Precision medicine: "Point of Care Ultrasound" (PoCUS) in the diagnostic approach to the patient with hyponatremia.

Hyponatremia is a multifactorial disorder defined as a decrease in plasma sodium concentration. Its differential diagnosis requires an adequate evaluation of the extracellular volume (ECV). However, ECV determination, simply based on the clinical history, vital signs, physical examination, and laboratory findings can leads to misdiagnosis and inappropriate treatment. The use of Point-of-Care Ultrasound (POCUS), through the combination of Lung Ultrasound (LUS), Venous Excess UltraSound (VExUS) and Focused Cardiac Ultrasound (FoCUS), allows a much more accurate holistic assessment of the patient's ECV status in combination with the other parameters.

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.

The Role of Ultrasonographic Inferior Vena Cava Measurement in the Volume-Based Classification of Patients With Hyponatremia.

OBJECTIVES: To demonstrate the role of inferior vena cava (IVC) collapsibility in the assessment of volume status in hyponatremic critically ill patients in the emergency department (ED) with bedside IVC imaging and to predict volume status with response to fluid therapy. METHODS: A prospective 110 hypotonic hyponatremic patients aged >18 years with a serum sodium level under 125 mEq/L and at least one symptom of hyponatremia, who presented or referred to the ED was conducted. Demographical, clinical, and laboratory characteristics with bedside measurement of IVC diameter of patients were recorded. Volume status was divided into 3 subgroups: hypovolemic-G1, euvolemic-G2, and hypervolemic-G3. An ED trainee with a certification to perform basic and advanced ultrasonography (USG) training carried out the USG examinations. A diagnostic algorithm approach was made according to the results. RESULTS: Symptom severity was significantly greater in the hypervolemic group than the other groups (P = .009 and P = .034, respectively). Systolic blood pressure (SBP) and mean arterial pressure (MAP) were significantly lower in the hypovolemic group compared with the other groups (P < .001 and P = .003, respectively). There was a significant difference between the ultrasonographically measured IVC min, IVC max, and mean IVC values across the three volume-based groups (P < .001). CONCLUSION: Considering the diversity of physical examination (PE) findings, with the highly heterogenous nature of hyponatremia, a new measurable algorithm can be developed on the basis of contemporary hyponatremic patient management guidelines.

Prognostic significance and extra-hypothalamus dysfunction of hyponatremia in anti-leucine-rich glioma-inactivated protein 1 encephalitis.

This study aimed to investigate prognostic significance and brain metabolic mechanism of hyponatremia in anti-leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis. After adjusting for confounders, patients with moderate and severe hyponatremia had significantly increased risk of poor functional outcome and sequelae of seizures. In addition, serum sodium was negatively correlated with normalized ratio of the standardized uptake value of medial temporal lobe (MTL), basal ganglia (BG), and hypothalamus on positron emission tomography (PET) and which was further validated using voxel-wise analysis, suggesting an extra-hypothalamus (BG and MTL) localization for hyponatremia.

The Difference Between Preoperative and Postoperative Pituitary Stalk Deviation Angles Can Predict Delayed Hyponatremia After Transsphenoidal Surgery.

OBJECTIVE: Our aim was to assess the factors influencing the development of delayed hyponatremia after transsphenoidal surgery (TSS) for pituitary adenomas and analyze the effect of the difference between preoperative and postoperative pituitary stalk deviation angles on delayed hyponatremia. METHODS: A retrospective study was performed on the clinical data of patients with pituitary adenomas who were treated with TSS at a single institution. On the basis of the observation of indicators such as pituitary stalk deviation angle and length of "measurable pituitary stalk" on magnetic resonance imaging, we determined the predictors of postoperative delayed hyponatremia through univariate and multivariate analyses. RESULTS: Microscopic TSS was performed in 422 patients with pituitary adenoma, of whom 66 experienced postoperative delayed hyponatremia. Logistic regression analysis showed that the risk of delayed hyponatremia was greater for patients with a large difference between preoperative and postoperative pituitary stalk deviation angle (odds ratio = 1.040, 95% confidence interval: 1.018-1.051; P < 0.001) and a large difference in the "measurable pituitary stalk" (odds ratio = 1.128, 95% confidence interval: 1.011-1.258; P = 0.032), and patients with high blood sodium on the second day after surgery have a lower probability of developing delayed hyponatremia. CONCLUSIONS: This study is the first to suggest the important role of the difference between preoperative and postoperative pituitary stalk deviation angles in predicting the development of delayed hyponatremia after TSS for pituitary adenomas.

Osmotic demyelination syndrome improving after immune-modulating treatment: Case report and literature review.

BACKGROUND: Osmotic demyelination syndrome (ODS), which embraces central pontine and extrapontine myelinolysis, is an uncommon neurological disorder that occurs due to plasma osmotic changes. CASE PRESENTATION: We present the case of a 55-year-old man, who presented with severe hyponatremia due to repeated vomiting, antidepressant treatment and consumption of large amounts of water. Fifteen days after sodium correction, the patient showed fluctuation of vigilance, dysarthria and dysphagia, tremor, cogwheel rigidity, bilateral facial palsy, ophthalmoplegia and tetraparesis. A brain MRI scan revealed extrapontine and later on pontine myelinolysis. He received intravenous steroids and subsequently immunoglobulin. His status began to improve gradually after completion of immunoglobulin and at three month-follow-up had no neurological deficit. LITERATURE REVIEW: A comprehensive literature search of all reported ODS cases that received immunoglobulin, steroids or plasmapheresis was conducted in the electronic databases PubMed and Web of science. CONCLUSIONS: Improvement was seen in most cases that received immunoglobulin either during treatment or in the first days after treatment. With regard to steroids, although most cases reported improvement in the following months their effect on the outcome is unclear. Most cases treated with plasmapheresis reported favorable outcome at variable follow-up time. Immunoglobulin and steroids have immunomodulatory effects, which could contribute to promotion of myelin repair in ODS. Plasmapheresis has effects on the immune system beyond removing myelinotoxins from the circulation. More evidence is required to support their use in ODS. However, in view of the disease severity, these therapeutic choices should be considered in the clinical management of ODS.

Trimethoprim-induced hyponatremia mimicking SIADH in a patient with pulmonary nocardiosis: use of point-of-care ultrasound in apparent euvolemic hypotonic hyponatremia.

A 72-year-old man with chronic obstructive pulmonary disease and depression presented to the emergency department (ED) with progressive worsening of shortness of breath. He required intubation and mechanical ventilation. The patient improved with therapy, but his endotracheal aspirate culture was positive for Nocardia cyriacigeorgica The patient was started on high dose Bactrim and discharged. He presented to the office 5 days later with confusion, and his serum sodium was 113 mmol/L. Based on a euvolemic physical examination, consistent serum and urine studies, he was diagnosed with syndrome of inappropriate antidiuretic hormone secretion (SIADH) likely from citalopram. However, treatment for SIADH failed to improve his serum sodium level. A bedside ultrasound revealed an inferior vena cava diameter of 0.7 cm with a complete inspiratory collapse that was inconsistent with SIADH. The patient was correctly diagnosed with salt-losing nephropathy from trimethoprim, and the medication was discontinued. He received therapy initially with intravenous normal saline and then salt tablets. His sodium improved within 2 weeks.

Point-of-care ultrasound to evaluate volume status in severe hyponatremia.

A 51-year-old man was hospitalised for severe hyponatremia. Initial history and physical examination suggested hypovolemia, and he was treated with normal saline at 100 mL/hour. After several days, his hyponatremia failed to improve, and then worsened without resolution of presenting ataxia and fatigue. He had no new complaints including no cough or orthopnea. He had no jugular venous distention or oedema, and his lungs were clear to auscultation. Point-of-care ultrasound was used, revealing a distended inferior vena cava, pulmonary oedema and pleural effusion, suggesting hypervolemia. Based on ultrasound findings, we treated with 60 mg oral torsemide two times per day. Hyponatremia resolved without complication within 48 hours. In this case, physical examination failed to recognise volume status change from hypovolemic to hypervolemic, increasing hospitalisation and morbidity. The point-of-care ultrasound proved to be an accurate tool for proper volume evaluation, and may be used as an adjunct to physical examination for hyponatremic patients.

Severe symptomatic hyponatraemia secondary to bowel preparation.

​A 62-year-old woman presented to a rural Australian hospital for a planned admission to receive bowel preparation 1 day prior to an upper endoscopy and colonoscopy. This admission was complicated by seizures and reduced levels of consciousness in the setting of hyponatraemia secondary to bowel preparation. Given the limited resources in a remote/rural Australian hospital, transfer to a tertiary level hospital was required for review and management of this rare complication of bowel preparation.

Hyponatremia and metabolic bone disease in patients with epilepsy: A cross-sectional study.

AIM: Patients with epilepsy frequently develop hyponatremia due to the treatment with antiepileptic drugs and have an increased risk of developing metabolic bone disease. Hyponatremia is known to be associated with osteoporosis. The aim of the study was to investigate the association between hyponatremia and osteoporosis in patients with epilepsy. METHOD AND MATERIAL: This cross-sectional study included patients with epilepsy from a tertiary epilepsy out-patient clinic in Denmark, who had a Dual Energy X-ray Absorptiometry scan performed and an accompanying plasma sodium (p-Na) measured prior to or a maximum of 14 days after the scan. Information regarding the patients' health and medical conditions were obtained from their medical reports. RESULTS: A total of 695 patients (females 53.8%, age 49 (34:63) years (median (quartiles)) were included. 10.4% had hyponatremia (p-Na ≤ 135 mmol/L). The hyponatremic patients had significantly lower T-scores in the lumbar spine, femoral neck and total femur (all p < 0.023) and the odds ratio of osteoporosis (T-score < -2.5) was significantly increased (2.91 (1.61-5.27) (95% confidence interval) (p = 0.001)). When adjusting for potential confounders the patients with moderate and severe hyponatremia (p-Na < 129 mmol/L) had a significantly lower mean T-score in the lumbar spine (p = 0.030). CONCLUSION: We conclude that hyponatremia is common in patients with epilepsy and that moderate and severe hyponatremia is independently associated with decreased bone mineral density in the lumbar spine. Therefore, hyponatremia in a patient with epilepsy should warrant further examination of the patient for bone loss and osteoporosis.

Neonatal Hyponatremia in the Setting of Untreated Progressive Hydrocephalus.

BACKGROUND: Hyponatremia in the neonatal population is an uncommon occurrence and can be associated with significant increase in morbidity and mortality. In the neonatal population, it is typically associated with an excess of antidiuretic hormone and rarely has been found to be associated with hydrocephalus, short of being caused by the subsequent treatment of hydrocephalus. CASE DESCRIPTION: We present a case report of a patient with neonatal hydrocephalus, secondary to intraventricular hemorrhage in the setting of prematurity, treated at our institution, in whom sodium levels reached a nadir as head circumference peaked and subsequent treatment of hydrocephalus resolved the associated hyponatremia. CONCLUSIONS: Hydrocephalus secondary to intraventricular hemorrhage is a notable complication in the premature neonatal population. Physicians should be aware of its potential association with hyponatremia and consider early neurosurgical intervention when other etiologies of the electrolyte disturbance cannot be identified.

Association of optic nerve sheath diameter measurement with hyponatremia in emergency department.

OBJECTIVE: Investigation of association of ONSD with hyponatremia in symptomatic patients. METHODS: 89 patients who were diagnosed to have hyponatremia (Na + <135 mmol/L) were prospectively analyzed and compared with 72 patients who have normal serum sodium levels presented to ED at the same time interval. Subjects' demographic properties including age and sex were recorded, as were admission symptoms, serum Na + level, and pre-treatment and post-treatment optic nerve sheath diameter (ONSD). RESULTS: The mean age of the study population was 62.3 ±â€¯17.6 years, and the control group 55.1 ±â€¯20.0 years (p < 0.05). There was a significant difference between the patient group's pre-treatment and post-treatment OSNDs compared to the controls (p < 0.05). There was a significant negative correlation between the admission sodium level and ONSD in the patient group (p < 0.05). In the pre-treatment period, patients with symptoms had a significantly greater mean ONSD than those without symptoms (0.546 ±â€¯0.068 mm vs 0.448 ±â€¯0.081 mm; p < 0.05). The area under the curve was 0.870; the cut-off level calculated for hyponatremia was 0.49 mm, which had a sensitivity of 81% and a specificity of 81.9%. CONCLUSION: Ultrasonic imaging of ONSD measurement in the emergency department appears to reflect changes consistent with ICP changes in hyponatremia and change in serum sodium.

Extrapontine Myelinolysis and Reversible Parkinsonism After Hyponatremia Correction in a Case of Pituitary Adenoma: Hypopituitarism as a Predisposition for Osmotic Demyelination.

BACKGROUND: Osmotic demyelination syndrome commonly follows rapid correction of hyponatremia. Although pons is a common location, extrapontine locations, such as striatum and thalamus, have been reported. CASE DESCRIPTION: A 48-year-old woman presented with masked facies, shuffling gait, and pill-rolling tremors suggestive of acute-onset parkinsonism. Hyponatremia was diagnosed following a bout of diarrhea, which was corrected with hypertonic saline. Magnetic resonance imaging of the brain showed a giant pituitary adenoma. Hyperintensities on T2-weighted imaging were also seen at the level of pons and bilateral striatum. Central pontine myelinolysis and extrapontine myelinolysis were diagnosed. Hormonal assay showed hypocortisolism, secondary hypothyroidism, and hypogonadism. The patient was started on levodopa-carbidopa, steroids, and thyroxine. She underwent transnasal pituitary adenoma excision. At 6 months postoperatively, she had recovered completely with normal gait. Repeat imaging showed complete resolution of myelinolysis. At 36 months, she continued to have hypocortisolism and hypothyroidism requiring replacement. CONCLUSIONS: Extrapontine myelinolysis with parkinsonism and asymptomatic central pontine myelinolysis is rare with few cases described in the literature. Our patient had a pituitary adenoma with hyponatremia requiring sodium correction, and we believe that hypopituitarism might have predisposed her to osmotic demyelination. We reviewed relevant literature on extrapontine myelinolysis in suprasellar tumors and the pathophysiology. Hypopituitarism is an underrecognized cause of hyponatremia. When treating a patient with hyponatremia, knowing the pituitary function status is a prerequisite for the physician to prevent osmotic demyelination syndrome.

Clinical characteristics of acute encephalopathy with acute brain swelling: A peculiar type of acute encephalopathy.

OBJECTIVES: Acute encephalopathy has been observed with acute brain swelling (ABS) that is characterized by rapid progression to whole-brain swelling. The objective of this study was to describe the clinical characteristics of ABS. METHODS: We encountered four patients with ABS and retrospectively investigated their clinical data with a medical chart review. RESULTS: Three patients had seizure clustering or status epilepticus in the clinical course. Signs of elevated intracranial pressure (ICP) appeared 3-9 h after the first convulsive attack in three patients. In all patients, signs of brainstem involvement appeared 1-8 h after signs of elevated ICP. Mild hyponatremia that progressed after signs of elevated ICP appeared was noted in three patients. Brain CT revealed mild brain swelling in the initial phase, which rapidly progressed to whole-brain swelling. No focal abnormalities were detected on brain MRI in one patient. Continuous electroencephalography was initially normal, but in two patients, high-amplitude slow waves appeared with rapid changes before signs of brainstem involvement. Although recovery was achieved without sequelae in two patients, outcome was fatal for the other two. CONCLUSIONS: The pathogenesis of ABS has yet to be clarified, but clinical features in our patients are not consistent with any established subtypes of acute encephalopathy. Therefore, we believe that ABS should be recognized as a new type of acute encephalopathy.

Development of severe hyponatremia due to cerebrospinal fluid leakage following meningomyelocele surgery in a newborn.

Cerebrospinal fluid leakage following meningomyelocele surgery is a frequent complication in the wound-healing period and is associated with wound dehiscence. CSF loss can cause severe hyponatremia, especially in the newborn and early infancy periods when dietary sodium content is relatively low. Hyponatremia in the newborn period can result in adverse neurodevelopmental outcomes. In addition, hyponatremia's cerebral effects can increase complications in neurosurgery patients. The authors present the case of a newborn in whom CSF leakage from the operative site and severe hyponatremia developed following meningomyelocele surgery. To the best of their knowledge, severe hyponatremia caused by CSF leakage after meningomyelocele surgery has not been previously reported in the literature.

A study of predictors for hyponatraemia in patients with cervical spinal cord injury.

STUDY DESIGN: A retrospective study. OBJECTIVES: The objectives of the study were to investigate the predictors for hyponatraemia in patients with cervical spinal cord injuries (CSCIs) and to define the relationship between magnetic resonance imaging (MRI) scans and hyponatraemia. SETTING: The study was carried out at The First Affiliated Hospital of Anhui Medical University. METHODS: A total of 292 patients with CSCIs were retrospectively reviewed to determine the predictors of hyponatraemia. Fourteen variables were extracted from the medical records: age, sex, blood pressure (BP), tracheostomy, serum potassium, serum chloride, serum bicarbonate, serum albumin, intravenous fluid intake and urine volume for 24 h, haematocrit, haemoglobin, neurological assessment and four MRI signal patterns. Univariate and multivariate analyses were used to determine the effect of each variable on hyponatraemia. RESULTS: Eighty-two of the 270 patients (30%) developed hyponatraemia. Univariate analyses indicated that the following variables were significant predictors of hyponatraemia: tracheostomy; the initial American Spinal Injury Association (ASIA) Impairment Scale (AIS) A assessment; and haemorrhage changes on T2-weighted MRI scans, and low BP. Multivariate regression analyses revealed two variables were significant predictors of hyponatraemia: haemorrhage changes on T2-weighted MRI scans and low BP. CONCLUSIONS: Haemorrhage changes on MRI scans were closely associated with the onset of hyponatremia and could provide objective data for forecasting hyponatraemia in CSCI patients. Low BP was also a reasonable predictor of hyponatremia.

A case report of hyponatremia after surgery for Conn's adenoma.

Primary aldosteronism (PA), also known as Conn's syndrome, is a frequent cause of secondary hypertension. If PA is due to a documented unilateral adrenal adenoma, adrenalectomy is the treatment of choice. Endocrine Society guidelines suggest monitoring potassium after adrenalectomy, while there is no mention of sodium disorders after surgery. Here we report the case of a patient with Conn's syndrome who developed hyponatremia after surgery. This was an unexpected event in the course of the treatment, which sheds light on the fact that low levels of aldosterone strongly influence sodium concentration, and advises clinicians to monitor sodium after adrenalectomy.

Elevated serum creatinine and hyponatraemia as prognostic factors in canine acute pancreatitis.

OBJECTIVE: To evaluate prognostic factors for canine acute pancreatitis (AP) based on clinical and laboratory data that can be easily assessed in veterinary practice. DESIGN: Retrospective study between January 2010 and December 2013. METHODS: The diagnosis of AP was based on clinical signs and an abnormal SNAP® cPL™ test result, concurrently with an ultrasound pattern suggestive of pancreatitis. Dogs were divided into survivors and non-survivors. We evaluated 12 clinical and laboratory parameters: respiratory rate, rectal temperature, white blood cells, haematocrit, total serum proteins, albumin, creatinine, cholesterol, total and ionised calcium, sodium and potassium. Clinical and clinicopathological data were statistically compared between survivors and non-survivors. A value of P < 0.05 was considered significant and P < 0.01 as highly significant. The odds ratio (OR) was calculated. RESULTS: The study enrolled 50 client-owned dogs with a diagnosis of AP. Serum creatinine (P = 0.017) and sodium (P = 0.004) correlated significantly with the outcome. Serum sodium < 139.0 mmol/L (139.0 mEq/L) and serum creatinine > 212 µmol/L (2.4 mg/dL) were associated significantly with poor prognosis. Azotaemia (OR 12.5; 95% confidence interval (CI) 1.32-118.48) and hyponatraemia (OR 4.9; 95% CI 1.36-17.64) were associated with increased risk of death. CONCLUSIONS: In dogs with AP, hyponatraemia and azotaemia seem to be significantly associated with an increased risk of death.

Hyponatremia in Traumatic Brain Injury: A Practical Management Protocol.

BACKGROUND: Hyponatremia (defined as serum sodium <135 mEq/L) is the most common electrolyte abnormality in traumatic brain injury (TBI) and is also an independent predictor of poor neurologic outcome. The reported incidence of hyponatremia varies widely in literature reports, and there is continuing difficulty in clearly differentiating between the 2 common causes of hyponatremia with natriuresis: the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and cerebral salt wasting (CSW). We encounter hyponatremia frequently in our practice, and we therefore decided to review data from our center to estimate the incidence of hyponatremia and the results of our management strategies, and attempt to formulate simple guidelines for the correction of hyponatremia in TBI. METHODS: A retrospective analysis of 1500 consecutively admitted patients with TBI was performed by the use of electronic records and radiographic review. Hyponatremia was defined as serum sodium <135 mEq/L, and natriuresis as a urine spot sodium of more than >40 mEq/L. The incidence of TBI, its management, and the effect of fludrocortisone were evaluated. RESULTS: The incidence of hyponatremia was 13.2%. Early therapy with fludrocortisone significantly reduced the duration of hospital stay (P < 0.05). Traumatic subarachnoid hemorrhage was the most common abnormality on the admission computed tomographic scan in patients who experienced hyponatremia. CONCLUSION: Early initiation of fludrocortisone in the setting of hyponatremia with natriuresis decreases the hospital stay. This protocol is probably safer in a tropical country where fluid restriction might be harmful. It also eliminates the need to differentiate between SIADH and CSW.