Hyponatraemia

oPatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

Serum sodium concentration is maintained by a homeostatic mechanism that involves thirst, antidiuretic hormone (ADH, also called vasopressin) secretion, the renin-angiotensin-aldosterone feedback system and the renal handling of sodium. Hyponatraemia represents a relative excess of water in relation to sodium and is defined as a serum sodium <135 mmol/L.[2] A level <120 mmol/L is considered severe. It is postulated that interleukin-6 is responsible for the non-osmotic release of vasopressin in many disease processes and this accounts for the subsequent development of hyponatraemia.[3]

Falsely low sodium values results can occur with very high circulating levels of lipids or proteins in which the concentration of sodium in the water phase is normal (plasma osmolality normal). This can also occur in severe hyperglycaemia as the high levels of glucose draw intracellular water into the extracellular space.

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Hyponatraemia is the most common electrolyte abnormality encountered in clinical practice.[4] An accurate incidence of mild hyponatraemia managed in the community is impossible, as it is rarely reported. A seminal study in 1985 found a daily incidence and prevalence of 0.97% and 2.48% respectively.[5] A Manchester study reported a prevalence rate as high as 15-30% among patients admitted to acute and intensive care units.[6] There is no sex predilection. Infants and the elderly are most at risk because they are less likely to be able to express their thirst and autonomously control their own fluid intake. Furthermore, infants with diarrhoea, given tap water instead of electrolyte replacement fluid, and those given watered-down milk formula for reasons of economy, are known to be at risk.

This depends upon severity and is dictated not only by the absolute serum sodium level but also by the rate of fall. Thus, chronic mild hyponatraemia may be asymptomatic whilst a sudden fall to only 125 mmol/L from normal values can result in convulsions (usually from inappropriate intravenous fluids).

Symptoms

The clinical picture can be confusing, because mild hyponatraemia can cause significant symptoms if the drop in sodium level is sudden, whereas severe chronic hyponatraemia can cause no symptoms, due to cerebral adaption.[4] However, as a rule of thumb, the following may be helpful:

  • Mild - anorexia, headache, nausea, vomiting, lethargy.
  • Moderate - personality change, muscle cramps and weakness, confusion, ataxia.
  • Severe - drowsiness.

Signs

These are again highly variable and depend on the level and rate of fall of the serum sodium. They may include:

  • Neurological signs:
    • Decreased level of consciousness.
    • Cognitive impairment (eg short-term memory loss, disorientation, confusion, depression).
    • Focal or generalised seizures.
    • Brain stem herniation - seen in severe acute hyponatraemia; signs include coma; fixed, unilateral, dilated pupil, decorticate or decerebrate posturing, respiratory arrest.
  • Signs of hypovolaemia - dry mucous membranes, tachycardia, diminished skin turgor.
  • Signs of hypervolaemia - pulmonary rales, S3 gallop (third heart sound), jugular venous distention, peripheral oedema, ascites.

The causes of true hyponatraemia can be divided into three groups based on their effect on extracellular fluid volume. These can further be subdivided by the concentration of sodium in the urine.

HypoNa flowchart

Syndrome of inappropriate ADH secretion (SIADH)[8][9]

Inappropriate ADH secretion from posterior pituitary or from ectopic source despite low serum osmolality.

Major diagnostic features

  • Hyponatraemia.
  • Plasma hypo-osmolality proportional to hyponatraemia.
  • Inappropriately elevated urine osmolality (>100 mOsmol/kg) commonly > plasma osmolarity.
  • Persistent urine [Na+] >40 mmol/L with normal salt intake.
  • Euvolaemia.
  • Normal thyroid and adrenal function.

Extra features include an elevated ADH level and low blood uric acid level.

Causes (not exhaustive)

  • Neurological: tumour, trauma, infection, Guillain-Barré syndrome, multiple sclerosis, systemic lupus erythematosus, intracranial haemorrhage, sinus thrombosis, AIDS, porphyria.
  • Pulmonary: lung small-cell cancer, mesothelioma, pneumonia, abscess, cystic fibrosis, asthma, tuberculosis, positive-pressure ventilation.
  • Other malignancy: oropharyngeal, stomach, pancreas, leukaemia, lymphoma, thymoma, and genitourinary tract cancers.
  • Drugs: chlorpropramide, carbamazepine, selective serotonin reuptake inhibitor (SSRI) antidepressants, tricyclic antidepressants, lithium, MDMA/ecstasy, tramadol, haloperidol, vincristine, desmopressin, fluphenazine.
  • Miscellaneous: idiopathic, hereditary, pain, postoperative, stress, endurance exercise and marathon runners, dermatomal herpes zoster.
  • Serum sodium. Before embarking on other investigations for hyponatraemia, consider whether the sample suffered from dilution by being taken near the site of an infusion, or whether there is any chance of laboratory error. If necessary, repeat the test.
  • Serum potassium. If raised, consider Addison's disease.
  • Plasma osmolality.
  • Urine sodium level. If this is >20 mmol/L, a renal cause should be sought.
  • Urine osmolality.
  • Serum thyroid-stimulating hormone and free thyroxine level. These should be checked to exclude hypothyroidism.
  • Random serum cortisol levels or adrenocorticotropic hormone (ACTH) stimulation test. Either of these should be considered in patients with suspected adrenal suppression (eg patients who have recently taken oral steroids).
  • Imaging. This may be contributory in some clinical situations. For example, a CXR may be required in suspected congestive cardiac failure, or a CT brain scan in patients with confusion or altered consciousness.
  • Correct underlying cause - eg stop diuretic. Beware correcting too rapidly.
  • Get expert help if hyponatraemia is severe, and follow local guidelines if available.
  • Formulae for rates of infusion or predicting [Na+] rise with a given volume of saline solution are not very accurate. They only provide a guide to initial replacement where needed.
  • The serum sodium should be checked often to ensure a safe rate of correction of no more than 8-10 mmol/L/day, generally keeping rises in [Na+] to less than 0.5 mmol/L/hour.
  • If the patient has an acute/severely symptomatic hyponatraemia (ie fitting, comatose), then an initial rise of <4-6 mmol/L over 1-2 hours is acceptable to terminate the severe symptoms, before more gradual correction is resumed:
    • For example, using aliquots of 3-5 ml/kg 3% (hypertonic) saline over 15 minutes-1 hour to increase [Na+] by ~2-4 mmol/L.
  • If not a severe case, then [Na+] correction method depends on fluid status:
    • Hypovolaemic:
      • 0.9% saline replacement. As euvolaemia is regained, ADH is suppressed and the resulting diuresis may elevate [Na+] overly rapidly; if so, give desmopressin (ADH analogue) ± 5% glucose (free water).
    • Normovolaemic:
      • Fluid restrict (500-1000 ml/day). If inadequate consider:
        • NaCl tablets PO (eg 3 g daily) or 3% saline IV - not 0.9% saline, as this may worsen the hyponatraemia in SIADH if the urine osmolality exceeds that of the plasma.
        • Furosemide may help if urine osmolality >2 x plasma osmolality.
        • Demeclocycline blocks ADH and induces partial nephrogenic diabetes insipidus.
        • Vaptans (new vasopressin receptor antagonists, eg tolvaptan) are becoming available and may be useful; however, they can induce thirst, are expensive, have limited availability and potentially may increase [Na+] too rapidly.
    • Hypervolaemic:
  • If KCl is given for concomitant hypokalaemia, it will also raise the [Na+] by subsequent transcellular ion shifts of K+, Cl- and H+.

Mild hyponatraemia is associated with gait disturbance in the elderly and with falls. It can also cause a reduction in bone mass and this combination of circumstances increases the incidence of fractures.[4]

A sudden fall in serum sodium concentration over a 24- to 48-hour period can result in severe cerebral oedema, leading to cerebral herniation and death.

Chronic hyponatraemia (over more than 48 hours) can result in cerebral oedema but is not associated with brain herniation. Permanent neurological sequelae can arise. Other complications include rhabdomyolysis, seizures and respiratory arrest.

Conversely, too rapid correction of hyponatraemia can cause central pontine myelinolysis (also known as osmotic demyelination syndrome). This is caused by large shifts of intracellular water affecting the pons and other parts of the CNS. Symptoms occur 2-4 days later, typically with quadriplegia and pseudobulbar palsy; however, it can take the form of mutism with paralysis ('locked-in' syndrome). Risk factors for this condition are female gender, hypokalaemia, alcoholism and liver transplant.

A 2009 study of hospitalised patients found that even a mild degree of hyponatraemia was associated with increased mortality rates.[6] Patients with cardiovascular disease, metastatic cancer and those undergoing orthopaedic surgery were particularly at risk. Another study, however, concluded that it was the underlying disease process rather than the severity of the hyponatraemia which explained the mortality rate.[10]

Further reading & references

  • Hyponatraemia in Adults, Guidelines and Audit Implementation Network (2010)
  • Hyponatraemia; NCE CKS, January 2011
  • Sterns RH; Overview of the treatment of hyponatremia. UpToDate version 19.3, Sep 2011
  • Moritz ML, Ayus JC; New aspects in the pathogenesis, prevention, and treatment of hyponatremic Pediatr Nephrol. 2010 Jul;25(7):1225-38. Epub 2009 Nov 6.
  1. Sterns RH, Nigwekar SU, Hix JK; The treatment of hyponatremia. Semin Nephrol. 2009 May;29(3):282-99.
  2. Craig S; Hyponatremia in Emergency Medicine, Medscape, Apr 2010
  3. Swart RM, Hoorn EJ, Betjes MG, et al; Hyponatremia and inflammation: the emerging role of interleukin-6 in Nephron Physiol. 2011;118(2):45-51. Epub 2010 Dec 22.
  4. Thompson CJ; Hyponatraemia: new associations and new treatments. Eur J Endocrinol. 2010 Jun;162 Suppl 1:S1-3. Epub 2010 Apr 20.
  5. Anderson RJ, Chung HM, Kluge R, et al; Hyponatremia: a prospective analysis of its epidemiology and the pathogenetic Ann Intern Med. 1985 Feb;102(2):164-8.
  6. Mittal R, Sheftel H, Demssie Y; Management of hyponatraemia. Br J Hosp Med (Lond). 2011 Feb;72(2):M22-5.
  7. Goh KP; Management of hyponatremia. Am Fam Physician. 2004 May 15;69(10):2387-94.
  8. Baylis PH; The syndrome of inappropriate antidiuretic hormone secretion. Int J Biochem Cell Biol. 2003 Nov;35(11):1495-9.
  9. Ellison DH, Berl T; Clinical practice. The syndrome of inappropriate antidiuresis. N Engl J Med. 2007 May 17;356(20):2064-72.
  10. Chawla A, Sterns RH, Nigwekar SU, et al; Mortality and serum sodium: do patients die from or with hyponatremia? Clin J Am Soc Nephrol. 2011 May;6(5):960-5. Epub 2011 Mar 24.

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Adrian Bonsall
Current Version:
Peer Reviewer:
Dr Laurence Knott
Last Checked:
13/06/2012
Document ID:
2298 (v28)
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