Baseline Serum Sodium Research Articles

Vasopressin induced hyponatremia in infants

Vasopressin is used for shock and acute pulmonary hypertension in the neonatal intensive care unit (NICU) and is associated with hyponatremia. The purpose of this study was to determine the incidence, severity, contributing risk factors associated with vasopressin-induced hyponatremia in neonates and infants <3 months of age in the NICU. The primary objective was to determine the incidence of hyponatremia (<130 mEq/L) and severe hyponatremia (<125 mEq/L). The secondary objectives were to compare clinical characteristics and the vasopressin regimen between those with and without hyponatremia. This retrospective cohort study included neonates and infants <3 months from 1/1/2017-12/31/2022 receiving vasopressin for >6 h. Analyses were performed using SAS v9.4, with a priori less than 0.05. A multiple variable logistic regression was employed to assess odds of hyponatremia. Of the 105 patients included, 57 (54.3%) developed hyponatremia, and 17 (29.8%) were classified as severe hyponatremia. Overall, the median (interquartile range, IQR) gestational and postnatal age at vasopressin initiation were 35.4 (27-38.7) weeks and 2 (1-12) days. There was no difference in vasopressin dose, but duration of treatment was longer in those with hyponatremia. Higher baseline serum sodium was associated with decreased odds of hyponatremia [adjusted odds ratio (OR): 0.90 (95% CI: 0.83-0.99), p = 0.03], and increased vasopressin duration was associated with increased odds of hyponatremia [aOR: 1.02 (95% CI: 1.01-1.03), p < 0.001]. Hyponatremia occurred in half of patients included. The pre-vasopressin sodium value and the vasopressin duration were independently associated with hyponatremia.

Association of baseline serum sodium with long-term outcomes in newly diagnosed coronary heart disease patients without heart failure: a prospective cohort study

Sodium is crucial for maintaining cardiovascular health, especially in relation to heart failure. The impact of baseline serum sodium concentrations on the outcomes of newly diagnosed coronary heart disease (CHD) without heart failure remains unclear. This prospective cohort study included 681 patients who were newly diagnosed with CHD. Cox proportional hazards models and restricted cubic spline (RCS) analysis were used to assess the relationship between serum sodium concentrations and major adverse cardiovascular events. The improvement in traditional prediction models by the addition of serum sodium concentrations was assessed using changes in the C-statistic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). During a median follow-up of 51.04 months (IQR: 40.88–53.80 months), 131 events were recorded. Multivariate Cox proportional hazards models showed that the L2 group (136–138.9 mmol/L) had the highest MACE risk. Compared to L2, the hazard ratios (HRs) and 95% confidence intervals (CIs) for the L1 (130–135.9 mmol/L), L3 (139–140.9 mmol/L), L4 (141–142.9 mmol/L), and L5 (143–147.0 mmol/L) groups were 0.31 (0.14–0.70, P = 0.005), 0.48 (030–0.78, P = 0.003), 0.56 (0.34–0.92, P = 0.022), and 0.37 (0.22–0.64, P < 0.001), respectively. Including serum sodium concentrations in the prediction model significantly improved the C-statistic from 0.647 to 0.679 (P = 0.022), with an NRI of 0.338 (P < 0.001) and an IDI of 0.026 (P < 0.001). RCS analysis showed a nonlinear relationship: within the 130–138 mmol/L sodium range, MACE risk gradually increased with higher sodium levels (HR 1.39, 95% CI 1.09–1.76, P = 0.008); whereas within the 138–147 mmol/L range, the risk gradually decreased (HR 0.88, 95% CI 0.80–0.98, P = 0.014). Baseline serum sodium concentrations are significantly associated with long-term cardiovascular risk in newly diagnosed CHD patients, showing an inverted U-shaped relationship, whereas low serum sodium may be specifically linked to higher risks of death and nonfatal myocardial infarction. Further research is needed to explore the impact of long-term changes in serum sodium concentrations on disease prognosis.

Impact of low sodium values on survival outcomes of patients with cancer receiving immune checkpoint inhibitors.

Background: Low serum sodium affects cancer prognosis, but its impact on immunotherapy is unclear.Objective: Assessing the association of pre- and post-ICI treatment sodium levels with survival.Methods: We retrospectively analyzed patients receiving ICI in January 2012-December 2023, collecting serum sodium levels at treatment initiation and 4weeks post-ICI, with overall survival (OS) as the primary outcome.Results: Low sodium was observed in 125 and 119 patients pre-and post-treatment respectively. Pre-ICI and post-ICI low sodium correlated with decreased OS [10.6 vs. 22.9months (p =0.001) and 11.6 vs. 27.2months (p =0.009)]. Multivariate analysis identified pre-ICI low sodium [HR: 1.685; 95% CI: 1.050-2.705; p =0.031] as an independent risk factor for worse OS.Conclusion: Low baseline serum sodium was an independent risk factor for poor OS in patients treated with ICIs.

High serum sodium predicts immunotherapy response in metastatic renal cell and urothelial carcinoma

ObjectivesThe development of reliable biomarkers for the prediction of immune checkpoint inhibition (ICI) response in patients with metastatic renal cell carcinoma (mRCC) and urothelial carcinoma (mUC) remains an unresolved challenge. Conventional ICI biomarkers typically focus on tumor-related factors such as PD-L1 expression. However, a comprehensive evaluation of the predictive value of serum electrolyte levels, a so far widely unexplored area, is still pending. MethodsWe conducted a post-hoc analysis of baseline sodium, potassium, chloride, magnesium and calcium levels in two independent phase 3 clinical trials: IMvigor211 for mUC comparing atezolizumab to chemotherapy, and IMmotion151 for mRCC comparing atezolizumab+bevacizumab to sunitinib. This analysis aimed to evaluate the prognostic and predictive value of these electrolyte levels in these clinical settings. A total of 1787 patients (IMvigor211 n = 901; IMmotion151 n = 886) were analyzed. ResultsWe found a linear correlation of baseline serum sodium and chloride with prognosis across both trials, which was not found for potassium, magnesium and calcium. In multivariate analysis, the prognostic capacity of sodium was limited to patients receiving ICI as compared to the control group. Interestingly, in both studies, the chance of achieving an objective response was highest in the patient subgroup with high baseline serum sodium levels of > 140 mmol/L (IMmotion151: Complete response in 17.9% versus 2.0% in patients with mRCC with baseline sodium < 135 mmol/L). Serum sodium outperformed tumor PD-L1 expression as a predictor for immunotherapy efficacy. ConclusionsPatients exhibiting elevated serum sodium levels derive the greatest benefit from immunotherapy, suggesting that baseline serum concentration could serve as a valuable and cost-effective predictive biomarker for immunotherapy across entities.

High Incidence of Refeeding Syndrome during the Transition from F75 to Ready-to-Use Therapeutic Feeds among Children 6 to 59 Months with Severe Acute Malnutrition at the Pediatric Nutritional Unit of Mulago Hospital.

Refeeding syndrome is a complication developed by children being managed for severe acute malnutrition (SAM). It is caused by changes in electrolyte balance once high-caloric feeding is reinitiated. Phosphorus, potassium, and magnesium are the main electrolytes affected when it occurs. However, hypophosphatemia is the hallmark of the diagnosis of refeeding syndrome. WHO recommends inpatient management of patients with complicated SAM with initially F75 which is low in calories and later transitioned to RUTF which is high in calories but also has a higher phosphorus content. This study aims to determine the incidence and factors associated with refeeding syndrome in the transition phase when treating children aged 6 to 59 months with severe acute malnutrition at the Mwanamugimu Nutritional Unit, Mulago. We conducted a prospective cohort study at the Mwanamugimu Nutritional Unit of Mulago National Referral Hospital. A total of 150 children between 6 and 59 months with SAM were enrolled into the study. We measured serum electrolytes (phosphorus, sodium, and potassium) at admission, initiation of RUTF, and 48 hours after transition. The refeeding syndrome was diagnosed by a drop in serum phosphorus of more than 0.3 mmol from baseline. The data were analyzed using STATA 17.0. Incidence of refeeding syndrome was determined as the proportion of participants whose serum phosphorus declined by more than 0.3 mmol from baseline. For factors associated, a multivariate-modified Poisson regression analysis reporting relative risk was performed with a 0.2 level of significance at bivariate and 0.05 at multivariate analyses. Of the 150 children recruited, 35 were lost to follow-up and 115 children had their data analyzed. Of the 115 participants in the study, 40 developed refeeding syndrome indicating a cumulative incidence of 34.8% with a 95% CI of 26.5-44%. A low baseline serum sodium (RR: 0.89, 95% CI: 0.80-0.99, and P value: 0.038) and having edematous malnutrition (RR: 0.90, 95% CI: 0.81-0.99, and P value; 0.042) at admission were found to be significant (P < 0.05) risk factors of refeeding syndrome. The cumulative incidence of RFS of 34.8% is very high. RFS is found to be associated with low baseline sodium and pedal edema. Children with a low baseline sodium and edema should undergo a cautious transition of feeds.

Use of Urea for the Syndrome of Inappropriate Secretion of Antidiuretic Hormone

Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) are associated with significant mortality and morbidity. The effectiveness and safety of oral urea for SIADH are still debated. To evaluate the efficacy and safety of urea for the treatment of SIADH. A systematic search of Medline and Embase was conducted for controlled and uncontrolled studies of urea for SIADH in adult patients. The primary outcome was serum sodium concentration after treatment. Secondary outcomes included the proportion of patients with osmotic demyelination syndrome (ODS), intracranial pressure, and resource use such as length of stay. Twenty-three studies involving 537 patients with SIADH were included, of which 462 were treated with urea. The pooled mean baseline serum sodium was 125.0 mmol/L (95% CI, 122.6-127.5 mmol/L). The median treatment duration with oral urea was 5 days. Urea increased serum sodium concentration by a mean of 9.6 mmol/L (95% CI, 7.5-11.7 mmol/L). The mean increase in serum sodium after 24 hours was 4.9 mmol/L (95% CI, 0.5-9.3 mmol/L). Adverse events were few, mainly consisting of distaste or dysgeusia, and no case of ODS was reported. Resource use was too infrequently reported to be synthesized. In this systematic review of the use of urea in SIADH and despite the lack of randomized clinical trials, lower-quality evidence was identified that suggests that urea may be an effective, safe, and inexpensive treatment modality that warrants further exploration.

Associations of Hyponatremia with Cognition Function and All-Cause Mortality: Post Hoc Analysis of the Systolic BP Intervention Trial.

Acute neurological effects of severe hyponatremia are well known. However, the long-term association of hyponatremia with cognitive impairment are unclear. In this post-hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), we examined whether incident hyponatremia is a risk factor for mild cognitive impairment (MCI) or probable dementia (PD). In those with baseline serum sodium ≥ 130 mmol/L, we defined incident hyponatremia in the first 6 months as a SPRINT safety alert for serum sodium < 130 mmol/L from randomization to the 6-month visit. In multivariate, Cox regression models adjusted for baseline cognitive function and other variables, we related incident hyponatremia in the first 6 months with subsequent MCI or PD in 8,540 participants with cognitive outcomes data and with all-cause mortality (ACM) in 9,135 participants with mortality data. Incident hyponatremia in the first 6 months was noted in 116 (1.4%) participants. Older age, female sex, non-African American race, lower body mass index and randomization to intensive systolic blood pressure control were associated with incident hyponatremia. Compared to those without hyponatremia, those with incident hyponatremia had higher risk of PD (2.1 versus 0.9 events/ 100 person years, HR 3.08, 95% CI 1.48 to 6.41) but not MCI (3.1 versus 3.6 events/ 100 person years, HR 0.95, 95% CI 0.54 to 1.68) and the composite of MCI/ PD (5.0 versus 4.2 events/ 100 person years, HR 1.28, 95% CI 0.82 to 2.0). There were no significant differences in ACM (HR 1.84, 95% CI 0.90 to 3.73). Biological plausibility for the association of incident hyponatremia with PD but not MCI or death is unclear. The association of incident hyponatremia with PD could reflect a chance finding or non-causal biological association or causal relationship.

Risk stratification and predictive value of serum sodium fluctuation for adverse prognosis in acute coronary syndrome patients

BackgroundSerum sodium fluctuation (SF) as an indicator of the extent of changes in serum sodium is associated with increased mortality in hospitalized patients. However, there is no consensus on diagnostic criteria for SF, and its impact on the outcome of patients with acute coronary syndrome (ACS) remains uncertain. We defined SF and assessed its association with adverse prognosis in hospitalized ACS patients. MethodsPatients diagnosed with ACS were consecutively recruited. The serum SF rate (SFR) was defined as the ratio of the difference between the highest and lowest serum sodium levels during hospitalization to the initial serum sodium level on admission. The Cox proportional hazards model was performed to evaluate the association between SFR and mortality. The dose–response relationships of SFR with mortality was characterized by restricted cubic splines (RCS) model. The predictive performance of SF for mortality was assessed by the area under the receiver operating characteristic curves (AUCs). ResultsThe study retrospectively enrolled 1856 ACS patients, of which 36 (1.94%) patients dead within 1 year. Multivariate Cox analysis showed that SFR was independently associated with higher risk of 1-year mortality (HR = 1.17, 95% CI: 1.111–1.244, P < 0.001). RCS analysis showed the optimal threshold for SFR was 5%, and the 1-year cumulative mortality was higher in the abnormal SF group (SFR ≥ 5%) compared with the normal SF group (SFR < 5%, P < 0.01). The AUCs of SF for predicting mortality within 1 month, 6 months, and 1 year were 0.842 (95% CI: 0.781–0.904), 0.830 (95% CI:0.736–0.926), 0.703 (95% CI:0.595––0.811), respectively. Even in patients with normal baseline serum sodium, abnormal SF group demonstrated a significantly higher 1-year mortality compared to normal SF group (HR = 4.955, 95% CI: 1.919–12.795). ConclusionThe SFR during hospitalization is an adequate predictor of adverse outcomes in ACS patients, independent of serum sodium level at admission. Additional research is warranted to ascertain whether interventions targeting SF confer measurable clinical benefits.

Impact of serum sodium concentrations, and effect modifiers on mortality in the Irish Health System

BackgroundAbnormalities of serum sodium are associated with increased mortality risk in hospitalised patients, but it is unclear whether, and to what extent other factors influence this relationship. We investigated the impact of dysnatraemia on total and cause-specific mortality in the Irish health system while exploring the concurrent impact of age, kidney function and designated clinical work-based settings.MethodsA retrospective cohort study of 32,666 participants was conducted using data from the National Kidney Disease Surveillance System. Hyponatraemia was defined as < 135 mmol/L and hypernatraemia as > 145 mmol/L with normal range 135–145 mmol/L. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HR’s) and 95% Confidence Intervals (CIs) while penalised spline models further examined patterns of risk.ResultsThere were 5,114 deaths (15.7%) over a median follow up of 5.5 years. Dysnatraemia was present in 8.5% of patients overall. In multivariable analysis, both baseline and time-dependent serum sodium concentrations exhibited a U-shaped association with mortality. Hyponatremia was significantly associated with increased risk for cardiovascular [HR 1.38 (1.18–1.61)], malignant [HR: 2.49 (2.23–2.78)] and non-cardiovascular/non-malignant causes of death [1.36 (1.17–1.58)], while hypernatremia was significantly associated with cardiovascular [HR: 2.16 (1.58–2.96)] and non-cardiovascular/ non-malignant deaths respectively [HR: 3.60 (2.87–4.52)]. The sodium-mortality relationship was significantly influenced by age, level of kidney function and the clinical setting at baseline (P < 0.001). For hyponatraemia, relative mortality risks were significantly higher for younger patients (interaction term P < 0.001), for patients with better kidney function, and for patients attending general practice [HR 2.70 (2.15–3.36)] than other clinical settings. For hypernatraemia, age and kidney function remained significant effect modifiers, with patients attending outpatient departments experiencing the greatest risk [HR 9.84 (4.88–18.62)] than patients who attended other clinical locations. Optimal serum sodium thresholds for mortality varied by level of kidney function with a flattening of mortality curve observed for patients with poorer kidney function.ConclusionSerum sodium concentrations outside the standard normal range adversly impact mortality and are associated with specific causes of death. The thresholds at which these risks appear to vary by age, level of kidney function, and are modified in specific clinical settings within the health system.

The role of initial sodium and globulin values in the prognosis prediction of patients diagnosed with colon cancer

Aims: Early prediction of prognosis in malignancies can help determine life expectancy and take necessary further measures accordingly. There is no consensus on using any biomarker in predicting prognosis in colon cancer cases. A study reported that the sodium/globulin ratio is a valuable biomarker in predicting the prognosis of gastric cancer. This study aimed to investigate the role of baseline sodium, globulin, and sodium/globulin ratio in the prediction of prognosis and survival in colon cancer cases. Methods: The files of patients diagnosed with colon cancer who applied to Kırıkkale University Faculty of Medicine Medical Oncology Clinic between January 1, 2015, and December 31, 2020, were retrospectively analyzed. The relationship between the clinical and laboratory characteristics of the cases and their progression and survival were investigated. Results: 140 patients diagnosed with colon cancer were included in the study (82 men, 58 women). The average age at diagnosis was 64.1±12.6 years, 99.3% of them were adenocarcinoma, and 32.9% of them were stage 4 cancers. It was determined that 42.1% of the patients died (average survival time 54.0±3.2 months), and progression developed in 18.6% during the study period. The average baseline sodium/globulin ratio was 51.10±8.70. No significant correlation was found between initial serum sodium level, globulin level, sodium/globulin ratio, survival time, and progression status (p&gt;0.05). Baseline serum globulin level showed a weak negative correlation with both progression-free and overall survival time (r=-0.23, p&lt;0.05 and r=-0.24, p&lt;0.05, respectively), while the sodium/globulin ratio showed a weak positive correlation with progression-free survival time (r=0.26, p&lt;0.01) and overall survival time (r=0.25, p&lt;0.01). The ROC curve analysis determined that initial serum sodium and globulin levels and sodium/globulin ratio were not predictive of progression and survival at any cut-off point (p&gt;0.05). Conclusion: Although baseline serum sodium level, globulin level, and serum sodium/globulin ratio were weakly correlated with progression-free and overall survival time of patients diagnosed with colon cancer, they were not valuable in predicting progression and survival.

Parenclitic network mapping identifies response to targeted albumin therapy in patients hospitalized with decompensated cirrhosis.

The efficacy of targeted albumin therapy in the management of decompensatory events in cirrhosis is unclear with different reports showing conflicting results. It is possible that only certain subgroups of patients may benefit from targeted albumin administration. However, extensive conventional subgroup analyses have not yet identified these subgroups. Albumin is an important regulator of physiological networks and may interact with homeostatic mechanism differently in patients according to the integrity of their physiological network. In the present study we aimed to assess the value of network mapping in predicting response to targeted albumin therapy in patients with cirrhosis. This is a sub-study of the ATTIRE trial; a multicentre, randomized trial conducted to assess the effect of targeted albumin therapy in cirrhosis. Baseline serum bilirubin, albumin, sodium, creatinine, CRP, and white cell count (WCC), international normalised ratio, heart rate, and blood pressure of 777 patients followed up for 6 months were used for network mapping using parenclitic analysis. Parenclitic network analysis involves measuring the deviation of each individual patient from the existing network of physiological interactions in a reference population. Overall network connectivity as well as deviations along WCC-CRP axis predicted 6-month survival independent of age and model for end-stage liver disease (MELD) in the standard care arm. Patients with lower deviation along the WCC-CRP axis showed lower survival in response to targeted albumin administration over 6-month follow-up period. Likewise, patients with higher overall physiological connectivity survived significantly less than the standard care group following targeted albumin infusion. The parenclitic network mapping can predict survival of patients with cirrhosis and identify patient subgroups that don't benefit from targeted albumin therapy.

Endocrine Abnormalities in Children With Traumatic Brain Injury at a Tertiary Care Center.

Objective Accidental traumatic brain injury (TBI) can lead to severe complications such as endocrine abnormalities and long-term morbidities and can negatively impact patient lives. These conditions are also associated with a high cost of treatment over a lifetime, a significant concern in low-to-middle-income countries (LMICs). In Pakistan, the prevalence of children with endocrine abnormalities secondary to TBI remains largely unexplored. We conducted a retrospective cross-sectional study to estimate the burden of endocrine abnormalities due to TBI among children in our population. Methods Twenty patients previously admitted with head injury between September and October 2019 were retrospectively reviewed with tests for baseline serum sodium, plasma osmolality, cortisol, adrenocorticotropin (ACTH), free thyroxine (fT4), growth hormone (GH), insulin growth factor-1 (IGF-1), follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), prolactin, estradiol, and testosterone. Data were collated from the electronic Health and Information Management System (HIMS) and analyzed using SPSS v25. Chi-square and t-tests were used to identify associations between variable groups. Outcomes of interest included correlations between hormonal levels and demographic factors, interventions and hormonal levels, and complication rates and hormonal levels. Results Our study reports three (15% of the total cohort) patients with pituitary hormone deficits (two with low IGF-1 and one with low TSH). High serum IGF-1 and ACTH levels were also observed in three (15%) children. High IGF-1 was associated with female gender (p=0.007), mechanical ventilation (p=0.038), and falls (p=0.028). IGF-1 (p=0.035) and GH (p=0.049) levels were associated with improvement in Extended Glasgow Outcome Scale (GOS-E) score. Testosterone was positively correlated with a high percentile for height (p=0.005) and GOS-E scores on follow-up (p=0.030). High testosterone levels (592.12 ± 102.28 ng/dl) were associated with good functional outcomes in post-pubescent patients (p<0.05). Serum fT4 was linked with a high GOS-E score at discharge in prepubescent patients (p=0.034). Neurosurgical decompression was the only risk factor for hormone deficiency, comprising 67% of the group with hormone deficiencies (p=0.028). The learning difficulties were observed exclusively in children with hormonal deficiencies (7 patients, p=0.000). Conclusion Hormonal dysfunction due to TBI in children can lead to poor outcomes. High serum IGF-1, testosterone, and free T4 levels were associated with improved functional outcomes in children with TBI. Limited follow-up and resources in LMICs are significant barriers to addressing the morbidity associated with these conditions and need to be addressed at a health policy level.

Renal dysfunction occurs following ileostomy formation and is independent of readmission.

Ileostomy formation may be permanent or intended as temporary to defunction a high-risk pelvic anastomosis to reduce the risk of septic consequences of anastomotic leak. However, these procedures have a high rate of readmission, most commonly due to dehydration and associated with acute kidney injury (AKI). A single centre retrospective cohort study of patients who underwent ileostomy formation from 2015 to 2020 and analysed in two groups: those who needed readmission within 60 days and those who did not. Data collected included demographics and renal function and electrolytes at baseline (ileostomy formation) and at elective ileostomy closure. A total of 171 patients were included in the analysis, with a readmission rate 38% within 60 days of discharge. There was a significant increase in creatinine from baseline blood tests compared to date of elective ileostomy closure in both the readmission and no readmission arms. There was a significant decrease in eGFR from baseline blood tests compared with date of ileostomy closure in both readmission and no readmission arms. There was no significant difference in creatinine or eGFR between readmission and no readmission arms at date of ileostomy closure. Baseline serum sodium levels were lower in the readmission arm compared to no readmission arm. Ileostomy formation is associated with a deterioration in renal function, which occurs independent of whether the patient requires readmission to hospital. Low serum sodium may be used as a predictor for patients with an increased risk of readmission.

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.

Early serum sodium changes in elderly patients with nocturia receiving desmopressin

Abstract Purpose: The purpose of the study is to identify early serum sodium changes that could happen in elderly patients with nocturia receiving desmopressin. Materials and Methods: This study was conducted on 28 patients complaining of nocturia and receiving desmopressin. Inclusion criteria were patients diagnosed as having nocturia (at least one or more voids per night) aging ≥55 years with normal baseline serum sodium (135–150 mEq/L). All patients received desmopressin in the form of 60 μg at bedtime. Close follow-up was done for any adverse effects that may have occurred related to hyponatremia and serum sodium was reevaluated for all patients at 3, 7, 14, and 30 days from the start of the treatment. Results: Desmopressin resulted in a significant decrease in nocturnal urine volume, a decrease in nocturnal polyuria index, number of night voids and the time to first void was delayed. Furthermore, statistically insignificant sodium drop in males and statistically significant sodium drop in females were noted with infrequent side effects, for example, headache (10.7%) and hyponatremia (7.14%) that started after treatment by 1 week. Conclusion: Hyponatremia can be avoided using the minimal effective dose of desmopressin. To receive desmopressin in elderly patients sodium baseline level must be ≥135 mmol/L. Close sodium monitoring has to be done at 7, 14, and 30 days from start of treatment for high-risk patients (especially elderly) or patients receiving other medication causing hyponatremia.

Efficacy and Safety of Conivaptan versus Tolvaptan in Neurocritically Ill Patients

Abstract Background: Vasopressin receptor antagonists increase serum sodium through increased aquaresis via inhibition of V2 receptors. The purpose of this study was to compare the efficacy and safety of conivaptan versus tolvaptan for the treatment of hyponatremia. Subject and Methods: This was a retrospective study of patients who received conivaptan or tolvaptan for hyponatremia admitted to the neurocritical care unit. Serum sodium values were collected at baseline and daily up to 4 days after the last dose. The primary efficacy outcome was an increase in serum sodium ≥4 mEq/L in 24 h after the first vaptan dose. The primary safety outcome was overcorrection defined by an increase in serum sodium &gt;12 mEq/L in 24 h. Results: Thirty-four encounters (14 conivaptan and 20 tolvaptan) were included. Baseline serum sodium was similar between groups (conivaptan 126 mEq/L and tolvaptan 125 mEq/L). Each group received a median of one vaptan dose received on days 5 and 7 of hospitalization for conivaptan and tolvaptan, respectively. The primary efficacy outcome was similar between conivaptan (9 of 14, 64.3%) and tolvaptan (14 of 20, 70%) groups, P = 1.0, and the median change in serum sodium 24 h after the first vaptan dose was 5 versus 7 mEq/L (P = 0.377), respectively. The rate of overcorrection was similar between conivaptan and tolvaptan patients (7.1% vs. 15% P = 0.627). Conclusion: In this study, conivaptan compared to tolvaptan for the treatment of hyponatremia in patients admitted with a primary neurological diagnosis appears efficacious and safe. Further studies are warranted given the sample size of this cohort.

Dysnatremia and risk of bloodstream infection in dialysis patients

Emerging data suggest that sodium disarrays including hyponatremia are potential risk factors for infection ensuing from impairments in host immunity, which may be exacerbated by coexisting conditions (i.e. mucosal membrane and cellular edema leading to breakdown of microbial barrier function). While dysnatremia and infection-related mortality are common in dialysis patients, little is known about the association between serum sodium levels and the risk of bloodstream infection in this population. Among 823 dialysis patients from the national Biospecimen Registry Grant Program who underwent serum sodium testing over the period January 2008-December 2014, we examined the relationship between baseline serum sodium levels and subsequent rate of bloodstream infection. Bloodstream infection events were directly ascertained using laboratory blood culture data. Associations between serum sodium level and the incidence of bloodstream infection were estimated using expanded case mix-adjusted Poisson regression models. In the overall cohort, ∼10% of all patients experienced one or more bloodstream infection events during the follow-up period. Patients with both lower sodium levels <134mEq/l and higher sodium levels ≥140mEq/l had higher incident rate ratios (IRRs) of bloodstream infection in expanded case mix analyses (reference 136-<138mEq/l), with adjusted IRRs of 2.30 [95% confidence interval (CI) 1.19-4.44], 0.77 (95% CI 0.32-1.84), 1.39 (95% CI 0.78-2.47), 1.88 (95% CI 1.08-3.28) and 1.96 (95% CI 1.08-3.55) for sodium levels <134, 134-<136, 138-<140, 140-<142 and ≥142Eq/l, respectively. Both lower and higher baseline serum sodium levels were associated with a higher rate of subsequent bloodstream infections in dialysis patients. Further studies are needed to determine whether correction of dysnatremia ameliorates infection risk in this population.

A Prediction Model for Neurological Deterioration in Patients with Acute Spontaneous Intracerebral Hemorrhage.

AimThe aim of this study was to explore factors related to neurological deterioration (ND) after spontaneous intracerebral hemorrhage (sICH) and establish a prediction model based on random forest analysis in evaluating the risk of ND.MethodsThe clinical data of 411 patients with acute sICH at the Affiliated Hospital of Jining Medical University and Xuanwu Hospital of Capital Medical University between January 2018 and December 2020 were collected. After adjusting for variables, multivariate logistic regression was performed to investigate the factors related to the ND in patients with acute ICH. Then, based on the related factors in the multivariate logistic regression and four variables that have been identified as contributing to ND in the literature, we established a random forest model. The receiver operating characteristic curve was used to evaluate the prediction performance of this model.ResultsThe result of multivariate logistic regression analysis indicated that time of onset to the emergency department (ED), baseline hematoma volume, serum sodium, and serum calcium were independently associated with the risk of ND. Simultaneously, the random forest model was developed and included eight predictors: serum calcium, time of onset to ED, serum sodium, baseline hematoma volume, systolic blood pressure change in 24 h, age, intraventricular hemorrhage expansion, and gender. The area under the curve value of the prediction model reached 0.795 in the training set and 0.713 in the testing set, which suggested the good predicting performance of the model.ConclusionSome factors related to the risk of ND were explored. Additionally, a prediction model for ND of acute sICH patients was developed based on random forest analysis, and the developed model may have a good predictive value through the internal validation.

Relationship of Dapagliflozin With Serum Sodium: Findings From the DAPA-HF Trial

ObjectivesThis study aimed to assess the prognostic importance of hyponatremia and the effects of dapagliflozin on serum sodium in the DAPA-HF (Dapagliflozin And Prevention of Adverse outcomes in Heart Failure) trial. BackgroundHyponatremia is common and prognostically important in hospitalized patients with heart failure with reduced ejection fraction, but its prevalence and importance in ambulatory patients are uncertain. MethodsWe calculated the incidence of the primary outcome (cardiovascular death or worsening heart failure) and secondary outcomes according to sodium category (≤135 and >135 mmol/L). Additionally, we assessed: 1) whether baseline serum sodium modified the treatment effect of dapagliflozin; and 2) the effect of dapagliflozin on serum sodium. ResultsOf 4,740 participants with a baseline measurement, 398 (8.4%) had sodium ≤135 mmol/L. Participants with hyponatremia were more likely to have diabetes, be treated with diuretics, and have lower systolic blood pressure, left ventricular ejection fraction, and estimated glomerular filtration rate. Hyponatremia was associated with worse outcomes even after adjustment for predictive variables (adjusted HRs for the primary outcome 1.50 [95% CI: 1.23-1.84] and all-cause death 1.59 [95% CI: 1.26-2.01]). The benefits of dapagliflozin were similar in patients with and without hyponatremia (HR for primary endpoint: 0.83 [95% CI: 0.57-1.19] and 0.73 [95% CI: 0.63-0.84], respectively, P for interaction = 0.54; HR for all-cause death: 0.85 [95% CI: 0.56-1.29] and 0.83 [95% CI: 0.70-0.98], respectively, P for interaction = 0.96). Between baseline and day 14, more patients on dapagliflozin developed hyponatremia (11.3% vs 9.4%; P = 0.04); thereafter, this pattern reversed and at 12 months fewer patients on dapagliflozin had hyponatremia (4.6% vs 6.7%; P = 0.003). ConclusionsBaseline serum sodium concentration was prognostically important, but did not modify the benefits of dapagliflozin on morbidity and mortality in heart failure with reduced ejection fraction. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]: NCT03036124)

Symptomatic Hyponatremia in a Patient With Hepatorenal Syndrome Treated with Terlipressin.

Terlipressin (vasopressin analogue) is considered most promising pharmacotherapy used for reversal of hepatorenal syndrome and esophageal variceal bleed. It occasionally results in hyponatremia, often complicated by serious central nervous system manifestation. We report here a case of a 60 years’ old female known case of chronic liver disease decompensated who presented with acute kidney injury secondary to hepatorenal syndrome. Treatment was started with terlipressin loading dose followed by maintenance dose. She developed acute confusion, however there was no obvious brain pathology on computed tomography. Her baseline serum sodium (146.8mol/L) decreased to 111.5mmol/L after terlipressin was initiated. Terlipressin was withdrawn and responded to 3% hypertonic saline. Terlipressin-induced hyponatremia may be a rare complication and treating physicians should be aware of the possible complications arising during the management of hepatorenal syndrome.