Initial dysnatremia and clinical outcomes in pediatric traumatic brain injury: a multicenter observational study.

PURPOSE: We aimed to investigate the association between initial dysnatremia (hyponatremia and hypernatremia) and in-hospital mortality, as well as between initial dysnatremia and functional outcomes, among children with traumatic brain injury (TBI). METHOD: We performed a multicenter observational study among 26 pediatric intensive care units from January 2014 to August 2022. We recruited children with TBI under 18 years of age who presented to participating sites within 24 h of injury. We compared demographics and clinical characteristics between children with initial hyponatremia and eu-natremia and between those with initial hypernatremia and eu-natremia. We defined poor functional outcome as a discharge Pediatric Cerebral Performance Category (PCPC) score of moderate, severe disability, coma, and death, or an increase of at least 2 categories from baseline. We performed multivariable logistic regression for mortality and poor PCPC outcome. RESULTS: Among 648 children, 84 (13.0%) and 42 (6.5%) presented with hyponatremia and hypernatremia, respectively. We observed fewer 14-day ventilation-free days between those with initial hyponatremia [7.0 (interquartile range (IQR) = 0.0-11.0)] and initial hypernatremia [0.0 (IQR = 0.0-10.0)], compared to eu-natremia [9.0 (IQR = 4.0-12.0); p = 0.006 and p < 0.001]. We observed fewer 14-day ICU-free days between those with initial hyponatremia [3.0 (IQR = 0.0-9.0)] and initial hypernatremia [0.0 (IQR = 0.0-3.0)], compared to eu-natremia [7.0 (IQR = 0.0-11.0); p = 0.006 and p < 0.001]. After adjusting for age, severity, and sex, presenting hyponatremia was associated with in-hospital mortality [adjusted odds ratio (aOR) = 2.47, 95% confidence interval (CI) = 1.31-4.66, p = 0.005] and poor outcome (aOR = 1.67, 95% CI = 1.01-2.76, p = 0.045). After adjustment, initial hypernatremia was associated with mortality (aOR = 5.91, 95% CI = 2.85-12.25, p < 0.001) and poor outcome (aOR = 3.00, 95% CI = 1.50-5.98, p = 0.002). CONCLUSION: Among children with TBI, presenting dysnatremia was associated with in-hospital mortality and poor functional outcome, particularly hypernatremia. Future research should investigate longitudinal sodium measurements in pediatric TBI and their association with clinical outcomes.

Updates in hyponatremia and hypernatremia.

PURPOSE OF REVIEW: Hyponatremia and hypernatremia are commonly encountered electrolyte abnormalities that require timely and careful intervention, as they can be associated with significant morbidity and mortality. RECENT FINDINGS: This review article addresses the etiology, presentation, diagnosis, and management of both hyponatremia and hypernatremia, emphasizing the latest advancements and emerging trends in pediatric care. SUMMARY: A methodical approach is needed to accurately assess and treat hyponatremia and hypernatremia. Both conditions continue to rely on serum and urine testing, however newer tests such as copeptin and stimulated testing may hold promise to further refine testing in the future.

Dapagliflozin induced hypernatremia via osmotic diuresis: a case report.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been widely used. They inhibit proximal tubular glucose reabsorption, resulting in glycosuria. Herein, we report the case of a 65-year-old woman who presented with hypernatremia during the perioperative period of a subarachnoid hemorrhage. The patient continued to take dapagliflozin postoperatively and subsequently developed severe hypernatremia. Based on the urinalysis findings, we diagnosed osmotic diuresis due to glycosuria as contributing to hypernatremia. Hypernatremia improved with the discontinuation of dapagliflozin and the administration of a hypotonic infusion. In the perioperative period, physicians should discontinue SGLT2 inhibitors owing to concerns about the development of hypernatremia.

Challenges in using fractional excretion of sodium in the assessment of salt poisoning.

AIM: Hypernatraemia typically reflects dehydration, yet in rare instances may be caused by salt poisoning. Identifying these rare cases is a difficult challenge. Making the diagnosis of salt poisoning can have severe consequences, such as the removal of the child from its home or even prison sentences for the implicated carer. It is therefore imperative to get the diagnosis right. Guidelines for the assessment of hypernatraemia emphasise the importance of the fractional excretion of sodium to distinguish between dehydration and salt poisoning, but no generally accepted cut-off value exists. Opinions about the diagnosis of salt poisoning in some cases consequently may differ. Here, we aim to highlight the challenges and stimulate discussion on how to improve the tools for the assessment of hypernatraemia. METHODS: Report of a case of unexplained hypernatraemia in which the treating paediatrician raised the suspicion of salt poisoning. RESULTS: Two consulted experts made opposing judgements about the aetiology of the observed hypernatraemia. CONCLUSION: Clear diagnostic criteria for the diagnosis of salt poisoning are lacking and more data are needed for their establishment. Without this, victims may experience further harm and carers are at risk of devastating, yet potentially erroneous accusations.

Hypodipsic hypernatremia after long-standing polydipsia in a cat with suspect neonatal head trauma.

A 16-month-old neutered male domestic shorthair cat weighing 2.7 kg was referred for further evaluation of acute generalized muscle weakness and paraparesis after a long-standing history of polyuria-polydipsia. The diagnosis of hypodipsic/adipsic hypernatremia relied on the key findings of absent spontaneous drinking despite hypernatremia and a hyperosmolar state (444.8 mOsm/kg, reference interval 280 to 310 mOsm/kg). Brain MRI revealed severe multifocal anatomic anomalies of the rostral calvarium and the forebrain, suggestive of encephaloclastic porencephaly. Involvement of the thalamic and hypothalamic regions could have been responsible for the cat's adipsic hypernatremia. The unique aspects of this case were the rare description of central nervous system disease leading to hypodipsia, and the history of chronic polydipsia before the acute onset of hypodipsia. Key clinical message: Multifocal abnormalities of the forebrain can present with polyuria-polydipsia syndrome, hypodipsia/adipsia, or both, depending on the stage of the disease. This likely happens when the hypothalamic and thalamic regions are affected, since they regulate antidiuretic hormone release and thirst, respectively.

Hypernatrémie hypodipsique après polydipsie ancienne chez un chat suspect de traumatisme crânien néonatal. Un chat domestique à poil court mâle castré âgé de 16 mois et pesant 2,7 kg a été référé pour une évaluation plus approfondie de faiblesse musculaire aiguë généralisée et de paraparésie après une longue histoire de polyurie-polydipsie. Le diagnostic d'hypernatrémie hypodipsique/adipsique reposait sur les principales conclusions de l'absence d'abreuvement spontané malgré l'hypernatrémie et un état hyperosmolaire (444,8 mOsm/kg, intervalle de référence de 280 à 310 mOsm/kg). L'IRM du cerveau a révélé des anomalies anatomiques multifocales sévères de la calotte crânienne rostrale et du prosencéphale évoquant une porencéphalie encéphaloclastique. L'atteinte des régions thalamique et hypothalamique pourrait être responsable de l'hypernatrémie adipsique du chat. Les aspects uniques de ce cas étaient la description rare d'une maladie du système nerveux central conduisant à l'hypodipsie, et l'histoire de la polydipsie chronique avant l'apparition aiguë de l'hypodipsie.Message clinique clé :Les anomalies multifocales du cerveau antérieur peuvent présenter un syndrome de polyurie-polydipsie, une hypodipsie/adipsie, ou les deux, selon le stade de la maladie. Cela se produit probablement lorsque les régions hypothalamique et thalamique sont affectées, car elles régulent respectivement la libération d'hormone antidiurétique et la soif.(Traduit par Dr Serge Messier).

Diagnosis and Management of Sodium Disorders: Hyponatremia and Hypernatremia.

Hyponatremia and hypernatremia are electrolyte disorders that can be associated with poor outcomes. Hyponatremia is considered mild when the sodium concentration is 130 to 134 mEq per L, moderate when 125 to 129 mEq per L, and severe when less than 125 mEq per L. Mild symptoms include nausea, vomiting, weakness, headache, and mild neurocognitive deficits. Severe symptoms of hyponatremia include delirium, confusion, impaired consciousness, ataxia, seizures, and, rarely, brain herniation and death. Patients with a sodium concentration of less than 125 mEq per L and severe symptoms require emergency infusions with 3% hypertonic saline. Using calculators to guide fluid replacement helps avoid overly rapid correction of sodium concentration, which can cause osmotic demyelination syndrome. Physicians should identify the cause of a patient's hyponatremia, if possible; however, treatment should not be delayed while a diagnosis is pursued. Common causes include certain medications, excessive alcohol consumption, very low-salt diets, and excessive free water intake during exercise. Management to correct sodium concentration is based on whether the patient is hypovolemic, euvolemic, or hypervolemic. Hypovolemic hyponatremia is treated with normal saline infusions. Treating euvolemic hyponatremia includes restricting free water consumption or using salt tablets or intravenous vaptans. Hypervolemic hyponatremia is treated primarily by managing the underlying cause (e.g., heart failure, cirrhosis) and free water restriction. Hypernatremia is less common than hyponatremia. Mild hypernatremia is often caused by dehydration resulting from an impaired thirst mechanism or lack of access to water; however, other causes, such as diabetes insipidus, are possible. Treatment starts with addressing the underlying etiology and correcting the fluid deficit. When sodium is severely elevated, patients are symptomatic, or intravenous fluids are required, hypotonic fluid replacement is necessary.

[Hypernatremia in hospital]. / Hypernatrémie en milieu hospitalier.

Hypernatremia, defined as a serum sodium concentration greater than 145 mmol/l, is an electrolyte disorder associated with increased in-hospital morbidity and mortality. Its prevalence is estimated between 1 to 3% in hospitalized patients and up to 11% in intensive care. It most often results from an impaired thirst mechanism or the inability to access water to drink. The clinical presentation varies depending on the severity of the hypernatremia. Patients may be pauci-symptomatic to comatose. Correcting too quickly the hypernatremia can lead to serious consequences (cerebral hemorrhage, demyelination). Prevention of the onset of hypernatremia is essential in the hospital. Its management consists of treating the underlying cause and correcting the hyperosmolarity by ensuring close monitoring of the sodium level.

L'hypernatrémie, définie par une concentration en sodium dans le sang supérieur à 145 mmol/l, est un trouble électrolytique associé à une morbimortalité hospitalière accrue. Sa prévalence est estimée entre 1 et 3 % chez les patients hospitalisés et jusqu'à 11 % aux soins intensifs. Elle résulte le plus souvent d'une altération du mécanisme de la soif ou d'une incapacité d'accès à l'eau. La présentation clinique varie en fonction de la sévérité de l'hypernatrémie. Les patients peuvent être paucisymptomatiques jusqu'à devenir comateux. Sa correction trop rapide peut engendrer des conséquences dévastatrices (hémorragies cérébrales, démyélinisation). La prévention de son apparition est essentielle à l'hôpital. Sa prise en charge consiste à traiter l'étiologie et corriger l'hyperosmolarité en assurant un suivi rapproché de la natrémie.

Congenital Diarrhoea In A Neonate With Hypernatraemia And Dehydration.

Diarrhoea, vomiting, and dehydration are frequently encountered in neonatal emergency. However, it is challenging to manage resistant hypernatraemia and metabolic acidosis associated with it. Diagnosing the exact cause is even more difficult. Glucose-galactose malabsorption commonly presents with hypernatraemia and repeated dehydration. In the case described here, the baby started to have diarrhoea in the first week of life and presented in the neonatal emergency with severe dehydration and hypernatraemia. Higher sodium levels were difficult to manage throughout the course of illness. Hypernatraemia and diarrhoea worsened on feeding, whether formula or mother's feed, which raised suspicion of glucose and galactose malabsorption. So, genetic testing was performed and fructose based formula was started which led to improvement in the condition. Later, genetic testing confirmed our diagnosis. This case report emphasises that clinicians should consider the possibility that congenital diarrhoea could be due to glucose- galactose malabsorption while managing a case with loose stool and significant electrolyte imbalance in a neonate.

Disorders of Sodium.

Sodium imbalances are a common occurrence in the emergency department. Although recognition and diagnosis are relatively straightforward, discovering the cause and management should be approached systematically. The most important history items to ascertain is if the patient has symptoms and how long this imbalance has taken to develop. Treatment rapidity depends on severity of symptoms with the most rapid treatment occurring in only the severely symptomatic. Overcorrection has dire consequences and must be approached in a careful and systematic fashion in order to prevent these devastating consequences.

Estudio EDEN-16: sodio plasmático determinado a la llegada a urgencias como indicador de gravedad en pacientes ancianos / Plasma sodium concentration in older patients as an indicator of severity in emergencies: Results from the Emergency Department and Elder Needs-16 study

Objetivo: Estudiar los factores basales asociados a hiponatremia e hipernatremia en pacientes mayores atendidos en urgencias y la relación de estas disnatremias con eventos indicadores de gravedad. Método: Se incluyeron durante una semana a todos los pacientes atendidos en 52 servicios de urgencias hospitalarios españoles de edad $ 65 años con determinación de sodio plasmático. Se formaron tres grupos: sodio normal (135-145 mmol/L), hiponatremia (< 135 mmol/L) e hipernatremia (> 145 mmol/L). Se investigó la relación de 24 factores sociodemográficos, de comorbilidad, estado funcional basal y tratamiento crónico con hipo e hipernatremia. Como eventos de gravedad se recogieron necesidad de hospitalización, mortalidad intrahospitalaria, estancia prolongada en urgencias (> 12 horas) en dados de alta y hospitalización prolongada (> 7 días) en hospitalizados, y se analizó su relación con la concentración de sodio mediante curvas spline cúbicas restringidas ajustadas, tomando el valor 140 mmol/L como referencia. Resultados: Se incluyeron 13.368 pacientes (13,5% hiponatremia, 2,9% hipernatremia). La hiponatremia se asoció a edad $ 80 años, hipertensión arterial, diabetes mellitus, neoplasia activa, hepatopatía crónica, demencia, tratamiento con quimioterápicos y ayuda para la deambulación, y la hipernatremia a dependencia, necesidad de ayuda para deambular y demencia. La hospitalización fue del 40,8%, la mortalidad intrahospitalaria del 4,3%, la estancia prolongada en urgencias del 15,9% y la hospitalización prolongada del 49,8%. (AU)

Objectives: To study baseline factors associated with hypo- and hypernatremia in older patients attended in emergency departments (EDs) and explore the association between these dysnatremias and indicators of severity in an emergency. Material and methods: We included patients attended in 52 Spanish hospital EDs aged 65 years or older during a designated week. All included patients had to have a plasma sodium concentration on record. Patients were distributed in 3 groups according to sodium levels: normal, 135-145 mmol/L; hyponatremia, 135 mmol/L; or hypernatremia > 145 mmol/L. We analyzed associations between sodium concentration and 24 variables (sociodemographic information, measures of comorbidity and baseline functional status, and ongoing treatment for hypo- or hypernatremia). Indicators of the severity in emergencies were need for hospitalization, in-hospital mortality, prolonged ED stay (> 12 hours) in discharged patients, and prolonged hospital stay (> 7 days) in admitted patients. We used restricted cubic spline curves to analyze the associations between sodium concentration and severity indicators, using 140 mmol/L as the reference. Results: A total of 13 368 patients were included. Hyponatremia was diagnosed in 13.5% and hypernatremia in 2.9%. Hyponatremia was associated with age ($ 80 years), hypertension, diabetes mellitus, an active neoplasm, chronic liver disease, dementia, chemotherapy, and needing help to walk. Hypernatremia was associated with needing help to walk and dementia. The percentages of cases with severity indicators were as follows: hospital admission, 40.8%; in-hospital mortality, 4.3%; prolonged ED stay, 15.9%; and prolonged hospital stay, 49.8%. (AU)

Plasma sodium concentration in older patients as an indicator of severity in emergencies: Results from the Emergency Department and Elder Needs-16 study. / Estudio EDEN-16: sodio plasmático determinado a la llegada a urgencias como indicador de gravedad en pacientes ancianos.

OBJECTIVES: To study baseline factors associated with hypo- and hypernatremia in older patients attended in emergency departments (EDs) and explore the association between these dysnatremias and indicators of severity in an emergency. MATERIAL AND METHODS: We included patients attended in 52 Spanish hospital EDs aged 65 years or older during a designated week. All included patients had to have a plasma sodium concentration on record. Patients were distributed in 3 groups according to sodium levels: normal, 135-145 mmol/L; hyponatremia, 135 mmol/L; or hypernatremia > 145 mmol/L. We analyzed associations between sodium concentration and 24 variables (sociodemographic information, measures of comorbidity and baseline functional status, and ongoing treatment for hypo- or hypernatremia). Indicators of the severity in emergencies were need for hospitalization, in-hospital mortality, prolonged ED stay (> 12 hours) in discharged patients, and prolonged hospital stay (> 7 days) in admitted patients. We used restricted cubic spline curves to analyze the associations between sodium concentration and severity indicators, using 140 mmol/L as the reference. RESULTS: A total of 13 368 patients were included. Hyponatremia was diagnosed in 13.5% and hypernatremia in 2.9%. Hyponatremia was associated with age ($ 80 years), hypertension, diabetes mellitus, an active neoplasm, chronic liver disease, dementia, chemotherapy, and needing help to walk. Hypernatremia was associated with needing help to walk and dementia. The percentages of cases with severity indicators were as follows: hospital admission, 40.8%; in-hospital mortality, 4.3%; prolonged ED stay, 15.9%; and prolonged hospital stay, 49.8%. Odds ratios revealed associations between lower sodium concentration cut points in patients with hyponatremia and increasing need for hospitalization (130 mmol/L, 2.24 [IC 95%, 2.00-2.52]; 120 mmol/L, 4.13 [3.08-5.56]; and 110 mmol/L, 7.61 [4.53-12.8]); risk for in-hospital death (130 mmol/L, 3.07 [2.40-3.92]; 120 mmol/L, 6.34 [4.22- 9.53]; and 110 mmol/L, 13.1 [6.53-26.3]); and risk for prolonged ED stay (130 mmol/L, 1.59 [1.30-1.95]; 120 mmol/L, 2.77 [1.69-4.56]; and 110 mmol/L, 4.83 [2.03-11.5]). Higher sodium levels in patients with hypernatremia were associated with increasing need for hospitalization (150 mmol/L, 1.94 [1.61-2.34]; 160 mmol/L, 4.45 [2.88-6.87]; 170 mmol/L, 10.2 [5.1-20.3]; and 180 mmol/L, 23.3 [9.03-60.3]); risk for in-hospital death (150 mmol/L, 2.77 [2.16-3.55]; 160 mmol/L, 6.33 [4.11-9.75]; 170 mmol/L, 14.5 [7.45-28.1]; and 180 mmol/L, 33.1 [13.3-82.3]); and risk for prolonged ED stay (150 mmol/L, 2.03 [1.48-2.79]; 160 mmol/L, 4.23 [2.03-8.84]; 170 mmol/L, 8.83 [2.74-28.4]; and 180 mmol/L, 18.4 [3.69-91.7]). We found no association between either type of dysnatremia and prolonged hospital stay. CONCLUSION: Measurement of sodium plasma concentration in older patients in the ED can identify hypo- and hypernatremia, which are associated with higher risk for hospitalization, death, and prolonged ED stays regardless of the condition that gave rise to the dysnatremia.

OBJETIVO: Estudiar los factores basales asociados a hiponatremia e hipernatremia en pacientes mayores atendidos en urgencias y la relación de estas disnatremias con eventos indicadores de gravedad. METODO: Se incluyeron durante una semana a todos los pacientes atendidos en 52 servicios de urgencias hospitalarios españoles de edad $ 65 años con determinación de sodio plasmático. Se formaron tres grupos: sodio normal (135-145 mmol/L), hiponatremia ( 135 mmol/L) e hipernatremia (> 145 mmol/L). Se investigó la relación de 24 factores sociodemográficos, de comorbilidad, estado funcional basal y tratamiento crónico con hipo e hipernatremia. Como eventos de gravedad se recogieron necesidad de hospitalización, mortalidad intrahospitalaria, estancia prolongada en urgencias (> 12 horas) en dados de alta y hospitalización prolongada (> 7 días) en hospitalizados, y se analizó su relación con la concentración de sodio mediante curvas spline cúbicas restringidas ajustadas, tomando el valor 140 mmol/L como referencia. RESULTADOS: Se incluyeron 13.368 pacientes (13,5% hiponatremia, 2,9% hipernatremia). La hiponatremia se asoció a edad $ 80 años, hipertensión arterial, diabetes mellitus, neoplasia activa, hepatopatía crónica, demencia, tratamiento con quimioterápicos y ayuda para la deambulación, y la hipernatremia a dependencia, necesidad de ayuda para deambular y demencia. La hospitalización fue del 40,8%, la mortalidad intrahospitalaria del 4,3%, la estancia prolongada en urgencias del 15,9% y la hospitalización prolongada del 49,8%. A mayor hiponatremia, mayor necesidad de hospitalización (sodio 130 mmol/L: OR:2,24; IC 95%: 2,00-2,52; 120 mmol/L: 4,13, 3,08-5,56; 110 mmol/L: 7,61, 4,53-12,8), mortalidad intrahospitalaria (130 mmol/L: 3,07, 2,40-3,92; 120 mmol/L: 6,34, 4,22-9,53; 110 mmol/L: 13,1, 6,53-26,3) y estancia prolongada en urgencias (130 mmol/L: 1,59, 1,30-1,95; 120 mmol/L: 2,77, 1,69-4,56; 110 mmol/L: 4,83, 2,03-11,5), y a mayor hipernatremia mayor necesidad de hospitalización (150 mmol/L: 1,94, 1,61-2,34; 160 mmol/L: 4,45, 2,88-6,87; 170 mmol/L: 10,2, 5,1-20,3; 180 mmol/L: 23,3, 9,03-60,3), mortalidad intrahospitalaria (150 mmol/L: 2,77, 2,16-3,55; 160 mmol/L: 6,33, 4,11-9,75; 170 mmol/L: 14,5, 7,45-28,1; 180 mmol/L: 33,1, 13,3-82,3) y estancia prolongada en urgencias (150 mmol/L: 2,03, 1,48-2,79; 160 mmol/L: 4,23, 2,03-8,84; 170 mmol/L: 8,83, 2,74-28,4; 180 mmol/L: 18,4, 3,69-91,7). No hubo asociación entre estas disnatremias y hospitalización prolongada. CONCLUSIONES: El sodio plasmático determinado en urgencias en pacientes mayores permite identificar hiponatremias e hipernatremias, las cuales se asocian a un riesgo incrementado de hospitalización, mortalidad y estancia prolongada en urgencias independientemente de la causa que haya generado la disnatremia.

Hypokalemia/Hyperkalemia and Hyponatremia/Hypernatremia.

Electrolyte disorders are very common in the pediatric population. Derangements in serum sodium and potassium concentrations are among the most frequently seen given the risk factors and comorbidities unique to children. Pediatricians, in both outpatient and inpatient settings, should be comfortable with the evaluation and initial treatment of disturbances in these electrolyte concentrations. However, to evaluate and treat a child with abnormal serum concentrations of sodium or potassium, it is critical to understand the regulatory physiology that governs osmotic homeostasis and potassium regulation in the body. Comprehension of these basic physiologic processes will allow the provider to uncover the underlying pathology of these electrolyte disturbances and devise an appropriate and safe treatment plan.

[Dysnatremia]. / Dysnatriämien.

Changes in serum sodium concentrations are frequently encountered by anesthesiologists, are complex and are often inadequately treated. Feared consequences include neurological complications, such as cerebral hemorrhage, cerebral edema and coma. Dysnatremia is always accompanied disturbances in the water balance. Accordingly, these are routinely classified based on the tonicity; however, in the daily routine and especially in the acute setting, the volume status and extracellular volume are often difficult to assess. Severe symptomatic hyponatremia with impending cerebral edema is treated by administration of hypertonic saline solution. If the rise in serum sodium is too rapid, there is a risk of central pontine myelinolysis. In a second step, the cause of the hyponatremia can be investigated and the appropriate treatment can be initiated. In the case of hypernatremia, the etiology of the disorder must be clarified before treatment. The goal is to compensate for the water deficiency by correcting the cause, specific volume therapy and, if necessary, drug support. A slow and controlled compensation must be closely monitored in order to avoid neurological complications. An algorithm has been developed that provides an overview of the dysnatremias, aids with making the diagnosis and gives recommendations for treatment measures in the clinical routine.

Electrolyte imbalances as poor prognostic markers in COVID-19: a systemic review and meta-analysis.

PURPOSE: Serum electrolyte imbalances are highly prevalent in COVID-19 patients. However, their associations with COVID-19 outcomes are inconsistent, and of unknown prognostic value. We aim to systematically clarify the associations and prognostic accuracy of electrolyte imbalances (sodium, calcium, potassium, magnesium, chloride and phosphate) in predicting poor COVID-19 clinical outcome. METHODS: PubMed, Embase and Cochrane Library were searched. Odds of poor clinical outcome (a composite of mortality, intensive-care unit (ICU) admission, need for respiratory support and acute respiratory distress syndrome) were pooled using mixed-effects models. The associated prognostic sensitivity, positive and negative likelihood ratios (LR + , LR-) and predictive values (PPV, NPV; assuming 25% pre-test probability), and area under the curve (AUC) were computed. RESULTS: We included 28 observational studies from 953 records with low to moderate risk-of-bias. Hyponatremia (OR = 2.08, 95% CI = 1.48-2.94, I2 = 93%, N = 8), hypernatremia (OR = 4.32, 95% CI = 3.17-5.88, I2 = 45%, N = 7) and hypocalcemia (OR = 3.31, 95% CI = 2.24-4.88, I2 = 25%, N = 6) were associated with poor COVID-19 outcome. These associations remained significant on adjustment for covariates such as demographics and comorbidities. Hypernatremia was 97% specific in predicting poor outcome (LR + 4.0, PPV = 55%, AUC = 0.80) despite no differences in CRP and IL-6 levels between hypernatremic and normonatremic patients. Hypocalcemia was 76% sensitive in predicting poor outcome (LR- 0.44, NPV = 87%, AUC = 0.71). Overall quality of evidence ranged from very low to moderate. CONCLUSION: Hyponatremia, hypernatremia and hypocalcemia are associated with poor COVID-19 clinical outcome. Hypernatremia is 97% specific for a poor outcome, and the association is independent of inflammatory marker levels. Further studies should evaluate if correcting these imbalances help improve clinical outcome.

Evaluation and management of hypernatremia in adults: clinical perspectives.

Hypernatremia is an occasionally encountered electrolyte disorder, which may lead to fatal consequences under improper management. Hypernatremia is a disorder of the homeostatic status regarding body water and sodium contents. This imbalance is the basis for the diagnostic approach to hypernatremia. We summarize the eight diagnostic steps of the traditional approach and introduce new biomarkers: exclude pseudohypernatremia, confirm glucose-corrected sodium concentrations, determine the extracellular volume status, measure urine sodium levels, measure urine volume and osmolality, check ongoing urinary electrolyte free water clearance, determine arginine vasopressin/copeptin levels, and assess other electrolyte disorders. Moreover, we suggest six steps to manage hypernatremia by replacing water deficits, ongoing water losses, and insensible water losses: identify underlying causes, distinguish between acute and chronic hypernatremia, determine the amount and rate of water administration, select the type of replacement solution, adjust the treatment schedule, and consider additional therapy for diabetes insipidus. Physicians may apply some of these steps to all patients with hypernatremia, and can also adapt the regimens for specific causes or situations.