Management of hyponatremia.

To recapitulate: what are the common causes of hypotonic hyponatremia? Serum tonicity is defined as the osmolar concentration of solutes that do not readily cross the cell membrane (effective osmoles). Serum sodium levels provide the effective osmoles. Hyponatremia without hypotonicity can occur in patients with hyperglycemia, in patients who have accumulated exogenous effective osmoles, and in patients with pseudohyponatremia caused by extreme hyperlipidemia or hyperproteinemia.

What should you be looking for? A common iatrogenic cause is the use of diuretics; remember hypokalemia may accompany the hyponatremia. Look for advance renal failure when the kidney cannot concentrate the urine and urinary specificity becomes fixed at 1010 or an osmolality between 40 to a 100 mosmol.

When do people tend to drink water without electrolytes? Think of beer drinkers potomania, the tea and toast diet and I have come across a case of strict adherence to the “rice diet”, a fad diet which enjoyed a brief popularity among people who wanted to lose weight in a hurry. The patient concerned was a 65 year old lady who had been on the rice diet for 3 months. She had been prescribed an ARB for her hypertension and when the response was poor, her doctor added a thiazide diuretic. She became disoriented, had nausea and a near-faint and her blood pressure fell down to 80/60 mmHg. She had a serum sodium of 120 mEq/l, her serum albumin was 1.2 gm/dl and serum potassium was 2.8 mEq/l. I have a picture of her sitting in her ICU bed after initial recovery, eating a beef burger and sprinkling extra salt on her fries and into her fresh orange juice. So much for a weight reducing diet!!! A low serum protein from near starvation, the thiazide diuretic and unrestricted water intake were the cause of her problem.

In true volume depletion (hypovolemic hyponatremia), heart failure and cirrhosis (hypervolemic hyponatremia), Addison’s disease urine dilution is impaired because of unsuppressed ADH secretion. Then there SIADH (euvolemic hyponatremia) or the syndrome of inappropriate antidiuretic hormone secretion for which there are many causes such as malignancy, CNS disease etc. The kidney may have abnormal V2 receptors and does not respond to ADH hence there is nephrogenic SIADH. The gene for the V2 receptor is located on the X chromosome, and loss-of-function mutations of the gene are responsible for X-linked nephrogenic diabetes insipidus. Or the osmostat may be reset abnormally as in chronic illness, genetic reset osmostat  (Polymorphisms in the genes encoding the hypothalamic osmoreceptor, transient receptor potential cation channel subfamily V member 4 (TRPV4), may cause mild hyponatremia). The reset osmostat of pregnancy in which human chorionic gonadotropin may be responsible for a reset of serum sodium to as much as 4 mEq/l below physiological levels. In exercise induced hyponatremia marathon runners develop hyponatremia from drinking only water.  A rare syndrome has been described in patients with cerebral disease that mimics all of the findings in the SIADH except that salt wasting is thought to be the primary defect, with the ensuing volume depletion causing a secondary rise in ADH release

Psychogenic polydipsia is a condition in which there is excessive thirst. In a study published in  the Am J Psychiatry. 1979;136(2):221 of 239 hospitalized patients with mental illness it was found that 6.6 percent had a history compatible with compulsive water drinking and that one-half of these had intermittent symptoms of hyponatremia due to transient water retention. It is presumed that a central defect in thirst regulation plays an important role in the pathogenesis of polydipsia.

Normal subjects can excrete more than 400 to 600 mL of urine per hour, a response that is mediated by suppression of ADH secretion and the subsequent formation of a dilute urine with a minimum osmolality between 40 and 100 mosmol/kg.

A thorough history and physical examination looking for the fluid volume status will help immensely with the management. The rapidity of onset of hyponatraemia and the manifesting symptoms will be essential to guide the management.

Investigations and assessment of hyponatremia.

Basic biochemical tests include urine osmolality paired with plasma osmolality, urinary sodium, urine dipstick, urea and electrolytes, plasma glucose, total protein, lipid profile, thyroid function tests and glucocorticoid/mineralocorticoid status.

The initial workup involves measuring plasma osmolality.  If this is normal or high, consider causes like hyperglycaemia, hyperproteinemia ( iatrogenic causes are the administration of IVIG, monoclonal gammopathy) and hyperlipidaemia (triglycerides, cholesterol). In pseudohyponatremia (fictitious hyponatraemia), the non-aqueous portion of plasma is increased due to high protein or triglyceride content. The serum osmolality will be in the normal range and the true sodium value can be obtained if the sample is processed in a blood gas analyser.

In hyperglycaemic hyponatraemia there is a shift of water from the intracellular compartment to the intravascular space due to the osmotic effect of glucose, which causes a translocational hyponatraemia. The effective osmolality is maintained during treatment when free water returns to the intracellular compartment, thereby leading to an improvement in hyponatraemia, as may be seen in the management of DKA, for example. A similar situation arises with the use of irrigation fluids like glycine and mannitol during urological and gynaecological procedures.

Non-hypotonic hyponatraemia does not cause brain oedema and the management varies from hypotonic hyponatraemia (which does cause brain oedema).

Urine osmolality and urine sodium are essential investigations that are often accidentally omitted in the medical unit. A very low urine osmolality (less than 100 mOsm/kg) in the context of intact renal function narrows the diagnosis to primary polydipsia, low solute intake or inappropriate intravenous fluid administration.

A low urine sodium (less than 30 mmol/L) in the context of urine osmolality above 100 mOsm/kg and clinical hypovolaemia is either due to gastrointestinal or third space fluid losses (burns, peritonitis, pancreatitis or fistulas). This requires appropriate fluid replacement, mostly in the form of normal saline. If the patient is found to have expanded extracellular fluid status, i.e. hypervolaemia, it is likely to be due to secondary hyperaldosteronism in the context of liver, cardiac or renal failure. The fluid from the third space needs to be removed or the cause such as intestinal obstruction needs to be treated.

When urine sodium is above 30 mmol/L, exclude diuretic therapy and intravenous saline administration which are common pitfalls encountered in clinical practice. Salt wasting renal disorders, primary adrenal failure and cerebral salt wasting all cause hypovolaemia with high urine sodium and can be worked up with urinalysis, urine protein excretion, synacthen test and exclusion of co-existing cerebral pathology such as subarachnoid haemorrhage or stroke. Interestingly, profound vomiting and dehydration can cause high urine sodium excretion due to renal compensation for the metabolic alkalosis. All these situations frequently require saline administration to address fluid and salt status.

A normal extracellular fluid volume with high urine sodium (above 30 mmol/L) is most likely to be due to SIADH once secondary adrenal insufficiency (normal renin–aldosterone axis) and profound hypothyroidism are excluded. Normal ACTH and renin (should not be elevated) can be tested in addition to synacthen testing to confirm the diagnosis.


Treatment is based on symptoms, clinical volume status and the rapidity of onset of hyponatraemia.

Aggressive intervention is required with acute presentations with severe symptoms such as seizures or obtundation.

150 ml of 3% saline infusion (2 ml/kg body weight) is given over 20 minutes and may be repeated twice if symptoms persist while sodium level is checked urgently at the end of each infusion (by venous blood gas analyser if required). The aim should be to increase plasma sodium by 4–6 mmol/L within an hour, which can reduce the intracranial pressure by 50%. This rise is adequate to stop active seizures and reverse impending brain herniation.

Moderate symptoms of acute hyponatraemia such as confusion, nausea and agitation can be treated with 3% saline at 0.5–2 ml/kg/h (e.g. 150 ml) over 60 minutes, once only.

It is estimated that 1 ml of 3% saline/kg body weight will increase plasma sodium by around 1 mmol/L in the absence of aquaresis. It is preferable to use 3% saline via a central venous access (risk of extravasation necrosis is minimal contrary to popular belief) though it may be given through a well-sited large bore peripheral venous cannula in emergencies. 250 ml of 1.8% saline (over 30 minutes) can be used as an alternative, where access to 3% saline is difficult, and this can be given safely through a peripheral cannula.

Chronic symptoms

Patients presenting with minimal symptoms or no clear onset of hyponatraemia should be managed by aiming for an increment of 8–10 mmol/L of sodium in the first 24 hours and of not more than 8 mmol/L per day thereafter, until the sodium is above 130 mmol/L. This should improve symptoms adequately whilst avoiding osmotic demyelination.

This should be supported by reviewing medications, fluid balance and identifying the aetiology. When the duration of onset is unclear, hyponatraemia should be presumed to be chronic; these patients are more at risk of osmotic demyelination with correction and should be managed cautiously. The options of management include fluid restriction, sodium chloride tablets, furosemide, desmopressin and vasopressin antagonists. Situations of low solute intake should be managed with better nutrition and dietary salt content.

Syndrome of inappropriate antidiuretic hormone (SIADH)

SIADH is a diagnosis of exclusion. It is defined as low plasma osmolality with hyponatraemia in the presence of urine osmolality above 100 mOsm/kg, with no evidence of fluid overload or dehydration and normal adrenal, thyroid and pituitary functions. SIADH is a common cause of hyponatraemia caused by a variety of infections (mainly respiratory), tumours, central nervous system disorders, pain and drugs.

The first step in managing chronic hyponatraemia due to SIADH is withholding any culprit medications. A chest X-ray is essential as this can be helpful in identifying the aetiology (such as pneumonia or lung cancer). Further imaging to look for the aetiology with computed tomography should be guided by the clinical picture.

SIADH is managed with fluid restriction alone if there are no or minimal symptoms. The aim is to reduce fluid intake by 500 ml from the previous day’s urine output, aiming for an intake of 1 litre per day if possible. It is advisable to improve salt and protein intake in those with low solute intake. The response to fluid restriction is usually slow and limited. Adherence to fluid restriction is difficult in some patient groups. It is ineffective when urine osmolality is above 500 mOsm/kg and a rise in plasma sodium of less than 2 mmol/day after 48 hours suggests failure of response. SIADH should not be treated with isotonic solutions as it leads to net retention of electrolyte-free water.

Demeclocycline causes nephrogenic diabetes insipidus and is effective when given at 600 to 1200 mg per day in divided doses and it takes 3 to 4 days to be effective.  It has been effective in treating SIADH in some patients when fluid restriction has failed. Careful monitoring of renal function is required as it can cause reversible azotaemia especially in patients with cirrhosis. Sodium chloride tablets can be used to increase salt intake which can be added to furosemide when patients already have high osmolality in the urine. Oral urea preparations have been advocated in the current European guidelines, though this is not available in the UK. Vaptans are V2-receptor antagonists licensed for use in euvolaemic hyponatraemia in Europe. These are for use by specialists only with very strict and close monitoring as there is high risk of rapid rise in sodium following initiation.

Further reading

Biswas, M, Davies, JS. Hyponatremia in clinical practicePostgrad Med J. 2007;83:373–78.

Reynolds, RM, Seckl, JR. Hyponatraemia for the clinical endocrinologistClin Endcrinol. 2005;63:366–74.

Spasovski, G. et alClinical practice guideline: diagnosis and treatment of hyponatraemiaEur J Endocrinol. 2014;170(3):G1–47.

Sterns, RH. Disorders of plasma sodium- causes, consequences and correctionN Engl J Med. 2015;372:55–65.

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I am a Professor of Medicine and a Nephrologist. Having served in the Army Medical College, Pakistan Army for 27 years I eventually became the Dean and Principal of the Bahria University Medical and Dental College Karachi from where I retired in 2016. My passion is teaching and mentoring young doctors. I am associated with the College of Physicians and Surgeons Pakistan as a Fellow and an examiner. I find that many young doctors make mistakes because they do not understand how they should answer questions; basically they do not understand why a question is being asked. My aim is to help them process the information they acquire as part of their education to answer questions, pass examinations and to best take care of patients without supervision of a consultant. Read my blog, interact and ask questions so that I can help you more.

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