Hypervolaemic Hyponatraemia

Hypervolaemic hyponatraemia is a low serum sodium with an expanded extracellular fluid volume and total body sodium excess. Water retention exceeds sodium retention. It indicates a reduced effective arterial blood volume with antidiuretic hormone release.

Causes:

• Heart failure (hyponatraemia in 20 to 30% of those admitted, and it predicts mortality)
• Cirrhosis with ascites (about 20 to 35% of patients with ascites)
• Nephrotic syndrome
• Advanced chronic kidney disease and acute kidney injury with oliguria
• Less often, hypoalbuminaemia of other causes and protein losing states

The sodium level marks severity. In cirrhosis, sodium under 130 mmol/L predicts hepatorenal syndrome, spontaneous bacterial peritonitis and hepatic encephalopathy. In heart failure it predicts hospital readmission and death.

Total body sodium is increased, but effective circulating volume is low. The baroreceptor response causes renin angiotensin and antidiuretic hormone activation, sodium and water retention, and low free water clearance.

Pathophysiology. Heart failure and cirrhosis lower effective arterial volume (low cardiac output or splanchnic vasodilation). This activates the sympathetic and renin angiotensin systems and arginine vasopressin. Diluted sodium results from water retention, loop diuretics and thiazides, and reduced distal delivery of filtrate. In kidney failure, reduced water excretion contributes.

• Oedema, ascites, pleural effusions, raised jugular venous pressure, weight gain, orthopnoea, hepatomegaly, third heart sound (heart failure).
• Cirrhosis: ascites, jaundice, spider naevi, encephalopathy, variceal bleeding, low blood pressure.
• Nephrotic syndrome: heavy proteinuria, periorbital oedema, low albumin.
• Neurological symptoms are usually mild (sodium 120 to 130 mmol/L): lethargy, confusion, falls; seizures rare.
• Diuretic use is almost universal and is a contributing cause.

Red flags

• Sodium under 125 mmol/L with ascites (hepatorenal syndrome risk) or acute decompensated heart failure.
• Rising creatinine, oliguria or hypotension.
• Spontaneous bacterial peritonitis (fever, abdominal pain, ascitic neutrophils over 250 cells/mm³).
• Encephalopathy or seizure.

• Sodium, potassium, chloride, bicarbonate, urea, creatinine, albumin, bilirubin, liver tests, INR, glucose, serum osmolality, brain natriuretic peptide, thyroid stimulating hormone, cortisol.
• Urine sodium (under 20 mmol/L in heart failure, cirrhosis and nephrotic syndrome when not on diuretics; over 20 mmol/L in kidney failure or after diuretics), urine osmolality (over 100 mosmol/kg), urine protein:creatinine ratio.
• Echocardiography for left ventricular function; abdominal ultrasound and diagnostic ascitic tap (cell count, culture, albumin gradient) in cirrhosis; kidney ultrasound.
• Weight and fluid balance, clinical assessment of volume.

Differential diagnosis

• Euvolaemic hyponatraemia (inappropriate antidiuresis, hypothyroidism), hypovolaemic hyponatraemia from over diuresis, pseudohyponatraemia, hyperglycaemia, adrenal insufficiency in advanced liver disease.

First line: treat the underlying disease and restrict water and sodium

• Fluid restriction 800 to 1000 mL daily when sodium is under 125 mmol/L (or under 130 mmol/L with symptoms), sodium under 2 g daily.
• Loop diuretic: furosemide 40 to 80 mg once or twice daily orally. Intravenous dosing is 40 to 120 mg, or infusion 5 to 20 mg each hour in decompensated heart failure; maximum 400 mg daily.
• In cirrhosis, give spironolactone 100 mg daily, increased every 3 to 5 days to 400 mg, with furosemide 40 mg daily to 160 mg. Stop thiazides.
• Heart failure: optimise disease modifying treatment (ACE inhibitor ramipril 2.5 to 10 mg daily, beta blocker, mineralocorticoid antagonist, dapagliflozin 10 mg daily with eGFR at least 25 or empagliflozin 10 mg daily with eGFR at least 20). Correct low output.
• Acetazolamide 250 to 500 mg intravenously or orally once or twice daily helps in diuretic resistance with bicarbonate over 27 mmol/L.
• Cirrhosis: large volume paracentesis (over 5 litres) with albumin 8 g for each litre removed.
• Hepatorenal syndrome: albumin 1 g/kg (maximum 100 g) on day 1, then 20 to 40 g daily, with terlipressin 0.5 to 1 mg every 4 hours increasing to 2 mg every 4 hours, or noradrenaline infusion 0.5 to 3 mg each hour. Stop diuretics and nephrotoxins. Assess for liver transplantation.
• Nephrotic syndrome: furosemide 40 to 80 mg once or twice daily, sodium under 2 g daily, and treat the glomerular disease.
• Kidney failure: loop diuretic in higher doses (furosemide 80 to 250 mg), fluid restriction, ultrafiltration or dialysis for fluid overload, potassium binders as needed.

Tolvaptan (selected patients)

• Heart failure: tolvaptan 7.5 to 15 mg daily (increase to 30 mg, maximum 60 mg) for sodium under 125 mmol/L unresponsive to fluid restriction. Start in hospital and stop fluid restriction. Check sodium at 6 and 24 hours, then daily. Maximum 30 days.
• Avoid tolvaptan in cirrhosis (liver injury and variceal bleeding) and when thirst is impaired.
• Urea 15 to 30 g daily is an alternative.

Severe hyponatraemia with severe symptoms

• Give 3% sodium chloride 100 to 150 mL over 20 minutes, only with careful volume monitoring (volume overload risk). Add loop diuretic furosemide 40 mg intravenously. Limit rise to 8 mmol/L in 24 hours.

Overcorrection. Stop treatment and give desmopressin 2 microg intravenously every 8 hours with 5% glucose 3 mL/kg over 1 hour.

Monitoring. Sodium, potassium, creatinine daily in hospital (every 2 hours with tolvaptan or hypertonic saline), daily weights, and fluid balance. Check outpatient sodium within 1 week.

Referral and escalation. Cardiology for heart failure; hepatology and transplant services for cirrhosis; nephrology for dialysis; intensive care for hepatorenal syndrome with shock; urgent for sodium under 120 mmol/L, anuria or encephalopathy.

Special groups

• Older adults: lower diuretic doses with careful potassium and sodium checks.
• Pregnancy: avoid ACE inhibitors, tolvaptan, urea and spironolactone. Use loop diuretics and bed rest, and seek specialist cardiology or hepatology care.
• Dialysis patients: sodium reflects water gain. Limit interdialytic fluid gain to 2 to 2.5 litres and avoid thirst by sodium restriction.
• Children: nephrotic syndrome hyponatraemia usually reflects pseudohyponatraemia and water retention. Avoid hypotonic fluids.