hyponatremia management

HyponatremiaManagement

Ganesh Shidham, MDDivision of Nephrology

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

Sodium Water

Hyponatremia

“Hyper-acquemia”

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

AVP = Vasopressin = ADH

Neurohypophysis

Consists of:

• Supraoptic Nucleus• Para ventricular nucleus• Axons of Pituitary stalk• Neuron terminals in posterior pituitary

ADH stimuli:

1-3% ↑ osmolality10-15% ↓ vol /BP

Other stimuli:

PainNauseaStressMedications

Changes in urinary volume and Osmolality along the Nephron

Maximal ADH

No ADH

ADH action on distal nephron

V2 receptor

AQP 2 – Aquaporins

Lumen

Hyponatremia

IncidenceAnd

Mortality

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

Hyponatremia and Mortality

HyponatremiaMortality (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 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

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

Hypertonic HyponatremiaEffect 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 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%

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

Euvolemic Hypotonic Hyponatremia SIADH : Treatment

1. Discontinue offending agent2. Treatment of etiology (infection, pain) 3. Fluid restriction (for Chronic

asymptomatic Hyponatremia)

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

• 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

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

Euvolemic Hypotonic hyponatremiaPoor 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

surgeryArieff 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 1997Moritz ML et al, J Am Soc Nephrol 2005

Clinical featuresAnd

Brain Adaption

HyponatremiaSymptoms

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 status2. Daily weight3. Frequent Serum Na, K4. Plasma Osmolality5. Urine Na, K, osmolality6. Strict Input and Output

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

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

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. 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

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

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

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 • 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

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/dayIdentify patients at risk