Hyponatraemia and SIADH
Hyponatraemia
Hyponatraemia is co m proximately 30% of patients in
hospital. It is classified as mild (>130 mmol/L), moderate (125–129 mmol/L)
or severe (<125 mmol/L), according to either the degree of biochemical
disturbance or the clinical state of the patient. The rate of change of sodium
is more important than the absolute sodium value so patients with chronic hyponatraemia
can be asymptomatic, while patients with a sudden drop can be very unwell.
Early symptoms of hyponatraemia are headache, nausea, vomiting and general
malaise. Later signs are confusion, agitation and drowsiness. Acute severe
hyponatraemia leads to seizures, respiratory depression, coma and can result in
death.
Investigation
Making an accurate diagnosis of hyponatraemia requires full
clinical assessment and a systematic approach. Drug history and hydration
status are particularly important. Thiazide diuretics are a common cause of
hyponatraemia and should be stopped if possible. Biochemical investigations
include serum osmolality, urine osmolality, urine sodium, thyroid function and
an assessment of cortisol reserve (09.00 cortisol or Synacthen test). It is not
possible to make an accurate diagnosis without all of these investigations
(Figure 8.2).
Diagnostic approach
In acute severe hyponatraemia with neurological compromise,
hypertonic saline should be considered whatever the cause. This is a senior
decision and should only be carried out under close supervision. In mild or
moderate hyponatraemia, the diagnostic algorithm should be followed (Figure
8.2).
Serum and urine osmolality
Confirmation of low serum osmolality is important to
exclude non-hypo-osmolar hyponatraemia (e.g. hyperglycaemia). Once hypotonic
hyponatraemia has been confirmed, urine osmolality should be checked. A low
urine osmolality (<100 mosmol/kg) suggests primary polydipsia or
inappropriate administration of IV fluids. If urine osmolality is >100
mosmol/kg, urine sodium will guide the differential diagnosis.
Urine sodium
A low urine sodium (<30 mmol/L) suggests a low effective
arterial volume. This is seen either resulting from true volume depletion (e.g.
gastrointestinal salt loss), or when patients are clinically overloaded but
have intravascular depletion (e.g. congestive cardiac failure, cirrhosis or
nephrotic syndrome).
If urine sodium is >30 mmol/L and the patient is
euvolaemic, syndrome of inappropriate ADH (SIADH) should be considered,
although ACTH deficiency must be excluded. If urine sodium is >30 mmol/L and
patients are hypovolaemic, Addison’s disease, renal and cerebral salt-wasting,
or a history of vomiting should be considered – vomiting causes loss of
hydrogen ions and a metabolic alkalosis, which is corrected by the renal
excretion of sodium bicarbonate.
Severe hypothyroidism can cause hyponatraemia, although the
mechanism is unclear.
Management
Cause-specific treatment leads to biochemical correction.
Appropriate fluid replacement in patients with hypovolaemic hyponatraemia with
normal saline typically leads to improvement. In patients with hypervolaemic
hyponatraemia, specialist treatment of cirrhosis, nephrotic syndrome or
congestive cardiac failure is indicated.
Syndrome of inappropriate ADH
SIADH has many causes (Table 8.1). It is characterised by
euvolaemic hypo-osmolar hyponatraemia in the context of low serum osmolality
(<275 mosmol/kg), urine osmolality >100 mosmol/kg and urine sodium >30
mmol/L. SIADH can only be diagnosed after the exclusion of hypothyroidism,
total salt depletion and ACTH deficiency.
ACTH deficiency appears identical to SIADH because it
causes reduced excretion of free water, because cortisol deficiency leads to
increased vasopressin activity. This is different from hyponatraemia caused by
mineralocorticoid deficiency in Addison’s disease.
SIADH can be caused by underlying malignancy, most commonly
lung cancer. Other respiratory and CNS pathology can also cause SIADH (Table
8.1). Many drugs can lead to SIADH, particularly anticonvulsants. If no cause
for SIADH is found, cross-sectional imaging or bowel investigation may be
necessary to search for an underlying malignancy. Idiopathic SIADH is a
diagnosis of exclusion.
Management
Reversal or treatment of the cause of SIADH and fluid
restriction are the key aspects of management. Strict fluid restriction (1–1.5
L/day) is poorly tolerated and difficult to achieve. Drug treatment of SIADH
includes demeclocycline and ADH antagonists. Demeclocycline reduces renal
response to ADH but its use is limited by side effects and unpredictable
pharmacokinetics. ADH antagonists (vaptans) directly block ADH action and are
of use in specific clinical situations.
Acute severe hyponatraemia
Patients with acute severe hyponatraemia and neurological
compromise require urgent management and intensive monitoring (Figure 8.1). In
life-threatening situations when ts are unconscious or fitting, hypertonic (3%)
saline can be considered.
