Guidelines for the management of hyponatraemia

Children’s Kidney Centre

University Hospital of Wales
Cardiff
CF14 4XW

DISCLAIMER: These guidelines were produced in good faith by the author(s) in conjunction with the
paediatric nephrology team at the University Hospital of Wales, Cardiff reviewing available
evidence/opinion. They were designed for use by paediatric nephrologists at the University Hospital of
Wales, Cardiff for children under their care. They are neither policies nor protocols but are intended to
serve only as guidelines. They are not intended to replace clinical judgment or dictate care of
individual patients. Responsibility and decision-making (including checking drug doses) for a specific
patient lie with the physician and staff caring for that particular patient.

Dr Graham Smith
October 2019
Summary
These guidelines are aimed at providing the doctors presented with a child with
hyponatraemia with information to help identify the underlying problem and to guide
treatment.

Introduction
Hyponatremia, defined as serum [Na+] sodium < 135 mmol/l, reflects deficiency of
sodium relative to water. Serum [Na+] is the main determinant of plasma osmolality
and hence hyponatraemia reflects hypo-osmolality. This will result in water
movement into cells including brain cells, accounting for the symptoms of
hyponatraemia.

Serum osmolality (calculated) = 2 × (serum [Na+]) + serum [urea] + serum [glucose]

Effective circulating volume refers to that part of the extracellular fluid (ECF) that is in
the vascular space and available to perfuse tissues.

Volume depletion refers to a decrease in ECF volume from any cause, most often
due to sodium and water loss.

Serum [Na+] and plasma osmolality are monitored by a very sensitive

osmoreceptor in the hypothalamus that regulates the secretion of the antidiuretic
hormone, arginine vasopressin (AVP). AVP facilitates urinary concentration
increasing the transcription and insertion of water channels (Aquaporin-2) into the
apical membrane of the distal convoluted tubule and collecting duct epithelial cells
and water excretion is enhanced in its absence.

Serum [Na+] is determined mainly by total body water but also by total body sodium
and renal excretion of sodium is regulated by effective plasma volume (not by
plasma osmolality). Water retention (due to a defect in excretion) leading to an
excess of water in relation to solute is the common denominator in almost all patients
with hyponatraemia. Virtually all (except those with renal failure & primary polydipsia)
will have an excess of antidiuretic hormone (ADH), most often due to effective
circulating volume depletion or rarely due to SIADH.

Causes
Mechanisms for hyponatremia:
1. Loss of sodium in excess of water
2. Gain of water in excess of sodium

Hypovolaemic - ECF volume contraction (Total body water ↓, total body sodium
↓↓)
Renal (Urine [Na+] > 20 mmol/l) -
 Mineralocorticoid deficiency/resistance
 Diuretics
 Polyuric acute renal failure
 Salt wasting renal disease
 Renal tubular acidosis
 Metabolic alkalosis
 Syndromes - Bartter`s / Gitelman`s
Gastrointestinal (Urine [Na+] < 20 mmol/l) -
 Diarrheal dehydration
 GI suction/fistula/stoma
 Laxative abuse
 Transcutaneous - Cystic fibrosis, heat exhaustion
 Third space loss
 Burns, major surgery
 Septic shock, trauma
 Intestinal obstruction

Euvolaemic - Normal ECF volume (Total body water ↑, total body sodium ↔)
 Glucocorticoid deficiency
 Hypothyroidism

Hypervolaemic - ECF volume expansion (Total body water ↑↑, Effective circulating
volume ↑, total body sodium ↑)
 Acute renal failure (e.g. PIGN)
 Chronic renal failure
 Cirrhosis / Congestive cardiac failure
 Nephrotic syndrome
 Capillary / vascular leak syndrome
 Psychogenic polydipsia / compulsive drinking

Mild hypervolaemia
 Antidiuretic drugs
 Reduced renal water excretion
 Inappropriate secretion of ADH (SIADH)

Factitious – hyperglycaemia / mannitol / sorbitol

History
1. Symptoms suggestive of underlying disorder
2. Symptoms of hyponatraemia

Symptoms of hyponatraemia primarily reflect neurological dysfunction (due to brain

cell swelling) induced by hypo-osmolality, the severity of which depends on the
speed and degree of the reduction in the serum [Na+]. The symptoms include
anorexia, nausea, vomiting, malaise, lethargy, confusion, agitation, headache,
seizure, coma and decreased reflexes. Hyponatraemia can also cause hypothermia,
muscle cramps and weakness.

Assessment of urine output, fluid balance and weight changes is essential.

Physical examination
In addition to basic parameters (e.g. Wt, BP), it should include clues of the
underlying cause and assessment of ECF volume status.
Investigations
In addition to the appropriate tests to confirm the underlying disorder, the following
investigations are essential:

Blood
 Osmolality
 Sodium, potassium, chloride, bicarbonate
 Urea, creatinine, glucose
 Blood gas if bicarbonate abnormal

Urine
 Osmolality
 Sodium, potassium, chloride
 Urea, creatinine
 Calculate fractional excretion of sodium and fractional excretion of water

Calculation of fractional excretions of water (FEH2O) and sodium (FENa)

FEH2O = serum [creatinine] / urine [creatinine]

FENa = (urine [Na+] / serum [Na+]) x (serum [creatinine] / urine [creatinine])

Convert serum [creatinine] to mmol/l

FE values are often expressed as % (multiply result by 100)

The FEH2O is the fraction of the glomerular filtrate volume (GFR) that appears as
urine.
The FENa is the fraction of the sodium filtered by the glomeruli which appears in the
urine.
The FE values in health vary because people’s water and salt intakes vary; there are
therefore no normal ranges. However, under stress they respond predictably, so can
be used to understand the pathophysiology. Even mild dehydration causes a release
of ADH and renin, and thus avid tubular reabsorption of water and salt leading to a
fall in FEH2O and FENa. Children with healthy kidney tubules can lower both FE
values to <1%, and often much lower.

Urine osmolality
Indicates whether water excretion is normal or impaired. The majority of patients with
hyponatraemia will have a value just above 100 mOsm/kg, but it may still be hypo-
osmotic to plasma and inappropriately high.
Syndrome of inappropriate ADH secretion (SIADH)
This rare but frequently over diagnosed condition is characterized by non-physiologic
release of ADH (not inhibited by either low serum osmolality or expanded
intravascular volume) and by the unusual finding of impaired water excretion at a
time when sodium excretion is normal.
Persistent ADH release leads to water retention resulting in dilution (hyponatremia
and hypoosmolality) and expansion of body fluids. The kidneys increase sodium
excretion (hence no oedema) in an effort to correct the volume status, leading to a
mild decrease in total body sodium.

Causes of SIADH
CNS disorders
 Infections
 Malignancy
 Trauma
 Hypoxic damage
 Cerebral malformations
 Vascular accidents
 Guillain-Barre syndrome
Post-surgery
 Abdominal
 Cardiothoracic
 Neurosurgery
 Anaesthetic or premedication
Pulmonary
 Infections
 Malignancy
 Cystic fibrosis
 Mechanical ventilation
Drugs
 Cyclophosphamide
 Carbamazepine
 Vincristine
 Vinblastine,
 Others
Others
 Leukaemia
 Lymphoma,
 Porphyria
 HIV infection
 Ectopic production of ADH

Diagnostic criteria
The term SIADH is a diagnosis of exclusion and is frequently misused in clinical
practice, since many patients thought to have SIADH have an alternative explanation
for hyponatraemia. Frequently the secretion of ADH is appropriate rather than
inappropriate and unrecognised hypovolaemia is present.
Presence of…. Absence of….
1. Hyponatremia & hypoosmolality 1. Dehydration/volume depletion or
2. Urine osmolality is inappropriately ingestion of diuretics
high, commonly >100 (usually > 2. Renal, hepatic or cardiac
plasma osmolality) failure/dysfunction
3. Decrease in haematocrit, plasma 3. Pituitary or thyroid dysfunction
albumin, urea & creatinine due to 4. Other known stimuli for ADH secretion
increased ECF volume - pain, nausea, drugs or thermal injury
4. Urine sodium >20,(usually >40 mmol/l)
and shows normal response to sodium
restriction

Management of hyponatraemia (see algorithm)

1. Identify and treat the underlying cause
2. If hyponatraemia has developed acutely (over 12-24 hours) and the patient has
severe neurological symptoms, urgent correction is needed (until symptoms are
controlled) - by infusing 4-6 ml/kg of 3% sodium chloride, which will increase
serum [Na+] by 3-5 mmol/l. Maximum infusion rate is 4 ml/kg/h (which raises
serum [Na+] by 3 mmol/l/h). Further correction can be done slowly.
3. Those with chronic hyponatraemia tend to be the least symptomatic and are at
higher risk of severe side effects (e.g. central pontine myelinolysis) if serum [Na+]
is corrected too rapidly.
4. If there is ECF volume depletion infusing a fluid isotonic to the patient is ideal in
order to avoid too rapid a rise in serum [Na+] if using 0.9% NaCl.
5. Hyponatraemia should be corrected slowly (rate of correction of serum [Na+]
should be < 0.3 mmol/l/h or <8 mmol/l/day). Regular measurement of serum [Na+]
is essential.
6. The focus of treatment depends on the clinical setting:
a. Create a negative balance for electrolyte free water (EFW)
b. Create a positive balance for Na+
c. Replace any deficit of K+

Sodium deficit = 0.6 × Wt (in Kg) × (desired serum [Na+] - current serum [Na+])
Assessment of hyponatraemia