I. Problem/Condition.

Hypernatremia is defined as a plasma sodium concentration greater than 145 millimoles/liter (mmol/L) and reflects a deficit of water relative to solute. It is always a hyperosmolar state.

In normal individuals, regulation of plasma osmolarity is so efficient that sustained hypernatremia will not occur as long as there is adequate free water ingestion. Therefore, insufficient hydration is nearly always a component of the pathophysiology of hypernatremia (Figure 1).

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Figure 1.n

Regulation of Osmolality.

Hypernatremia is seen less commonly than hyponatremia in hospitalized patients, with an overall incidence of 1-5% of inpatients. The incidence in critically ill patients is higher, between 10-25%. However, over 60% of hypernatremic patients develop it while hospitalized and only 0.1-1.4% patients present to the hospital with it. Thus, hypernatremia is often a syndrome of iatrogenesis and those at extremes of age and infirmity are most susceptible.

The hyperosmolarity associated with hypernatremia adversely affects neurologic function, as well as cardiac contractility, hepatic gluconeogenesis and peripheral insulin sensitivity. It can also lead to rhabdomyolysis and impaired lactate clearance. It is associated with increased mortality (>40% in some studies) and in intensive care unit (ICU) settings, it is an independent predictor of mortality, complications and increased length of stay (LOS).

II. Diagnostic Approach

A. What is the differential diagnosis for this problem?

Hypernatremia can result from any of the following three basic mechanisms:

1. Net water deficit (i.e. dehydration)

This is the most common etiology. A result of excessive fluid loss and/or inadequate water intake. Fluid loss can be classified into either renal or extra-renal causes; in each case, the fluid lost can be either hypotonic or electrolyte free (i.e., pure water):

Renal water loss (dilute urine)
  • Pharmacologic diuresis (e.g., loop diuretics)

  • Osmotic diuresis:

    Most commonly hyperglycemia, intravenous (IV) mannitol, and urea (caused by a high protein diet such as with certain enteral feedings).

  • Diabetes insipidus:


    Post-acute tubular necrosis (ATN) diuresis

    Post-obstructive diuresis



    Medications (lithium, demeclocycline, amphotericin and others)

    Sickle cell anemia



    Hereditary (e.g. Wolfram syndrome)

    Trauma or pituitary surgery


    Sheehan’s Syndrome (post-partum pituitary necrosis)

    Meningitis, encephalitis, tuberculosis

    Autoimmune (lymphocytic neurohypophysitis)

Extra-renal water loss (concentrated urine)
  • Insensible losses:



    Severe burns

    Respiratory tract

  • Gastro-intestinal (GI) losses:

    Osmotic diarrhea (water loss exceeds electrolyte loss)

    Infectious enteritides (viral > bacterial)

    Osmotic laxatives (lactulose, polyethylene glycol [PEG], sorbitol, etc.)

    Inadequate water intake due to:

    Impaired access to water (extremes of age, altered mental status)

    Diminished thirst (hypodipsia)

    Usually due to hypothalamic osmoreceptor dysfunction:



    Vascular insults

    Infiltrative disorders, such as




2. Primary Na+gain (hypervolemic hypernatremia)

  • This is uncommon.

  • Occurs with:

    administration of hypertonic saline or sodium bicarbonate solutions.

    massive sodium ingestion (e.g. saline gargle, emetic solutions, salt water drowning).

    mineralocorticoid excess (Cushing’s syndrome, Conn’s Syndrome).

    accidental or non-accidental salt ingestion in infants/children.

  • Generally corrects spontaneously if renal function is intact:

    loop diuretics can facilitate urinary excretion of sodium.

    urine output should be replaced with a similar amount of water.

3. Water loss into cells

  • This is seen rarely.

  • Can occur with seizures or strenuous exercise.

    Intracellular glycogen breakdown into smaller, osmotically active molecules draws water out of the intravascular space and into cells (Figure 2).

  • Generally transient and resolves quickly after cessation of exertion.

Figure 2.n

Intracellular and Extracellular Fluid Compartments in Hypernatremia.

B. Describe a diagnostic approach/method to the patient with this problem

Since net free water loss is the most common etiology, a thorough history can frequently reveal the underlying cause of the patient’s hypernatremia. Less common causes of hypernatremia should be sought once water loss has been thoroughly ruled out. In the event that the history is unhelpful or cannot be obtained, assessments of the patient’s volume status and renal concentrating ability are necessary next steps.

Hypovolemic hypernatremia (Figure 3) develops when a patient loses sodium-containing (i.e. hypotonic) fluid, with relatively greater losses of water than sodium. Physical examination reflects diminished total body water, including orthostasis, tachycardia, jugulo-venous collapse, dry mucous membranes and poor skin turgor.

Figure 3.n

Diagnostic Algorithm for Hypernatremia.

The appropriate renal response to hypovolemia is conservation of water and sodium, resulting in a minimal volume of maximally concentrated urine. Thus, measurement of urinary sodium and osmolality can differentiate renal vs. extra-renal water loss. Urinary Na+ less than 20mmol/L indicates renal sodium conservation and extra-renal loss of hypotonic fluid (frequently from the GI tract or skin). If the urinary sodium concentration is greater than 20mmol/L, then there is renal sodium wasting with concomitant renal water loss (e.g. loop diuretics)

Water loss without accompanying sodium loss does not cause clinically apparent hypovolemia, though the extracellular fluid (ECF) is mildly contracted. Thus, patients with pronounced pure water loss and without water repletion develop euvolemic hypernatremia. It is important to note that both loss of pure water and inadequate water intake (either due to impaired thirst or lack of access) are necessary to develop hypernatremia. In these patients, urinary sodium measurements may vary. Thus, urinary osmolality needs to be measured.

High urine osmolality (>700-800 milliosmolar/kilogram [mOsm/kg]) indicates intact renal concentrating mechanisms and therefore extra-renal water loss. Dilute urine in the setting of hypernatremia is physiologically inappropriate (since the kidneys should be conserving water). This suggests Diabetes insipidus.

Hypervolemic hypernatremia is always a result of sodium gain rather than water depletion. The clinician’s dilemma is to determine the source. Potential etiologies include IV administration of hypertonic saline or sodium bicarbonate solutions, ingestion of hypertonic solutions or sodium chloride, hypertonic dialysis, and mineralocorticoid excess.

1. Historical information important in the diagnosis of this problem.

Hypernatremia is nearly always preventable with adequate intake of water. Thus, the treating physician should determine if the patient’s water intake is restricted by:

  • impaired mental status?

  • intubation?

  • frailty/infirmity (i.e. extremes of age)?

  • impaired thirst?

Next, investigate sources of fluid loss:

  • “Has your urine output increased/decreased recently?”

    “increased” suggests renal free water loss

    “decreased” suggests extra-renal losses

  • “Have you had vomiting or diarrhea recently?”

  • “Have you been eating/drinking normally?”

  • “Have you been more thirsty than usual?”

    “yes” implies an intact thirst mechanism

    “no” suggests inadequate thirst response (due to osmoreceptor dysfunction)

  • “Have you had any fevers?”

  • “Have you started any new medications or supplements?”

2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.

  • Measurement of orthostatic blood pressure and heart rate.

  • Assessment of skin turgor and mucous membranes.

  • Thorough neurologic examination including mental status.

3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.

  • plasma sodium

  • urine sodium

  • urine osmolality

  • 24 hour urine volume, water deprivation test (if diabetes insipidus is suspected)

D. Over-utilized or “wasted” diagnostic tests associated with the evaluation of this problem.

Serum osmolality.

III. Management while the Diagnostic Process is Proceeding

A. Management of hypernatremia.

Management of hypernatremia requires repletion of free water (and intravascular volume if necessary). To do so, answer the following questions:

  • What is the underlying etiology of the hypernatremia?

  • What is the water deficit?

  • What is the appropriate rate of correction of the water deficit, given the clinical context?

The clinician’s initial step should be to address the underlying cause of the hyperosmolar state. For example, in a febrile patient with insensible losses causing hypernatremia, the fevers should be addressed with anti-pyretic therapy (and anti-microbial therapy, if indicated).

Next, the patient’s water deficit must be calculated so that re-hydration can begin. This can be calculated using the equation:

  • Water Deficit = TBW x [(plasma Na+/140) – 1]

Total body water (TBW) of young, healthy patients is approximately 50-60% of lean body weight (for women and men, respectively). However, for elderly patients in whom the osmoreceptor response may be chronically blunted or in very young patients with significant dehydration, 45-50% of body weight may be a more accurate estimation of TBW. Note: This equation does not account for ongoing insensible losses and assumes constant total body sodium levels.

Thus, for a 70-year-old female who weighs 65 kilograms (kg) and whose measured plasma sodium is 155 mmol/L, the water deficit is:

  • (65 x 0.45) x [(155/140) – 1] = 3.1 L

This is the amount of free water required to return the plasma sodium concentration to 140 mmol/L. Now the clinician must determine how quickly to replete the water.

Acute symptomatic hypernatremia which has developed in less than 48 hours requires rapid correction, since cerebral shrinkage can result in seizures, subarachnoid hemorrhage, coma and death. The plasma sodium should be reduced 1 mmol/L per hour in this situation.

In patients with hypernatremia of longer or unknown duration, a slower correction is necessary to minimize the risk of cerebral edema. The maximal rate of correction in such patients is 0.5 mmol/L per hour (or 12 mmol per day). Most experts agree, however, that reducing the sodium concentration 10 mmol/L per day is safe and prudent.

Let’s go back to the elderly female patient with hypernatremia. Her calculated water deficit is 3.1 L. Assume that yesterday her measured plasma sodium was 140. Her sodium is now 155 and she is encephalopathic, perhaps post-ictal. Her sodium needs to be corrected rapidly to reduce her risk of further morbidity and mortality. The rate at which free water should be infused is calculated as follows (assuming 1 mmol/L per hour correction):

  • 3100 mL free water deficit /15 hours* = 207 milliliters/hour (mL/hr) (a 15 mmol/L rise in sodium corrected at 1 mmol/L/hr will take 15 hours)

However, this infusion rate dose not take into account ongoing insensible losses (which occur at 30-40 ml per hour) . Thus, a free water solution (such as D5W) should be infused at 250 ml/hour. Frequent serum sodium measurements must be made.

But what if the hypernatremia is of an unknown duration? Then the water deficit must be corrected slowly. In this situation, judicious correction of serum sodium should occur at about 10 mmol/L per day, but not more than 12 mmol/L per day. Thus, to correct the 15 mmol/L rise in sodium at a rate of 10 mmol/L per day:

  • 15 mmol/L divided by 10 mmol/L per day = 1.5 days = 36 hours

  • 3100 mL free water/36 hours = 86 mL/hr

Again, insensible water losses may require an additional 30-40 ml/hr. Thus, a D5W infusion at 125 ml/hr is reasonable. It remains imperative that plasma sodium measurements be made every one to two hours (at least initially) to ensure the appropriate rate of correction.

B. Common Pitfalls and Side-Effects of Management of this Clinical Problem

Rapid correction of hypernatremia present for over 48 hours is more dangerous than hypernatremia itself as it can cause cerebral edema, resulting in seizures, coma and cerebral herniation. Thus, even after careful calculation of the water deficit, the sodium concentration should be measured every two hours for the first 8-12 hours, and then every four hours.

While overly rapid correction is the most dangerous aspect of treating hypernatremia, it may be more commonly under-corrected. Under-correction may occur for several reasons:

  • In patients with depletion of total body sodium due to loss of hypotonic fluid (i.e., hypovolemic hypernatremia), the free water deficit is underestimated by the above equation.

  • The addition of solutes reduces the amount of free water being delivered (e.g. 1L of 0.45 normal saline [NS] consists of 500 milliliters [ml] of free water and 500 ml of 0.9 NS).

  • Dextrose containing solutions (e.g., D5W) administered to hyperglycemic or diabetic patients can cause osmotic diuresis and worsen free water losses.

In the first situation, the solution is to rehydrate the patient more aggressively. Isontonic saline should be used if the patient is hemodynamically compromised; otherwise hypotonic solutions are required.

Certain clinical situations may require solute-added fluids (e.g., 0.45% saline with 20 mol potassium). In this case, the calculations of volume to be infused and infusion rate must be modified to account for the solute. The effect of 1L of any type of fluid on plasma sodium concentration can be estimated using the formula below; the necessary volume and infusion rate can then be determined (Figure 4).

Figure 4.n

Formulas for use in management of hypernatremia and characteristics of infusates.

Using the 70-year-old woman with a plasma sodium of 155 mmol/L, the change in sodium concentration after 1L of 0.45% saline would be:

(77-155)/[(0.45 x 65) + 1] = -2.58 mmol/L

Thus, to correct the sodium concentration 15 mmol/L (i.e., to 140 mmol/L), the patient needs 5.8L of 0.45% saline (15/2.58 = 5.8). With the addition of 1L to account for ongoing losses, 6.8L will need to be administered over the next 36 hours at 190 ml/hr.

What’s the evidence?

Snyder, NA, Feigal, DW, Arieff, AI. “Hypernatraemia in elderly patients”. A heterogeneous, morbid and iatrogenic entity. Ann Intern Med. vol. 107. 1987. pp. 309-319.

Stelfox, HT, Ahmed, SB, Khandwala, F. “The epidemiology of intensive care unit-acquired hyponatremia and hypernatremia in medical-surgical intensive care units”. Crit Care. vol. 12. 2008. pp. R162

Lukitsch, I, Pham, TQ. “Hypernatremia”.

Linder, G, Funk, G-C, Schwarz, C. “Hypernatremia in the Critically Ill Is an Independent Risk Factor for Mortality”. Am J of Kidney Dis. vol. 50. 2007. pp. 952-957.

Darmon, M, Timsit, JF, Francais, A. “Association between hypernatremia acquired in the ICU and mortality: a cohort study”. Nephrol Dial Transplant. vol. 25. 2010. pp. 2510-2515.

Pavelsky, PM, Bhagrath, R, Greenberg, A. “Hypernatremia in Hospitalized Patient”. Ann Intern Med 1996,. vol. 124. 1996. pp. 197-203.

Bagshaw, SM, Townsend, DR, McDermid, RC. “Disorders of sodium and water balance in hospitalised patients”. Can J Anesth. vol. 56. 2009. pp. 151-167.

Darmon, M, Diconne, E. “Prognostic consequences of dysnatremia: pay attention to minimum serum sodium change”. Crit Care. vol. 17. 2013.

Adrogue, HJ, Madias, NE. “Hypernatremia”. NEJM. vol. 342. 2000. pp. 1493-1499.

Adler, SM, Verbalis, JG. “Disorders of Body Water Homeostasis. Acute Endocrinology: From Cause to Consequence”. Contemporary Endocrinology Series. 2008. pp. 277-304.

Howard, C, Berl, T. “Disorders of Water Balance: Hyponatremia & Hypernatremia”. Chapter 3 in: CURRENT Diagnosis and Treatment: Nephrology & Hypertension. 2008. pp. 22-31.

Lerma, EV, Berns, JS, Nissenson, AR. “CURRENT Diagnosis & Treatment: Nephrology & Hypertension”.