> Table of Contents > Hypernatremia
Hypernatremia
Nilgun Ozturk, MD
Pang-Yen Fan, MD
image BASICS
DESCRIPTION
  • Serum sodium (Na) concentration >145 mEq/L (1)
  • Usually represents a state of hyperosmolality (1)
  • Na concentration reflects balance between total body water (TBW) and total body Na. Hypernatremia occurs from deficit of water relative to Na.
  • Hypernatremia results from net water loss or, more rarely, from primary Na gain (1).
  • May exist with hypo-, hyper-, or euvolemia, although hypovolemia is by far most common type
    • Hypovolemic: occurs with a decrease in TBW and a proportionately smaller decrease in total body Na
    • Euvolemic: no change in TBW with a proportionate increase in total body Na
    • Hypervolemic: increase in TBW and a proportionately greater increase in total body Na
  • It has been shown to be an indicator for higher mortality in critically ill patients and patients with chronic kidney disease (CKD) (2)[B].
EPIDEMIOLOGY
Incidence
  • More common in elderly and young
  • Occurs in 1% of hospitalized elderly patients (3)
  • Seen in about 9% of ICU patients (3). Gastroenteritis with diarrhea is the most common cause of hypernatremia in infants.
  • Women are at an increased risk due to decreased TBW, as compared with men.
ETIOLOGY AND PATHOPHYSIOLOGY
  • Pure water loss (total body Na normal) resulting from the following:
    • Adipsia/hypodipsia (e.g., impaired thirst regulation, decreased access to water) (4)
    • Nephrogenic diabetes insipidus (DI) (congenital or due to renal dysfunction, hypercalcemia, hypokalemia, medication-related, particularly lithium)
    • Central DI (due to head trauma, stroke, meningitis) (3)
    • Increased insensible water loss (e.g., fever, hyperventilation, hypermetabolic state, heat exposure, newborns under radiant warmers)
  • Hypotonic fluid loss (total body Na decreased) resulting from the following:
    • Loss of fluid containing relatively more water than Na (e.g., excessive sweating, severe burns)
    • Urinary loss
      • Osmotic diuresis: hyperglycemia, mannitol
      • Diuretics, especially loop diuretics
      • Diabetes mellitus, particularly new presentation/decompensated
      • Post acute tubular necrosis (ATN) or post obstructive diuresis
      • Intrinsic renal disease
    • Gastrointestinal loss
      • Diarrhea, especially in children
      • Vomiting, nasogastric (NG) lavage
      • Enterocutaneous fistula
  • Excess Na (increase in total body Na) resulting from the following:
    • IV NaCl or NaHCO3 during cardiopulmonary resuscitation, metabolic acidosis, or hyperkalemia (3)
    • Sea water ingestion
    • Excessive use of NaHCO3 antacid.
    • Incorrect infant formula preparation
    • Intrauterine NaCl for abortion
    • Excessive Na in dialysate solutions
    • Disorders of the adrenal axis (Cushing syndrome, Conn syndrome, congenital adrenal hyperplasia)
    • Tube feeding
With acute hypernatremia, the rapid decrease in brain volume can cause rupture of the cerebral veins, leading to focal intracerebral and subarachnoid hemorrhages and possibly irreversible neurologic damage (5).
Genetics
Some forms of DI may be hereditary.
RISK FACTORS
  • Patients at increased risk include those with an impaired thirst mechanism or restricted access to water, as well as those with increased water loss
  • Infants/children
  • Elderly patients (may also have a diminished thirst response to osmotic stimulation via an unknown mechanism)
  • Patients who are intubated/have altered mental status.
  • Diabetes mellitus
  • Prior brain injury
  • Surgery
  • Diuretic therapy, especially loop diuretics
  • Lithium treatment
GENERAL PREVENTION
  • Treatment/prevention of underlying cause
  • Properly prepare infant formula and never add salt to any commercial infant formula.
  • Keep patients well hydrated.
COMMONLY ASSOCIATED CONDITIONS
  • Gastroenteritis
  • Altered mental status
  • Burns
  • Hypermetabolic conditions
  • Head injury
  • Renal dysfunction
image DIAGNOSIS
PHYSICAL EXAM
  • Sinus tachycardia, hypotension, orthostatic hypotension, poor O2 saturation
  • Dry mucous membranes, cool/gray skin
  • Neurologic abnormalities: lethargy, weakness, focal deficits (in cases of intracerebral bleeding/lesion), confusion, coma, seizures
DIFFERENTIAL DIAGNOSIS
  • DI
  • Hyperosmotic coma
  • Salt ingestion
  • Hypertonic dehydration
  • Hypothyroidism
  • Cushing syndrome
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • Serum Na, potassium, BUN, creatinine, calcium, and osmolality (serum lithium if appropriate)
  • Urine Na and osmolality
    • DI: urine osmolality (usually <300 mosmol/kg) < serum osmolality, and urine Na usually low normal/slightly low (due to dilution) (4)
    • Osmotic diuresis: urine osmolality intermediate, urine Na low/low-normal, total daily osmole excretion high
    • Salt ingestion: increased urine osmolality (above 600 mosmol/kg) and high urine Na
    • Hypertonic dehydration: increased urine osmolality and decreased urine Na
  • Serum glucose
  • Special tests for DI
    • Water deprivation test: In DI, urine osmolality does not increase as it normally should when hypernatremic.
    • Antidiuretic hormone (ADH) stimulation: distinguishes central versus nephrogenic DI
      • Urine osmolality does not increase after ADH or desmopressin (DDAVP) in nephrogenic DI.
  • Head CT/MRI in DI to rule out craniopharyngioma, other brain tumor or masses, or median cleft syndrome
Diagnostic Procedures/Other
History, physical, laboratory studies, family history for central DI
image TREATMENT
GENERAL MEASURES
  • The treatment of hypernatremia involves treating the underlying cause and correcting the water deficit.
  • Goal for corrected Na is 145 mEq/L (1).
  • Speed of correction depends on symptom severity/rate of development of hypernatremia. Avoid rapid correction to prevent development of cerebral edema if chronic hypernatremia (>24 hours):
    • Maximum of 0.5 mEq/L/hr or 10 mEq/L/day (6)[C]
    • May correct at up to 1 mEq/L/hr if acute hypernatremia (<24 hours) (1)
  • Treat volume depletion first, then hypernatremia:
    • Restore intravascular volume with IV fluids to normalize serum Na levels.
  • Replace water orally if patient is conscious.
  • Important formulas in determining rate of fluid administration
    • TBW = coefficient × wt (kg), where coefficient = 0.6 for children, 0.5 for nonelderly women and elderly men, 0.45 for elderly women
    • P.511

    • Calculated free water deficit (liters) = TBW × [1 - (Na_t/Na_m)], where Na_t = target Na+, and Na_m = measured Na+. Note: wt = weight in kilograms.
    • Change in serum Na per 1 L infusate = [(infusate Na + infusate K) - serum Na]/[TBW + 1]
  • Account for ongoing fluid losses during calculation of rate of fluid administration.
  • Dialysis can be considered if acute kidney injury is present concomitantly and if conventional treatment has failed (7)[B].
MEDICATION
First Line
  • See “General Measures” for overall approach.
  • Volume depletion: Use isotonic fluids initially if signs of hemodynamic compromise, then change to hypotonic fluids when stable:
    • Hypotonic fluids (0.45% NaCl or dextrose 5% in water)
      • Important not to decrease serum Na by >10 mEq/L/day to prevent cerebral edema (4)[C]
  • Hypervolemia: Give furosemide along with hypotonic fluids. Dose varies depending on desired urine output. Loop diuretics with fluid restriction worsen hypernatremia (4)[C].
  • Central DI
    • DDAVP acetate: Use parenteral form for acute symptomatic patients, and use intranasal or oral form for chronic therapy (4).
    • Free water replacement: may use 2.5% dextrose in water if giving large volumes of water in DI to avoid glycosuria
    • May consider sulfonylureas/thiazide diuretics for chronic, but not acute, treatment
  • Nephrogenic DI
    • Treat with diuretics and NSAIDs.
    • Lithium-induced nephrogenic DI: hydrochlorothiazide 25 mg PO BID or indomethacin 50 mg PO TID, or amiloride hydrochloride 5 to 10 mg PO BID (8)
  • Precautions
    • Rapid correction of hypernatremia can cause cerebral edema, central pontine myelinosis, seizures, or death (9).
    • Hypocalcemia and more rarely acidosis can occur during correction.
    • DI: High rates of dextrose 5% in water can cause hyperglycemia and glucose-induced diuresis.
Second Line
  • Consider NSAIDs in nephrogenic DI.
  • Modalities requiring further investigations
  • Continuous renal replacement therapy (CRRT): Multiple case reports and case series have shown success and safety in using CRRT to treat hypernatremia in critically ill patients with CHF and severe burns (7,10).
ISSUES FOR REFERRAL
Underlying renal involvement associated with hypernatremia would benefit from a nephrology referral.
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
Symptomatic patient with serum Na >155 mEq/L requires IV fluid therapy.
IV Fluids
Refer to “Medication” section.
Nursing
Bed rest until stable or underlying condition resolved/controlled
Discharge Criteria
Stabilization of serum Na level and symptoms are minimal.
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
  • Frequent reexams in an acute setting
  • Frequent electrolytes and blood glucose: initially q4-6h
  • Urine osmolality and urine output in DI
  • Ensure adequate ingestion of calories because patients may ingest so much water that they feel full and do not eat.
  • Measure ongoing losses of water and solute and replace as needed.
  • Daily weights
DIET
  • Ensure proper nutrition during acute phase.
  • After resolution of acute phase, may want to consider Na-restricted diet for patient
  • Low-salt, low-protein diet in nephrogenic DI
PATIENT EDUCATION
Patients with nephrogenic DI must avoid salt and drink large amounts of water.
PROGNOSIS
Most recover but neurologic impairment can occur.
REFERENCES
1. Adrogué HJ, Madias NE. Hypernatremia. N Engl J Med. 2000;342(20):1493-1499.
2. Kovesdy CP, Lott EH, Lu JL, et al. Hyponatremia, hypernatremia, and mortality in patients with chronic kidney disease with and without congestive heart failure. Circulation. 2012;125(5): 677-684.
3. Bagshaw SM, Townsend DR, McDermid RC. Disorders of sodium and water balance in hospitalized patients. Can J Anaesth. 2009;56(2): 151-167.
4. Hannon MJ, Finucane FM, Sherlock M, et al. Clinical review: disorders of water homeostasis in neurosurgical patients. J Clin Endocrinol Metab. 2012;97(5):1423-1433.
5. Sterns RH. Disorders of plasma sodium—causes, consequences, and correction. N Engl J Med. 2015;372(1):55-65.
6. Al-Absi A, Gosmanova EO, Wall BM. A clinical approach to the treatment of chronic hypernatremia. Am J Kidney Dis. 2012;60(6):1032-1038.
7. Huang C, Zhang P, Du R, et al. Treatment of acute hypernatremia in severely burned patients using continuous veno-venous hemofiltration with gradient sodium replacement fluid: a report of nine cases. Intensive Care Med. 2013;39(8):1495-1496.
8. Libber S, Harrison H, Spector D. Treatment of nephrogenic diabetes insipidus with prostaglandin synthesis inhibitors. J Pediatr. 1986;108(2):305-311.
9. Mastrangelo S, Arlotta A, Cefalo MG, et al. Central pontine and extrapontine myelinolysis in a pediatric patient following rapid correction of hypernatremia. Neuropediatrics. 2009;40(3): 144-147.
10. Park HS, Hong YA, Kim HG, et al. Usefulness of continuous renal replacement therapy for correcting hypernatremia in a patient with severe congestive heart failure. Hemodial Int. 2012;16(4):559-563.
Additional Reading
&NA;
Waite MD, Fuhrman SA, Badawi O, et al. Intensive care unit-acquired hypernatremia is an independent predictor of increased mortality and length of stay. J Crit Care. 2013;28(4):405-412.
See Also
&NA;
  • Diabetes Insipidus
  • Algorithm: Hypernatremia
Codes
&NA;
ICD10
E87.0 Hyperosmolality and hypernatremia
Clinical Pearls
&NA;
  • Occurs from water deficit in comparison to total body Na stores
  • Common causes include dehydration, DI, impaired access to fluids
  • Determine if the patient has hypervolemic, euvolemic, or hypovolemic hypernatremia in the differential diagnosis of etiology; most commonly hypovolemic; other entities rare
  • Avoid rapid correction of hypernatremia to prevent development of cerebral edema when hypernatremia is chronic (goal rate is 10 meq/L in 24 hours).
  • Use hypotonic fluids unless patient has hemodynamic compromise, which necessitates use of isotonic fluids.
  • Use oral replacement in conscious patients if possible.
  • Use the estimated water deficit, desired rate of correction, and estimation of ongoing free water losses to calculate a fluid repletion regimen.