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Hyponatremia
Management
Ganesh Shidham, MD
Division of Nephrology
Outline ……
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Role of ADH in Hyponatremia
Incidence and Mortality
Mechanism of Hyponatremia
Identifying types of Hyponatremia
Clinical features and Brain Adaption
Treatment
Complications of treatment
Hyponatremia
Sodium
Water
“Hyper-acquemia”
Normal water balance
Normal water intake
1-1.5 L/d
Water
Of
Cellular
Metabol
0.3-0.5
L/d
Intracellular
Compartment
28 L
Extracellular
compartment
14 L
Fixed water excretion
Stool
0.1 L/d
Sweat
0.1 L/d
Lungs
0.3 L/d
Total insensible losses
0.5 L/d
Water
intake
42 L TBW
60% of body
weight
Variable water excretion
ADH
Kidney
Total urine output
1-1.5 L/d
Water
excretion
AVP = Vasopressin = ADH
Neurohypophysis
Consists of:
•
•
•
•
Supraoptic Nucleus
Para ventricular nucleus
Axons of Pituitary stalk
Neuron terminals in
posterior pituitary
ADH stimuli:
1-3% ↑ osmolality
10-15% ↓ vol /BP
Other stimuli:
Pain
Nausea
Stress
Medications
Changes in urinary volume and Osmolality
along the Nephron
Maximal ADH
No ADH
Lumen
V2
receptor
AQP 2 – Aquaporins
ADH action on distal nephron
Hyponatremia
Incidence
And
Mortality
Prevalence of Dysnatremia
303,577 samples from 120,137 patients
30
28.2
Prevalence %
25
Acute Hospital care
Ambulatory hospital care
21
20
Community care
15
7.2
10
5
1.43 0.53 0.72
0.49 0.17 0.03
0.06
0.01 0.01
0
Na <
Na
116
< 116
Na
Na
<135
< 135
Na
Na > 145
>145
Na>
Na165
> 165
Hawkins. Clin Chim Acta 337:169-172, 2003
Hyponatremia and Mortality
Hyponatremia
Mortality (due to change in Brain volume)
Mechanism
of
Hyponatremia
Hyponatremia
Supervenes when
free water intake >> free water excretion
Main defense
excretion of free water by kidneys
Hypotonic Hyponatremia
caused by:
Dilution from retained water
OR
Depletion of electrolytes in
excess of water
Identifying
types of
Hyponatremia
Hyponatremia
Serum Osmolality
Normal
(280-295 mOsm/kg)
Isotonic
Hyponatremia
(Pseudohyponatremia)
Low
(<280 mOsm/kg)
Hypotonic
Hyponatremia
High
(>295 mOsm/kg)
Hypertonic
Hyponatremia
(Translocational)
1.Hyperglycemia 
2.Mannitol, Sorbitol
Glycine
3.Radiocontrast agent
1.Hyperproteinemia
2.Hyperlipidemia
Volume status
Hypotonic Hyponatremia
Hypovolemic
Urine Na
<30
ExtraRenal
1.Diarrhea
2.Vomiting
3.Hemorrhage
4.Sweating
>30
Renal
Euvolemic
Hypervolemic
1.SIADH 
2.Glucocorticoid def
3.Hypothyroidism
4.Poor solute intake 
-Tea Toast syndrome
- Beer potomania
5.Post op / Hospital acquired
1.Diuretics
2.Mineralocorticoid def
3.Salt loosing Nephropathies
4.Cerebral salt wasting 
1.CHF
2.Cirrhosis
3.Nephrotic synd
4.Advanced CRF
Hypertonic Hyponatremia
Effect of Glucose on Serum Na
Correction factor: Increase Na by 1.6 to 2.4 per 100 glucose
Hypotonic hyponatremia
(Vol status indeterminate)
Urine Na <30 :
Respond to 0.9 NS
Volume depleted
Urine Na > 30 :
No response to 0.9 NS
Likely to have SIADH
Euvolemic Hypotonic Hyponatremia
SIADH
Criteria for diagnosis:
1. P osm <275 mOsm/kg
2. U osm >100 mOsm/kg
3. Clinical euvolemia
4. Urine Na > 30mmol/L while on normal salt intake
5. Normal thyroid, adrenal and renal functions
6. Inappropriately elevated AVP levels in 85-90%
Euvolemic Hypotonic Hyponatremia
SIADH : Common Causes
Tumors
small cell CA, Head & Neck
CNS
Trauma, tumors, meningitis, CVA
Pulmonary
Pneumonia, PTB, resp failure, asthma
Mechanical ventilation, COPD
Drugs
DDAVP, Diabinese, NSAIDS, opiates,
Carbamazepine, SSRI, Tricyclic, Thiazides
Ecstasy, ACE-I, Omeprazole
Miscellaneous Pain, Nausea, surgery, stress,
Alcohol withdrawal
Euvolemic Hypotonic Hyponatremia
SIADH : Treatment
1. Discontinue offending agent
2. Treatment of etiology (infection, pain)
3. Fluid restriction (for Chronic asymptomatic
Hyponatremia)
Euvolemic Hypotonic hyponatremia
Poor solute Intake
Beer Potomania, Tea Toast syndrome
Urinary solute excretion
Urine Volume =
Urinary Osmolality
Urinary solute excretion
in person on normal diet800-900 mM/day
Normal Urinary Electrolytes
Normal Urinary Urea
Na+ , K+ = 150 + 50 = 200
Catabolism= 75-100
Accompanying anions= 200
Diet ~50 mM/10 gm of dietary
protein
Total 400 mM/day
Total 400-500 mM/day
Clinical setting of low solute intake:
- Alcoholism (Beer Potomania)
- Anorexia (Tea and Toast Diet)
Euvolemic Hypotonic hyponatremia
Poor solute Intake
Beer Potomania, Tea Toast syndrome
• Normal Solute excretion = 900 mOsm/d
• Assume maximal urine dilution= 60 mOsm/kg
Urine Volume = 900/60 = 15 L/d
• With solute excretion of 300 mOsm
Urine Volume = 300/60 = 5 L/d
• With solute excretion of 300 mOsm and
maximal urine dilution of 150 mOsm/kg
Urine volume = 300/150 = 2 L/d
Euvolemic Hypotonic hyponatremia
Poor solute Intake
Beer Potomania
•
Assume Beer consumption of 5 L:
Na intake
10 mM
K intake
50 mM
Obligatory urea excretion
90 mM
Total solutes
150 mOsm
• Assume urine dilution of 50 mOsm/kg
Beer:
Na 2 mM/L
K 10 mM/L
• Urine volume = 150/50 = 3 L
• 2 L of fluids (hypotonic) is retained to produce
hyponatremia
Euvolemic Hypotonic hyponatremia
Poor solute Intake
Treatment
1. Increase solute intake –
• High protein diet
• Salt tablets or high dietary salt
• Urea
2. Fluid restriction
Hospital acquired Hyponatremia
• Virtually every hospitalized patient has
potential stimulus for AVP excess
• Administration of hypotonic fluid with
excess AVP are at risk for
Hyponatremia
Chung HM et al, Arch Inter Med 2002
Hospital acquired hyponatremia
• Series of 15 women with Hyponatremia
and permanent neurological damage
• Following elective surgery
• 11 had received 5% Dextrose post
surgery
Arieff AI et al, NEJM 1986
Hospital acquired hyponatremia
• Series of 65 patients with Hyponatremia
and encephalopathy
• Following elective surgery
• All had received hypotonic fluid
Ayus JC et al, Ann Intern Med, 1992
Hospital acquired hyponatremia
• Odds ratio for developing hyponatremia
was 3.7 for each liter of electrolyte-free
water given to 70 kg patient
Aronson D et al, Am J Kid Dis. 2002
Hospital acquired hyponatremia
• Ringer’s Lactate (Sodium 77) is hypotonic
and can produce hyponatremia
• No justification for Ringers lactate in post op
period
• Administration of 0.9 saline is safe
• No reports of 0.9 Saline causing neurological
complications of hyponatremia
Steele A et al, Ann Intern Med 1997
Moritz ML et al, J Am Soc Nephrol 2005
Clinical features
And
Brain Adaption
Hyponatremia
Symptoms
Cerebral adaption to decrease
cerebral edema
• Early 1-3 hrs
– CSF distribution
• Later (> 3 hrs)
– Loss of Osmolytes and electrolytes:
– Glutamate, Inositol, Taurine,
– Urea, K, Na, Creatinine
IDIOGENIC
Treatment
Acute Hyponatremia:
• Less than 48 hrs
• Neurologic symptoms due to brain edema
• Rapid correction well tolerated
Chronic Hyponatremia:
•
•
•
•
More than 48 hrs or unknown time
Mild brain edema (<10%)
Sensitive to Na correction rate
Aim to increase Na by 10% (not more than 12 in 24 hrs)
Treatment of
Hyponatremia:
Balance –
Risk of
Hyponatremia
Vs
Risk of
Correction
Treatment of Hyponatremia
• How long has hyponatremia been present?
• Does the patient have symptoms?
• Does the patient have risk factors for development of
neurologic complications?
Monitoring of patients:
1. Volume status
2. Daily weight
3. Frequent Serum Na, K
4. Plasma Osmolality
5. Urine Na, K, osmolality
6. Strict Input and Output
Treatment of Hyponatremia
Basic concept
1. Free water intake << Free water output
AND
Na, K intake >> Na, K output
2. Needed Info:
•
•
•
Serum Na , osmolality
Urine Na, K, Osmolality
Strict Input/ Output
3. Rate of correction
Treatment
Symptomatic Hyponatremia
1. Treatment based on neurological symptoms and
not on Sodium
2. Needs aggressive management with 3%NaCl
3. No role of fluid restriction alone
4. Treatment should precede any neuroimaging
5. Treatment in monitored setting
6. Sodium levels measured every 2 hours
Treatment
Symptomatic Hyponatremia
1.
Impending herniation: Sz, resp arrest,, obtundation,
Decorticate posturing, dilated pupils:
- 100 ml of 3% NaCl as a bolus over 10 min to rapidly
reverse brain edema.
- Repeat bolus as required till symptoms improve
2.
Encephalopathy: Headache, N/V, Altered mental status:
- 3% NaCl @ 50-100 ml/hr
3.
Calculating 3% saline rate:
Weight in kg x desired rate of increase in Serum Na
Treatment
Symptomatic Hyponatremia
4.
5.
6.
Monitor [Na] every 2-4 hrs
Stop active correction when appropriate end point is
reached:
- Patient becomes asymptomatic
- Safe Na levels reached (generally 120)
- Total correction 12 mmol in 24 hrs or
18-20 mmol in 48 hrs
Complete rest of correction with - fluid restriction
Treatment
Asymptomatic Hyponatremia
• Attend to underlying cause
• No immediate correction needed
• Fluid restriction
Urine Na + K
Plasma Na
Recommended water intake
>1
< 500 ml/day
-1
500 to 700 ml/day
<1
< 1000 ml/day
D Ellison, T Berl. NEJM 2007;356:2064-72
Treatment
Asymptomatic Hyponatremia
Treatment
Mechanism Dose
Advantage
Limitations
Fluid
restriction
Decreases
availability of
free water
Variable
Effective
Inexpensive
Non
compliance
Encourage
dietary salt and
protein
Solutes
required for
free water
excretion
Variable
Demeclocycline
↓ ADH
response
300-600 mg
BID
Effective
Unrestricted
water intake
Nephrotoxic,
Polyuria,
Photosensitive
V-2 Receptor
antagonist Conivaptan
Antagonize
ADH receptor
20-40 mg/day
IV (Vaprisol)
Effective
Available only
as IV
Conivaptan (Vaprisol)
• Only Vaptan, FDA approved for :
– Hospitalized patients with asymptomatic chronic
hyponatremia (Euvolemic or Hypervolemic)
• Available only in IV form
• Given as 20 mg bolus over 4 hrs followed by
continuous infusion of 20-40 mg/day for 4 days
• At end of 4 days, Serum Na ↑ by 6.1 mmol/L
• Time to ↑ Serum Na by 4 mmol/L was 23 hrs
• Should not be used as an alternate to 3% sodium
chloride in symptomatic Hyponatremia
• Commonest side effect was increased thirst
Complications of treatment
Risk of Neurological Complications
Acute Cerebral edema
Osmotic Demyelination
• Post-op: menstruating F
(Risk 30 X men)*
• Alcoholics
• Malnourished
(Risk 25 X postmenopausal F)*
• Hypokalemia
• Children
• Hypoxemia
• Brain injury
• Elderly F on HCTZ
(No safe degree of ↓ Na)
• Hypoxemia
• Elderly F on HCTZ
• Psych Polydipsia
* Ayus JC et al, Ann Intern Med 1992
Osmotic demyelination
• Iatrogenic brain damage when chronic hyponatremia
is treated rapidly
• Biphasic course
• Brain damage presents clinically in 1-7 days after treatment
• Shows pontine and extrapontine myelinolysis
• Clinically presents as pseudobulber palsy and quadriparesis,
behavioral changes, mutism, locked in syndrome, seizures
• Uremia protects against myelinolysis
• Reinduction of hyponatremia – aborts development of
subsequent myelinolysis (Oya, Neurology 2001)
(Brown WD, Curr Opin Neurol 2000; Lampl, Eur Neurol 2002)
Take home message
1. In presence of ADH concentrated urine is formed
2. Treatment – Basic concept:
Free water Input << Free water Output
Na+K Input >> Na+K Output
3. Symptomatic hyponatremia –
Symptoms due to brain swelling
Treat aggressively with hypertonic saline
4. Asymptomatic Hyponatremia – Identify why ADH is high
Osmotic demyelination - if correction is >12 mEq/day
Identify patients at risk