Hyponatremia
Adult-Gerontology Acute Care Practice Guidelines
Definition
A.See Box 5.5 for further details.
B.Serum sodium less than 135 mEq/L (measured by ion-specific electrode; see Box 5.5).
a.Mild: 130 to 135 mEq/L.
b.Moderate: 125 to 129 mEq/L.
c.Severe or profound: Less than 125 mEq/L.
C.Acute hyponatremia: Low serum sodium documented for 48 or fewer hours.
D.Chronic hyponatremia: Low serum sodium that is either documented for greater than 48 hours or onset is unknown.
Incidence
A.The incidence is 15% to 38% in hospitalized patients, with only ∼7% incidence in ambulatory settings.
B.In institutionalized geriatric patients, an incidence as high as 53% has been reported.
C.The incidence of moderate and severe hyponatremia (serum sodium <130 mEq/L) is 1%, with a prevalence of 2.5%.
1.67% of cases are hospital acquired, and 30% occur in the ICU.
D.Admission of patients with hyponatremia is directly associated with inpatient mortality.
Pathogenesis
A.Pseudohyponatremia.
1.Apparent low sodium with plasma and urine osmolality and tonicity, as well as hyperlipidemia or hyperproteinemia.
2.Normal serum sodium that appears falsely low when using indirect ion-selective electrode (ISE) method to assess plasma for sodium.
a.The original sample is diluted to 1:10 ratio, measuring whole plasma sodium, assuming the sample contains 93% water and 7% proteins/lipids.
b.But increased proteins or lipids decrease the ratio of total water, causing a perceived lower than actual sodium level.
3.Solution: Measurement of sodium via direct ion-sensitive electrode and serum sample (undiluted blood).
a.This is usually a point of care test.
B.Dilutional hyponatremia (↑ total body water [TBW] +/− ↓ Solutes).
1.Due to transcellular water shifts—hypertonicity.
a.Hyperglycemia (>250 mg/dL).
b.Hypertonic solutions (e.g., mannitol, intravenous immunoglobulin [IVIG]).
C.Solute depletion hyponatremia (↓ Solutes + ↑ TBW; requires water intake).
1.Loss of solute while maintaining water intake.
D.Potassium and sodium.
1.Potassium is an active cation; Sodium is an anion. To maintain electroneutrality, potassium + chloride exchange across cell membranes for sodium.
2.As a result, when infusing potassium, some potassium ions become intracellular, and some sodium ions become extracellular, thus raising sodium levels.
Predisposing Factors
A.Elderly patients.
B.Taking psychiatric medications.
C.Cardiac disease.
D.Chronic kidney disease.
E.Malignancy.
F.Alcoholism.
Subjective Data
A.Common complaints/symptoms.
1.Neurological symptoms: Range from mild and nonspecific to severe and potentially fatal.
a.Severity of symptoms increases with acuity of onset.
i.Chronic hyponatremia often presents with relatively mild symptoms.
ii.Acute, severe hyponatremia is associated with marked neurological deficits.
2.Neurological and other symptoms grouped by severity.
a.Mild symptoms (nonspecific and rarely progress to herniation).
i.Headache.
ii.Nausea and vomiting.
iii.Mild confusion.
b.Moderate (sometimes known as moderately severe): Most often seen in chronic hyponatremia, and thus not associated with impending herniation.
i.Anorexia.
ii.Fatigue/malaise.
iii.Confusion, agitation, disorientation, or forgetfulness.
iv.Gait disturbance.
v.Abnormal sensorium (i.e., dizziness).
c.Severe.
i.Vomiting.
ii.Cardiopulmonary distress.
1)Pulmonary edema.
2)Acute respiratory failure secondary to tentorial herniation with subsequent brainstem compression.
3)Cheyne–Stokes respiration.
iii.Delirium.
iv.Somnolence/obtundation.
v.Seizures (10% incidence with severe hyponatremia).
vi.Pathologic or depressed reflexes.
vii.Pseudobulbar palsy.
viii.Coma (Glasgow Scale ≤ 8).
d.Other signs (e.g., falls).
3.Possible hypovolemia or hypervolemia depending on the etiology of the hyponatremia.
Physical Examination
A.Physical examination to assess volume status.
1.Check skin, mucous membranes, heart, lungs, jugular venous distension (JVD), edema.
2.Assess blood pressure and orthostatic changes.
3.Determine weight changes.
B.Neurological assessment (initial and ongoing).
Diagnostic Tests
A.Serum sodium.
B.Serum osmolality.
C.Complete chemistry panel including potassium.
D.Spot urine osmolality.
1.Greater than 300 mOsm/kg: Urine is concentrated/hypertonic but not necessarily because of sodium. This indicates a relative increase in solute compared to water.
2.Less than 150 mOsm/kg: Urine is dilute/hypotonic. This indicates a relative increase in water and/or decrease in solute.
E.Spot urine sodium.
1.Less than 20 mEq/L: Renal sodium retention as in low effective arterial blood volume.
2.20 mEq/L or more: Diuretics will induce increased urine sodium.
F.Determination of patient volume status.
1.Volume assessment is known to be unreliable as initial diagnostic criteria in hyponatremia but is necessary when interpreting hyponatremia-related lab tests.
2.Physical examination to include assessments.
a.Skin, mucous membranes, heart, lungs, JVD, edema, and weight changes.
b.Blood pressure and orthostatic changes (especially in patients using diuretics).
G.Other lab tests to consider.
1.Fractional excretion of uric acid (FEUA %) or chloride (FECL %).
a.These have better specificity and sensitivity than fractional excretion of sodium (FENA %) to help determine volume status and renal clearance of solutes.
2.Vasopressin levels.
3.Thyroid-stimulating hormone (TSH).
4.Glucose and glycosylated hemoglobin.
5.Cortisol.
Differential Diagnosis
A.Pseudohyponatremia.
1.Hypertriglyceridemia greater than 1,000 mg/dL.
2.Familial hypercholesterolemia.
3.Proteinemia greater than 10 gm/dL (i.e., multiple myeloma).
B.Dilutional hyponatremia (↑ TBW +/− ↓ Solutes).
1.Impaired free water excretion: Renal tubular water losses.
a.Endocrine: Hypothyroidism or adrenal/glucocorticoid insufficiency.
b.Physical/emotional stress.
c.Syndrome of inappropriate antidiuretic hormone (SIADH).
i.Central nervous system (CNS) etiologies: Tumor, meningitis, intracranial hemorrhage/hematoma, stroke, or trauma.
ii.Pulmonary disease: Pneumonia, acute respiratory failure, tuberculosis, or aspergillosis.
iii.Neoplasm: Small cell carcinoma lung, pancreatic cancer, or duodenal cancer.
iv.HIV/AIDS.
v.Postoperative.
d.Edema syndromes: Nephrotic syndrome, cirrhosis, or heart failure.
e.Drugs: Amitriptyline, carbamazepine, chlorpropamide, clofibrate, cyclophosphamide, haloperidol, narcotics, nicotine, nonsteroidal anti-inflammatory drugs (NSAIDs), serotonin reuptake inhibitors, thiothixene, thioridazine, vincristine, ecstasy, or oxytocin.
f.Thiazide diuretics.
g.Diminished solute intake with ongoing water intake: Tea and toast diet or beer potomania.
2.Excess water intake.
a.Primary polydipsia.
b.Dilute infant formula.
c.Hypotonic intravenous (IV) fluids.
C.Solute depletion hyponatremia (↓ Solutes + ↑ TBW; requires water intake).
1.Renal solute loss.
a.Diuretic.
b.Solute diuresis: Bicarbonaturia, ketonuria, glucose, mannitol, or urea diuresis.
c.Salt wasting nephropathy (i.e., cystic renal diseases, interstitial disease, chronic glomerular disease, partial obstruction).
d.Mineralocorticoid deficiency.
2.Nonrenal solute loss.
a.Gastrointestinal loss (diarrhea, vomiting, pancreatitis, bowel obstruction).
b.Cutaneous (sweating, burns).
c.Blood loss.
d.Excessive intake of water and sports drinks in athletes, combined with excessive body fluid losses.
Evaluation and Management Plan
A.Step 1—Choose therapy goal and timing of sodium correction based on the following (obtained from history).
1.Acute hyponatremia with severe symptoms: Emergency treatment (more aggressive treatment).
a.Sodium 129 mEq/L or less that fell within the past 48 hours, causing severe patient symptoms.
2.Acute hyponatremia with moderately severe symptoms: Emergency treatment.
a.Sodium 129 mEq/L or less that fell within the past 48 hours. causing moderate patient symptoms.
3.Acute hyponatremia with mild symptoms: Nonemergency treatment (most cases).
a.Sodium 129 mEq/L or less that fell within the past 48 hours, causing mild patient symptoms.
4.Acute hyponatremia asymptomatic: Nonemergency treatment (most cases).
a.Sodium 129 mEq/L or less that fell within the past 48 hours, without causing symptoms.
5.Chronic hyponatremia with any symptoms: Nonemergency treatment.
a.Sodium 129 mEq/L or less for greater than 48 hours or an unknown period of time, causing any related patient symptoms.
6.Chronic hyponatremia asymptomatic: Outpatient treatment.
a.Sodium 129 mEq/L or less for greater than 48 hours, without causing symptoms.
B.Step 2—Set up appropriate monitoring to provide safe care and prevent overcompensation of sodium levels.
1.Emergency treatment.
a.Monitor closely in an intensive care setting.
b.Monitor complete fluid intake and output hourly.
i.Do not allow water intake to exceed output as this will exacerbate hyponatremia.
c.Perform neurological and symptom assessment frequently.
d.Measure sodium levels every 2 to 4 hours; then take them once daily until stable and sodium greater than 130 mEq/L.
2.Nonemergency treatment.
a.Monitor in an ED, ICU, or other nursing floor with trained staff.
b.Monitor complete fluid intake and output hourly.
i.Do not allow water intake to exceed output as this will exacerbate hyponatremia.
c.Perform neurological and symptom assessment frequently.
d.Measure sodium levels every 4 to 6 hours; then take them once daily until stable and sodium greater than 130 mEq/L.
3.Outpatient treatment.
a.Only for chronic patients with stable but low sodium.
b.Monitoring and follow-up vary according to cause of hyponatremia.
C.Step 3—Initiate volume correction if hypovolemic.
D.Step 4—Initiate sodium correction therapy according to severity of symptoms.
1.Acute or severe symptomatic hyponatremia.
a.Initial treatment: 3% sodium chloride 100 mL bolus over 10 to 20 minutes.
i.Repeat as needed: Up to 3 times.
ii.Goal: To raise sodium 5% or 4 to 6 mEq/L and resolve symptoms.
iii.Once goal is met, change to 3% sodium chloride infusion initiated at 0.5 to 2 mL/kg/hr and titrated based on sodium levels until sodium reaches 130 mEq/L.
1)Raise the sodium: 1 mEq/hour.
2)Maximum rise in sodium: 10 mEq/L above baseline per 24 hours.
b.Day 1 (first 24 hours): Maximum rise in sodium: 10 mEq/L or 10%.
c.Following days: Raise the sodium 8 mEq/L or 10%.
2.Acute or moderate symptomatic hyponatremia.
a.Initial treatment: 3% sodium chloride infusion given at 0.5 to 2 mL/kg/hour and titrated based on sodium levels until sodium reaches 130 mEq/L.
b.Day 1 (first 24 hours).
i.Goal for day 1: To raise sodium 5% or 4 to 6 mEq/L and resolve symptoms.
ii.Maximum rise in sodium: 10 mEq/L or 10%.
c.Following days.
i.Raise the sodium 8 mEq/L or 10%.
3.Asymptomatic hyponatremia.
a.Water diuresis (unless hypovolemic): Loop diuretics.
b.If not resolved: 3% sodium chloride infusion initiated at 0.5 to 2 mL/kg/hour and titrated based on sodium levels until sodium reaches 130 mEq/L.
c.Day 1 (first 24 hours).
i.Maximum rise in sodium: 10 mEq/L or 10%.
d.Following days.
i.Raise the sodium 8 mEq/L or 10%.
E.Step 5—Other related interventions.
1.Treatment of other electrolyte and acid–base disorders; correct hypokalemia to a potassium of 3.5 to 4.5 mEq/L.
2.Strict fluid intake and output; restrict or supplement intake as needed.
3.Head trauma or hemodynamic instability: Consider consulting nephrology for continuous renal replacement therapy (CRRT) hyponatremia protocols.
a.Slower sodium titration.
b.Controlled management of sodium levels using CRRT.
4.Chronic hyponatremia.
a.Initial therapy.
i.Restrict all water intake (enteral and parenteral) to 1,000 to 2,000 mL/day.
ii.Correct hypokalemia to a potassium of 3.5 to 4.5 mEq/L.
iii.Euvolemic and hypovolemic patients.
1)Administer isotonic saline or balanced crystalloid solution.
2)Discontinue existing/chronic diuretics (assess as possible cause).
iv.Hypervolemic patients.
1)Further restrict all water intake (enteral and parenteral) to 800 to 1,500 mL/day.
2)Give loop diuretics.
v.Replace sodium deficit only if necessary.
1)3% sodium chloride infusion initiated at 0.5 to 2 mL/kg/hour and titrated based on sodium levels until sodium reaches 130 mEq/L.
2)+/– desmopressin (dDAVP) 1 to 2 mcg IV or SC every 8 hours for 24 to 48 hours. Only use dDAVP to support a therapy plan that includes sodium replacement and water restriction; dDAVP alone will not correct hyponatremia. Do not use dDAVP in psychogenic polydipsia, or edematous hyponatremia (i.e., congestive heart failure [CHF], cirrhosis).
3)Day 1 (first 24 hours): Maximum rise in sodium: 10 mEq/L or 10%.
4)Following days: Raise the sodium 8 mEq/L or 10%.
b.Patients with high urine cation concentrations.
i.Give loop diuretics.
ii.Give vasopressin type 2 (V2) receptor antagonists, also called vaptans.
iii.Give salt tablets.
iv.If resistant to the previously noted therapies, consider demeclocycline, or urea in conjunction with nephrology (demeclocycline likely to damage kidney function).
5.Overcorrecting hyponatremia.
a.Risks: Seizures, cerebral edema, osmotic demyelinating syndrome (ODS), and death.
b.If baseline serum sodium is 120 mEq/L or more, no intervention necessary.
c.If baseline serum sodium is less than 120 mEq/L or if correction exceeds 6 to 8 mEq/L or 10% per day.
i.Give electrolyte free water (D5W) 10 mL/kg and repeat as needed.
ii.Consider also dDAVP 2 mcg IV.
iii.Correct sodium level back to the most recent sodium that was within guidelines for correcting at 6 to 8 mEq/L or 10% per day.
iv.Correct sodium quickly, within a few hours of overcorrecting.
Follow-Up
A.Follow-up depends on underlying cause of hyponatremia.
B.Follow-up should be managed by the primary service who is managing the underlying cause.
Consultation/Referral
A.Consult nephrology if hyponatremia is due to renal disorders.
B.Consult neurology for CNS disorders causing hyponatremia.
Special/Geriatric Considerations
A.A spectrum of diseases and disorders is associated with the geriatric population that predisposes them to hyponatremia, including pulmonary, endocrine, and CNS diseases, as well as cancers.
B.A careful assessment of overall fluid status in elderly patients should be ascertained.
C.Bone stress and fractures.
1.Sodium is stored in bone. Hyponatremia induces osteoclasts and thus bone loss.
2.Chronic hyponatremia is associated with a fourfold increase in osteoporosis (dose and time dependent), gait instability, falls in the elderly, and increased risk of fractures.
D.Cerebral edema.
1.Sodium enters the brain only in plasma. Acute changes to plasma tonicity/osmolality cause water to shift in and out of astrocytes. Acute rises in osmolality cause astrocytes to shrink.
2.Within 48 hours, astrocytes adapt to hyponatremia and intracellular osmolality becomes equal to plasma osmolality without changing cell volume due to adaptive solutes and osmolytes.
3.However, this adaptation has consequences such as increased astrocyte susceptibility to injury and poor long-term outcomes.
E.ODS.
1.Sudden rises in extracellular tonicity/osmolality caused by the treatment/overcorrection of
hyponatremia can cause osmotic stress on astrocytes, resulting in demyelination.
2.ODS initially seems to improve with improvement of hyponatremia.
3.There is a delayed onset of additional symptoms: Seizures, behavior changes, delusions, swallowing and speech dysfunction, movement disorders, paralysis, and potentially death. Symptoms can be temporary or permanent.
F.Mortality: Mild hyponatremia is associated with increased mortality, but deaths from cerebral edema and ODS are rare.
G.Monitor sodium closely in high risk populations.
1.Geriatrics.
2.Liver disease.
3.CHF.
4.CKD.
H.Before treating hyponatremia, rule out and/or treat hypothyroidism, adrenal insufficiency, hyperglycemia, hypertriglyceridemia, and hyperproteinemia.
I.For refractory hyponatremia in patients with CHF, consider adding a low dose angiotensin-converting enzyme (ACE) inhibitor to the diuretic regimen. Consult nephrology and cardiology experts.
J.For patients with cirrhosis, primary therapy for hyponatremia is water restriction and a low salt diet. If diuretics are required, use loop diuretics in combination with potassium-sparing diuretics and monitor potassium carefully.
K.Thiazide diuretics impair urine-diluting capacity, thus exacerbating hyponatremia.
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