++
Hyponatremia arises from a net loss in sodium or a net gain in
water. Any gain of water must be associated with a restriction of
the renal excretion of water. Hyponatremia usually follows the ingestion
of water or other hypotonic fluids with concurrent loss of sodium.
Hypertonic fluid losses due to thiazide diuretics may also cause
hyponatremia. The relation between serum sodium, total body sodium,
and total body water (TBW) is: serum sodium = sodium
(mmol)/TBW (L). Measurement of serum sodium, per se,
does not reflect serum osmolarity when mannitol or glycine are administered,
since they remain in the ECF and cause a shift of water into the
ECF that results in hyponatremia but no change in the effective
osmolality; although serum sodium is low, there is not a true loss
of total body sodium or a true gain in TBW. In contrast, urea and
glucose usually do not contribute to effective osmolality because
they cross the cell membrane. However, if insulin is absent (diabetes
mellitus), glucose acts as an effective osmole and causes water
to shift from the ICF to the ECF, resulting in a fall in serum sodium
(translocational hyponatremia). Diabetic ketoacidosis with prolonged
glucosuria is also associated with a reduction in total body sodium.
++
Symptoms of hyponatremia result from cellular swelling and dysfunction,
especially in the brain, and include headache, lethargy, irritability,
muscle cramps, seizures, disorientation, agitation, anorexia, nausea,
and even death due to cerebral edema and herniation of the brain.
The symptoms and signs depend on the duration and severity of the
hyponatremia. Most patients with acute hyponatremia (defined ⩽ 48
h in duration) or those with chronic hyponatremia and a further
acute decline in serum sodium will be symptomatic.
+++
Assessment of
Hyponatremia
++
Determination of ECF volume is the first step in identifying
the underlying cause of hyponatremia.10 If the ECF volume
is reduced, the primary problem is sodium loss. In these cases,
measurement of UNa is useful because the normal kidney
retains sodium such that the UNa should be less than 10
mmol/L. In such cases, the source of sodium loss is extrarenal
(Table 466-5) except in the case of prior
vomiting or diuretic use. If the UNa and UK are
high, the disorder is one of a sodium-wasting nephropathy (Bartter
syndrome), diuretic use, or vomiting. When ECF volume is normal
or high, the primary problem is water gain (Table
466-6). Most often, it is due to increased release and/or
activity of ADH, whether caused by a low effective circulating volume
or other nonosmotic and nonbarometric stimuli. The causes of syndrome
of inappropriate ADH (SIADH) are many and include neoplasia, central
nervous system and pulmonary disorders, psychosis, pain, nausea, vomiting,
and drugs. Water gain may also be due to low water delivery to the
distal nephron (renal failure) resulting in decreased water excretion
(see Chapter 525).
++
++
+++
Therapy for Hyponatremia
++
Hyponatremia requires correction, but the approach and urgency
may vary depending on presenting symptoms and
chronicity. All patients without a previously documented serum sodium
(most patients presenting to the emergency department) should be
considered to have chronic hyponatremia. Rapid correction of serum
sodium in patients with chronic hyponatremia can result in neurologic
consequences, including osmotic demyelination syndrome (previously known
as central pontine myelinolysis), hemorrhage, or cerebral edema,
and should therefore be avoided. If the patient has acute symptoms
such as seizures that are determined to be due to the hyponatremia,
it is safe to rapidly raise the serum sodium by 4 to 5 mmol/L.11 This
can be achieved by administering 3% sodium chloride (NaCl), which
has approximately 513 mmol of sodium in each liter. The volume of
3% NaCl administered is calculated as weight (kg) × 0.6 × 5 × 1.95,
where 0.6 adjusts for TBW volume of 60%, 5 is the target
increase in mmol/L for serum sodium, and 1.95 is a correction
factor (1000 ÷ 513). For example, if a 10-kg child has 60% TBW,
the sodium required to raise the serum sodium by 5 mmol/L
is 30 mmol (10 × 0.6 × 5).
The volume of 3% NaCl to be administered
is then calculated to be 58 mL.
++
Once the acute symptoms subside, the goal of therapy is to raise
the serum sodium by no more than 3 mmol/L during the rest
of the 24 hours so that the total correction for the 24 hours is
only 8 mmol/L.12 This is equivalent to a rate
of correction of 0.3 mmol/L/h. Depending on the
etiology of the hyponatremia (primary water gain or sodium loss),
either water should be restricted or sodium should be given. In
order to accomplish this, all water and electrolyte losses (insensible,
urine and others) must be accounted for. Therefore, all losses have
to be measured accurately and frequently and replaced or restricted
accordingly.
++
In the example of a 10-kg child, if sodium loss is felt to be
the etiology, then a total of 18 mmol of sodium must be given over
24 hours in addition to what was already given and what is being replaced
for losses. If water gain is felt to be the cause, and the serum
sodium is 120 mmol/L after the initial 3% NaCl
administration, then all electrolyte losses have to be replaced
1:1 and the negative water balance calculated as percentage increase
in serum sodium desired = (3 mmol/L ÷ 120 mmol/L) × 100 = 2.5%;
percentage decrease in TBW should be 2.5% = 6
kg × 2.5% = 150 mL,
where 6 kg is the TBW (60% of 10 kg).
++
Another way to calculate this is as follows: Assume that the
fall in serum sodium is due to water gain and that the number of
total osmoles in the body have not changed. Since plasma osmolality
is primarily due to sodium, the following equations will solve for
the water deficit: current TBW × current
serum sodium = new TBW × new
serum sodium; water gain = current TBW – new TBW;
new TBW = (6 × 120)/123 = 5.85;
therefore, water gain = 6 – 5.85 L = 150
mL. Thus, this gain of water needs to be lost. Since the IWL in
this child with 10 kg body weight is close to 300 mL/d,
and IWL has very little electrolytes, the child can be given only 150
mL of the IWL as replacement to allow for a negative water balance
of 150 mL (~ 6 mL/h).
++
In cases of hyponatremia without significant neurologic symptoms, 3% NaCl
should not be administered even if the serum sodium is very low.
In an asymptomatic patient, the hyponatremia is probably a chronic,
long-standing condition. Gradual correction of hyponatremia is safer.
Once ECF volume is restored, the stimulus for ADH release can be
abolished, resulting in water diuresis. If such a diuresis is not
anticipated, the serum sodium may rise much more rapidly than anticipated.
Slow correction is preferable with careful monitoring of serum sodium
to prevent too rapid a change. Administration of 1-desamino-8d-arginine vasopressin (dDAVP) can be considered in patients with a rapid correction
of serum sodium. However, this should be approached with careful consideration.
In the case of overcorrection, animal studies and some case reports
in adult patients have shown that the development of osmotic demyelination
syndrome can be prevented by relowering serum sodium with dDAVP.13