Hyponatremia medical therapy: Difference between revisions

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__NOTOC__
__NOTOC__
{{Hyponatremia}}
{{Hyponatremia}}
{{CMG}}
{{CMG}}; {{AE}}{{Saeedeh}}
 
==Overview==
Hyponatremia, serum sodium < 135 mEq/L, is the most common electrolyte disturbances in the clinical encounter. Treatment of hyponatremia based on the etiologies is the best approach because in most cases, hyponatremia resolves with the treatment of underlying causes.
 
The rate of correction for hyponatremia is very important to prevent the syndrome of osmotic demyelination.


==Medical Therapy==
==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.<ref name="pmid10544728">{{cite journal |author=Bernsen HJ, Prick MJ |title=Improvement of central pontine myelinolysis as demonstrated by repeated magnetic resonance imaging in a patient without evidence of hyponatremia |journal=Acta Neurol Belg |volume=99 |issue=3 |pages=189–93 |year=1999 |month=September |pmid=10544728 |doi= |url=}}</ref> During treatment of hyponatremia, the serum sodium should not be allowed to rise by more than 8&nbsp;mmol/l over 24 hours (i.e. 0.33&nbsp;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&nbsp;mmol/l/h over several hours, vasopressin may be administered to prevent ongoing rapid water diuresis.<ref>{{cite web|url=http://www.nejm.org/doi/full/10.1056/NEJM200005253422107|title=Hyponatremia|date=2000-05-25|author=Horacio J. Adrogué, M.D. and Nicolaos E. Madias, M.D|work=N Engl J Med 2000; 342:1581-1589|publisher=[[The New England Journal of Medicine]]}}</ref>
Hyponatremia must be corrected slowly in order to lessen the chance of the development of [[central pontine myelinolysis|Osmotic demyelination syndrome]] or [[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.<ref name="pmid10544728">{{cite journal |author=Bernsen HJ, Prick MJ |title=Improvement of central pontine myelinolysis as demonstrated by repeated magnetic resonance imaging in a patient without evidence of hyponatremia |journal=Acta Neurol Belg |volume=99 |issue=3 |pages=189–93 |year=1999 |month=September |pmid=10544728 |doi= |url=}}</ref> During treatment of hyponatremia, the serum sodium should not be allowed to rise by more than 8&nbsp;mmol/l over 24 hours (i.e. 0.33&nbsp;mmol/l/h rate of rise). In practice, rapid correction of hyponatremia and then 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&nbsp; mmol/l/h over several hours, [[vasopressin]] may be administered to prevent ongoing rapid water diuresis.<ref>{{cite web|url=http://www.nejm.org/doi/full/10.1056/NEJM200005253422107|title=Hyponatremia|date=2000-05-25|author=Horacio J. Adrogué, M.D. and Nicolaos E. Madias, M.D|work=N Engl J Med 2000; 342:1581-1589|publisher=[[The New England Journal of Medicine]]}}</ref>  
 
'''<big>Treatment based on  the conditions</big>''' <ref name="Assadi2012">{{cite journal|last1=Assadi|first1=Farahnak|title=Hyponatremia: a problem-solving approach to clinical cases|journal=Journal of Nephrology|volume=25|issue=4|year=2012|pages=473–480|issn=1121-8428|doi=10.5301/jn.5000060}}</ref> <ref>{{Cite journal
 
| author = [[Joseph G. Verbalis]], [[Steven R. Goldsmith]], [[Arthur Greenberg]], [[Cynthia Korzelius]], [[Robert W. Schrier]], [[Richard H. Sterns]] & [[Christopher J. Thompson]]
 
| title = Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations
 
| journal = [[The American journal of medicine]]
 
| volume = 126
 
| issue = 10 Suppl 1
 
| pages = S1–42
 
| year = 2013
 
| month = October
 
| doi = 10.1016/j.amjmed.2013.07.006
 
| pmid = 24074529
 
}}</ref> <ref>{{Cite journal
 
| author = [[Joseph G. Verbalis]], [[Steven R. Goldsmith]], [[Arthur Greenberg]], [[Cynthia Korzelius]], [[Robert W. Schrier]], [[Richard H. Sterns]] & [[Christopher J. Thompson]]
 
| title = Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations
 
| journal = [[The American journal of medicine]]
 
| volume = 126
 
| issue = 10 Suppl 1
 
| pages = S1–42
 
| year = 2013
 
| month = October
 
| doi = 10.1016/j.amjmed.2013.07.006
 
| pmid = 24074529
 
}}</ref> <ref>{{Cite journal
 
| author = [[Richard H. Sterns]], [[Sagar U. Nigwekar]] & [[John Kevin Hix]]
 
| title = The treatment of hyponatremia
 
| journal = [[Seminars in nephrology]]
 
| volume = 29
 
| issue = 3
 
| pages = 282–299
 
| year = 2009
 
| month = May
 
| doi = 10.1016/j.semnephrol.2009.03.002
 
| pmid = 19523575
 
}}</ref> <ref name="VerbalisGoldsmith2013">{{cite journal|last1=Verbalis|first1=Joseph G.|last2=Goldsmith|first2=Steven R.|last3=Greenberg|first3=Arthur|last4=Korzelius|first4=Cynthia|last5=Schrier|first5=Robert W.|last6=Sterns|first6=Richard H.|last7=Thompson|first7=Christopher J.|title=Diagnosis, Evaluation, and Treatment of Hyponatremia: Expert Panel Recommendations|journal=The American Journal of Medicine|volume=126|issue=10|year=2013|pages=S1–S42|issn=00029343|doi=10.1016/j.amjmed.2013.07.006}}</ref> <ref>{{Cite journal
 
| author = [[Richard H. Sterns]], [[John Kevin Hix]] & [[Stephen Silver]]
 
| title = Treatment of hyponatremia
 
| journal = [[Current opinion in nephrology and hypertension]]
 
| volume = 19
 
| issue = 5
 
| pages = 493–498
 
| year = 2010
 
| month = September
 
| doi = 10.1097/MNH.0b013e32833bfa64
 
| pmid = 20539224
 
}}</ref> ''':''' 
 
{| class="wikitable"
!Conditions
!Treatment
|-
!'''Pseudohyponatremia'''
|
*'''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 [[Diuretics|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, [[fludrocortisone]] rarely
|-
!'''Hypervolemic hyponatremia'''
|
*'''Heart failure :''' [[Diuretics]], [[angiotensin-converting enzyme inhibitors]], [[beta blockers]], [[vaptans]]
*'''Hepatic failure/cirrhosis :''' [[Furosemide]] (Lasix), [[spironolactone]] (Aldactone), transplant, vaptans (not tolvaptan for cirrhosis)
*'''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, [[demeclocycline]], consider vaptans (second line), oral salt tablets, urea
*'''Nephrogenic SIAD :''' Fluid restriction, [[loop diuretics]], oral salt tablets, [[urea]]
*'''Hight fluid intake :''' [[Diuresis]]
*'''Hypothyriodism :''' Thyroid replacement therapy
*'''Glucocorticoid deficiency :''' Steroid replacement therapy
*'''Reset osmostat :''' Treat underlying disease
|-
!'''Rate of correction'''
|
*'''Goal:''' Raise the serum sodium concentration by 4 to 6 mEq/L in a 24-hour period
 
*'''Maximum:''' Should be ≤ 8 mEq/L in any 24-hour period, '''pediatric:''' rates ≤ 9 mEq/ L
|-
!'''Acute hyponatremia'''
 
*'''For severe symptoms :'''
**'''Adult:''' 100 mL of 3% saline (NaCl) infused intravenously over 10 minutes X 3 ( if needed) in 30 minutes
**'''Pediatric:''' 3 to 5 mL/kg of 3 % saline is the suggested initial therapy
 
*'''For mild to moderate symptoms :'''
**'''Adult:''' 3% saline infused at 0.5-2 mL / kg / h, with a low risk of herniation
**'''Pediatric:''' 6 to 8 mEq/L over 24 hours
 
<small>(The rate of correction need not be restricted in patients with true acute hyponatremia, nor is relowering of excessive corrections indicated, however, if there is any uncertainty as to whether the hyponatremia is chronic versus acute, then the limits for correction of chronic hyponatremia should be followed)</small>
|-
!'''Chronic hyponatremia'''
|'''Asymptomatic:''' Primary management <sup>‡</sup>
'''Mild to moderate symptoms :'''
 
*'''With intracranial pathology:'''100 mL bolus of 3 % saline x 2 (to a total dose of 300 mL) in 30 minutes
*'''Without intracranial pathology:'''
**'''Severe hyponatremia (< 120 mEq/L):''' 3 % saline at 15 to 30 mL/ h + desmopressin in patients with risk of overcorrection and osmotic demyelination syndrome
**'''Mild to moderate hyponatremia (120-129  mEq/L):''' Primary management <sup>‡</sup>
 
'''Severe symptoms :''' 100 mL of 3% saline infused intravenously over 10 minutes X 3 ( if needed ) in 30 minutes
 
'''Pediatric:'''
 
*Treat based on the cause, 6 to 8 mEq/L over 24 hours
*Primary management <sup>‡</sup>
*Hyponatremic sodium deficit = Current total body water (TBW) x (desired plasma sodium - actual sodium)
 
( TBW= 0.6 x weight)
|-
!'''Management of overcorrection'''
|'''Baseline Serum <small>Na</small> ≥ 120 mmol/L:''' probably unnecessary, start once limit is exceeded
'''Baseline Serum <small>Na</small> < 120 mmol/L:''' start relowering with electrolyte-free water or desmopressin after correction exceeds 6–8 mmol/L per d
|}
 
<br>
<small>‡ Primary management:</small>
 
*<small>Treat the underlying cause of hyponatremia</small>
*<small>Discontinue responsible drugs unless there is no other substitute</small>
*<small>Treat chronic hyponatremia and [[SIADH]] with loop diuretics, oral salt tablets, urea</small>
*<small>Reduce intake of electrolyte-free water(IV fluid, oral intake)</small>
 
<br>
<small>
{| class="wikitable"
!Medications
!Clinical use
|-
!Salt tablets
|
*'''Dose:''' 5-15 gr daily
*'''Side effects:''' [[Hypernatremia]], fluid overload
*'''Indications:''' [[SIADH|SIAD]] combined with furosemide
|-
!Furosemide
|
*'''Dose:'''20-80 mg daily
*'''Side effects:''' [[Orthostatic hypotension]], [[impaired glucose tolerance]], [[hyperuricemia]], [[azotemia]], [[ototoxicity]], [[pancreatitis]]
*'''Indications:''' [[SIADH|SIAD]], [[CHF]], and [[Liver diseases|liver disease]] with [[ascites]]
|-
!Urea
|
*'''Dose:''' 15–30 g daily
*'''Side effects:''' Too rapid an increase in serum sodium, [[azotemia]]
*'''Indications:''' [[SIADH|SIAD]], hyponatremia of [[heart failure]]
|-
!Demeclocycline
|
*'''Dose:''' 600–1200 mg total daily dose, dosed 3 to 4 times daily
*'''Side effects:''' CNS side effects, [[nausea]], [[vomiting]], [[diarrhea]], [[photosensitivity]], [[azotemia]], [[acute renal failure]], hematologic effects with long-term therapy
*'''Indications:''' [[SIADH|SIAD]]
|}
</small>
<br>
 
<br>
===Practical approach to treatment of hyponatremia <ref name="HoornZietse2017">{{cite journal|last1=Hoorn|first1=Ewout J.|last2=Zietse|first2=Robert|title=Diagnosis and Treatment of Hyponatremia: Compilation of the Guidelines|journal=Journal of the American Society of Nephrology|volume=28|issue=5|year=2017|pages=1340–1349|issn=1046-6673|doi=10.1681/ASN.2016101139}}</ref>===
<small>
{{familytree/start |}}
{{familytree | | | | | | | | A01 | | | | | | A01=<table><tr><th>Duration of hyponatremia</th></tr><tr><td>• Acute hyponatremia develops < 48 hours<br>
• Chronic hyponatremia > 48hours or unknown duration</td></tr></table>}}
{{familytree | | | | | | | | |!| | | | | | | }}
{{familytree | | | | | | | | A02 | | | | | |A02=<table><tr><th>Hospitalize the patients if</th></tr><tr><td>• The patient is symptomatic regardless of duration<br>• Serum sodium < 125 mEq/L<br>• Acute hyponatremia</td></tr></table>}}
{{familytree | | | |,|-|-|-|-|^|-|-|-|-|-|-|-|-|-|-|.| | | }}
{{familytree | | | B01 | | | | | | | | | | | | | | B02 | | |B01='''Chronic'''|B02='''Acute'''}}
{{familytree | | | |!| | | | | | | | | | | | | | | |!| | | |}}
{{familytree | | | C01 | | | | | | | | | | | | | | B03 | |C01=Is the patient '''symptomatic'''<br>( Whether mild, moderate, severe)|B03='''Hospitalize''' the patient and check for symptoms of hyponatremia<br>( Whether mild, moderate, severe)|}}
{{familytree | | | |)|-|-|-|.| | | | | | | | | | | |!| |}}
{{familytree | | | D01 | | D02 | | | | | | |,|-|-| D03 |D01='''Asymptomatic''' but '''serum Na < 120 mEq/L'''|D02='''Symptomatic''' patients must be admitted|D03=No symptoms}}
{{familytree | |,|-|^|.| | |!| | | | | | | |!| | | |!| | | |}}
{{familytree | |!| | |!| | E04 |-|-|.| | | |!| | | E05 | |E04=Are the '''symptoms severe'''?|E05=Recheck '''serum Na if the patient is hyponatremic ( incase of water diuresis autocorrectiom may happen}}
{{familytree | E01 | |!| | |!| | | E01 | | E02 | |,|^|-|.|E01=Yes|E02=Yes}}
{{familytree | |!| | |!| | F02 | | |!| | | |!| | |!| | F01 | |F02=No|F01=No}}
{{familytree | H01 | |!| | |!| | | |`|-|-| F01 | |!| | F03 | |H01=<table><tr><th>Manage the patient in the hospital</th></tr><tr><td>• Primary management <sup>‡</sup><br>• Monitor serum Na every 4 hours to ensure appropriate rate of correction ≤ 8 mEq/L in 24 hours</td></tr></table> |F01=<table><tr><th>Therapy</th></tr><tr><td>• 100 ml bolus of 3% saline,repeat as needed if symptoms persist<br>• Monitor serum Na hourly till it is increased by 4 to 6 mEq/L<br>• Primary management<sup>‡</sup></td></tr></table>|F03= • Primary management <sup>‡</sup><br>• Monitor serum Na every 4 hour<br>(Na rise ≤ 8 mEq/L in 24 h)}}
{{familytree | | | | G01 | |!| | | | | | | |!| | |!| | | | |G01=If no, Primary management <sup>‡</sup>|F03=<table><tr><th>Treatment</th></tr><tr><td>• 50 ml bolus of 3% saline to prevent further decline in serum Na<br>• Monitor serum Na hourly<br>• Primary management <sup>‡</sup></td></tr></table>}}
{{Family tree| | | | | | | |!| | | | | | | |!| | G03 | | |G03=Yes}}
{{Family tree| | | | | | | G01 |-|-|.| | | |!| | G03 | | |G01=Is there any history of '''[[intracranial pathology]]'''?Trauma, surgery, hemorrhage, neoplasm, space occupying lesions|G03=<table><tr><th>Treatment</th></tr><tr><td>• Monitor serum Na hourly till it is increased by 4 to 6 mEq/L<br>• Further decline in serum Na means delayed water absorbtion<br>• If serum Na declines give 50ml bolus of 3% saline<br>• Primary management<sup>‡</sup></td></tr></table>}}
{{Familytree | | | | | | | |!| | | |!| | | |!| | | | | ||}}
{{familytree | | | | | | | A01 | | G04 |-|-|'| |A01=No|G04=Yes}}
{{familytree | | | | | | | |!| | | | | | | | | }}
{{familytree | | | | | | | A02 | | | | | | | | |A02=Is the serum Na < 120 mEq/L?}}
{{familytree | | | | |,|-|-|^|-|-|.| | | | | | }}
{{familytree | | | | A02 | | | | A03 | | | | |A02=Yes|A03=No}}
{{familytree | | | | |!| | | | | |!| | | | | | }}
{{familytree | | | | A04 | | | | A05 | | | | | A04=Is the hyponatremia due to self-induced '''water intoxication'''?|A05=• Primary management <sup>‡</sup><br>• Monitor serum Na every 6-12 hours }}
{{familytree | | |,|-|^|-|-|.| | | | | | | | | }}
{{familytree | | A05 | | | A06 | | | | | | | | |A05=Yes|A06=No}}
{{familytree | | |!| | | | |!| | | | | | | | | }}
{{familytree | | A07 | | | A08 | | | | | | | | |A07=<table><tr><th>Therapy</th></tr><tr><td>• Primary management <sup>‡</sup><br>• Monitor serum Na every 6-12 hours</td></tr></table>|A08=Is the patient hypervolemic/edematous ([[CHF]],[[RF]],[[cirrhosis]])}}
{{familytree | | | | |,|-|-|^|-|-|.| | | | | | }}
{{familytree | | | | A09 | | | | A10 | | | | |A09=Yes|A10=No}}
{{familytree | | | | |!| | | | | |!| | | | | | }}
{{familytree | | | | A11 | | | | A12 | | | | | |A11=<table><tr><th>Treatment</th></tr><tr><td>• Primary management <sup>‡</sup><br>• Infusion of 3% saline at the rate of 15-30 ml/hour plus IV furosemide(40 mg or higher)twice daily<br>• Monitor serum Na frequently to adjust rate of furosemide and saline to achieve 4-6mEq/L rise in serum Na<br>• Discontinue regimen when serum Na is at least 125 mEq/L</td></tr></table>|A12=<table><tr><th>Is the cause of hyponatremia reversible?</th></tr><tr><td>•True hypovolemia<br> •[[Adrenal insufficiency]]<br>•Transient [[SIADH|SIAD]]</td></tr></table> }}
{{familytree | | | | | | | | |,|-|^|-|.| | | | | | | | |}}
{{familytree | | | | | | | | A13 | | A14 | | | | | | |A13=No|A14=Yes}}
{{familytree | | | | | | | | |!| | | |!| | | | | | | | | |}}
{{familytree | | | | |,|-|-| A15 | | |!| | | | | | | |A15=<table><tr><th>Evaluate the risk for osmotic demyelination syndrome</th></tr><tr><td>• Serum Na ≤ 105 mEq/L<br>• Associated [[hypokalemia]]<br>• Alcoholic patient<br>• [[Malnourished]] patient<br>• Advanced [[liver disease]]</td></tr></table>|A14=No}}
{{familytree | | | | |!| | | |!| | | |!| | | | | | | |}}
{{familytree | | | | A15 | | A13 | | |!| | | | | |A13=Yes|A14=No|A15=No}}
{{familytree | | | | |!| | | |!| | | |!| | | | | | }}
{{familytree | | | | A15 | | A13 |-|-|'| | | | | |A13=<table><tr><th>Treatment</th></tr><tr><td>• Infusion of 3% saline at 15-30 ml/hour plus IV or subcutaneous desmopressin 1 to 2 mcg every 6-8 hours<br>• Monitor serum Na to achieve rate of correction 4-6 mEq/L<br>• Discontinue regimen when serum Na is atleast 125 mEq/L<br>• Primary management <sup>‡</sup></td></tr></table>|A14=<table><tr><th>Treatment</th></tr><tr><td>• Primary management <sup>‡</sup><br>• Infusion of 3% salin at 15-30 ml/hour<br>• Monitor serum Na to achieve rate of correction 4-6 mEq/L<br>•  Discontinue regimen when serum Na is atleast 125 mEq/L</td></tr></table>|A15=<table><tr><th>Treatment</th></tr><tr><td>• Primary management <sup>‡</sup><br>• Infusion of 3% salin at 15-30 ml/hour<br>• Monitor serum Na to achieve rate of correction 4-6 mEq/L<br>•  Discontinue regimen when serum Na is at least 125 mEq/L</td></tr></table>}}
{{familytree/end}}
</small>
 
<small>‡ Primary management:</small>
 
*<small>Treat the underlying cause of hyponatremia</small>
*<small>Discontinue responsible drugs unless there is no other substitute</small>
*<small>Treat chronic hyponatremia and SIADH with loop diuretics, oral salt tablets, urea</small>
*<small>Reduce intake of electrolyte-free water(IV fluid, oral intake)</small>
 
<br>
 
===Vaptan Drugs===
The “vaptan” class of drugs contains a number of compounds with varying selectivity for [[Hyponatremia pathophysiology#Pathophysiology|ADH receptors]], several of which are either already in clinical use or in clinical trials. Tolvaptan improves short term survival in most decompensated cirrhotic hyponatremia patients with resolved serum sodium. <ref name="WangZhang2018">{{cite journal|last1=Wang|first1=Shuzhen|last2=Zhang|first2=Xin|last3=Han|first3=Tao|last4=Xie|first4=Wen|last5=Li|first5=Yonggang|last6=Ma|first6=Hong|last7=Liebe|first7=Roman|last8=Weng|first8=Honglei|last9=Ding|first9=Hui-Guo|title=Tolvaptan treatment improves survival of cirrhotic patients with ascites and hyponatremia|journal=BMC Gastroenterology|volume=18|issue=1|year=2018|issn=1471-230X|doi=10.1186/s12876-018-0857-0}}</ref>
 
<div style="column-count: 4;">
'''Unselective (mixed V1A, V2):'''
 
*[[Conivaptan]]
 
 
 
 
 
'''V1A selective:'''
 
*Relcovaptan
 
 
 


=== 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)
'''V1B selective:'''


* [[Conivaptan]]
*Nelivaptan


V1A selective


* Relcovaptan


V1B selective


* Nelivaptan


V2 selective
'''V2 selective:'''


* [[Lixivaptan]]
*[[Lixivaptan]]


* Mozavaptan
*Mozavaptan


* Satavaptan
*Satavaptan


* [[Tolvaptan]]
*[[Tolvaptan]]
</div>
<small>
{| class="wikitable"
! rowspan="2" |Name
! colspan="6" |Characteristics
|-
!Receptors
!Route of administration
!Urine volume
!Urine osmolality
!Sodium excretion in 24 hours
!Dosage
|-
![[Conivaptan]]
|V1a/V2
|IV
|↑
|↓
|↔
|20 mg loading dose followed by a continuous infusion of either 40 or 80 mg/day for four days
|-
!Lixivaptan
|V2
|Oral
|↑
|↓
|↔ at low dose ↑ at
high dose
|Tial
|-
!Satavaptan
|V2
|Oral
|↑
|↓
|↔
|Trial
|-
![[Tolvaptan]]
|V2
|Oral
|↑
|↓
|↔
|15 mg once daily then after at least 24 hours, may increase to 30 mg once daily to a maximum of 60 mg once daily titrating at 24-hour intervals to desired serum sodium concentration. Avoid fluid restriction during the first 24 hours of therapy. Do not use for more than 30 days due to the risk of hepatotoxicity
|}
</small>
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.<ref name="Hospital Practice 2010">{{cite journal | author= Robert D. Zenenberg,D, et. al | title= Hyponatremia: Evaluation and Management | journal=Hospital Practice. | month=February | pages=89–96 | pmid= 20469629 | volume=38 | issue=1 | url=http://hosppract.com/index.php?article=283#none | doi=10.3810/hp.2010.02.283 | date=2010-04-27}}</ref>


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.<ref name="Hospital Practice 2010">{{cite journal | author= Robert D. Zenenberg,D, et. al | title= Hyponatremia: Evaluation and Management | journal=Hospital Practice. | month=February | pages=89–96 | pmid= 20469629 | volume=38 | issue=1 | url=http://hosppract.com/index.php?article=283#none | doi=10.3810/hp.2010.02.283 | date=2010-04-27}}</ref>
'''Cautions  for use Vaptans in hyponatremia:'''


===Rate of Na Correction===
*Vaptans should not be used in hypovolemic hyponatremia.
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<sup>+</sup>]<115 meq/li), correction can be attempted at up to 2 meq/L/hr, but only while [[seizure activity]] lasts and the [Na<sup>+</sup>] exceeds 125-130 meq/Li.
 
*Vaptans should not be used in conjunction with other treatments for hyponatremia.
*Do not start vaptans immediately after cessation of other treatments for hyponatremia, particularly 3% NaCl.
*Monitor serum sodium closely (every 6-8 hours) for the first 24-48 hours after initiating treatment.
*Adequate fluid intake should be maintained during the first 24-48 hours of treatment; hyponatremia may be corrected too quickly with coincidental fluid restriction; in patients with an impaired or inadequate thirst mechanism ( intubated or unconscious patients), sufficient fluid should be provided to prevent overly rapid correction due to overly rapid aquaresis.
*Serum sodium should be monitored frequently to consider stopping the vaptans if there is a deterioration or change in the patient’s condition ([[NPO]] status, [[intubation]]) that restrict the ability to ingest fluid, request, access.
*Severe, symptomatic hyponatremia should be managed with 3% NaCl, for quicker and more certain correction of serum sodium than vaptans.
 
*Currently, there are no sufficient data for use of vaptans in severe asymptomatic hyponatremia (serum sodium <120 mmol/L)—caution and more frequent monitoring is necessary for these patients.
 
*Overcorrection should be treated with re-lowering the serum sodium to safe limits (see Managing Excessive Correction of Chronic Hyponatremia).


===Contraindicated medications===
===Contraindicated medications===
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===Disease Name===


==References==
==References==
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Latest revision as of 13:51, 18 August 2021

Hyponatremia Microchapters

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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

Hyponatremia, serum sodium < 135 mEq/L, is the most common electrolyte disturbances in the clinical encounter. Treatment of hyponatremia based on the etiologies is the best approach because in most cases, hyponatremia resolves with the treatment of underlying causes.

The rate of correction for hyponatremia is very important to prevent the syndrome of osmotic demyelination.

Medical Therapy

Hyponatremia must be corrected slowly in order to lessen the chance of the development of Osmotic demyelination syndrome or 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, rapid correction of hyponatremia and then 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.[2]

Treatment based on the conditions [3] [4] [5] [6] [7] [8] :

Conditions Treatment
Pseudohyponatremia
  • 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, fludrocortisone rarely
Hypervolemic hyponatremia
Euvolemic

Hyponatremia

  • Drugs : Stop causative medications
  • SIADH/SIAD : Fluid restriction, demeclocycline, consider vaptans (second line), oral salt tablets, urea
  • Nephrogenic SIAD : Fluid restriction, loop diuretics, oral salt tablets, urea
  • Hight fluid intake : Diuresis
  • Hypothyriodism : Thyroid replacement therapy
  • Glucocorticoid deficiency : Steroid replacement therapy
  • Reset osmostat : Treat underlying disease
Rate of correction
  • Goal: Raise the serum sodium concentration by 4 to 6 mEq/L in a 24-hour period
  • Maximum: Should be ≤ 8 mEq/L in any 24-hour period, pediatric: rates ≤ 9 mEq/ L
Acute hyponatremia  
  • For severe symptoms :
    • Adult: 100 mL of 3% saline (NaCl) infused intravenously over 10 minutes X 3 ( if needed) in 30 minutes
    • Pediatric: 3 to 5 mL/kg of 3 % saline is the suggested initial therapy
  • For mild to moderate symptoms :
    • Adult: 3% saline infused at 0.5-2 mL / kg / h, with a low risk of herniation
    • Pediatric: 6 to 8 mEq/L over 24 hours

(The rate of correction need not be restricted in patients with true acute hyponatremia, nor is relowering of excessive corrections indicated, however, if there is any uncertainty as to whether the hyponatremia is chronic versus acute, then the limits for correction of chronic hyponatremia should be followed)

Chronic hyponatremia Asymptomatic: Primary management

Mild to moderate symptoms :

  • With intracranial pathology:100 mL bolus of 3 % saline x 2 (to a total dose of 300 mL) in 30 minutes
  • Without intracranial pathology:
    • Severe hyponatremia (< 120 mEq/L): 3 % saline at 15 to 30 mL/ h + desmopressin in patients with risk of overcorrection and osmotic demyelination syndrome
    • Mild to moderate hyponatremia (120-129 mEq/L): Primary management

Severe symptoms : 100 mL of 3% saline infused intravenously over 10 minutes X 3 ( if needed ) in 30 minutes

Pediatric:

  • Treat based on the cause, 6 to 8 mEq/L over 24 hours
  • Primary management
  • Hyponatremic sodium deficit = Current total body water (TBW) x (desired plasma sodium - actual sodium)

( TBW= 0.6 x weight)

Management of overcorrection Baseline Serum Na ≥ 120 mmol/L: probably unnecessary, start once limit is exceeded

Baseline Serum Na < 120 mmol/L: start relowering with electrolyte-free water or desmopressin after correction exceeds 6–8 mmol/L per d


‡ 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)


Medications Clinical use
Salt tablets
  • Dose: 5-15 gr daily
  • Side effects: Hypernatremia, fluid overload
  • Indications: SIAD combined with furosemide
Furosemide
Urea
  • Dose: 15–30 g daily
  • Side effects: Too rapid an increase in serum sodium, azotemia
  • Indications: SIAD, hyponatremia of heart failure
Demeclocycline



Practical approach to treatment of hyponatremia [9]

 
 
 
 
 
 
 
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 Na < 120 mEq/L
 
Symptomatic patients must be admitted
 
 
 
 
 
 
 
 
 
 
No symptoms
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Are the symptoms severe?
 
 
 
 
 
 
 
 
 
 
 
Recheck serum Na if the patient is hyponatremic ( 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
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Therapy
• 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, space occupying lesions
 
 
 
 
 
 
 
 
 
 
Treatment
• 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
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Therapy
• Primary management
• Monitor serum Na every 6-12 hours
 
 
Is the patient hypervolemic/edematous (CHF,RF,cirrhosis)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
 
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment
• 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 SIAD
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Evaluate the risk for osmotic demyelination syndrome
• Serum Na ≤ 105 mEq/L
• Associated hypokalemia
• Alcoholic patient
Malnourished patient
• Advanced liver disease
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment
• 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 at least 125 mEq/L
 
Treatment
• 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)


Vaptan Drugs

The “vaptan” class of drugs contains a number of compounds with varying selectivity for ADH receptors, several of which are either already in clinical use or in clinical trials. Tolvaptan improves short term survival in most decompensated cirrhotic hyponatremia patients with resolved serum sodium. [10]

Unselective (mixed V1A, V2):



V1A selective:

  • Relcovaptan



V1B selective:

  • Nelivaptan



V2 selective:

  • Mozavaptan
  • Satavaptan

Name Characteristics
Receptors Route of administration Urine volume Urine osmolality Sodium excretion in 24 hours Dosage
Conivaptan V1a/V2 IV 20 mg loading dose followed by a continuous infusion of either 40 or 80 mg/day for four days
Lixivaptan V2 Oral ↔ at low dose ↑ at

high dose

Tial
Satavaptan V2 Oral Trial
Tolvaptan V2 Oral 15 mg once daily then after at least 24 hours, may increase to 30 mg once daily to a maximum of 60 mg once daily titrating at 24-hour intervals to desired serum sodium concentration. Avoid fluid restriction during the first 24 hours of therapy. Do not use for more than 30 days due to the risk of hepatotoxicity

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.[11]

Cautions for use Vaptans in hyponatremia:

  • Vaptans should not be used in hypovolemic hyponatremia.
  • Vaptans should not be used in conjunction with other treatments for hyponatremia.
  • Do not start vaptans immediately after cessation of other treatments for hyponatremia, particularly 3% NaCl.
  • Monitor serum sodium closely (every 6-8 hours) for the first 24-48 hours after initiating treatment.
  • Adequate fluid intake should be maintained during the first 24-48 hours of treatment; hyponatremia may be corrected too quickly with coincidental fluid restriction; in patients with an impaired or inadequate thirst mechanism ( intubated or unconscious patients), sufficient fluid should be provided to prevent overly rapid correction due to overly rapid aquaresis.
  • Serum sodium should be monitored frequently to consider stopping the vaptans if there is a deterioration or change in the patient’s condition (NPO status, intubation) that restrict the ability to ingest fluid, request, access.
  • Severe, symptomatic hyponatremia should be managed with 3% NaCl, for quicker and more certain correction of serum sodium than vaptans.
  • Currently, there are no sufficient data for use of vaptans in severe asymptomatic hyponatremia (serum sodium <120 mmol/L)—caution and more frequent monitoring is necessary for these patients.
  • Overcorrection should be treated with re-lowering the serum sodium to safe limits (see Managing Excessive Correction of Chronic Hyponatremia).

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:

Disease Name

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. Richard H. Sterns, Sagar U. Nigwekar & John Kevin Hix (2009). "The treatment of hyponatremia". Seminars in nephrology. 29 (3): 282–299. doi:10.1016/j.semnephrol.2009.03.002. PMID 19523575. Unknown parameter |month= ignored (help)
  7. Verbalis, Joseph G.; Goldsmith, Steven R.; Greenberg, Arthur; Korzelius, Cynthia; Schrier, Robert W.; Sterns, Richard H.; Thompson, Christopher J. (2013). "Diagnosis, Evaluation, and Treatment of Hyponatremia: Expert Panel Recommendations". The American Journal of Medicine. 126 (10): S1–S42. doi:10.1016/j.amjmed.2013.07.006. ISSN 0002-9343.
  8. Richard H. Sterns, John Kevin Hix & Stephen Silver (2010). "Treatment of hyponatremia". Current opinion in nephrology and hypertension. 19 (5): 493–498. doi:10.1097/MNH.0b013e32833bfa64. PMID 20539224. Unknown parameter |month= ignored (help)
  9. Hoorn, Ewout J.; Zietse, Robert (2017). "Diagnosis and Treatment of Hyponatremia: Compilation of the Guidelines". Journal of the American Society of Nephrology. 28 (5): 1340–1349. doi:10.1681/ASN.2016101139. ISSN 1046-6673.
  10. Wang, Shuzhen; Zhang, Xin; Han, Tao; Xie, Wen; Li, Yonggang; Ma, Hong; Liebe, Roman; Weng, Honglei; Ding, Hui-Guo (2018). "Tolvaptan treatment improves survival of cirrhotic patients with ascites and hyponatremia". BMC Gastroenterology. 18 (1). doi:10.1186/s12876-018-0857-0. ISSN 1471-230X.
  11. 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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