mia and hypernatremia-deepak madhu

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Hyponatremia andhypernatremia



… are disorders of waterbalance



Hyponatremia



Hyponatremia is a common clinicalproblem developing in around2.5% of hospitalized patients.

The case fatality rate was 60 timeshigher in patients in whomhyponatremia was present.

Problem statement

Deepak Madhu



Sodium is the main extracellular osmole,

A reduction in serum sodium is associated with areduction in osmolarity.

The clinical approach to hyponatremia begins byexcluding conditions in which osmolarity is not reduced.

Deepak Madhu



All conditions in which hyponatremia does

not result in hypo-osmolarity is called“pseudohyponatremia”

There are two conditions in which

pseudohyponatremia is really alaboratory artifact namely hyperlipidemiaand hyperproteinemia. Serum osmolarityis normal in such cases.

Deepak Madhu



Conditions in which an osmoticallyactive substance such as glucoseor mannitol accumulates in theserum and draws water out of the

intracellular space also is referredto as a kind of “pseudohyponatremia”. Serum

osmolarity is increased hereDeepak Madhu



Once pseudohyponatremia isexcluded, hyponatremia may beclassified on the basis of ECFvolume status.

Deepak Madhu



Hyponatremia

Serum OSM

Low Normal High

HypotonicHyponatremia

ECFv *

Low Normal

High

HyperglycemiaMannitol

Marked hyperlipidemia(lipemia, TG >35mM)Hyperproteinemia(Multiple myeloma)

•CHF•Cirrhosis• Nephrosis

•Hypothyroidism•AI•SIADH•Reset Osmostat•Water Intoxication

1° PolydipsiaTURP post-op

Renal loss (UNa > 20)• Diuretics

• Thiazide• K-sparing

• ACE-I, ARB• IV RTA, Hypoaldo• Cerebral salt

wastin

Extra-renal loss (UNa <10)• Bleeding• Burns• GI (N/V, diarrhea)• Pancreatitis

* Note: all have ↑ADH•SIADH: inappropriate•Rest: appropriate

Deepak Madhu



Depend on magnitude of thehyponatremia and rapidity of

its development.Acute (< 48 hrs): Symptoms at[Na+] of ≤ 125 mEq/L. Seizures

and coma at ≤ 115 mEq/L.Chronic: often asymptomatic

Hyponatremia:

Clinical Manifestations

Deepak Madhu



Symptoms - mainly CNSEarly: nausea, malaise,headache, muscle twitching,

lethargyLate/Severe: obtundation,seizures, coma, respiratory

arrestDeepak Madhu



Patients with ECF volume depletion

and hyponatremia have a deficit intotal body Na that is more than thedeficit in water.

Hyponatremia withextracellular volume depletion

Deepak Madhu



There is depletion of body solutesand a concomitant failure toexcrete water as the osmoreceptorand volume receptor receive

opposing stimuli and the osmoticset-point is lowered.

Hyponatremia with

extracellular fluid volumedepletion (cont)

Deepak Madhu



Clinical:

Orthostasis,

Flat neck veins

Decreased skin turgor

Dry mucous membranes

Tachycardia

Hyponatremia with

extracellular fluid volumedepletion

Deepak Madhu

● U● R● E● U● R● E



● U Na

>20

● Rena

l los

s

● Extr

arena

l

● U

● Rena

l los

s

● Extr

arena

l

Deepak Madhu



Diuretic excess

Mineralocorticoid deficiency

Salt losing nephropathy

Bicarbonaturia with RTA and metabolic

alkalosis

Cerebral salt wasting

Renal loss

Deepak Madhu



Vomiting

Diarrhoea

Third spacing

Burns

Pancreatitis

Trauma

Extra renal loss

Deepak Madhu



Here total body water increases

Total body sodium also increases The rise in total body waterexceeds the rise in total body

sodium

Hyponatremia with excess ECFvolume

Deepak Madhu

● U● N● C● C● A● U● N● C● C● A



● U Na

<20

● Neph

rotic

● Cirr

hosis

● Card

iac F

ailu

re

● Acut

e or

Chro

nic r

e

● U Na

>20

● Neph

rotic

● Cirr

hosis

● Card

iac F

ailu

re

● Acut

e or

Chro

nic r

e

Hypervolemic hyponatremia

Deepak Madhu



Decreased cardiac outputresults in limited delivery of tubule fluid to the distalnephron.

Decrement in arterial filling aresensed by aortic and carotidsinus baroreceptors andstimulate AVP release.

Congestive Cardiac Failure

Deepak Madhu



Patients with advanced cirrhosis develop

hyponatremia due to their inability toexcrete a water load.

Effective arterial blood volume is contracteddue to decreased osmolality as a result of

hypoalbuminemia and due to splanchnicpooling of blood.

This results in a high AVP state

Hepatic failure

Deepak Madhu



Hypoalbuminemia results inintravascular volume contractionand a high AVP state that results inan inability to excrete a water

load.

Nephrotic syndrome

Deepak Madhu



A decrement in GFR and anincrease in thirst underlies thehyponatremia of renal failure

Renal failure

Deepak Madhu



Not orthostatic

Not dehydrated

Not edematous .

Hyponatremia with normalECF volume

Deepak Madhu



Glucocorticoid deficiency

Hypothyroidism

Psychosis- primary polydipsia

Postoperative hyponatremia

Strenuous exercise

Pharmacologic agents

SIADH

Causes

Deepak Madhu



Isolated glucocorticoiddeficiency occurs withsecondary adrenalinsufficiency caused bypituitary disorders that impairnormal ACTH secretion butleave other stimuli to


Deepak Madhu



Hyponatremia occurs relativelyfrequently in patients with pituitaryinsufficiency who do not havediabetes insipidus


(cont)

Deepak Madhu



The exact mechanism by which

hypothyroidism causes hyponatremia isnot known

Impaired water excretion is often presentand diminished distal fluid delivery andpersistent avp release mediate theimpaired water excretion in this disorder.

Hypothyroidism

Deepak Madhu



Defects in osmoregulation that results in

AVP secretion at plasma osmolalities lowerthan normal

Psychotic exacerbations are also associatedwith increased vasopressin levels in

schizophrenic patients with hyponatremia.

Thirst perception is also increased.

Psychosis – Primary

polydipsia

Deepak Madhu



Primarily as a cosequence of hypotonic fluid administration,hyponatremia can also occur inthis high AVP state even when

isotonic fluids are given

Post-operative

hyponatremia

Deepak Madhu



Military training, marathons,triathlons…

Associated with weight gainrelated to excessive fluid intake

Symptomatic hyponatremia canresult

Strenuous excercise

Deepak Madhu



ADH analogues

Drugs that enhance AVP

Drugs that potentiate renal action

renal action of AVPDrugs that cause hyponatremia byunknown mechanism

Drugs

Deepak Madhu



Desmopressin acetate

Oxytocin

ADH hormone analogues

Deepak Madhu



Chlorpropamide

Clofibrate

Carbamazepine

Vincristine

Nicotine

Narcotics

Antipsychotics, antidepressants

Ifosfamide

Drugs that enhance AVP

Deepak Madhu



Chlorpropamide

Cyclophosphamide

NSAIDs

Acetaminophen

Drugs that potentiate renalaction of AVP

Deepak Madhu



Haloperidol

Fluphenazine

Amitryptiline

Thioridazine

SSRI

Ecstacy

Drugs that causehyponatremia by unknown

mechanisms

Deepak Madhu



SIADH

Deepak Madhu



SIADH is the most common cause of

euvolemic hyponatremia

The criteria was defined by Bartter

and Schwartz in 1967 in the originalclassic article that described thesyndrome

SIADH

Deepak Madhu



1. True ECF hypo-osmolarity must be present.

Pseudohyponatremia and hyperglycemia must beexcluded.

2. Urinary osmolality must be inappropriate. Withserum hypo-osmolarity, urine should be less than

maximally dilute (Uosm >100)

SIADH - Criteria

Deepak Madhu



3. Clinical euvolemia must be

present.

4. Urine sodium >20 the presenceor absence of this, does not,

however diagnose or excludeSIADH.

5. Other causes should be

excluded.

SIADH – Criteria (cont)

Deepak Madhu



Carcinomas

Pulmonary disorders

CNS disorders

Other

SIADH - Causes

Deepak Madhu



Bronchogenic carcinoma

Carcinoma of the duodenum

Carcinoma of the pancreas

Thymoma

Carcinoma of the stomach

Lymphoma

Ewing sarcoma

SIADH causing carcinomas

Deepak Madhu



Carcinoma of the bladder

Prostatic carcinoma

Oropharyngeal tumor

SIADH causing carcinomas(cont)

Deepak Madhu



Encephalitis

Meningitis

Head trauma

Brain abscess

GBS

Acute intermittent porphyria

SAH

Neurological disorders

Deepak Madhu



Cerebellar and cerebral atrophy

Cavernous sinus thrombosis

Neonatal hypoxia

Shy – Drager syndrome

Rocky mountain spotted fever

Delirium tremens

CVA

Neurologic disorders (cont)

Deepak Madhu



Acute psychosis

Peripheral neuropathy

Multiple sclerosis

Neurologic disorders (cont)

Deepak Madhu



Nephrogenic syndrome of

inappropriate antidiuresis.

Gain of function mutations in the

V2R results in antidiuresis in theabsence of AVP.

NSIAD

Deepak Madhu



Management of

hyponatremia

Deepak Madhu



Overly rapid correction of

hyponatremia can result in osmoticdemyelination

This can occur irrespective of the

etiology of hyponatremia or themethod used to correct it

Rate of correction

Deepak Madhu



Limits for the correction of hyponatremia:

<10-12mEq/L in 24 hrs and upto

<18 mEq/L in 48 hrs

Rate limits

Deepak Madhu



Subgroups at increased risk for ODS:

Severe malnutrition

Alcoholism

Advanced liver disease

In these patients, correction rate should bewell below the ‘normal’ correction limits.

High risk groups for ODS

Deepak Madhu



Correction by <3-4 mEq/L in 24hrs maybe

associated with excess mortality

But correction in excess of 10mmol/L in 24hrs or 18 mEq/L in 48hrs have not beenshown to improve outcome.

Rate of correction shouldneither be too slow nor too

fast…

Deepak Madhu



If volume depletion is present, the

volume deficit has to be corrected.And the relative water excess willcorrect itself

Correction of hypovolemichyponatremia

Deepak Madhu



Voulme resuscitation has to be

done with isotonic fluid until thepatient has attained clinicaleuvolemia.

Correction of hypovolemichyponatremia (cont)

Deepak Madhu



When the initial volume estimate is

equivocal, a fluid challenge with0.5 to 1 L of isotonic saline can beboth therapeutic and diagnostic.

Correction of hypovolemichyponatremia (cont)

Deepak Madhu



Isotonic saline is the mainstay of

treatment

KCl should be added if hypokalemia andmetabolic alkalosis are present due to

vomitingAn isonatric mixture of NaCl andNaHCO3 may be used if metabolicacidosis is present due to diarrhoea

Hypovolemic hyponatremiaassociated with excess

gastrointestinal loss

Deepak Madhu



Specific therapy for the underlying

disorder should be initiated, andantiemetics and antidiarrhoealsused as appropriate

Deepak Madhu

l i h i



Obvious signs of dehydration and

volume depletion to be treatedpromptly with rehydration usingisotonic saline.

Hypovolemic hyponatremiaassociated with excess

sweating

Deepak Madhu



In the absence of obvious

dehydration, if hyponatremia ispresent, guidelines for EAH to befollowed. Isotonic saline should not

be started.

Deepak Madhu

H l i h i



All diuretics to be withheld

The patient has to be repleted with isotonicfluid if the CNS abnormalities are mild

Hypertonic saline maybe used to raise theserum sodium level 4-5 mEq/L whenseizures or significant altered sensorium ispresent

Hypovolemic hyponatremiaassociated with diuretic

therapy

Deepak Madhu



Patients with thiazide induced

hyponatremia are at high risk of recurrence and should not berechallenged with a thiazide.

Deepak Madhu

C b l lt ti



Patients with volume depletion from CSW

should be resuscitated by administrationof isotonic saline until they are euvolemicand maintained in neutral fluid balance

Hypertonic saline to be used if altered

sensorium believed to be due tohyponatremia is present.

Cerebral salt wasting

Deepak Madhu

C 1



83 year old lady presented with a 3 week

history of memory disturbances. She has ahistory of hypertension and has recentlystarted antihypertensive medication,hydrochlorothiazide tablets. Otherwise she ishealthy and does not take any othermedications.

Case 1

Deepak Madhu

C 1 ( t)



She also reports no nausea, vomiting or diarrhoea,

and the rest of her systems review is normal. Herheart rate is 100bpm and her BP is 110/70 mm Hg.When standing her pulse rate increases to 110/minand BP decreases to 90/60 mm Hg. RR – 12 bpm

Case 1 (cont)

Deepak Madhu

C 1 ( t)



The physical examination reveals an elderly

woman in no acute distress. She is alert andoriented. The patient has dry mucous membranesand poor skin turgor. The rest of her examinationis within normal limits. Laboratory data show thatthe patient has dry mucous membranes and poor

skin turgor.

Case 1 (cont)

Deepak Madhu

C 1 ( t)



The rest of her examination is within normal

limits. Laboratory data show that the patienthas Na -125Meq/L, a K-3.4 Meq/L, a plasmaosmolality of 270 mOsm/Kg H2O, UNa – 23MEq/Kg; BUN – 48mg/dl, S.Cr – 1.2mg/dl and aUrine osmolality of 400 mOsm/Kg of water.

Case 1 (cont)

Deepak Madhu

Q C 1



What is the likely diagnosis for the

patient?

a) SIADH

b)

Thiazide induced hyponatremiac) Hypertonic hyponatremia

d) Renal insufficiency

Q: Case1

Deepak Madhu

A Q1



What is the likely diagnosis for the

patient?

a) SIADH

b)

Thiazide induced hyponatremiac) Hypertonic hyponatremia

d) Renal insufficiency

Ans Q1

Deepak Madhu

Q2



What is the next step in management?

a) Start IV normal saline

b) Start aggressive oral hydration

c) Start 3% saline to reach a 5% increase

in Na for the next 24 hours.d) Discontinue thiazide and continue

hydration using IV normal saline.

Q2

Deepak Madhu

A Q2



What is the next step in management?

a) Start IV normal saline

b) Start aggressive oral hydration

c) Start 3% saline to reach a 5% increase

in Na for the next 24 hours.d) Discontinue thiazide and continue

hydration using IV normal saline.

Ans Q2

Deepak Madhu

Discussion Case 1



Kindly note that it is wise to check

Na levels 1 week after startingthiazide diuretic

Discussion Case 1

Deepak Madhu

Dicsussion Case 1 ( Cont)



The differences in the risk of hyponatremia

between thiazides and loop diuretics is due to thedifference in their mechanism of action.

With loop diuretics, the reabsorption of water dueto ADH is interfered , even though loop diureticsalso increase ADH levels by inducing volume

depletion

Dicsussion Case 1 ( Cont)

Deepak Madhu

Discussion Case 1 (cont)



Thiazide induced hyponatremia

occurs in the first 1-2 weeks afterstarting thiazides .

Elderly women are more at risk.

Discussion Case 1 (cont)

Deepak Madhu

Euvolemic Hyponatremia



Acute symptomatic hyponatremia -

3% saline

IV furosemide 20-40mg to be givento prevent fluid overload

Euvolemic Hyponatremia-SIADH

Management

Deepak Madhu

SIADH Management



Infusion rate of hypertonic saline:

body wt(kg)Xrate of correctiondesired(mEq/L/hr)

For example a 70 kg man requiring

1meq/l/hr requires 70ml/hr of 3%saline.

SIADH - Management

Deepak Madhu



Acute treatment should be interrupted

once any of the three end points areachieved:

1. Patient ‘s symptoms are abolished

2. A safe serum Na+ level >120mEq/L is

achieved

3. A magnitude of correction18mEq/L isachieved

Deepak Madhu



In SIADH with reset osmostat, no

treatment is required

Most other cases of mild-moderatehyponatremia can be managed

with fluid restriction.

Deepak Madhu

Fluid restriction measures



1. All fluids not only water, should be included in thisrestriction.

2. The degree of restriction required depends on urineoutput plus insensible fluid loss- non food fluids restrictedto 500ml/day below the average daily urine volume.

3. Several days of restriction are necessary

4.

Only fluid, not sodium, should be restricted


Deepak Madhu




5. Because of the high negative

sodium balance, patients withSIADH need to be started on ahigh NaCl diet unless otherwise

contraindicated.7. Any drug potentially causing

SIADH should be

substituted/discontinued

Fluid restriction measures(cont)

Deepak Madhu

Pharmacologic therapy of



Pharmacologic therapy is reserved

for cases refractory to fluidrestriction.

SIADH associated with tumors will

resolve with treatment of thelesion.

Pharmacologic therapy

Demeclocycline 600-1200 mg/day

Pharmacologic therapy of SIADH

Deepak Madhu

Pharmacologic therapy of



Urea 30g/day PO may also be

used.

Vaptans are a new group of drugsthat have been found to be

effective.

Pharmacologic therapy of SIADH(cont)

Deepak Madhu

NSIAD



Same as SIADH

Urea therapy has been found to beparticularly effective

Urea has to be dissolved in orange juice or any such solvent tocamouflage the taste.

NSIAD

Deepak Madhu




If there is suspicion of adrenal

insufficiency, glucocorticoidreplacement should be startedimmediately after a rapid ACTH

stimulation test

Glucocorticoid deficiency-management

Deepak Madhu




Prompt water diuresis after initiation of

glucocorticoid therapy confirms diagnosisAbsence of a quick response does notnegate this diagnosis

In such cases, primary treatment of the

hyponatremia is indicated if the patient issymptomatic

Glucocorticoid deficiency –management (cont)

Deepak Madhu

Hypothyroidism



Hyponatremia associated with hypothyroidism

is generally mild and only modest fluidrestriction necessary

Symptomatic hyponatremia is seen in patientswith more severe hypothyroidism and alteredmental status, primary treatment of thehyponatremia is indicated

Hypothyroidism

Deepak Madhu

Exercise associated



Can be severe and life threatening

as a result of cerebral oedema andnon-cardiogenic pulmonaryoedema.

Exercise associatedhyponatremia

Deepak Madhu

Exercise associated



Runners are frequently fatigued, light

headed, pre-syncopal, or dizzy at theconclusion of exercise but seizures,profoundly altered level of consciousness,ataxia or focal neurological deficits should

raise suspicion of hyponatremia

Exercise associatedhyponatremia (cont)

Deepak Madhu

Exercise associated



With significant CNS impairment,

hypertonic saline should be startedat once and continued till S. Na is>125 or symptoms resolve.

Exercise associatedhyponatremia (cont)

Deepak Madhu

Psychosis-polydipsia



Clozapine has been found to be

useful in reducing and preventingrecurrent hyponatremia in a subsetof patients

Psychosis-polydipsiamanagement

Deepak Madhu

Case 2



The patient is a 78 year old man who is

a cigarette smoker and presents withincreasing cough, hemoptysis, anddrowsiness. He is taking nomedications. During the last one year

he has lost approximately 8 Kg and hiscurrent weight is 72 Kg.

Case 2

Deepak Madhu

Case 2 (cont)



His mucous membranes are moist, skin

turgor normal and does not have anorthostatic fall in BP. Other thannicotine staining of right index andmiddle fingers, his physical

examination is normal. His chestexamination reveals a 4 cms lung massin the right.

Case 2 (cont)

Deepak Madhu

Case2 (cont)



His S. Na is 123Meq/L , K is 4.3

Meq/L and creatinine is 1.1mg/dl.Measured osmolality is270mOsm/Kg. Uric acid level is

4.2mg/dl. And U Na – 45mEq/L. The TSH level is normal

Case2 (cont)

Deepak Madhu

Case 2: Q 1



What is the cause of the patients

hyponatremia?a) Renal failure

b) Treatment with thiazides

c)

Hypothyroidismd) SIADH

Case 2: Q 1

Deepak Madhu

Case2:A1



What is the cause of the patients

hypoonatremia?a) Renal failure

b) Treatment with thiazides

c)

Hypothyroidismd) SIADH

Case2:A1

Deepak Madhu

Further



The patient insists on being

treated at home and agrees torestrict his fluid intake to 800mleach day. The next morning the

patients son brings the patientwith complaints of disorientationand unresponsiveness

Further …

Deepak Madhu



The patient is comatose on examination and does notrespond to verbal or painful stimuli. His physical

examination, apart from mental status changes, issignificant for depressed reflexes. His repeatelectrolytes are as follows:

S.Na – 108mEq/L, K -4.0, S.Cr-4.0, S. Osm –264mOsm/Kg, Urine Osm – 600mOsm/Kg H20.

Deepak Madhu

Case2:Q2



How sould the patient be managed?

a) Begin fluid restriction and administer NSb) Begin 3%saline and administer vasopressin

c) Begin fluid restriction and administer 3% salineinfusion.

d) Administer vasopressin and furosemide

Case2:Q2

Deepak Madhu

Case2:A1



How sould the patient be managed?

a) Begin fluid restriction and administer NSb) Begin 3%saline and administer vasopressin

c) Begin fluid restriction and administer 3% salineinfusion.

d) Administer vasopressin and furosemide

Case2:A1

Deepak Madhu

Hypervolemic



CHF – Fluid restriction is the

approach. Other options includedemeclocycline, Urea, and fluidrestriction.

Hypervolemichyponatremia-CHF

Deepak Madhu

Hypervolemic hyponatremia



Cirrhosis: Fluid restriction should

be instituted. Demeclocycline –contraindicated due to the highincidence of nephrotoxicity. Urea

has not been tried often

Hypervolemic hyponatremia- Cirrhosis

Deepak Madhu

Nephrotic syndrome, ARF



Fluid restriction is the only option

Nephrotic syndrome, ARFand CRF

Deepak Madhu

Case 3



The patient is a 64 year old man who

presents with increasing shortness of breath, fatigue, paroxysmal nocturnaldyspnoea and marked oedema. He hasa long history of coronary artery

disease and underwent coronarybypass surgery 6 years ago.

Case 3

Deepak Madhu

Case 3 (cont)



The patients physical examination

reveals JVD, rales and S3. His chestradiographs show B/L pleural effusions,cardiomegaly and interstitial infiltrates.His sodium levels is 121mEq/L, his K

-3.5, his urine sodium -5 mEq/L andplasma osmolality 260 mOsm/Kg of H2O

Case 3 (cont)

Deepak Madhu

Case3:Q1



Which is the appropriate diagnosis for the patient?

a) Iso-osmotic hyponatremia

b) Isovolemic hypo-osmotic hyponatremia

c) Hypovolemic hypo-osmotic hyponatremia

d) Hypervolemic hypo-osmotic hyponatremia

Case3:Q1

Deepak Madhu

Case3:A1



Which is the appropriate diagnosis for the patient?

a) Iso-osmotic hyponatremia

b) Isovolemic hypo-osmotic hyponatremia

c) Hypovolemic hypo-osmotic hyponatremia

d) Hypervolemic hypo-osmotic hyponatremia

Case3:A1

Deepak Madhu

Case3:Q2



What is the reason for the

hyponatremia in this patient?a) Impairment of water excretion due to

ADH excess

b) Increased water intakec) SIADH

d) Adrenal failure

Case3:Q2

Deepak Madhu

Case3:A2



What is the reason for the

hyponatremia in this patient?a) Impairment of water excretion due to

ADH excess

b) Increased water intakec) SIADH

d) Adrenal failure

Case3

Deepak Madhu

Case3:Q3



How should the patient be treated?

a) Administer IV 3% saline solution

b) Start IV normal saline and loop diuretics

c) Implement fluid restriction and start

loop diureticsd) Start high doses of beta blockers

Q

Deepak Madhu

Case3:A3



How should the patient be treated?

a) Administer IV 3% saline solution

b) Start IV normal saline and loop diuretics

c) Implement fluid restriction and start

loop diureticsd) Start high doses of beta blockers

Deepak Madhu

Infusates



Infusate Meq/L

Normal Saline 154

3% saline 513

Deepak Madhu

Common salt



Sodium chloride consists of 40%

w/w Na and 60% w/w Cl.One level teaspoon (US) contains5750mg salt which is 2300mg

sodium which is inturn 100mEq of Na

Deepak Madhu

Correction of Hyponatremia-



1. Estimate total body water

2. Estimate the change in Na perlitre of infusate

3. Calculate the amount of infusaterequired

4. Calculate the rate of infusion

ypsteps

Deepak Madhu

For example



A 70 kg man of age 45 years, with Na 0f 110mEq/L, is obtunded . The goal: his S.Na shouldincrease rapidly by 4 mEq/L over the next 2-4hours.

p

Deepak Madhu

Calculation of total body



TBW = total body water

This is calculated by multiplyingbody weight with a correctionfactor

The correction factors vary withage and sex and is as follows…

ywater

Deepak Madhu

Correction factors



Patient Correction factor

Pediatric 0.6

Male, non elderly 0.6

Female, non elderly 0.5

Male, elderly 0.5

Female, elderly 0.45Deepak Madhu

Formulas for calculating



gchanges in sodium levels in

hypo/hyper-natremia

Deepak Madhu

The patient’s hyponatremia



p ypcorrection

Deepak Madhu

Aquaretics



Antagonists of the kidney

vasopressin V2 receptors(nicknamed vaptans) have longbeen predicted to be the ideal

agent for treatment of patientswith dilutional hyponatremia.

q

Deepak Madhu

Aquaretics (cont)



These agents stimulate renal free

water excretion (aquaresis) andthereby lead to increased serum[Na+] in most patients with

dilutional hyponatremia due toSIADH, congestive heart failure, orcirrhosis.

q

Deepak Madhu

Conivaptan



In 2005 the U.S. Food and DrugAdministration (FDA) approved conivaptan, acombined V1a and V2 vasopressin receptorantagonist, for treatment of euvolemichyponatremia, and in 2006 this approval wasextended to patients with hypervolemic

hyponatremia.

Deepak Madhu

Conivaptan (cont)



Phase 3 clinical trials of conivaptan

demonstrated a prompt correctionof serum [Na+] in most treatedhyponatremic patients, averaging

6 to 8 mEq/L over a 2- to 4-daycourse of treatment.

Deepak Madhu

Conivaptan (cont)



Conivatan is an inhibitor of the

hepatic cytochrome P450isoenzyme CYP3A4, and henceinhibits metabolism of many drugs

therefore, its use has been limitedto short-term (<4 days)intravenous administration inhospitalized patients.Deepak Madhu

Conivaptan (cont)



Conivaptan was found to be useful

in that it corrected serum [Na+]more rapidly than fluid restrictionin patients with non–life-

threatening degrees of hyponatremia.

Deepak Madhu

Tolvaptan



Tolvaptan, a selective V2

vasopressin receptor antagonist,was approved by the FDA in 2009for treatment of euvolemic and

hypervolemic hyponatremia.

Deepak Madhu

Tolvaptan (cont)



Clinical trials of tolvaptan showed

normalization of serum [Na+] in mosthyponatremic patients treated, and thiseffect was sustained over a 30-daytreatment period with recurrence of the

hyponatremia by 7 days after cessationof the drug.

Deepak Madhu

Tolvaptan (cont)



The use of tolvaptan in the United States islimited to patients with severe hyponatremia(serum [Na+] < 125 mEq/L) and those withmilder degrees of hyponatremia who aresymptomatic and for whom treatment withfluid restriction has failed.

Deepak Madhu



Hypernatremia



Hypernatremia is a rise in serum

sodium concentration to a valueexceeding 145 mEq/L.

Hypernatremia invariably denotes

hypertonic hyperosmolality andalways causes cellular dehydrationatleast transiently

Deepak Madhu

Hypernatremia can result



Net water loss or hypertonic sodium

gainNet water loss accounts for themajority of cases

Net water loiss can be pure water loss(no sodium deficit) or hypotonic fluidloss.

from…

Deepak Madhu



Hypertonic sodium gain usually

results from accidental sodiumloading.

Deepak Madhu

Pure water loss



Insensible losses

Hypodipsia

Neurogenic diabetes insipidus

Congenital nephrogenic diabetesinsipidus

Acquired nephrogenic diabetes

insipidusDeepak Madhu

Hypotonic fluid loss



Renal causes: loop diuretics, Osmotic

diuretics, Postobstructive diuresis,polyuric phase of ATN, intrinsic renaldisease

GI causes: Vomiting, nasogastric

drainage, enterocutaneous fistula,diarrhoea, use of osmotic catharticagents

Deepak Madhu



Cutaneous causes: excessive

sweating, burns

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Hypertonic sodium gain



Hypertonic sodabicarb infusion

Hypertonic feeding preparation

Ingestion of sodium chloride

Ingestion of sea water

Sodium chloride – rich emetics

Hypertonic saline enemas

Deepak Madhu

Hypertonic sodium gain( )



Intrauterine injection of hypertonic

salineHypertonic sodium chlorideinfusions

Hypertonic dialysis

Primary hyperaldosteronism

Cushing’s syndrome

(cont)

Deepak Madhu

Clinical manifestations of h i ( )



• Symptoms may start as lethargy, weaknessand irritability

• May progress to twitching, seizures,obtundation or coma

• Cell dehydration and resulting decrease in

brain volume can lead to rupture of cerebral veins leading to hemorrhage

hypernatremia (cont)

Deepak Madhu

Clinical manifestations of h t i ( t)



• Severe symptoms usually occur

with rapid increase of sodiumconcentration to 158 mEq ormore

•

Sodium concentration greaterthan 180 mEq are associatedwith high mortality

hypernatremia (cont)

Deepak Madhu

Management



Two pronged apprroach which

requires management of theunderlying cause as well asmanagement of the hypernatremiaitself

Deepak Madhu

Management (cont)



Hypernatremia that developed

over a period of hours can becorrected rapidly.

In such patients, the sodium

maybe reduced at a rate of 1mEq/L/hr

Deepak Madhu

Management (cont)



In hypernatremia of longer or

unknown duration, a slower rate of correction is required.

The maximum rate of correction in

such patients is 0.5mEq/L/hr.

Deepak Madhu

Management (cont)



In a hypovolemic patient, volumeresuscitation for a hemodynamicallyunstable patient should be accomplished byisotonic 0.9% saline. One the patient ishemodynamically stable, intravenous fluidsshould be changed to a hypotonic 0.45%

saline.

Deepak Madhu

Management (cont)



The euvolemic patient: pure water

replacement with iv hypotonicsaline or free water.

Dextrose containing solutions may

be used but blood sugar should bemonitored as hyperglycemia wouldcontribute to osmolarity

Deepak Madhu

Management (cont)



For significantly hypernatremic

individuals in whom central DI isconsidered, 5-10 units of aqueousvasopressin should be givensubcutaneously every 3-4 hours.

Deepak Madhu

Management (cont)



Sodium levels in the serum should

be checked every 4 hours.Cerebral oedema is an importantcomplication of hyponatremia

correction.

Deepak Madhu

Management (cont)



In order to avoid cerebral oedema, a

maximum decrease of 10 mEq/L per 24hour period is recommended.

The free water deficit has to becalculated first,and no more than half of

the water deficit is to be corrected in thefirst 24 hours and the remainder has tobe corrected over the next 1-2 days.

Deepak Madhu

Calculation of free waterdeficit



deficit

Deepak Madhu

Calculation of total bodywater



TBW = total body water

This is calculated by multiplyingbody weight with a correctionfactor

The correction factors vary withage and sex and is as follows…

water

Deepak Madhu

Correction factors



Patient Correction factor

Pediatric 0.6

Male, non elderly 0.6

Female, non elderly 0.5

Male, elderly 0.5

Female, elderly 0.45Deepak Madhu

For example…



Deepak Madhu

How is the free water deficitcorrected?



The free water deficit maybe

corrected over 3 days. Total intake = (total output +insensible + 1/3 – 1/2 water

deficit) each day for the next threedays.

corrected?

Deepak Madhu

Formulas for calculatingchanges in sodium levels in



changes in sodium levels in

hypo/hyper-natremia

Deepak Madhu

Infusate composition



Infusate Infusate Na ECF distribution

5%D 0 40

0.2% NaCl in 5%D 34 55

0.45% NaCl inwater

77 73

Ringers lactate 130 97

0.9% NaCl in water154 100Deepak Madhu

Case 4



A 76-year-old man presents with a severeobtundation, dry mucous membranes,decreased skin turgor, fever, tachypnea, anda blood pressure of 142/82mm Hg withoutorthostatic changes. The serum sodiumconcentration is 168 mmol per liter, and the

body weight is 68 kg. How would youmanage the patient?

Deepak Madhu



Deepak Madhu



The patient’s serum glucose level also has tobe monitored regularly and insulin given at

the slightest signs of hyperglycemia

Other parameters have to be monitoredatleast every 6 hours.

Deepak Madhu

Case 5



A 58-year-old woman with postoperativeileus is undergoing nasogastric suction. Sheis obtunded and has diminished skin turgorand mild orthostatic hypotension. The serumsodium concentration is 158 mEq per liter,the potassium concentration is 4.0 mEq per

liter, and the body weight is 63 kg. howwould she be managed?

Deepak Madhu



She has hyponatremia due to hypotonicfluid loss and therefore an infusion of 0.45 percent NaCl maybe planned.

The initial administration of isotonicsaline is not warranted as her

hemodynamic status is not socompromised as to require it.

Deepak Madhu



Deepak Madhu

Q continued



The patients S.Na levels rechecked

came as 155mEq/L at the end of 12 hours and the patient continuesto be somnolent.How would youproceed?

Deepak Madhu



More aggressive lowering of the

S.Na levels is required and thepatient maybe shifted to analternative agent, say, 0.2% saline.

Therapy maybe resumed with theaim of reducing the S.Na levels by10mmols over the next 24 hours.

Deepak Madhu



One litre of 0.2%NaCl is expected to reducethe S.Na levels by 3.7L and thus 2.7 L of fluid

is required to achieve the goal.

With the allowance for ongoing loss + urineoutput + insensible loss, say 2L, the total fluidrequired, 4.7L, maybe given IV over 24 hours

at the rate of 200ml/hr.

Deepak Madhu

Case 6



A 60-year-old man has received 10

ampules of sodium bicarbonateover a period of six hours duringresuscitation after recurrentcardiac arrest. He is stuporous andis undergoing mechanicalventilation..

Deepak Madhu



His blood pressure is 138/86 mm

Hg, and peripheral edema (+++)is present. The serum sodiumconcentration is 156 mmol perliter, the body weight is 85 kg, andthe urinary output is 30 ml perhour. How will you proceed tomanage this patient?Deepak Madhu



The patient has hyponatremia due tohypertonic sodium gain and itscorrection requires excess sodium andwater to be excreted.

The administration of furosemide along

with electrolyte free water will berequired.

The estimated TBW =0.6*85 = 51LDeepak Madhu



The retention of 1 L of 5%D is expected todecrease S.Na levels by 3mEq/L and 2L

maybe infused over 8 hours. The patientsvolume status and clinical status should beclosely watched. The correction will beopposed by hypotonic renal and extrarenal

loss. Allowance for ongoing fluid but notsodium loss may also be taken into account.

Deepak Madhu

Complications of hypo/hypernatremia



Rapid overcorrection of

hyponatremia and hypernatremiacan result in osmotic demyelinationand cerebral oedema respectively.

Rapid transcellular shift of water canresult in cellular damage,particularly in the CNS

hypo/hypernatremia

Deepak Madhu



As an initial compensatory

mechanism to preserve cellvolume, there is rapid shift of sodium , potassium, chloride andwater out of the cells inhyponatremia and into the cells inhypernatremia.

Deepak Madhu



After 48 – 72 hours, a slower

adaptive phase takes effect.Cells mobilize organic osmolytes,comprised mostly of amino acids,

to continue efforts to maintainnormal cellular volume

Deepak Madhu



The initial and gradual flux of ions

help maintain normal cellularvolume.

Excessively rapid correction of

hypo and hypernatremia can resultin extreme cellular volumechanges and cellular damage

Deepak Madhu

Click to edit Master text stylesS d l l



Second level●

Third level● Fourth level

● Fifth level

Deepak Madhu

Osmotic demyelinationsyndrome



Occurs when water moves too

rapidly out of brain cells duringadministration of relativelyhypertonic saline solutions.

Classically described in the pons,this has also been described inother parts of the brain also

syndrome

Deepak Madhu

ODS



These patients classically present

with deteriorating mental statusand progressive neurologicaldeficits, such as pseudobulbarpalsies and spastic quadriparesis,after a transient period of improvement with fluidadministration.Deepak Madhu

ODS



ODS typically occurs 1 to 6 days

after treatment. It is associatedwith dismal prognosis and has noeffective treatment.

Chronic alcoholism andmalnutrition have also beenassoiciated with ODS.

Deepak Madhu



Thank You

mia and hypernatremia-deepak madhu

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