NICE CKS guideline hyponatraemia

Definition

Hyponatraemia is defined as a serum sodium concentration <135 mmol/L
Hyponatraemia results from a relative excess of body water to sodium

Normal 135-145 mmol/L
Mild 130–135 mmol/L
Moderate 125–129 mmol/L
Severe <125 mmol/L

Acute < 48 hours
Chronic ≥ 48 hours

Pseudo-hyponatraemia:
Hyponatraemia can also be artefactual due to high serum protein or lipid levels, or hyper-osmolar due to severe hyperglycaemia.

Common causes

1. Drugs

2. Syndrome of Inappropriate antidiuretic hormone (SIADH)

3. Heart failure

4. Addison’s disease

5. Thyroid disease

Drug causes:
Diuretics (especially thiazides), SSRis, carbamazepine, PPIs, antipsychotics, TCAs, opiates, NSAIDs, ACEi/ARBs, vasopressin analogues (terlipressin), MDMA (‘ecstasy’)

Symptoms: hyponatraemia is an adverse prognostic indicator

• Usually asymptomatic

• Symptoms: nausea, vomiting, headache, drowsiness, muscle cramps, lethargy, gait instability, falls, cognitive decline and delirium.

• Medical emergency indicated by:
  severe symptoms: seizures, coma, altered GCS, encephalopathy, cerebral oedema and cardio-respiratory arrest
  severe (<125 mmol/L) hyponatraemia that is often acute onset (< 48 hours)

• Hyponatraemia in hospitalized people is associated with an increased mortality

Diagnostic algorithm

1. Asses fluid volume status

2. Measure serum osmolality

3. Stop interfering drugs

4. Specialist investigations:
   Serum osmolality AND urine sodium + urine osmolality
   9am cortisol (if low or borderline consider short Synacthen test)
   Thyroid function tests
   Glucose
   Lipids
   U&E and LFTs

Abbreviations

• SIADH: Syndrome of Inappropriate Antidiuretic Hormone 

• PPI: Proton Pump Inhibitor 

1. Check serum osmolality to confirm if ‘true’ hypotonic hyponatraemia vs. pseudo-hyponatraemia

LOW serum osmolality
(<275 mOsmol/kg)
hypotonic
most common
hypotonic hyponatraemia

NORMAL serum osmolality
(275–295 mOsmol/kg)
normotonic
—> measure serum lipids and total protein concentrations (consider myeloma screen)

HIGH serum osmolality
(> 295 mOsmol/kg)
hypertonic
—> measure serum glucose to exclude hyperglycaemia
—> causes osmotic diuresis (urinary sodium>30 mmol/L)

2. Clinical fluid volume status

Hypovolaemic hyponatraemia

Renal loss
Osmotic diuresis*
Diuretic therapy*
Addison’s (primary adrenal insufficiency)*
Salt-losing nephropathy*
Cerebral salt-wasting*

Extra-renal losses
diarrhoea, vomiting, burns, fistulae, pancreatitis, bowel obstruction, sepsis

Treat cause
Fluid replacement (0.9% saline)

Euvolaemic hyponatraemia

SIADH*
Drugs and diuretics*

Thyroid, adrenal, pituitary disease
Hypothyroidism*
Addison’s disease (+secondary ADH response)*
Hypopituitarism—>secondary adrenal insufficiency *

High water low solute intake
primary polydipsia
anorexia nervosa
beer potomania (excess beer consumption with a low solute diet)

Treat cause
Fluid restriction (<1L/day)
Salt restriction

Hypervolaemic hyponatraemia

Raised JVP, pulmonary oedema, oedema, ascites

Congestive cardiac failure
Diuretic therapy for heart failure*
Chronic Kidney Disease*
Nephrotic syndrome
Liver failure

Treat cause
Fluid restriction (<1L/day)
Salt restriction

Key:
Asterix * means urinary sodium>30 mmol/L

Urine osmolality ≤100 mOsm/kg

Primary polydipsia
Low solute intake (for example 'tea and toast diets')

Urine osmolality >100 mOsm/kg

AND urine sodium concentration> 30 mmol/L:

If hypovolaemic: excess Na loss: osmotic diuresis, diuretic therapy, Addison’s disease, salt-losing nephropathy, cerebral salt-wasting
If euvolaemic: SIADH, hypopituitarism (—>secondary adrenal insufficiency), Addison’s disease (+ secondary ADH response), hypothyroidism, diuretic therapy, drugs
If hypervolaemic: chronic kidney disease, diuretic therapy for heart failure, pregnancy

AND urine sodium concentration ≤ 30 mmol/L:

If hypervolaemia: nephrotic syndrome, cirrhosis, cardiac failure
If hypovolaemia: extra-renal losses (diarrhoea, vomiting, burns, fistulae, pancreatitis, bowel obstruction, sepsis)

Diagnostic Criteria for SIADH

1. Clinically euvolaemic

2. Serum osmolality < 275 mOsm/Kg

3. Inappropriately concentrated urine > 100 mOsm/Kg, usually > 300 mOsm/Kg

4. Increased urine Na+ (> 30 mmol/L)

5. Absence of adrenal, thyroid, pituitary, renal insufficiency or diuretic therapy

Primary care treatment

1. Management strategies depend on the rate of onset of hyponatraemia, the person's symptoms, and volume status.

2. Aim to identify the underlying cause of hyponatraemia

3. A combination of hyponatraemia and hyperkalaemia is suggestive of Addison's disease.

4. If acute illness is contributory, recheck serum sodium after 2 weeks

5. Drugs that may be contributing to the hyponatraemia should be modified and the serum sodium concentration rechecked after 2 weeks.

6. Reset osmostat syndrome: chronic stable hyponatraemia in pregnancy and chronic conditions arising from secretion of antidiuretic hormone (ADH) at a lower plasma osmolality threshold resulting in persistent and stable euvolaemic hyponatraemia.

Secondary care treatment

1. ADMIT if hyponatraemia is severe, symptomatic, significant hypovolaemia or Addison disease is suspected

2. ENDOCRINOLOGY advice If asymptomatic AND moderate hyponatraemia

3. SIADH
   SIADH is associated with: pulmonary causes (pneumonia, lung abscess, TB), neoplastic causes (small cell lung cancer, lymphoma) or CNS disease (meningitis, stroke, tumours)
   Arrange tests to find underlying cause (e.g. CT chest/abdo/pelvis/head)
   Commence fluid restriction: 1 litre, if no response, 0.5 litres, assess response at 24-48hr
   If poor response to fluid restriction, consider short trial of V2 receptor antagonist (tolvaptan) or demeclocycline

4. Acute onset symptomatic hyponatraemia (severe symptoms: seizures, coma, altered GCS, encephalopathy)
   iv bolus of 100mls of hypertonic sodium chloride solution (1.8%), over 30 mins and HDU care.
   Check serum Na concentration
   May need to repeat iv bolus
   Consider slow iv infusion 0.9% saline

   Inappropriate rapid correction of hyponatraemia can cause osmotic demyelination syndrome
   Therefore, rate of correction of hyponatremia should be 6-9mmol/L/24 hours (never exceed 12mmol/L/24 hours)