Question 14

College Answer

Severe hyponatraemia implies either a very low level (eg. < 120 mmol/L) or one associated with significant symptoms (eg. neurologic).   Approach should allow determination of aetiology by history, examination and simple investigations (and/or repetition of test).  An approach involves measurement of plasma osmolality, urine osmolality and urine sodium concentration. Causes are multiple, and include:

Factitious: contaminated by hypotonic intravenous fluid

Isotonic: pseudohyponatraemia (eg. hyperlipidaemia, hyperproteinaemia)

Hypertonic:  (eg.  hyperglycaemia, mannitol)  where  hypertonicity induces  movement  of water out of cells, and lowers Na by dilution. No specific treatment is usually required.

Hypotonic:

•    Water  retention:  (urinary  Na  is  usually  >  40  mmol/L)  SIADH,  inappropriate antidiuresis (eg. hypovolaemia, cardiac failure, pain, post-operative, renal failure), psychogenic polydipsia

•    Salt depletion: (urinary Na is low, eg.  < 20 mmol/L) adrenocortical failure, diuretic excess

Management includes diagnosis and, if appropriate, specific treatment of underlying cause. Most patients are asymptomatic, with plasma Na > 120.

Initial treatment obviously depends on the specific cause (eg. corticosteroids), but water restriction and isotonic saline is usually sufficient. More aggressive therapy (eg. hypertonic saline) is indicated if Na < 110, or if patient is symptomatic (eg. confusion, coma, seizures). Relationship of rate of correction of Na and risk of osmotic demyelination (central pontine myelinolysis) is controversial, but appears reduced if rate of correction of Na is less than 10-

12 mmol/L over the initial 24 hours (ie. < 0.5 mmol/hr). Desmopressin (dDAVP) may be required to slow the rate of water excretion. Consider even administration of sterile water to lower sodium if rising too quickly.

Discussion

This is an easy question for the sodium enthusiast.

Somewhere, a chapter about the diagnosis of hyponatremia is waiting for me to finish it. However, that classification and diagnostic algorithm is based around urine osmolality rather than volume assessment, and thus is not the canonical view. Classically, hyponatremia is separated into classifications according to serum osmolality and volume status. In the answer, the college goes even further towards raw practicality and separates hypoosmolar hyponatremia into disorders which waste sodium , and disorders which retain water.

In any case, this question calls for a systematic approach.

History

The following bits of historical information are important:

• Medication history (diuretics, steroids, drugs which cause SIADH eg. SSRIs)
• Fluid chart (has somebody been mindlessly charting dextrose)
• Psychosocial history (is psychogenic polydipsia even a possibility; are they on a weird diet)
• Alcohol history (liver disease, cirrhosis, beer potomania)
• Oedema history (Ascites worse recently? Sleep on twenty pillows?)
• Trauma history (cerebral salt wasting, pituitary injury)
• Urine output (massive diuresis of HONK or ATN recovery phase, or oliguria or chronic renal failure)
• Recent procedures: TURP, contrast CT, recent surgery, etc.

The following standard battery of tests can be launched; particularly if history is unhelpful, or one cannot bring oneself to interview the patient or their family.

Essential tests:

• Serum osmolality (to classify the disorder)
• Urine osmolality
• Urinary sodium

Optional tests:

• Serum triglycerides
• Serum protein level
• TFTs
• LFTs
• Urea and creatinine
• Random cortisol
• Short synacthen test

Potential causes:

This is essentially the content of Box 93.1 from Anthony Delaney and Simon Finfer's chapter for Oh's Manual.

Causes of Hyponatremia

Spurious result Isotonic High triglycerides High serum protein Glycine (TURP syndrome) Hypertonic Hyperglycaemia Mannitol Sorbitol Maltose Radiocontrast dye

Water retention High urine sodium Renal failure Cirrhosis Congestive cardiac failure Diuretics (but not enough!) SIADH Low urine sodium Psychogenic polydipsia True hypovolemia

Sodium excretion Post-ATN diuresis Hypoaldosteronism Diuretic excess Cerebral salt wasting Inappropriate fluid replacement (5% dex)

Diagnosis on the basis of the above lab tests and historical findings:

• Serum osmolality testing:
  • Hyperosmolar hyponatremia:
    • Hyperglycaemia
    • Mannitol therapy
    • Other unmeasured solutes, eg. glycine
    • Glycine (TURP syndrome)
  • Isoosmolar hyponatremia
    • High triglycerides
    • High serum protein
  • Hypoosmolar hyponatremia
    • Further investigations will be required to distinguish between water retention and sodium excretion.
• Urinary sodium and urinary osmolality
  • Low urinary sodium: water retention disorders;
    • Polydipsia, beer potomania - low urine osmolality
    • true hypovolemia, heart failure, cirrhosis, nephrotic syndrome - high urine osmolality
  • High urinary sodium: sodium wasting disorders;
    • Acute renal failure, post-obstructive diuresis, polyuric phase of ATN - low urine osmolality
    • Thiazides, SIADH, cerebral salt wasting, hypoadrenalism, hypothyrodism - high urine osmolality

Treatment:

• Reverse the reversible causes
• Restore volume and sodium with isotonic saline (if appropriate)
• If there are severe symptoms, hypertonic saline infusion is required.
• Sodium replacement rate should not excess 12mmol/day, or about 0.5mmol/hr.

Chung HM, Kluge R, Schrier RW, Anderson RJ. Clinical assessment of extracellular fluid volume in hyponatremia. Am J Med. 1987 Nov;83(5):905-8.

 

Milionis, Haralampos J., George L. Liamis, and Moses S. Elisaf. "The hyponatremic patient: a systematic approach to laboratory diagnosis."Canadian Medical Association Journal 166.8 (2002): 1056-1062.