Reducing the risk of hyponatraemia when administering intravenous infusions to children (2007) is an oustanding resource from the National Health Service.

A second outstanding resource is Reducing the Risk of Hyponatremia BMJ Learning Module. This learning module takes less than an hour to complete and includes a pretest and post test.

What follows is all from the BMJ Learning Module:

Key points

• Intravenous hypotonic solutions can kill and should be prescribed with caution as all children are at risk. Wherever possible, carefully managed oral fluids are preferable to intravenous fluids
• Hyponatraemia can develop within a short time frame. A robust fluid monitoring regimen is essential
• Intravenous fluids should be prescribed with the same rigour as other prescription medicines, particularly in respect of the volume given
• Hyponatraemic encephalopathy is a medical emergency and should be treated using hypertonic intravenous fluids

Clinical tips

• In the perioperative period children should only ever receive isotonic intravenous fluids. During surgery, the majority of children may be given fluids without glucose; blood glucose should be monitored if no glucose is being administered. Neonates in the first 48 hours of life and any infants already receiving glucose containing solutions should continue with them during surgery
• Some children at high risk of hyponatraemia should receive only isotonic solutions, such as:
  • Sodium chloride 0.9%
  • Sodium chloride 0.9% and glucose 5%
  • Hartmann’s solution or other balanced electrolyte solutions (such as Plasma-Lyte 148)
• Check the child’s weight before starting fluids and daily thereafter
• Measure the sodium, potassium, urea, and creatinine levels before starting fluids (apart from prior to elective surgery) and regularly during intravenous infusion therapy
• Monitor the fluid balance (including oral intake) as accurately as possible
• Sodium chloride 0.18% with glucose 4% should only be available in specialist areas to replace ongoing losses of hypotonic fluids. Specialist areas may include high dependency, renal, liver, and intensive care units

Definition of hyponatraemia

The specified normal range for plasma sodium varies between laboratories, but it is often quoted as being 135-145 mmol/l.

Hyponatraemia is defined as having a plasma sodium of less than 135 mmol/l, severe hyponatraemia is defined as having a plasma sodium of less than 130 mmol/l, while severe acute hyponatraemia is defined as a decrease in plasma sodium from normal to less than 130 mmol/l in less than 48 hours.

Mechanism of hyponatraemia and hyponatraemic encephalopathy

Hyponatraemia can be due to too much water or too little sodium in the extracellular fluid. Most commonly it indicates an expanded extracellular fluid volume and is rarely caused by sodium (or salt) depletion.

Under normal physiological conditions, the usual stimulus for release of antidiuretic hormone is a rise in plasma osmolality or other non-osmotic triggers.

Non-osmotic secretion of antidiuretic hormone can be induced from a variety of clinical situations, including:

• Pain
• Anxiety
• The postoperative state
• Nausea and vomiting
• Certain drugs, including lithium and tetracyclines
• Pyrexia
• Sepsis
• Reduced circulating volume
• Respiratory disorders
• Central nervous system infections
• Metabolic and endocrine disorders.

All unwell children should be assumed to have elevated levels of antidiuretic hormone.

Infusing hypotonic fluids in children in circumstances associated with elevated levels of antidiuretic hormone (see above) may result in hyponatraemia. [ 4 ]

Severe hyponatraemia may produce a variety of clinical features as water enters the brain cells and causes them to swell. These include:

• Headache
• Lethargy
• Disorientation
• Agitation
• Seizures
• Focal neurological deficits
• Respiratory arrest.

Progressive cerebral swelling may result in raised intracranial pressure, tentorial herniations, and, ultimately, death.

Clinical tips

Although there is much debate about the management of fluid therapy, some basic principles are agreed, such as [ 5 ] [ 6 ] :

• You should prescribe fluids with the same care that you would prescribe drugs (with reference to indications, contraindications, and appropriate dose)
• You must individualise the prescribing of fluids
• Whichever fluid you use, the optimal way of avoiding dangerous hyponatraemia or hypernatraemia is to calculate the fluid balance and monitor the plasma sodium concentration regularly.

When prescribing fluids you should use the following principles.

Resuscitation

Manage intravascular volume depletion using bolus doses of isotonic solution such as sodium chloride 0.9%.

Deficit

You should estimate and replace any fluid deficit with an isotonic solution such as sodium chloride 0.9% or a balanced electrolyte solution (such as Plasma-Lyte 148) over a minimum of 24 hours.

Ongoing losses

Ongoing losses should be reassessed every four hours. Fluids used to replace ongoing losses should reflect the electrolyte composition of the fluid being lost, and in most circumstances an isotonic solution is the safest choice; for example, sodium chloride 0.9%, Hartmann’s solution, or balanced electrolyte solution (such as Plasma-Lyte 148).

Maintenance

You should calculate the volume of fluid infused according to body weight (up to a maximum of 2500 ml a day in males and 2000 ml a day in females; see table 2).

Table 2: Calculating maintenance volumes of fluid
Less than 10 kg	100 ml/kg a day or 4 ml/kg an hour
10-20 kg	1000 ml plus 50 ml/kg a day for each kg over 10 kg or 40 ml an hour plus 2 ml/kg/hr for each kg over 10 kg
Over 20 kg	1500 ml plus 20 ml/kg a day for each kg over 20 kg or 60 ml an hour plus 1 ml/kg an hour for each kg over 20 kg

 

While most children will tolerate the standard maintenance fluid requirement, some acutely ill children with increased antidiuretic hormone secretion (for example, postoperative patients or those with intracranial infections or head injury) may benefit from restriction of their maintenance fluid requirement to two thirds of the normal recommended volume.

When considering which type of fluid to give, you need to remember:

• Most children may be safely administered sodium chloride 0.45% with glucose 5%
• Some children at high risk of hyponatraemia should receive only isotonic (with reference to the cell membrane) solutions (see table 1)
• You should never use sodium chloride 0.18% with glucose 4% as a maintenance fluid.

Children with the following risk factors should receive only isotonic solutions:

• Plasma sodium at the lower normal reference range; particularly if less than 135 mmol/l
• Intravascular volume depletion
• Hypotension
• Central nervous system infection
• Head injury
• Bronchiolitis
• Sepsis
• Peri- and postoperative patients
• Excessive gastric or diarrhoeal losses
• Salt wasting syndromes
• Chronic conditions such as diabetes, cystic fibrosis, or pituitary deficits
• Those requiring replacement of ongoing losses.

Children found to have significant hypernatraemia, with a plasma sodium concentration of greater than 160 mmol/l, should also receive only isotonic solutions to reduce the risk of neurological injury associated with a rapid fall in the plasma sodium concentration.

Monitoring

You need to check the child’s weight before starting them on fluids and daily thereafter. You should monitor their fluid balance and include the fluid intake. Measure the sodium, potassium, and urea or creatinine levels (or both):

• At baseline, before fluids are given (apart from before elective surgery)
• At least once daily while intravenous fluids are being administered.

Consider measuring electrolytes four to six hourly if you find an abnormality, and definitely if the plasma sodium is below 130 mmol/l.

Check plasma electrolytes immediately if clinical features that suggest hyponatraemia develop, such as:

• Nausea
• Vomiting
• Headache
• Irritability
• Altered level of consciousness
• Seizure
• Apnoea.

You need to monitor the fluid balance (including oral intake) as accurately as possible.

To avoid potentially misleading changes in serial sodium measurements, the same sampling technique (that is, capillary or venous blood) and analytical method should be used on each occasion.

Acute hyponatraemic encephalopathy

Acute symptomatic hyponatraemia is a medical emergency that must be treated immediately and aggressively.

You should use a hypertonic solution such as sodium chloride 3% solution (513 mmol/l) to rapidly correct the plasma sodium concentration over 10 to 20 minutes, up to 130 mmol/l in patients with acute symptomatic hyponatraemia. [ 7 ] You should never manage this life threatening complication with fluid restriction alone. [ 8 ]

Treatment is as follows:

• Maintain the airway – undertake endotracheal intubation and mechanical ventilation, if required, and give 100% oxygen
• Ensure that there is an adequate circulation
• Stop any hypotonic infusions
• Give hypertonic saline to rapidly correct the serum sodium concentration using the formula described below
• Admit the child to an appropriate critical care unit
• Frequently reassess the fluid and tonicity balance of the child.

You should calculate the amount of sodium needed according to the following formula:

Amount of sodium required (mmol) = (desired plasma sodium concentration – current plasma sodium concentration) x 0.6 x weight (kg)

What factors can increase the risk of hyponatraemia?

• Hypotonic fluids are still used too widely
• Clinical scenarios leading to an increased secretion of antidiuretic hormone increase the risk of developing hyponatraemia (for example, in postoperative patients)
• Some children are at greater risk of developing hyponatraemia; for example, patients with any of the following conditions:
  • Intravascular volume depletion
  • Hypotension
  • Central nervous system infection
  • Head injury
  • Bronchiolitis
  • Sepsis
  • Excessive gastric or diarrhoeal losses
  • Salt wasting syndromes
  • Where the plasma sodium is at the lower normal reference range, and definitely if it is less than 135 mmol/l
  • Peri- and postoperative patients, and
  • Patients with chronic conditions such as diabetes, cystic fibrosis, and pituitary deficits
• Most prescriptions for intravenous fluids are written by trainee doctors who may not have been given adequate training or supervision
• Children prescribed intravenous fluids may be inadequately monitored in terms of fluid balance, plasma electrolytes, and body weight
• Intravenous fluid prescriptions and fluid balance charts may be poorly designed. Fluid balance charts are often not completed or completed incorrectly
• There is often a lack of effective audit to ensure that the prescription of intravenous fluids is safe.

Which patients are at risk?

Significant hyponatraemia may occur as a complication of any fluid regimen, including situations where there is an uncontrolled intake of oral fluids.

A review of the literature suggests that children in the perioperative period and those with gastroenteritis and dehydration are at particular risk. [ 9 ]

Children with gastroenteritis and dehydration are at increased risk.

Children have a higher risk than adults of developing symptomatic hyponatraemia because they tend to develop hyponatraemic encephalopathy at higher plasma sodium concentrations.

Children also have a poorer prognosis because of a combination of physical and physiological differences, such as [ 10 ] :

• They have a higher brain:skull size ratio than adults; children’s brains reach adult size at around 6 years of age, whereas their skulls only reach their final adult dimensions at 16 years of age
• They have twice as much brain water as adults and 10% less intracerebral volume of cerebrospinal fluid for the brain to expand into
• In older adults there is a progressive loss of brain volume, while the volume inside the skull remains constant.

How can I help prevent iatrogenic hyponatraemia?

The majority of deaths and incidences of permanent neurological disability appear to be associated with the most hypotonic fluids, although neurological disability has been described after administration of sodium chloride 0.45%.

While it is valid to argue that hypotonic fluids may be safely prescribed if the volume of fluid given is tightly restricted, tragic episodes involving the deaths of previously healthy children show that in the real world it is not always possible to administer these fluids with sufficient monitoring to make this practice safe. [ 11 ] Sodium chloride 0.18% with glucose 4% intravenous solution is one such fluid and should never be used routinely.

Many experts propose that children should only be given isotonic solutions. [ 12 ]