Hyponatremia

Diagnosis

What's serum osmolality?

Not hypotonic:

• Hypertonic (>295): hyperglycemia, mannitol, IVIG
• Isotonic (275–295): pseudohyponatremia from severe hypertriglyceridemia, paraproteinemia, lipemia

Hypotonic (<275) means true hyponatremia and you move on.

What's urine osmolality?

Urine osm <100:

• ADH off, kidney appropriately diluting urine
• Think primary polydipsia, low solute intake such as beer potomania or tea/toast, reset osmostat
• These patients often auto-correct once intake/solute issue is addressed

Urine osm >100:

• ADH on, impaired free water excretion
• Then assess volume status

What is their volume status?

Hypovolemic:

• GI losses, hemorrhage, diuretics, adrenal insufficiency
• Urine Na ≤30 suggests extrarenal loss
• Urine Na >30 suggests renal loss

Euvolemic:

• SIADH, hypothyroidism, adrenal insufficiency
• Urine Na often >30

Hypervolemic:

• CHF, cirrhosis, nephrotic syndrome
• Urine Na often ≤30

Uosm & UNa

• Urine osm <100 means the kidney can dilute and the issue is excess water intake or low solute intake
• Urine osm >300 means the patient is not excreting free water and IV fluids may worsen sodium
• Urine Na ≤30 suggests low effective arterial volume
• Urine Na >30 suggests SIADH or renal salt loss

Workup

• Serum osm
• Urine osm
• Urine Na
• Glucose and corrected Na if hyperglycemic
• Creatinine
• K and bicarbonate
• Cortisol
• TSH

Helpful clues from the history

• Thiazides, SSRIs, antiepileptics, DDAVP
• CNS disease, pulmonary disease, malignancy
• Recent surgery
• Low protein/low solute intake
• Polydipsia

Symptoms

Severe symptoms

• Seizure
• Coma
• Respiratory arrest

Mild to moderate symptoms

• Nausea, vomiting
• Headache
• Confusion
• Gait issues
• Muscle cramps

Acute hyponatremia has higher herniation risk. Chronic hyponatremia has lower herniation risk but much higher risk from overcorrection.

Treatment

• Severe symptoms
  • 3% NaCl 100 mL IV over 10 min
  • Repeat up to 2 more times if needed
  • Initial goal: Na ↑ 4–6 mEq/L
• Low solute / primary polydipsia
  • Restrict free water
  • Increase dietary protein/solute
  • Watch closely for rapid autocorrection
• Hypovolemic hyponatremia
  • 0.9% saline
  • Stop ongoing losses / offending diuretics
  • Replete K and Mg
  • Expect Na to rise once volume is restored
• SIADH
  • Stop offending drugs and treat underlying trigger
  • Fluid restrict ~800–1000 mL/day
  • If persistent: oral urea 15–30 g/day, up to 60 g/day
  • Consider loop diuretic in selected patients
  • Avoid routine normal saline if urine is concentrated
• Hypervolemic hyponatremia
  • Fluid restrict ~1–1.5 L/day
  • Loop diuresis if congested
  • Treat HF, cirrhosis, nephrotic syndrome, or kidney failure
  • Avoid routine isotonic saline
• Adrenal insufficiency / crisis
  • Hydrocortisone 100 mg IV once
  • Then 50 mg IV q6h
  • Give isotonic fluids if volume depleted
• Monitoring
  • Na q2–4h during active or rapid correction
  • Otherwise q4–6h during treatment
  • Usual initial target: +4–6 mEq/L
  • High ODS risk: keep ≤8 mEq/L in 24 h
  • Avoid >18 mEq/L in 48 h
  • If overcorrecting: desmopressin 2 mcg IV/SC q6–8h + D5W as needed

• Correction guardrails
  • Severe neurologic symptoms: 3% saline 100 mL IV over 10 minutes, repeat up to 2 more times as needed; initial goal +4 to 6 mEq/L
  • Chronic or unknown duration: keep correction ≤8 mEq/L/24 h when high risk for ODS and ≤10 mEq/L/24 h otherwise; avoid >18 mEq/L/48 h
  • High ODS risk: Na ≤105, hypokalemia, alcohol use disorder, malnutrition, advanced liver disease
  • During active correction follow Na about every 2 to 4 hours and urine output closely; potassium repletion also raises Na
  • If overcorrecting: stop active correction, consider desmopressin 2 mcg IV/SC every 6 to 8 hours plus D5W to match urine losses or re-lower Na

High demyelination risk

• Na ≤105
• Hypokalemia
• Alcohol use disorder
• Malnutrition
• Liver disease

Prevent overcorrection

• DDAVP clamp when needed
• Check Na every 4 to 6 hours
• Overcorrection often happens after giving volume, fixing adrenal insufficiency, or restricting water in polydipsia
• Calculate their free water deficit to determine how much free water to give if you overcorrect

References

1. Spasovski, G. (2024). Hyponatraemia—treatment standard 2024. Nephrology Dialysis Transplantation, 39(10), 1583–1592. https://doi.org/10.1093/ndt/gfae162
2. Spasovski, G., Vanholder, R., Allolio, B., Annane, D., Ball, S., Bichet, D., Decaux, G., Fenske, W., Hoorn, E. J., Ichai, C., Joannidis, M., Soupart, A., Zietse, R., Haller, M., van der Veer, S., Van Biesen, W., & Nagler, E. (2014). Clinical practice guideline on diagnosis and treatment of hyponatraemia. Intensive Care Medicine, 40(3), 320–331. https://doi.org/10.1007/s00134-014-3210-2
3. Verbalis, J. G., Goldsmith, S. R., Greenberg, A., Korzelius, C., Schrier, R. W., Sterns, R. H., & Thompson, C. J. (2013). Diagnosis, evaluation, and treatment of hyponatremia: Expert panel recommendations. The American Journal of Medicine, 126(10 Suppl 1), S1–S42. https://doi.org/10.1016/j.amjmed.2013.07.006
4. Seay, N. W., Lehrich, R. W., & Greenberg, A. (2020). Diagnosis and management of disorders of body tonicity: Hyponatremia and hypernatremia. American Journal of Kidney Diseases, 75(2), 272–286. https://doi.org/10.1053/j.ajkd.2019.07.014
5. Sterns, R. H., Riggs, J. E., & Schochet, S. S., Jr. (1986). Osmotic demyelination syndrome following correction of hyponatremia. The New England Journal of Medicine, 314(24), 1535–1542. https://doi.org/10.1056/NEJM198606123142402
6. Sood, L., Sterns, R. H., Hix, J. K., Silver, S. M., & Chen, L. (2013). Hypertonic saline and desmopressin: A simple strategy for safe correction of severe hyponatremia. American Journal of Kidney Diseases, 61(4), 571–578. https://doi.org/10.1053/j.ajkd.2012.11.032
7. Sterns, R. H. (2010). Treatment of hyponatremia. Current Opinion in Nephrology and Hypertension, 19(5), 493–498. https://doi.org/10.1097/MNH.0b013e32833bfa64
8. Bornstein, S. R., Allolio, B., Arlt, W., Barthel, A., Don-Wauchope, A., Hammer, G. D., Husebye, E. S., Merke, D. P., Murad, M. H., Stratakis, C. A., & Torpy, D. J. (2016). Diagnosis and treatment of primary adrenal insufficiency: An Endocrine Society clinical practice guideline. Journal of Clinical Endocrinology & Metabolism, 101(2), 364–389. https://doi.org/10.1210/jc.2015-1710