Hyponatremia medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Saeedeh Kowsarnia M.D.[2]

Overview

There is no treatment for [disease name]; the mainstay of therapy is supportive care.

OR

Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].

OR

The majority of cases of [disease name] are self-limited and require only supportive care.

OR

[Disease name] is a medical emergency and requires prompt treatment.

OR

The mainstay of treatment for [disease name] is [therapy].

OR   The optimal therapy for [malignancy name] depends on the stage at diagnosis.

OR

[Therapy] is recommended among all patients who develop [disease name].

OR

Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].

OR

Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].

OR

Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].

OR

Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].

Medical Therapy

Hyponatremia must be corrected slowly in order to lessen the chance of the development of central pontine myelinolysis (CPM), a severe neurological disease. In fact, overly rapid correction of hyponatremia is the most common cause of that potentially devastating disorder. During treatment of hyponatremia, the serum sodium should not be allowed to rise by more than 8 mmol/l over 24 hours (i.e. 0.33 mmol/l/h rate of rise). In practice, too rapid correction of hyponatremia and thence CPM is most likely to occur during the treatment of hypovolemic hyponatremia. In particular, once the hypovolemic state has been corrected, the signal for ADH release disappears. At that point, there will be an abrupt water diuresis (since there is no longer any ADH acting to retain the water). A rapid and profound rise in serum sodium can then occur. Should the rate of rising of serum sodium exceed 0.33  mmol/l/h over several hours, vasopressin may be administered to prevent ongoing rapid water diuresis.

Treatment based on conditions :

Conditions	Treatment
Puedohyponatremia	Hyperglycemia: Insulin, IV fluids, Isotonic saline Hyperproteinemia: Chemotherapy( Multiple myeloma), Stop IVIG Hyperglycemia: Statin therapy Lab error: Repeat the test
Hypovolemic Hyponatremia	Gastrointestinal loss:Intravenous fluids Renal loss Osmotic diuresis:Correct glucose level, stop mannitol use Renal tubular acidosis : Correct acidosis, sodium bicarbonate Salt-wasting nephropathies : Correct underlying cause Diuretic use : Stop diuretic therapy Mineralocorticoid deficiency : Steroid replacement therapy, Isotonic saline Third spacing : Intravenous fluids, treat the underlying cause Cerebral salt-wasting syndrome : Isotonic or hypertonic saline
Hypervolemic hyponatremia	Heart failure : Diuretics, angiotensin-converting enzyme inhibitors, beta blockers Hepatic failure/cirrhosis : Furosemide (Lasix), spironolactone (Aldactone), transplant Renal failure (acute or chronic),Nephrotic syndrome : Correct underlying disease with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers,treat underlying cause for nephrotic syndrome
Euvolemic Hyponatremia	Drugs :Stop causative medications SIADH/SIAD : Fluid restriction, consider vaptans Nephrogenic SIAD : Fluid restriction, loop diuretics Hight fluid intake : Diuresis Hypothyriodism : Thyroid replacement therapy Glucocorticoid deficiency : Steroid replacement therapy Reset osmostat : Treat underlying disease
Acute hyponatremia	For severe symptoms, 100 mL of 3% NaCl infused intravenously over 10 minutes � 3 as needed; � For mild to moderate symptoms with a low risk of herniation, 3% NaCl infused at 0.5-2 mL/kg/h; � The rate of correction need not be restricted in patients with true acute hyponatremia, nor is relowering of excessive corrections indicated

Duration of hyponatremia • Acute hyponatremia develops < 48 hours • Chronic hyponatremia > 48hours or unknown duration

Hospitalize the patients if • The patient is symptomatic regardless of duration • Serum sodium < 125 mEq/L • Acute hyponatremia

Chronic

Acute

Is the patient symptomatic ( Whether mild, moderate, severe)

Hospitalize the patient and check for symptoms of hyponatremia ( Whether mild, moderate, severe)

Asymptomatic but serum sodium level < 120 mEq/L

Symptomatic patients must be admitted

No

Are the symptoms severe?

Recheck serum Na still hyponatremia( incase of water diuresis autocorrectiom may happen

Yes

Yes

Yes

No

No

Manage the patient in the hospital • Primary management‡ • Monitor serum Na every 4 hours to ensure appropriate rate of correction ≤ 8 mEq/L in 24 hours

• 100 ml bolus of 3% saline,repeat as needed if symptoms persist • Monitor serum Na hourly till it is increased by 4 to 6 mEq/L • Primary management‡

Primary management‡ Monitor serum Na every 4 hour (Na rise ≤ 8 mEq/L in 24 h)

If no, Primary management‡

Yes

Is there any history of intracranial pathology?Trauma, surgery, hemorrhage, neoplasm, SOP

• Monitor serum Na hourly till it is increased by 4 to 6 mEq/L • Further decline in serum Na means delayed water absorbtion • If serum Na declines give 50ml bolus of 3% saline • Primary management‡

No

Yes

Is the serum Na < 120 mEq/L?

Yes

No

Is the hyponatremia due to self-induced water intoxication?

• Primary management‡ • Monitor serum Na every 6-12 hours

Yes

No

• Primary management‡ • Monitor serum Na every 6-12 hours

Is the patient hypervolemic/edematous (CHF,RF,cirrhosis)

Yes

No

• Primary management‡ • Infusion of 3% saline at the rate of 15-30 ml/hour plus IV furosemide(40 mg or higher)twice daily• Monitor serum Na frequently to adjust rate of furosemide and saline to achieve 4-6mEq/L rise in serum Na• Discontinue regimen when serum Na is at least 125 mEq/L

Is the cause of hyponatremia reversible? (True hypovolemia, adrenal insufficiency, transient SIADH

No

Yes

Evaluate the risk for osmotic demyelination syndrome • Serum Na ≤ 105 mEq/L • Asociated hypokalemia • Alcoholic patient • Malnourished patient • associated liver disease

No

Yes

• Primary management‡• Infusion of 3% salin at 15-30 ml/hour • Monitor serum Na to achieve rate of correction 4-6 mEq/L • Discontinue regimen when serum Na is atleast 125 mEq/L

• Infusion of 3% saline at 15-30 ml/hour plus IV or subcutaneous desmopressin 1 to 2 mcg every 6-8 hours • Monitor serum Na to achieve rate of correction 4-6 mEq/L • Discontinue regimen when serum Na is atleast 125 mEq/L • Primary management‡

‡ Primary management:

• Treat the underlying cause of hyponatremia
• Discontinue responsible drugs unless there is no other substitute
• Treat chronic hyponatremia and SIADH with loop diuretics, oral salt tablets, urea
• Reduce intake of electrolyte-free water(IV fluid, oral intake)

$$$$$

Hyponatremia serum sodium < 135 mEq/L

check for pseudohyponatremia (Hyperglycemia, Hyperlipidemia, Hyperproteinemia, lab errors)

Symptomatic

Asymptomatic

confusion, ataxia, seizures, obtundation, coma, respiratory depression

Determine serum osmolality Serum Osmolality = (2 x (Na + K)) + (BUN (mg/dL) / 2.8) + (glucose (mg/dL) / 18) + (Ethanol (mg/dL) /3.7)

Infuse 3% saline (1 to 2 mL per kg per hour) with goal of increasing serum sodium level by 6 to 8 mEq per L (not to exceed 10 to 12 mEq per L in the first 24 hours or 18 mEq per L in 48 hours) Consider desmopressin, 1 to 2 mcg every four to six hours

Give single intravenous bolus of 100 to 150 mL 3% saline with goal of increasing serum sodium level by 2 to 3 mEq per L; check sodium level every 20 minutes until symptoms resolve; may repeat bolus twice if symptoms do not resolve

Normal 275-295 mOsm/kg Isotonic hyponatremia (pseudohyponatremia)

Low <275mOsm/kg Hypotonic hyponatremia

High >295 mOsm/kg Hypertonic hyponatremia

Assess for hyperproteinuria or hyperlipidemia

Assess volume status

Assess for hyperglycemia, check for mannitol or sorbitol use or recent administration of radiocontrast media

Symptom resolution

Evaluate vital signs, orthostatics, jugular venous pressure, skin turgor, mucous membranes, peripheral edema, and blood urea nitrogen and uric acid levels

Check serum sodium level every two hours; adjust infusion rate and switch to isotonic saline

Determine underlying cause

Hypovolemic (decreased total body water and sodium level)

Euvolemic (increased total body water, normal total body sodium level)

Hypervolemic (increased total body water)

Urinary sodium > 20 mEq per L

Urinary sodium < 20 mEq per L

Urinary sodium usually > 20 mEq per L

Urinary sodium < 20 mEq per L

Urinary sodium > 20 mEq per L

Renal loss (from diuretics or mineralocorticoid deficiency)

Extrarenal loss (fromv omiting, diarrhea,third spacing, or bowel obstruction)

Urinary osmolality > 100 mOsm per kg

Urinary osmolality < 100 mOsm per kg

Variable urinaryosmolality

Heart failure,cirrhosis, nephrosis,hypoalbuminemia

Renal failure

Isotonic saline(see Table 1for specifitreatments)

Isotonic saline(see Table 1for specifictreatments)

Syndrome ofinappropriate antidiuretichormonesecretion, hypothyroidism,adrenal insufficiency,stress, drug use

Primary polydipsia,low solute intake (beer potomania syndrome)

Resetosmostat

Diuresis, fluid andsodium restriction(see Table 1 for specific treatments)

Fluid and sodium restriction, dialysis (see Table 1 for specific treatments)

Fluid restriction(see Table 1for specifictreatments)

Fluid restriction(see Table 1for specific treatments)

Fluid restriction(see Table 1for specifictreatments)

Vaptan Drugs

The “vaptan” class of drugs contains a number of compounds with varying selectivity, several of which are either already in clinical use or in clinical trials as of 2010.

Unselective (mixed V1A, V2)

• Conivaptan

V1A selective

• Relcovaptan

V1B selective

• Nelivaptan

V2 selective

• Lixivaptan

• Mozavaptan

• Satavaptan

• Tolvaptan

The V2-receptor antagonists tolvaptan and conivaptan allow excretion of electrolyte free water and are effective in increasing serum sodium in euvolemic and hypervolemic hyponatremia.

Rate of Na Correction

The rate of correction of hyponatremia should be 0.5-1.0meq/L/hr, with not more than a 12 meq/l correction in 24 hrs. If the patient has ongoing seizures (or [Na⁺]<115 meq/li), correction can be attempted at up to 2 meq/L/hr, but only while seizure activity lasts and the [Na⁺] exceeds 125-130 meq/Li.

Contraindicated medications

Hyponatremia is considered an absolute contraindication to the use of the following medications:

• Acetazolamide

Hypovolemic hyponatremia is considered an absolute contraindication to the use of the following medications:

• Tolvaptan
• Conivaptan

• Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
• Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
• Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
• Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].

Disease Name

• 1 Stage 1 - Name of stage
  • 1.1 Specific Organ system involved 1
    • 1.1.1 Adult
      • Preferred regimen (1): drug name 100 mg PO q12h for 10-21 days (Contraindications/specific instructions)
      • Preferred regimen (2): drug name 500 mg PO q8h for 14-21 days
      • Preferred regimen (3): drug name 500 mg q12h for 14-21 days
      • Alternative regimen (1): drug name 500 mg PO q6h for 7–10 days
      • Alternative regimen (2): drug name 500 mg PO q12h for 14–21 days
      • Alternative regimen (3): drug name 500 mg PO q6h for 14–21 days
    • 1.1.2 Pediatric
      • 1.1.2.1 (Specific population e.g. children < 8 years of age)
        • Preferred regimen (1): drug name 50 mg/kg PO per day q8h (maximum, 500 mg per dose)
        • Preferred regimen (2): drug name 30 mg/kg PO per day in 2 divided doses (maximum, 500 mg per dose)
        • Alternative regimen (1): drug name10 mg/kg PO q6h (maximum, 500 mg per day)
        • Alternative regimen (2): drug name 7.5 mg/kg PO q12h (maximum, 500 mg per dose)
        • Alternative regimen (3): drug name 12.5 mg/kg PO q6h (maximum, 500 mg per dose)
      • 1.1.2.2 (Specific population e.g. 'children < 8 years of age')
        • Preferred regimen (1): drug name 4 mg/kg/day PO q12h（maximum, 100 mg per dose）
        • Alternative regimen (1): drug name 10 mg/kg PO q6h (maximum, 500 mg per day)
        • Alternative regimen (2): drug name 7.5 mg/kg PO q12h (maximum, 500 mg per dose)
        • Alternative regimen (3): drug name 12.5 mg/kg PO q6h (maximum, 500 mg per dose)
  • 1.2 Specific Organ system involved 2
    • 1.2.1 Adult
      • Preferred regimen (1): drug name 500 mg PO q8h
    • 1.2.2 Pediatric
      • Preferred regimen (1): drug name 50 mg/kg/day PO q8h (maximum, 500 mg per dose)

• 2 Stage 2 - Name of stage
  • 2.1 Specific Organ system involved 1

    Note (1):

    Note (2):

    Note (3):

    • 2.1.1 Adult
      • Parenteral regimen
        • Preferred regimen (1): drug name 2 g IV q24h for 14 (14–21) days
        • Alternative regimen (1): drug name 2 g IV q8h for 14 (14–21) days
        • Alternative regimen (2): drug name 18–24 MU/day IV q4h for 14 (14–21) days
      • Oral regimen
        • Preferred regimen (1): drug name 500 mg PO q8h for 14 (14–21) days
        • Preferred regimen (2): drug name 100 mg PO q12h for 14 (14–21) days
        • Preferred regimen (3): drug name 500 mg PO q12h for 14 (14–21) days
        • Alternative regimen (1): drug name 500 mg PO q6h for 7–10 days
        • Alternative regimen (2): drug name 500 mg PO q12h for 14–21 days
        • Alternative regimen (3):drug name 500 mg PO q6h for 14–21 days
    • 2.1.2 Pediatric
      • Parenteral regimen
        • Preferred regimen (1): drug name 50–75 mg/kg IV q24h for 14 (14–21) days (maximum, 2 g)
        • Alternative regimen (1): drug name 150–200 mg/kg/day IV q6–8h for 14 (14–21) days (maximum, 6 g per day)
        • Alternative regimen (2):  drug name 200,000–400,000 U/kg/day IV q4h for 14 (14–21) days (maximum, 18–24 million U per day) '(Contraindications/specific instructions)'
      • Oral regimen
        • Preferred regimen (1): drug name 50 mg/kg/day PO q8h for 14 (14–21) days (maximum, 500 mg per dose)
        • Preferred regimen (2): drug name (for children aged ≥ 8 years) 4 mg/kg/day PO q12h for 14 (14–21) days (maximum, 100 mg per dose)
        • Preferred regimen (3): drug name 30 mg/kg/day PO q12h for 14 (14–21) days (maximum, 500 mg per dose)
        • Alternative regimen (1): drug name 10 mg/kg PO q6h 7–10 days (maximum, 500 mg per day)
        • Alternative regimen (2): drug name 7.5 mg/kg PO q12h for 14–21 days (maximum, 500 mg per dose)
        • Alternative regimen (3): drug name 12.5 mg/kg PO q6h for 14–21 days (maximum,500 mg per dose)
  • 2.2 'Other Organ system involved 2'

    Note (1):

    Note (2):

    Note (3):

    • 2.2.1 Adult
      • Parenteral regimen
        • Preferred regimen (1): drug name 2 g IV q24h for 14 (14–21) days
        • Alternative regimen (1): drug name 2 g IV q8h for 14 (14–21) days
        • Alternative regimen (2): drug name 18–24 MU/day IV q4h for 14 (14–21) days
      • Oral regimen
        • Preferred regimen (1): drug name 500 mg PO q8h for 14 (14–21) days
        • Preferred regimen (2): drug name 100 mg PO q12h for 14 (14–21) days
        • Preferred regimen (3): drug name 500 mg PO q12h for 14 (14–21) days
        • Alternative regimen (1): drug name 500 mg PO q6h for 7–10 days
        • Alternative regimen (2): drug name 500 mg PO q12h for 14–21 days
        • Alternative regimen (3):drug name 500 mg PO q6h for 14–21 days
    • 2.2.2 Pediatric
      • Parenteral regimen
        • Preferred regimen (1): drug name 50–75 mg/kg IV q24h for 14 (14–21) days (maximum, 2 g)
        • Alternative regimen (1): drug name 150–200 mg/kg/day IV q6–8h for 14 (14–21) days (maximum, 6 g per day)
        • Alternative regimen (2):  drug name 200,000–400,000 U/kg/day IV q4h for 14 (14–21) days (maximum, 18–24 million U per day)
      • Oral regimen
        • Preferred regimen (1): drug name 50 mg/kg/day PO q8h for 14 (14–21) days (maximum, 500 mg per dose)
        • Preferred regimen (2): drug name 4 mg/kg/day PO q12h for 14 (14–21) days (maximum, 100 mg per dose)
        • Preferred regimen (3): drug name 30 mg/kg/day PO q12h for 14 (14–21) days (maximum, 500 mg per dose)
        • Alternative regimen (1): drug name 10 mg/kg PO q6h 7–10 days (maximum, 500 mg per day)
        • Alternative regimen (2): drug name 7.5 mg/kg PO q12h for 14–21 days (maximum, 500 mg per dose)
        • Alternative regimen (3): drug name 12.5 mg/kg PO q6h for 14–21 days (maximum,500 mg per dose)