Hypernatraemia

Hypernatraemia is defined as a serum sodium concentration > 145 mmol/L.

Hypernatraemia is commonly encountered in clinical practice. Normal serum sodium concentration is 135-145 mmol/L. Elevations above 145 mmol/L are consistent with hypernatraemia.

Hypernatraemia should be considered a problem with total body water (TBW), rather than a problem with sodium homeostasis. There is typically a fall in TBW relative to sodium with failure of normal adaptive mechanisms including thirst and anti-diuretic hormone (ADH).

Acute vs chronic

When the differentiation between acute and chronic is unknown, patients should always be assumed to have chronic hypernatraemia due to the risk of cerebral oedema on correcting sodium too rapidly.

• Acute: a rise in serum sodium to > 145 mmol/L that occurs within a 24 hour period.
• Chronic: a rise in serum sodium to > 145 mmol/L and sustained for > 48 hours.

Dehydration vs hypovolaemia

• Dehydration: water loss in the absence of salt (i.e. sodium)
• Hypovolaemia: loss of water and salt together

Hypernatraemia is a common electrolyte abnormality.

Elderly patients and children are most at risk of hypernatraemia. The overall prevalence varies depending on the study. It is roughly seen in 1% of hospital admissions through A&E, although the condition tends to develop in more patients during an inpatient admission.

In the majority of cases, hypernatraemia results from water depletion.

Sodium is one of the main determinants of effective osmolality within the extracellular fluid. Osmolality is the concentration of a solute dissolved in a solution. Effective osmolality or ‘tonicity’ is essentially the effective osmotic pressure gradient. In other words, tonicity governs the transcellular distribution of water.

Normal plasma osmolality is approximately 275-295 mOsm/L. It can be estimated using the formula 2Na + urea + glucose. Therefore, hypernatraemia, by definition, causes a state of hyperosmolality.

Plasma sodium concentration

The relationship between unbound plasma sodium and body electrolytes and water can be represented in the following equation:

Plasma Na = Total body (Na + K) / Total body water (TBW)

Based on this equation, we can see that hypernatraemia may develop due to a loss of free water (TBW), gain of sodium, or a combination of both.

Thirst and ADH

TBW can be regulated to alter the plasma sodium concentration. There are two predominant mechanisms:

• ADH system: leads to free reabsorption of water in the kidneys. Released from posterior pituitary gland.
• Thirst: osmoreceptors in the hypothalamus are stimulated by a rise in osmolality. Causes us to drink.

At an osmolality > 280 mOsm/L, both the ADH system and thirst may be stimulated leading to an increase in free water (via drinking or renal reabsorption). This maintains serum sodium at a normal level.

ADH, also known as vasopressin, is synthesised in magnocellular neurons in areas of the hypothalamus (supraoptic and paraventricular nuclei). It is transported via axons to the posterior pituitary where it may be released after activation of osmoreceptors at an osmolality > 280 mOsm/L. In the kidneys, it promotes the insertion of aquaporins into the collecting ducts of nephrons that allows the free absorption of water in the absence of sodium. ADH may also be released in response to hypovolaemia (i.e. decreased in arterial blood volume).

The rise in plasma osmolality activates osmoreceptors within the hypothalamus that stimulate our thirst mechanism. Thirst is such a powerful mechanism for maintaining normal osmolality that even with extreme urine outputs seen in diabetes insipidus (> 10 L/day) hypernatraemia will not develop if the patient can continue to drink. Therefore, sustained hypernatraemia will usually only occur when the thirst mechanism is impaired or water is not available.

The predominant cause of hypernatraemia is unreplaced water losses.

There are three main mechanisms that lead to hypernatraemia:

• Unreplaced water losses (most common)
• Sodium overload: excess salt ingestion, may be oral (e.g. salt poisoning) or intravenous (e.g. hypertonic saline)
• Water loss into cells: usually temporary event that occurs following extreme exercise or seizure

Unreplaced water losses

Most commonly seen in the elderly presenting with a concurrent illness such as urinary tract infection or gastroenteritis. Typically seen in patients with dementia due to the reliance on others for maintaining oral intake.

There are three major systems through which water is lost:

• Skin: water loss from skin can be insensible (transepidermal diffusion) and sensible (sweating). The normal volume of sweat is 500-700 ml/day. Sweat is hypotonic, so increased sweating leads to free water loss.
• Gastrointestinal losses: diarrhoea and vomiting can both lead to hypernatraemia.
• Urinary: most commonly due to osmotic diuresis (e.g. from hyperglycaemia) or polyuria from diabetes insipidus (discussed below).

Diabetes insipidus

Diabetes insipidus is caused by a decreased release or increased resistance to anti-diuretic hormone:

• Central: reduced secretion of ADH. May be idiopathic (most common) or occur secondary to many conditions including tumours, hypopituitarism or surgery.
• Nephrogenic: resistance to the effect of ADH. Often due to an inherited defect in the gene for the ADH receptor on the X-chromosome. Other causes include chronic lithium use and hypercalcaemia.

The clinical consequence of an inadequate ADH response is polyuria (increased urine) and polydipsia (increased thirst). If the thirst mechanism remains functioning (will be in most cases) and the patient can continue to drink, then hypernatraemia should not develop.

Any compromise in the thirst mechanism or ability of the patient to drink (e.g. peri-operatively) can lead to a dramatic loss of free water and rise in plasma sodium concentration.

NOTE: a form of diabetes insipidus known as adipsic diabetes insipidus occurs when both the ADH and thirst mechanism are impaired. This leads to dangerous, recurrent episodes of hypernatraemia. May be congenital or acquired (e.g. sarcoidosis).

The primary symptom of hypernatraemia is usually pronounced thirst.

The clinical features can often indicate the underlying cause. It is important to exclude polyuria, which may be suggestive of diabetes insipidus.

Symptoms

• Thirst
• Dehydration
• Lethargy
• Fever (if concurrent illness)
• Nausea & vomiting (may precipitate hypernatraemia)
• Diarrhoea (may precipitate hypernatraemia)
• Confusion
• Abnormal speech

Signs

• Dry mucous membranes
• Postural hypotension
• Tachycardia, hypotension (signs of volume depletion)
• Altered mental status
• Oliguria (if dehydrated)
• Polyuria (may indicate diabetes insipidus)

The diagnosis of hypernatraemia is based on a laboratory sample of plasma sodium > 145 mmol/L.

The diagnosis of hypernatraemia is easily made from a urea and electrolyte (U&E) blood sample. Further investigations depend on the suspected underlying cause (e.g. chest x-ray or urine culture if infection suspected).

Urine electrolytes

Urinary sodium is a useful marker of TBW. A urinary sodium < 10 mEq/L is suggestive of volume depletion and overactivation of the renin-angiotensin aldosterone system (RAAS).

Urine osmolality

Urine osmolality is useful at differentiating suspected cases. It should be used in context of the urinary sodium and volume status of the patient (e.g. hypovolaemia, euvolaemia, hypervolaemia).

• Osmolality > 300 mOsm/kg: appropriately high if non-renal cause (e.g. diarrhoea, increased insensible losses).
• Osmolality < 300 mOsm/kg: inappropriately low if renal cause (e.g. diabetes insipidus, renal disease, diuretics).

Bloods

A series of routine blood tests help determine the cause.

• FBC
• U&E
• LFT
• Bone profile (hypercalcaemia can cause nephrogenic diabetes insipidus)
• Plasma osmolality
• Blood glucose
• CRP/ESR (if infection suspected)
• Creatine kinase

The principal treatment of hypernatraemia involves restoration of total body water and treating the underlying cause.

The goal is to provide fluid replacement but to reduce serum sodium concentration by no more than 10 mmol/L in a 24-hour period. More rapid correction can lead to rapid shifts of water intracellularly. In the brain, this can lead to major neurological injury from cerebral oedema.

Estimating fluid replacement

The amount of fluid needed to replace the fluid deficit and carefully reduce serum sodium can be estimated using different formulas.

• Formula 1 (total body water): TBW = weight (kg) x correction factor*
• Formula 2 (sodium correction): serum sodium change = (infused sodium - serum sodium) ÷ (TBW + 1)

*Correction factors: Children and men (0.6), women and elderly men (0.5), elderly women (0.45)

Formula 2 is based on the infusion of 1L of fluid that may have a variable content of sodium:

• One litre 5% dextrose: sodium concentration 0 mmol/L
• One litre 0.45% sodium chloride: sodium concentration 77 mmol/L
• One litre of balanced crystalloid (e.g. Hartmann’s): sodium concentration ~130 mmol/L
• One litre of 0.9% sodium chloride: sodium concentration 154 mmol/L

Example

An elderly male is 70 kg and found to have a serum sodium concentration of 161 mmol/L

First step

• TBW = 70 x 0.5 = 35 L

Second step

Two scenarios are listed below. In one he is prescribed a litre of a balanced crystalloid and the other a litre of 5% dextrose.

• Serum sodium change (if 1L Hartmann’s) = (133 - 161) ÷ (35 + 1) = -0.8 mmol/L
• Serum sodium change (if 1L 5% dextrose) = (0 - 161) ÷ (35 + 1) = -4.5 mmol/L

Third step

The aim is to reduce serum sodium by no more than 10 mmol/L within 24 hours:

• Serum sodium change over 24 hours (Hartmann’s) = 10 ÷ 0.8 = 12.5 L (i.e. with 12.5L of balanced crystalloid over 24 hours, sodium would fall by 10 mmol/L)
• Serum sodium change over 10 hours (5% dextrose) = 10 ÷ 4.5 = 2.2 L (i.e. with 2.2 L of 5% dextrose over 24 hours, sodium would fall by 10 mmol/L)

Additional litres of fluid can be added to these regimens to account for fluid losses.

Clinical practice

The above formulas are good for guiding fluid management in patients with hypernatraemia, but one size does not fit all. Compounding factors may be present such as marked hyperglycaemia or hypervolaemic hypernatraemia.

Usually, a combination of crystalloids are used to help restore water depletion while not over correcting the serum sodium. It is vital that serum sodium is checked regularly and the patients fluid balance frequently assessed. This allows clinicians to adapt management to changes in serum sodium and fluid status.

Diabetes insipidus

The management of diabetes insipidus depends on whether it is central or nephrogenic. It is a complex condition and should always be managed based on advice of the endocrinology team.

General management principles:

• Central: administration of desmopressin (synthetic ADH)
• Nephrogenic: remove offending agents (e.g. lithium) if required. Options include combination of low-salt diet, low-protein diet, diuretics, and non-steroidal anti-inflammatory drugs.

Last updated: May 2021