Hypernatremia

Hypernatremia is defined as a serum sodium concentration exceeding 145 mEq/L. Sodium is the most important osmotically active particle in the extracellular space and closely linked to the body's fluid balance. An increase in the serum sodium concentration is most often due to a free water deficit caused by excessive fluid loss (e.g., diarrhea/vomiting, sweating, increased diuresis) or insufficient water intake (e.g., altered mental status, impaired thirst mechanism). In some cases, hypernatremia is due to a real sodium overload caused by high sodium intake (e.g., hypertonic infusion, drinking sea water) or inadequately high sodium reabsorption by the kidneys (e.g., primary hyperaldosteronism, Cushing syndrome). Symptoms are predominantly neurological and nonspecific (e.g., lethargy, confusion, focal neurological deficits, seizures, coma), and they are often accompanied by signs of cellular dehydration (e.g., dry mucous membranes, decreased salivation). Assessing the patient's volume status (during physical examination) and their renal ability to reabsorb free water (urine osmolality) can help determine the etiology of hypernatremia. Acuity of onset, volume status, and etiology should all be considered in order to determine the appropriate therapeutic approach and avoid complications. In children, a rapid decrease in the serum sodium concentration can cause cerebral edema, which carries the risk of brain herniation. In adults, a relationship between rapid correction and cerebral edema has not been observed; however, guidelines still recommend cautious correction.

• Eunatremia: a normal concentration of sodium in the blood (i.e., 136–145 mEq/L).
• Hypernatremia: elevated serum sodium concentration (> 145 mEq/L) ^[1][2]

In hypernatremia, serum osmolality is always increased, resulting in a hypertonic state. This is either due to a free water deficit (due to low intake or loss) or increased sodium (due to high intake or retention).

Hypovolemic hypernatremia

• Description: high serum Na⁺ levels with decreased extracellular volume as a result of hypotonic fluid loss
• Extrarenal cause (manifests with oliguria due to dehydration)
  • Gastrointestinal loss; (e.g. diarrhea , vomiting, drainage from nasogastric tubes, fistula)
  • Dermal fluid loss (e.g., burns, excessive sweating)
  • Third-spacing (peritonitis, ascites)
• Renal cause (leads to dehydration due to polyuria)
  • Diuretics
  • Osmotic diuresis (e.g., hyperglycemia, mannitol, uremia, high-protein tube feeding, osmotic diuretics)
  • Recovery (polyuric) phase of acute tubular necrosis

Euvolemic hypernatremia

• Description: high serum Na⁺ levels with normal or minimal changes in extracellular volume as a result of pure water deficit
• Extrarenal causes (manifests with oliguria due to decreased water intake)
  • Lack of access to water
    • Altered mental status (e.g., dementia, drug-induced)
    • Immobilization
    • Physically restrained patients
    • Quadriparesis
  • Impaired thirst mechanism: primary hypodipsia
  • Mechanical ventilation
• Renal cause (causes increased thirst due to polyuria)
  • Diabetes insipidus
    • Central: complete or partial lack of ADH secretion
    • Nephrogenic: complete or partial resistance to the action of ADH

Hypervolemic hypernatremia

• Description: high serum Na⁺ levels with increased extracellular volume as a result of intake of hypertonic water or retention of sodium in excess of water
• Extrarenal causes (initially manifests with polyuria due to fluid overload, followed by dehydration due to polyuria)
  • Iatrogenic: excessive infusion of NaCl, sodium bicarbonate solutions, or hypertonic saline; hemodialysis
  • Seawater consumption
• Renal causes (causes hypertension and hypokalemia with normal urine output and no fluid overload)
  • Primary hyperaldosteronism
  • Cushing syndrome

Overview of fluid compartment changes

Hypernatremia is always a hyperosmolar state!

References:^[3]

Acute hypernatremia (onset < 48 hours) ^[4][5]

Symptoms are primarily neurological and depend on the severity of hypernatremia.

• Mild symptoms: signs of dehydration
  • Decreased salivation
  • Dry mucous membranes and skin
• Moderate symptoms
  • Confusion
  • Irritability, restlessness
  • Lethargy
  • Muscle weakness
  • Hyperreflexia
• Severe symptoms: typically occur only with severe hypernatremia (serum concentration > 160 mEq/L) ^[2]
  • Focal neurological deficits
  • Seizures
  • Altered consciousness
  • Stupor
  • Coma

Chronic hypernatremia (onset > 48 hours ago)

• Often asymptomatic or nonspecific, mild symptoms
• Commonly: signs of dehydration (especially in hypovolemic hypernatremia)
• Rarely: irritability, anorexia, nausea, weakness, and/or altered mental status

Approach ^[3]

• Confirm hypernatremia (repeat BMP).
• Determine the etiology through clinical evaluation, and, if unclear, perform diagnostic studies.
  • Patient history (e.g., low fluid intake, diarrhea)
  • Clinical assessment of volume status (i.e., hypovolemia, euvolemia, versus hypervolemia) and fluid balance monitoring
  • Urine osmolality and urine sodium concentration help differentiate renal causes from extrarenal causes.
  • Additional studies as needed (e.g., water deprivation test for diabetes insipidus)

Laboratory studies ^[3]

• BMP
  • Serum sodium concentration (Na⁺): > 145 mEq/L
  • Laboratory findings of hypovolemia
• CBC: Hematocrit level depends on volume status.
• Increased serum osmolality (S_Osm) ^[6]
• Urine osmolality; (U_Osm) ^[4]
  • High U_Osm (> 600 mOsmol/kg) supports an extrarenal mechanism.
  • Low U_Osm (< 600 mOsmol/kg) supports an intrarenal mechanism.
• Urine sodium concentration (U_Na)
  • U_Na < 20 mEq/L supports hypovolemia. ^[3]
  • U_Na > 100 mEq/L supports sodium overload. ^[4]
• Water deprivation test and exogenous ADH challenge, if indicated (see “Diagnostics” in “Diabetes insipidus”)

In a state of free water deficit, highly concentrated urine (↑ urine osmolality) is a sign of normal kidney function.

Hypernatremia is always a hypertonic state!

Treatment of hypernatremia requires replacing the free water deficit with sterile water enterally (oral, nasogastric tube, PEG tube) or 5% dextrose in water (D5W) intravenously. All patients should be carefully monitored with serial labs and some may need additional therapies to restore volume status.

Approach ^[2][4]

• Hypovolemic patients: volume resuscitation
  • Severe volume depletion or shock: Restore euvolemia with isotonic solutions (e.g., normal saline) before correcting hypernatremia.
  • Mild to moderate volume depletion: simultaneous volume resuscitation and hypernatremia correction
• Identify and treat underlying causes
  • Prevent ongoing fluid loss: e.g., fever control, symptomatic management of gastrointestinal symptoms
  • Treat underlying conditions: e.g., desmopressin for central diabetes insipidus, insulin for hyperglycemia (see “Hyperglycemic crises” for management of severe hyperglycemia)
• Hypernatremia correction
  • Determine Na⁺ correction rates based on whether hypernatremia is acute or chronic.
  • Replace the free water deficit orally with water or IV via an effective hypotonic solution (typically D5W, or hypotonic saline).
• Treat complications
  • Of disease: Treat acute seizures.
  • Of treatment: Begin ICP management if cerebral edema develops.

The cornerstone of hypernatremia management is replacing the free water deficit.

Calculation of free water deficit in hypernatremia ^[4]

Calculations of the free water deficit and ongoing water losses are more accurate than rough estimates. Electrolytes must be carefully monitored during treatment and regimens should be individually tailored.

• Combine free water deficit (FWD) and ongoing losses.
  • Estimate the patient's total body water (TBW): TBW (L) = k x weight (kg).
  • Calculate FWD (L) = TBW (L) x ((serum Na⁺ concentration/140)-1).
  • Estimate ongoing free water losses (input/output chart, insensible losses). ^[2][6]
• Timeframe of volume replacement
  • Acute hypernatremia: over 24 hours
  • Chronic hypernatremia: over 48– 72 hours ^[12]

Correction of free water deficit ^[2][4]

• Acute hypernatremia (onset within < 48 hours)
  • Decrease Na⁺ concentration by 1–2 mEq/L/hour (i.e., replace entire free water deficit in < 24 hours). ^[4]
  • Estimated fluid replacement regimen: ∼ 3 mL/kg/hour of IV D5W or enteral water ^[4]
• Chronic hypernatremia (onset within > 48 hours)
  • Gradually restore a normal Na⁺ level by decreasing Na⁺ concentration by 0.5 mEq/L/hour (max. 10–12 mEq/L per 24 hours). ^[4][13][14]
  • Oral rehydration with free access to water may be sufficient in stable and alert patients.
  • Estimated fluid replacement regimen: 1.35 mL/kg/hour of IV D5W or enteral water ^[15]
• Adjustment of infusion rate
  • Fluids other than D5W or sterile water require a different flow rate to provide the same amount of free water.
  • Depending on serial Na⁺ concentration

Additional fluid management strategies

• Hypervolemic hypernatremia: Consider loop diuretics (e.g., furosemide oral or IV bolus ) alongside free water replacement. ^[16][17][18]
• Severe renal impairment or refractory fluid overload: Consider nephrology referral for hemodialysis. ^[5]
• Sodium restriction to < 2 grams per day ^[19][20][21]

Alleviate Acute hypernatremia Aggressively and Correct Chronic hypernatremia Carefully!

Monitoring and disposition

• Serial BMPs every 1–2 hours for acute hypernatremia; every 4–6 hours for chronic hypernatremia
• Adjust free water infusion rate according to target Na⁺ correction rates.
• Monitor for hyperglycemia. ^[16]
• Replace electrolyte deficiencies (see “Electrolyte repletion").
• Consider ICU admission for patients with severe hypernatremia (Na⁺ > 160 mEq/L) and high-risk symptoms (e.g., seizures).

• Confirm hypernatremia (repeat BMP).
• Assess volume status.
• If the patient is hypovolemic, volume resuscitate first with isotonic fluids (e.g., normal saline).
• Determine whether hypernatremia is acute or chronic in nature.
• Free water replacement (enterally or D5W IV): Correct aggressively for acute hypernatremia and gradually for chronic hypernatremia.
• Order serial BMPs, monitor closely, and adjust fluid rate as needed.
• Treat the underlying cause and prevent further fluid losses.
• Consider ICU admission in patients with severe hypernatremia (i.e., > 160 mEq/L).

Complications of hypernatremia

• Intracranial hemorrhage
  • Cell dehydration and shrinkage of brain tissue can cause intracranial vessels to rupture.
  • Hemorrhages may lead to irreversible neurological deficits.
• Osmotic demyelination syndrome
  • Demyelinating brain lesions from the acute rise in serum sodium levels and serum osmolality
  • More commonly seen with overcorrection of hyponatremia
• Rhabdomyolysis: Severe hypernatremia can damage the cell membranes of muscle cells.

Complications of hypernatremia treatment

• Cerebral edema: may develop from rapid correction of chronic hypernatremia ^[4][13][14]
• Hypervolemia complications: secondary to hypernatremia correction with large-volume IV fluid administration (e.g., noncardiogenic pulmonary edema)

We list the most important complications. The selection is not exhaustive.