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LogoWarningBox4.pngRapid correction of hyponatraemia can lead to significant and severe neurological problems such as central pontine myelinosis. Much hyponatraemia is subacute or chronic. However acute severe hyponatraemia (< 48 hours) will need rapid correction and may be an indication for I.T.U. admission. It is a reasonable assumption that senior doctors will be interested in the presence of a severely hyponatraemic patient in their beds. Please seek senior help if unsure how to proceed.



Serum osmolality is tightly regulated and is normally between 275 and 290 mmol/l (mOsm/kg). Expected serum osmolality (mmol/l) is = (2 X Na) + (glucose) + (urea). The sodium (Na) content of the blood will be adjusted by physiological mechanisms, mainly depending upon antidiuretic hormone and renal tubular mechanisms to maintain this value. You need to understand this physiology to manage any electrolyte disturbance optimally. There is much poor understanding and accordingly you are referred to the review references to this article, and subsequent correspondence for the finer points.[1] [2] [3]. Common errors are a failure to consider acute hyponatraemia, missing modest degree of extracellular fluid contraction because of a belief that this can be detected by physical examination and routine laboratory data, and diagnosing the syndrome of inappropriate secretion of antidiuretic hormone prior to excluding other causes of hyponatraemia [4].

  • Mild Hyponatraemia is a serum [Na+] of less than 130 mmol/litre (values between 130 to 135 mmol/l appear to be tolerated well but note below)
    • Independent predictor of deaths and myocardial infarction in middle-aged and elderly community subjects not on diuretics - Na 129 to 134 hazard ratio 8.00 (95% CI, 3.04-21.0) Na 135 to 137 hazard ratio 3.2 (95% CI, 1.8-5.7)[5].
  • Significant Hyponatraemia is a serum [Na+] of less than 125 mmol/litre especially with symptoms
    • In unselected acute medical patients it is associated with an increased mortality (unadjusted OR of death within 30 days of admission 3.4 (95% CI 2.6-4.4)[6]
  • Severe Hyponatraemia is a serum [Na+] of less than 115 mmol/litre especially with symptoms


LogoKeyPointsBox.pngVague symptoms like weakness or falls justify checking electrolyte amongst other tests


  • Falls - increased risk starts at Na of 128mmol/l[7]
  • Anorexia, nausea, vomiting
  • Tiredness, lethargy
  • Reducing consciousness
  • Fits and confusion
  • Coma and death
LogoKeyPointsBox.pngThe following symptoms and signs have proved to be reversible in patients presenting with hyponatraemia[8]:


Almost any focal CNS sign can be mimicked by the effects of a low sodium on the CNS. Another catch is that rhabdomyolysis can happen with acute hyponatraemia and a subacute myopathy with only borderline rise in CK has been described in the elderly[9].

Subacute Features

These were defined by a study reported in 1936[10]. A 11 day fall in deliberately salt deprived healthy volunteers of sodium from 147 to 131mmol/l resulted in:

  • Loss of flavour and taste
  • Nocturnal diuresis
  • Nightmares
  • Nausea and abdominal discomfort....
  • Mild cramps
  • Mild breathlessness progressing to distress on the least exertion
  • Fatigue progressing to general exhaustion
  • Apathy and mental processes dulled
  • Blood pressure preserved

Recovery on salt added to diet was within hours


Hyponatraemia can be due to one of the following or a mixture of both.

Relative loss of sodium

  1. Diarrhoea vomiting
  2. Fistula
  3. Burns
  4. Addison's disease
  5. Small bowel obstruction
  6. Subarachnoid haemorrhage causes a natriuresis
  7. Tubulointerstitial disease and other Renal disease
  8. Excessive diuretics

Relative excess of water

  1. Syndrome of inappropriate antidiuretic hormone release (SIADH)
  2. Excessive IV fluids eg 5% dextrose
  3. Excessive water intake eg. with Ectascy [MDMA], Psychogenic polydipsia
  4. Cardiac failure, renal failure, nephrotic syndrome, liver failure
  5. Severe hypothyroidism (The association has been claimed by some to be false)[11]


  • Unrepresentative sample
    • Sample taken from drip arm
  • Total serum osmolarity normal
    • High circulating lipids/protein or other compound such as ethanol/mannitol
    • Severe hyperglycaemia


The causes are quite broad but can be quickly narrowed down.

Hepatic disease is the commonest cause in those less than 65 and iatrogenesis in those over 65 years.

  1. Determine from history or previous lab results the duration of the hyponatraemia
  2. Assess Airway Breathing circulation
  3. Assess Glasgow coma scale
  4. Assess Pulse and Blood pressure looking for signs of volume depletion and dehydration
  5. Assess medications (many can cause this and only some of the most common are listed below),
    1. Thiazide diuretics, such as bendroflumethiazide, indapamide, metolazone
    2. Carbamazepine
    3. Proton pump inhibitors such as omeprazole, lansoprazole, pantoprazole (important as under emphasised in BNF)
    4. All antidepressants, most commonly SSRIs such as citalopram, fluoxetine. paroxetine, sertraline
    5. More rarely, ACE inhibitors or angiotensin II receptor blockers(all at high relative doses due to how they work!), sulphonylureas (chlorpropamide, glimepiride, glipizide, tolbutamide), amiloride (the catch is that the ignorant blame the loop diuretic), NSAIDs, opiates, amiodarone, antidiuretic hormone analogues (vasopressin, desmopressin, terlipressin- how they work again !), amphotericin, haloperidol, Ecstasy and other amphetamines. In the elderly there is also an association with digoxin and lactulose use.
  • Initial Investigations
    1. Look at the potassium (which should be available, but is often overlooked).
    2. Serum osmolality (to confirm that we have true hyponatraemia- pseudonatraemia from alcohol or other cause is common)
    3. Urinary osmolality - With impairment of water secretion most have urine osmolality of > 200 mOsm/kg (mmol/l). Those < 100 mOsm/kg are appropriately excreting very dilute urine, as occurs in primary polydipsia and resetting of the osmostat.
    4. Urinary Sodium - the usual response to dehydration is to retain sodium with urinary [Na+] < 20 mmol/l however this assumes normal renal function and mineralocorticoid function. This suggests which of the mechanisms is predominant. Urinary [Na+] > 30 mmol/l suggests euvolaemia and endocrine causes. In usual internal medical practice < 30 mmol/l suggests hypovolaemic hyponatremia, with the major exceptions of fluid overload due to glucose containing iv fluids and bladder irrigation surgery (in particularly this last case sodium excretion is usually high).
  • Investigations for Chronic and Subacute presentations without other explanation
    1. Chest X-ray (Bronchial neoplasm)
    2. U/S abdomen (Hepatic disease and hydronephrosis)
    3. Short synACTHen test (Addison's disease)
    4. Thyroid function test (although advanced myxoedema should have been suspected on other grounds, and the association is weak)
  • Directed investigations
    1. In patients on diuretics as the urinary sodium excretion can be more than 30 mmol/liter the fractional excretion of uric acid (>12%) may distinguish the etiology of hyponatremia[12] Urate is also useful to suggest ISADH as it tends to be low, as is anion gap[13]. Renin and aldosterone levels along with fractional secretion phosphate can help distinguish difficult differential diagnoses such as the rarer renal or cerebral salt loss[14].


The main issue is that poor and illogical management, which is amazingly common (in up to a third of cases) in acute hospitals, and has been shown to be associated with a doubling in the mortality rate. [15]. Naturally poor assessment and management go together.

LogoKeyPointsBox.pngA possible misconception is that isotonic saline is a reasonable treatment for ISADH. This is not the case if urine osmolatity is greater than about 530 mOsm/kg. Then desalination will take place as the 300mOsm/l odd of 'normal' saline actually represents a source of free water relative to the total anions (Na and K) excreted in the urine[16].

Treatment depends on the cause and hyponatraemia is an independent predictor of deaths and myocardial infarction in middle-aged and elderly community subjects. Risk depends upon presentation, so that an acute presentation with rapid change in plasma sodium may produce severe symptoms needing active and aggressive therapy. There is good evidence that correcting hyponatraemia in some subgroups of hospitalised patients, such as those with heart failure reduces long term mortality[17]. Such therapy in a chronic presentation with the same plasma sodium is extremely dangerous. Broadly hypertonic saline will only be indicated when acute symptomatic hyponatraemia has occurred over a period of less than 48 hours. Some use 8.4% sodium bicarbonate initially in severe hypnotraemia after TURP which has the advantage of being more readily available but introduces potential acid base considerations into management.[18] The initial rate of sodium correction with hypertonic saline should not normally exceed 1 mmol/l per hour in such cases to a maximium of 12mmol/l in first 24 hours. Infusion rates below these maxima are safer unless symptoms are severe where cerberal oedema from too slow initial correction is the feared complication. Low dose frusemide may be indicated (depending upon cause). The degree of monitoring (and nature of complications) are such that I.T.U. management should be considered where such correction is indicated. In chronic cases pontine demylination generally does not occur in patients whose low sodium is corrected at less than 1 mmol/l in first 24 hours and a total of 1.4 mmol/l in first 48 hours.

  1. Withdraw identified cause(s)
  2. Sodium deficiency will require sodium and volume replacement cautiously. Urea has been used in some countries (Belgium) as there is some evidence that it will reduce osmotic demylination and allow more rapid correction.
  3. Correct potassium deficiency (the nephron reabsorbs sodium by exchange with potassium or hydrogen ions!)
  4. Water excess will require water restriction
  5. Demeclocycline in persistent cases due to inappropriate secretion ADH
  6. Vaptans such as conivaptan, satavaptan and tolvaptan are already being tried outside indications their vasopressin receptor antagonist properties would predict the most effectiveness. They are likely to evolve to be a treatment of choice for euvolemic and hypervolemic hyponatraemia.


Poor prognosis with severe hyponatremia in inpatients is suggested by the presence of symptoms of hyponatraemia, sepsis, and respiratory failure.

Evidence base gaps

We really do not know yet outcome of correct correction of hyponatraemia in many patients. Indeed this could be very hard to study as so much patient management might be suboptimal compared to literature recommendations. Thus it is unclear as to when as a compromise plasma sodium makes community management safest course rather than hospitalisation. Indeed any arbitary hyponatraemia level outside the normal range can not be chosen as the acuteness of the change/correction is also to be factored in.

Case Studies

Case 1

A 73 year old man is seen post inguinal hernia repair on the surgical wards. His pulse is 89 and BP 167/89. He is drowsy. His [Na+] is 117. He has received 6 Litres of 5% glucose and 1 litre of 0.9% saline in the past 48 hours. He has been too drowsy to eat and has vomited several times.

  • What would your management plan be ?

Case 2

A 37 year old lady is seen in outpatients referred with dizziness, tiredness and apathy. BP 97/60. P 100. Na+ = 125, K+ = 5.1.

  • What would your management be ?

Case 3

A 87 year old lady with hypertension is seen in outpatients referred with dizziness, tiredness and apathy. BP 122/60 lying and 115/70 standing. P 100. Na+ = 125, K+ = 3.3. She takes aspirin, bendrofluazide and atenolol.

  • What would your management be?

Case 4

An 80 year old lady in a residential home taking among other drugs thyroxine for hypothyroidism and ramipril and frusemide which have provided effective relief of her periodically wet lungs has a routine measurement revealing Na+ = 123.

  • What would your management be?


  1. Reynolds RM, Padfield PL, Seckl JR. Disorders of sodium balance. BMJ. 2006 ; 332(7543):702-5
  2. Adrogue HJ, Madias NE. Hyponatremia. N Engl J Med. 2000 ;342(21):1581-9.
  3. Kumar S, Berl T. Sodium. Lancet. 1998;352(9123):220-8
  4. Hoorn EJ, Halperin ML, Zietse R. Diagnostic approach to a patient with hyponatraemia: traditional versus physiology-based options. QJM. 2005 Jul;98(7):529-40
  5. Sajadieh A, Binici Z, Mouridsen MR, Nielsen OW, Hansen JF, Haugaard SB. Mild hyponatremia carries a poor prognosis in community subjects. The American journal of medicine. 2009 Jul; 122(7):679-86.(Link to article – subscription may be required.)
  6. Whelan B, Bennett K, O'Riordan D, Silke B. Serum sodium as a risk factor for in-hospital mortality in acute unselected general medical patients. QJM : monthly journal of the Association of Physicians. 2009 Mar; 102(3):175-82.(Link to article – subscription may be required.)
  7. Decaux G. Is asymptomatic hyponatremia really asymptomatic? The American journal of medicine. 2006 Jul; 119(7 Suppl 1):S79-82.(Link to article – subscription may be required.)
  8. Weiner M, Epstein FH. Signs and symptoms of electrolyte disorders. The Yale journal of biology and medicine. 1970 Oct; 43(2):76-109.
  9. Sasaki M, Yuzawa M, Saito T, Ikoma A, Tamemoto H, Kawakami M, Ishikawa SE. Clinical and laboratory features of hyponatremia-induced myopathy. Clinical and experimental nephrology. 2007 Dec; 11(4):283-6.(Link to article – subscription may be required.)
  10. McCance RA. Experimental sodium chloride deficiency in man. Proc. roy. Soc. B, 1936,119, 245
  11. Croal BL, Blake AM, Johnston J, Glen AC, O'Reilly DS. Absence of relation between hyponatraemia and hypothyroidism. Lancet. 1997;350(9088):1402
  12. Fenske W, Störk S, Koschker AC, Blechschmidt A, Lorenz D, Wortmann S, Allolio B. Value of fractional uric acid excretion in differential diagnosis of hyponatremic patients on diuretics. The Journal of clinical endocrinology and metabolism. 2008 Aug; 93(8):2991-7.(Link to article – subscription may be required.)
  13. Decaux G, Musch W. Clinical laboratory evaluation of the syndrome of inappropriate secretion of antidiuretic hormone. Clinical journal of the American Society of Nephrology : CJASN. 2008 Jul; 3(4):1175-84.(Link to article – subscription may be required.)
  14. Bitew S, Imbriano L, Miyawaki N, Fishbane S, Maesaka JK. More on renal salt wasting without cerebral disease: response to saline infusion. Clinical journal of the American Society of Nephrology : CJASN. 2009 Feb; 4(2):309-15.(Link to article – subscription may be required.)
  15. Huda MS, Boyd A, Skagen K, Wile D, van Heyningen C, Watson I, Wong S, Gill G. Investigation and management of severe hyponatraemia in a hospital setting. Postgrad Med J. 2006;82(965):216-9.
  16. Steele A, Gowrishankar M, Abrahamson S, Mazer CD, Feldman RD, Halperin ML. Postoperative hyponatremia despite near-isotonic saline infusion: a phenomenon of desalination. Annals of internal medicine. 1997 Jan 1; 126(1):20-5.
  17. Rusinaru D, Buiciuc O, Leborgne L, Slama M, Massy Z, Tribouilloy C. Relation of serum sodium level to long-term outcome after a first hospitalization for heart failure with preserved ejection fraction. The American journal of cardiology. 2009 Feb 1; 103(3):405-10.(Link to article – subscription may be required.)
  18. Konarzewski WH. Hyponatraemia can occur during transurethral resection of prostate. BMJ 2006;332:853-4