Hyponatremia – Fishing in troubled waters

K.SAMPATHKUMAR . MD, DNB, DM, FISN,FRCP ( Glasgow)

MEENAKSHI MISSION HOSPITAL MADURAI, INDIA

Homer Smith

Crucial role of Kidneys in evolution‘Mileu interior’

Danger of osmotic lysis

Kidneys provide “milieu interior”

Hyponatremia < 135 mEq/L

True = Hypo osmolar Plasma

Water excess state

Osmolality of various body fluid compartments govern the fluid and solute distribution

• Plasma Osmolality:Calculated

Posm = 2 (Na) + glucose + urea

Normal = 2 (140) + 5 + 5 = 290 (275-290 )• Effective Osm= Remove urea from eq.• Measured Osmolality- Osmometer- Freezing point

depression

• Osmolal gap= Mannitol,urea,glycine etc

S.Na ~ Na e + K e

TBW

K 140 Na – 140

280 mOsm

280 mOsm

25 L 17 L

H2O balance – ICF VolumeNa balance – ECF Volume

Na,KATPase

Kidney’s capacity to concentrate and dilute the urine

AVERAGE U Osm = 400. 1.5 L of Urine to excrete 600 mOsm

Hyponatremia – Basics

Na + K

Total Body Water

Loss of Na,K

Excess water IntakeRetention

Classic experiments of verney

V2R

5

0

1200

50

140

130

Osmoreg. Vs Vol.reg

• What is sensed?• Plasma OSMOLALITY• Sensor?• OsmoR • Effector?• ADH and thirst• Final say• Water excretion /

retention

• What is sensed?• Eff.Circ.BV • Sensor?• CAROTID BARO R,ATR.• Renal AA• Effector?• RAAS,ANP,SS• Final say• Urine Na

excretion/Retention

In volume depletion states when ADH is stimulated which takes

precedence ?

Water is retained more and serum sodium lowered

Clinical approach to HypoNa

•1% of healthy population

•5-8 % of hospitalised patients

•30% of ICU patients

Is it serious ?• Marker of severity of underlying disease• CCF.• Cirrhosis.• Advanced cancer.

• Marker of increased mortality

• Treatment may be more deleterious in some !

4 essentials

1. History

2. Plasma osm.

3. Volume status

4. Urine Sodium

Don’t jump to treatment!!Avoid misdiagnosis !

• Sampling error ? Common • Hyperlipidemia ? Use ISE ( Not Flame

Photometer)• Multiple Myeloma ? Use ISE ( - do - )• Hyperglycemia ? Every 100 mg increase in glucose

reduces serum Sodium by 1.6 - 2.4 mEq/L

• Drugs and chemicals? Glycine,Mannitol.

Hyperglycemia – Hyperosmolar hyponatremia

Water

Glucose is osmotically Active

Translocational hyponatremia

Serum osmolality will be high

LOOP D block both conc.and dilution

THIAZIDES BLOCK DILUTION ALONE

Urine Na and K very high Urine Na and K moderate

Management and special situations

Therapeutic Strategy Based On

• 1. Volume Status of Patient• 2. Presence of Absence of Symptoms• 3. Duration of Hypoosmolality• 4. Presence of absence of risk factors for

development of neurological complication

(Osmotic demyelination is rare in patients with initial Na+ > 120mEq/L)

Clinical scenario 1

• 28 years old female • Admitted for delivery• Prolonged labour• Had to be taken up for cesarian• Post op coma • Seizures • Fluid orders – NS 3000 ml /24 hrs• BP 100/80- Serum Sodium 110 mEq/L

Why hyponatremia

Source of free water

Was given Normal saline3 Litres /24 hours

Free water intake due to anxiety

ADH is acting

Post op painAnxietyNausea due to analgesics

DESALINATION syndrome

e- 300 mOsm x 3

900 Mosm

ADH CONCENTRATES

URINE

600 Mosm /L = 1.5 L of urine

3 L of Saline

Thus 1.5 Litres of free water is retained in body !

1.5 L WATER

K 135 Na – 135

270 mOsm

270 mOsm

26 L 17 .5 L

1L

0.5L

Cerebral edema and Brain herniation

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CNS ENCASED IN SKULL

Neuronal edemaTentorial herniationNeurog.Pul.edema

Acute water excess

Aggressive treatment • 3% saline 2 ml/kg/hour

• Furosemide 40 mg i.v

• Hourly sodium estimation

• Sodium 118 after 2 hours

• No seizures .

Scenario 2 56 years old maleAlcoholic cirrhosisEdema , AscitesOliguriaSleepinessS.Sodium 113/K 2.3 ?Chronic hyponatremia – beware!

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Chronic hyponatremia – Brain adapts to keep the edema within limits

Aminoacids.Myoinositol

Rapid correction leads on to cell shrinkage and Demyelination.

Calculation• 60% of body weight is water • 65 x 0.6 = 39 L• 123-113 = 8 • 39x 8 = 312 Meq needed• 1ml of 3% saline = 0.5 mEq of Na• Sodium deficit = 624 ml• 624 /24 hours = 26 ml/hr• Serum Na measure q2-4 hrs

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Adrogue’s Formula*

• Change in serum Sodium=

(Bottle Na+ + Bottle K+) - serum Na+

total body water + 1

• Easier to calculate

*Horacio J Adrogue, Nicholas E Madias: Hyponatremia; NEJM Vol 342, No 21May 25 (2000)

Janinic and Verbalis formula

• Rate ml/Kg/Hr = Goal rate of rise mmol/Kg/Hr

• 1ml/kg/hr = 1ml/kg/hr rise in Serum Na

• Ideal for those allergic to Math !!

Chronic hyponatremia

• Water restriction• Demeclorcycline 300 -600 mg tid• Lithium • Oral urea • VAPTANS

K

Na moves into cell producing hyponatremia

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Tirunelveli API , TVMC Auditorium

Treat with Intravenous potassium Replenish the IC deficit of Potassium . Sodium automatically comes up If not replaced , then there is danger of

osmotic demyelination.

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Tirunelveli API , TVMC Auditorium

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Insufficient Correction

CEREBRAL EDEMA Herniation

Too Rapid Correction

OSMOTICDEMYELINATION

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Tirunelveli API , TVMC Auditorium

Vasopressin receptor antagonists

Vasopressin-Receptor Antagonists.

Ellison DH, Berl T. N Engl J Med 2007;356:2064-2072.

SALT -1 ,SALT-2 and SALTWATER

• Oral Tolvaptan increased the serum sodium levels significantly and safely in CCF,SIAD and Cirrhosis.

• NOT USED IN ACUTE SYMPTOMATIC HYPONATREMIA

• 2 CONCERNS• INCREASED THIRST• OVERLY RAPID CORRECTION OCCURRED in 1.8%• No ODM ENCOUNTERED

VAPTANS –PURE WATER EXCRETION

Why ODS is not a major threat

• Short acting • Possible to reverse the effect • Frequent Na monitoring in major clinical

trials• No threat of hypok as with diuretic +

Hypertonic saline regimen• FDA Warning- Liver toxicity on prolonged

use in Cirrhosis

Who should be treated with vaptans

SIADH v.s. Cerebral Salt Wasting

SIADH CSW

Serum Na ↓ ↓

ECFv Normal ↓

UNa ↑ ↑↑

UOSM ↑ ↑

Urine volume N or ↓ ↑

Serum urate ↓ N or ↓

Urine urate ↑ N or ↑

Some Interesting Issues not discussed

• Reset Osmostat• Beer Potomania• Glycine in TURP• Exertional hyponatremia• Ecstacy and hyponatremia

THANK YOU