Management of Hyponatraemia (E.Society for Endocrinology)

Question 1

What are the symptoms of low sodium?

Answer 1

Nausea
Confusion
Headaches
Vomiting
Cardiorespiratory distress
Abnormal and deep somnolence
Seizures
Coma

Question 2

What is the pathophysiolgical mechanism that causes the symptoms of low sodium?

Answer 2

Brain swelling and raised ICP because of a difference in effective osmolality between brain and plasma
Normally occurs when low sodium develops rapidly, with not enough time for the brain to adapt to the hypotonic environment
Over 24-48 hours the brain reduces the amount of osmotically active particles (mainly potassium and active solutes) from its cells in an attempt to restore brain volume

Question 3

What is pseudohyponatraemia?

Answer 3

A laboratory artifact that occurs when abnormally high levels of lipids of proteins in the blood interfere with accurate measurement of sodium

Question 4

What are the different types of non-hypotonic hyponatraemia?

Answer 4

Isotonic hyponatraemia - additional osmoles present in the blood increase effective osmolality by drawing water out from the intracellular compartment e.g. glucose, mannitol, glycine (irrigation fluid e.g. prostate ops)
Hypertonic hyponatraemia

Question 5

What are the causes of hypotonic hyponatraemia with decreased extracellular fluid volume?

Answer 5

Non-renal sodium loss
           - Gastrointestinal
           - transdermal sodium loss e.g. sweating, burns
Renal sodium loss:
           - diuretics
           - primary adrenal insufficiency
           - salt-losing nephropathies e.g.analgesic nephropathy, medullary cystic kidney disease, post-chemo tubulopathy
Third-spacing: 
           - bowel obstruction
           - sepsis
           - pancreatitis
           - muscle trauma

Question 6

Explain the difference in urinary sodium loss that occurs in diarrhoea vs vomiting

Answer 6

In vomiting metabolic alkalosis causes renal sodium loss as sodium accompanies bicarbonate in the urine despite activation of the renin-angiotensin system
In diarrhoea the kidneys respond by preserving sodium and urinary sodium levels are therefore very low

Question 7

How does primary adrenal insufficiency cause hyponatraemia?

Answer 7

Hypoaldosteronism causes renal sodium loss, contracted extracelluar fluid volume and hyponatreamia
Hyponataemia may be its first and only sign

Question 8

What are the causes of hypotonic hyponatraemia with normal extracellular fluid volume?

Answer 8

Due to an absolute increase in body water resulting from excessive fluid intake in the presence of impaired free water excretion
Caused by
SIADH
Secondary adrenal insufficiency
Hypothyroidism (rare)
High water and low solute intake

Question 9

What are the causes of SIADH?

Answer 9

Cancers e.g. SCC of the lung
Lung disease e.g. pneumonia
CNS diseases e.g. SAH

Question 10

What are the diagnostic criteria for diagnosing SIADH?

Answer 10

Essential criteria
Effective serum osmolality < 275 mOsm/kg
Urine osmolality > 100 mOsm/kg at some level of decreased effective osmolality
Clinical euvolaemia
Urine sodium concentration >30 mmol/l with normal dietary salt and water intake
Absence of adrenal, thyroid, pituitary or renal insufficiency
No recent use of diuretic agents
Supplemental criteria
Serum uric acid < 0.24 mmol/l (< 4 mg/dl)
Serum urea < 3.6 mmol/l (< 21.6 mg/dl)
Failure to correct hyponatraemia after 0.9% saline infusion
Fractional sodium excretion > 0.5%
Fractional urea excretion > 55%
Fractional uric acid excretion >12%
Correction of hyponatraemia through fluid restriction

Question 11

What are the causes of hypotonic hyponatraemia with increased extracellular fluid volume?

Answer 11

Kidney disease without appropriate fluid restriction
Peritoneal dialysis
Heart failure
Liver failure in itself, also spironolactone can contribute
Nephrotic syndrome

Question 12

What levels are sodium in mild, moderate and profound hyponatraemia?

Answer 12

Mild: 130-135
Moderate:125-129
Profound: <125

Question 13

Over what time periods do acute and chronic hyponatraemia develop?

Answer 13

Acute < 48 hours
Chronic > 48 hours
Unknown - normally considered to be chronic unless evidence suggests otherwise

Question 14

What drugs and conditions are associated with acute hyponatraemia?

Answer 14

Postoperative phase
Post-resection of the prostate, post-resection of endoscopic uterine surgery
Polydipsia
Exercise
Recent thiazides prescription
3,4-Methylenedioxymethamfetamine (MDMA, XTC)
Colonoscopy preparation
Cyclophosphamide (i.v.)
Oxytocin
Recently started desmopressin therapy
Recently started terlipressin, vasopressin

Question 15

Which formula allows you to correct serum sodium levels in the face of hyperglycaemia?

Answer 15

Corrected serum Na
= measured Na + 2:4
x ((glucose mg/dl -100 mg/dl) / 100 mg/dl)

Question 16

Why do you get neurological symptoms in TURP syndrome?

Answer 16

Due to the glycine
The glycine acts as an effective osmole resulting in an isotonic hyponatraemia and therefore there are no extracellular shifts in fluid so the symptoms arise from neurotoxic effects of the glycine and not the low sodium

Question 17

Give some examples of ineffective osmoles

Answer 17

Urea
Ethanol
Methanol

Question 18

How should we differentiate different causes of hypotonic hyponatraemia?

Answer 18

1. Check urine osmolality:
   ->If < 100 mOsm/kg, accept relative excess water intake as a cause.
   ->If >100 mOsm/kg, check urine sodium concentration taken simultaneously with a blood sample.
   ->If urine sodium is <30 mmol/l, we accept low effective arterial volume as a cause of the hypotonic hyponatraemia.
   ->If urine sodium is >30 mmol/l, we assess extracellular fluid status and use of diuretics to further differentiate likely causes of hyponatraemia.(SIADH diagnosis involves exclusion of other causes)
   We suggest against measuring vasopressin for
   confirming the diagnosis of SIADH .

Question 19

In what conditions does low effective arterial volume occur?

Answer 19

If ECF expanded - liver failure, heart failure, nephrotic syndrome
If ECF reduced - D+V, third spacing, diuretics

Question 20

What are the differences between SIADH and cerebral salt-wasting in terms of serum urea, urine volume, urine sodium, BP, CVP

Answer 20

SIADH Cerebral salt wasting
Serum urea Concentration Normal-low Normal-high
Serum uric acid concentration Low Low
Urine volume Normal–low High
Urine sodium concentration >30 &raquo_space;30
Blood pressure Normal Normal–orthostatic hypotension
Central venous pressure Normal Low

Question 21

What is the immediate management of hyponatraemia with severe symptoms?

Answer 21

Prompt i.v. infusion of 150ml (or 2mls/kg) 3%hypertonic over 20 min
Check the serum sodium concentration after 20 min while repeating an infusion of 150 ml 3% hypertonic saline for the next 20 min
Repeat twice or until a target of 5 mmol/l increase in serum sodium concentration is achieved

Question 22

What are the general principles of managing hyponataemia after initial treatment of the severe symtpoms?

Answer 22

Stop the hypertonic saline
Start a diagnosis-specific treatment if available, aiming at least to stabilise sodium concentration
Limit the increase in serum sodium to 10 mmol/l during
the first 24 h and an additional 8 mmol/l during every
24 h thereafter until the serum sodium concentration
reaches 130 mmol/l
Check sodium after 6 and 12 hours and daily until corrected

Question 23

How should hyponataemia with moderate symtptoms be managed?

Answer 23

Similar to severe but only give 1 x 150ml 3% sodium

Question 24

How do you calculate how much fluid to give to patients to correct their sodium?

Answer 24

2 formulas either the classical or the Androgue-Madias
Watch for overshot as urine output may pick up dramatically and increase sodium faster - patient may need DDAVP to slow urine output down.