Diagnosis and Management of

Sodium Disorders:​Hyponatremia
and Hypernatremia
Nathaniel E. Miller, MD, and David Rushlow, MD, MBOE, Mayo Clinic, Rochester, Minnesota
Stephen K. Stacey, DO, La Crosse-Mayo Family Medicine Residency, Mayo Clinic Health System, La Crosse, Wisconsin

Hyponatremia and hypernatremia are electrolyte disorders that can be associated with poor outcomes. Hyponatremia is consid-
ered mild when the sodium concentration is 130 to 134 mEq per L, moderate when 125 to 129 mEq per L, and severe when less
than 125 mEq per L. Mild symptoms include nausea, vomiting, weakness, headache, and mild neurocognitive deficits. Severe
symptoms of hyponatremia include delirium, confusion, impaired consciousness, ataxia, seizures, and, rarely, brain herniation
and death. Patients with a sodium concentration of less than 125 mEq per L and severe symptoms require emergency infusions
with 3% hypertonic saline. Using calculators to guide fluid replacement helps avoid overly rapid correction of sodium concen-
tration, which can cause osmotic demyelination syndrome. Physicians should identify the cause of a patient’s hyponatremia, if
possible;​however, treatment should not be delayed while a diagnosis is pursued. Common causes include certain medications,
excessive alcohol consumption, very low-salt diets, and excessive free water intake during exercise. Management to correct
sodium concentration is based on whether the patient is hypovolemic, euvolemic, or hypervolemic. Hypovolemic hyponatre-
mia is treated with normal saline infusions. Treating euvolemic hyponatremia includes restricting free water consumption or
using salt tablets or intravenous vaptans. Hypervolemic hyponatremia is treated primarily by managing the underlying cause
(e.g., heart failure, cirrhosis) and free water restriction. Hypernatremia is less common than hyponatremia. Mild hypernatre-
mia is often caused by dehydration resulting from an impaired thirst mechanism or lack of access to water;​however, other
causes, such as diabetes insipidus, are possible. Treatment starts with addressing the underlying etiology and correcting the
fluid deficit. When sodium is severely elevated, patients are symptomatic, or intravenous fluids are required, hypotonic fluid
replacement is necessary. (Am Fam Physician. 2023;​108(5):476-486. Copyright © 2023 American Academy of Family Physicians.)

Sodium abnormalities are common electrolyte disor- concentration is too low, water moves from the extracellular
ders associated with significant morbidity and mortality. space into cells, causing cellular swelling.
Abnormalities include hyponatremia (serum sodium con- The body uses compensatory mechanisms to maintain
centration less than 135 mEq per L) and the less common sodium concentration to prevent cell shrinkage or swelling.
hypernatremia (greater than 145 Eq per L). Understanding One key mechanism is the changing levels of antidiuretic
the pathophysiology of these conditions can be helpful in hormone (ADH) from the hypothalamus in response to
diagnosis and treatment. changing sodium concentration in plasma.
In hypernatremia, increased ADH secretion stimulates
Pathophysiology water reabsorption by the kidneys. The resulting water reten-
Osmolarity is the concentration of solutes (primarily sodium) tion lowers serum sodium concentration. Conversely, in
in a body fluid. Water easily moves through cell membranes, hyponatremia, the suppression of ADH secretion results in
whereas sodium ions do not. Water moves through cell mem- excretion of free water by the kidneys. This loss of free water
branes from lower sodium concentration areas to higher increases serum sodium concentration. Factors such as kid-
sodium concentration areas to achieve equal osmolarity ney disease or taking certain medications (e.g., diuretics) can
inside and outside cells. If the extracellular sodium con- limit the kidneys’ ability to dilute or concentrate urine in
centration exceeds the intracellular sodium concentration, response to ADH levels.1
water moves from within cells into the extracellular space,
causing cell shrinkage. Conversely, if extracellular sodium Hyponatremia
Hyponatremia is categorized as mild (130 to 134 mEq per L),
CME This clinical content conforms to AAFP criteria for CME.
moderate (125 to 129 mEq per L), or severe (less than 125
See CME Quiz on page 447. mEq per L).2 Hyponatremia is treated as acute when occur-
Author disclosure:​ No relevant financial relationships. ring within 48 hours and as chronic when occurring over 48
hours or more or when the duration is unknown.

476 American
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 SODIUM DISORDERS
SORT:​KEY RECOMMENDATIONS FOR PRACTICE

Evidence
Clinical recommendation rating Comments

Patients with a sodium concentration of less than 125 mEq per L and B Consensus guidelines, expert opin-
moderate or severe symptoms can be treated with bolus or continu- ion, one randomized controlled trial
ous infusions of 3% hypertonic saline without increased risk of osmotic
demyelination syndrome or mortality. Bolus infusion improves sodium
concentration more quickly with less overcorrection.1,2,10,13

Sodium concentration should be monitored after each hypertonic saline C Consensus guidelines, expert
bolus and every six hours during the first 24 hours of treatment for severe opinion
symptomatic hyponatremia.1,2,10

Sodium correction should be limited to 8 mEq per L over 24 hours in C Consensus guidelines
patients with chronic hyponatremia who are at increased risk of osmotic
demyelination syndrome. For patients without risk factors, sodium cor-
rection should be limited to 12 mEq per L over 24 hours and 18 mEq per L
over 48 hours to minimize the risk of osmotic demyelination syndrome. 2

In the absence of severe hyponatremia, the next steps in the manage- C Consensus guidelines
ment of hypotonic hyponatremia (true hyponatremia) are based on
whether the patient is hypovolemic, euvolemic, or hypervolemic. 2,10

Hypernatremia in adults can be corrected at a rate of 12 mEq per L over B Observational study, expert opinion
24 hours;​however, if this rate is exceeded, therapeutically increasing the
serum sodium again should be avoided. 30,37

A = consistent, good-quality patient-oriented evidence;​B = inconsistent or limited-quality patient-oriented evidence;​C = consensus, disease-
oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://​w ww.
aafp.org/afpsort.

PREVALENCE
In outpatient settings, the prevalence of hyponatremia may FIGURE 1
be as high as 7%.3 Hyponatremia is the most common elec-
trolyte abnormality in patients presenting to emergency Serum sodium < 135 mEq per L
departments.3-5
Additionally, in outpatient settings, chronic hypona- Serum sodium < 125 mEq per L
tremia is associated with an increased risk of all-cause with severe symptoms present?*
mortality, cancer (lung, head, and neck), gait instability,
osteoporosis, falls, and fractures.4-8 These risks are more
pronounced in older adults.3,5 Approximately 28% of hos- Yes No

pitalized patients have hyponatremia, which is associated Emergent referral Is the patient symptomatic with
with increased length of hospitalization, higher costs, and a Treat with hypertonic moderate hyponatremia or at
twofold increase in mortality.9 saline (Figure 3) high risk of progression due to
severity or comorbidities?†

SYMPTOMS
Mild symptoms include nausea, vomiting, weakness, head- Yes No
ache, and mild neurocognitive deficits. Severe symptoms of
acute hyponatremia include delirium, confusion, impaired Consider Outpatient evaluation
hospitalization with close follow-up
consciousness, ataxia, seizures, and, rarely, brain herniation
and death due to rapid water shifts from extracellular tissues *—Severe symptoms include confusion, ataxia, seizures, coma, and
respiratory depression.
into the brain. In chronic hyponatremia, mildly and moder-
†—Patients at high risk include those who have a sodium level < 120
ately depressed sodium concentration may be asymptomatic. mEq per L or moderate to severe hyponatremia with comorbidities
such as heart disease, alcoholism, malnutrition, liver disease, and
INITIAL ASSESSMENT active pulmonary disease.

The patient’s symptoms and sodium concentration guide

the initial assessment. A sodium concentration of less Initial assessment of patients with hyponatremia.
than 125 mEq per L with severe symptoms requires emer- Information from references 2 and 10.

gency intervention with 3% hypertonic saline infusion.2,10

November 2023 ◆ Volume 108, Number 5 www.aafp.org/afp American Family Physician 477
 TABLE 1 FIGURE 2

Commonly Prescribed Medications Serum sodium < 135 mEq per L?

Implicated in Hyponatremia
Hypovolemic hyponatremia Hyperglycemia present?
Loop diuretics
Thiazide diuretics
No Yes
Euvolemic hyponatremia/syndrome of inappropriate
antidiuretic hormone secretion Assess serum Correct sodium
Barbiturates osmolality for glucose*; if
still hyponatremic,
Carbamazepine
continue evaluation
Clozapine (Clozaril)
Desmopressin
Narcotic medications (opioids) Normal (280 to 295 Low (< 280 mOsm High (> 295
Oxytocin mOsm per kg) per kg) mOsm per kg)

Selective serotonin reuptake inhibitors

Tricyclic antidepressants Isotonic hyponatremia Hypotonic Hypertonic
Vincristine (pseudohyponatremia) hyponatremia hyponatremia*
confirmed
Information from reference 11. (Figure 4)
Evaluate for hyper- Evaluate for history of
lipidemia, elevated unmeasured solutes
protein levels (e.g., mannitol, glycine
solutions used in recent
TABLE 2 surgery, contrast media)

*—Hyperglycemia is a type of hypertonic hyponatremia and should

Laboratory Testing to Evaluate be considered immediately because of how commonly it is encoun-
for Hyponatremia tered in patients.

Test Considerations
Distinguishing hyponatremia from other hyponatre-
Comprehensive Hyperglycemia may suggest false mia variants.
metabolic panel low sodium (hypertonic hypona-
Information from reference 11.
tremia) instead of true hypotonic
hyponatremia
Abnormal liver function test results
may suggest liver dysfunction as a active pulmonary disease. Figure 1 provides guidelines for
contributor the initial assessment of hyponatremia.2,10
Elevated creatinine or blood urea
nitrogen helps determine volume sta- HISTORY
tus and may indicate a kidney-related The medical history can identify potential causes of hypona-
etiology
tremia. Many commonly prescribed medications can cause
Serum Differentiates between true hypo- hyponatremia (Table 111). The history can also identify other
osmolality tonic hyponatremia and alternate possible causes, including excessive alcohol consumption,
etiologies use of illicit drugs (e.g., ecstasy), diets with very low solute
Urine screening Helps distinguish etiologies based on intake (e.g., tea and toast diet), and prolonged exercise in
(urine sodium, volume status which free water intake exceeds water loss from sweat (dilu-
creatinine, tional hyponatremia).2,12
osmolality)

Information from reference 11. LABORATORY TESTING

When the history does not identify a cause, laboratory test-
ing can be helpful. Common initial tests include serum
Hospitalization should be considered when the sodium osmolality, a comprehensive metabolic profile, and urine
concentration is less than 125 mEq per L and symptoms screening for sodium, creatinine, and osmolality (Table 211).
are present, or in high-risk patients with moderate to severe Serum osmolality can distinguish between isotonic, hypo-
hyponatremia. High-risk patients have a sodium concen- tonic, and hypertonic hyponatremia (Figure 211).
tration of less than 120 mEq per L or comorbidities such as If symptoms of specific comorbidities are present,
heart disease, alcoholism, malnutrition, liver disease, and additional testing may be necessary, such as obtaining

478 American Family Physician www.aafp.org/afp Volume 108, Number 5 ◆ November 2023
 SODIUM DISORDERS

B-type natriuretic peptide to evaluate for heart failure,

thyroid-stimulating hormone for thyroid disease, and urine FIGURE 3
drug screening for suspected illicit drug use.
Other substances in the blood can result in a false low Sodium < 125 mEq per L
with severe symptoms
sodium concentration. This includes elevated levels of pro-
tein or triglycerides, which results in isotonic hyponatremia
(i.e., pseudohyponatremia) or elevated glucose or exogenous
substances (e.g., mannitol, contrast media) causing hyper- Administer a single intravenous Alternative therapy:
tonic hyponatremia. bolus of 100 to 150 mL 3% hyper- 3% hypertonic saline
tonic saline over 10 to 20 minutes infused at 1 to 2 mL per
Repeat up to two times if kg per hour
SEVERE HYPONATREMIA
symptoms do not resolve Recheck sodium hourly
Hyponatremia with sodium concentrations less than Check sodium after every bolus
125 mEq per L and severe symptoms is an emergency that
requires rapid correction (Figure 311). Infusion of hypertonic
saline is the recommended treatment.
Guidelines recommend up to three 100-mL boluses of Sodium overcorrection?
3% saline administered at 10-minute intervals or 150 mL at
20-minute intervals, with an initial goal of increasing sodium
by 4 to 6 mEq per L.1,2,10 Sodium concentration should be Yes No

monitored after each hypertonic saline bolus and every six Stop ongoing measures to Follow with sodium every
hours during the first 24 hours of treatment for severe symp- increase sodium 4 to 6 hours until > 125
tomatic hypernatremia.1,2,10 Overly rapid sodium correction Replace urinary free water loss mEq per L is achieved
with oral hydration or 5% dextrose Switch to isotonic saline
should be avoided because this may lead to osmotic demy- infused at 3 mL per kg per hour, Determine underlying
elination syndrome (ODS), a rare but severe complication with or without 2 to 4 mcg of cause
caused by the loss of myelin sheaths in brainstem axons. desmopressin every 8 hours
One randomized controlled trial found that patients with
a sodium concentration of less than 125 mEq per L and Treatment of severe symptomatic hyponatremia.
moderate or severe symptoms can be treated with bolus or Information from reference 11.
continuous infusions. Both treatments have been shown to
correct hyponatremia without an increased risk of ODS or
mortality;​however, bolus infusion improves sodium levels ASSESSING VOLUME STATUS
more quickly with less overcorrection.13 In the absence of severe hyponatremia, management of
ODS is more likely when sodium concentration is less than hypotonic hyponatremia (true hyponatremia) is based on
105 mEq per L. Other predisposing contributors to ODS whether the patient is hypovolemic, euvolemic, or hyper-
include malnutrition, alcohol use, and hypokalemia.2,14 In volemic2,10 (Figure 411). Volume status is often challenging
patients with chronic hyponatremia (occurring over 48 hours to assess on physical examination, and algorithms are not
or more) at increased risk of ODS, guidelines recommend always accurate.15 Laboratory findings can also be mis-
limiting sodium correction to 8 mEq per L over 24 hours. For leading indicators of volume status or causes of hypona-
patients without risk factors, sodium correction should be tremia.16,17 For example, patients who are euvolemic due
limited to 12 mEq per L over 24 hours or 18 mEq per L over to fluid retention in the syndrome of inappropriate ADH
48 hours to minimize the risk of ODS.2 Online calculators secretion (SIADH) and patients who are hypovolemic
for determining optimal infusion rates are listed in Table 3.11 due to diuretic use can both have the same findings of low
Overcorrection of sodium in a patient whose initial serum sodium and high urine sodium.15 Low-quality evi-
serum level was less than 125 mEq per L should be aggres- dence suggests that calculating the fractional excretion of
sively managed (Figure 311). This includes stopping ongo- uric acid can help distinguish high urine sodium concen-
ing efforts to increase sodium and replacing urinary water tration caused by SIADH vs. loop diuretics, although not
losses with free water orally or dextrose 5% infused at 3 mL thiazide diuretics.18
per kg per hour.2 Desmopressin (a synthetic analogue of Point-of-care ultrasonography may be used to assess vol-
ADH) infusion of 2 to 4 mcg every eight hours may be used ume status through visualization of stroke volume of the infe-
as an adjunct treatment with free water or dextrose 5% rior vena cava;​however, it is unclear whether this approach
replacement. improves outcomes in patients with hyponatremia.19,20

November 2023 ◆ Volume 108, Number 5 www.aafp.org/afp American Family Physician 479
 SODIUM DISORDERS

When a diagnosis is unclear, normal saline should be underlying cause, if possible.2,10 Guidelines do not specify
administered cautiously, typically starting at 0.5 to 1 L over the volume and rate of saline administration. The clinical
60 minutes. The sodium concentration should improve in assessment of volume needs should guide repletion. Occa-
patients with hypovolemia, whereas it usually does not and sionally, salt tablets may help with correction when oral
may worsen in patients with SIADH.2,10 therapy is appropriate, but data are lacking on outcomes and
how much to prescribe.21
HYPOVOLEMIC HYPONATREMIA
Hypovolemic hyponatremia may result from vomiting, EUVOLEMIC HYPONATREMIA
diarrhea, small bowel obstruction, burns, diuretics, pri- Etiologies of euvolemic hyponatremia include primary
mary adrenal insufficiency, and salt-losing nephropathy 2 polydipsia; decreased solute intake; cortisol deficiency; and
(Table 411). SIADH, which can be caused by medications, pain, psy-
When no severe symptoms are present, treatment is chosis, and surgery 2,7,22 (Table 511). Reset osmostat, another
volume repletion with normal saline and addressing the cause of SIADH, occurs when plasma osmolality is low but

TABLE 3

Equations and Online Calculators for Evaluating Sodium Disorders

Measurement Calculator Equations and comments

Sodium correction https://​w ww.mdcalc.​com/​sodium- Measured sodium + 0.016 × (serum glucose − 100)
for hyperglycemia ​correction-​for-​hyperglycemia Measured sodium + 0.024 × (serum glucose − 100)*

Serum osmolality https://​w ww.mdcalc.com/ Serum osmolality = (sodium × 2) + (glucose ÷ 18) + (blood urea
serum-osmolality-osmolarity nitrogen ÷ 2.8)
Normal osmolality = 280 to 295 mOsm per kg
In patients with hyperglycemia, uncorrected sodium should be
used to calculate osmolality

Sodium deficit https://​w ww.mdcalc.com/ Sodium deficit = total body water % × body weight (kg) ×
sodium-deficit-in-hyponatremia (desired sodium − actual sodium)
For total body water %, use 0.6 for men and 0.5 for women

Infusion rate of https://​w ww.mdcalc. Serum sodium correction should not proceed faster than 0.5 mEq
sodium com/​sodium-​correction-​rate-​ per L per hour for the first 24 to 48 hours;​however, in patients
hyponatremia-​hypernatremia with severe symptoms, a rate of 1.0 to 2.0 mEq per L per hour is
acceptable (these situations typically require use of 3% saline)
The goal is to increase the serum sodium concentration by
6 to 8 mEq per L, not to exceed 10 to 12 mEq per L in the first
24 hours and 18 mEq per L in the first 48 hours

Free water deficit https://​w ww.mdcalc.com/free- 0.6 × body weight (kg) × [(serum sodium ÷ 140) – 1]
in hypernatremia water-deficit-in-hypernatremia Results of this formula are in liters
Administer the total volume as free water over 24 hours using
oral or enteral free water (preferred), or hypotonic fluids such as
dextrose 5% in water

Fractional excre- https://​w ww.scymed.com/en/ Fractional excretion of uric acid = (urinary uric acid × serum
tion of uric acid smnxps/pspdj228.htm creatinine) ÷ (serum uric acid × urine creatinine)
Less than 0.1 suggests prerenal causes, while > 0.1 indicates
syndrome of inappropriate antidiuretic hormone secretion or
renal etiologies

*—Use this formula when the glucose level is > 400 mg per dL.
Adapted with permission from Braun MM, Barstow CH, Pyzocha NJ. Diagnosis and management of sodium disorders:​hyponatremia and hyper-
natremia. Am Fam Physician. 2015;​91(5):​online. https://www.aafp.org/pubs/afp/issues/2015/0301/p299.html

480 American Family Physician www.aafp.org/afp Volume 108, Number 5 ◆ November 2023
 SODIUM DISORDERS
FIGURE 4

Hypotonic hyponatremia

Does the patient take a thiazide diuretic

or have end-stage renal disease?

Taking a thiazide No End-stage renal

disease present

Stop thiazide and reassess

Does hyponatremia persist? Refer to nephrology

No Yes

Diuretic induced, Assess volume status based on

evaluate alternative history, examination, vital signs,
therapy options laboratory results, and, if available,
point-of-care ultrasonography

Hypovolemic (decreased Euvolemic (increased total Hypervolemic

total body water and body water level, normal (increased total
sodium levels) total body sodium level) body water level)

Urine sodium usually

> 20 mEq per L
Urine sodium Urine sodium Urine sodium Urine sodium
> 20 mEq per L ≤ 20 mEq per L < 20 mEq per L ≥ 20 mEq per L

Renal losses Extrarenal loss Urine osmolality Urine osmolality Variable Heart failure, cir- Acute kidney
(e.g., diuretics, (e.g., vomiting, > 100 mOsm per kg ≤ 100 mOsm per kg urine rhosis, nephrosis, injury, chronic
mineralocorticoid diarrhea, third osmolality hypoalbuminemia kidney disease
deficiency) spacing, bowel
obstruction) Syndrome of inap- Primary polydipsia,
propriate antidiuretic low solute intake Reset Diuresis; fluid Fluid and
hormone secretion, osmostat and sodium sodium restric-
severe hypothyroidism, restriction tion, dialysis
adrenal insufficiency, (Table 7) (Table 7)
Isotonic saline stress, drug use
(Table 4)

Fluid restriction, address underlying

etiologies (Tables 5 and 6)

Evaluation of hypotonic hyponatremia.

Adapted with permission from Braun MM, Barstow CH, Pyzocha NJ. Diagnosis and management of sodium disorders:​hyponatremia and hyper-
natremia. Am Fam Physician. 2015;​91(5):​301.

ADH secretion is elevated. SIADH is considered a diagnosis to 500 mL per 24 hours. However, adherence to that degree
of exclusion;​therefore, ruling out other causes of euvolemic of water restriction can be difficult for patients, and allowing
hyponatremia is recommended.2 1 L fluid restriction has also been effective.2,23,24
First-line management for nonsevere euvolemic hypo- Other supplemental therapies include salt tablets, oral
natremia includes discontinuing offending medications, urea, or vaptans (Table 6 2,21,25). Vaptans are ADH antag-
addressing underlying etiologies, and restricting free water onists that increase water diuresis and improve sodium

November 2023 ◆ Volume 108, Number 5 www.aafp.org/afp American Family Physician 481
 SODIUM DISORDERS

TABLE 4

Diagnosis and Treatment of Hypovolemic Hyponatremia Etiologies

Etiology Diagnosis Treatment

Diuretic use Clinical;​urinary sodium > 20 mEq per L Stop diuretic therapy

Gastrointestinal loss (e.g., diarrhea, Clinical;​urinary sodium ≤ 20 mEq per L Intravenous fluids (normal saline)
vomiting)

Osmotic diuresis Elevated glucose level, mannitol use Correct glucose level;​stop mannitol use

Salt-losing nephropathies (previously Urinary sodium > 20 mEq per L Isotonic or hypertonic saline;​address
known as cerebral salt wasting) underlying cause

Third spacing (e.g., bowel obstruc- Clinical;​computed tomography Intravenous fluids;​relieve obstruction
tion, burns)

Information from reference 11.

normalization.2,26 Complications such as hypernatremia and ingestion, iatrogenically (i.e., when patients receive excess
ODS have been reported with vaptan use.27 sodium through hypertonic saline infusions), or diabetes
insipidus31,32 (Table 811,29,31-33).
HYPERVOLEMIC HYPONATREMIA
Common causes of hypervolemic hyponatremia include SYMPTOMS
heart failure, severe liver disease, chronic kidney disease, Symptoms of hypernatremia in adults are typically nonspe-
and nephrotic syndrome (Table 7 11). Initial therapy for mild cific and include fatigue, lethargy, and weakness.32,34 Symp-
to moderate hypervolemic hyponatremia with heart failure toms in children may be similarly nonspecific, including
includes fluid restriction of 1 L per day, decreasing or dis- weight loss, poor feeding, irritability, restlessness, lethargy,
continuing contributing medications, such as diuretics, and decreased urine output, constipation, and vomiting.29 In
increasing dietary sodium if possible.2 Urea or vaptans may children and adults with severe hypernatremia, symptoms
also be used. may progress to seizures, coma, and death.28,29,32,34
For patients with cirrhosis and mild hypervolemic hypo-
natremia, fluid restriction of 750 mL per day and loop DIAGNOSIS
diuretics are indicated.2 In patients with moderately severe The cause of hypernatremia is often apparent from the
liver failure and hypervolemic hyponatremia, decreasing or patient’s history. Physical examination may find evidence of
discontinuing diuretics and relying on fluid restriction alone dehydration, including orthostatic hypotension.
may be appropriate to prevent further sodium loss. Further laboratory evaluation is occasionally required
to identify uncommon causes, such as diabetes insipidus.
Hypernatremia Hypernatremia should be considered when patients report
Hypernatremia (greater than 145 mEq per L) occurs in large urine volumes and extreme thirst.
1% to 2% of patients without chronic kidney disease who Urinalysis showing dilute urine in the presence of dehy-
present to emergency departments.28 Although less com- dration suggests diabetes insipidus. A diagnosis of diabetes
mon than hyponatremia, it can be life-threatening when insipidus is complex.35 The first step is to perform a water
severe.3,29,30 deprivation test, in which the patient does not drink liquid
Hypernatremia most commonly results from decreased for an extended time. Continued polyuria with dilute urine
water intake, often due to impaired thirst mechanisms, is consistent with diabetes insipidus.35
restricted access to water, or excess water loss (e.g., sweat-
ing, diuresis). Patients at the extremes of age, with poor MANAGEMENT
functional status, or with limited cognitive capabilities are Hypernatremia is associated with increased mortality rates
at higher risk due to their dependence on others for hydra- in hospitalized patients, especially when not quickly iden-
tion.3,29 Hypernatremia can also occur from excessive salt tified and corrected.27,34,36 First-line treatment is addressing

482 American Family Physician www.aafp.org/afp Volume 108, Number 5 ◆ November 2023
 SODIUM DISORDERS

the underlying cause and correcting the fluid deficit. The for- possible. If intravenous fluids are required, hypotonic fluids
mula and calculator for computing the free water deficit are such as dextrose 5% in water should be used. Isotonic saline
listed in Table 3.11 should be avoided because it can worsen hypernatremia.33
The calculated deficit volume can be administered over 24 Rapid correction of hypernatremia in dehydrated infants
hours. Oral or enteral free water should be used whenever has been associated with poor neurologic outcomes,

TABLE 5

Diagnosis and Treatment of Euvolemic Hyponatremia Etiologies

Etiology Diagnosis Treatment

3,4-methylenedioxymethamphetamine Urine drug screening Stop drug use;​support-

(ecstasy) use ive care

Alcohol use with low solute intake (i.e., Excessive alcohol consumption, low serum Therapy to decrease
beer potomania syndrome) osmolality alcohol use;​nutritional
counseling to increase
protein intake

Exercise-associated hyponatremia (e.g., Clinical;​excessive free water consumption Isotonic or hypertonic

in endurance athletes or military trainees) saline, depending on
symptoms

Glucocorticoid deficiency Low aldosterone, morning cortisol, and adrenocor- Steroid replacement
(hypocortisolism) ticotropic hormone levels;​hyperkalemia;​increased therapy
plasma renin level

Severe hypothyroidism Elevated thyroid-stimulating hormone level, low Thyroid replacement

free thyroxine level therapy

Low solute intake (e.g., tea and toast diet) Clinical;​low urine osmolarity Increase sodium intake

Nephrogenic SIADH (results from rare Decreased osmolality, urinary osmolality > 100 Fluid restriction;​loop
genetic conditions) mOsm per kg, euvolemia, urinary sodium > 20 mEq diuretics
per L, absence of thyroid disorders or hypocorti-
solism, normal renal function, no diuretic use

Psychogenic polydipsia History of schizophrenia with excessive water intake Psychiatric therapy

Reset osmostat Elevated antidiuretic hormone secretion;​normal No therapy needed

fractional excretion of uric acid (urate)

SIADH Decreased osmolality, urinary osmolality > 100 Treat the underlying
mOsm per kg, euvolemia, urinary sodium > 20 mEq condition with fluid
per L, absence of thyroid disorders or hypocorti- restriction, salt tablets,
solism, normal kidney function, no diuretic use urea;​consider vaptans

SIADH secondary to medication use (e.g., SIADH with use of causative agent Stop causative
barbiturates, carbamazepine, diuretics, medication
opioids, selective serotonin reuptake
inhibitors, tolbutamide, vincristine)

Water intoxication Clinical;​excessive water intake Stop free water inges-

tion;​hypertonic saline if
needed for symptoms

SIADH = syndrome of inappropriate antidiuretic hormone secretion.

Adapted with permission from Braun MM, Barstow CH, Pyzocha NJ. Diagnosis and management of sodium disorders:​hyponatremia and hyper-
natremia. Am Fam Physician. 2015;​91(5):​302-303.

November 2023 ◆ Volume 108, Number 5 www.aafp.org/afp American Family Physician 483
 SODIUM DISORDERS

TABLE 6

Supplemental Therapies for Euvolemic Hyponatremia

Treatment Dosage Comments

Empagliflozin 25 mg administered orally once per day Limited evidence;​not supported by guidelines or FDA
(Jardiance) approved for this indication

Salt tablets Commonly administered as 1 g of sodium Limited evidence

chloride three times per day;​can be followed
by 20 mg of furosemide

Urea (oral) Initiated at 15 to 60 g per day, often dissolved Considered a medical food instead of a medication;​
in a liquid drink to mask the taste therefore, its safety has not been rigorously evaluated;​the
FDA says it is “generally recognized as safe,” but it is not
FDA approved;​some evidence shows that urea improves
sodium concentration

Vaptans Vaptans should be initiated in a hospital set- Should not be combined with fluid restriction because of
ting;​intravenous conivaptan (Vaprisol) may be potential for rapid sodium recovery;​no evidence of long-
used for four days;​oral tolvaptan may be used term benefits, and use has not been assessed in severe
for up to 30 days, including after discharge symptomatic hyponatremia

FDA = U.S. Food and Drug Administration.

Information from references 2, 21, and 25.

TABLE 7

Diagnosis and Treatment of Hypervolemic Hyponatremia Etiologies

Etiology Diagnosis Treatment

Heart failure Clinical (e.g., jugular venous distention, edema), elevated Diuretics, angiotensin-converting
B-type natriuretic peptide level, echocardiography, enzyme inhibitors, beta blockers
urinary sodium < 20 mEq per L

Kidney failure (acute Blood urea nitrogen to creatinine ratio, glomerular filtra- Treat kidney failure;​correct the
or chronic) tion rate, proteinuria, urinary sodium > 20 mEq per L underlying disease when possible
Serum osmoles can be normal or high due to elevated
blood urea nitrogen level
To correct:​tonicity = measured serum osmolality –
(blood urea nitrogen ÷ 2.8)

Liver failure/cirrhosis Elevated liver function test results, ascites, elevated Furosemide, spironolactone,
ammonia level, biopsy, urinary sodium < 20 mEq per L transplant

Nephrotic syndrome Urinary protein, urinary sodium < 20 mEq per L Treat underlying cause

Information from reference 11.

including seizures. 29 The maximum acceptable rate of within 72 hours has been associated with worsening mor-
sodium correction in infants is unclear;​however, rates of less tality in hospitalized patients.27,30 Although a correction
than 0.5 mEq per L per hour (less than 12 mEq per L in 24 of less than 10 mEq per L per 24 hours has been recom-
hours) are associated with the lowest risk.29,37 mended based on expert opinion, more recent evidence
In adults, rapid correction does not appear to cause poor suggests that hypernatremia in adults can be corrected at
neurologic outcomes, and failure to correct hypernatremia a rate of 12 mEq per L over 24 hours. However, if 12 mEq

484 American Family Physician www.aafp.org/afp Volume 108, Number 5 ◆ November 2023
 SODIUM DISORDERS
TABLE 8

Evaluation of Hypernatremia Etiologies

Etiology Description Evaluation

Increased free water loss

Diabetes insipidus May be due to central diabetes insipidus (insufficient pro- Serum and urine electrolytes
duction of antidiuretic hormone [arginine vasopressin]) or showing hypotonic urine
nephrogenic diabetes insipidus (decreased renal respon- Water deprivation testing
siveness to arginine vasopressin) can confirm diagnosis, and
Low activity causes the excretion of inappropriately dilute arginine vasopressin (desmo-
urine pressin) stimulation test can
Patients may compensate by increasing fluid intake, determine central vs. nephro-
resulting in polydipsia and polyuria;​this increased intake genic diabetes insipidus
of free water may attenuate the increase in sodium

Environmental exposure Prolonged exposure to hot, arid environments Clinical history

Gastrointestinal losses Fluid loss from vomiting or diarrhea;​nausea may prevent History of nausea, vomiting,
patients from consuming enough fluid or diarrhea

Iatrogenic Overdiuresis History of diuretic use

Increased metabolic demands Fever or increased physical activity Clinical history

Sweating Fluid lost through sweat, such as from environmental Clinical history
exposure or exercise

Decreased free water intake

Hypodipsia Patients who are physically and cognitively capable of Clinical history
obtaining free water yet fail to do so;​may be due to
decreased thirst response, which can occur in older adults
or people with psychiatric disorders such as depression

Iatrogenic Patients who are restrained, sedated, intubated, not Clinical history
allowed to drink, or housed in a long-term care facility
may not receive adequate amounts of water from medical
personnel

Physical and cognitive Patients who are reliant on others to provide sufficient Clinical history
limitations water or those who are unable to obtain safe water;​may
include young children, patients with disabilities, or those
with poor access to water due to disaster, falls, or other
adverse circumstances

Increased sodium intake

Iatrogenic Hypertonic dialysis or administration of fluids with a History of dialysis or medica-
supraphysiologic salt load such as hypertonic saline or tion administration
sodium bicarbonate

Salt toxicity Rapid ingestion of excessive amounts of salt can acutely History of excessive salt
increase the serum sodium concentration ingestion
A rare condition with high mortality

Information from references 11, 29, and 31-33.

per L per 24 hours is exceeded, therapeutically increasing hyponatremia, and treatment. Also searched were the Cochrane
the serum sodium again should be avoided. 30,37 database, Agency for Healthcare Research and Quality, Google
Scholar, and PubMed from January 1, 2010, to October 2022.
This article updates a previous article on this topic by Braun, The searches were limited to English-language studies. Second-
et al.11 ary references from the key articles identified by the searches
Data Sources:​We were provided a search from Essential Evi- were also used. Our review did not incorporate race or gender
dence Plus using the key term hyponatremia. A search was com- as patient categories. Search dates:​August to October 2022, and
pleted using the key terms hyponatremia, diagnosis, euvolemic September 2023.

November 2023 ◆ Volume 108, Number 5 www.aafp.org/afp American Family Physician 485
 SODIUM DISORDERS

15. Fenske W, Maier SKG, Blechschmidt A, et al. Utility and limitations of the
The Authors traditional diagnostic approach to hyponatremia [published correction
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core faculty member and an assistant professor in the Depart- lar fluid volume in hyponatremia. Am J Med. 1987;​83(5):​905-908.
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and chair of the Midwest Department of Family Medicine at the differential diagnosis of hypotonic hyponatraemia in patients with
Mayo Clinic. diuretic therapy. Cureus. 2020;​1 2(4):​e7762.
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Crosse (Wis.)-Mayo Family Medicine Residency, Mayo Clinic
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Address correspondence to Stephen K. Stacey, DO, Mayo 21. Nagler EV, Haller MC, Van Biesen W, et al. Interventions for chronic
non-hypovolaemic hypotonic hyponatraemia. Cochrane Database Syst
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486 American Family Physician www.aafp.org/afp Volume 108, Number 5 ◆ November 2023