Metabolic and electrolyte disturbances

Hyponatraemia

Aetiology

The cause can usually be determined from a few simple investigations combined with clinical examination. The central role of clinical determination of volume status can be seen from figure 1. The cause of hypo-osmotic hyponatraemia cannot be determined from simple investigations without clinical examination.

• Determine whether the patient has hypo-osmolar or non-hypo-osmolar hyponatraemia.
• Non-hypo-osmolar hyponatraemia may be due to pseudo-hyponatraemia (secondary to hyperproteinaemia or hypercholesterolaemia), excess effective osmoles in the extracellular fluid (ECF) or excess ineffective osmoles in the ECF (eg urea).
• Patients with pseudohypnatraemia and those in who hyponatraemia is purely due to excess effective osmoles in the ECF are not at risk of cerebral oedema.
  • Excess effective osmoles in the ECF (most commonly glucose, mannitol or glycine) result in a shift of water from intracellular to extracellular fluid. This increase in water in the ECF causes hyponatraemia.
  • When the excess effective osmoles are eliminated (eg after treatment of hyperglycaemia) the fluid will shift back into the intracellular space and the serum sodium will return to normal
  • To check whether hyponatraemia is purely due to hyperglycaemia use the following equations to calculate a corrected sodium concentration:
    
    when glucose is measured in mmol/L or
    
    when glucose is measured in mg/dl
• Patients with non-hypo-osmolar hyponatraemia with excess ineffective osmoles (eg urea) have hypotonic hyponatraemia (the ineffective osmoles do not contribute to tonicity because urea passes freely into cells) and are at risk of cerebral oedema
• Patients with hypo-osmolar hyponatraemia are hypotonic

Clinical features and management

• Initial step is to determine the severity of symptoms and whether the symptoms are due to hyponatraemia
• Severe symptoms include:
  • Vomiting
  • Coma or deep somnolence
  • Seizures
• Moderate symptoms:
  • Nausea (without vomiting)
  • Confusion
  • Headache
• Severity of symptoms related to degree of hyponatraemia and speed of development. Rarely causes symptoms when sodium > 125 mmol/L except when decrease in concentration has been rapid

Hyponatraemia with severe symptoms

• Control airway/ventilation/seizures
• Call for help
• In the meantime give 2 mL/kg 3% saline over 20 minutes then send sample for serum sodium concentration. Give a further 2 mL/kg 3% saline while waiting for the result
• Make a diagnosis and start cause-specific treatment
• Do not allow the serum sodium concentration to rise by more than 10 mmol/L in the first 24 h and 8 mmol/L in subsequent 24 h periods until the concentration reaches 130 mmol/L

Hyponatraemia with moderate symptoms

• Make a diagnosis of the cause of hyponatraemia and start cause-specific treatment
• In the meantime give 2 mL/kg 3% saline over 20 min once
• Aim for rise of 5 mmol/L per 24 h and do not allow the sodium rise by more than 10 mmol/L in the first 24 h and 8 mmol/L in subsequent 24 h periods until the concentration reaches 130 mmol/L

Excessively rapid correction of hyponatraemia

• May cause osmotic demyelination, resulting in severe permanent brain damage
• If the sodium rises more rapidly than the limits given above, lower the serum sodium concentration so that it is within the target range:
  • Stop on-going active treatment aimed at increasing sodium (eg sodium infusion)
  • Consult an expert whether it is appropriate to give sodium-free fluid (eg 5% glucose) IV ± IV desmopressin

Hyponatraemia due to diuretics

• Pathogenesis multifactorial
• Hyponatraemia due to diuretic therapy for hypertension is usually mild but may be moderate or severe in patients who drink large volumes of hypotonic fluids
• Elderly women are especially prone to develop severe hyponatraemia
• Treatment is water restriction and K replacement

Hyponatraemia associated with oedematous states

• Despite the oedema, usually associated with intravascular fluid depletion or decreased cardiac output
• Severity of hyponatraemia correlates to some extent with magnitude of oedema and seriousness of underlying condition
• Hyponatraemia often of little clinical significance and principal features usually those of underlying disease
• Symptomatic hyponatraemia occurs most often following aggressive diuretic therapy or excessive oral or parenteral intake of dilute fluids
• Responds to effective therapy of underlying disease but fluid restriction to 1-1.5 L/day may be necessary in patients with severe or progressive hyponatraemia
• Hypertonic saline should not be given (total body sodium is high) except for clinical manifestations of extreme hyponatraemia (eg coma, convulsions). Give frusemide concurrently to avoid expansion of extracellular fluid (ECF) volume
• Renal replacement therapy can be used to correct severe hyponatraemia without reducing ECF volume but requires great care to avoid over-rapid correction

Syndrome of inappropriate anti-diuresis

• May be caused by inappropriate ADH secretion (SIADH) but can also be caused by hereditary conditions and drugs (including antidepressants, anticonvulsants, antipsychotics, NSAIDs, opiates, vasopressin analogues)
• Essential criteria for diagnosis:
  • Hypotonic hyponatraemia
  • Clinical euvolaemia
  • Urine osmolality > 100 mOsm/kg with hypotonic serum
  • Urine sodium > 30 mmol/L with normal dietary salt and water intake
  • No recent diuretic use
  • No thyroid, adrenal, renal and pituitary insufficiency
• During fluid loading (even if fluid is saline) hyponatraemia increases due to water retention and urinary sodium wasting
• Management:
  • Treat cause
  • Limit fluid intake. Usually 1-1.2 l/day is sufficient restriction
  • Initial therapy with hypertonic saline for patients with severe symptoms (see above)

Hypernatraemia

Aetiology

• Excess sodium intake
• Water depletion
  • No access to water (coma, desert)
• Water loss
  • Diabetes insipidus
  • Diarrhoea, vomiting
  • Burns, sweating

Clinical features

• Headache, irritability, convulsions, rarely intracerebral or subarachnoid haemorrhage

Management

• Free water either enterally or as 5% glucose
• Specific management of diabetes insipidus
• Correct no faster than 10 mmol/L/day

Diabetes insipidus

Aetiology

Diagnosis

• Inappropriately low urine osmolality. Normal relationship during dehydration is given in table 2

Acute management of cranial diabetes insipidus

• Water repletion using 5% dextrose
• If needed, intravenous arginine vasopressin may be given, titrated to response

Management of renal diabetes insipidus

• Oral fluid often all that is necessary
• Thiazides. Amiloride is specifically useful in lithium toxicity as it blocks lithium entry into collecting duct cells
• Non steroidal anti-inflammatory drugs
• Treat underlying cause/stop causative agent

Hypokalaemia

Aetiology

See table 3

Clinical features

• Weakness, hypotonicity
• Depression
• Ileus, constipation
• Ventricular arrhythmias (classically torsades), atrial arrhythmias
• Ventilatory failure
• Coma
• Rhabdomyolysis in severe and prolonged cases
• Nephrogenic diabetes insipidus (chronic hypokalaemia)
• ECG changes: prolonged PR, inverted T waves and U waves

Treatment

Replace potassium, usually by the enteral route. Indications for intravenous administration:

• moderate hypokalaemia, high risk of arrhythmias and enteral administration contraindicated
  • repeated doses of 10-20 mmol infused over 1 hour
• severe hypokalaemia (serum concentration <2.5 mmol/L)
  • more rapid correction may be required in the presence of cardiac arrhythmias
  • this is a potentially life threatening condition and urgent senior advice should be obtained

Hyperkalaemia

Aetiology

Clinical features

• Tingling, parasthesia, weakness, flaccid paralysis
• Hypotension, bradycardia
• ECG:
  • Peaked T waves
  • P wave flattened
  • PR prolonged
  • Sinus arrest and nodal rhythm
  • Widened QRS
  • Deep S
  • Sine wave
  • Asystole

Management

Severe hyperkalaemia (>6.5 mmol/L or wide QRS complexes)

• Calcium gluconate 10% 10 mL by slow IV injection
• Insulin and glucose
  • 10 U insulin IV bolus
  • 50 mL 50% glucose
  • monitor blood glucose concentration carefully
• ± Sodium bicarbonate
  • only likely to be effective in the presence of acidosis because Na/H antiport only active when there is intracellular acidosis
• ± Inhaled 2 agonist (25-40% of patients do not respond)
• Arrange renal replacement therapy while above treatment is being given

NB severe hyperkalaemia MUST be treated urgently

Moderate hyperkalaemia (5.5-6.5 mmol/L)

• Loop diuretic
• Potassium restriction
• Insulin and glucose (as above)

Diabetic ketoacidosis

Causes

• 20% cases initial presentation of diabetes mellitus
• Failure to take insulin (Type I diabetes)
• Infection
• Sterile inflammation eg MI
• Excessive physical activity

Clinical features

Symptoms

• When history available varies from a few weeks to a few days
• Osmotic symptoms: thirst, polydipsia, polyuria
• Anorexia
• Vomiting diarrhoea. Vomiting particularly useful as a warning in known diabetic
• Abdominal pain: dull persistent discomfort often affecting whole abdomen but usually centred on the umbilicus

Signs

3 cardinal signs:

• Dehydration
• Overbreathing
• Ketones on breath

Others:

• Confusion/coma
• Shock
• Signs of diabetes and complications
• Signs of precipitating factor

Investigations

• Hyperglycaemia
• Metabolic acidosis. Initially high anion gap but as ketones excreted becomes normal anion gap acidosis
• Hyperkalaemia usual, but hypokalaemia possible
• Biochemical and haematological features of dehydration
• Glycosuria and ketonuria while urine flow adequate
• ECG
• CXR
• Microbiological cultures
• Full blood count

Treatment

General

• Unrinary catheter (severe cases)
• Consider ICU referral for severe cases with signs of shock or severe acidosis

Fluids

• NB patients with rapid onset of diabetic ketoacidosis are not necessarily severely dehydrated unlike patients who have gone out of control slowly
• Start replacement with 1L N/saline over 1 hour and then decrease to 100 mL/hr but titrate against urine flow
  • If serum K⁺ concentration is normal or below normal and the urine output is normal, add KCl to fluid replacement to produce a concentration of 20 mmol/L
  • If serum K⁺ concentration is above normal wait until the concentration falls into the normal range and then add KCl to the fluid replacement (as above)
  • Monitor potassium concentration hourly then 2 hrly
• When plasma glucose has decreased to 10 mmol/L start giving IV glucose. Hyperglycaemia is more rapidly corrected then acidosis and it is important to continue infusion of insulin

Acidosis

• Use of bicarbonate controversial. No evidence that administration improves outcome
• Note that administration of bicarbonate will exacerbate hypokalaemia and is associated with the development of cerebral oedema

Insulin

• Initially 5-10 U/hr. Titrate against glucose
• Aim to lower plasma glucose by 5 mmol/hr. Excessively rapid correction of hyperosmolality associated with the development of cerebral oedema
• Do not give insulin until K⁺ >3.5 mmol/L as insulin may cause hypokalaemia

Complications

Cerebral oedema

• >95% of cases occur in patients < 20 yrs with 1/3 in those <5yrs
• More common in newly diagnosed diabetics
• Pesentation varies: may be a gradual worsening of coma from admission or more commonly a gradual improvement followed by a sudden deterioration with LOC, fixed dilated pupils or respiratory arrest. Only 1/2 have a period of neurological deterioration during which intervention may be effective before respiratory arrest
• Most cases occur 4-12 h after start of treatment
• Aetiology is unknown. Possible factors include excessive rates of IV fluid infusion, fall in plasma sodium concentration and tissue hypoxia due to rapid infusion of bicarbonate (left shift of Hb dissociation curve)
• Management: exclude hypoglycaemia, 0.5 g/kg of mannitol over 5-10 mins, intracranial pressure monitoring and hyperventilation, CT brain

Diabetic hyperosmolal non-ketotic coma

Clinical features

• More common in elderly
• Slow onset
• Infection, cardiovascular disease, steroids, diuretics and intake of glucose rich fluids are precipitant causes
• Dehydration
• ±Hyperventilation due to cerebral dehydration
• ±Focal neurological signs due to dehydration or thrombosis

Investigation

• Marked hyperglycaemia. Often >50 mmol/L
• No detectable ketonuria or acidosis
• Hypernatraemia (may be hypo-)
• Uraemia
• ±Respiratory alkalosis
• Increased osmolality

Treatment

• Fluid replacement with isotonic saline
• Insulin infusion
• Potassium replacement - less required than in ketocacidosis

Hypoglycaemia

• Always consider hypoglycaemia in patients with decreased level of consciousness or fits
• Causes include:
  • Drugs: insulin, oral hypoglycaemics (sulphonylureas)
  • Severe critical illness
  • Insulinoma
  • Severe liver disease, especially combined with alcoholism
• Treatment
  • Intravenous thiamine 100 mg
    • Can be omitted if the cause of hypoglycaemia is known not to be alcohol-related
    • Should precede administration of glucose
  • Intravenous glucose
    • 50 mL 50% glucose intravenously