HYPONATREMIA: MANAGEMENT PEARLS

"The difficulty lies, not in new ideas but escaping old ones, 

which ramifies, for those brought up with them, 

as most of us has been, into every corner of our minds"

- John Maynard Keynes 

Hyponatremia is defined as serum sodium concentration less than 135 mmol/L.

Biochemical severity of hyponatremia has been described as mild (S. Na of 130-135 mmol/L), moderate (125- 129 mmol/L) and Severe/ profound (125 mmol/L).

Clinical severity of hyponatremia is recognized based on urgency of treatment.

Severe symptoms are the result of cerebral edema and increased intracranial pressure with risk herniation. It manifests as vomiting, seizures, obtundation and cardiorespiratory distress.                      

        

Moderately severe symptoms of hyponatremia are due to mild cerebral edema but no risk of herniation. Clinically it presents as headache, nausea and confusion.

Hyponatremia is classified as acute and chronic depending upon time profile of existence. It takes about 48 hours for cerebral adaptation to place, in response to decreased serum osmolality.

Hyponatremia of less than 48 hours duration is defined as acute hyponatremia. As cerebral adaptation has not taken place, there is higher risk of cerebral edema and raised intracranial pressure with herniation.

Hyponatremia of more than 48 hours duration is defined as chronic hyponatremia. Cerebral adaptive mechanism obviates the risk of cerebral edema but at heightened risk of osmotic demyelination.

Severity of symptoms correlates with rapidity and magnitude of fall in serum sodium concentration.

UNPREDICTABLE CHANGE IN SERUM SODIUM CONCENTRATION:

After treatment of hyponatremia is begin, unpredictable rapid correction and paradoxical fall (desalination) in serum sodium concentration may occur, which should be watched for and prevented or corrected.

Unpredictable Rapid Correction of serum sodium concentration: Renal capacity of excrete electrolyte free water fluctuates markedly once treatment is begin, which results in unpredictable rise in serum sodium concentration.

This results due to interplay of various factors. Serum vasopressin level rises appropriately in various conditions like hypovolemia, pain, anxiety, surgery and drugs. Once these causative factor are removed or treated, serum vasopressin is suppressed and urine output increases. This brisk diuresis in turn leads to rapid rise in serum sodium concentration.

This may be the reason why Androgue- Madius formula underestimated correction of serum sodium.

This is seen in-

·         Hypovolemic hyponatremia, once intravascular volume is optimized,

·         Glucocorticoid deficient patients, when steroid is started,

·         Psychogenic polydipsia and bear potomania, if oral fluids is restricted.

Sudden increased in urine output (more than 100 ml/hour) during treatment is warning sign for this phenomenon. Desmopressin makes excretion of electrolyte free water constant and rise in serum sodium concentration more predictable.

Desmopressin is given as 1-2 microgram intravenous every eight hourly along with 5%DW to replace lost electrolyte free water in urine.

Desalination (paradoxical fall in serum sodium concentration): in isovolemic and hypervolemic hyponatremia where serum vasopressin level is high like SIADH, congestive heart failure, cirrhosis, nephrotic syndrome, infusion of isotonic saline leads to worsening of hyponatremia.

                          

Intermittent boluses of frusemide many prevent this phenomenon by brisk diuresis.

HYPONATREMIA WITH SEVERE SYMPTOMS:

It is a life threatening condition where risk of cerebral edema outweighs the risk of osmotic demyelination syndrome.

Therefore it is justified to rapidly increase serum sodium irrespective of biochemical degree or time (acute or chronic) of hyponatremia.

 Rapidly raising serum osmolality is an urgency to prevent brain herniation.

Observational studies have suggested that rapid increase of 5 mmol/L of serum sodium in the first hour may be sufficient to decrease brain edema and risk of herniation.

In first hour give 2ml/kg of 3% saline (150 ml in 75 kg body weight) over 20 minutes. Measure serum sodium and repeat 3% saline over next 20 minutes till symptoms improve or serum sodium rises by 5 mmol/L in one hour.

If symptoms improve, stop 3% saline and start small volume of isotonic saline. Evaluate cause of hyponatremia and start treatment accordingly.

Send serum sodium at 6 and 12 hours and then daily until serum sodium has stabilized.

If symptoms do not improve, continue 3% saline to achieve 1 mmol/L/hour increase in serum sodium. Stop 3% saline if symptoms improve or serum sodium increases by 10 mmol/L in total or reaches 130 mmol/l.

Evaluate and rule out other causes of symptoms.

Once symptoms improve or limit of sodium rise is achieved, etiology specific treatment should begin.

HYPONATREMIA WITH MODERATELY SEVERE SYMPTOMS:

Moderately severe symptoms are also the result cerebral edema but there is no threat of herniation.  However this risk rises significantly with further fall in serum sodium level.

Weighing the risk of cerebral edema versus osmotic demyelination in these patients is tricky, especially if hyponatremia is chronic. Thus priority is to prevent further fall in serum sodium concentration rather than increasing it.

In acute hyponatremia with a decrease of more than 10 m mol/L, 150 ml of 3% saline should be given over 20 minutes and serum sodium should be rechecked after 4 hours.

Hypovolemic hyponatremia should be treated with isotonic saline to optimize the intravascular volume.

Euvolemic and hypervolemic hyponatremia should be managed with fluid restriction. Isotonic saline with intermittent frusemide may also be used to prevent fall in serum sodium concentration.

ASYMPTOMATIC HYPONATREMIA:

These patients should be evaluated and treated according to etiology.

Intravascular volume should be corrected with isotonic saline in hypotonic hyponatremia.

Fluid restriction with daily intake less than 500 ml of total urine output is the first line management of isovolemic and hypervolemic hyponatremia.

Oral solute like urea and V2 receptor antagonist are the second line treatment of isovolemic and hypervolemic hyponatremia.

RENAL REPLACEMENT THERAPY IN HYPONATREMIA:

RRT in these patients may lead to rapid correction of serum sodium concentration. Fortunately osmotic demyelination is rare in these patients, probably due to uremia. Uremia has been shown to protect against osmotic demyelination in experimental animals.

However rapid correction should be avoided.

Choosing the lowest dialysate sodium concentration, hypotonic fluid, low blood flow, decreased duration of dialysis and CRRT may prevent rapid rise in serum sodium concentration.

RAPID OVER-CORRECTION OF HYPONATREMIA:

All fluids should be stopped, desmopressin 2-4 microgram intravenous should be given along with free water (D5W) @ 3 ml/kg intravenous bolus.

Serum sodium should be checked and D5W is repeated. Desmopressin can be repeated every 8 hourly.

Goal is to decrease serum sodium concentration to 8 mmol/L higher than previous day level.

POINTS NOT TO FORGET:

·        Limit to increase serum sodium is 10 mmol/L in first 24 hour and 8 mmol/L in each of subsequent 24 hours till it rises to 130 mmol/L to prevent osmotic demyelination.

·    Severe symptoms are result of increased intracranial pressure and impending herniation, hence urgency to treat by rapidly increasing serum osmolality.

·       If potassium is being replaced, reduce dose of hypertonic saline as it may lead to rapid correction of serum sodium and osmolality.

·  Sudden increase in urine output during treatment is a warning sign of rapid correction. Desmopressin and D5W should be given to replace lost free water in urine.

·       Infusion of 3% saline @ 1 ml/kg/hr will increase serum sodium by 1 mmol/L/hr, considering 514 mmol L of sodium in one liter of 3% saline.

·     Osmolality of infusing fluid should be higher than that of urine, alas paradoxical worsening of hyponatremia may result by desalination process.

·         Total body water is 50% and 45% of body weight in elderly males and females respectively.

·         Total body water is 60% and 0% of body weight in non-elderly males and females respectively.

REFERENCES:

1.  Clinical practice guidelines on diagnosis and treatment of hyponatremia. European Journal of Endocrinology, 2014.

2.     Treatment of hyponatremia. Seminars in Nephrology 2009.

3.     Management of hyponatremia in the ICU. Chest 2013.

4.     Hyponatremia. NEJM 2000.