Approach to a Patient with Hyponatremia

Speaker: Dr Sushant Wattal Chairperson: Dr Sanjeev Kumar

HYPONATREMIA: Plan for Discussion

Introduction Frequency Age and Sex predisposition Physiology & Pathophysiology Types And Causes Clinical Approach Management Take Home Messages

Introduction

Hyponatremia “decrease in serum sodium conc. < 135 mmol/L”. Normal level is 135-145 mmol/l .

Hyponatremia represents relative excess of water in relation to sodium.

Whereas hypernatremia always denotes: hypertonicity hyponatremia can be associated with low, normal or high tonicity. Serum sodium and serum osmolarity are regulated by stimulation of thirst , secretion of antidiuretic hormone(ADH) and renal handling of filtered sodium.

Frequency

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 unitHyponatremia’s prevalence is lower in the ambulatory

setting.

Age and Sex Predisposition

Infants fed tap water in an effort to treat gastroenritis. Infants fed dilute formula . Elderly patients with diminished sense of thirst,especially when

physical infirmity limits independent access to food & drink. More common in elderly persons due to increased incidence of

comorbid conditions(e.g. cardiac, hepatic or renal failure) No sex predilection exists. However more likely to occur in

young women>men.

Physiology

Physiology contd.

Physiology contd.

Secretion of ADH

1. Synthesized by the neuroendocrine cells in the supraoptic and paraventricular nuclei of the hypothalamus

2. Triggers:–Osmolality of body fluids

»A change of about 1%–Volume and pressure of the vascular system

3. Increases the permeability of the collecting duct to water and urea

Physiology contd.

Renin-angiotensin-aldosterone:

1. Renin– Stimuli are perfusion pressure, sympathetic activity, and NaCl delivery to the

macula densa– Increase in NaCl delivery to the macula the GFR by decrease in the renin

secretion2. Aldosterone

– Reduces NaCl excretion by stimulating its reabsorption » Ascending loop of Henle» Distal tubule» Collecting duct

Renal handling of Na and Water

Pathophysiology

Types of Hyponatremia:

Hypovolemic Hyponatremia Euvolemic Hyponatremia Hypervolemic Hyponatremia Redistributive Hyponatremia Pseudohyponatremia Low sodium hyponatremia Acute hyponatremia Chronic hyponatremia

Hypovolemic Hyponatremia

Hypovolemic Hyponatremia develops as sodium and free water are lost and replaced by Inappropriately hypotonic fluids (tap water, half-normal

saline or dextrose in water).Total body water (TBW) decreases. But Total

body sodium decreases to a greater extent.Extracellular fluid (ECF) volume is decreased which

stimulates hypothalamic thirst center and vasopressin release causing free water accumulation.

Causes of Hypovolemic Hyponatremia

Renal Loss:

Acute or Chronic Renal Insufficiency, in which patient may be unable to excrete adequate amounts of free water.

Salt losing Nephropathies in which there is impaired renal tubular function; causes- reflux nephropathy, medullary cystic disease, interstitial nephropathies, post obstructive uropathy and the recovery phase of acute tubular necrosis.

Diuretic excess: Thiazide diuretics more than loop diuretics.

Mineralocorticoid Deficiency due to primary adrenal insufficiency and other causes of hypoaldosteronism leads to hyponatremia and hyperkalemia

Renal losses contd. Increased excretion of an osmotically active non

reabsorbable solute -glycosuria, ketonuria (starvation, diabetic or alcoholic ketoacidosis) and bicarbonaturia (in renal tubular acidosis or metabolic alkalosis ).

Cerebral salt-wasting syndrome Inappropriate renal natriuresis in association with traumatic

brain injury, aneurysmal subarachnoid hemorrhage, meningitis, encephalitis and intracranial surgery

Hypovolemic hyponatremia contd.

Nonrenal lossGI losses Vomiting, Diarrhea, fistulas, pancreatitis

Excessive sweatingThird spacing of fluids ascites, peritonitis, pancreatitis, and burns

Causes of Euvolemic Hyponatremia1. Total body water increases while total body sodium remains

normal.2. In moderate to severe Hypothyroidism due to decreased cardiac

output and GFR and increased vasopressin secretion in response to hemodynamic stimuli.

3. Secondary adrenal insufficiency due to pituitary causes - glucocorticoid deficiency resulting in euvolemic hyponatremia due to the loss of negative feedback on release of AVP release from posterior pituitary exerted by Glucocorticoids.

4. Syndrome of inappropriate anti diuresis (SIAD)

SIAD1. Most common cause of euvolemic hyponatremia2. Due to the non physiologic release of vasopressin from

posterior pituitary or an ectopic source.3. Pulmonary Disorders- pneumonia, Tuberculosis,

Aspergillosis, Asthma, Cystic fibrosis ,Pulmonary Abcess, Respiratory Failure associated with positive pressure breathing

4. Disorders of the Central Nervous System-Encephalitis, Meningitis, Head Trauma, Brain Abcess, Brain tumors, CVA ,Peripheral Neuropathy, Subarachnoid Hge, Guillain Barre Syndrome, acute intermittent porphyria.

SIADH Contd.Malignant Diseases- Bronchogenic Ca (small cell), Mesothelioma, Ca Duodenum, pancreas, stomach, bladder, ureter, prostateDrugs- SSRI, Tricyclic Antidepressants, Carbamezepine,

vincristine, chlorpropamide, Cyclophosphamide, Ifosfamide , desmopressin, oxytocin, MDMA(Ecstasy), Narcotics, NSAIDS, Antipsychotic drugs.

Other causes- Hereditary(gain of function mutations in V2 receptors),endurance exercise, general anesthesia ,HIV, pain, stress.

Causes of Hypervolemic HyponatremiaTotal Body sodium increases but Total Body Water increases

to a greater extent due to stimulation of thirst and release of vasopressin caused by reduced effective circulating volume.

The ECF volume increases markedly with the presence of oedema.

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, or nephrotic syndrome

Redistributive Hyponatremia Is caused by an increase in concentration of solute that is largely restricted

to ECF compartment. Water shifts from the intracellular to the extracellular compartment,

with a resultant dilution of sodium. The TBW and total body sodium are unchanged.

This condition occurs with Hyperglycemia and administration of Mannitol.

Plasma Na falls by 1.6-2.4 mM for every 100 mg/dl rise in plasma glucose.

PseudohyponatremiaOccurs as a result of a decrease in aqueous portion

of plasma. The TBW and total body sodium are unchanged. hypertriglyceridemiamultiple myeloma

Causes of Acute Hyponatremia

Postoperative: premenopausal womenHypotonic fluids in settings of increased vasopressinGlycine irrigation: TURP , uterine surgeryRecent institution of thiazidesPolydypsiaMDMA –methylenedioxymethamphetamine ingestion

(ECSTASY)

Low salt intake and Hyponatremia

1. Occurs in alcoholics whose sole nutrient is beer, hence labelled as “beer protamania”.

2. Also seen in non alcoholic patients with highly restricted solute intake e.g. extreme vegetarian diets.

3. The fundamental abnormality is the inadequate intake of solutes; the reduced urinary solute excretion limits water excretion so that hyponatremia ensues after modest polydypsia.

4. The ability to excrete a free water load is thus a function of urinary solute excretion.

5. Urine osmolality is <100 mosm/kg with a urine Na <10-20mM.

Clinical Approach

HistoryPhysical examination with attention to the

patient’s extracellular fluid volume statusLaboratory measurementsManagement

Symptoms

Water movement down the osmotic gradient from hypotonic ECF to ICF causes significant hyponatremia presenting with non specific symptoms attributable to cerebral oedema. Most patients with a serum sodium concentration > 125 mEq/L are

asymptomatic Patients with acutely developing hyponatremia are typically

symptomatic at a level of approximately 120 mEq/LSymptoms include anorexia, nausea and vomiting, decreased

concentration, confusion, lethargy, agitation, headache, seizures.

Physical Examination

Most findings neurologic in origin.Level of alertness : alert to comatose. Variable degrees of cognitive impairment e.g. Difficulty in short term

recall, disorientation to time, place and person, frank confusion or depression.

Focal or generalised seizures .Signs due to brainstem herniation: coma, fixed unilateral, dilated pupil;

decorticate or decerebrate posturing;sudden severe hypertension and respiratory arrest.

Examination contd.

In addition patients may exhibit signs of hypo/hypervolemia .Dry mucous membranes, tachycardia, diminished skin turgor and

orthostasis suggest hypovolemic hyponatremia due to excessive loss of body fluids and replacement with inappropriately dilute fluids.

Pulmonary rales, S3 gallop, jugular venous distention, peripheral oedema or ascites suggest hypervolemic hyponatremia due to excess retention of sodium and free water(i.e. cirrhosis, nephrotic syndrome, congestive heart failure).

Non specific signs : muscle weakness and cramping. Rhabdomyolysis is an occasional consequence and should be considered in patients with muscle pain or tenderness.

Laboratory tests 1. Serum osmolality, urine osmolality or urine specific

gravity.2. Urine levels of sodium and creatinine and calculation

of fractional excretion of sodium; serum levels of potassium, chloride, bicarbonate.

3. Serum levels of glucose, urea, creatinine, total proteins, triglyceride and uric acid.

4. Serum levels of thyroid stimulating hormone and cortisol.

Seum Sodium<135meq/l

Serum osmolality>290mosm/kg

Serum osmolality<275

Serum osmolality275-290

Hyperglycemia,Mannitol

Hyperproteinemia,Hyperlipidemia

Urine osmolality

<100 mosm/kgPsychogenic

polydypsia, beer protamania, reset

osmostat

>100mosm/kg-True Hyponatremia

True Hyponatremia

ECF VOLUME

Hypovolemia Euvolemia Hypervolemia

Urine osmolality>500mosm/kg

YESSyndrome of

inappropriate ADH

NOHypothyroidism,

Glucocorticoid deficiency

HYPOVOLEMIA

Urine Na>20

Renal losses,Diuretic Excess,

Aldosterone deficiency,Salt losing

nephropathy,Bicarbonaturia in renal

tubular acidosis and metabolic alkalosis,

Ketonuria,osmotic diuresis,

cerebral salt wasting syndrome

Urine Na<20

Extrarenal losses,Vomiting,Diarrhoea,

Third spacing of fluids,Burns,

Pancreatitis,Trauma

HYPERVOLEMIA

Urinary Na>20 Urinary Na<20

Acute or Chronic renal failure

Nephrotic SyndromeLiver Cirrhosis

Congestive Heart Failure

Step wise approach summary

Management

Pre hospital careHyponatremia a hospital based diagnosis, but may exhibit signs of

severe neurologic dysfunction during pre-hospital evaluation and transport.

Establish intravenous access and give supplemental oxygen when lethargy or obtundation.

Administer anticonvulsant therapy for seizures . Seizures secondary to hyponatremia are unlikely to respond, but treatment be given until diagnosis & therapy are available.

Intubate to hyperventilate to reduce intracranial pressure when signs of brainstem herniation (e.g. fixed, unilateral, dilated pupil, decorticate or decerebrate posturing) until definitive therapy.

Avoid hypotonic I/V fluids: may exacerbate cerebral oedema.

Emergency Department Care The ultimate danger is brain stem herniation when sodium levels

<120 meq/l. The source of free water identified and eliminated. Patients with seizures, severe confusion, coma or signs of brain

stem herniation should receive hypertonic (3%) saline to correct serum sodium level towards normal but only enough to arrest the progression of symptoms.

An increase in serum sodium level of 4-6 meq/l is sufficient. Any further correction is dangerous and be avoided unless

necessary to correct continued seizures or other severe CNS abnormality.

Treatment contd. Patients with chronic hyponatremia and severe symptoms(severe confusion,

coma, seizures) should receive hypertonic saline only to raise the serum sodium level by 4-6 meq/l and to arrest seizure .

Regardless of the therapy, serum sodium be monitored and corrected no faster than 10-12 meq/l in the first 24hrs and 18 meq/l in the first 48 hours.

A goal increase of 1.5-2meq/l/hr for 3-4 hours until symptoms resolve but not to exceed 10meq/l in the first 24 hours appears to be safe.

The 3% saline infused at the rate of <0.05ml/kg body wt per min; the effect be monitored every 2 hrs and infusion be stopped when serum sodium increases by 12 meq/l or to 130meq/l, whichever comes first.

Therapeutic lowering of serum sodium with hypotonic fluids and desmopressin (DDAVP) may avert neurologic sequelae in chronic hyponatremia when it is inadvertently corrected too quickly.

Formulas for correcting Hyponatremia

1. Sodium Deficit is calculated as: TBW * (140-serum sodium)2. To estimate the effect of 1 litre of any infusate containing Na+ and

K+ on serum Na+ is : Change in serum Na+= (infusate sodium + infusate potassium)- serum sodium / (Total Body Water +1)1. ΔSNa = {[Na + K]inf − SNa} ÷ (TBW + 1)2. ΔSNa is a change in Serum Na3. [Na + K]inf is infusate Na and K concentration in 1 liter of solution

3. TBW=0.6 body weight for males and 0.5 body weight for females.

Hyponatremia

Infusate Infusate Na+ Infusate K+

5% Saline 855 mmol/L 0

3% 513 mmol/l 0

0.9% Saline 154mmol/l 0

Ringer Lactate 130mmol/l 4

0.45% saline 77mmol/l 0

5% Dextrose 000 0

ExampleIf one wants to correct a Na+= 108 meq/l in a 70 kg man with

hypertonic saline, then the change in serum sodium with 1 L of this fluid will be {(513+0)-108} / (0.6*70+1)= +9.4 meq/L

This means to correct Na+ at rate of 2meq/L/hr, 200 ml/hr of hypertonic saline needs to be given as (2meq/l/hr)/(9.4meq/l)per thousand ml of saline = 200ml/hr approx.

But not to exceed 1000ml [(10meq/l/hr) / 9.4 meq/l per thousand ml of saline] in 24 hours.

Osmotic demyelination syndrome

The syndrome is due to rapid correction or overcorrection of chronic hyponatremia.

Chronic hyponatremia causes efflux of organic osmolytes (creatine,betaine,glutamate,myo-inositol and taurine) from brain cells to reduce the intracellular osmolality and osmotic gradient favouring water entry.

However re-accumulation of these organic osmolytes by brain cells is delayed and not in sync with the correction of hyponatremia,resulting in loss of oligodendrogliocytes and ODS.

Osmotic demyelination syndrome: contd.

Some investigators note that osmotic demyleination may be a form of hypoxic encephalopathy associated with hyponatremia and not a complication of therapy.

Symptoms of osmotic demyelination - dysarthria, dysphagia, diplopia, seizures, altered mental status, quadriparesis (locked in syndrome), hypotension, begin 1-3 days after correction of serum sodium .

Patients with hypokalemia, female gender, malnutrition or history of alcoholism or liver transplant, seem to be particularly prone to develop osmotic demyelination.

Treatment of chronic Hyponatremia

Water deprivation is cornerstone of therapy. The urine:plasma electrolyte ratio(urine Na+urine K/plasma Na) is

indicator of electrolyte free water excretion Patients with ratio >1 require aggressive fluid restriction of <500

ml/day, with ratio 1 need restriction to 500-700ml/day and <1 ratio requires fluid restriction to <1L /day

In hypokalemia potassium replacement increases plasma sodium concentration as plasma sodium is a function of both exchangable Na and exchangable K divided by total body water.

Plasma sodium concentration also responds to an increase in dietary solute intake as it increases the ability to excrete free water.

Chronic Hyponatremia Rx contd.

Patients in whom fluid restriction, potassium replacement and increased dietary solute intake fails may require pharmacological therapy.

SIADH respond to a combination of oral furosemide 20 mg twice a day ; furosemide inhibits the countercurrent mechanism and blunts the urinary concentrating ability while salt tablets counteract diuretic associated natriuresis.

Vasopressin(V2 receptor) antagonists(conivaptan and tolvaptan)are highly effective in treating SIAD and hypervolemic hyponatremia due to heart failure or cirrhosis by increasing free water clearance.

Demeclocycline antagonises the effect of ADH and can also be used, azotemia and photosensitivity being its side effects.

Hypovolemic Hyponatremia

If symptoms are mild to moderate, treat with isotonic saline, monitor serum sodium levels frequently to ensure that serum sodium level increases slowly.

Correcting any K+ deficit ,as occurs, not uncommonly in this type, will further increase plasma sodium.

V2 receptor antagonists are not suitable for hypovolemic causes of hyponatremia, acute hyponatremia, cerebral salt wasting syndrome, psychogenic polydypsia/protamania and others.

Hypervolemic hyponatremia

Treatment consists of restriction of sodium and water intake, correcting K+, promotion of water loss in excess of Na using loop diuretics and correcting the underlying cause.

The vasopressin antagonists conivaptan and tolvaptan are now approved for use in hospitalised patients with hypervolemic hyponatremia, though clinical experience is scant.

Euvolemic hyponatremia

Treatment consists of free water restriction, promoting free water excretion using loop diuretics and correction of the underlying condition causing SIAD.

Conivaptan (vaprisol) given I.V and Oral tablets of tolvaptan(samsca) show promise as effective and well tolerated therapy for SIAD.

Demeclocycline 150-300 mg TDS and Fludracortisone 0.05-0.2 mg BD are also used.

PreventionHyponatremia that is acquired in the hospital is largely

preventable. A defect of water excretion can be present on admission, or it

can worsen or develop during the course of hospitalisation as a result of hypotonic fluids and several anti-diuretic influences (e.g. medications, organ failure and the post-operative state).

The presence of such a defect notwithstanding hyponatremia will not develop as long as the intake of electrolyte free water does not exceed the capacity for water excretion plus insensible losses.

Take Home Messages1. Hyponatremia is a more of a disorder of water balance than

sodium itself.2. Consider hyponatremia in a drowsy patient when cause is

unclear. Always look for it in an unconscious I.C.U patient. Look for offending drugs (diuretics..)

3. Start low-Go slow applies for hypertonic saline treatment.4. Avoid hypertonic saline in asymptomatic patient.5. Free oral water restriction is an important but ignored step in

treatment.6. Monitor renal parameters and daily fluid balance.