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Purpose: Effective treatment options for patients with hypernatremia are limited. Free water administration (parenterally or enterally) is the mainstay of treatment but the impact of each strategy on lowering serum sodium (Na) is not known. The purpose of the study was thus to assess the effectiveness of enteral free water vs. parenteral dextrose 5% in water (D5W) in treating ICU-acquired hypernatremia. Methods: An electronic medical record-based, retrospective cohort study was conducted in a 30-bed mixed medical-surgical intensive care unit (ICU) in Japan. All adult patients admitted to the ICU from August 2017 to July 2021 were reviewed. After a 2-step exclusion, patients who stayed in the ICU ≥ 24 h and received either or both treatments for ICU-acquired hypernatremia (Na ≥ 145 mEq/L) constituted the study cohort. The primary outcome was a change in serum Na during the 24 h before treatment each day (ΔNa); the secondary outcomes were gastrointestinal complications, serum glucose levels, ICU/hospital mortality, ICU/hospital length of stay, and the duration of mechanical ventilation. Repeated measurements on each patient were addressed using a generalized estimated equation (GEE) for multiple linear regression analysis. Analysis was conducted with R version 4.0.3. Results: In total, 256/6596 (131: D5W, 125: enteral free water) patients were analyzed. Median treatment lasted 6 days [3–17] for the D5W group vs 7 days [3–14] for the enteral free water group with a total median daily treatment volume of 799 [IQR 299–1221] mL vs. 400 [IQR 262–573] mL. GEE multiple linear regression analysis showed an estimated mean ΔNa per liter of treatment fluid of − 2.25 [95% CI − 2.76 to − 1.74] mEq/L per liter of parenteral D5W vs. − 1.91 mEq decrease [95% CI − 2.75 to − 1.07] per liter of enteral free water. Hydrochlorothiazide was the only medication associated with a statistically significant negative ΔNa by− 0.89 [− 1.57 to − 0.21] mEq/L. There were no significant inter-group differences for secondary outcomes. Conclusions: These results suggest that both enteral free water and parenteral D5W are effective for treating ICU-acquired hypernatremia. Parenteral D5W was slightly more effective than enteral free water to lower serum Na levels in patients with ICU-acquired hypernatremia. Trial registration: Not applicable. [ABSTRACT FROM AUTHOR]

Dysnatremia is an electrolytic disorder commonly associated with mortality in various diseases. However, little is known about dysnatremia in out-of-hospital cardiac arrest (OHCA) cases. Here, we investigated the association between serum sodium level on hospital arrival and neurological outcomes after OHCA. This nationwide hospital-based observational study (The Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest registry) enrolled patients with OHCA between 2014 and 2017. We included adult patients aged ≥ 18 years with non-traumatic OHCA who achieved return of spontaneous circulation (ROSC) and whose serum sodium level on hospital arrival was available. Based on the serum sodium level, patients were divided into three levels: hyponatremia (Na < 135 mEq/L), normal sodium level (Na ≥ 135 or ≤ 145 mEq/L), and hypernatremia (Na > 145 mEq/L). The primary outcome was 1-month survival with favourable neurological outcomes. Altogether, 34 754 patients with OHCA were documented, and 5160 patients with non-traumatic OHCA and who achieved ROSC were eligible for our analyses. The proportion of favourable neurological outcomes was highest in patients with normal sodium levels at 17.6% (677/3854), followed by patients with hyponatremia at 8.2% (57/696) and patients with hypernatremia at 5.7% (35/610). Moreover, hyponatremia and hypernatremia were associated with a decreased probability of favourable neurological outcomes compared with normal sodium level (vs. hyponatremia, adjusted odds ratio [AOR] 0.97, 95% confidence interval [CI] 0.95–0.99; vs. hypernatremia, AOR 0.96, 95% CI 0.94–0.98). Hypo- and hypernatremia on hospital arrival were associated with a decreased probability of favourable neurological outcomes in patients with non-traumatic OHCA who achieved ROSC. [ABSTRACT FROM AUTHOR]

Purpose: Older individuals are at high risk for hypernatremia. However, actual data on serum sodium levels and differences between the sexes remain unclear in the older Japanese population. This study aimed to describe the data regarding serum sodium level and hypernatremia prevalence and to investigate whether female sex is associated with an increased risk of hypernatremia. Patients and Methods: We retrospectively analyzed the data of adults aged ≥ 65 years without severely reduced kidney function who underwent an annual health checkup in 2019. Serum sodium levels were investigated as the outcome and corrected for glucose, if necessary. Clinical characteristics were compared between women and men. Results: In the 903 participants consisting of 273 women and 630 men who were enrolled in this study, the overall prevalence of hypernatremia, defined as a serum sodium level ≥ 145 mmol/L, was 12.5%. Female participants showed significantly more frequent hypernatremia than male participants (17.6% vs 10.3%, p = 0.003) and higher serum sodium levels (median [interquartile range]; 143.0 [142.0, 144.0] vs 142.4 [141.5, 144.0], p < 0.001). Serum creatinine (sCr), but not estimated glomerular filtration rate (eGFR), was correlated with serum sodium levels (rs = − 0.108, p = 0.001). In the binary logistic regression analysis, female sex was significantly associated with hypernatremia (odds ratio, 1.89; 95% confidence interval, 1.23– 2.89; p = 0.004) even after adjusting for age, alcohol use, antihypertensive agent use, body mass index, and winter season. The association between female sex was reduced and no longer significant after adjusting for sCr, although the association remained unchanged after adjustment for eGFR. Conclusion: One-eighth of the older community dwellers in Japan exhibits hypernatremia after an overnight fast, and female sex is a significant risk factor. Since sCr is a surrogate of muscle mass, smaller muscle mass possibly mediates the association between female sex and hypernatremia. [ABSTRACT FROM AUTHOR]

Background: Hypernatremia is a major electrolyte disorder associated with death among critically ill patients. Glucocorticoid therapy may cause hypernatremia in refractory septic shock patients, but the association between glucocorticoid and intensive care unit (ICU)-acquired hypernatremia (IAH) remains unclear. The aim of this study was to clarify whether glucocorticoid administration was associated with IAH. Methods: This was a nested case–control study using data from an established cohort including 121 IAH cases identified from 1756 patients who were admitted to ICU in a tertiary care facility in Japan. We included patients who were admitted with a normal range of serum sodium concentrations (130–149 mEq/L) from January 1, 2013 to December 31, 2015 and remained in ICU for ≥ 2 days. Hypernatremia was defined as serum sodium concentration ≥ 150 mEq/L. Each case was matched to one control. Results: Multivariable conditional logistic regression revealed high-dose glucocorticoid {odds ratio (OR), 4.15 [95% confidence interval (CI) 1.29–13.4]}, acute kidney injury (AKI) [OR, 2.72 (95% CI 1.31–5.62)], and osmotic diuretics [OR, 3.44 (95% CI 1.41–8.39)] to be significantly associated with IAH. The contents and amounts of fluid infusion were not significantly associated with IAH. There were also significant duration–response effects between duration of glucocorticoid use and IAH; however, pulse glucocorticoid administration was not associated with IAH. Conclusion: In this nested case–control study, we demonstrated a significant association between IAH and high-dose glucocorticoid with significant duration–response effects. Serum sodium concentrations should be monitored carefully in critically ill patients administered prolonged high-dose glucocorticoid. [ABSTRACT FROM AUTHOR]

Background: Tolvaptan is used in Japan to reduce fluid retention caused by cirrhosis. However, hypernatremia is one of the most important side effects. This report is the first case report of a patient who developed hypernatremia after tolvaptan administration in the early stages following hepatectomy. Case presentation: A female patient in her 60s, who was admitted to the psychiatric department of a different hospital for bipolar disorder, developed hepatocellular carcinoma with cirrhosis. She was transferred to our hospital, and hepatectomy was performed in October 2019, after which pleural effusion and severe edema due to fluid retention were evident. Thus, the patient was started on tolvaptan (7.5 mg/day) from postoperative day (POD) 1. The patient began to experience disturbance of consciousness after POD 4. On the fifth day, the serum sodium (Na) level increased to 174 mEq/L, and hypernatremia was diagnosed. The Na level gradually improved with fluid infusion therapy, dropping to preoperative levels on the ninth day; her consciousness also gradually improved. Conclusions: Tolvaptan administration must be performed under strictly controlled conditions, followed by careful observation during the early postoperative period, when the patient's physical status is unstable. [ABSTRACT FROM AUTHOR]

Background: Hypernatremia and liver injury are typical adverse effects of tolvaptan. Therefore, hospitalization and frequent monitoring of serum sodium concentration and liver function are necessary for tolvaptan initiation. We performed a cross-sectional survey to evaluate these situations., Research Design and Methods: We employed the Japanese claims database, which contains data of patients aged < 75 years. Patients who were newly prescribed tolvaptan for fluid accumulation induced by chronic heart failure (FA-CHF) or liver cirrhosis (FA-LC) from January 2011 to June 2017 were included. We evaluated the hospitalization status and implementation of serum sodium and liver function tests in the evaluation period, based on the Japanese package insert., Results: Of 1,173 patients, 347 and 117 were enrolled in FA-CHF and FA-LC groups, respectively. Among them, 10.7% (FA-CHF group) and 5.13% (FA-LC group) were prescribed tolvaptan without hospitalization. In the FA-CHF group, 11.0% and 17.6% did not undergo serum sodium and liver function tests even once in the evaluation period, respectively, compared with 12.0% and 12.8% in the FA-LC group., Conclusions: Our results highlight the deviation from Japanese package insert recommendations. This approach can be applied to other drugs and provides important perspectives on pharmacovigilance research.

Background: Hypernatremia is one of the most commonly encountered electrolyte disorders in the emergency department (ED). Few studies have reported the seasonal fluctuations of the prevalence of hypernatremia with conflicting results. We investigated the seasonal prevalence of hypernatremia in an emergency department in Japan. Methods: A total of 12,598 patients presented to the ED between January 2015 and December 2017 were reviewed. The adult group aged between 18 and 64 years old consisted of 5427 patients and the elderly group aged over 65 years consisted of 7171 patients. Information collected included age, sex, serum sodium, and serum creatinine. Hypernatremia was defined as a serum sodium leve1 > 145 mEq/L, and moderate to severe hypernatremia was defined as a serum sodium level ≥ 150 mEq/L. Results: The prevalence of hypernatremia was significantly higher in the elderly group than in the adult group (2.6% vs. 0.7%; p < 0.001). Similarly, the prevalence of moderate to severe hypernatremia was significantly higher in the elderly group than in the adult group (1.0% vs. 0.1%; p < 0.001). The prevalence of hypernatremia and moderate to severe hypernatremia was significantly higher in the elderly group than in the adult group in all seasons. In the elderly group, the seasonal prevalence of moderate to severe hypernatremia was significantly higher during the winter. Also, there was a correlation between weather temperature and the prevalence of moderate to severe hypernatremia in the elderly group (r = − 0.34, p = 0.04). Conclusions: Hypernatremia is prevalent in the elderly and the prevalence is highest during the winter. Special attention should be paid in the elderly patients to prevent hypernatremia especially in the winter. [ABSTRACT FROM AUTHOR]

Background: It has been 7 years since tolvaptan was approved in Japan for the indication of heart failure in patients with volume overload; the drug can be used in patients with normonatremia. Hypernatremia was identified as a significant adverse event to be prevented., Methods and results: We compiled and analyzed data from 3,349 patients over 5 years to identify patients at high risk of hypernatremia with tolvaptan treatment. The incidence of hypernatremia, defined as serum sodium ≥150 mEq/L, was 3.65%. Baseline serum sodium concentrations, serum potassium concentrations, blood urea nitrogen : creatinine ratio, initial tolvaptan dose, and age were identified as risk factors for hypernatremia. A hypernatremia risk score was developed using the odds ratios for these factors. The high-risk population was defined as patients with a risk score ≥17.80., Conclusions: To prevent the occurrence of hypernatremic events in patients taking tolvaptan, we recommend a very low starting dose (i.e., 3.75 mg/day) in patients identified as being at high risk of hypernatremia using our new scoring process.