Hyponatraemia

OVERVIEW

• common problem in ICU (30% of patients have a Na < 134mmol/L)
• independent predictor of mortality in ICU
• goals = to determine:

1. severity
2. type
3. treat cause
4. prevent complications

SEVERITY

Na+ < 135mmol/L

• Mild 125-134
• Moderate 120-124
• Severe <120

TYPES AND CAUSES

• Hypoosmolar/Hypotonic
  • -> hypovolaemic, euvolaemic and hypervolaemic
• Iso-osmolar
• Hypertonic

Hypotonic/Hypoosmolar

• causes = solute depletion or solute dilution

Hypovolaemic

• loss of H2O and Na from the ECF -> increased ADH secretion -> decreased free H2O excretion and H2O retention -> hyponatraemia
• renal or extra-renal causes

RENAL LOSS

• diuretics
• osmotic diuresis (glucose, mannitol)
• bicarbonaturia (RTA)
• salt wasting nephropathy
• mineralocorticoids deficiencies
• ketones

NON-RENAL LOSS

• upper GI: vomiting
• middle GI: pancreatitis, bowel obstruction
• lower GI: diarrhoea, bowel preparation
• other losses: sweat, bleeding

• the way to sort out whether it is a renal or extra-renal source = to do a urinary Na+
• if urinary Na+ < 10mmoL/L -> extra-renal (as kidney appropriately attempting to hold onto Na+)
• if urinary Na+ > 20mmol/L -> renal (as if clinically hypovolaemic then this is an inappropriate response)

Euvolaemic

• causes = SIADH (most common), psychogenic polydipsia, hypotonic IVF therapy, adrenal insufficiency, hypothyroidism
• any disease state causing hypoosmolality can present with a normal state of hydration
• clinical examination of volume status is not sensitive
• more sensitive = a normal or low urea and an elevated urinary Na+

See SIADH document for further information

Causes of SIADH (=MAD CHOP)

• Malignancy
• ADH secretion (ectopic)
• Drugs (e.g. SSRIs, ecstasy)
• CNS disease
• Hormone deficiency (hypothyroidism, adrenal insufficiency)
• Others
• Pulmonary

Hypervolaemic

• increase in total body Na+ and H2O -> however, total body H2O is out of proportion to Na+
• clinically evident oedema or ascites
• causes: CHF, cirrhosis, nephrotic syndrome, hypothyroidism, pregnancy, TURP/hysteroscopy syndrome

Isotonic

• known as “pseudohyponatraemia”
• plasma osmolality can be measured directly in the laboratory using a osmometer or by the formula: calculated osmolarity = (2xNa+) + glucose + urea
• serum is made up of 93% H2O and 7% non-aqueous factors including lipids and proteins
• normally the nonaqueous components do not effect the tonicity but in states of marked hyperproteinaemia or hyperlipidaemia (elevated chylomicrons or triglycerides) -> this ratio is changed artifactually decreasing the apparent concentration of Na+ in serum.

Hypertonic

• translocational hyponatraemia
• osmotically active particles in the plasma induces movement of H2O from ICF -> ECF -> decreasing serum Na+ even though the serum osmolality remains elevated.
• agents that cause this: glucose, mannitol, sorbitol, radiocontrast
• for each 1mmol/L rise in blood glucose the serum sodium will decrease by 0.3mmol/L

*** Advanced renal disease = an important cause of a normal or high serum osmolality

• hyponatraemia from the inability to excrete H2O -> lowers osmolality but because of high urea this acts to normalise osmolality or can make it high.
•  however, urea is an ineffective osmole (as it freely crosses cell membranes) -> therefore does not cause H2O to moved out of cells.
• you need to correct serum osmolality for the effect of urea: Corrected serum osmolality = measure osmolality – [urea]

HISTORY

• speed of onset more important than level
• most patients won’t be symptomatic until Na+ < 125mmol/L
• fluid intake/output
• nausea
• vomiting
• neuropsychiatric symptoms
• muscular weakness
• headache
• lethargy
• psychosis
• raised ICP
• seizures
• coma

• medications!
• ROS to find precipitant and organ dysfunction
• co-morbidities: adrenal disease, liver disease

EXAMINATION

• cause!
• volume status
• neurological complications (increased ICP, lateralizing signs)

INVESTIGATIONS

• diagnostic
• U+E (Na+, glucose, renal function)
• plasma osmolality
• plasma proteins and lipids
• urinary Na+

MANAGEMENT

• treat cause
• ideally correct slowly to avoid central pontine myelinolysis
• quantify duration, severity and type
• treatment is dependent on cause

(1) fluid restriction (< 800mL/day)
(2) diuretics
(3) isotonic saline (in true volume depletion)
(4) oral Na+ tablets
(5) hypertonic saline (3%):

-> rapid reversal – 100mL (raises Na+ by 2-3mmol/L) Q 10 min until seizures stops
-> less rapid – 1mL/kg/hr of LBW

• can use desmopressin or dextrose if inadvertent rapid correction takes place

Acute (<48hrs) and symptomatic

• seizing and coma
• raise by 1-5mmol/L/hr until symptoms resolve or Na+ 125-130mmol/L
• hypertonic saline (3%) 1-2ml/kg/hr
• frusemide 20mg IV

Chronic symptomatic (>48 hrs or unknown duration)

• calculate Na+ deficit
• correct Na+ by 10mmol/L/day
• frusemide 20mg IV
• N/S
• fluid restrict
• repeat Na+ every 2 hours
• high risk patients = young premenopausal woman

Asymptomatic from SIADH

• fluid restrict
• frusemide 20-40mg/day
• NaCl tablets 3-18g/day
• urea 30g/day
• demclocycline 600-1200mg/day
• current trials underway looking @ AVP V2 receptor antagonists

NORMAL RANGES

• Serum osmolality: 272-295mOsm/kg water (panic values = 240 and 320!)
• Urine osmolality: from 50-1400mOsm/kg water (average 500-800) – after an overnight fast urine osmolality should be 3 times the plasma osmolality
• Urinary Na+ – 15 to 250 mmol/L

CALCULATIONS

• Use calculators at
  • MedCalc: Hyponatremia & Hypernatremia
  • MDcalc: Sodium Correction for Hyperglycemia
• sodium deficit = TBW x [Na desired – Na measured]
• rate of infusion (mL/hr) = Na requirement (mmol) x 1000 / infusate Na (mmol/L) x time (hours)
• Androgue formula: Change in serum Na+ = (infusate Na + infusate K) – serum Na /TBW + 1

Total body water

• Children = 0.6 x weight
• Women =0.5 x weight
• Men = 0.6 x weight
• Elderly Women = 0.45 x weight
• Elderly Men = 0.5 x weight

Sodium content of different fluids (i.e. infusate Na in mmol/L)

• 5% NaCl = 855
• 3% NaCl = 513
• 0.9% NaCl (NS) = 154
• Lactate Ringer’s = 130
• 0.45% NaCl (½ NS) = 77
• 0.2% NaCl (¼ NS) = 34
• 5%Dextrose in water (D5W) = 0

References and Links

• CCC – Hypernatraemia
• CCC – Hypernatraemia Mind map (PDF)
• CCC – Hyponatraemia
• CCC – Hyponatraemia Mind map (PDF)
• CCC – Hyponatraemia Interpretation (PNG)
• CCC – SIADH – SIADH DDx
• CCC – Diabetes Insipidus Central – Diabetes Insipidus DDx
• Case – Exercise-associated Hyponatremia
• Case – Seizures, hyponatremia and ADH
• CCC – Sodium

Journal articles

• Adrogué HJ, Madias NE. Hyponatremia. N Engl J Med. 2000 May 25;342(21):1581-9.Review. [pubmed] [article]
• Spasovski G, Vanholder R, Allolio B, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. European journal of endocrinology. 2014; 170(3):G1-47. [pubmed] [article]

FOAM and web resources

• EM Basic – Hyponatremia (2012)
• EMCrit – Severe Hyponatremia in the Emergency Department (2011)