Hyponatremia: Difference between revisions

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==Background==
==Background==
[[File:Hyponatremia.png|thumb|Algorithm for Hyponatremia]]
*Defined as sodium concentration <135meq/L<ref>Upadhyay A, Jaber BL, Madias NE. Epidemiology of hyponatremia. Seminars in Nephrology 2009 29 227–238</ref>
*Defined as sodium concentration <135meq/L<ref>Upadhyay A, Jaber BL, Madias NE. Epidemiology of hyponatremia. Seminars in Nephrology 2009 29 227–238</ref>
*Patients often not symptomatic until <120meq/L although this level varies by patients and may be higher if the change occurred abruptly<ref>Spasovski G. et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Nephrol Dial Transplant. 2014</ref>
*Patients often not symptomatic until <120meq/L, although this level varies by patients and may be higher if the change occurred abruptly<ref name="Spasovski">Spasovski et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Nephrol Dial Transplant (2014) 0: 1–39. [http://ndt.oxfordjournals.org/content/early/2014/02/21/ndt.gfu040.full.pdf fulltext]</ref>
*Generally accepted recommendations are to avoid correction of more than 12 mmol/L/day (0.5mmol/L/hr) to avoid central pontine myelinolysis.  Faster correction (1-2mmol/L/hr) is acceptable with 3% hypertonic saline if the patient is seizing.<ref name="NEJM">Adrogué HJ, Madias NE. Hyponatremia. N Engl J Med. 2000 May 25;342(21):1581-9.</ref>
*Too fast of sodium correction (>10 mmol/L/day), especially if chronic, can cause [[osmotic demyelination syndrome]] (central pontine myelinolysis)<ref name="NEJM">Adrogué HJ, Madias NE. Hyponatremia. N Engl J Med. 2000 May 25;342(21):1581-9.</ref>
*Often described in terms of tonicity and volume status of the patient with the main types by tonicity being: <ref>Understanding Lab Testing for Hyponatremia. Clin J Am Soc Nephrol 2008;3:1175</ref>
**Hypertonic Hyponatremia
**Isotonic (pseudo) hyponatremia
**Hypotonic Hyponatremia


==Clinical Features==
==Clinical Features==
*[[Nausea and Vomiting]]
===Hyponatremia Symptoms by Severity<ref name="Spasovski" />===
*Anorexia
{| {{table}}
*Muscle cramps
| align="center" style="background:#f0f0f0;"|'''Severity'''
*[[AMS]]
| align="center" style="background:#f0f0f0;"|'''NOT severe'''
*[[Seizure]] (esp if Na < 113)
| align="center" style="background:#f0f0f0;"|'''Moderately severe'''
*Coma
| align="center" style="background:#f0f0f0;"|'''Severe'''
*Rapid correction can cause [[CHF]] & CPM ([[AMS]], dysphagia, dysarthria, paresis)
|-
| '''Symptoms'''
||
*Gait disturbances
*Falls
*Concentration
*Cognitive deficits
||
*[[Nausea]] without vomiting
*[[Confusion]]
*[[Headache]]
||
*[[Vomiting]]  
*Cardiorespiratory distress
*Abnormal and deep somnolence
*[[Seizures]]
*[[Coma]] (GCS <8)
|}


==Differential Diagnosis==
===Symptoms from Rapid Correction of Sodium===
===Types by Tonicity===
*[[CHF]]
====Hypertonic Hyponatremia ====
*[[Osmotic demyelination syndrome]] (central pontine myelinolysis)
*Defined as osmolarity > 295mmol/L with the following causes:
**[[Altered mental status]]
#[[Hyperglycemia]]
**[[Dysphagia]]
#*Traditional teaching: [Na+] decreases by 1.6-1.8mEq/L for each 100mg/dL increase in glucose over 100mg/dL
**[[Dysarthria]]
#*2.4mEq/L may be a more accurate correction factor (Hillier 1999)
**[[Weakness|Paresis]]
#[[Mannitol]] excess


====Isotonic (pseudo) hyponatremia====
==Differential Diagnosis of '''Hypotonic''' Hyponatremia (by Volume Status)==
*Defined as osmolarity > 275-295mmol/L.  Often referred to as pseudo hyponatremia because the elevated lipids or proteins interfere with the laboratory sodium reading.  The following are common causes:
===Hypovolemic===
#Hyperlipidemia
====Renal Causes====
#Hyperproteinemia
*Thiazide [[diuretic]] use
*Na-wasting nephropathy ([[renal tubular acidosis|RTA]], CKD)
*Osmotic diuresis ([[hyperglycemia|glucose]], urea)
*Aldosterone deficiency


====Hypotonic Hyponatremia====
====Extra-renal Causes====
*Defined as an osmolarity < 275 mmol/L and categorized as [[Hyponatremia#Hypovolemic|hypovolemic]], [[Hyponatremia#Hypervolemic|hypervolemic]] or [[Hyponatremia#Euvolemic|euvolemic]]
 
===Hypotonic Types by Volume===
====Hypovolemic====
=====Renal Causes=====
*Thiazide diuretic use
*Na-wasting nephroathy (RTA, CRF)
*Osmotic diuresis (glucose, urea)
*Aldosterone deficiency
=====Extra-renal Causes=====
*GI loss
*GI loss
*3rd space loss
*3rd space loss
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*[[Peritonitis]]
*[[Peritonitis]]


====Hypervolemic====
===Hypervolemic===
*Urinary Na >20
*Urinary Na >20
**[[Renal failure]]
**[[Renal failure]]
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**[[CHF]]
**[[CHF]]


====Euvolemic====
===Euvolemic===
*[[SIADH]]
*[[SIADH]]
**urine sodium is greater than 20-40 mEq/L
**urine sodium is greater than 20-40 mEq/L
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*Psychogenic polydipsia
*Psychogenic polydipsia
*[[Hypothyroidism]]
*[[Hypothyroidism]]
*Drugs<ref>Review of Drug-Induced Hyponatremia. Am J Kidney Dis 2008;52:144</ref>
*Drugs<ref>Review of Drug-Induced Hyponatremia. Am J Kidney Dis 2008;52:144</ref><ref>Kate M, Grover S.  Bupropion-Induced Hyponatremia.  General Hospital Psychiatry Volume 35, Issue 6, November–December 2013, 681-683.</ref>
**[[NSAIDs]], [[sulfonylureas]]
**[[NSAIDs]], [[sulfonylurea]], [[bupropion]]
*H<sub>2</sub>0 intoxication
*H<sub>2</sub>0 intoxication
*Glucocorticoid deficiency
*[[Adrenal insufficiency|Glucocorticoid deficiency]]


====Pseudohyponatremia====
===Pseudohyponatremia===
*Hyperglycemia
*[[Hyperglycemia]]
**Na+ drops 1.6 mEq/L for every 100 mg/dL increase in glucose over 100
**Na+ decreases by 2.4mEq/L for each 100mg/dL increase in glucose over 100mg/dL<ref name="Hillier">Hillier TA, Abbott RD & Barrett EJ. Hyponatremia: evaluating the correction factor for hyperglycemia. American Journal of Medicine 1999 106 399–403</ref>
*Displaced sodium in lab specimen
*Displaced sodium in lab specimen
**Hyperlipidemia
**[[Hypertriglyceridemia|Hyperlipidemia]]
**Hyperproteinemia
**Hyperproteinemia


==Diagnosis==
==Evaluation==
*Must determine volume status and calculated osm
**In true hyponatremia the osm is reduced
 
===Work-Up===
===Work-Up===
Prior to giving treatment
''Prior to giving treatment''
 
*Urine
*Urine
**UA
**[[Urinalysis]]
**Urine electrolytes
**Urine electrolytes (Urine sodium)
**Urine urea
**Urine urea
**urine uric acid
**urine uric acid
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**urine creatinine
**urine creatinine
*Serum
*Serum
**Chemistry
**Chemistry including Ca/Mg/Phos
**Serum osmolality
**Serum osmolality
**Uric acid
**Uric acid
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**Cortisol
**Cortisol


==Treatment by Patient Status==
===Diagnosis===
===Symptomatic===
[[File:Hyponatremia correction.png|thumb|True serum sodium (corrected) based on serum glucose<ref name="Spasovski" />]]
{{Symptomatic Hyponatremia Treatment}}
[[File:Hyponatremia.png|thumb|Algorithm for hyponatremia diagnosis]]
*Fluid restrict
#Correct for glucose (see table)
#Determine volume status
#Calculated osm (in true hyponatremia the osm is reduced)
 
====Hypertonic Hyponatremia====
''Defined as osmolarity > 295mmol/L with the following causes:''
#[[Hyperglycemia]]
#*Sodium decreases by 2.4mEq/L for each 100mg/dL increase in glucose over 100mg/dL<ref name="Hillier" />
#[[Mannitol]] excess
 
====Isotonic (pseudo) hyponatremia====
''Defined as osmolarity > 275-295mmol/L.  Often referred to as pseudo hyponatremia because the elevated lipids or proteins interfere with the laboratory sodium reading.  The following are common causes:''
#Hyperlipidemia
#Hyperproteinemia
 
====Hypotonic Hyponatremia====
''Defined as an osmolarity < 275 mmol/L and categorized as [[Hyponatremia#Hypovolemic|hypovolemic]], [[Hyponatremia#Hypervolemic|hypervolemic]] or [[Hyponatremia#Euvolemic|euvolemic]]''
 
==General Management==
''Must have sufficient confidence that the symptoms are '''caused''' by hyponatraemia; see Clinical Features for definition of categories.''
 
===NOT Severe/Moderately-Severe (Including Asymptomatic)===
'''Adults:<ref name="Spasovski" />'''
#Start prompt diagnostic assessment and provide cause-specific treatment
#Check serum sodium concentration after 4 hours
#*Aim for a 5 mmol/l per 24-h increase in serum sodium concentration
#*Limit increase to 10 mmol/l in the first 24 h (8 mmol/l during every 24 h thereafter), until a serum sodium concentration of 130 mmol/l is reached
#Manage the patient as in moderately-severe symptomatic hyponatraemia if the serum sodium concentration decreases 10 mmol/l
 
===Moderately Severe Symptoms===
'''Adults:<ref name="Spasovski" />'''
#3% hypertonic saline 150 mL bolus over 20 min
#Start prompt diagnostic assessment and provide cause-specific treatment
#Check serum sodium concentration after 1, 6 and 12 hours
#*Aim for a 5 mmol/l per 24-h increase in serum sodium concentration
#*Limit increase to 10 mmol/l in the first 24 h (8 mmol/l during every 24 h thereafter), until a serum sodium concentration of 130 mmol/l is reached
#Consider DDAVP (2mcgs IV q8h) to prevent overcorrection
#Manage the patient as in severely symptomatic hyponatraemia if the serum sodium concentration further decreases despite treating the underlying diagnosis (2D).


===Asymptomatic===
===Severe Symptoms===
====Step 1====
'''Adults:<ref name="Spasovski" />'''
Calculate total body water<ref>The hyponatremia formulas do not work so well (Clin J Am Soc Nephrol 2007;2:1110 and Nephrol Dial Transplant 2006;21:1564)</ref>
#3% hypertonic saline 150 mL bolus over 20 min
*TBW(kg) = Wt(kg) x 0.6 = [Wt(lb) x 0.45] x 0.6 = Wt(lb) x 0.27
#Check serum sodium concentration after 20 min
====Step 2====
#Repeat infusion of 150 ml 3% hypertonic saline for the next 20 min
Calculate mEq deficit
#Repeat twice or until a target of 5 mmol/l increase in serum sodium concentration is achieved
*(Desired Na - Measured Na) ~ must be ≤ 10
#*Each 100 mL will raise sodium by ~2 mmol/l
====Step 3====
#*In general, 200-400 mL of 3% hypertonic saline is reasonable dose in most adult patients with severe symptomatic hyponatremia, which may be given IV over 1-2 hr until resolution of seizures. 
Calculate NS rate to be given over 24hr
#If you do not have 3% hypertonic saline you can give two ampules (100ml) of crash cart hypertonic bicarbonate (1 mEq/ml sodium bicarbonate equivalent to giving ~200 ml of 3% saline, which will raise the serum sodium by ~3 mM)<ref>[https://emcrit.org/ibcc/hyponatremia/ Josh Farkas IBCC Hyponatremia]</ref>.  
*NS rate (cc/hr) = TBW x mEq deficit x 0.27
#*Sodium bicarbonate should be given slowly (each ampule over 5-10 minutes).  Bicarbonate is contraindicated in patients with metabolic alkalosis.
*If using 3% sodium chloride (to avoid volume overload) divide above rate by 3.33
'''Pediatrics:<ref>Moritz ML, Ayus JC. 100cc 3% sodium chloride bolus: a novel treatment for hyponatremic encephalopathy. Metab Brain Dis. 2010 Mar; 25(1): 91-6.</ref>'''
*2 mL/kg  of 3% over 10-60 minutes can be infused with a repeat of up to 3 times.


==Treatment by Type of Hyponatremia==
==Cause-Specific Treatment==
===Hypertonic hyponatremia===
===Hypertonic hyponatremia===
*Correct underlying disorder which is often hyperglycemia<ref name="treatment">Schrier RW, Bansal S. Diagnosis and management of hyponatremia in acute illness. Curr Opin Crit Care 2008;14:627-34</ref>
*Correct underlying disorder which is often hyperglycemia<ref name="treatment">Schrier RW, Bansal S. Diagnosis and management of hyponatremia in acute illness. Curr Opin Crit Care 2008;14:627-34</ref>
*Often volume depleted due to osmotic diuresis and normal saline provides adequate volume repletion
*Often volume depleted due to osmotic diuresis and normal saline provides adequate volume repletion
===Isotonic (pseudo) hyponatremia===
===Isotonic (pseudo) hyponatremia===
*No treatment needed <ref name="treatment"></ref>
*No treatment needed <ref name="treatment"></ref>
===Hypotonic hyponatremia===
===Hypotonic hyponatremia===
#Hypovolemic
#Hypovolemic
#*Give NS but be cautious of raising the serum sodium more than 12 mmol/L/day (0.5mmol/L/hr) and causing central pontine demylinosis<ref name="NEJM"></ref>
#*Give normal saline, but be cautious of raising the serum sodium more than 10 mmol/L/day and causing [[osmotic demyelination syndrome]] (central pontine myelinolysis)''<ref name="Nagler">Nagler EV1, Vanmassenhove J, van der Veer SN et al. Diagnosis and treatment of hyponatremia: a systematic review of clinical practice guidelines and consensus statements.  [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276109/ BMC Med. 2014 Dec 11;12:1]</ref>''
#Euvolemic<ref name="treatment"></ref>
#Euvolemic<ref name="treatment"></ref>
#*Water restrict
#*Water restrict
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#*Treat underlying cause
#*Treat underlying cause


===Na Therapy===
==Calculating Sodium Replacement Therapy==
Max correction 10mEq/L in 24hr (avoids central pontine demylinosis)
''Max correction 10mEq/L in first 24hr (8 mmol/l during every 24 h thereafter), until a serum sodium concentration of 130 mmol/l is reached (lowers risk of [[osmotic demyelination syndrome]]) <ref name="Nagler" />''
===Step 1===
Calculate total body water<ref>The hyponatremia formulas do not work so well (Clin J Am Soc Nephrol 2007;2:1110 and Nephrol Dial Transplant 2006;21:1564)</ref>
*TBW(kg) = Wt(kg) x 0.6 = [Wt(lb) x 0.45] x 0.6 = Wt(lb) x 0.27
 
===Step 2===
Calculate mEq deficit
*(Desired Na - Measured Na) ~ must be ≤ 10
 
===Step 3===
Calculate NS rate to be given over 24hr
*NS rate (cc/hr) = TBW x mEq deficit x 0.27
*If using 3% sodium chloride (to avoid volume overload) divide above rate by 3.33


{|class="wikitable"
{|class="wikitable"
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| 3% Saline||513 mEq/L
| 3% Saline||513 mEq/L
|}
|}
==[[DDAVP]] Combined with Hypertonic Saline==
*Limited evidence suggests usage of [[DDAVP]] in combination with HTS can safely increase sodium, while lowering risk for over-correction<ref>Sood L et al. Hypertonic saline and desmopressin: a simple strategy for safe correction of severe hyponatremia. Am J Kidney Dis. 2013 Apr;61(4):571-8.</ref>
**DDAVP prevents free water excretion renally
**Give 3% hypertonic saline based on calculations above
**Give [[desmopressin]] 1-2 µg IV q6 hours
**Patients must be PO water restricted
*Goal sodium is 6 mEq/L over first 24 hours


==Disposition==
==Disposition==
*Admit if symptomatic or if Na <125mEq/L
*Admit if symptomatic or if Na <125mEq/L
*Manage severely symptomatic patients in "an environment where close biochemical and clinical monitoring can be provided" (e.g. ICU)


==See Also==
==See Also==
*[[Electrolyte Abnormalities (Main)]]
*[[Electrolyte abnormalities]]
*[[Osmotic demyelination syndrome]]


==External Links==
==External Links==
* [http://ddxof.com/electrolyte-abnormalities/ DDxOf: Differential Diagnosis of Electrolyte Abnormalities]
*[https://emcrit.org/ibcc/hyponatremia/ IBCC Hyponatremia Josh Farkas]
*[http://emcrit.org/podcasts/hyponatremia/ EMCrit Hyponatremia Management]
*[http://ddxof.com/electrolyte-abnormalities/ DDxOf: Differential Diagnosis of Electrolyte Abnormalities]
*[https://emcrit.org/pulmcrit/taking-control-of-severe-hyponatremia-with-ddavp/ PulmCrit DDAVP Clamp]


==References==
==References==

Latest revision as of 07:06, 15 February 2020

Background

  • Defined as sodium concentration <135meq/L[1]
  • Patients often not symptomatic until <120meq/L, although this level varies by patients and may be higher if the change occurred abruptly[2]
  • Too fast of sodium correction (>10 mmol/L/day), especially if chronic, can cause osmotic demyelination syndrome (central pontine myelinolysis)[3]

Clinical Features

Hyponatremia Symptoms by Severity[2]

Severity NOT severe Moderately severe Severe
Symptoms
  • Gait disturbances
  • Falls
  • Concentration
  • Cognitive deficits

Symptoms from Rapid Correction of Sodium

Differential Diagnosis of Hypotonic Hyponatremia (by Volume Status)

Hypovolemic

Renal Causes

  • Thiazide diuretic use
  • Na-wasting nephropathy (RTA, CKD)
  • Osmotic diuresis (glucose, urea)
  • Aldosterone deficiency

Extra-renal Causes

Hypervolemic

Euvolemic

Pseudohyponatremia

  • Hyperglycemia
    • Na+ decreases by 2.4mEq/L for each 100mg/dL increase in glucose over 100mg/dL[6]
  • Displaced sodium in lab specimen

Evaluation

Work-Up

Prior to giving treatment

  • Urine
    • Urinalysis
    • Urine electrolytes (Urine sodium)
    • Urine urea
    • urine uric acid
    • urine osmolality
    • urine creatinine
  • Serum
    • Chemistry including Ca/Mg/Phos
    • Serum osmolality
    • Uric acid
    • TSH
    • Cortisol

Diagnosis

True serum sodium (corrected) based on serum glucose[2]
Algorithm for hyponatremia diagnosis
  1. Correct for glucose (see table)
  2. Determine volume status
  3. Calculated osm (in true hyponatremia the osm is reduced)

Hypertonic Hyponatremia

Defined as osmolarity > 295mmol/L with the following causes:

  1. Hyperglycemia
    • Sodium decreases by 2.4mEq/L for each 100mg/dL increase in glucose over 100mg/dL[6]
  2. Mannitol excess

Isotonic (pseudo) hyponatremia

Defined as osmolarity > 275-295mmol/L. Often referred to as pseudo hyponatremia because the elevated lipids or proteins interfere with the laboratory sodium reading. The following are common causes:

  1. Hyperlipidemia
  2. Hyperproteinemia

Hypotonic Hyponatremia

Defined as an osmolarity < 275 mmol/L and categorized as hypovolemic, hypervolemic or euvolemic

General Management

Must have sufficient confidence that the symptoms are caused by hyponatraemia; see Clinical Features for definition of categories.

NOT Severe/Moderately-Severe (Including Asymptomatic)

Adults:[2]

  1. Start prompt diagnostic assessment and provide cause-specific treatment
  2. Check serum sodium concentration after 4 hours
    • Aim for a 5 mmol/l per 24-h increase in serum sodium concentration
    • Limit increase to 10 mmol/l in the first 24 h (8 mmol/l during every 24 h thereafter), until a serum sodium concentration of 130 mmol/l is reached
  3. Manage the patient as in moderately-severe symptomatic hyponatraemia if the serum sodium concentration decreases 10 mmol/l

Moderately Severe Symptoms

Adults:[2]

  1. 3% hypertonic saline 150 mL bolus over 20 min
  2. Start prompt diagnostic assessment and provide cause-specific treatment
  3. Check serum sodium concentration after 1, 6 and 12 hours
    • Aim for a 5 mmol/l per 24-h increase in serum sodium concentration
    • Limit increase to 10 mmol/l in the first 24 h (8 mmol/l during every 24 h thereafter), until a serum sodium concentration of 130 mmol/l is reached
  4. Consider DDAVP (2mcgs IV q8h) to prevent overcorrection
  5. Manage the patient as in severely symptomatic hyponatraemia if the serum sodium concentration further decreases despite treating the underlying diagnosis (2D).

Severe Symptoms

Adults:[2]

  1. 3% hypertonic saline 150 mL bolus over 20 min
  2. Check serum sodium concentration after 20 min
  3. Repeat infusion of 150 ml 3% hypertonic saline for the next 20 min
  4. Repeat twice or until a target of 5 mmol/l increase in serum sodium concentration is achieved
    • Each 100 mL will raise sodium by ~2 mmol/l
    • In general, 200-400 mL of 3% hypertonic saline is reasonable dose in most adult patients with severe symptomatic hyponatremia, which may be given IV over 1-2 hr until resolution of seizures.
  5. If you do not have 3% hypertonic saline you can give two ampules (100ml) of crash cart hypertonic bicarbonate (1 mEq/ml sodium bicarbonate equivalent to giving ~200 ml of 3% saline, which will raise the serum sodium by ~3 mM)[7].
    • Sodium bicarbonate should be given slowly (each ampule over 5-10 minutes). Bicarbonate is contraindicated in patients with metabolic alkalosis.

Pediatrics:[8]

  • 2 mL/kg of 3% over 10-60 minutes can be infused with a repeat of up to 3 times.

Cause-Specific Treatment

Hypertonic hyponatremia

  • Correct underlying disorder which is often hyperglycemia[9]
  • Often volume depleted due to osmotic diuresis and normal saline provides adequate volume repletion

Isotonic (pseudo) hyponatremia

  • No treatment needed [9]

Hypotonic hyponatremia

  1. Hypovolemic
  2. Euvolemic[9]
    • Water restrict
    • Treat underlying cause
  3. Hypervolemic
    • Water restriction
    • Diuresis
    • Treat underlying cause

Calculating Sodium Replacement Therapy

Max correction 10mEq/L in first 24hr (8 mmol/l during every 24 h thereafter), until a serum sodium concentration of 130 mmol/l is reached (lowers risk of osmotic demyelination syndrome) [10]

Step 1

Calculate total body water[11]

  • TBW(kg) = Wt(kg) x 0.6 = [Wt(lb) x 0.45] x 0.6 = Wt(lb) x 0.27

Step 2

Calculate mEq deficit

  • (Desired Na - Measured Na) ~ must be ≤ 10

Step 3

Calculate NS rate to be given over 24hr

  • NS rate (cc/hr) = TBW x mEq deficit x 0.27
  • If using 3% sodium chloride (to avoid volume overload) divide above rate by 3.33
Sodium Containing fluid Concentrations
Fluid type Sodium Concentration
1/2 Normal Saline 77 mEq/L
Normal Saline 154 mEq/L
Lactated Ringers 130 mEq/L
3% Saline 513 mEq/L

DDAVP Combined with Hypertonic Saline

  • Limited evidence suggests usage of DDAVP in combination with HTS can safely increase sodium, while lowering risk for over-correction[12]
    • DDAVP prevents free water excretion renally
    • Give 3% hypertonic saline based on calculations above
    • Give desmopressin 1-2 µg IV q6 hours
    • Patients must be PO water restricted
  • Goal sodium is 6 mEq/L over first 24 hours

Disposition

  • Admit if symptomatic or if Na <125mEq/L
  • Manage severely symptomatic patients in "an environment where close biochemical and clinical monitoring can be provided" (e.g. ICU)

See Also

External Links

References

  1. ↑ Upadhyay A, Jaber BL, Madias NE. Epidemiology of hyponatremia. Seminars in Nephrology 2009 29 227–238
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 Spasovski et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Nephrol Dial Transplant (2014) 0: 1–39. fulltext
  3. ↑ Adrogué HJ, Madias NE. Hyponatremia. N Engl J Med. 2000 May 25;342(21):1581-9.
  4. ↑ Review of Drug-Induced Hyponatremia. Am J Kidney Dis 2008;52:144
  5. ↑ Kate M, Grover S. Bupropion-Induced Hyponatremia. General Hospital Psychiatry Volume 35, Issue 6, November–December 2013, 681-683.
  6. ↑ 6.0 6.1 Hillier TA, Abbott RD & Barrett EJ. Hyponatremia: evaluating the correction factor for hyperglycemia. American Journal of Medicine 1999 106 399–403
  7. ↑ Josh Farkas IBCC Hyponatremia
  8. ↑ Moritz ML, Ayus JC. 100cc 3% sodium chloride bolus: a novel treatment for hyponatremic encephalopathy. Metab Brain Dis. 2010 Mar; 25(1): 91-6.
  9. ↑ 9.0 9.1 9.2 Schrier RW, Bansal S. Diagnosis and management of hyponatremia in acute illness. Curr Opin Crit Care 2008;14:627-34
  10. ↑ 10.0 10.1 Nagler EV1, Vanmassenhove J, van der Veer SN et al. Diagnosis and treatment of hyponatremia: a systematic review of clinical practice guidelines and consensus statements. BMC Med. 2014 Dec 11;12:1
  11. ↑ The hyponatremia formulas do not work so well (Clin J Am Soc Nephrol 2007;2:1110 and Nephrol Dial Transplant 2006;21:1564)
  12. ↑ Sood L et al. Hypertonic saline and desmopressin: a simple strategy for safe correction of severe hyponatremia. Am J Kidney Dis. 2013 Apr;61(4):571-8.
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