Development Of Hyponatremia Research Articles

Serum sodium level is inversely correlated with body temperature in children.

Several studies have demonstrated that non-osmotic antidiuretic hormone activity contributes to the development of hyponatremia in children with common febrile diseases. However, the relationship between hyponatremia and body temperature has remained unclear. We therefore examined this relationship in children with common diseases. In this retrospective case study based on a chart review, 1,973 children presenting with acute illnesses at Hirakata City Hospital between November 2008 and October 2009, and for whom blood test data were available, were enrolled. The median age of this cohort was 2.7 years and the mean serum sodium concentration was 136.4 mEq/L; 454 patients showed hyponatremia (<135 mEq/L). The patients were classified into four groups on the basis of body temperature, <37 °C, 37 °C (37.0-37.9 °C), 38 °C (38.0-38.9 °C) and ≥39 °C, and their serum sodium concentration was compared. The mean sodium level was significantly lower in febrile (135.9 mEq/L) than in non-febrile (138.5 mEq/L) patients. The mean serum sodium levels in the four temperature groups were, in ascending order, 138.5 mEq/L (95% CI, 138.3-138.8 mEq/L), 137.3 mEq/L (137.1-137.5 mEq/L), 136.1 mEq/L (135.8-136.3 mEq/L) and 134.6 mEq/L (134.4-134.9 mEq/L), respectively. The serum sodium level in each individual temperature range became significantly lower as body temperature increased (P < 0.001). There is a clear inverse correlation between serum sodium level and body temperature in children with common febrile diseases, and fever may play an important role in this relationship.

Analysis of the incidence and influencing factors of hyponatremia before 131I treatment of differentiated thyroid carcinoma.

BACKGROUNDHyponatremia is a common clinical electrolyte disorder. However, the association between hyponatremia and acute hypothyroidism is unclear. Acute hypothyroidism is usually seen in patients who undergo preparation for radioactive iodine therapy.AIMTo analyze the incidence and influencing factors of hyponatremia in a condition of iatrogenic acute hypothyroidism in patients with differentiated thyroid cancer (DTC) before 131I treatment.METHODSThe study group consisted of 903 DTC patients who received 131I treatment. The clinical data before and after surgery, as well as on the day of 131I treatment were analyzed. According to the blood sodium level before 131I treatment, patients were divided into the non-hyponatremia group and hyponatremia group. Correlations between serum sodium levels before 131I treatment and baseline data were analyzed. Univariate analysis and binary logistic regression were performed to identify the influencing factors of hyponatremia.RESULTSA total of 903 patients with DTC, including 283 (31.3%) males and 620 (68.7%) females, with an average age of 43.8 ± 12.7 years, were included in this study. The serum sodium levels before surgery and 131I treatment were 141.3 ± 2.3 and 140.5 ± 2.1 mmol/L, respectively (P = 0.001). However, the serum sodium levels in males and females before 131I treatment were lower than those before surgery. Patients aged more than 60 years and less than 60 years also showed decreased serum sodium levels before 131I treatment. In addition, the estimated glomerular filtration rate (eGFR) in males and females decreased before 131I treatment compared with those before surgery (P = 0.001). Moreover, eGFR in patients over 60 years and under 60 years decreased before 131I treatment, when compared with that before surgery. There were no significant differences in serum potassium, calcium, albumin, hemoglobin, and blood glucose in patients before surgery and 131I treatment (P > 0.05). Among the 903 patients, 23 (2.5%) were diagnosed with hyponatremia before 131I treatment, including 21 cases (91.3%) of mild hyponatremia and 2 cases (8.7%) of moderate hyponatremia. Clinical data showed that patients with mild hyponatremia had no specific clinical manifestations, while moderate hyponatremia cases were mainly characterized by fatigue and dizziness, which were similar to neurological symptoms caused by hypothyroidism and were difficult to distinguish. Correlation analysis showed a correlation between serum sodium before 131I treatment and the preoperative level (r = 0.395, P = 0.001). There was no significant correlation between blood sodium and thyroid-stimulating hormone (TSH) levels and urine iodine before 131I treatment (r = 0.045, P = 0.174; r = 0.013, P = 0.697). Univariate analysis showed that there were significant differences in age, sex, history of diuretic use, distant metastasis, preoperative blood sodium, blood urea nitrogen (BUN), eGFR, TSH and urinary iodine between the two groups (all P < 0.05). Logistic regression analysis showed that factors such as history of diuretic use, distant metastases, preoperative sodium and BUN were all influencing factors of hyponatremia. The Hosmer and Lemeshow test (c2 = 2.841, P = 0.944) suggested a high fit of the model. Omnibus tests of model coefficients indicated the overall significance of the model in this fitted model (P < 0.05). Preoperative serum sodium was a significant factor associated with pre-131I therapy hyponatremia (OR = 0.763; 95%CI: 0.627-0.928; P = 0.007).CONCLUSIONThe incidence of hyponatremia induced by 131I treatment preparation was not high. Preparation for radioactive iodine therapy was not a risk factor for the development of hyponatremia in thyroid cancer patients.

Development and Internal Validation of Machine Learning Algorithms for Predicting Hyponatremia After TJA.

The development of hyponatremia after total joint arthroplasty (TJA) may lead to several adverse events and is associated with prolonged inpatient length of stay as well as increased hospital costs. The purpose of this study was to develop and internally validate machine learning algorithms for predicting hyponatremia after TJA. A consecutive cohort of 30,703 TJA patients from an institutional registry at a large, tertiary academic hospital were included. A total of 19 potential predictor variables were collected. Hyponatremia was defined as a serum sodium concentration of <135 mEq/L. Five machine learning algorithms were developed using a training set and internally validated using an independent testing set. Algorithm performance was evaluated through discrimination, calibration, decision-curve analysis, and Brier score. The charts of 30,703 patients undergoing TJA were reviewed. Of those patients, 5,480 (17.8%) developed hyponatremia postoperatively. A combination of 6 variables were demonstrated to optimize algorithm prediction: preoperative serum sodium concentration, age, intraoperative blood loss, procedure time, body mass index (BMI), and American Society of Anesthesiologists (ASA) score. Threshold values that were associated with greater hyponatremia risk were a preoperative serum sodium concentration of ≤138 mEq/L, an age of ≥73 years, an ASA score of >2, intraoperative blood loss of >407 mL, a BMI of ≤26 kg/m2, and a procedure time of >111 minutes. The stochastic gradient boosting (SGB) algorithm demonstrated the best performance (c-statistic: 0.75, calibration intercept: -0.02, calibration slope: 1.02, and Brier score: 0.12). This algorithm was turned into a tool that can provide real-time predictions (https://orthoapps.shinyapps.io/Hyponatremia_TJA/). The SGB algorithm demonstrated the best performance for predicting hyponatremia after TJA. The most important factors for predicting hyponatremia were preoperative serum sodium concentration, age, intraoperative blood loss, procedure time, BMI, and ASA score. A real-time hyponatremia risk calculator was developed, but it is imperative to perform external validation of this model prior to using this calculator in clinical practice. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Нарушение осмотического баланса в условиях нетравматического субарахноидального кровоизлияния

Актуальность. Аневризматическое субарахноидальное кровоизлияние является распространенным и серьезным заболеванием, которое может приводить к летальным последствиям. Цель исследования: изучить динамику натриемии в контексте ее клинико-патогенетического значения у пациентов с субарахноидальным кровоизлиянием. Материалы и методы. Обследовано 87 пациентов с субарахноидальным кровоизлиянием, из них 38 (43,68 %) — с изолированным субарахноидальным кровоизлиянием, 14 (16,09 %) — с субарахноидально-паренхиматозным, 29 (33,33 %) — с субарахноидально-желудочковым, 6 (6,9 %) — с субарахноидально-паренхиматозно-желудочковым кровоизлиянием, общее количество смешанных кровоизлияний составляло 56,32 %. Для проведения полного ангиографического исследования использовали ангиографический комплекс AXIOM Artis MP «Siemens». Результаты. Исследование SIADH-синдрома (синдром неадекватной секреции антидиуретического гормона) с развитием гипонатриемии у пациентов с субарахноидальным кровоизлиянием нетравматического генеза свидетельствует о тесной ассоциации между выраженностью нарушений осмотического гомеостаза и тяжестью клинического течения субарахноидального кровоизлияния согласно модифицированной шкале Fisher, шкале WFNS, шкале Нunt &amp; Неss, шкале результатов GOSE (Glasgow Outcome Scale Extended) и обобщающей классификационной шкале для оценки прогноза исхода субарахноидального кровоизлияния (Ogilvy C.S. et Carter B.S.). У лиц с гипонатриемией на фоне субарахноидального кровоизлияния сопряженность сывороточного уровня натрия и показателя сывороточного уровня копептина адекватно и достоверно аппроксимируется уравнением регрессии логарифмического характера (по основанию 10), при значениях копептина более 0,70 нг/мл в более чем 50 % случаев регистрировалась натриемия средней тяжести. Выводы. Была обнаружена достоверная тесная взаимосвязь между уровнем данного пептида с нейроэндокринными свойствами — копептина и нарушением осмотического гомеостаза ионов натрия на фоне субарахноидального кровоизлияния с различной тяжестью клинического течения.

CLINICO-ETIOLOGICAL PROFILE OF HYPONATREMIA AMONG ADMITTED PATIENTS AT DR. RADHA KRISHNAN GOVT. MEDICAL COLLEGE AND HOSPITAL HAMIRPUR HIMACHAL PRADESH

Hyponatremia is a common electrolyte disturbance encountered in hospitals. It is dened as serum concentration &lt;135 meq/l. Various comorbidities predispose to the development of hyponatremia. Patient has symptoms of both hyponatremia as well as comorbidities. This contributes to increased morbidity and mortality .However early recognition and treatment makes prognosis better. Aim: To study clinical features of patients admitted with hyponatremia and investigate them to nd out various aetiologies. Methods And Material: Study was conducted at newly opened medical college at Hamirpur in Himachal Pradesh with limited facilities. A total of 50 patients with symptoms and documented hyponatremia were enrolled in study. Detailed history, clinical examination and laboratory investigations were done. Data thus collected was analysed. Results: Total number of patients was 50. Females were more as compared to males. Mean age of presentation was 67 years and lethargy ,nausea and vomiting were the most common symptoms. Diabetes mellitus and hypertension were the most common comorbidities. Among drugs diuretics were the most commonly used causing hyponatremia. Out of 50 patients 45 patients recovered and ve patients have to be referred because of comorbidities. Conclusions: Hyponatremia is a common problem and clinicians need to be aware of it mainly in the elderly patients. A systemic approach and simple diagnostic algorithm can signicantly improve the outcome in these patients. Treatment of hyponatremia is governed by levels of hyponatremia not by its etiology along with comorbid conditions.

Concurrent central diabetes insipidus and cerebral salt wasting disease in a post-operative case of craniopharyngioma: a case report

BackgroundWater and electrolyte disorders commonly encountered in children post-surgery involving hypothalamus and posterior pituitary, are central diabetes insipidus, syndrome of inappropriate secretion of anti-diuretic hormone and cerebral salt wasting disease. Delayed diagnosis and inadequate management of such cases may lead to worsened neurological outcomes with a high mortality rate.Case presentationHere we report the case of a 7-year-old girl who underwent surgical resection of a craniopharyngioma, following which she initially developed central diabetes insipidus. However, later on in the course of her illness she developed symptomatic hyponatremia with natriuresis which was diagnosed to be due to cerebral salt wasting disease. This combination of central diabetes insipidus and cerebral salt wasting syndrome is a rare occurrence and poses a diagnostic challenge. Diagnosis and management can be even more difficult when these conditions precede or coexist with each other.ConclusionIn such cases development of hyponatremia should always prompt consideration of unusual causes like cerebral salt wasting disease in addition to the classically described syndrome of inappropriate secretion of anti-diuretic hormone. Hence, a thorough knowledge of these disorders along with intensive monitoring of fluid and sodium status is critical for timely diagnosis and management of these patients.

Antipsychotic induced hyponatremia: Clinical case report

Akvilė Gaupšaitė1 1Vilnius University, Faculty of Medicine Abstract Introduction. Antipsychotics are one of the most commonly used medications in a psychiatric practice treating acute or chronic psychotic disorders. They often cause various adverse drug reactions (ADR), such as extrapyramidal symptoms, parkinsonism or metabolic syndrome. However, there is an increasing number of clinical cases of antipsychotic-induced hyponatremia, requiring hospitalization. Clinical case: we report the clinical case of a 52 year old patient with paranoid schizophrenia who has been taking antipsychotic medication for more than 5 years. He was admitted to the emergency department after a first tonic-clonic seizure due to severe hyponatremia. The patient was diagnosed with impaired antidiuretic hormone secretion syndrome, possibly caused by antipsychotic medications. Literature review: hyponatremia is one of the most common electrolyte disorders that afflict hospitalized patients. There are an increasing number of clinical cases where antipsychotics cause this electrolyte imbalance. One of the possible mechanisms for the development of hyponatremia is the syndrome of impaired antidiuretic hormone secretion, although further research on this topic remains needed. Conclusion: this case, like many others, highlights the gap in the outpatient treatment of psychiatric illnesses and the need to periodically monitor patients’ blood electrolytes or change treatment in a timely manner when prescribing antipsychotics. Keywords: antipsychotics, hyponatremia, syndrome of inappropriate antidiuretic hormone secretion.

Hyponatremia During Induction Therapy in Distinct Pediatric Oncological Cohorts: A Retrospective Study.

BackgroundHyponatremia is a well-known adverse event of repeated therapy with vincristine in oncological patients. However, to date, data in pediatric patients with malignant diseases other than acute lymphoblastic leukemia (ALL) are sparse or lacking.Materials and MethodsA retrospective study of 98 pediatric patients was conducted to analyze the incidence of hyponatremia in a Caucasian cohort of newly diagnosed ALL. For comparison, we further examined five other pediatric oncological cohorts (Hodgkin’s disease, Ewing sarcoma, Wilms tumor, benign glioma of the CNS, Langerhans cell histiocytosis) that receive alkaloids in their induction regimes.ResultsWe found a high incidence of hyponatremia (14.7%) in our ALL cohort with a trend toward male patients of elementary school age. None of the affected patients showed neurological symptoms. By comparison, patients from other malignancy groups did not show significant hyponatremia, regardless of their comparable therapy with alkaloids. We here show a noticeable coincidence of hyponatremia and hypertriglyceridemia in ALL patients, indicating a possible role of L-asparaginase-related hypertriglyceridemia in the development of severe hyponatremia in such patients.ConclusionWe report a higher incidence of hyponatremia following vincristine therapy in Caucasian children with ALL than published before. This hyponatremia could not be demonstrated in other oncologic cohorts treated with alkaloids. L-Asparaginase-induced hypertriglyceridemia may play a role in the certainly multifactorial development of hyponatremia in childhood leukemia.

Metabolic Acidosis and Hyponatremia in a Patient With Metastatic Melanoma

Metabolic Acidosis and Hyponatremia in a Patient With Metastatic Melanoma

Drugs associated with drug-induced hyponatremia. Focus on antihypertensive drugs and proton pump inhibitors

Hyponatremia (HN) is one of the leading water-electrolyte disorders in daily medical practice. A decrease in sodium level is dangerous with the development of various complications. Therefore, for effective prevention of HN and its complications, special attention should be paid to modifiable risk factors. One of the important causes leading to HN is drugs. Most often, HN develops during therapy with thiazide and thiazidelike diuretics. Risk factors for its development are history of thiazide-induced HN, advanced age, female sex, low body weight, and hypokalemia. The problem of thiazide-induced HN requires further study of the pathogenetic mechanisms and determination of the genetic factors underlying it. It is also necessary to remember about the possibility of HN development against the background of such drugs widely used in therapeutic practice as blockers of the renin-angiotensin-aldosterone system and proton pump inhibitors. In patients receiving therapy with the listed drugs, it is necessary to pay attention to the possible clinical manifestations of HN and to determine the sodium level in dynamics, which will effectively prevent the development of this disorder.

Drugs associated with drug-induced hyponatremia

Hyponatremia (HN) is a significant disturbance of the water-electrolyte balance in clinical practice. Drugs are one of the leading causes of low sodium level. Antidepressants, antiepileptic, antipsychotic, antineoplastic drugs and opioid analgesics are the most common medications that induce hyponatremia. Special attention should be paid to people with cancer, who often receive several drugs that induce HN. Risk factors for the development of drug-induced (DI) HN when taking most medications are female sex, weight loss, and old age. In persons receiving therapy with the listed drugs, it is necessary to assess the risk factors for a decrease in the sodium level, clinical manifestations from the nervous system, and to determine the sodium level in dynamics. Special care must be taken when treating elderly patients, since they have several risk factors for the development of DI HN. These measures will help prevent the development of HN and its severe and sometimes fatal complications.

Efficacy and Safety of Isotonic and Hypotonic Intravenous Maintenance Fluids in Hospitalised Children: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Hyponatraemia is a known complication in hospitalised children receiving maintenance intravenous fluid. Several studies have been published to investigate the efficacy and safety of intravenous fluids in children. However, there is still an ongoing debate regarding the ideal solution to be used in the paediatric population. Therefore, the aim of this meta-analysis was to investigate the safety and efficacy of administering isotonic versus hypotonic intravenous maintenance fluid in hospitalised children. An extensive search was undertaken on PubMed, Web of Science, Scopus, ScienceDirect, Google Scholar and Cochrane Library on 28 December 2020. Only randomised controlled trials (RCTs) were included. We used the random-effects model for all analyses. Risk ratio (RR) and mean difference with 95% confidence intervals (CIs) were used for dichotomous and continuous outcomes, respectively. The quality of each study was assessed using the Joanna Briggs Institute critical appraisal tool for RCTs. This study is registered with PROSPERO (CRD42021229067). Twenty-two RCTs with a total of 3795 participants were included. The studies encompassed surgical and medical patients admitted to intensive care unit as well as to general wards. We found that hypotonic fluid significantly increases the risk of hyponatremia at both ≤24 h (RR 0.34; 95% CI: 0.26–0.43, p < 0.00001) and >24 h (RR 0.48; 95% CI: 0.36–0.64, p < 0.00001). Isotonic fluid increases the risk of hypernatraemia at ≤24 h (RR 2.15; 95% CI: 1.24–3.73, p = 0.006). The prevalence of hyponatraemia was also higher in the hypotonic group at both ≤24 h (5.7% vs. 23.3%) and >24 h (6.0% vs. 26.3%). There was no statistically significant difference in the risk of developing adverse outcomes between the two groups. Mean serum and urine sodium as well as serum osmolality/osmolarity was lower in the hypotonic group. Isotonic solution is protective against the development of hyponatraemia while hypotonic solution increases the risk of hyponatraemia.

Iatrogenic hyponatremia in pediatrics: pathophysiology, classification and prevention

Dovile Gineityte1, Greta Habdanke1 1Lithuanian University of Health Sciences, Medical Academy, Faculty of Medicine, Kaunas, Lithuania Summary Introduction. Hyponatremia – it is an electrolyte natrium disbalance and it appears when serum natrium concentration decreases to <135 mmol/l. The development of iatrogenic hyponatremia is still a serious problem in clinical practice, often associated with infusion therapy […]

Hereditary tubulopathies accompanying polyuia

Tubulopathies are a group of heterogeneous diseases that are manifested in the malfunction of the renal tubules. This review addresses tubulopathies associated with polyuria syndrome, namely renal glucosuria syndrome, nephrogenic diabetes insipidus and pseudohyperaldosteronism. Types of renal glucosuria are described, namely: type A, type B and the most severe type 0. Type A is characterized by a low filtration threshold and low glucose reabsorption. The type of inheritance is autosomal recessive. Type B, autosomal dominant, is characterized by uneven activity of glucose transport, in which its reabsorption is reduced only in some nephrons. That is, normal reabsorption of glucose is maintained, but the filtration threshold of the latter is reduced. Type 0 with a severe course is characterized by complete inability of epithelial cells of the proximal tubules to reabsorb glucose. Nephrogenic diabetes insipidus is a rare inherited disease caused by impaired response of the renal tubules to antidiuretic hormone (ADH). Depending on the degree of inability to concentrate urine, there are complete and partial forms. It is divided into nephrogenic diabetes insipidus type I (X-linked recessive); nephrogenic diabetes insipidus type II (autosomal recessive and autosomal dominant) and nephrogenic diabetes insipidus syndrome with dementia and intracerebral calcifications (type of inheritance remains unknown). Children with autosomal recessive type of inheritance suffer from the more severe disease course. Pseudohypoaldosteronism is characterized by a special condition of the renal tubules which is due to insufficient sensitivity of the tubular epithelium to aldosterone, which in turn leads to hyperaldosteronism, the development of hyponatremia, metabolic acidosis with hyperkalemia, polydipsia and polyuria, decreased sodium reabsorption and retardation of the child's physical development. The classification includes three syndromes of pseudohypoaldosteronism, namely: type I (PHA1), which is divided into PHA1A (autosomal dominant, renal), PHA1B (autosomal recessive, systemic); type II (PHA2; Gordon’s syndrome), type III (secondary), which develops as a result of renal pathology.

Diaphragma sellae sinking can predict the onset of hyponatremia after transsphenoidal surgery for pituitary adenomas.

Sinking of the diaphragma sellae (DS) may stretch the pituitary stalk, which in turn impairs neurohypophyseal function; thus, it may play a role in the development of postoperative hyponatremia. We aimed to assess the factors influencing the development of hyponatremia after transsphenoidal surgery (TSS) for pituitary adenomas and analyze the effect of DS sinking on hyponatremia. After applying the inclusion and exclusion criteria, we retrospectively analyzed the clinical data of patients with pituitary adenoma who underwent TSS. The pituitary gland was scanned using a 3.0-T magnetic resonance imaging, and sagittal and coronal images were acquired. We evaluated the following: preoperative and postoperative hypothalamus‒pituitary‒thyroid axis function, hypothalamus‒pituitary‒adrenal axis function, intra-operative cerebrospinal fluid leaks, diabetes insipidus, hyponatremia, time from the day of surgery to the day of discharge, and time of hyponatremia onset. Of the 460 patients who had microscopic TSS for pituitary adenoma, 83 experienced postoperative hyponatremia. Hyponatremia occurred approximately 5.25days postoperatively and persisted for 5.54days. The lowest average blood sodium level was 123.9mEq/L, which occurred at 7.49days after surgery. Logistic regression analysis showed that the risk of hyponatremia was greater for patients with a significant DS sinking depth, a large pituitary stalk deviation angle difference, and a longer postoperative "measurable pituitary stalk". The difference in blood sodium levels between pre-TSS and 2days post-TSS was also an independent predictor of postoperative hyponatremia onset. DS sinking plays an important role in predicting hyponatremia onset after TSS for pituitary adenomas.

Approach to Hyponatremia

Hyponatremia is a common laboratory finding in numerous patients. It is defined as a serum sodium concentration &lt;135 mmol/L and represents an excess of water in the extracellular compartment. The severity of this electrolyte abnormality ranges from asymptomatic to seizures, coma and death as a consequence of cerebral swelling. There are multiple medical conditions, medications and disease states that can cause hyponatremia. This article summarizes the important pathophysiological pathways involved in the development of hyponatremia, describes an approach to common causes and reviews the initial steps in management.

Non‐thiazide diuretics and hospitalization due to hyponatraemia: A population‐based case‐control study

Diuretics are often implicated in hyponatraemia. While thiazides constitute one of the most common causes of hyponatraemia, data on loop diuretics and potassium-sparing agents are limited and partly conflicting. The objective of this investigation was to study the association between use of different types of non-thiazide diuretics and hospitalization due to hyponatraemia. This was a register-based case-control study on the adult Swedish population. By linking national registers, patients hospitalized with a principal diagnosis of hyponatraemia (n=11,213) from 1 October 2005 through 31 December 2014 were compared with matched controls (n=44,801). Multivariable logistic regression, adjusted for multiple confounders, was used to analyse the association between use of diuretics and hyponatraemia. In addition, newly initiated use (≤90days) and ongoing use were examined separately. Adjusted odds ratios (aORs) (95% CI) were 0.61 (0.57-0.66) for the use of furosemide, 1.69 (1.54-1.86) for the use of amiloride and 1.96 (1.78-2.18) for the use of spironolactone and hospitalization due to hyponatraemia. For newly initiated therapy, aORs ranged from 1.23 (1.04-1.47) for furosemide to 3.55 (2.75-4.61) for spironolactone. The aORs for ongoing use were 0.52 (0.47-0.57) for furosemide, 1.62 (1.47-1.79) for amiloride and 1.75 (1.56-1.98) for spironolactone. Ongoing use of furosemide was inversely correlated with hospitalization due to hyponatraemia, suggesting a protective effect. Consequently, if treatment with furosemide precedes the development of hyponatraemia by some time, other causes of hyponatraemia should be sought. Spironolactone and amiloride may both contribute to hyponatraemia; this effect is most prominent early in treatment.

Factors Associated with Hyponatremia in Patients Newly Prescribed Citalopram: A Retrospective Observational Study.

BackgroundHyponatremia is a common and under-recognized adverse drug reaction of selective serotonin re-uptake inhibitor (SSRI) antidepressants. Despite its clinical importance, there are few large-scale studies on the factors associated with hyponatremia.ObjectiveThe aim of this study was to determine the incidence of hyponatremia and to identify patient factors associated with hyponatremia in a large, population-based cohort initiating new prescriptions for citalopram.MethodsWe included all patients with a new prescription for citalopram during 2010–2017, inclusive, with baseline and post-initiation serum sodium values available. Data were obtained from an Alberta Health Pharmacy database to identify new citalopram prescriptions. Laboratory values for patients with new prescriptions were obtained from linked Calgary Laboratory Services data. Incident hyponatremia was defined as serum sodium level < 135 mmol/L, following prescription initiation. Associations were determined by performing Cox regression with time-varying covariate analysis, with the development of hyponatremia as the dependent variable.ResultsA total of 19,679 patients with new prescriptions were identified; 12,842 females and 6837 males. The mean age was 55.48 years (SD 21.35). Of these patients, 3250 (16.5%) developed hyponatremia, 1996 (15.5% of) females and 1254 (18.3% of) males (p = 0.002). Cox regression showed significant associations of hyponatremia with lower baseline sodium (HR 0.788), older age (HR 1.029), thiazide diuretic use (HR 1.141), and male sex (HR 1.168). Pharmaceutical manufacturer or strength of citalopram did not have significant effects on the development of hyponatremia.ConclusionThis study provides additional data on the predictors of hyponatremia among patients initiating citalopram therapy. We report a 16.5% incidence of hyponatremia after starting citalopram treatment, and significant new findings include a higher incidence in males. This is the first published incidence of hyponatremia following the initiation of citalopram treatment across all ages in Canada.

Serum sodium and eplerenone use in patients with a myocardial infarction and left ventricular dysfunction or heart failure: insights from the EPHESUS trial.

Sodium changes are common in myocardial infarction (MI) complicated with left ventricular systolic dysfunction (LVSD) and/or heart failure (HF). Sodium handling is fine-tuned in the distal nephron, were eplerenone exhibits some of its pleotropic effects. Little is known about the effect of eplerenone on serum sodium and the prognostic relevance of sodium alterations in patients with MI complicated with LVSD and/or HF. The EPHESUS trial randomized 6632 patients to either eplerenone or placebo. Hyponatremia and hypernatremia were defined as sodium < 135mmol/L or > 145mmol/L, respectively. Linear mixed models and time updated Cox regression analysis were used to determine the effect of eplerenone on sodium changes and the prognostic importance of sodium changes, respectively. The primary outcomes were all-cause mortality and a composite of cardiovascular (CV) mortality and CV-hospitalization. A total of 6221 patients had a post-baseline sodium measurement, 797 patients developed hyponatremia (mean of 0.2 events/per patient) and 1476 developed hypernatremia (mean of 0.4 events/per patient). Patients assigned to eplerenone had a lower mean serum sodium over the follow-up (140 vs 141mmol/L; p < 0.0001) and more often developed hyponatremia episodes (15 vs 11% p = 0.0001) and less often hypernatremia episodes (22 vs. 26% p = 0.0003). Hyponatremia, but not hypernatremia was associated with adverse outcome for all outcome endpoints in the placebo group but not in the eplerenone group (interaction p value < 0.05 for all). Baseline sodium values did not influence the treatment effect of eplerenone in reducing the various endpoints (interaction p value > 0.05 for all). Development of new-onset hyponatremia following eplerenone initiation did not diminish the beneficial eplerenone treatment effect. Eplerenone induces minor reductions in serum sodium. The beneficial effect of eplerenone was maintained regardless of the baseline serum sodium or the development of hyponatremia. Sodium alterations should not refrain clinicians from prescribing eplerenone to patients who had an MI complicated with LVSD and/or HF. ClinicalTrials.gov identifier: NCT00232180. Serum sodium and eplerenone use in patients with a myocardial infarction and left ventricular dysfunction or heart failure: insights from the EPHESUS trial.

PECULIARITIES OF IONOREGULATORY RENAL FUNCTION OF RATS IN THE DYNAMICS OF EXPERIMENTAL DIABETES MELLITUS DEVELOPMENT WITH UNDERLYING PHARMACOLOGICAL BLOCADE OF RENIN-ANGIOTENSINALDOSTERONE SYSTEM

The aim of the study – to explore the role of the renin-angiotensin-aldosteronesystem (RAAS) in the disturbance of ionoregulatory renal function in alloxan-inducedexperimental diabetes mellitus (EDM).Material and methods. The experiments were carried out on 78 white non-linearmature male rats with 11-, 26- and 46-day long alloxan-induced EDM with underlyingpharmacological blockade of RAAS by administration of kaptopril. The study ofionoregulating function of the kidneys was provided by the clearance method under thecondition of water 2-hour diuresis.Results. Pharmacological blockade of RAAS in rats with alloxan-induced EDM causedan intensification of natriuresis at all stages of the experiment: increased urinaryconcentration of sodium ions, its excretion and clearance. On the 11th day of EDM, thesodium filtration charge increased with the development of hyponatremia, proximal anddistal sodium reabsorption standardized in volume of glomerular filtrate (GF) decreased,kaliuresis was suppressed, and sodium-free water clearance elevated. In case of 26-daylong EDM, the sodium filtration charge decreased, its absolute and relative reabsorption,the distal sodium reabsorption standardized by GF increased. Kaliuresis increased. In46-day long EDM, the sodium filtration charge decreased, and hyponatremia enhanced.Absolute and relative sodium reabsorption reduced due to both – proximal and distal.Kaliuresis augmented, the clearance of sodium-free water declined.Conclusions. The increase in urinary sodium loss during the 11-day EDM is stipulatedby glomerular hyperfiltration, causing a functional weakening of the tubulotubularbalance and relative dysfunction of the distal segment of the nephron, emphasizing therenoprotective effect of RAAS on ionoregulatory function of the kidneys. The decrease inthe total reabsorption potential of the tubular segment of the nephron in the dynamics ofEDM development reflects on the proximal tubules, and preserved tubulotubular balancecertifies functional intactness of the distal tubules in 26-day long EDM. RAAS pathologicalactivation and attenuation of the renal blood flow autoregulation by tubuloglomerularfeedback may serve as an initiating factor in the development of tubular disorders in 26-day long alloxan diabetes with following progression in 46-day long EDM.