Guideline sources The following summarized guidelines for the evaluation and management of hyponatremia are prepared by our editorial team based on guidelines from the American Heart Association (AHA/ASA 2023), the Korean Society of Nephrology (KSN/KSEBPR 2022), the American Association for the Study of Liver Diseases (AASLD 2021), the Wilderness Medical Society (WMS 2020), the European Association for the Study of the Liver (EASL 2018; 2010), and the European Society of Intensive Care Medicine (ESICM/ERA-EDTA/ESE 2014). 1 2 3 4 5 6 7 8 8 8 8 9 Definition Hyponatremia an electrolyte disorder characterized by low serum sodium concentration, and is typically defined as a serum sodium of less than 135 mEq/L. 8 Epidemiology Causes of hyponatremia include increased water intake (psychogenic polydipsia), low dietary solute intake (tea and toast diet), decreased water excretion secondary to elevated plasma ADH levels (volume depletion, SIADH secretion, severe hypothyroidism, adrenal insufficiency), and expansion of plasma volume in the context of edematous states. 8 Pathophysiology The prevalence of hyponatremia in the general population of the United States is 1.72%. 9 https://web.pathway.md/diseases/recBYiXbMCoztp9CG 1/7 6/24/23, 12:47 PM Hyponatremia Pathway Disease course Treatment of hyponatremia requires careful attention to avoid overly rapid correction of serum sodium, which can lead to osmotic demyelination syndrome, permanent neurological impairment, and death. 8 Prognosis and risk of recurrence Approximately 40% of patients with osmotic demyelination syndrome recover fully, whereas 25% have persistent neurological deficits. Mortality associated with osmotic demyelination syndrome is approximately 6%. 8 Guidelines 1. Classification and risk stratification Classification: Classify hyponatremia based on the documented duration: Situation Guidance < 48 hours Acute 48 hours Chronic If it cannot be classified unless there is clinical or anamnestic evidence of the contrary. Chronic (presumably) Severity grading (based on sodium concentration): Classify hyponatremia based on the serum sodium concentration: Situation Guidance 130-135 mmol/L Mild 125-129 mmol/L Moderate < 125 mmol/L. Profound Severity grading (based on symptoms): Classify hyponatremia based on the symptomatic presentation: moderate: any biochemical degree of hyponatremia in the presence of moderate symptoms (nausea without vomiting, confusion, or headache) severe: any biochemical degree of hyponatremia in the presence of severe symptoms (vomiting, altered level of consciousness, seizures, or cardiorespiratory distress). https://web.pathway.md/diseases/recBYiXbMCoztp9CG 2/7 6/24/23, 12:47 PM Hyponatremia Pathway Risk of osmotic demyelination: Recognize that the risk of osmotic demyelination syndrome depends on the following factors: biochemical degree and duration of hyponatremia at presentation speed of increase in serum sodium concentration history of alcohol abuse and/or liver disease use of thiazide or antidepressant medications. 2. Diagnostic investigations Urine sodium: measure urine sodium concentration on a spot urine sample (obtained and interpreted with concomitant serum sodium concentration) in patients with urine osmolality > 100 mOsm/kg. B Show 2 more Urine osmolality: Obtain and interpret urine osmolality on a spot urine sample as the initial step in the evaluation of patients with hypotonic hyponatremia. B Attribute hyponatremia to relative excess water intake in patients with a urine osmolality 100 mOsm/kg. B Serum osmolality: View hyponatremia as hypotonic hyponatremia in the absence of causes of non-hypotonic hyponatremia, such as: effective osmoles raising serum osmolality causing hyponatremia: isotonic or hypertonic glucose, mannitol, glycine, histidine-tryptophan-ketoglutarate, hyperosmolar radiocontrast media, maltose presence of endogenous solutes causing pseudohyponatremia (laboratory artifact): triglycerides, cholesterol, protein, IVIG, monoclonal gammopathies. Recognize that hyponatremia with a measured serum osmolality < 275 mOsm/kg reflects hypotonic hyponatremia. Serum glucose: measure serum glucose concentration to exclude hyperglycemic hyponatremia, and correct the measured serum sodium concentration for the serum glucose concentration if the latter is increased. B Fractional urinary excretion of uric acid: consider obtaining an additional measurement of fractional urinary excretion of uric acid in patients with hyponatremia to differentiate likely causes of hyponatremia, such as syndrome of inappropriate antidiuresis or diuretic-induced hyponatremia. E Copeptin-to-urinary sodium ratio: insufficient evidence to recommend obtaining copeptin-to- urinary sodium ratio to assess patient volume status. I Vasopressin levels: avoid measuring vasopressin as part of the diagnostic evaluation for the SIADH secretion. D https://web.pathway.md/diseases/recBYiXbMCoztp9CG 3/7 6/24/23, 12:47 PM Hyponatremia Pathway 3. Medical management Management of mildly symptomatic patients, acute setting: As per KSEBPR/KSN 2022 guidelines, obtain rigorous evaluation for the causes of mild hyponatremia and manage causative diseases to improve clinical outcomes. E As per ERA-EDTA/ESE/ESICM 2014 guidelines, obtain prompt diagnostic assessment in mildly symptomatic patients with hyponatremia. B Show 5 more Management of mildly symptomatic patients (chronic setting): discontinue non-essential fluids, medications, and other factors likely to contribute to or provoke hyponatremia. Show 4 more Management of moderately symptomatic patients: obtain prompt diagnostic assessment in moderately symptomatic patients with hyponatremia. B Show 8 more Management of severely symptomatic patients, initial management: As per KSEBPR/KSN 2022 guidelines, consider administering rapid intermittent boluses of hypertonic saline in patients with symptomatic severe hypotonic hyponatremia. C As per ERA-EDTA/ESE/ESICM 2014 guidelines, administer IV infusion of 3% hypertonic saline (150 mL IV, over 20 minutes) promptly in patients with severely symptomatic hyponatremia. B Show 3 more Management of severely symptomatic patients (adequate response to initial management): discontinue hypertonic saline infusion in patients with severely symptomatic hyponatremia displaying an adequate response to initial management. B Show 4 more Management of severely symptomatic patients (inadequate response to initial management): continue IV infusion of 3% hypertonic saline in patients with severely symptomatic hyponatremia displaying an inadequate response to initial treatment, aiming for an additional increase in serum sodium concentration by 1 mmol/L per hour. B Show 2 more Management of overly rapid correction: As per KSN 2022 guidelines, consider administering desmopressin individually according to risk factors affecting overcorrection, hypertonic saline therapeutic regimen, and whether to administer dextrose solution during overcorrection in patients with hyponatremia. C As per ESE 2014 guidelines, discontinue any ongoing treatments aimed at raising serum sodium in patients with overly rapid correction. B Show 3 more 4. Specific circumstances https://web.pathway.md/diseases/recBYiXbMCoztp9CG 4/7 6/24/23, 12:47 PM Hyponatremia Pathway Patients with hypovolemic hyponatremia: administer IV infusion of a crystalloid solution (0.9% saline or a balanced crystalloid, 0.5-1.0 mL/kg/hour) to restore extracellular volume in patients with hypovolemic hyponatremia. A Show 2 more Patients with hypervolemic hyponatremia: do not implement therapeutic measures aimed solely at increasing the serum sodium concentration in patients with mild or moderate hyponatremia. D Show 2 more Patients with SIADH: As per KSN 2022 guidelines, consider administering vaptans in patients with the syndrome of inappropriate antidiuresis and moderate-to-severe hyponatremia. C As per ESE 2014 guidelines, avoid measuring vasopressin as part of the diagnostic evaluation for the SIADH secretion. D Show 3 more Patients with exercise-associated hyponatremia (prevention): advise avoiding sustained overhydration during exercise, as it is the primary risk factor for development of all variants of exercise-associated hyponatremia. A Show 3 more Patients with exercise-associated hyponatremia (assessment): obtain point-of-care testing in at-risk symptomatic patients when available. Integrate all available clinical and historical information into an assessment of the patient's hydration status (history of fluid intake, food intake, presenting signs and symptoms, body weight if available, and urine output), if testing is unavailable. B Patients with exercise-associated hyponatremia (outpatient management): Advise restricting oral fluids if exercise-associated hyponatremia from fluid overload is associated with mild symptoms. Do not administer hypotonic fluids in patients with suspected exercise-associated hyponatremia. B Consider adding oral sodium in hypertonic solutions or advising foods with high sodium content (salty snacks) for increasing serum sodium levels and enhancing symptom relief (over fluid restriction) in patients with mild exercise-associated hyponatremia, if tolerated. C Patients with exercise-associated hyponatremia (inpatient management): inform receiving caregivers about the potential diagnosis of exercise-associated hyponatremia and appropriate fluid management (withhold hypotonic fluids) when transferring care. B Show 7 more Patients with exercise-associated hyponatremia (observation): observe patients for at least 60 minutes after exercise to ensure no decompensation from delayed symptomatic exercise- associated hyponatremia occurs after cessation of exercise. B Patients with heart failure: consider administering vaptans in patients with HF and hypervolemic hyponatremia in terms of rapid sodium correction. C Patients with liver disease: https://web.pathway.md/diseases/recBYiXbMCoztp9CG 5/7 6/24/23, 12:47 PM Hyponatremia Pathway As per KSN 2022 guidelines, insufficient evidence to support the use of vaptans in patients with liver cirrhosis and hypervolemic hyponatremia. I As per AASLD 2021 guidelines, obtain monitoring and advise water restriction in patients with mild hyponatremia (126-135 mEq/L) without symptoms. E Show 6 more As per EASL 2018 guidelines, recognize that the development of hyponatremia (serum sodium concentration < 130 mmol/L) in patients with cirrhosis carries an ominous prognosis, as it is associated with increased mortality and morbidity. Evaluate patients with hyponatremia for liver transplantation. B Show 5 more As per EASL 2010 guidelines, consider administering albumin in patients with hypervolemic hyponatremia in the setting of liver disease. C Show 3 more Patients with cerebral disease: As per AHA 2023 guidelines, consider administering mineralocorticoids for the treatment of natriuresis and hyponatremia in patients with aneurysmal subarachnoid hemorrhage. C As per KSN 2022 guidelines, individualize administration of hypertonic or isotonic saline infusion, oral sodium chloride, or fludrocortisone for the correction of hypoosmolar hyponatremia in patients with cerebral diseases. E 5. Preventative measures Primary prevention in hospitalized patients: Administer isotonic fluids as maintenance fluid therapy to prevent hyponatremia in hospitalized pediatric patients over 1 month and under 18 years of age. A Insufficient evidence to support administrating isotonic fluids as maintenance fluid therapy to prevent hyponatremia in neonates because of the risk of hypernatremia. I References 1. Spasovski G, Vanholder R, Allolio B et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Eur J Endocrinol. 2014 Feb 25;170 3 G1 47. Open 2. Scott W Biggins, Paulo Angeli, Guadalupe Garcia-Tsao et al. Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome: 2021 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021 Aug;74 2 1014 1048. Open 3. Brad L Bennett, Tamara Hew-Butler, Mitchell H Rosner et al. Wilderness Medical Society Clinical Practice Guidelines for the Management of Exercise-Associated Hyponatremia: 2019 Update. Wilderness Environ Med. 2020 Mar;31 1 50 62. Open 4. European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018 Aug;69 2 406 460. Open https://web.pathway.md/diseases/recBYiXbMCoztp9CG 6/7 6/24/23, 12:47 PM Hyponatremia Pathway 5. Yeonhee Lee, Kyung Don Yoo, Seon Ha Baek et al. Korean Society of Nephrology 2022 Recommendations on controversial issues in diagnosis and management of hyponatremia. Kidney Res Clin Pract. 2022 Jul;41 4 393 411. Open 6. European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol. 2010 Sep;53 3 397 417. Open 7. Brian L Hoh, Nerissa U Ko, Sepideh Amin-Hanjani et al. 2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage: A Guideline From the American Heart Association/American Stroke Association. Stroke. 2023 May 22. Online ahead of print. Open 8. Rondon-Berrios H, Agaba EI, Tzamaloukas AH. Hyponatremia: pathophysiology, classification, manifestations and management. Int Urol Nephrol. 2014 Nov;46 11 2153 65. Open 9. Mohan S, Gu S, Parikh A et al. Prevalence of hyponatremia and association with mortality: results from NHANES. Am J Med. 2013 Dec;126 12 1127 37. Open https://web.pathway.md/diseases/recBYiXbMCoztp9CG 7/7