Hyponatraemia

Dr Samir Sahu

Sr Consultant

Critical Care & Pulmonology Apollo Hospitals, Bhubaneswar

• Definition:– Commonly defined as a serum sodium concentration

135 meq/L

– Hyponatremia represents a relative excess of water in relation to sodium.

• Epidemiology:– Frequency

• Hyponatremia is the most common

electrolyte disorder• incidence of approximately 1%• prevalence of approximately 2.5%• surgical ward, approximately 4.4%• 30% of patients treated in the intensive care unit• 15 to 22% in tertiary care setting

• Epidemiology Cont.

– Mortality/Morbidity• Acute hyponatremia (developing over 48 h or less) are

subject to more severe degrees of cerebral edema

– sodium level is less than 105 mEq/L, the mortality is over 50%

• Chronic hyponatremia(developing over more than 48 h) experience milder degrees of cerebral edema

– Brainstem herniation has not been observed in patients with chronic hyponatremia

Normal Water Metabolism• Na+ metabolism is primarily controlled by renin-

angiotension-aldoserone mechanism• Water is controlled by arginine vasopressin

(ADH)• Hypothalmic osmoreceptors • Osmoreceptors maintain serum osmolality

between 280 – 295 mOsm/kg• Increase of 2% can increase urine osmolality

due to water reabsorption & stimulate thirst. Decrease of 2% cause maximal dilution of urine

Normal Water Metabolism• Baroreceptors in cardiac atria, aorta &

carotid arteries, carotid bodies & area postrema

• Non-osmotic stimulus from CVS requires a change of 10-20% in circulating volume or BP to influence ADH

• ADH production is also stimulated by nausea, hypoxia, hypercapnea, stress, hypoglycaemia, IPPV & diminished by opoids

Pathogenesis• The main factor that contributes to development of

hyponatremia is impaired ability to excrete free water generated in response to ADH excess.

• Hypertonic urinary losses of electrolytes will result in hyponatremia in the absence of fluid administration - thiazide diuretics, cerebral salt wasting

• Excretion of free water will be impaired when there is a marked reduction in GFR, renal hypoperfusion or ADH excess

• ADH increases the permeability of the collecting duct to water, leading to retention of free water.

Pathogenesis

• Hypovolemic and hypervolemic states of ADH excess are usually associated with avid salt and water retention; administration of hypotonic fluids results in dilutional hyponatremia

• In euvolemic states of ADH excess, hyponatremia results from a combination of free water retention and urinary sodium losses due to a natriuresis that preserves volume at the expense of serum sodium

Physiology of vasopressin

PATHOPHYSIOLOGY(cont.)

PathophysiologyPathophysiology

• Types– Hypovolemic hyponatremia– Euvolemic hyponatremia– Hypervolemic hyponatremia– Redistributive hyponatremia– Pseudohyponatremia

• Develops as sodium and free water are lost and/or replaced by inappropriately hypotonic fluids

• Sodium can be lost through renal or non-renal routes

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• Nonrenal loss– GI losses

• Vomiting, Diarrhea, fistulas, pancreatitis– Excessive sweating– Third spacing of fluids

• ascites, peritonitis, pancreatitis, and burns – Cerebral salt-wasting syndrome

• traumatic brain injury, aneurysmal subarachnoid hemorrhage, and intracranial surgery

• Must distinguish from SIADH

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• Renal Loss– Acute or chronic renal

insufficiency– Diuretics

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• Normal sodium stores and a total body excess of free water.– Psychogenic polydipsia, often in psychiatric patients – Administration of hypotonic intravenous or irrigation

fluids in the immediate postoperative period – Administration of hypotonic maintenance intravenous

fluids– Infants who may have been given inappropriate

amounts of free water – Bowel preparation before colonoscopy or colorectal

surgery

• High levels of ADH are secreted intermittently at an abnormally low threshold or continuously despite low osmolality from Post. Pituitary

• Reduced ability to excrete dilute urine <20mq/l• Ingested fluid is retained• Extracellular fluid Expands (hyposm<290)• Mild natruresis by water expansion• Excrete daily ingested Na (Na balance zero)• Plasma osmolality Aldosterone

Hypokalaemia

SIADH - CAUSES

• DRUGS - Thiazides, Frusemide- NSAIDS-Brufen, Piroxican Diclofenac - Narcotic Analgesics -Morphine- Anti-depressant Fluoxetine SSRI- Anti Neoplastic-Vincristine Cis-platin Cyclophospamide- Amiodarone, Carbamazepine

• Pulmonary Diseases Pneumonia, Asthma, Carcinoma.• CNS Dis-CVA, Brain Surg, Head Inj. • Malignancy, Stress.

• Total body sodium increases, and TBW increases to a greater extent.

• Can be renal or non-renal– acute or chronic renal failure

• dysfunctional kidneys are unable to excrete the ingested sodium load

– cirrhosis, – congestive heart failure,– nephrotic syndrome

Clinical Diagnosis of Acute & Chronic Hyponatremia

Symptoms related to degree of Na insufficiency:

ACUTE121-130 mEq/L Nausea, malaise, headache, lethargy, muscle cramps disorientation, restlessness <120 mEq/L Obtundation, seizures, respiratory arrest, coma, death

CHRONIC Usually Asymptomatic / Non-SpecificNausea, fatigue, gait disturbance, forgetfulness, muscle cramps, confusion, lethargy

Thiazides• Hyponatraemia with low doses (12.5-25 mg/day)

• Usually evident within 14 days of onset of therapy, but can occur up to 2 years later.

• More common in women and elderly with low body wt

• Initial volume depletion induced by thiazides can stimulate the release of ADH, susceptible patients appear to have a reduced innate ability to excrete water load. These patients may not have clinical features of volume depletion & can be also classified as euvolaemic hypotonic hyponatraemia.

• Cerebral oedema is extremely rare

• In many of these patients, hyponatraemia is reproducible with a thiazide rechallenge

APPROACH TO CAUSE OF HYPONATRAEMIA

S.Na< 130 Assess ECV

______________________________________

LOW NOR MAL HIGH Ur. Na Urine Na Ur. Na

_______________ _________________ _______________ >20 < 20 > 20 < 20 > 20 <

20 DIURETIC DIARR SIADH PSY POL RENAL F. CCF

ADRENAL Insf RENAL FAIL. PR.DIL Hypothyroidism CIRRHOSIS

MANAGEMENT

LOW ECV-Diarrhoea, Diuresis, Adrenal Insufficiency

Plasma NS 5%DNS RLNa 141 154 154 130K 4.5 - - 4.0

- Rapid correction is necessary in Acute & Severe Hyponatraemia(S.Na<120) where there is severe symptoms-seizure, coma

MANAGEMENT

II. HIGH ECV-Renal Failure CCF, Cirrhosis

• Frusemide induced diuresis till S.Na>120

• ACE inhibitors in CCF-Inhibits ADH directly

• Sometimes Oral Salts & Isotonic Saline may be necessary

HYPONATREMIA - TREATMENT

CHARACTERISTICS OF INFUSATES

Infusate

Infusate Na(meq/L)

Extracellular Fluid

Distribution (%)

5% Sodium chloride in water 855 100

3% Sodium chloride in water 513 100

0.9% Sodium chloride in water 154 100

Ringer’s Lactate solution 130 97

0.45% Sodium chloride in water 77 67

0.2% Sodium chloride in 5% dextrose in water

34 47

5% Dextrose saline 154 100

5% Dextrose in water 0 33

Less severe symptoms – 0.9% Nacl Soln.

(154meq/L)

Severe Symptoms – 3% Nacl

(250ml bottle – 513 meq/L)

HYPONATREMIA- TREATMENT

Normal Saline

• Use of 0.9% saline (308 mOsm/l) alone may make the hyponatraemia worse, depending on the patient's serum and urine osmolality.

• 0.9% saline may be attempted in selected patients with urine osmolality of < 500 mOsm/kg water.

MANAGEMENTNORMAL ECV-SIADH• Free water intake from all sources should be restricted

to less than 1-1.5 l/day• Mild symptoms- Isotonic Saline

- Fluid Restriction (<1500 ml/d)

- Oral Salts-No 5D or free water

Salt therapy is generally contraindicated in patients with hypertension and oedema, as it leads to exacerbation of both conditions

• Severe symptoms - Frusemide diuresis (delivers more dilute urine by inhibiting ADH effect in the collecting tubule) followed by 3% saline infusion.

TREATMENT OF ACUTE HYPONATREMIA

• Patients with symptomatic hyponatremia need aggressive management with 3% NaCl (513 mmol/l, 1026 mOsm/l)

• Patients with severe symptoms such as seizures, respiratory arrest or neurogenic pulmonary edema should receive 100 ml of 3% NaCl as a bolus over 10 min in order to rapidly reverse brain edema.

• Patients with less-severe symptoms, such as headache, nausea, vomiting or lethargy, can be treated via an infusion pump to achieve a correction of 4–8 mmol/l in the first 4 h.

TREATMENT OF ACUTE HYPONATREMIA

• To prevent complications arising from excessive therapy, 3% NaCl should be discontinued when symptoms subside or rise is > 10 mmol/l in 5 hours

• The rate of correction should not exceed 20 mmol/l in the first 48 h, and correction should be to mildly hyponatremic values(120), avoiding normonatremia and hypernatremia in the first 48 h.

• In general, 1 ml/kg body weight of 3% NaCl will increase the serum sodium level by about 1 mmol/l. Continuous infusion of 3% NaCl at a rate of 50–100 ml/h administered over 4 h is usually sufficient to reverse symptoms

CHRONIC HYPONATREMIA

Slow correction

Usually Not > 8meq/L/day

Oral route is better – Salt

NaCl 1gm = 17 meq of Na

If symptomatic –

↑ Plasma Na > 1meq/Lhr then slowly

HYPONATREMIA - TREATMENT

Tolvaptan: Vasopressin Antagonist

Dose & Administration:

•Blocks the V2 receptors in the kidney that mediate the diuretic effect of ADH

Can be administered without regard to meals . The recommended starting dose is 15 mg once daily. Dosage may be increased at intervals ≥24 hr to 30 mg once daily, and to a maximum of 60 mg once daily. No dosage adjustments necessary based on Age/Gender Patients can take water in response to thirst. No dosage adjustments are necessary based on cardiac, hepatic or renal function. Tolvaptan is not recommended in patients with creatinine clearance <10 ml/min.

Tolvaptan: Adverse Effects

ThirstDry mouthFrequent urinationNauseaConstipationLoss of AppetiteFeverWeakness

Tolvaptan:

ContraindicationsndicationsUrgent need to raise serum sodium levels

Inability of the patients to sense or appropriately respond to thirst

HypovolemicConcomitant use with CYP3A

inhibitors.Anuric patients.

Central (Pontine) Myelinolysis• Patients with chronic gradual onset

hyponatraemia are typically asymptomatic because of the brain adaptation to changes in osmolality.

• This adaptation occurs at the expense of loss of intracellular osmolytes, which normally protect the brain from a sudden increase in osmolality of the ECF.

• In these patients, rapid increase in plasma osmolality results in water moving out of neurons, leading to shrinkage of cerebral tissue.

Central (Pontine) Myelinolysis• Central myelinolysis, which was first described in the pons,

but can occur diffusely throughout the brain.

• Neurological deterioration typically develops over several days with fluctuating consciousness, convulsions, hypoventilation and hypotension.

• Eventually, patients may develop pseudobulbar palsy with difficulty in swallowing, inability to speak and quadriparesis.

• Recovery from this syndrome is variable, and many neurological complications are permanent.

• The magnetic resonance imaging (MRI) scans demonstrate the demyelinated lesions 3-4 weeks after the correction of hyponatraemia.

CLASSICAL CASE15.10.99

• GP 72 yrs, M,-COPD, BEP• On Thiazide for oedema feet• Devoloped AcGE & became unconscious• GCS-7, No localized neurological deficit• S.Na-110, S.K-2.9, CT-normal• Stopped thiazide, corrected Hyponatraemia by

isotonic saline and fluid restrictions• Discharged in 5 days

Case

• 10/04/2000• Took Ditide for oedema feet for 5 days• Vomiting-Seizure-Unconscious• Admitted at DHH / given Mannitol suspecting Stroke• GCS-5, no localized deficit• S.Na-101-103-112-119-123• S.K -2.3- 2.3- 3.- 3.0• Urinary Spot Na-96mEq/l• Stopped thiazide, corrected Hyponatraemia by isotonic

saline and fluid restrictions• Discharged in 7 days

2006

• Post cataract operation seizure & drowsiness

• Na 100 mEq/l

• Improved with NS & fluid restriction

HYPONATRAEMIA PRECIPITATING CAUSES

• Elderly Age• - Exaggerated response to ADH release• - Attenuated response to RAS• Fever, Vomiting, Inadequate intake• Salt restriction due to HTN/Oedema• Thiazides, Frusemide.• Fluid replacement with 5D • Mannitol suspecting Stroke.

Thanks for Kind Attention

Hypokalaemia

Potassium Balance

Physiology

Normal a) 98% potassium - Intracellular

(151 meq/L)

b) 2% potassium - E.CF

(3.5 - meq/L)

ICF / ECF = 38;1

Total body content 2500 - 4500 mmol

Potassium Balance

• Total Body Potassium – 45-50 mmol/Kg males, 35-40 mmol/Kg females

• 95% exchangeable

• 90% intracellular

• 2% ECF, 8% bones, 70% skelatal muscles

• Total body content 2500 - 4500 mmol

Potassium Balance

Small loss or gain by cells

Large changes in serum K+

Potassium Balance

Daily K+ intake 1meq/kg/day

50-150- meq/day

Normally - 90% excreted by kidney secretion by CCT

10% excreted through gut

Renal failure GIT losses > 30% sweat

Potassium Balance

Secretion of K+ by cortical collecting Duct

Increases Decreases1. Aldosterone 1. Absence of aldosterone2. High serum K+ level 2. Low serum K+ level3. High urine flow 3. Low urine flow (osmotic diuresis)4. High sodium delivery 4. Low sodium delivery to to CCT CCT

Potassium Shift

Shift from ECF to ICF

• Alkalosis

• Insulin

• B-adrenergics

Shift from ICF to ECF

• Acidosis

• Alfa-agonists

Potassium excretion

1. Renal excretion is the major route of

elimination

2. Filtered load of K+ = 720

GFR x plasma K+ concentration

180 x 4 = 720 mmol/d

3. 90% is reabsorbed in the proximal

convoluted tubule and loop of henle

Hypokalemia

Defined as a plasma K+ concentration

< 3.5 meq/lt

Decreased Redistribution Increasedintake into cells loss. Elderly. Starvation. Total parenteral nutrition

HYPOKALEMIA DUE TOEXCESS POTASSIUMLOSS IN STOOL

PhenolphthaleinSodium polystyrenesulfonate

HYPOKALEMIA DUE TOTRANSCELLULARPOTASSIUM SHIFT

Adrenergic agonistsAdrenalineBronchodilatorsSalbutamol

HYPOKALEMIA DUE TOINCREASED RENALPOTASSIUM LOSS

DiureticsThiazidesMetolazoneFurosemideTorsemideMineralocorticoidsFludrocortisoneSubstances with mineralocorticoid effectsHigh-dose glucocorticoids

TheophyllineInsulin overdose

AminoglycosidesAmphotericin B

Hypokalemia

Normal - 3.5-5 meq /lt

20% of the hospitalized patients have

hypokalemia

75% patients of Hypokalemia - 3-3.5

25% patients of Hypokalemia less than 3 meq/l

Clinical Features

Vary between different individuals

Severity depend on degree of hypokalemia

Asymptomatic >3 meq/lit

Clinical Features

Skeletal - Fatigue- Myalgia- Weakness of lower extremities - Cramps

More severe

Progressive weakness Complete paralysis Rhabdomyolysis

Clinical Features

GI Tract - Nausea, vomiting, constipation,

distension, paralytic ileaus

Renal - Polyuria, Polydipsia

Respiratory - Respiratory Fatigue,

Hypoventilation

(Usually less than 2 meq/l)

Psychiatry – Psychosis, Delirium, Depression,

Physical examination

Hypotension Signs of ileus Bradycardia, Tachycardia Premature ventricular beats, Cardiac arrest Hypoventilation, Respiratory distress Lethargy, Decreased muscular strength Decreased tendon reflexes

Hypokalemia clinical features

Usually Present with serum K+ < 2.5 meq/L With rapid fall of serum K+

(1) Cardiac Predisposition of digoxin toxicity Ventricular irritability Abnormal ECG - T wave flattening

- U wave / ST- Ectopics

Cardiac necrosis

Lab examination »Serum electrolytes »Urine analysis routine»Urine K+» Na+»24 hr urinary K+»Serum Mg»Arterial blood gases»Calcualtion of transtubular Potassium gradient

(TTKG)»Blood sugar»Creatine kinase

Treatment of Hypokalemia

Basic Aim - to avoid life threatening

consequences

No need to correct entire deficit immediately

Treatment of Hypokalemia

Estimation of potassium deficit

Assessment of the physiologic effect

a. Electrocardiography

b. Muscle strength

Speed of potassium repletion

Potassium repletion is rarely an urgent

undertaking.

Always err on the lower side of estimate

to avoid hyperkalemia

Ideal - Administer from mouth over days

to weeks to correct deficits.

Selecting appropriate rate of administration

Mild hypokalemia 3-3.5 mEq/lWell tolerated except patients - on digitalis - severe hepatic disease

No urgent treatment Prevent further lossOral KCl - 60-80 mEq/dayIf loss persistent - 100 mEq/day

Route of administration Oral - Preferred in general if bowel sounds positive.Less chances of hyperkalemia.KCl 15 ml - 1.5 g KCl = 20meq KCl

Intravenous - severe hypokalemia Can not take orallyLife threatening situationsa) Paralysisb) Digitalis toxicity c) arrhythmiad) ECG abnormalitye) hypokalemia - hepatic complaints

Intravenous administration

KCl - 2 meq/ml (10ml )ampoules

1. Do not give more than 40 meq/l by peripheral

vein, 60 meq/l by central vein

2. Prepare KCl in normal saline solution

3. Do not use dextrose, use glucose free

solution

4. Higher concentration can cause irritation,

pain or sclerosis of vein.

Selecting appropriate rate of administration

Severe hypokalemia requiring emergent therapy

1. Patient to go for emergent surgery

2. Known CAD

3. Patient on digitalis

4. Acute MI with Ectopic

can give I/V 5-10 meq over 15-20 min. Repeat as

needed to achieve K+ > 3.0 Meq/l.

Rapid correction is always in ICU with cardiac

monitor.

Correction of severe hypokalemia

1.Rapid correction should only be done in life

threatening situations - rarely

2.Frequent potassium estimation 4-6 hr

continuous ECG monitoring

3.Concentrated solutions should contain limited

amount of potassium per container.

Correction of associated fluid and electrolyte disorders

Potassium depletion is rarely an isolated

phenomenon

Correct - Volume, Acid base equilibrium

Metabolic alkalosis

Magnesium

Hypophosphatemia

Correction of hypomagnesemia

• Hypomagnesemia

- Renal potassium wasting

- Refractoriness to potassium

replacement

- Unexplained hypokalemia always look

for Hypomagnesemia

Hypokalemia

Elimination of the cause of potassium loss

- Eliminate cause (eg. Diarrhea ) will repair

potassium deficit from diet (50-150 mmol/day)

- Spontaneous recovery, removal of tumors

- Alkalotic patient - dietary low chloride, potassium

not enough

-Correct kaliureteric mechanism

Primary aldosteronism - K+ sparing diuretic

- TTKG

Hypokalaemic Periodic Paralysis

• Autosomal-dominant

• Ion channels in muscle sarcolema

• Adolescence

• Transcellular shift

• Needs K+ replacement

Increased Renal Loss: increase mineralocorticoid effect

• Conn Syndrome – increase aldosterone production

• Cushings Syndrome – generalized adrenal hyperplasia

• Congenital Adrenal hyperplasia

Increased Renal Loss

• Increased delivery of Na+ to distal segment

THANK YOU