Point-of-care ultrasound is a useful adjunct tool to a clinician's assessment in the evaluation of severe hyponatraemia.

INTRODUCTION: Hyponatraemia is the most common electrolyte disorder in inpatients resulting mainly from an imbalance in water homeostasis. Intravascular fluid status assessment is pivotal but is often challenging given multimorbidity, polypharmacy and diuretics use. We evaluated the utility of point-of-care ultrasound (POCUS) as an adjunct tool to standard practice for fluid assessment in severe hyponatraemia patients. METHODS: Patients presenting with severe hyponatremia (Serum Sodium [Na] < 120 mmol/L; Normal range: 135-145 mol/L), managed by standard care were included. Hyponatraemia biochemistry work-up and POCUS examination were undertaken. Both clinician and POCUS independently assigned one of the three fluid status groups of hypovolaemia, hypervolaemia or euvolaemia. The final diagnosis of three fluid status groups at admission was made at the time of discharge by retrospective case review. Clinician's (standard of care) and POCUS fluid assessments were compared to that of the final diagnosis at the time of discharge. RESULTS: n = 19 patients were included. Median Na on admission was 113 mmol/L (109-116), improved to 129 ± 3 mmol/L on discharge. POCUS showed the higher degree of agreement with the final diagnosis (84%; n = 16/19), followed by the clinician (63%; n = 12/19). A trend towards higher accuracy of POCUS compared to clinician assessment of fluid status was noted (84% vs. 63%, p = 0.1611). Biochemistry was unreliable in 58% (n = 11/19) likely due to renal failure, polypharmacy or diuretic use. Inappropriate emergency fluid management was undertaken in 37% (n = 7/19) of cases based on initial clinician assessment. Thirst symptom correlated to hypovolaemia in 80% (4/5) cases. CONCLUSION: As subjective clinical and biochemistry assessments of fluid status are often unreliable due to co-morbidities and concurrent use of medications, POCUS can be a rapid objective diagnostic tool to assess fluid status in patients with severe hyponatraemia, to guide accurate emergency fluid management.

Serum sodium improvement: change in Comprehensive Geriatric Assessment parameters in geriatric patients with hyponatremia.

BACKGROUND: Hyponatremia presents with symptoms considered age-associated in the elderly. We assess the change in Comprehensive Geriatric Assessment (CGA) parameters after hyponatremia improvement in hospitalized geriatric patients. METHODS: We took 100 hyponatremic and same number of eunatremic geriatric patients (> 60 years) who were comorbidity, presenting-complaints, and age-matched. Four CGA parameters were utilized, the new Hindi Mental State Examination (HMSE), Barthel's index of activities of daily living (ADL), Timed up and go Test (TUG), and handgrip strength by hand dynamometer (HG). We analyzed these at admission and discharge, and their relationship with change in sodium levels. RESULTS: Average age was 68.1 ± 5.8 years, with males constituting 75%. The CGA parameters demonstrated worse values amongst the hyponatremia than the normonatremia group. Severe hyponatremia group showed worse CGA scores in comparison with moderate and mild. With improvement in sodium level, the improvements in ADL, TUG, and HMSE scores were greater in the hyponatremia group (8.8 ± 10.1, 2.2 ± 2.5, and 1.7 ± 2.3 respectively) in comparison to the normonatremia reference group (4.7 ± 9.0, 1 ± 2.0, and 0.7 ± 1.3 respectively, P < 0.05). CONCLUSION: Our study is the first utilizing HMSE to assess change in cognitive ability with improvement in serum sodium levels in the Indian elderly. Hyponatremic patients show worse baseline CGA parameters, and hyponatremia severity correlates with worse motor and cognitive function. Improvement in the serum sodium level improves the CGA parameters. Correction of hyponatremia in the geriatric age group significantly impacts life quality.

Chloride and Potassium Assessment Is a Helpful Tool for Differential Diagnosis of Thiazide-Associated Hyponatremia.

CONTEXT: Differential diagnosis of thiazide-associated hyponatremia (TAH) is challenging. Patients can either have volume depletion or a syndrome of inappropriate antidiuresis (SIAD)-like presentation. OBJECTIVE: To evaluate the impact of the simplified apparent strong ion difference in serum (aSID; sodium + potassium - chloride) as well as the urine chloride and potassium score (ChU; chloride - potassium in urine) in the differential diagnosis of TAH, in addition to assessment of fractional uric acid excretion (FUA). METHODS: Post hoc analysis of prospectively collected data from June 2011 to August 2013 from 98 hospitalized patients with TAH < 125 mmol/L enrolled at University Hospital Basel and University Medical Clinic Aarau, Switzerland. Patients were categorized according to treatment response in volume-depleted TAH requiring volume substitution or SIAD-like TAH requiring fluid restriction. We computed sensitivity analyses with ROC curves for positive predictive value (PPV) and negative predictive value (NPV) of aSID, ChU, and FUA in differential diagnosis of TAH. RESULTS: An aSID > 42 mmol/L had a PPV of 79.1% in identifying patients with volume-depleted TAH, whereas a value < 39 mmol/L excluded it with a NPV of 76.5%. In patients for whom aSID was inconclusive, a ChU < 15 mmol/L had a PPV of 100% and a NPV of 83.3%, whereas FUA < 12% had a PPV of 85.7% and a NPV of 64.3% in identifying patients with volume-depleted TAH. CONCLUSION: In patients with TAH, assessment of aSID, potassium, and chloride in urine can help identifying patients with volume-depleted TAH requiring fluid substitution vs patients with SIAD-like TAH requiring fluid restriction.

A Nationwide Analysis of Aneurysmal Subarachnoid Hemorrhage Mortality, Complications, and Health Economics in the USA.

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating neurological condition. Endovascular coiling or surgical clipping have equivocal success rates, but relatively little is known regarding the health economics and complications of these procedures at the population level. We aimed to analyze the complication profiles and healthcare resource utilization (HRCU) associated with the treatment of aSAH in the USA. We performed a retrospective analysis utilizing the IBM MarketScan database between 2008 and 2015. Primary outcomes included economic analysis stratified by post-operative complication; determination of the effect of several factors on total cost by multivariable regression; and analysis of the incidence, timing, and associated HCRU of aSAH-related post-operative complications. Of the 2374 patients meeting inclusion criteria for economic analysis, 1783 (75.1%) patients had at least one of the ten complications. The most common complications included hydrocephalus (43.8%), transient cerebral ischemia (including vasospasm) (30.6%), ischemic stroke (29.1%), syndrome of inappropriate antidiuretic hormone (SIADH)/hyposmolarity/hyponatremia (22.1%), and seizures (14.9%). Patients who experienced complications had higher median 90-day total costs [$161,127 (Q1 to Q3, $101,411 to $257,662)] than those who did not [$97,376 (Q1 to Q3, $55,692 to $147,447)]. Length of stay was longest for those with pulmonary embolism and pneumonia (27 days) and shortest for those with SIADH/hyposmolarity/hyponatremia (16 days). Brain compression/herniation had the highest mortality rate (19.5%). In total, 14.6% of all patients experienced a readmission within 30 days. In conclusion, patients with aSAH have high post-operative complication rates and costs. Development of novel interventions to reduce complications and improve outcomes is crucial.

Sodium assessment in neonates, infants, and children: a systematic review.

Hyponatremia is a common disorder in childhood. The indirect and the direct potentiometry are currently the most popular techniques employed for sodium assessment, although discrepancies between the two techniques may be > 10 mmol/L. It is known that < 20% of the recently published articles report information about the technique used for sodium analysis, but no data are available on pediatric studies. This study aimed at investigating the laboratory technique employed for sodium measurement in studies conducted in childhood. A systematic literature search in PubMed, Embase, and Web of Science was undertaken to identify articles containing the word "hyponatremia" in the title between 2013 and 2020. Papers with < 10 subjects were excluded. A total of 565 articles were included. Information on the laboratory technique used for sodium analysis was more commonly (p = 0.035) reported in pediatric (n = 15, 28%) than in non-pediatric (n = 81, 16%) reports. The frequency of reports with and without information on the technique for sodium assessment was not different with respect to the study characteristics, the quartile of the journal where the paper was published, the country income setting, and the inclusion of neonates among the 54 pediatric studies.   Conclusion: Most pediatric papers do not report any information on the technique used for sodium analysis. Although international authorities have recommended the implementation of direct potentiometry, a low awareness on this issue is still widespread in pediatric research. What is Known: • Direct potentiometry and indirect potentiometry are currently employed for sodium analysis in blood. • Direct potentiometry is more accurate. What is New: • Less than 30% of pediatric articles provide information on the technique employed for sodium analysis in blood. • Indirect potentiometry is more frequently employed than direct potentiometry in pediatric studies.

Serum Sodium Improvement: Effect on Comprehensive Geriatric Assessment Parameters in Hyponatremic Geriatric Patients in a Tertiary Care Center.

Hyponatremia prevalence is 22.2% in the geriatric age group as compared to 6% for other patients. Symptomatology of hyponatremia is subtle and is often interpreted as age-related in the geriatric patients. We use various Comprehensive Geriatric Assessment (CGA) parameters to analyze the impact of improvement in serum sodium levels. MATERIAL: We utilized four simple CGA parameters, the new Hindi Mental State Examination (HMSE) for assessing the cognition, Barthel index of activities of daily living (ADL) for the level of independence, Timed up and go test (TUG test) for risk of fall evaluation, and handgrip strength (HG) by hand dynamometer for frailty. All parameters were analyzed at admission and at discharge, and their relation with the severity of hyponatremia in 100 geriatric patients (>60 years) was seen. Equal number of hyponatremic geriatric patients were taken, matched for comorbidity, reason for presentation, and age. OBSERVATION: Mean age of the study population was 68.1 ± 5.8 years, with a male: female ratio of 3:1. Baseline sodium level in hyponatremia and normonatremia groups were 129.7 ± 5.1 and 139 ± 3.4 meq/L (P=2.4) respectively. All CGA parameters tested showed lower values among hyponatremic patients compared to normonatremic patients, although only ADL (71.6 ± 12.3 v/s 76.7 ± 11.5, P=0.001) and HMSE (23.4 ± 3.1 v/s 24.4 ± 2.4, P=0.01) were statistically significant. All parameters were worse in the severe hyponatremia group (Na<125 meq/L) compared to moderate (Na=125-130 meq/L) and mild (Na=130-135 meq/L), but significant only for TUG (17.9 ± 3.4 v/s 16.4 ± 4.2 v/s 14.6 ± 3.5, P=0.003, higher value being worse) and HMSE (21.1 ± 4.0 v/s 22.6 ± 2.8 v/s 24.1 ± 2.5, P=0.0007). Improvement in ADL, TUG, and HMSE scores with serum sodium improvement was significantly higher in the hyponatremia group (8.8 ± 10.1, 2.2 ± 2.5, and 1.7 ± 2.3 respectively) when compared to the normonatremic reference group (4.7 ± 9.0, 1 ± 2.0, and 0.7 ± 1.3 respectively, P<0.05). Although HG improvement was also greater, the difference was not statistically significant. CONCLUSION: Ours is the first study utilizing HMSE for assessing the cognition in the Indian patients. Hyponatremic patients have poor baseline CGA parameter values, and severity of hyponatremia correlates with poor motor and cognitive functions. Improvement in serum sodium levels improve CGA parameters. Hyponatremia correction should be prioritized in the elderly as it significantly impacts the quality of life in the elderly.

Multicentre randomised controlled trial: protocol for Plasma-Lyte Usage and Assessment of Kidney Transplant Outcomes in Children (PLUTO).

INTRODUCTION: Acute electrolyte and acid-base imbalance is experienced by many children following kidney transplantation. When severe, this can lead to complications including seizures, cerebral oedema and death. Relatively large volumes of intravenous fluid are administered to children perioperatively in order to establish perfusion to the donor kidney, the majority of which are from living and deceased adult donors. Hypotonic intravenous fluid is commonly used in the post-transplant period due to clinicians' concerns about the sodium, chloride and potassium content of isotonic alternatives when administered in large volumes.Plasma-Lyte 148 is an isotonic, balanced intravenous fluid that contains sodium, chloride, potassium and magnesium with concentrations equivalent to those of plasma. There is a physiological basis to expect that Plasma-Lyte 148 will reduce the incidence of clinically significant electrolyte and acid-base abnormalities in children following kidney transplantation compared with current practice.The aim of the Plasma-Lyte Usage and Assessment of Kidney Transplant Outcomes in Children (PLUTO) trial was to determine whether the incidence of clinically significantly abnormal plasma electrolyte levels in paediatric kidney transplant recipients will be different with the use of Plasma-Lyte 148 compared with intravenous fluid currently administered. METHODS AND ANALYSIS: PLUTO is a pragmatic, open-label, randomised controlled trial comparing Plasma-Lyte 148 to current care in paediatric kidney transplant recipients, conducted in nine UK paediatric kidney transplant centres.A total of 144 children receiving kidney transplants will be randomised to receive either Plasma-Lyte 148 (the intervention) intraoperatively and postoperatively, or current fluid. Apart from intravenous fluid composition, all participants will receive standard clinical transplant care.The primary outcome measure is acute hyponatraemia in the first 72 hours post-transplant, defined as laboratory plasma sodium concentration of <135 mmol/L. Secondary outcomes include symptoms of acute hyponatraemia, other electrolyte and acid-base imbalances and transplant kidney function.The primary outcome will be analysed using a logistic regression model adjusting for donor type (living vs deceased donor), patient weight (<20 kg vs ≥20 kg pretransplant) and transplant centre as a random effect. ETHICS AND DISSEMINATION: The trial received Health Research Authority approval on 20 January 2020. Findings will be presented to academic groups via national and international conferences and peer-reviewed journals. The patient and public involvement group will play an important part in disseminating the study findings to the public domain. TRIAL REGISTRATION NUMBERS: 2019-003025-22 and 16586164.

Prevalence, prognostic value, pathophysiology, and management of hyponatraemia in children and adolescents with COVID-19.

Hyponatraemia is frequently encountered in adults with coronavirus disease 2019 (COVID-19) and is associated with poor prognosis. This review aims to describe for the first time the prevalence, aetiology, prognostic value, pathophysiology, and management of hyponatraemia in children and adolescents with COVID-19, taking into account all relevant studies published in PubMed and Cochrane Library studies until 26th September 2021. Literature search did not detect any studies evaluating the prevalence and prognostic value of sodium disorders in paediatric patients with COVID-19. A broader literature review showed a high prevalence of hyponatraemia in children with bacterial pneumonia, while some studies have reported that hyponatraemia is relatively common in Multisystem Inflammatory Syndrome in Children (MIS-C). In adults with COVID-19, an inverse association between sodium and interleukin-6 levels has been found, indicating that hyponatraemia could be used as a surrogate marker for the risk of cytokine storm and may facilitate the identification of patients who could benefit from immunomodulatory agents. Studies are urgently needed to evaluate the frequency and prognostic impact of electrolyte abnormalities in children with COVID-19. In the meantime, clinicians are urged to consider hyponatraemia in children with COVID-19 as a potential red flag, investigate the cause and administer fluids and other therapies accordingly.

MANAGEMENT OF ENDOCRINE DISEASE: Dysnatraemia in COVID-19: prevalence, prognostic impact, pathophysiology, and management.

This review examines the prevalence, aetiology, pathophysiology, prognostic value, and investigation of dysnatraemia in hospitalised COVID-19 patients, taking into account all relevant studies published in PubMed and Cochrane Library studies until March 2021. Hyponatraemia is commonly observed in patients with bacterial pneumonia and is an independent predictor for excess mortality and morbidity. However, it remains unknown whether this association applies to coronavirus disease-2019 (COVID-19). Several studies reported a 20-35% prevalence for hyponatraemia and 2-5% for hypernatraemia in patients admitted with COVID-19. In addition, hyponatraemia on admission was a risk factor for progression to severe disease, being associated with an increased likelihood for the need for invasive mechanical ventilation, with an odds ratio (OR) of 1.83-3.30. Hyponatraemia seems to be an independent risk factor for mortality, with an OR of 1.40-1.50 compared to normonatraemia, while hypernatraemia is related to even worse outcomes than hyponatraemia. Furthermore, preliminary data show an inverse association between serum sodium and interleukin-6 levels, suggesting that hyponatraemia might be used as a surrogate marker for the risk of a cytokine storm and the need for treatment with interleukin antagonists. In conclusion, dysnatraemia is common and carries a poor prognosis in COVID-19 patients, indicating that it may play a future role in risk stratification and individualising therapy.

Electrolyte and acid-base disorders in cancer patients and its impact on clinical outcomes: evidence from a real-world study in China.

Background: This study aims to delineate the incidence of electrolyte and acid-base disorders (EAD) in cancer patients, to figure out the risk factors of EAD, then to assess the impact of EAD on patients' in-hospital clinical outcomes.Methods: Patients with the diagnosis of malignancies hospitalized during 1 October 2014 and 30 September 2015 were recruited in Zhongshan Hospital, Fudan University in Shanghai of China. Demographic characteristics, comorbidities, and clinical data, including survival, length of stay and hospital cost, were extracted from the electronic medical record system. Electrolyte and acid-base data were acquired from the hospital laboratory database.Results: Of 25,881 cancer patients with electrolyte data, 15,000 (58.0%) cases had at least one electrolyte and acid-base abnormity. Hypocalcemia (27.8%) was the most common electrolyte disorder, followed by hypophosphatemia (26.7%), hypochloremia (24.5%) and hyponatremia (22.5%). The incidence of simple metabolic acidosis (MAC) and metabolic alkalosis (MAL) was 12.8% and 22.1% respectively. Patients with mixed metabolic acid-base disorders (MAC + MAL) accounted for 30.2%. Lower BMI score, preexisting hypertension and diabetes, renal dysfunction, receiving surgery/chemotherapy, anemia and hypoalbuminemia were screened out as the major risk factors of EAD. In-hospital mortality in patients with EAD was 2.1% as compared to those with normal electrolytes (0.3%). The risk of death significantly increased among patients with severe EAD. Similarly, the length of stay and hospital cost also tripled as the number and grade of EAD increased.Conclusion: EAD is commonly encountered in cancer patients and associated with an ominous prognosis. Patients with comorbidities, renal/liver dysfunction, and anti-tumor therapy have a higher risk of EAD. Regular monitoring of electrolytes, optimum regimen for intravenous infusion, timely correction of modifiable factors and appropriate management of EAD should not be neglected during anti-tumor treatment.

Clinical experience with Tolvaptan outpatient use. Cost and effectiveness in 9 cases.

INTRODUCTION: Tolvaptan introduction has constituted the main therapeutic novelty in the management of hyponatremia in recent years. OBJECTIVE: To describe the experience with this drug at Complejo Asistencial Universitario de León, Spain. METHOD: Retrospective, observational study of tolvaptan outpatient use in a tertiary care hospital from March 2014 to August 2017. RESULTS: A total of 9 patients were treated with tolvaptan in the outpatient setting. Eunatremia was reached in 24 h by 23.1%. After tolvaptan administration, a reduction in days of hospitalization was recorded (361 vs. 70; p = 0.007), especially in those days of hospitalization that were attributable to hyponatremia (306 vs. 49; p = 0.009). CONCLUSIONS: Long-term use of tolvaptan appears to be safe and is associated with a decrease in days of hospitalization.

INTRODUCCIÓN: La introducción de tolvaptan ha supuesto la principal novedad en el tratamiento de la hiponatremia en los últimos años. OBJETIVO: Describir la experiencia con tolvaptan en el Complejo Asistencial Universitario de León, España. MÉTODO: Estudio observacional retrospectivo de utilización ambulatoria de tolvaptan en un hospital de tercer nivel, de marzo de 2014 a agosto de 2017. RESULTADOS: Fueron tratados con tolvaptan de forma ambulatoria nueve pacientes, 23.1 % alcanzó eunatremia en 24 horas. Posterior a la administración de tolvaptan se registró reducción en días de hospitalización (361 versus 70, p = 0.007), especialmente por hiponatremia (306 versus 49, p = 0.009). CONCLUSIONES: El uso a largo plazo de tolvaptan parece ser seguro y se relaciona con descenso en los días de hospitalización.

Experiencia clínica con el uso ambulatorio de tolvaptan. Costes y efectividad en nueve casos / Clinical experience with Tolvaptan outpatient use. Cost and effectiveness in 9 cases

Resumen Introducción: La introducción de tolvaptan ha supuesto la principal novedad en el tratamiento de la hiponatremia en los últimos años. Objetivo: Describir la experiencia con tolvaptan en el Complejo Asistencial Universitario de León, España. Método: Estudio observacional retrospectivo de utilización ambulatoria de tolvaptan en un hospital de tercer nivel, de marzo de 2014 a agosto de 2017. Resultados: Fueron tratados con tolvaptan de forma ambulatoria nueve pacientes, 23.1 % alcanzó eunatremia en 24 horas. Posterior a la administración de tolvaptan se registró reducción en días de hospitalización (361 versus 70, p = 0.007), especialmente por hiponatremia (306 versus 49, p = 0.009). Conclusiones: El uso a largo plazo de tolvaptan parece ser seguro y se relaciona con descenso en los días de hospitalización.

Abstract Introduction: Tolvaptan introduction has constituted the main therapeutic novelty in the management of hyponatremia in recent years. Objective: To describe the experience with this drug at Complejo Asistencial Universitario de León, Spain. Method: Retrospective, observational study of tolvaptan outpatient use in a tertiary care hospital from March 2014 to August 2017. Results: A total of 9 patients were treated with tolvaptan in the outpatient setting. Eunatremia was reached in 24 h by 23.1%. After tolvaptan administration, a reduction in days of hospitalization was recorded (361 vs. 70; p = 0.007), especially in those days of hospitalization that were attributable to hyponatremia (306 vs. 49; p = 0.009). Conclusions: Long-term use of tolvaptan appears to be safe and is associated with a decrease in days of hospitalization.

Costs associated with unplanned readmissions among patients with heart failure with and without hyponatremia.

PURPOSE: Costs associated with unplanned readmissions among patients with heart failure with and without hyponatremia were studied. METHODS: This study estimated the costs of patients hospitalized for heart failure (HF) discharged with or without corrected sodium. A model was developed to monetize the 30-day readmission risk based on hyponatremia correction. Costs of discharging patient with corrected versus uncorrected hyponatremia were estimated using readmission rates from a previously published study and hospitalization costs from the Healthcare Costs and Utilization Cost Project and the Premier Healthcare Database. RESULTS: Discharging patients with HF and hyponatremia increased costs from $488-$569 per discharge compared to patients with corrected hyponatremia. This range reflected differences in readmission rates and sources of hospitalization costs. Sensitivity analyses showed hospitalization costs and readmission rates had the largest impact on model results. CONCLUSION: A retrospective study supports the value of upfront monitoring and correction of low serum sodium levels before discharge among patients with HF and hyponatremia by presenting an economic argument in addition to the clinical rational for reducing risk of readmission.

ICU Emergencies Simulation Curriculum for Critical Care Fellows: Neurologic Emergencies.

Introduction: The management of neurologic emergencies is an important component of critical care fellowship training. Additional training in neurocritical care has been demonstrated to improve clinical outcomes, though exposure to these emergencies during training can be limited. Methods: Three simulation cases are presented as part of a comprehensive neurologic emergencies curriculum for critical care trainees. The cases represent neurologic catastrophes encountered in the intensive care unit consisting of symptomatic hyponatremia, severe alcohol withdrawal syndrome, and brain herniation syndrome. The case descriptions are complete with learning objectives, critical actions checklists, and debriefing material for facilitators, as well as all necessary personnel briefs and required equipment. Results: The scenarios were completed over the course of the 2016-2017 academic year by first-year critical care fellows. Following curriculum implementation, there was an improvement in self-perceived confidence of fellows in neurologic emergency management skills. Discussion: The cases were felt to be realistic and beneficial and led to perceived improvement in management of neurologic emergencies and leadership during clinical crises.

Clinical characteristics of autoimmune GFAP astrocytopathy.

The clinical features of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy remain to be elucidated. We describe here the clinical features of 14 patients with GFAP astrocytopathy confirmed by detection of GFAP-IgG in cerebrospinal fluid (CSF). The novel findings of this study are as follows. First, over half of the patients presented with movement disorders (tremor, myoclonus, and ataxia), autonomic dysfunction (mainly urinary dysfunction), and hyponatremia. Second, most patients showed transient elevation of adenosine deaminase activity levels in CSF. Finally, some patients showed bilateral hyperintensities in the posterior part of the thalamus on brain magnetic resonance imaging.

Association of Hyponatraemia and Antidepressant Drugs: A Pharmacovigilance-Pharmacodynamic Assessment Through an Analysis of the US Food and Drug Administration Adverse Event Reporting System (FAERS) Database.

BACKGROUND: Hyponatraemia induced by antidepressant drugs is a rare but potentially life-threatening adverse reaction. Whether it is associated with all or only some antidepressant drugs is still unclear. This needs to be clarified to guide antidepressant therapies, especially in patients with electrolytic imbalances. OBJECTIVES: The primary objective of this study was to quantify the strength of association between the use of different antidepressant drugs and hyponatraemia by using information reported to the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). The secondary objective was to investigate the putative relationship between different antidepressant pharmacological targets and the risks of hyponatraemia induced by antidepressant drugs using the 'pharmacovigilance-pharmacodynamic' method. METHODS: We used the FAERS database to conduct a case/non-case analysis on spontaneous reports, focusing on events of hyponatraemia/syndrome of inappropriate antidiuretic hormone secretion (SIADH) reported in connection with the use of antidepressant drugs. Risk was expressed as a measure of disproportionality using the reporting odds ratio while adjusting for sex, age and concomitant medications associated with hyponatraemia/SIADH. We assessed to what extent the receptor-binding properties of antidepressant drugs could associate with the reporting odds ratios of hyponatraemia/SIADH of antidepressant drugs, building a linear regression model that included as independent variables the binding affinities (pKi) to the serotonin transporter, dopamine transporter, norepinephrine transporter, and serotonin 5-HT2C, 5-HT2A and 5-HT1A, and α1- and α2-adrenergic receptors. RESULTS: There were 2233 reports identified. The adjusted reporting odds ratio for the association between antidepressant drug use and hyponatraemia was 1.91 (95% confidence interval 1.83-2.00). The association was strongest for mirtazapine, followed by selective serotonin reuptake inhibitors, and lowest with serotonin-modulating antidepressant drugs. A significant linear correlation was found between the adjusted reporting odds ratios for hyponatraemia and pKi for the adrenergic receptors α1 and α2. CONCLUSIONS: Hyponatraemia is reported at a disproportionately higher level with classes of antidepressant drugs (noradrenergic and specific serotonergic antidepressant [mirtazapine] and serotonin modulators [vortioxetine]) that are in general considered to have a better profile of tolerability in terms of hyponatraemia. With regard to the presented results, the risk of hyponatraemia with mirtazapine appears to be greater than what was reported in the literature; however, confounding by indication cannot be ruled out. Our pharmacovigilance-pharmacodynamic analysis also indicates that inhibition of the serotonin transporter may not be involved in the hyponatraemia linked to the use of antidepressant drugs.

Successful management of severe hyponatremia in CKD-VD: In a cost limited setting.

Patients with end stage renal disease (ESRD) and severe hyponatremia always pose a challenge to manage. It is necessary to correct biochemical parameters, advanced azotemia, and fluid overload with conventional haemodialysis (HD) but it may correct serum sodium (Na) rapidly resulting in neurological complications like seizures and osmotic demyelination syndrome. Continuous renal replacement therapy (CRRT) is an ideal modality to manage such patients. However, most of the centers in the developing or underdeveloped nations do not have CRRT facility. We present two cases of ESRD, who had advanced azotemia requiring dialysis, also had persistent vomiting and severe hyponatremia (one with Na 107, another with Na 109 mEq/L), both cases were managed with conventional HD using dialysate Na concentration of 128 mEq/L (lowest permissible level of Na in a traditional HD machine) and keeping the blood flow of 50 mL/min. The serum Na increased by 1 mEq/L/h during first HD session, during the next session blood flow increased to 100 mL/min, and serum Na increased by two mEq/L/h. At the end of 48 hours, we were able to successfully correct serum Na by 18 mEq/L, with complete resolution of uremic manifestations and no neurological deficits. The current reports highlight management of hyponatremia in newly diagnosed ESRD in a cost limited setting.