HypoNa+

Selecting a therapy
Emergency therapy : hypertonic saline (100 mL bolus over 10 to 15 minutes).
- severe symptoms due to hyponatremia,
- acute hyponatremia + mild to moderate symptoms,
- hyperacute hyponatremia even if there are no symptoms,
- symptomatic patients who have either acute postoperative hyponatremia or
hyponatremia associated with intracranial pathology

non-emergency :
asymptomatic acute or subacute hyponatremia: hypertonic saline (either as a 50
mL bolus or slow continuous infusion) unless the hyponatremia is already
autocorrecting due to a spontaneous water diuresis.
chronic severe hyponatremia who have mild to moderate symptoms (eg,
dizziness, forgetfulness, gait disturbance, nausea, vomiting, confusion, and lethargy),
initially: hypertonic saline (typically as a slow ivi15 - 30 mL/hour, but a 50 mL bolus can
be used). In addition, we often treat concurrently with both hypertonic saline
and desmopressin (1 to 2 mcg /8hrs iv/sc for 24 to 48 hours). Desmopressin makes
the rate of correction resulting from hypertonic saline more predictable because it
prevents an unexpected water diuresis from occurring during the course of therapy.
If desmopressin is used, it is important to restrict free water intake to avoid an
unwanted decrease in the serum sodium concentration. For this reason, we
do not use desmopressin in patients
-

at high risk for self-induced water intoxication (eg, psychotic patients).

edematous patients with heart failure or cirrhosis because it may increase

the amount of hypertonic saline required to achieve the desired increase
in serum sodium concentration and because the likelihood of overly rapid
correction in such patients is low.

with recurrent hyponatremia caused by chronic SIADH (due, for example,

to small cell lung cancer).

In patients with chronic moderate hyponatremia who have mild to moderate

symptoms, we do not typically use hypertonic saline. Rather, our choice of initial
therapy depends upon the underlying disease:
-In patients with edematous states (such as heart failure and cirrhosis), SIADH,
advanced kidney disease, or primary polydipsia, we implement a fluid restriction.
In general, fluid intake should be less than 800 mL/day.
-In patients with heart failure or in patients with SIADH who also have a high
urinary cation concentration, loop diuretics may be necessary. Vasopressin
receptor antagonists are another option in such patients, although these drugs
are associated with serious limitations. Patients with SIADH may also be treated
with oral sodium chloride tablets.
-In patients with true volume depletion, we usually treat with isotonic saline. With
true volume depletion, the administration of saline will usually correct the
hypovolemia, thereby removing the stimulus to the release of antidiuretic
hormone (ADH) and allowing the excess water to be excreted in the urine.
-In patients with diuretic-induced hyponatremia or drug-induced SIADH,
discontinuation of the responsible medication may be all that is required.
Regimen of hypertonic saline in the emergency setting In patients who require emergency
therapy, a 4 to 6 meq/L increase in the serum sodium concentration should be achieved as soon
as possible [4,5]. Based upon broad clinical experience, the administration of hypertonic
saline is the only rapid way to raise the serum sodium concentration and improve neurologic
manifestations and outcomes in patients with severe symptomatic hyponatremia [4,6,9,23-26].
We suggest a regimen that was first suggested for the treatment of hyponatremic athletes
participating in endurance events such as marathon races. It consists of 100 mL of 3 percent
saline given as an intravenous bolus, which should acutely raise the serum sodium concentration
by 2 to 3 meq/L and thereby reduce the degree of cerebral edema. If severe neurologic
symptoms persist or worsen, or if the serum sodium is not improving, a 100 mL bolus of 3 percent
saline can be repeated one or two more times at 10-minute intervals [4,27,28]. The rationale for
this approach is that, among patients requiring emergency therapy, rapid increases in serum
sodium of approximately 4 to 6 meq/L can prevent or reverse severe symptoms such as seizures
[4,21,29-31]. (See "Exercise-associated hyponatremia", section on 'Use of hypertonic saline'.)
Avoidance of overly rapid correction (9 meq/L in any 24-hour period) is often difficult in patients
with primary polydipsia. These patients tend to autocorrect since ADH is physiologically
suppressed, permitting rapid excretion of large volumes of free water. Autocorrection can also
occur in patients with exercise-associated hyponatremia or ecstasy use. Fortunately, the
hyperacute onset of hyponatremia in these disorders is associated with a low risk of osmotic
demyelination due to overly rapid correction. (See 'Risk of osmotic demyelination' above.)

In addition, desmopressin should not be given to psychotic patients with self-induced water
intoxication as a means to slow or reverse overcorrection. Despite careful observation in the
inpatient setting, such patients may covertly ingest large amounts of water that cannot be
excreted because of the antidiuretic effect of desmopressin. This can produce recurrent severe
hyponatremia.
Regimen of hypertonic saline with or without desmopressin in the non-emergency
setting Asymptomatic patients with acute hyponatremia and mildly or moderately symptomatic
patients with chronic severe hyponatremia should generally receive hypertonic saline. As noted
above, the total elevation in serum sodium should be 4 to 6 meq/L and no more than 8 meq/L in
any given 24-hour period. The same rate of increase should be continued on subsequent days.
(See 'Goals of therapy' above.)
We use the following regimens, although the treatment may vary according to local expertise:
Acute asymptomatic hyponatremia An intravenous bolus of hypertonic saline (50 mL over
10 minutes). Two or three additional boluses of 50 to 100 mL of hypertonic saline can be
given if symptoms develop and/or the serum sodium does not improve.
Severe chronic hyponatremia with mild or moderate symptoms A slow intravenous
infusion of hypertonic saline at 15 to 30 mL/hour, usually in combination
with desmopressin at 1 to 2 mcg intravenously or subcutaneously every eight hours for 24 to
48 hours. The infusion rate should be titrated, aiming for a correction rate of 6 meq/L per
day. However, this regimen should be modified in certain settings:
In patients with moderate symptoms (eg, nausea, vomiting, confusion), an initial 50
mL bolus of hypertonic saline may be justified prior to beginning the slow infusion.
We do not use desmopressin in patients who are at high risk for self-induced water
intoxication (eg, psychotic patients), in edematous patients (those with heart failure or
cirrhosis), or in patients with known chronic SIADH who have recurrent hyponatremia.
In edematous patients, such as those with heart failure, coadministration
of furosemide with hypertonic saline may be required to prevent worsening hypervolemia.
Several groups have reported favorable outcomes treating heart failure patients in this
manner [32-34].
The concurrent use of both hypertonic saline and desmopressin has been proposed to achieve a
controlled, steady increase in the serum sodium concentration while avoiding overly rapid
correction. The effectiveness of this regimen was shown in two retrospective studies of
symptomatic patients with severe hyponatremia (serum sodium less than 120 meq/L) who were
treated with hypertonic saline plus desmopressin [12,35]. In one of these studies, 25 patients
received 3 percent saline (dose varied depending upon the severity of symptoms, with some
patients receiving a 50 mL bolus of 3 percent saline) and desmopressin (1 to 2 mcg intravenously
or subcutaneously every eight hours for 24 to 48 hours), aiming for a correction rate of
6meq/L/day [35]. The mean increase in serum sodium was 6 meq/L in the first 24 hours and

4meq/L in the second 24 hours; one patient corrected by 11 meq/L in the first 24 hours, but there
were no other instances of overly rapid correction. With this approach, desmopressin is given to
eliminate the potential for urinary water losses, in essence creating a state of iatrogenic SIADH
that can be managed more predictably with hypertonic saline. The approach can be used to treat
both hypovolemic hyponatremia and SIADH. It should generally not be used in patients with
hyponatremia caused by heart failure or cirrhosis, since inadvertent overcorrection due to a water
diuresis is unlikely in this setting, or in psychotic patients with polydipsia, because of the risk of
water ingestion combined with impaired water excretion due to desmopressin. It is particularly
attractive in patients who are at high risk of developing osmotic demyelination from overly rapid
correction of hyponatremia.
Some experts prefer to withhold desmopressin initially, giving it only if a water diuresis develops
during the course of therapy [7,36]. However, we find this strategy to be labor intensive and often
unsuccessful, associated with an unacceptably high incidence of unintentional overcorrection.
Once a water diuresis begins, washout of the renal medullary gradient may result in a delay in
achieving the full antidiuretic effect of desmopressin.
Although isotonic saline will raise the serum sodium in hyponatremic patients with true
hypovolemia, we prefer hypertonic saline if the hyponatremia is acute or severe and symptomatic.
Isotonic saline will initially raise the serum sodium more slowly than hypertonic saline (until neareuvolemia is attained and ADH secretion is suppressed). In addition, some patients with
hypovolemia may have coexistent SIADH due to stress and will not respond well to isotonic
saline. Thus, hypertonic saline will be predictably more effective in rapidly alleviated symptoms of
severe hyponatremia. After euvolemia is established, the slow correction in patients receiving
isotonic saline may accelerate due to suppression of ADH, leading to a marked water diuresis.
This rapid rise in serum sodium in patients who were, until that point, correcting slowly may
produce an excessive 24-hour increase in the serum sodium. Initial therapy with a combination of
hypertonic saline and desmopressin can quickly improve symptoms of hyponatremia while
preventing overly rapid correction.
When hypertonic saline is not required We do not typically use hypertonic saline in patients
with chronic moderate hyponatremia who have mild to moderate symptoms, or in asymptomatic
patients with severe hyponatremia. Such patients are typically treated with fluid restriction, with or
without loop diuretics and oral sodium chloride. Vasopressin receptor antagonists are
occasionally used, but are associated with serous limitations.
In addition, we usually attempt to normalize the serum sodium in patients with asymptomatic
moderate hyponatremia and mild hyponatremia, although such patients do not require
hospitalization for correction of the serum sodium. The rationale for treating such patients is
described below.
Detailed discussions of chronic therapy for hyponatremia are presented in the following relevant
topics:
Patients with SIADH (see "Treatment of hyponatremia: Syndrome of inappropriate
antidiuretic hormone secretion (SIADH) and reset osmostat")

Patients with heart failure (see "Hyponatremia in patients with heart failure")
Patients with cirrhosis (see "Hyponatremia in patients with cirrhosis")