol/l. Primary endpoint was composite of all-cause death and heart failure rehospitalization one year after discharge. Results Among 3805 patients enrolled, 486 patients with hyponatremia at admission showed higher in-hospital mortality (13.3% vs. 5.4%, p&lt;0.001). Of 486 hyponatremic patients, 396 patients were discharged alive. One hundred forty-three patients showed persistent hyponatremia at discharge (group P), whereas 253 patients showed improvement of hyponatremia (group I). Baseline characteristics are shown in the table. Patients in group I showed higher sodium concentration at admission (132±3 mmol/l vs. 130±4 mmol/l, p&lt;0.001) and more increase in serum sodium concentration at discharge (7±4 mmol/l vs. 1±5 mmol/l, p&lt;0.001). One-year survival rate free from primary endpoint was not different between the groups (56.4% in group P vs. 58.5% in group I, p=0.79). After adjusting for confounders, improvement of hyponatremia was not associated with better prognosis (hazard ratio 1.00; 95% confidence interval 0.70–1.45, p=0.99). Hyponatremia improvement showed significant interaction with left ventricular ejection fraction (LVEF) less than 40% (p=0.01). In patients with LVEF&lt;40%, improvement of hyponatremia was associated with better prognosis (hazard ratio 0.48, 95% confidence interval 0.28–0.85, p=0.01) whereas not in patients LVEF≥40%. Patient characteristics Group P (n=143) Group I (n=253) p value Age (years) 81 (72–86) 81 (72–87) 0.73 Female 71 (49.7) 110 (43.5) 0.24 Ischemic etiology 42 (29.4) 81 (32.0) 0.58 Prior hospitalization 62 (43.7) 98 (39.5) 0.42 SBP at admission (mmHg) 140±36 144±38 0.40 HR at admission (bpm) 92±23 95±29 0.27 Atrial Fibrillation 47 (32.9) 103 (40.7) 0.12 NYHA class IV 60 (42.2) 138 (54.8) 0.02 Intravenous inotropic use 35 (24.5) 59 (23.3) 0.80 LVEF &lt;40% 54 (37.8) 95 (37.6) 0.97 Values are median (interquartile range), mean ± standard deviation or number (%). Conclusion Improvement of hyponatremia at discharge was not associated with better prognosis in patients hospitalized for ADHF.

Effect of single dose administration activated charcoal containing sorbitol on serum sodium concentration and hydration status in dogs.

To assess the administration of a commercially available activated charcoal suspension with sorbitol (ACS) on serum sodium concentrations and hydration status in healthy dogs. Prospective study. Private referral hospital. Nine healthy adult dogs. Dogs were administered 1 mg/kg maropitant (Cerenia; Pfizer Animal Health, New York, NY) intravenously 1 hour prior to charcoal administration. Dogs were administered a single dose of 2g/kg ACS. Blood samples and body weights were obtained prior to charcoal administration and 2, 4, 6, 8, 10, and 12 hours post ACS administration. Venous sodium, potassium, chloride, blood urea nitrogen, creatinine, lactate, packed cell volume, and total plasma protein were measured at each time interval. All dogs returned 2-4 weeks after ACS administration for a 12 hour period of water restriction and to serve as their own control group. The same measurements were repeated during water restriction period as following ACS administration. The increase in serum sodium concentration was significantly higher following ACS administration when compared to control period (P = 0.0002). All dogs administered ACS experienced a significant degree of weight loss (P = 0.0371) when compared to the control period. Following administration of ACS, the hematocrit of the dogs administered ACS was found to be significantly increased (P = 0.0001), when compared to the control period. Patients that are administered a single dose of ACS are at risk of developing dehydration and secondary hypernatremia as observed in the dogs during the study period. Patients receiving ACS should have electrolytes monitored and would benefit from fluid therapy as previously recommended.

The association between serum sodium concentration, hypertension and primary cardiovascular events: a retrospective cohort study.

The mechanisms underlying the adverse cardiovascular effects of increased salt intake are incompletely understood, but parallel increases in serum sodium concentration may be of importance. The aim of this retrospective cohort study was to investigate the relationship between serum sodium, hypertension and incident cardiovascular disease (CVD). Routinely collected primary care data from the Royal College of General Practitioners Research and Surveillance Centre were analysed. A total of 231,545 individuals with a measurement of serum sodium concentration at baseline were included. Exclusion criteria were: age <40 years; abnormal serum sodium; diabetes mellitus; prior CVD event; stage 5 chronic kidney disease; and liver cirrhosis. The primary outcome was incident CVD (myocardial infarction, acute coronary syndrome, coronary revascularisation, stroke, transient ischaemic attack or new heart failure diagnosis) over 5 years. There was a 'J-shaped' relationship between serum sodium concentration and primary cardiovascular events that was independent of established risk factors, medications and other serum electrolytes. The lowest cardiovascular risk was found with a serum sodium between 141 and 143 mmol/l. Higher serum sodium was associated with increased risk in hypertensive individuals, whereas lower concentrations were associated with increased risk in all individuals. Therefore, alterations in serum sodium concentration may be a useful indicator of CVD risk. Higher serum sodium could have a direct effect on the vasculature, particularly in hypertensive individuals. Lower serum sodium may be a reflection of complex volume and neuroendocrine changes.

Interventions for chronic non-hypovolaemic hypotonic hyponatraemia.

Interventions for chronic non-hypovolaemic hypotonic hyponatraemia.

Rapidity of Correction of Hyponatremia Due to Syndrome of Inappropriate Secretion of Antidiuretic Hormone Following Tolvaptan

Tolvaptan effectively corrects hyponatremia due to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), but undesired overcorrection can occur. We hypothesized that pretherapy parameters can predict the rapidity of response to tolvaptan in SIADH. Multicenter historical cohort study. Adults with SIADH or congestive heart failure (CHF) treated with tolvaptan for a serum sodium concentration≤ 130 mEq/L at 5 US hospitals. Demographic and laboratory parameters. Rate of change in serum sodium concentration. Spearman correlations, analysis of variance, and multivariable linear mixed-effects models. 28 patients with SIADH and 39 patients with CHF treated with tolvaptan (mean baseline serum sodium, 120.6 and 122.4 mEq/L, respectively) were studied. Correction of serum sodium concentration > 12 mEq/L/d occurred in 25% of patients with SIADH compared to 3% of those with CHF (P<0.001). Among patients with SIADH, the increase in serum sodium over 24hours was correlated with baseline serum sodium concentration (r=-0.78; P<0.001), serum urea nitrogen concentration (SUN; r=-0.76; P<0.001), and estimated glomerular filtration rate (r=0.58; P=0.01). Baseline serum sodium and SUN concentrations were identified as independent predictors of change in serum sodium concentration in multivariable analyses. When patients were grouped into 4 categories according to baseline serum sodium and SUN median values, those with both low baseline serum sodium (≤121 mEq/L) and low baseline SUN concentrations (≤10mg/dL) exhibited a significantly greater rate of increase in serum sodium concentration (mean 24-hour increase of 15.4 mEq/L) than the other 3 categories (P<0.05). Among patients with CHF, only baseline SUN concentration was identified as an independent predictor of change in serum sodium concentration over time. Lack of uniformity in serial serum sodium concentration determinations and documentation of water intake. Baseline serum sodium and SUN values are predictive of the rapidity of hyponatremia correction following tolvaptan use in SIADH. We advise caution when dosing tolvaptan in patients with both low serum sodium and SUN concentrations.

Osmotic Demyelination Unrelated to Hyponatremia

Osmotic demyelination unrelated to hyponatremia is rarely reported. We present a case of osmotic demyelination in a patient with hypernatremia in the absence of preceding hyponatremia and review previously reported cases of osmotic demyelination in nonhyponatremic patients. We conclude that a rapid increase in serum sodium concentration and plasma tonicity even in the absence of preceding hyponatremia may surpass the brain's capacity for adaptation to hypertonicity and lead to osmotic demyelination in predisposed individuals. Risk factors for osmotic demyelination in patients with chronic hyponatremia and without hyponatremia are probably similar and are usually associated with states of limited brain osmolyte response, such as alcoholism, liver disease (including those undergoing orthotopic liver transplantation), malnutrition, malignancy, pregnancy/postpartum state, severe illness/sepsis, adrenal insufficiency, and metabolic derangements. Clinicians should be vigilant in identifying individuals who may, even in the absence of hyponatremia, have increased susceptibility to osmotic demyelination and avoid rapid fluctuations in serum sodium concentrations in such patients.

Treatment of Cirrhosis-Associated Hyponatremia with Midodrine and Octreotide.

Hyponatremia in the setting of cirrhosis is a common electrolyte disorder with few therapeutic options. The free water retention is due to non-osmotic vasopressin secretion resulting from the cirrhosis-associated splanchnic vasodilatation. Therefore, vasoconstrictive therapy may correct this electrolyte abnormality. The aim of this study was to assess the efficacy of midodrine and octreotide as a therapeutic approach to increasing urinary electrolyte-free water clearance (EFWC) in the correction of cirrhosis-associated hyponatremia. This observational study consisted of 10 patients with cirrhosis-associated hyponatremia. Hypovolemia was ruled out as the cause of the hyponatremia with a 48-h albumin challenge (25 g IV q6 h). Patients whose hyponatremia failed to improve with albumin challenge were started on midodrine and octreotide at 10 mg po tid and 100 μg sq tid, respectively, with rapid up-titration as tolerated to respective maximal doses of 15 mg tid and 200 μg tid within the first 24 h. We assessed urinary EFWC and serum sodium concentration before and 72 h after treatment. Pretreatment serum sodium levels ranged from 119 to 133 mmol/L. The mean pretreatment serum sodium concentration ± SEM was 124 mmol/L ± 1.6 vs 130 mmol/L ± 1.5 posttreatment (p = 0.00001). The mean pretreatment urinary EFWC ± SEM was 0.33 L ± 0.07 vs 0.82 L ± 0.11 posttreatment (p = 0.0003). Our data show a statistically significant increase in serum sodium concentration and urinary EFWC with the use of midodrine and octreotide in the treatment of cirrhosis-associated hyponatremia.

Diagnosing and Treating the Syndrome of Inappropriate Antidiuretic Hormone Secretion

BackgroundThe syndrome of inappropriate antidiuretic hormone secretion is the most common cause of hyponatremia in clinical practice, but current management of hyponatremia and outcomes in patients with syndrome of inappropriate antidiuretic hormone secretion are not well understood. The objective of the Hyponatremia Registry was to assess the current state of management of hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion in diverse hospital settings, specifically which diagnostic and treatment modalities are currently used and how rapidly and reliably they result in an increase in serum sodium concentration ([Na+]). A secondary objective was to determine whether treatment choices and outcomes differ across the United States and the European Union. MethodsThe Hyponatremia Registry recorded selected diagnostic measures and use, efficacy, and outcomes of therapy for euvolemic hyponatremia diagnosed clinically as syndrome of inappropriate antidiuretic hormone secretion in 1524 adult patients with [Na+] ≤130 mEq/L (1034 from 146 US sites and 490 from 79 EU sites). A subgroup of patients with more rigorously defined syndrome of inappropriate antidiuretic hormone secretion via measurement of relevant laboratory parameters was also analyzed. ResultsThe most common monotherapy treatments for hyponatremia in syndrome of inappropriate antidiuretic hormone secretion were fluid restriction (48%), isotonic (27%) or hypertonic (6%) saline, and tolvaptan (13%); 11% received no active agent. The mean rate of [Na+] change (mEq/L/d) was greater for all active therapies than no active treatment. Hypertonic saline and tolvaptan produced the greatest mean rate of [Na+] change (interquartile range, both 3.0 [6.0] mEq/L/d) compared with lower interquartile range rates of [Na+] change for isotonic saline (1.5 [3.0] mEq/L/d) and fluid restriction (1.0 [2.3] mEq/L/d). The general pattern of responses was similar in both the US and EU cohorts. At discharge, [Na+] was <135 mEq/L in 75% of patients and ≤130 mEq/L in 43% of patients. Overly rapid correction occurred in 10.2% of patients. ConclusionsCurrent treatment of hyponatremia in syndrome of inappropriate antidiuretic hormone secretion often uses therapies with limited efficacy; the most commonly chosen monotherapy treatments, fluid restriction and isotonic saline, failed to increase the serum [Na+] by ≥5 mEq/L in 55% and 64% of monotherapy treatment episodes, respectively. Appropriate laboratory tests to diagnose syndrome of inappropriate antidiuretic hormone secretion were obtained in <50% of patients; success rates in correcting hyponatremia were significantly higher when such tests were obtained. Few outcome differences were found between the United States and the European Union. A notable exception was hospital length of stay; use of tolvaptan was associated with significantly shorter length of stay in the European Union but not in the United States. Despite the availability of effective therapies, most patients with syndrome of inappropriate antidiuretic hormone secretion were discharged from the hospital still hyponatremic.

Conivaptan for Treatment of Hyponatremia in Neurologic and Neurosurgical Adults

To review the literature evaluating the clinical safety and efficacy of conivaptan in the management of hyponatremia in a neurologic and neuro-surgical adult patient population. A literature search was conducted using MEDLINE, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials (1966-May 2013). Search limits were English, human, and adult using the terms vasopressin receptor antagonist, conivaptan, tolvaptan, lixivaptan, neurology, neurological disorder, neurosurgery, neurointensive care, and neurocritical care. All case reports, case series, and clinical trials investigating the use of conivaptan in neurosurgical patients were included. Seven reports were identified using conivaptan as monotherapy or adjunctive treatment for hyponatremia in a neurosurgical patient population. One study was a prospective, randomized, controlled trial, while 6 reports were case reports or case series. The prospective randomized trial found a significant increase in serum sodium concentration over baseline with a conivaptan 20-mg intravenous bolus dose followed by a 20-mg/day continuous infusion for 24 hours compared to "usual care" at 6 hours (7.0 ± 1.7 vs -0.6 ± 2.1 mEq/L, respectively; p = 0.008) and 36 hours (8.0 ± 5.6 vs -1.7 ± 2.1 mEq/L, respectively; p = 0.05) after treatment. One case series found that the mean serum sodium remained significantly increased from baseline up to 72 hours (5.12 ± 4.0 mEq/L; p < 0.001) after a single conivaptan 20-mg intravenous bolus dose. All reports demonstrated clinical effectiveness of conivaptan in significantly increasing serum sodium concentrations following administration compared to baseline. However, the clinical significance of this finding remains debatable since some of these patients remained hyponatremic. Overall, conivaptan is a promising and well-tolerated agent for the management of hyponatremia in neurologic and neurosurgical patients. However, its use should be limited to patients in whom conventional therapies fail or as adjunctive therapy.

Hourly oral sodium chloride for the rapid and predictable treatment of hyponatremia

Hypertonic NaCl is first-line therapy for acute, severe and symptomatic hyponatremia; however, its use is often restricted to the intensive care unit (ICU). A 35-year-old female inpatient with an optic chiasm glioma and ventriculoperitoneal shunt for hydrocephalus developed acute hyponatremia (sodium 122 mEq/L) perhaps coinciding with haloperidol treatment. The sum of her urinary sodium and potassium concentrations was markedly hypertonic vis-à-vis plasma; it was inferred that serum sodium concentration would continue to fall even in the complete absence of fluid intake. Intravenous (IV) 3% NaCl was recommended; however, a city-wide public health emergency precluded her transfer to the ICU. She was treated with hourly oral NaCl tablets in a dose calculated to deliver the equivalent of 0.5 mL/kg/h of 3% NaCl with an objective of increasing the serum sodium concentration by 6 mEq/L. She experienced a graded and predictable increase in serum sodium concentration. A slight overshoot to 129 mEq/L was rapidly corrected with 0.25 l of D5W, and she stabilized at 127 mEq/L. We conclude that hourly oral NaCl, in conjunction with careful monitoring of the serum sodium concentration, may provide an attractive alternative to IV 3% NaCl for selected patients with severe hyponatremia.