Hypovolaemic Hyponatraemia

Hypovolaemic hyponatraemia is a low serum sodium (under 135 mmol/L) with a reduced extracellular fluid volume, caused by sodium losses that exceed water losses, together with intake or retention of hypotonic fluid. Volume depletion stimulates antidiuretic hormone release regardless of osmolality, so water is retained and sodium is diluted.

Causes are renal and extrarenal.

Renal causes:

• thiazide diuretics
• loop diuretics
• mineralocorticoid deficiency or adrenal insufficiency
• salt wasting nephropathy including reflux nephropathy and polycystic kidney disease
• cerebral salt wasting after subarachnoid haemorrhage or neurosurgery
• osmotic diuresis in uncontrolled diabetes or from mannitol
• post-obstructive diuresis
• recovering acute tubular necrosis
• bicarbonaturia with vomiting

Extrarenal causes:

• vomiting
• diarrhoea
• small bowel fistulae
• burns
• pancreatitis
• third spacing
• excessive sweating

Thiazides are the commonest cause in older adults and often present 7 to 14 days after starting.

Pathophysiology. Reduced effective arterial volume activates baroreceptor mediated antidiuretic hormone release, the renin angiotensin system and sympathetic activity; the kidney retains water, and solute free water intake dilutes sodium; restoring volume switches off the stimulus and causes a rapid water diuresis.

• Thirst, postural dizziness, weakness, muscle cramps, reduced urine output (extrarenal) or polyuria (renal causes).
• Dry mucous membranes, reduced skin turgor, low jugular venous pressure, postural hypotension (fall in systolic pressure over 20 mmHg), tachycardia, cool peripheries.
• Weight loss; history of vomiting, diarrhoea, burns, diuretic use or poor intake.
• Cerebral salt wasting: polyuria, negative sodium balance, hypovolaemia after intracranial disease.
• Adrenal insufficiency: fatigue, hyperpigmentation, hypotension, hypoglycaemia, hyperkalaemia.

Red flags

• Hypotension, shock or oliguria.
• Hyperkalaemia with hyponatraemia (adrenal insufficiency).
• Recent subarachnoid haemorrhage or neurosurgery.
• Sodium under 120 mmol/L with neurological symptoms.
• Rapid urine output after fluid resuscitation (risk of overcorrection).

• Sodium, potassium, urea (raised, with raised urea to creatinine ratio over 100 in extrarenal losses), creatinine, bicarbonate, glucose, calcium, serum and urine osmolality, uric acid (raised in volume depletion; low in cerebral salt wasting and inappropriate antidiuresis).
• Urine sodium: under 20 mmol/L suggests extrarenal losses or previous diuretic effect; over 30 mmol/L suggests renal loss (diuretics, adrenal insufficiency, cerebral salt wasting, salt wasting nephropathy); fractional excretion of urea under 35% supports diuretic induced hypovolaemia.
• Cortisol and synacthen test, renin and aldosterone, thyroid stimulating hormone.
• Clinical volume assessment including weight change, central venous pressure or inferior vena cava ultrasound.
• Response to isotonic saline: a rise in sodium and urine osmolality falling confirms hypovolaemia.

Differential diagnosis

• Euvolaemic hyponatraemia (inappropriate antidiuresis, hypothyroidism, cortisol deficiency), hypervolaemic hyponatraemia, cerebral salt wasting versus inappropriate antidiuresis, hyperglycaemia, pseudohyponatraemia, reset osmostat.

First line: restore volume with isotonic fluid and stop the cause

• Mild or moderate: 0.9% sodium chloride 500 to 1000 mL over 1 to 2 hours, then 100 to 150 mL/hour, adjusted to blood pressure, urine output and sodium.
• Oral rehydration solution (sodium 60 to 90 mmol/L) when able to drink.
• Potassium chloride 20 to 40 mmol in each litre of fluid for hypokalaemia. Potassium replacement also raises sodium.
• Stop thiazide and loop diuretics. Treat vomiting with ondansetron 4 to 8 mg intravenously, and treat diarrhoea and its cause.
• Check sodium every 2 to 4 hours. Once volume is restored and the antidiuretic hormone stimulus falls, urine becomes dilute (over 100 mL each hour, urine osmolality under 100 mosmol/kg) and sodium can rise quickly.
• Limit the rise to 8 to 10 mmol/L in 24 hours (4 to 6 mmol/L in high risk patients).
• If the sodium rises too quickly: stop saline, give 5% glucose 3 mL/kg over 1 hour and desmopressin 2 microg intravenously every 8 hours. Repeat according to sodium checks every hour.

Specific causes

• Adrenal insufficiency: hydrocortisone 100 mg intravenously, then 200 mg over 24 hours (or 50 mg every 6 hours), with saline. Later, fludrocortisone 0.05 to 0.2 mg daily.
• Cerebral salt wasting: 0.9% sodium chloride (or 3% saline 150 mL over 20 minutes for severe symptoms) and sodium chloride tablets 3 to 9 g daily. Give fludrocortisone 0.1 to 0.4 mg daily in two doses (for 3 to 7 days after subarachnoid haemorrhage), monitoring potassium and blood pressure. Do not fluid restrict.
• Salt wasting nephropathy: sodium chloride 3 to 9 g daily (50 to 150 mmol) and unrestricted fluid. Treat the underlying disease.
• Diabetic ketoacidosis or hyperglycaemia: correct sodium for glucose and replace with insulin infusion 0.1 unit/kg each hour after fluids and potassium.
• Severe symptoms (seizures, coma): 3% sodium chloride 150 mL over 20 minutes, repeated up to two further times to a 5 mmol/L rise, with careful volume monitoring.

Monitoring. Sodium and urine output hourly during the first 6 hours in severe cases. Potassium and creatinine every 12 to 24 hours. Weight and blood pressure each shift. Review diuretic need after recovery.

Referral and escalation. Endocrinology for adrenal insufficiency; neurosurgery or neurology for cerebral salt wasting; nephrology for salt wasting disease; high dependency for shock or sodium under 120 mmol/L.

Special groups

• Older adults: gradual rehydration. Recheck sodium 1 to 2 weeks after restarting any diuretic and use the lowest effective dose.
• Children: gastroenteritis hyponatraemia is treated with isotonic fluids (0.9% sodium chloride 10 to 20 mL/kg boluses for shock, then maintenance with glucose), not water.
• Athletes and heat illness: replace sodium as well as water.
• Pregnancy: hyperemesis causes hypovolaemic hyponatraemia. Replace with 0.9% sodium chloride with potassium and give thiamine 100 mg daily.