Hyponatremia on the Wards: Classify, Treat, and Avoid Osmotic Demyelination

1) Hyponatremia on the Wards: How Step 2 Tests It and What to Do First

On Step 2 CK, hyponatremia questions hinge on two decisions you must make quickly: (1) Is this true hypotonic hyponatremia causing cerebral edema (emergent)? and (2) What does the urine tell you about the mechanism (hypovolemic, SIADH/euvolemic, or hypervolemic)? Begin with basic stratification: confirm low measured serum sodium, check serum osmolality, and assess volume status at the bedside. If serum osmolality is normal or high, think pseudohyponatremia (hyperlipidemia, paraproteinemia) or translocational hyponatremia (hyperglycemia, mannitol)—not hypotonic water retention. True hypotonic hyponatremia plus moderate–severe neurologic symptoms (confusion, seizures, obtundation) mandates immediate 3% hypertonic saline bolus to raise Na⁺ by ~4–6 mEq/L in the first hour. Limit total correction to ≤10–12 mEq/L in 24 hours for average risk and ≤8 mEq/L if high risk for osmotic demyelination (Na ≤105, alcoholism, malnutrition, liver disease, hypokalemia). Continuous neurologic checks and q2–4h chemistries are expected in exam vignettes.

Urine osmolality separates impaired water excretion (U_osm > 100 mOsm/kg) from excess water intake/low solute states (U_osm ≤ 100). Next, urine Na⁺ helps: low (<30 mEq/L) usually signals hypovolemia with avid sodium retention; higher values (>30) suggest SIADH or renal salt loss. Endocrine checks (AM cortisol; TSH) appear frequently in “refractory hyponatremia” stems. For SIADH, euvolemia on exam is paired with U_osm >100, U_Na >30, low serum uric acid, and normal adrenal/thyroid testing. Step 2 often tests pitfalls: rapid overcorrection after isotonic saline in hypovolemic hyponatremia (an “aquaresis” once ADH turns off), and the role of early desmopressin (“DDAVP clamp”) to cap the correction rate in high-risk patients.

2) Mechanisms: Why Sodium Falls and How the Brain Adapts

Hyponatremia is predominantly a disorder of water balance. Plasma tonicity is governed by the osmostat in the hypothalamus (osmoreceptors), arginine vasopressin (AVP/ADH) release, thirst, and renal free water clearance. In hypotonic hyponatremia, ADH is inappropriately present (SIADH, hypovolemia, pain/nausea, medications) or water intake overwhelms excretory capacity (primary polydipsia, “tea and toast,” beer potomania). Hypovolemia—true or effective (heart failure, cirrhosis)—stimulates non-osmotic ADH despite low tonicity. Thiazides uniquely increase distal Na⁺ loss and impair urine dilution; loops blunt the medullary gradient and tend to help with free-water excretion when combined with salt. Pseudohyponatremia occurs with severe hyperlipidemia or hyperproteinemia when sodium is measured by indirect ion-selective electrode; measured serum osmolality remains normal. Hyperglycemia causes translocational hyponatremia (water shift from intracellular to extracellular), which corrects as glucose normalizes.

The brain adapts to chronic hyponatremia (≥48 hours) by extruding electrolytes and organic osmolytes, reducing cerebral edema and dulling symptoms. This adaptation makes rapid “back-correction” dangerous: as plasma Na⁺ rises abruptly, brain cells—now osmotically depleted—shrink, risking osmotic demyelination syndrome (ODS). Clinical ODS ranges from dysarthria and quadriparesis to “locked-in” syndrome. High-risk substrates (alcohol use disorder, malnutrition, advanced liver disease, hypokalemia, very low Na⁺ ≤105) underpin Step 2’s stringent correction limits and justify DDAVP strategies to slow overcorrection.

3) Diagnostic Algorithm: Osmolality → Urine Osm → Urine Na

1. Confirm hypotonicity. Serum osmolality <275 mOsm/kg defines hypotonic hyponatremia. If normal/high, think pseudo/translocational causes (lipids/proteins, hyperglycemia, mannitol). Correct Na⁺ for severe hyperglycemia on exams; treat the glucose derangement rather than giving hypertonic saline.
2. Urine osmolality. ≤100 mOsm/kg = maximally dilute urine (primary polydipsia, low-solute states). >100 mOsm/kg = ADH effect (SIADH, hypovolemia, hypervolemia, endocrine causes).
3. Urine sodium. U_Na <30 mEq/L suggests hypovolemia; U_Na >30 mEq/L suggests SIADH/renal salt loss. Correlate with exam findings (mucous membranes, orthostasis, edema).
4. Rule endocrine mimics. Check AM cortisol and TSH when patterns are inconsistent or unresponsive to standard measures.

Exam cue: a euvolemic patient with small cell lung cancer, U_osm 500 mOsm/kg, U_Na 60 mEq/L, normal thyroid/adrenal testing → SIADH; start fluid restriction, consider salt tablets + loop, and treat the malignancy.

4) Emergencies: Hypertonic Saline, Targets, and Preventing Overcorrection

For moderate–severe symptoms (seizures, obtundation, impending herniation), give 3% NaCl boluses and reassess mental status and serum sodium. Common protocols: 100 mL over 10 minutes (repeat up to two additional times), or 150 mL over 20 minutes per European guidance. The goal is an initial rise of ~4–6 mEq/L to reverse encephalopathy, then slow down. Titrate with frequent chemistry checks (q20–60 minutes during boluses, then q2–4 hours). Avoid continuous high-rate infusions except under strict monitoring. Once the patient improves, do not chase a normal sodium quickly.

To prevent osmotic demyelination, cap correction: average-risk ≤10–12 mEq/L in 24 hours and ≤18 in 48 hours; high-risk ≤8 mEq/L in 24 hours. The “DDAVP clamp” (scheduled desmopressin with titrated 3% NaCl) deliberately fixes a high urine osmolality so you add sodium at a controlled rate, especially when a brisk water diuresis is expected (hypovolemic hyponatremia, low-solute states). If overcorrection occurs, therapeutic re-lowering with desmopressin and D5W to bring Na⁺ back within limits is acceptable and tested.

Board trap: a patient with hypovolemic hyponatremia gets isotonic saline and then rapidly diureses water; Na⁺ shoots up by 12 mEq/L overnight—initiating DDAVP and D5W to re-lower is the best next step to avoid ODS.

5) Chronic & Etiology-Specific Management: SIADH, Hypovolemia, Hypervolemia, Low-Solute

SIADH (euvolemic). First-line is fluid restriction (typically <800–1000 mL/day, or ~500 mL below 24-h urine volume). If inadequate, add increased solute (oral NaCl ± loop diuretic to increase free-water excretion), or urea (15–30 g BID where available). Treat drivers (e.g., small cell lung cancer, SSRIs, carbamazepine, CNS/pulmonary disease). Vasopressin antagonists (tolvaptan) can raise Na⁺, but Step 2 expects caution (cost, liver toxicity, rapid correction risk); they’re seldom first-line for chronic outpatient SIADH.

Hypovolemic hyponatremia. Restore volume with isotonic saline; as effective arterial volume normalizes, ADH falls and a free-water diuresis may trigger overcorrection—anticipate with frequent Na⁺ checks and consider a proactive or reactive DDAVP clamp in high-risk patients. Replace concurrent potassium deficits (hypokalemia heightens ODS risk and contributes to apparent Na⁺ rise as K⁺ shifts intracellularly).

Hypervolemic hyponatremia (HF, cirrhosis, nephrotic). Sodium and fluid restriction, loop diuretics, and aggressive optimization of the underlying disease (afterload reduction, diuresis; transplant evaluation in cirrhosis). Vaptans may transiently improve Na⁺ but have not improved outcomes; avoid in advanced liver disease on exams.

Low-solute states and primary polydipsia. Increase dietary protein/solute and correct slowly; these patients are notorious overcorrectors after a single meal or IVF. Consider early DDAVP if the initial U_osm ≤100 and the clinical story fits (“beer and pretzels,” poor dietary intake).

When to search for endocrine disease. Unexplained or refractory hyponatremia warrants AM cortisol (adrenal insufficiency) and TSH (severe hypothyroidism). Correct the endocrine disorder first; sodium usually follows.

6) Pharmacology & Dosing: 3% NaCl, Desmopressin, Loops, Urea, and Vaptans

Hypertonic saline (3%). For severe symptoms, use bolus dosing (100–150 mL), repeating with q20–60-minute Na⁺ checks until symptoms abate (~4–6 mEq/L rise). For controlled correction (e.g., with a DDAVP clamp), small titrated boluses or low-rate infusions (e.g., 0.5–2 mL/kg/h) are acceptable with ICU-level monitoring. Peripheral administration is generally safe with vigilance for phlebitis; central access is not required for brief boluses. The sodium deficit can be estimated as: TBW × (Na_target − Na_current), where TBW ≈ 0.6 × weight (men), 0.5 (women), 0.45 (elderly). Avoid “chasing” the full deficit acutely.

Desmopressin (DDAVP). IV/SC 1–2 μg (or 10 μg intranasal) every 6–8 hours in a proactive (start early), reactive (start when Na⁺ rises too fast), or rescue strategy (after overshoot). Pair with hypertonic saline to “clamp” urine output/osmolality and meet correction targets. If overshoot occurs, combine DDAVP with D5W to re-lower.

Loop diuretics with salt. Furosemide promotes electrolyte-free water excretion by abolishing the medullary gradient; use with oral salt in SIADH to increase solute delivery and protect against volume expansion. Monitor K⁺, Mg²⁺, and volume status.

Urea. Oral urea (commonly 15–30 g BID where available) increases osmotic excretion of water and is effective in chronic SIADH; palatability and access limit use in some regions. Check local availability and protocols.

Vaptans. Tolvaptan selectively antagonizes V2 receptors, increasing free-water excretion and raising Na⁺. Consider only in carefully selected chronic euvolemic/hypervolemic cases when conventional measures fail, with attention to hepatic toxicity, cost, drug interactions, and overcorrection risk. Avoid in severe liver disease.

7) Classic Vignettes & Integrations: What the Question Is Really Asking

Beer potomania (low solute). Middle-aged person with alcohol use, Na⁺ 118, U_osm 65 mOsm/kg, U_Na 10 mEq/L. After a sandwich and IVF, Na⁺ jumps by 10 overnight. Best next step: DDAVP + D5W to re-lower, then slow solute repletion with careful monitoring.

Thiazide-induced hyponatremia. Older woman started on hydrochlorothiazide presents with confusion; labs show U_osm 400 mOsm/kg, U_Na 50 mEq/L. Stop thiazide, restrict fluids; severe symptoms → 3% bolus. Expect gradual improvement; counsel against future thiazide use.

SIADH from small cell lung cancer. Smoker with weight loss and hyponatremia; serum uric acid low, U_osm 550, U_Na 60. Manage with restriction, salt + loop, consider urea; definitive control requires tumor therapy. Avoid rapid correction; consider DDAVP strategy if Na⁺ begins to climb too quickly.

Postoperative hyponatremia. Post-op nausea/pain ↑ADH; hypotonic fluids worsen hyponatremia. Treat with fluid restriction; moderate symptoms may need cautious 3% NaCl. Prevent with isotonic maintenance and minimizing nausea/pain stimuli for ADH.

Adrenal insufficiency. Hyponatremia with hypotension, hyperkalemia, hyperpigmentation, and eosinophilia. Low AM cortisol with inadequate cosyntropin response. Treat with stress-dose steroids first—sodium typically corrects without hypertonic saline unless severely symptomatic.

Pregnancy and cirrhosis/heart failure overlays. These etiologies produce effective arterial hypovolemia with non-osmotic ADH. On exams, prioritize disease-directed therapy (afterload reduction/diuresis for HF; transplant/cirrhosis care) plus sodium/water restriction and loops, not vaptans in decompensated cirrhosis.

Takeaway: Map the triad—U_osm, U_Na, and volume status—to mechanism; then apply correction physics (initial 4–6 mEq/L if symptomatic; daily caps) while anticipating aquaresis and using DDAVP/D5W to keep sodium movement deliberate.

8) Pitfalls, Rapid-Review Checklist, and Board-Style Associations

• Rapid-Review Checklist
• Confirm hypotonicity (serum Osm). If not low, think pseudo/translocational.
• U_osm ≤100 = low-solute/polydipsia; U_osm >100 = ADH effect.
• U_Na <30 hypovolemia; U_Na >30 SIADH/renal salt loss.
• Severe symptoms → 3% NaCl bolus to +4–6 mEq/L; then slow.
• Daily caps: ≤10–12 mEq/L (average risk) or ≤8 (high risk). If overshoot, DDAVP + D5W to re-lower.
• Hypovolemic cases can overcorrect after isotonic saline—anticipate aquaresis with DDAVP strategy.
• SIADH: fluid restriction first; add solute + loop; consider urea; vaptans rarely first-line.
• Check AM cortisol and TSH when the pattern is atypical or refractory.

Board-style associations: Small cell lung cancer → SIADH; marathon runner who drinks only water → exercise-associated hyponatremia; elderly on thiazide → confusion & falls; beer potomania → U_osm ≤100 and dramatic overcorrection after a meal. The most point-dense mistake is allowing a chronic hyponatremia to correct too fast; the best answer is often to slow down with DDAVP, add free water, and adhere to caps.

References

1. European Society of Endocrinology Clinical Guideline: Management of Hyponatraemia
2. Lawless SJ, et al. The management of acute and chronic hyponatraemia (2022)
3. EMCrit IBCC: Hyponatremia (2024)
4. Rondon-Berrios H, et al. Hypertonic Saline for Hyponatremia (2021)
5. Sterns RH. Treatment Guidelines for Hyponatremia (2024)
6. MacMillan TE, et al. ODS in hospitalized patients (2023)
7. Hoorn EJ, Zietse R. Diagnosis and Treatment of Hyponatremia (2017)
8. Chifu I, et al. Treatment of symptomatic hyponatremia with hypertonic saline (2021)
9. Rondon-Berrios H, et al. Therapeutic re-lowering after overcorrection (2020)
10. UCSF Hospital Handbook: Hyponatremia
11. Pakchotanon K, et al. Proactive vs reactive DDAVP strategies (2024)
12. Adrogué HJ, Madias NE. JAMA Review of Hyponatremia (2022)