Management of symptomatic hyponatraemia

Hyponatraemia is defined as plasma sodium <135mmol/L. There is an excess of water relative to sodium in the extracellular fluid compartment, due to an excess of water, a deficit of sodium or more commonly a combination of both. In order for hyponatraemia to develop ADH has to be present and there has to be a source of water. Acute hyponatraemia is arbitrarily defined as < 48 hours duration.

• Hyponatraemia is the commonest electrolyte abnormality in hospitalized patients
• Hospital acquired hyponatraemia occurs because too much fluid and or hypotonic fluid is given to patients who have a non-osmotic stimulation for antidiuretic hormone release
• Oliguria does not have to be due to dehydration, it may secondary to non osmotic stimulation of ADH secretion
• 0.45% Sodium chloride 5% glucose is isosmolar but hypotonic because the glucose is metabolized to water in vivo
• The tonicity (effective osmolality) determines water movement between the intracellular and extracellular compartments
• Hyponatraemia is usually asymptomatic
• Symptoms are more likely to occur if the plasma Na <125mmol/L or if there has been a rapid fall in the sodium level. This is because the brain has a time-limited ability to cope with the accompanying change in plasma tonicity. There is significant inter-individual variation in the process of cellular volume regulation that can be influenced by intercurrent disease, and physiological status e.g. hypoxia, acidosis.
• Hypoxia limits the ability of the brain to adapt to hyponatraemia
• Hyponatraemic seizures may be resistant to normal anticonvulsant therapy
• Symptoms are due to cerebral oedema. The brain has a maximum capacity to increase in volume due to its constraint within the skull (estimated at 5-10%).
• The deterioration to respiratory arrest from the onset of symptoms can be precipitous in children. Children have the potential to develop symptoms at a higher plasma sodium level and earlier during a decrease because they have a higher brain:skull volume ratio, higher brain water content, a proportionately smaller intra-cerebral CSF volume and higher cerebral intracellular sodium content than adults. As such they have decreased capacity to adapt to hypotonicity.
• There is no way of predicting which children will develop symptoms or have a respiratory arrest
• Ill children have many non-osmotic stimuli to ADH secretion, pain, nausea, stress, drugs and surgery.
• Traditional maintenance fluid requirements overestimate requirements in ill children.
• Any hospitalised child is at risk of hyponatreamia whether receiving oral or intravenous therapy
• Early symptoms of hyponatraemic encephalopathy are non specific and maybe attributed to the post operative state or accepted as the child being unwell.
• Acknowledging that children are at risk from iatrogenic hyponatraemia, anticipating symptoms and monitoring appropriate biochemistry and fluid balance should minimise the risks and allow timely institution of appropriate therapy.
• The evidence for therapy is based on case reports, small case series, retrospective reviews, cohort studies, mainly in the adult population, and animal studies. There is a complete lack of controlled therapeutic trials. As such optimal treatment strategies have not been established.

• The Syndrome of Inappropriate Diuretic Hormone (SIADH) is a diagnosis of exclusion
• Most hyponatraemic patients can be managed safely and appropriately with fluid restriction
• Hypertonic sodium chloride is usually not necessary for the asymptomatic patient (exception cerebral salt wasting)
• During correction of symptomatic hyponatraemia patients should be managed in a setting where adequate frequent detailed assessment can occur- ideally an HDU or PICU
• The decision to treat with 2.7% sodium chloride should be based on the presence of symptoms rather than duration of hyponataremia
• Duration of hyponatraemia will modify the rate of correction
• During correction, fluid balance and biochemical data should be repeatedly assessed to ensure that correction of hyponatraemia is occurring without overcorrection ie ≥ normonataremia
• Chronic hyponatraemia should be corrected slowly unless it is symptomatic
• The rate of correction should be slowed once the patient is asymptomatic Chronic hyponatraemia arbitrarily defined as being >48 hours in duration is usually asymptomatic because the brain has adapted to the hypotonic state. The process of adaptation occurs over 48 hours in animal models and the equivalent duration in humans has not been accurately determined. Aggressive correction can be too quick for the brain to de-adapt, and can itself result in severe neurological disability secondary to osmotic demyelination.
• In treating hyponatraemia the risk of correction must be balanced against the risk of the hyponatraemic state.
• There are very few cases of reported osmotic demyelination secondary to treatment of hyponatraemia (though as with symptomatic hyponatraemia this could easily be under reporting)
• Osmotic demyelination is associated with correction to nomonatraemia and above
• Osmotic demyelination has not been reported following correction of acute hyponatraemia unless there are associated risk factors, such as burns, malnutrition, alcoholism
• It is the increment in plasma sodium during a 24 hour period rather than the rate of correction that predisposes to osmotic demyelination
• Rates of correction quoted in articles have been derived by averaging an increment over a time period retrospectively rather than been targeted prospectively
• Initial rapid correction of symptomatic hyponataremia is appropriate so long as the 24 hour increment is <12mmol/l and correction to normonataremia does not occur
• Accepting that there is an accepted safe increment, targeting below this is likely to avoid overcorrection
• Equations that predict correction rates and deficits fail to consider the effects of the added water and solutes and assume that there is no ongoing loss of fluid. As such they should not replace meticulous attention to detail and frequent sampling
• Rate of rise of plasma sodium following 2.7% sodium chloride infusion is a function of the volume of free water in the patient’s urine.
• 1ml/kg 2.7% sodium chloride will increase serum sodium by approximately 0.8mmol/l
• It is not possible to give precise recommendations for each individual case
• In most cases, the appropriate treatment of hyponatraemia relies on the identification of the underlying ECF volume status, the rate at which the hyponatraemia developed, and the severity of neurological symptoms present