hyponatremia management
DESCRIPTION
Hyponatremia Management. Ganesh Shidham, MD Division of Nephrology. Outline ……. 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. - PowerPoint PPT PresentationTRANSCRIPT
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HyponatremiaManagement
Ganesh Shidham, MDDivision of Nephrology
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Outline ……
1. Role of ADH in Hyponatremia2. Incidence and Mortality3. Mechanism of Hyponatremia4. Identifying types of Hyponatremia5. Clinical features and Brain Adaption6. Treatment7. Complications of treatment
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Sodium Water
Hyponatremia
“Hyper-acquemia”
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Normal water balance
Normal water intake1-1.5 L/d
Intracellular ExtracellularCompartment compartment28 L 14 L
42 L TBW60% of body weight
Fixed water excretion
Stool Sweat Lungs0.1 L/d 0.1 L/d 0.3 L/d
Total insensible losses0.5 L/d
WaterOfCellularMetabol0.3-0.5 L/d
Variable water excretion
Kidney
Total urine output1-1.5 L/d
Waterintake
WaterexcretionADH
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AVP = Vasopressin = ADH
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Neurohypophysis
Consists of:
• Supraoptic Nucleus• Para ventricular nucleus• Axons of Pituitary stalk• Neuron terminals in posterior pituitary
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ADH stimuli:
1-3% ↑ osmolality10-15% ↓ vol /BP
Other stimuli:
PainNauseaStressMedications
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Changes in urinary volume and Osmolality along the Nephron
Maximal ADH
No ADH
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ADH action on distal nephron
V2 receptor
AQP 2 – Aquaporins
Lumen
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Hyponatremia
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IncidenceAnd
Mortality
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0
5
10
15
20
25
30
Na <116
Na<135
Na>145
Na>165
Acute Hospital care
Ambulatory hospital care
Community care
Na < 116 Na < 135 Na > 145 Na > 165
0.49 0.17 0.03
28.2
21
7.2
Prevalence of Dysnatremia303,577 samples from 120,137 patients
Hawkins. Clin Chim Acta 337:169-172, 2003
Pre
vale
nce
%
1.43 0.53 0.72 0.06 0.01 0.01
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Hyponatremia and Mortality
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HyponatremiaMortality (due to change in Brain volume)
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Mechanism of
Hyponatremia
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Hyponatremia
Supervenes when free water intake >> free water
excretion
Main defense excretion of free water by kidneys
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Hypotonic Hyponatremia caused by:
Dilution from retained water
OR
Depletion of electrolytes in excess of water
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Identifying types of
Hyponatremia
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Hyponatremia
Serum Osmolality
Normal Low High(280-295 mOsm/kg) (<280 mOsm/kg) (>295 mOsm/kg)
Isotonic Hypotonic HypertonicHyponatremia
(Pseudohyponatremia)Hyponatremia Hyponatremia
(Translocational)
1.Hyperproteinemia
2.Hyperlipidemia
Volume status
1.Hyperglycemia 2.Mannitol, Sorbitol Glycine3.Radiocontrast agent
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Hypotonic Hyponatremia
Hypovolemic Euvolemic Hypervolemic
Urine Na
<30 >30
ExtraRenal Renal
1.Diarrhea2.Vomiting3.Hemorrhage4.Sweating
1.Diuretics2.Mineralocorticoid def3.Salt loosing Nephropathies4.Cerebral salt wasting
1.SIADH 2.Glucocorticoid def3.Hypothyroidism4.Poor solute intake -Tea Toast syndrome - Beer potomania5.Post op / Hospital acquired
1.CHF2.Cirrhosis3.Nephrotic synd4.Advanced CRF
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Hypertonic HyponatremiaEffect of Glucose on Serum Na
Correction factor: Increase Na by 1.6 to 2.4 per 100 glucose
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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
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Euvolemic Hypotonic HyponatremiaSIADH
Criteria for diagnosis:
1. P osm <275 mOsm/kg2. U osm >100 mOsm/kg3. Clinical euvolemia4. Urine Na > 30mmol/L while on normal salt intake5. Normal thyroid, adrenal and renal functions6. Inappropriately elevated AVP levels in 85-90%
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Tumors small cell CA, Head & Neck
CNS Trauma, tumors, meningitis, CVA
Pulmonary Pneumonia, PTB, resp failure, asthmaMechanical ventilation, COPD
Drugs DDAVP, Diabinese, NSAIDS, opiates, Carbamazepine, SSRI, Tricyclic,
ThiazidesEcstasy, ACE-I, Omeprazole
Miscellaneous
Pain, Nausea, surgery, stress, Alcohol withdrawal
Euvolemic Hypotonic Hyponatremia SIADH : Common Causes
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Euvolemic Hypotonic Hyponatremia SIADH : Treatment
1. Discontinue offending agent2. Treatment of etiology (infection, pain) 3. Fluid restriction (for Chronic
asymptomatic Hyponatremia)
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Euvolemic Hypotonic hyponatremiaPoor solute Intake
Beer Potomania, Tea Toast syndrome
Urine Volume =
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
Urinary solute excretion
Urinary Osmolality
Clinical setting of low solute intake: - Alcoholism (Beer Potomania) - Anorexia (Tea and Toast Diet)
Urinary solute excretion in person on normal diet-800-900 mM/day
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• 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 mOsmUrine 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 hyponatremiaPoor solute Intake
Beer Potomania, Tea Toast syndrome
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Euvolemic Hypotonic hyponatremiaPoor solute Intake
Beer Potomania
• Assume Beer consumption of 5 L:Na intake 10 mMK intake 50 mMObligatory urea excretion 90 mMTotal solutes 150 mOsm
• Assume urine dilution of 50 mOsm/kg
• Urine volume = 150/50 = 3 L
• 2 L of fluids (hypotonic) is retained to produce hyponatremia
Beer:Na 2 mM/LK 10 mM/L
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Euvolemic Hypotonic hyponatremiaPoor solute Intake
Treatment
1. Increase solute intake –• High protein diet• Salt tablets or high dietary
salt• Urea
2. Fluid restriction
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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
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Hospital acquired hyponatremia
• Series of 15 women with Hyponatremia and permanent neurological damage
• Following elective surgery• 11 had received 5% Dextrose post
surgeryArieff AI et al, NEJM 1986
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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
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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
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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 1997Moritz ML et al, J Am Soc Nephrol 2005
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Clinical featuresAnd
Brain Adaption
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HyponatremiaSymptoms
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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
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IDIOGENIC
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Treatment
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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)
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Treatment of Hyponatremia:
Balance – Risk of Hyponatremia
Vs
Risk of Correction
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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?
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Monitoring of patients:
1. Volume status2. Daily weight3. Frequent Serum Na, K4. Plasma Osmolality5. Urine Na, K, osmolality6. Strict Input and Output
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Treatment of HyponatremiaBasic concept
1. Free water intake << Free water output ANDNa, K intake >> Na, K output
2. Needed Info: • Serum Na , osmolality• Urine Na, K, Osmolality• Strict Input/ Output
3. Rate of correction
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TreatmentSymptomatic Hyponatremia
1. Treatment based on neurological symptoms and not on Sodium
2. Needs aggressive management with 3%NaCl
3. No role of fluid restriction alone4. Treatment should precede any
neuroimaging5. Treatment in monitored setting6. Sodium levels measured every 2 hours
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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
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Treatment Symptomatic Hyponatremia
4. Monitor [Na] every 2-4 hrs5. 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
6. Complete rest of correction with - fluid restriction
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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
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TreatmentAsymptomatic 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
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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
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Complications of treatment
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Risk of Neurological Complications
Acute Cerebral edema • Post-op: menstruating F (Risk 30 X men)* (Risk 25 X postmenopausal F)*• Children• Brain injury (No safe degree of ↓ Na)
• Hypoxemia• Elderly F on HCTZ• Psych Polydipsia
Osmotic Demyelination
• Alcoholics• Malnourished• Hypokalemia• Hypoxemia• Elderly F on HCTZ
* Ayus JC et al, Ann Intern Med 1992
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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)
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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/dayIdentify patients at risk