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].

Diagnostic Study of Choice

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.[1] 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 rise of serum sodium exceed 0.33 mmol/l/h over several hours, vasopressin may be administered to prevent ongoing rapid water diuresis.[2]

Treatment based on conditions [3] [4] [5]:

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
Initial treatment of moderate to severe hyponatremia serum sodium < 130 mEq/L
 
 
 
 
 
 
 
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)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum sodium level < 120 mEq/L
 
 
 
Symptomatic patients must be admitted
 
 
 
 
 
 
 
 
 
D03
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
 
 
No
 
 
 
 
 
 
E02
 
 
E03
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Manage the patient in hospital
Monitor serum Na every 4 hour
(Na rise ≤ 8 mEq/L in 24 h)
 
 
 
 
 
 
 
 
 
 
 
 
F01
 
 
 
F02
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treat as outpatient
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
$$$$$
 
 
 
 
 
 
 
 
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)

V1A selective

  • Relcovaptan

V1B selective

  • Nelivaptan

V2 selective

  • Mozavaptan
  • Satavaptan

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.[6]

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:


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

  • 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)

References

  1. Bernsen HJ, Prick MJ (1999). "Improvement of central pontine myelinolysis as demonstrated by repeated magnetic resonance imaging in a patient without evidence of hyponatremia". Acta Neurol Belg. 99 (3): 189–93. PMID 10544728. Unknown parameter |month= ignored (help)
  2. Horacio J. Adrogué, M.D. and Nicolaos E. Madias, M.D (2000-05-25). "Hyponatremia". N Engl J Med 2000; 342:1581-1589. The New England Journal of Medicine.
  3. Assadi, Farahnak (2012). "Hyponatremia: a problem-solving approach to clinical cases". Journal of Nephrology. 25 (4): 473–480. doi:10.5301/jn.5000060. ISSN 1121-8428.
  4. Joseph G. Verbalis, Steven R. Goldsmith, Arthur Greenberg, Cynthia Korzelius, Robert W. Schrier, Richard H. Sterns & Christopher J. Thompson (2013). "Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations". The American journal of medicine. 126 (10 Suppl 1): S1–42. doi:10.1016/j.amjmed.2013.07.006. PMID 24074529. Unknown parameter |month= ignored (help)
  5. Joseph G. Verbalis, Steven R. Goldsmith, Arthur Greenberg, Cynthia Korzelius, Robert W. Schrier, Richard H. Sterns & Christopher J. Thompson (2013). "Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations". The American journal of medicine. 126 (10 Suppl 1): S1–42. doi:10.1016/j.amjmed.2013.07.006. PMID 24074529. Unknown parameter |month= ignored (help)
  6. Robert D. Zenenberg,D, et. al (2010-04-27). "Hyponatremia: Evaluation and Management". Hospital Practice. 38 (1): 89–96. doi:10.3810/hp.2010.02.283. PMID 20469629. Unknown parameter |month= ignored (help)

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