Hypernatraemia is defined as plasma sodium concentration of >145 mmol/L (145 mEq/L). Symptoms of hypernatraemia are fairly non-specific. Symptoms of concurrent or past illnesses may point to the likely cause.
A thorough physical examination should be completed, including evaluation of volume status, mental status, and neurological assessment. Signs of hypernatraemia usually involve central nervous system (CNS) manifestations and include irritability, restlessness, muscle twitching, spasticity, and hyperreflexia, which are all due to a decreased water content in the brain.
Severe hypernatraemia (plasma sodium concentration >158 mmol/L [158 mEq/L]) may present with serious signs and symptoms, such as hyperthermia, delirium, seizures, and coma. Having established the presence of hypernatraemia, the underlying aetiology should be sought.
First, consider the age and mobility of the patient. Lack of access to water is a consideration in infants, disabled people, people with impaired mental status, postoperative patients, and intubated patients. The history should include the following:
Enquire about symptoms of hypernatraemia: irritability, restlessness, lethargy, muscle twitches, delirium and seizures.
Enquire about symptoms of concurrent illness that could lead to water loss. Symptoms of viral gastroenteritis include nausea, vomiting, and abdominal pain, in addition to diarrhoea. These patients may also have a history of contact with infected people, food, or fluids. Regardless of the cause, these patients may lose more water than sodium, leading to volume depletion and hypernatraemia. Increased body temperature and exposure to the elements should also be considered. Prolonged exposure to heat, fever, excessive sweating, exercise, and severe cutaneous burns result in insensible water loss due to evaporation from the skin and may cause hypernatraemia.
Take a past medical history to identify comorbidities that could lead to hypernatraemia, particularly severe uncontrolled diabetes mellitus (may lead to hyperglycaemia resulting in glycosuria, hypernatraemia, and hyperosmolar hyperglycaemic state), Cushing syndrome, primary aldosteronism, underlying kidney disorder (e.g., sickle cell disease, obstructive uropathy, and reflux nephropathy), or Crohn's disease (may have underlying enteric fistulae). Exclude conditions that can cause carbohydrate malabsorption (tropical sprue, pancreatitis, lactose intolerance and a history of bowel surgery). A history of traumatic brain injury or any other insult to the brain (vascular syndromes, infections, tumours, or aggressive neurosurgery for craniopharyngioma, Rathke cleft cyst, or other hypothalamic tumour) may be suggestive of central diabetes insipidus. On rare occasions, the presence of a brain tumour, or vascular occlusion in the brain, may cause primary hypodipsia that presents with hypernatraemic volume depletion.
A complete medication history is important. Drugs such as colchicine, gentamicin, lithium, rifampin, and propoxyphene may induce nephrogenic diabetes insipidus. Loop diuretics (e.g., furosemide and torsemide) and intravenous mannitol can cause an osmotic diuresis resulting in hypernatraemia. If a history of diarrhoea or loose stools is present, the patient should be asked about the use of any laxative or bowel cleansing agent (e.g., lactulose or sorbitol).
Iatrogenic causes may be a possibility in those patients currently being treated in hospital. These include inadvertent administration of hypertonic sodium chloride or sodium bicarbonate, or even the use of isotonic saline in a patient with an osmotic diuresis.
Take a dietary history. Inadequate breastfeeding without supplementation may lead to severe and potentially life-threatening hypernatraemia in the infant. Replacing sugar with salt in infant formula (accidental or intentional) can also result in hypernatraemia. High-protein diets, including high-protein tube feeds, lead to increased urea production and consequently osmotic diuresis, increasing the risk of hypernatraemia. In addition, consider ingestion of a highly concentrated emetic agent or gargle (e.g., Epsom salts).
The aetiology is most easily elicited by considering the patient's volume status. However, it is important to note that extracellular volume status is better preserved with hypernatraemia, at the expense of greater intracellular water depletion, and physical examination can therefore underestimate the total fluid deficit.
Includes renal and non-renal losses. In patients with signs of volume depletion (dry mucous membranes, poor skin turgor, sunken eyes, irritability, tachycardia, hypotension or postural hypotension, decreased urine output, and weight loss), severe diarrhoea, vomiting, and significant burns should be excluded. Temperature measurement is essential because fever may be the cause. The possibility of an enteric fistula should also be taken into account. Patients with hyperosmolar hyperglycaemic state (HHS) typically present with signs of severe volume depletion and may have neurological deficits (hemianopia or hemiparesis). In many cases, the clinical features of HHS and hypernatraemia overlap and are observed simultaneously.
These patients may present with signs of volume overload, including weight gain, peripheral oedema, hypertension, irritating cough, dyspnoea, jugular vein distention, and crepitations on auscultation. Usually due to exogenous sodium ingestion and mineralocorticoid excess. Therefore, signs of Cushing's syndrome as well as primary aldosteronism should be sought.
Cushing's syndrome: moon face, facial plethora, supraclavicular and/or dorsicocervical fat pads, truncal obesity, purple striae, proximal muscle weakness, hirsutism, growth retardation (children), hypertension.
Primary aldosteronism: hypertension, proximal muscle weakness.
Signs of volume depletion and overload absent. Nephrogenic diabetes insipidus or central diabetes insipidus are usually the underlying cause. A patient with central diabetes insipidus may show signs of recent trauma, pituitary surgery, or hypoxic or ischaemic encephalopathy.
Signs of hypernatraemia include muscle twitches, spasticity, hyperreflexia, hyperthermia, delirium, seizures and coma.
Baseline laboratory investigations
A plasma sodium concentration of >145 mmol/L (145 mEq/L) confirms the presence of hypernatraemia. Serum sodium levels of 150-170 mmol/L (150-170 mEq/L) usually indicate volume depletion and the causes thereof. Serum sodium of >170 mmol/L (170 mEq/L) is usually associated with diabetes insipidus (nephrogenic or central). Serum sodium of >190 mmol/L (190 mEq/L) is usually a result of exogenous sodium gain.
Urine osmolality may help determine the underlying aetiology. Normal kidney response to hypernatraemia is to excrete a minimal amount of urine that is maximally concentrated (urine osmolality >800 mmol/kg [800 mOsm/kg]). Hypertonic urine is usually observed with extra-renal fluid losses, as is the case with vomiting, diarrhoea, burns, and excessive sweating. Isotonic urine can be seen with diuretic use, osmotic diuresis, and salt wasting. Hypotonic urine associated with polyuria is seen with diabetes insipidus (central or nephrogenic).
A metabolic panel, including serum glucose, potassium, chloride, urea, and creatinine, should also form part of the initial work-up to exclude associated electrolyte abnormalities and renal impairment. In addition, an FBC should be considered a baseline investigation in cases of severe burns to exclude sepsis, and an ABG may be necessary in patients with prolonged vomiting or breastfeeding hypernatraemia to rule out an associated acid-base disturbance.
Specific laboratory investigations
For patients with severe diarrhoea, stool studies (faecal leukocytes, faecal pH, faecal reducing substance/sugar) may be of use in determining whether the aetiology is infectious in origin or is a consequence of carbohydrate malabsorption. Stool ion gap helps distinguish between the presence of an osmotic or secretory diarrhoea; secretory diarrhoea does not typically produce hypernatraemia.
Diabetes insipidus can usually be confirmed on the basis of hypertonic hypernatraemia and increased output of hypotonic urine (>3 L/24 hours), with commensurately increased thirst-driven fluid intake. Partial or more subtle cases may need to be confirmed by elective investigation in a specialist unit with a water deprivation test. Plasma arginine vasopressin (AVP) levels may not readily distinguish central diabetes insipidus from nephrogenic diabetes insipidus; the medical background will typically indicate whether central diabetes insipidus or nephrogenic diabetes insipidus is most likely, with confirmation arising from the response (or lack of it) to an AVP (desmopressin) stimulation test.
If primary aldosteronism is suggested by history or physical examination findings, an abnormally low plasma renin activity (PRA) level and an abnormally high plasma aldosterone concentration (PAC) level, resulting in high PAC:PRA ratio, supports this diagnosis. Diagnostic specificity can be improved by ensuring that the patient has first been rendered potassium replete and, where possible, by temporarily withdrawing drugs such as diuretics, beta blockers, ACE inhibitors, and angiotensin-II receptor antagonists several weeks beforehand. Confirmation of the diagnosis may require an aldosterone suppression test. A 24-hour urinary potassium may be considered if plasma renin activity and plasma aldosterone concentration are normal or if there is a clinical suspicion of surreptitious vomiting or laxative abuse.
Serum osmolality of >320 mmol/kg (320 mOsm/kg) together with a plasma glucose of >33.3 mmol/L (600 mg/dL) in a patient with altered mental status is strongly suggestive of hyperosmolar hyperglycaemic state (HHS). A markedly elevated serum osmolality is also seen with primary hypodipsia.
If Cushing's syndrome is suspected, diagnosis may be confirmed with a 24-hour urinary free cortisol, low-dose (or overnight) dexamethasone suppression test, and midnight serum or salivary cortisol levels.
Head CT scan or MRI may reveal a central cause for hypernatraemia and should be performed in all patients with severe hypernatraemia and no occult aetiology. In addition, brain imaging helps to exclude intracranial haemorrhage caused by traction on the dural bridging veins and sinuses as a result of brain shrinkage. Dural sinus thrombosis may occur from the haemoconcentration of total body water loss and can also be detected with head CT scan or MRI. CT scan or MRI of the adrenal glands may reveal an underlying adrenal mass lesion in patients with suspected primary aldosteronism.
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