17:I[462708,["/_next/static/chunks/3yo3kiro3bmlp.js","/_next/static/chunks/3vr2wvd8f2efb.js","/_next/static/chunks/2vtmb68_vu-9t.js","/_next/static/chunks/2s8mt6_8wrpfo.js","/_next/static/chunks/3vkulz2i3l61y.js","/_next/static/chunks/1cqw2i1silz0i.js","/_next/static/chunks/14dbm3lm_t629.js","/_next/static/chunks/335_v2mb569ld.js","/_next/static/chunks/1jvnwmb7jnkpz.js","/_next/static/chunks/3cmavum774kjt.js","/_next/static/chunks/3th-0-a2xf9qs.js","/_next/static/chunks/0p0xpwde6kzmv.js","/_next/static/chunks/401-sxxnzbtf_.js","/_next/static/chunks/0wywtv698a1v0.js","/_next/static/chunks/2botzqwpnrzyj.js"],"ArticleReader"] 18:T5269,## Summary Hyponatremia is serum sodium **<135 mmol/L** and usually reflects excess water relative to exchangeable sodium and potassium. The first two decisions are whether the patient has **true hypotonic hyponatremia** and whether neurologic symptoms require immediate hypertonic saline. Serum sodium concentration alone does not determine urgency; the rate of fall, duration, cause, and neurologic state are critical.[1-3] Seizure, coma, profound obtundation, or another severe neurologic syndrome plausibly caused by hyponatremia warrants prompt **3% hypertonic saline** while the cause is investigated. European guidance uses **150 mL IV over 20 minutes**, reassessing sodium and symptoms and repeating as needed to achieve about a **5 mmol/L early rise**. A widely used US expert approach uses **100 mL IV over 10 minutes**, repeatable up to three times, with an early goal of roughly **4–6 mmol/L**.[1,2] The purpose is to reverse cerebral edema, not to normalize sodium. The major preventable harm after initial stabilization is **overcorrection**, especially in chronic or unknown-duration hyponatremia. Patients at greatest risk for osmotic demyelination include those with very low starting sodium (particularly around ≤105 mmol/L), alcohol use disorder, malnutrition, advanced liver disease, and hypokalemia. In such patients, keep the rise **≤8 mmol/L in any 24 hours**; many clinicians use this conservative ceiling for chronic or uncertain-duration disease more broadly. European guidance allows up to 10 mmol/L in the first 24 hours and 8 mmol/L during each subsequent 24 hours.[1-3] If correction is exceeding the safe trajectory, stop active therapy and consider **desmopressin plus electrolyte-free water such as D5W** with frequent sodium monitoring.[3] For diagnosis, obtain **measured serum osmolality, urine osmolality, and urine sodium** early, ideally before large volumes of IV fluid or diuretics alter the pattern. Urine osmolality ≤100 mOsm/kg indicates near-maximal water excretion; >100 mOsm/kg indicates antidiuretic activity. A urine sodium around **30 mmol/L** is a useful branch point, but diuretics, kidney disease, dietary sodium, and recent fluid therapy can confound interpretation.[1] Treat the mechanism. Hypovolemic hyponatremia usually requires isotonic volume replacement; syndrome of inappropriate antidiuresis (SIAD) often begins with treatment of the cause, adequate solute intake, and fluid restriction; hypervolemic hyponatremia requires treatment of heart failure, cirrhosis, or kidney disease. Once the antidiuretic stimulus resolves, a brisk water diuresis can raise sodium rapidly, so urine output and sodium trajectory are as important as the initial treatment order.[1,3] ## Definition and classification ### By serum sodium | Category | Serum sodium | |---|---:| | Mild | 130–134 mmol/L | | Moderate | 125–129 mmol/L | | Profound | <125 mmol/L | Terminology varies across guidance. Clinical danger is determined more by symptoms and rate of fall than by any single biochemical category. ### By duration - **Acute:** documented duration <48 hours. - **Chronic:** ≥48 hours. - **Unknown duration:** use chronic correction safeguards unless there is convincing evidence of recent onset.[1] The brain adapts to sustained hypo-osmolality by losing intracellular electrolytes and organic osmolytes. Rapid correction after this adaptation can cause osmotic demyelination syndrome (ODS). ### By tonicity - **Hypotonic hyponatremia:** measured serum osmolality <275 mOsm/kg; this is the main water-balance disorder. - **Hypertonic hyponatremia:** usually due to hyperglycemia or another effective extracellular osmole that draws water out of cells. - **Isotonic or pseudohyponatremia:** laboratory artifact, classically with extreme hypertriglyceridemia or paraproteinemia when sodium is measured by an indirect ion-selective method. ## Pathophysiology When plasma osmolality falls, arginine vasopressin should be suppressed, allowing the kidneys to excrete dilute urine. Hyponatremia persists when water intake exceeds renal free-water excretion because of one or more of the following: - persistent vasopressin release from hypovolemia or low effective arterial volume; - inappropriate vasopressin activity in SIAD; - nausea, pain, stress, pulmonary disease, or central nervous system disease; - glucocorticoid deficiency; - impaired kidney water excretion; - very low solute intake limiting maximal urine volume; - excessive water intake that exceeds renal diluting capacity; - medication effects. ### Cerebral edema An acute fall in extracellular tonicity shifts water into brain cells. Severe acute hyponatremia can therefore cause headache, vomiting, confusion, seizures, respiratory arrest, herniation, and neurogenic pulmonary edema. ### Osmotic demyelination After chronic adaptation, rapid sodium correction produces abrupt extracellular hypertonicity and cellular dehydration. ODS often becomes clinically apparent **2–6 days** after overcorrection and may cause dysarthria, dysphagia, behavioral change, parkinsonism, quadriparesis, locked-in syndrome, or coma.[2,3] ## Immediate assessment ### Severe symptoms Treat first when the clinical syndrome is strongly compatible with hyponatremic cerebral edema: - seizure; - coma; - profound somnolence or obtundation; - rapidly worsening neurologic status; - respiratory compromise plausibly related to cerebral edema. Mild headache, nausea, gait instability, or chronic cognitive symptoms usually permit a more deliberate cause-directed approach unless symptoms are worsening or sodium is falling rapidly. ### Initial bedside priorities - Stabilize airway and breathing. - Check point-of-care glucose. - Confirm sodium promptly if the result is unexpected, but do not delay lifesaving hypertonic saline in a compatible severe syndrome. - Establish IV access and continuous clinical monitoring in severe disease. - Review recent sodium values to determine trajectory and duration. - Identify thiazides, desmopressin, antidepressants, antiseizure drugs, antipsychotics, chemotherapy, opioids, and recent IV fluids. ## Emergency hypertonic saline ### European bolus strategy For severe symptoms, the 2014 European guideline recommends **150 mL of 3% saline IV over 20 minutes**, with sodium reassessment and repeat boluses until symptoms improve or sodium has increased by about **5 mmol/L**.[1] ### US bolus strategy A US expert-panel strategy uses **100 mL of 3% saline IV over 10 minutes**, repeatable up to three times for severe symptoms, targeting an initial rise of about **4–6 mmol/L**.[2] Both strategies use small controlled boluses rather than attempting rapid normalization. ### What to do after initial improvement Once the dangerous neurologic syndrome improves or the initial target rise is reached: 1. Stop repeated hypertonic boluses. 2. Reassess the diagnosis and cause. 3. Calculate the sodium rise from the starting value and track it against 24-hour limits. 4. Measure sodium frequently; every 2–4 hours is reasonable during active correction or unstable trajectories, with shorter intervals when correction is unexpectedly rapid. 5. Track urine output because sudden polyuria often precedes overcorrection. 6. Begin cause-specific treatment. > **Caution:** A patient can overcorrect after hypertonic saline has stopped if the underlying vasopressin stimulus disappears and a brisk water diuresis begins. ## Safe correction limits No correction limit completely eliminates ODS risk. Conservative limits are therefore appropriate in chronic or unknown-duration disease.[1-3] | Clinical context | Practical correction goal/limit | |---|---| | Severe symptomatic initial rescue | Raise approximately 4–6 mmol/L, then reassess | | High ODS risk | Do not exceed 8 mmol/L in any 24 hours | | European general limit | ≤10 mmol/L first 24 h; ≤8 mmol/L per 24 h thereafter | | Unknown duration | Treat with chronic safeguards unless evidence clearly supports acute onset | Potassium replacement can increase serum sodium and should be included in the correction plan. Resolution of hypovolemia, stopping a thiazide, treating adrenal insufficiency, restoring solute intake, or stopping desmopressin can all trigger rapid spontaneous correction. ### Preventing or reversing overcorrection If sodium is rising faster than intended: - stop hypertonic saline and other active sodium-raising measures; - monitor urine output and sodium frequently; - replace urinary water losses with D5W when appropriate; - consider **desmopressin** to stop an uncontrolled aquaresis; - involve nephrology or endocrinology early in severe or high-risk cases.[3] A common specialist approach uses desmopressin in a proactive, reactive, or rescue strategy depending on overcorrection risk. Dose and timing should be individualized because unnecessary desmopressin can prolong hyponatremia, while delayed use can permit ODS-risk correction. ## Diagnostic approach ### Step 1: verify sodium and glucose Hyperglycemia causes translocational hyponatremia. As glucose falls during treatment, measured sodium will rise. Use a corrected-sodium calculation when marked hyperglycemia is present and interpret it as a physiologic estimate rather than a treatment target. When pseudohyponatremia is possible, compare measured serum osmolality and, if needed, sodium measured with a direct ion-selective electrode. ### Step 2: measure serum osmolality | Measured osmolality | Interpretation | |---|---| | <275 mOsm/kg | True hypotonic hyponatremia | | Approximately 275–295 mOsm/kg | Consider pseudohyponatremia or mixed physiology | | >295 mOsm/kg | Hypertonic process, commonly hyperglycemia | ### Step 3: urine osmolality - **≤100 mOsm/kg:** vasopressin is largely suppressed. Consider primary polydipsia, very low solute intake, or recovery from a transient antidiuretic stimulus. - **>100 mOsm/kg:** vasopressin effect is present. This can be appropriate in hypovolemia or reduced effective arterial volume and inappropriate in SIAD after exclusions.[1] ### Step 4: urine sodium A urine sodium threshold near **30 mmol/L** is useful but not absolute.[1] - **<30 mmol/L:** suggests renal sodium conservation from true hypovolemia or reduced effective arterial volume, unless low sodium intake or another confounder is present. - **>30 mmol/L:** can occur with SIAD, diuretics, adrenal insufficiency, renal salt loss, or kidney disease. Thiazides can produce a biochemical pattern that closely resembles SIAD. ## Pattern-based differential diagnosis | Pattern | Urine osmolality | Urine sodium | Common causes | Next step | |---|---:|---:|---|---| | Dilute urine | ≤100 | Variable | Primary polydipsia, low-solute intake | Stop excess water; restore solute cautiously; watch for rapid correction | | Hypovolemic, extrarenal loss | >100 | Often <30 | Vomiting, diarrhea, burns, third spacing | Isotonic volume replacement and cause treatment | | Hypovolemic, renal loss | >100 | Often >30 | Thiazides, mineralocorticoid deficiency, renal salt loss | Stop causative drug; assess adrenal and renal causes | | Euvolemic SIAD pattern | >100 | Usually >30 | Pulmonary/CNS disease, malignancy, drugs, postoperative states | Exclude adrenal deficiency and major thyroid/renal confounders; treat cause and restrict fluid | | Hypervolemic | >100 | Often <30 | Heart failure, cirrhosis | Treat underlying low effective arterial volume state | | Advanced kidney failure | Variable | Variable | Reduced free-water clearance | Kidney-directed fluid and solute management | ## SIAD: diagnostic framework SIAD is a diagnosis of exclusion. Typical findings include:[1] - hypotonic plasma osmolality <275 mOsm/kg; - urine osmolality >100 mOsm/kg despite hypotonicity; - clinically euvolemic state; - urine sodium usually >30 mmol/L with adequate intake; - absence of clinically important renal failure that prevents interpretation; - glucocorticoid deficiency excluded; - no major thyroid disorder sufficient to explain the sodium abnormality; - no recent diuretic effect that invalidates the urine pattern. Supporting findings can include low serum uric acid or urea and increased fractional urate excretion, but none substitutes for excluding adrenal insufficiency. > **Clinical pearl:** Secondary adrenal insufficiency can produce a nearly identical biochemical pattern to SIAD. Do not label unexplained euvolemic hyponatremia as SIAD before considering cortisol deficiency. ## Etiology ### Hypovolemic hypotonic hyponatremia **Extrarenal losses** - vomiting or diarrhea; - high-output ostomy or fistula; - burns; - pancreatitis or other third spacing; - sweating with hypotonic replacement. **Renal losses** - thiazide diuretics; - mineralocorticoid deficiency; - salt-wasting nephropathy; - osmotic diuresis; - selected cerebral or renal salt-wasting states. ### Euvolemic hypotonic hyponatremia - SIAD; - glucocorticoid deficiency; - primary polydipsia; - low-solute intake; - postoperative antidiuresis; - desmopressin; - reset osmostat; - severe hypothyroidism in selected cases. Common SIAD associations include pneumonia, tuberculosis, acute respiratory failure, stroke, intracranial hemorrhage, meningitis, seizures, small-cell lung cancer, pain, nausea, and multiple medications. ### Hypervolemic hypotonic hyponatremia - heart failure; - cirrhosis; - nephrotic syndrome; - advanced kidney failure. Total body sodium may be increased, but water retention is greater. ## Cause-specific treatment ### Hypovolemic hyponatremia Restore effective circulating volume with **0.9% saline** or another appropriate isotonic crystalloid, stop ongoing losses, and stop offending diuretics when possible. Correct potassium deficiency. Once volume is restored, vasopressin can switch off abruptly and urine output may rise sharply. Monitor sodium closely because this is a classic setting for unplanned overcorrection. ### Thiazide-associated hyponatremia Stop the thiazide. Treat severe neurologic symptoms with hypertonic saline. Correct potassium and volume abnormalities carefully. Avoid routine thiazide rechallenge after a serious episode because recurrence is common. ### SIAD 1. Treat or remove the cause when possible. 2. Stop contributing medication when safe. 3. Ensure adequate dietary protein and solute. 4. Use fluid restriction as initial chronic therapy when appropriate. 5. If persistent and clinically important despite restriction, consider oral urea or another specialist-directed second-line therapy.[3] The 2024 treatment standard describes oral **urea 15–60 g/day** as an effective osmotic therapy; dose should be titrated to sodium response, urine osmolality, tolerance, and local formulation.[3,4] Fluid restriction often fails when urine remains highly concentrated or total urinary electrolyte concentration approaches plasma sodium. Do not continue increasingly severe restriction indefinitely without reassessing strategy and nutrition. ### Vaptans Vasopressin-receptor antagonists can raise sodium in selected euvolemic or hypervolemic states, but guideline positions differ and overcorrection can occur. They are **not** emergency therapy for severe symptomatic hyponatremia. Initiation should follow jurisdiction-specific labeling and specialist protocols, with close sodium monitoring. Liver disease, drug interactions, volume status, and access materially affect choice.[1,3] ### Heart failure Treat congestion and the heart-failure syndrome. Fluid restriction and loop diuresis may be appropriate depending on hemodynamics. Hypertonic saline is reserved for severe neurologic symptoms attributable to hyponatremia, not for the sodium value alone. ### Cirrhosis Treat precipitating decompensation, review diuretics, assess effective volume and kidney function, and avoid indiscriminate isotonic saline in a congested patient. Vaptan use is limited by jurisdiction, liver-safety considerations, and guideline differences. Coordinate persistent profound hyponatremia with hepatology, especially around transplant evaluation. ### Primary polydipsia Stop excess water intake and address the driver. Because the kidney may rapidly excrete a large water load once intake stops, monitor sodium closely in profound cases. ### Low-solute intake Restore protein and solute cautiously. A sudden increase in solute can produce brisk aquaresis and rapid sodium correction; frequent monitoring and readiness to use desmopressin/D5W are important in profound chronic disease. ### Adrenal insufficiency Give glucocorticoid replacement when adrenal insufficiency is confirmed or strongly suspected in an unstable patient. Sodium may rise rapidly after cortisol replacement, so correction limits still apply. See [Primary Adrenal Insufficiency in Adults](../endocrinology/primary-adrenal-insufficiency-in-adults.md) and [Adrenal Crisis](../endocrinology/adrenal-crisis.md). ## Monitoring during active correction Record: - serum sodium trajectory from the pretreatment value; - total sodium rise over 6, 12, 24, and 48 hours; - neurologic status; - urine output, especially sudden polyuria; - urine osmolality when mechanism or aquaresis is uncertain; - potassium, glucose, and creatinine; - all sodium-containing infusions and medications; - oral fluid intake and ongoing gastrointestinal losses. During hypertonic saline therapy or unstable correction, sodium often needs measurement every **2–4 hours**, with more frequent checks when the trajectory is rapid or rescue therapy is being used. ## Special scenarios ### Hypokalemia Potassium repletion increases effective body solute and can raise serum sodium. Severe hypokalemia also increases ODS risk. Replace potassium appropriately but include its effect in the total correction plan. ### Hyperglycemia Treat the hyperglycemic emergency. Sodium usually rises as glucose falls because water shifts back intracellularly. Follow measured and corrected sodium trends to avoid misinterpreting the expected change. ### Desmopressin-associated hyponatremia Abruptly withholding desmopressin in severe chronic hyponatremia can trigger uncontrolled water diuresis and dangerous overcorrection. In selected severe cases, specialists may continue scheduled desmopressin while using controlled hypertonic saline, then taper the strategy once the correction trajectory is safe. ### Exercise-associated hyponatremia Suspect in an endurance participant with excessive hypotonic intake, weight gain, headache, confusion, seizure, or pulmonary edema. Do not reflexively give large isotonic fluid volumes to a fluid-overloaded athlete. Severe neurologic symptoms require hypertonic saline. ## Disposition ### Intensive or high-acuity monitoring Appropriate for: - seizure, coma, or severe neurologic symptoms; - active 3% saline bolus therapy; - rapidly changing sodium; - sodium profound enough to create high ODS risk during correction; - need for desmopressin/D5W rescue; - respiratory failure or other critical illness. ### Hospital admission Usually needed for symptomatic profound hyponatremia, uncertain chronicity with high correction risk, significant adrenal or neurologic disease, uncontrolled vomiting, major volume disturbance, or inability to perform safe serial sodium monitoring. ### Discharge Discharge is reasonable only when the dangerous cause has been addressed, neurologic status is stable, sodium is on a safe and predictable trajectory, the treatment plan is feasible, and follow-up sodium measurement is arranged at an interval appropriate to the cause and therapy. ## Related library topics - [Adrenal Crisis](../endocrinology/adrenal-crisis.md) - [Primary Adrenal Insufficiency in Adults](../endocrinology/primary-adrenal-insufficiency-in-adults.md) - [Heart Failure With Reduced Ejection Fraction](../cardiology/heart-failure-with-reduced-ejection-fraction.md) - [Cirrhosis and Portal Hypertension](../gastroenterology/cirrhosis-and-portal-hypertension.md) - [Hepatic Encephalopathy in Cirrhosis](../hepatology/hepatic-encephalopathy-in-cirrhosis.md) ## References 1. Spasovski G, Vanholder R, Allolio B, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. *Eur J Endocrinol*. 2014;170(3):G1-G47. PMID: 24569125. DOI: 10.1530/EJE-13-1020. https://pubmed.ncbi.nlm.nih.gov/24569125/ 2. Verbalis JG, Goldsmith SR, Greenberg A, et al. Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. *Am J Med*. 2013;126(10 Suppl 1):S1-S42. PMID: 24074529. DOI: 10.1016/j.amjmed.2013.07.006. https://pubmed.ncbi.nlm.nih.gov/24074529/ 3. Spasovski G. Hyponatraemia—treatment standard 2024. *Nephrol Dial Transplant*. 2024;39(10):1583-1592. PMID: 39009016. DOI: 10.1093/ndt/gfae162. https://pubmed.ncbi.nlm.nih.gov/39009016/ 4. Spasovski G. Correction to: Hyponatraemia—treatment standard 2024. *Nephrol Dial Transplant*. 2025;40(6):1259. DOI: 10.1093/ndt/gfae213. Correction clarifies the urea dose as 15–60 g. https://doi.org/10.1093/ndt/gfae21319:T5269,## Summary Hyponatremia is serum sodium **<135 mmol/L** and usually reflects excess water relative to exchangeable sodium and potassium. The first two decisions are whether the patient has **true hypotonic hyponatremia** and whether neurologic symptoms require immediate hypertonic saline. Serum sodium concentration alone does not determine urgency; the rate of fall, duration, cause, and neurologic state are critical.[1-3] Seizure, coma, profound obtundation, or another severe neurologic syndrome plausibly caused by hyponatremia warrants prompt **3% hypertonic saline** while the cause is investigated. European guidance uses **150 mL IV over 20 minutes**, reassessing sodium and symptoms and repeating as needed to achieve about a **5 mmol/L early rise**. A widely used US expert approach uses **100 mL IV over 10 minutes**, repeatable up to three times, with an early goal of roughly **4–6 mmol/L**.[1,2] The purpose is to reverse cerebral edema, not to normalize sodium. The major preventable harm after initial stabilization is **overcorrection**, especially in chronic or unknown-duration hyponatremia. Patients at greatest risk for osmotic demyelination include those with very low starting sodium (particularly around ≤105 mmol/L), alcohol use disorder, malnutrition, advanced liver disease, and hypokalemia. In such patients, keep the rise **≤8 mmol/L in any 24 hours**; many clinicians use this conservative ceiling for chronic or uncertain-duration disease more broadly. European guidance allows up to 10 mmol/L in the first 24 hours and 8 mmol/L during each subsequent 24 hours.[1-3] If correction is exceeding the safe trajectory, stop active therapy and consider **desmopressin plus electrolyte-free water such as D5W** with frequent sodium monitoring.[3] For diagnosis, obtain **measured serum osmolality, urine osmolality, and urine sodium** early, ideally before large volumes of IV fluid or diuretics alter the pattern. Urine osmolality ≤100 mOsm/kg indicates near-maximal water excretion; >100 mOsm/kg indicates antidiuretic activity. A urine sodium around **30 mmol/L** is a useful branch point, but diuretics, kidney disease, dietary sodium, and recent fluid therapy can confound interpretation.[1] Treat the mechanism. Hypovolemic hyponatremia usually requires isotonic volume replacement; syndrome of inappropriate antidiuresis (SIAD) often begins with treatment of the cause, adequate solute intake, and fluid restriction; hypervolemic hyponatremia requires treatment of heart failure, cirrhosis, or kidney disease. Once the antidiuretic stimulus resolves, a brisk water diuresis can raise sodium rapidly, so urine output and sodium trajectory are as important as the initial treatment order.[1,3] ## Definition and classification ### By serum sodium | Category | Serum sodium | |---|---:| | Mild | 130–134 mmol/L | | Moderate | 125–129 mmol/L | | Profound | <125 mmol/L | Terminology varies across guidance. Clinical danger is determined more by symptoms and rate of fall than by any single biochemical category. ### By duration - **Acute:** documented duration <48 hours. - **Chronic:** ≥48 hours. - **Unknown duration:** use chronic correction safeguards unless there is convincing evidence of recent onset.[1] The brain adapts to sustained hypo-osmolality by losing intracellular electrolytes and organic osmolytes. Rapid correction after this adaptation can cause osmotic demyelination syndrome (ODS). ### By tonicity - **Hypotonic hyponatremia:** measured serum osmolality <275 mOsm/kg; this is the main water-balance disorder. - **Hypertonic hyponatremia:** usually due to hyperglycemia or another effective extracellular osmole that draws water out of cells. - **Isotonic or pseudohyponatremia:** laboratory artifact, classically with extreme hypertriglyceridemia or paraproteinemia when sodium is measured by an indirect ion-selective method. ## Pathophysiology When plasma osmolality falls, arginine vasopressin should be suppressed, allowing the kidneys to excrete dilute urine. Hyponatremia persists when water intake exceeds renal free-water excretion because of one or more of the following: - persistent vasopressin release from hypovolemia or low effective arterial volume; - inappropriate vasopressin activity in SIAD; - nausea, pain, stress, pulmonary disease, or central nervous system disease; - glucocorticoid deficiency; - impaired kidney water excretion; - very low solute intake limiting maximal urine volume; - excessive water intake that exceeds renal diluting capacity; - medication effects. ### Cerebral edema An acute fall in extracellular tonicity shifts water into brain cells. Severe acute hyponatremia can therefore cause headache, vomiting, confusion, seizures, respiratory arrest, herniation, and neurogenic pulmonary edema. ### Osmotic demyelination After chronic adaptation, rapid sodium correction produces abrupt extracellular hypertonicity and cellular dehydration. ODS often becomes clinically apparent **2–6 days** after overcorrection and may cause dysarthria, dysphagia, behavioral change, parkinsonism, quadriparesis, locked-in syndrome, or coma.[2,3] ## Immediate assessment ### Severe symptoms Treat first when the clinical syndrome is strongly compatible with hyponatremic cerebral edema: - seizure; - coma; - profound somnolence or obtundation; - rapidly worsening neurologic status; - respiratory compromise plausibly related to cerebral edema. Mild headache, nausea, gait instability, or chronic cognitive symptoms usually permit a more deliberate cause-directed approach unless symptoms are worsening or sodium is falling rapidly. ### Initial bedside priorities - Stabilize airway and breathing. - Check point-of-care glucose. - Confirm sodium promptly if the result is unexpected, but do not delay lifesaving hypertonic saline in a compatible severe syndrome. - Establish IV access and continuous clinical monitoring in severe disease. - Review recent sodium values to determine trajectory and duration. - Identify thiazides, desmopressin, antidepressants, antiseizure drugs, antipsychotics, chemotherapy, opioids, and recent IV fluids. ## Emergency hypertonic saline ### European bolus strategy For severe symptoms, the 2014 European guideline recommends **150 mL of 3% saline IV over 20 minutes**, with sodium reassessment and repeat boluses until symptoms improve or sodium has increased by about **5 mmol/L**.[1] ### US bolus strategy A US expert-panel strategy uses **100 mL of 3% saline IV over 10 minutes**, repeatable up to three times for severe symptoms, targeting an initial rise of about **4–6 mmol/L**.[2] Both strategies use small controlled boluses rather than attempting rapid normalization. ### What to do after initial improvement Once the dangerous neurologic syndrome improves or the initial target rise is reached: 1. Stop repeated hypertonic boluses. 2. Reassess the diagnosis and cause. 3. Calculate the sodium rise from the starting value and track it against 24-hour limits. 4. Measure sodium frequently; every 2–4 hours is reasonable during active correction or unstable trajectories, with shorter intervals when correction is unexpectedly rapid. 5. Track urine output because sudden polyuria often precedes overcorrection. 6. Begin cause-specific treatment. > **Caution:** A patient can overcorrect after hypertonic saline has stopped if the underlying vasopressin stimulus disappears and a brisk water diuresis begins. ## Safe correction limits No correction limit completely eliminates ODS risk. Conservative limits are therefore appropriate in chronic or unknown-duration disease.[1-3] | Clinical context | Practical correction goal/limit | |---|---| | Severe symptomatic initial rescue | Raise approximately 4–6 mmol/L, then reassess | | High ODS risk | Do not exceed 8 mmol/L in any 24 hours | | European general limit | ≤10 mmol/L first 24 h; ≤8 mmol/L per 24 h thereafter | | Unknown duration | Treat with chronic safeguards unless evidence clearly supports acute onset | Potassium replacement can increase serum sodium and should be included in the correction plan. Resolution of hypovolemia, stopping a thiazide, treating adrenal insufficiency, restoring solute intake, or stopping desmopressin can all trigger rapid spontaneous correction. ### Preventing or reversing overcorrection If sodium is rising faster than intended: - stop hypertonic saline and other active sodium-raising measures; - monitor urine output and sodium frequently; - replace urinary water losses with D5W when appropriate; - consider **desmopressin** to stop an uncontrolled aquaresis; - involve nephrology or endocrinology early in severe or high-risk cases.[3] A common specialist approach uses desmopressin in a proactive, reactive, or rescue strategy depending on overcorrection risk. Dose and timing should be individualized because unnecessary desmopressin can prolong hyponatremia, while delayed use can permit ODS-risk correction. ## Diagnostic approach ### Step 1: verify sodium and glucose Hyperglycemia causes translocational hyponatremia. As glucose falls during treatment, measured sodium will rise. Use a corrected-sodium calculation when marked hyperglycemia is present and interpret it as a physiologic estimate rather than a treatment target. When pseudohyponatremia is possible, compare measured serum osmolality and, if needed, sodium measured with a direct ion-selective electrode. ### Step 2: measure serum osmolality | Measured osmolality | Interpretation | |---|---| | <275 mOsm/kg | True hypotonic hyponatremia | | Approximately 275–295 mOsm/kg | Consider pseudohyponatremia or mixed physiology | | >295 mOsm/kg | Hypertonic process, commonly hyperglycemia | ### Step 3: urine osmolality - **≤100 mOsm/kg:** vasopressin is largely suppressed. Consider primary polydipsia, very low solute intake, or recovery from a transient antidiuretic stimulus. - **>100 mOsm/kg:** vasopressin effect is present. This can be appropriate in hypovolemia or reduced effective arterial volume and inappropriate in SIAD after exclusions.[1] ### Step 4: urine sodium A urine sodium threshold near **30 mmol/L** is useful but not absolute.[1] - **<30 mmol/L:** suggests renal sodium conservation from true hypovolemia or reduced effective arterial volume, unless low sodium intake or another confounder is present. - **>30 mmol/L:** can occur with SIAD, diuretics, adrenal insufficiency, renal salt loss, or kidney disease. Thiazides can produce a biochemical pattern that closely resembles SIAD. ## Pattern-based differential diagnosis | Pattern | Urine osmolality | Urine sodium | Common causes | Next step | |---|---:|---:|---|---| | Dilute urine | ≤100 | Variable | Primary polydipsia, low-solute intake | Stop excess water; restore solute cautiously; watch for rapid correction | | Hypovolemic, extrarenal loss | >100 | Often <30 | Vomiting, diarrhea, burns, third spacing | Isotonic volume replacement and cause treatment | | Hypovolemic, renal loss | >100 | Often >30 | Thiazides, mineralocorticoid deficiency, renal salt loss | Stop causative drug; assess adrenal and renal causes | | Euvolemic SIAD pattern | >100 | Usually >30 | Pulmonary/CNS disease, malignancy, drugs, postoperative states | Exclude adrenal deficiency and major thyroid/renal confounders; treat cause and restrict fluid | | Hypervolemic | >100 | Often <30 | Heart failure, cirrhosis | Treat underlying low effective arterial volume state | | Advanced kidney failure | Variable | Variable | Reduced free-water clearance | Kidney-directed fluid and solute management | ## SIAD: diagnostic framework SIAD is a diagnosis of exclusion. Typical findings include:[1] - hypotonic plasma osmolality <275 mOsm/kg; - urine osmolality >100 mOsm/kg despite hypotonicity; - clinically euvolemic state; - urine sodium usually >30 mmol/L with adequate intake; - absence of clinically important renal failure that prevents interpretation; - glucocorticoid deficiency excluded; - no major thyroid disorder sufficient to explain the sodium abnormality; - no recent diuretic effect that invalidates the urine pattern. Supporting findings can include low serum uric acid or urea and increased fractional urate excretion, but none substitutes for excluding adrenal insufficiency. > **Clinical pearl:** Secondary adrenal insufficiency can produce a nearly identical biochemical pattern to SIAD. Do not label unexplained euvolemic hyponatremia as SIAD before considering cortisol deficiency. ## Etiology ### Hypovolemic hypotonic hyponatremia **Extrarenal losses** - vomiting or diarrhea; - high-output ostomy or fistula; - burns; - pancreatitis or other third spacing; - sweating with hypotonic replacement. **Renal losses** - thiazide diuretics; - mineralocorticoid deficiency; - salt-wasting nephropathy; - osmotic diuresis; - selected cerebral or renal salt-wasting states. ### Euvolemic hypotonic hyponatremia - SIAD; - glucocorticoid deficiency; - primary polydipsia; - low-solute intake; - postoperative antidiuresis; - desmopressin; - reset osmostat; - severe hypothyroidism in selected cases. Common SIAD associations include pneumonia, tuberculosis, acute respiratory failure, stroke, intracranial hemorrhage, meningitis, seizures, small-cell lung cancer, pain, nausea, and multiple medications. ### Hypervolemic hypotonic hyponatremia - heart failure; - cirrhosis; - nephrotic syndrome; - advanced kidney failure. Total body sodium may be increased, but water retention is greater. ## Cause-specific treatment ### Hypovolemic hyponatremia Restore effective circulating volume with **0.9% saline** or another appropriate isotonic crystalloid, stop ongoing losses, and stop offending diuretics when possible. Correct potassium deficiency. Once volume is restored, vasopressin can switch off abruptly and urine output may rise sharply. Monitor sodium closely because this is a classic setting for unplanned overcorrection. ### Thiazide-associated hyponatremia Stop the thiazide. Treat severe neurologic symptoms with hypertonic saline. Correct potassium and volume abnormalities carefully. Avoid routine thiazide rechallenge after a serious episode because recurrence is common. ### SIAD 1. Treat or remove the cause when possible. 2. Stop contributing medication when safe. 3. Ensure adequate dietary protein and solute. 4. Use fluid restriction as initial chronic therapy when appropriate. 5. If persistent and clinically important despite restriction, consider oral urea or another specialist-directed second-line therapy.[3] The 2024 treatment standard describes oral **urea 15–60 g/day** as an effective osmotic therapy; dose should be titrated to sodium response, urine osmolality, tolerance, and local formulation.[3,4] Fluid restriction often fails when urine remains highly concentrated or total urinary electrolyte concentration approaches plasma sodium. Do not continue increasingly severe restriction indefinitely without reassessing strategy and nutrition. ### Vaptans Vasopressin-receptor antagonists can raise sodium in selected euvolemic or hypervolemic states, but guideline positions differ and overcorrection can occur. They are **not** emergency therapy for severe symptomatic hyponatremia. Initiation should follow jurisdiction-specific labeling and specialist protocols, with close sodium monitoring. Liver disease, drug interactions, volume status, and access materially affect choice.[1,3] ### Heart failure Treat congestion and the heart-failure syndrome. Fluid restriction and loop diuresis may be appropriate depending on hemodynamics. Hypertonic saline is reserved for severe neurologic symptoms attributable to hyponatremia, not for the sodium value alone. ### Cirrhosis Treat precipitating decompensation, review diuretics, assess effective volume and kidney function, and avoid indiscriminate isotonic saline in a congested patient. Vaptan use is limited by jurisdiction, liver-safety considerations, and guideline differences. Coordinate persistent profound hyponatremia with hepatology, especially around transplant evaluation. ### Primary polydipsia Stop excess water intake and address the driver. Because the kidney may rapidly excrete a large water load once intake stops, monitor sodium closely in profound cases. ### Low-solute intake Restore protein and solute cautiously. A sudden increase in solute can produce brisk aquaresis and rapid sodium correction; frequent monitoring and readiness to use desmopressin/D5W are important in profound chronic disease. ### Adrenal insufficiency Give glucocorticoid replacement when adrenal insufficiency is confirmed or strongly suspected in an unstable patient. Sodium may rise rapidly after cortisol replacement, so correction limits still apply. See [Primary Adrenal Insufficiency in Adults](../endocrinology/primary-adrenal-insufficiency-in-adults.md) and [Adrenal Crisis](../endocrinology/adrenal-crisis.md). ## Monitoring during active correction Record: - serum sodium trajectory from the pretreatment value; - total sodium rise over 6, 12, 24, and 48 hours; - neurologic status; - urine output, especially sudden polyuria; - urine osmolality when mechanism or aquaresis is uncertain; - potassium, glucose, and creatinine; - all sodium-containing infusions and medications; - oral fluid intake and ongoing gastrointestinal losses. During hypertonic saline therapy or unstable correction, sodium often needs measurement every **2–4 hours**, with more frequent checks when the trajectory is rapid or rescue therapy is being used. ## Special scenarios ### Hypokalemia Potassium repletion increases effective body solute and can raise serum sodium. Severe hypokalemia also increases ODS risk. Replace potassium appropriately but include its effect in the total correction plan. ### Hyperglycemia Treat the hyperglycemic emergency. Sodium usually rises as glucose falls because water shifts back intracellularly. Follow measured and corrected sodium trends to avoid misinterpreting the expected change. ### Desmopressin-associated hyponatremia Abruptly withholding desmopressin in severe chronic hyponatremia can trigger uncontrolled water diuresis and dangerous overcorrection. In selected severe cases, specialists may continue scheduled desmopressin while using controlled hypertonic saline, then taper the strategy once the correction trajectory is safe. ### Exercise-associated hyponatremia Suspect in an endurance participant with excessive hypotonic intake, weight gain, headache, confusion, seizure, or pulmonary edema. Do not reflexively give large isotonic fluid volumes to a fluid-overloaded athlete. Severe neurologic symptoms require hypertonic saline. ## Disposition ### Intensive or high-acuity monitoring Appropriate for: - seizure, coma, or severe neurologic symptoms; - active 3% saline bolus therapy; - rapidly changing sodium; - sodium profound enough to create high ODS risk during correction; - need for desmopressin/D5W rescue; - respiratory failure or other critical illness. ### Hospital admission Usually needed for symptomatic profound hyponatremia, uncertain chronicity with high correction risk, significant adrenal or neurologic disease, uncontrolled vomiting, major volume disturbance, or inability to perform safe serial sodium monitoring. ### Discharge Discharge is reasonable only when the dangerous cause has been addressed, neurologic status is stable, sodium is on a safe and predictable trajectory, the treatment plan is feasible, and follow-up sodium measurement is arranged at an interval appropriate to the cause and therapy. ## Related library topics - [Adrenal Crisis](../endocrinology/adrenal-crisis.md) - [Primary Adrenal Insufficiency in Adults](../endocrinology/primary-adrenal-insufficiency-in-adults.md) - [Heart Failure With Reduced Ejection Fraction](../cardiology/heart-failure-with-reduced-ejection-fraction.md) - [Cirrhosis and Portal Hypertension](../gastroenterology/cirrhosis-and-portal-hypertension.md) - [Hepatic Encephalopathy in Cirrhosis](../hepatology/hepatic-encephalopathy-in-cirrhosis.md) ## References 1. Spasovski G, Vanholder R, Allolio B, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. *Eur J Endocrinol*. 2014;170(3):G1-G47. PMID: 24569125. DOI: 10.1530/EJE-13-1020. https://pubmed.ncbi.nlm.nih.gov/24569125/ 2. Verbalis JG, Goldsmith SR, Greenberg A, et al. Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. *Am J Med*. 2013;126(10 Suppl 1):S1-S42. PMID: 24074529. DOI: 10.1016/j.amjmed.2013.07.006. https://pubmed.ncbi.nlm.nih.gov/24074529/ 3. Spasovski G. Hyponatraemia—treatment standard 2024. *Nephrol Dial Transplant*. 2024;39(10):1583-1592. PMID: 39009016. DOI: 10.1093/ndt/gfae162. https://pubmed.ncbi.nlm.nih.gov/39009016/ 4. Spasovski G. Correction to: Hyponatraemia—treatment standard 2024. *Nephrol Dial Transplant*. 2025;40(6):1259. DOI: 10.1093/ndt/gfae213. Correction clarifies the urea dose as 15–60 g. https://doi.org/10.1093/ndt/gfae2137:["$","$L17",null,{"article":{"id":"medical-hyponatremia","title":"Hyponatremia","slug":"hyponatremia","description":"Hyponatremia is serum sodium <135 mmol/L and usually reflects excess water relative to exchangeable sodium and potassium. The first two decisions are whether the patient has true hypotonic hyponatremia and whether neu…","aliases":[],"category":"Nephrology","tags":["Nephrology"],"updatedAt":"$undefined","body":"$18","headings":[{"id":"summary","text":"Summary","level":2},{"id":"definition-and-classification","text":"Definition and classification","level":2},{"id":"by-serum-sodium","text":"By serum sodium","level":3},{"id":"by-duration","text":"By duration","level":3},{"id":"by-tonicity","text":"By tonicity","level":3},{"id":"pathophysiology","text":"Pathophysiology","level":2},{"id":"cerebral-edema","text":"Cerebral edema","level":3},{"id":"osmotic-demyelination","text":"Osmotic demyelination","level":3},{"id":"immediate-assessment","text":"Immediate assessment","level":2},{"id":"severe-symptoms","text":"Severe symptoms","level":3},{"id":"initial-bedside-priorities","text":"Initial bedside priorities","level":3},{"id":"emergency-hypertonic-saline","text":"Emergency hypertonic saline","level":2},{"id":"european-bolus-strategy","text":"European bolus strategy","level":3},{"id":"us-bolus-strategy","text":"US bolus strategy","level":3},{"id":"what-to-do-after-initial-improvement","text":"What to do after initial improvement","level":3},{"id":"safe-correction-limits","text":"Safe correction limits","level":2},{"id":"preventing-or-reversing-overcorrection","text":"Preventing or reversing overcorrection","level":3},{"id":"diagnostic-approach","text":"Diagnostic approach","level":2},{"id":"step-1-verify-sodium-and-glucose","text":"Step 1: verify sodium and glucose","level":3},{"id":"step-2-measure-serum-osmolality","text":"Step 2: measure serum osmolality","level":3},{"id":"step-3-urine-osmolality","text":"Step 3: urine osmolality","level":3},{"id":"step-4-urine-sodium","text":"Step 4: urine sodium","level":3},{"id":"pattern-based-differential-diagnosis","text":"Pattern-based differential diagnosis","level":2},{"id":"siad-diagnostic-framework","text":"SIAD: diagnostic framework","level":2},{"id":"etiology","text":"Etiology","level":2},{"id":"hypovolemic-hypotonic-hyponatremia","text":"Hypovolemic hypotonic hyponatremia","level":3},{"id":"euvolemic-hypotonic-hyponatremia","text":"Euvolemic hypotonic hyponatremia","level":3},{"id":"hypervolemic-hypotonic-hyponatremia","text":"Hypervolemic hypotonic hyponatremia","level":3},{"id":"cause-specific-treatment","text":"Cause-specific treatment","level":2},{"id":"hypovolemic-hyponatremia","text":"Hypovolemic hyponatremia","level":3},{"id":"thiazide-associated-hyponatremia","text":"Thiazide-associated hyponatremia","level":3},{"id":"siad","text":"SIAD","level":3},{"id":"vaptans","text":"Vaptans","level":3},{"id":"heart-failure","text":"Heart failure","level":3},{"id":"cirrhosis","text":"Cirrhosis","level":3},{"id":"primary-polydipsia","text":"Primary polydipsia","level":3},{"id":"low-solute-intake","text":"Low-solute intake","level":3},{"id":"adrenal-insufficiency","text":"Adrenal insufficiency","level":3},{"id":"monitoring-during-active-correction","text":"Monitoring during active correction","level":2},{"id":"special-scenarios","text":"Special scenarios","level":2},{"id":"hypokalemia","text":"Hypokalemia","level":3},{"id":"hyperglycemia","text":"Hyperglycemia","level":3},{"id":"desmopressin-associated-hyponatremia","text":"Desmopressin-associated hyponatremia","level":3},{"id":"exercise-associated-hyponatremia","text":"Exercise-associated hyponatremia","level":3},{"id":"disposition","text":"Disposition","level":2},{"id":"intensive-or-high-acuity-monitoring","text":"Intensive or high-acuity monitoring","level":3},{"id":"hospital-admission","text":"Hospital admission","level":3},{"id":"discharge","text":"Discharge","level":3},{"id":"related-library-topics","text":"Related library topics","level":2},{"id":"references","text":"References","level":2}],"readingMinutes":13},"linkedMarkdown":"$19","backlinks":[],"related":[],"previewBySlug":{"abcde-approach":{"title":"ABCDE Approach","description":"The ABCDE approach is a structured method for the immediate assessment and treatment of a deteriorating or critically ill patient: Airway, Breathing, Circulation, Disability, Exposure. 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