Definition

Hypernatremia is defined as serum [Na+] >135 mmol/L. Hypernatremia is associated with hypertonicity, contributing to fluid shifts across cell membranes. Hypernatremia has been associated with higher mortality in hospitalized patients.

Etiology/Risk Factors

• Hypernatremia represents a relative deficit of free water, which may be from:
  • Renal water loss
    • Central diabetes insipidus (DI): decreased ADH.
      • Causes: trauma/post-surgical, pituitary lesions, mass effect, granulomatous disease, Sheehan’s syndrome.
    • Nephrogenic diabetes insipidus: decreased kidney responsiveness to ADH.
      • Causes: congenital, amyloidosis, granulomatous disease, sickle cell disease, obstructive uropathy, hypercalcemia, hypokalemia, drugs (vaptans, lithium).
    • Loop diuretics.
    • Osmotic diuresis (hyperglycemia, mannitol, urea).
    • Post-obstructive or post-ATN auto-diuresis.
  • Extrarenal water loss
    • Vomiting/NG suction.
    • Hypotonic diarrhea/osmotic cathartics.
    • High output surgical drains.
    • Increased insensible losses: large surface area burns or open surgical sites, mechanical ventilation, excess sweating.
  • Hypertonic intake: hypertonic saline, hypertonic sodium bicarbonate pushes, excess salt or soy sauce ingestion, salt water drowning.
• In normal circumstances, any rise in serum [Na+] triggers thirst, increasing water intake to correct hypertonicity. Sustained hypernatremia requires either:
  • Impairment of ability to consume free water: altered mental status, sedation, immobility, difficulty communicating thirst, NPO status.
  • Impairment of the thirst mechanism: hypothalamic lesions.

Evaluation

• Cause of hypernatremia is often apparent from history and review of medications, nutrition, and intake/output, especially when onset is during hospitalization.
• Determine whether there is inappropriate renal free water loss:
  • In DI, urine will be inappropriately dilute (<300 mOsm/L).
    • Water deprivation test will result in rising serum [Na+] and persistently dilute urine.
    • Desmopressin response after water deprivation can differentiate nephrogenic (no response) from central DI (concentration of urine).
    • Most patients with DI are normonatremic due to adequate water intake, and will not become hypernatremic unless water access is impaired (e.g. NPO for surgery).

Management

Traditionally, rapid correction of hypernatremia was thought to cause cerebral edema. However, this is a theoretical concern extrapolated from the pediatric literature; there is no evidence for neurological harms in adults.

• Step 1: calculate the free water deficit. 
  • Free water deficit = TBW * ((serum [Na+] / goal [Na+]) - 1)
    • TBW (total body water) may be estimated by weight (kg) * 0.6 (for men) or weight (kg) * 0.5 (for women).
    • Goal [Na+] should be no more than 10 mEq/L/day less than current [Na+].
  • Note: free water deficit will underestimate true need because it does not account for ongoing water losses. If substantial, then that water loss will need to be estimated and added to the calculated deficit in order to achieve the goal.
• Step 2: choose your method and rate of correction.
  • Free water may be equivalently administered IV (D5W) or enterally (oral or free water flushes if tube fed).
  • Divide your free water deficit by 24 hours, and give accordingly.
  • Check serum Na every 6-12 hours to adjust correction rate and follow urine output.
• Helpful tips:
  • Because water distributes evenly to all body compartments, its effect on vascular congestion is minimal (~11% intravascular). However, if necessary, loop diuretics can be used to avoid volume overload. 
  • Likewise for volume depleted patients, water is an ineffective resuscitation fluid, and isotonic crystalloid may be given in parallel to correct hypovolemia, preferably LR (130 mEq/L) or plasmalyte (140 mEq/L) due to lower Na content relative to NS (154 mEq/L). The effect of resuscitative isotonic fluids on free water deficit calculations is minimal.

Key Points

• Hypernatremia is most often due to inadequate water intake (relative to water output), occasionally from excess sodium intake, and rarely from diabetes insipidus.
• Mainstay of treatment is giving free water after calculating a free water deficit.
• Goal rate of correction is not to exceed 10 mEq/L/day.
• A common error in management is not giving enough water to account for ongoing losses.

Reynolds RM, Padfield PL, Seckl JR. Disorders of sodium balance. BMJ 2006;332:702-705.

Chauhan K, Pattharanitima P, Patel N, et al. Rate of correction of hypernatremia and health outcomes in critically ill patients. Clin J Am Soc Nephrol. 2019;14(5):656-663.

Seay NW, Lehrich RW, Greenberg A. Diagnosis and Management of Disorders of Body Tonicity—Hyponatremia and Hypernatremia: Core Curriculum 2020. Am J Kidney Dis 2019;75(2):272-286.