Postgraduate Medicine

ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20

Ten pitfalls in the proper management of patients

with hyponatremia

Theodosios D. Filippatos, George Liamis & Moses S. Elisaf

To cite this article: Theodosios D. Filippatos, George Liamis & Moses S. Elisaf (2016) Ten pitfalls
in the proper management of patients with hyponatremia, Postgraduate Medicine, 128:5,
516-522, DOI: 10.1080/00325481.2016.1186488

To link to this article: http://dx.doi.org/10.1080/00325481.2016.1186488

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POSTGRADUATE MEDICINE, 2016
VOL. 128, NO. 5, 516–522
http://dx.doi.org/10.1080/00325481.2016.1186488

CLINICAL FEATURE
REVIEW

Ten pitfalls in the proper management of patients with hyponatremia

Theodosios D. Filippatos , George Liamis and Moses S. Elisaf
Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece

ABSTRACT ARTICLE HISTORY

Hyponatremia (serum sodium <135 mEq/L) is a common electrolyte disorder in community or hospi- Received 23 February 2016
talized patients. Serum sodium levels should be corrected at a proper rate in patients with hypona- Accepted 3 May 2016
tremia, since overcorrection of serum sodium levels is related to devastating neurologic consequences, Published online 23 May 2016
such as the osmotic demyelination syndrome (ODS). However, a number of pitfalls, which could lead to KEYWORDS
undercorrection or overcorrection of hyponatremia, are common during the treatment of hyponatremic Sodium; hyponatremia;
patients. Hereby, we describe ten common pitfalls that are observed during the correction of serum syndrome of inappropriate
sodium concentration in hyponatremic patients. These refer to pitfalls in the goals and limits of the antidiuretic hormone
correction rate of serum sodium, pitfalls in the means (e.g. solutions but also drugs) and formulas used secretion; vaptans; formulas;
for achieving the desired correction rate and pitfalls associated with inadequate management or treatment; overcorrection
overcorrection. The knowledge of these common-in-clinical-practice pitfalls could assist clinicians in
the proper management of patients with hyponatremia.

1. Introduction It should be mentioned that patients with intracranial dis-

eases, postoperative patients (especially premenopausal
Hyponatremia (serum sodium <135 mEq/L) is a common elec-
women), and patients with acute water intoxication (observed
trolyte disorder both in community and in hospitalized
in primary polydipsia, psychiatric disorders, and ecstasy use)
patients.[1,2] Decreased sodium concentration (especially
have very high risk for developing the devastating conse-
acute, <48 h) may produce nausea, vomiting, headache, sei-
quences of acute hyponatremia.[13–15]
zures, coma, or death from cerebral edema and herniation,
In cases of acute symptomatic hyponatremia, an acute
whereas chronic hyponatremia (even mild) may cause fatigue,
increase of serum sodium levels by 4–6 mEq/L within the first
cognition impairment, gait deficits, falls and fractures, and
4–6 h is strongly recommended in published guidelines in order
even increased mortality.[3–7] The proper correction rate of
to reverse the symptoms, which is the primary goal of treat-
serum sodium levels in patients with hyponatremia is of spe-
ment.[11] Additionally, if symptoms do not improve in the first
cial importance since overcorrection of serum sodium levels
hour after correction of serum sodium levels by 5 mEq/L in
may result in devastating neurologic consequences, such as
patients with acute significant reduction of serum sodium levels
the osmotic demyelination syndrome (ODS).[8–10] On the
associated with severe neurologic symptoms, a goal of 1 mEq/
other hand, undercorrection can also lead to permanent dis-
L/h increase in serum sodium levels (without a specific limit of
ability or even death, especially in patients with severe neu-
correction) is recommended until the symptoms subside.[12,16]
rologic symptoms. According to current guidelines, serum
In both oligosymptomatic acute hyponatremia and mainly
sodium levels should be corrected at a proper rate.[11,12]
in chronic hyponatremia, even symptomatic, the rate of the
However, a number of pitfalls are common during the treat-
increase in serum sodium levels should be limited at <10 mEq/
ment of hyponatremic patients, which could lead to under-
L/24 h and preferably <6–8 mEq/L/24 h.[12,17]
correction or overcorrection of hyponatremia. Hereby, we
describe 10 common pitfalls that are observed during the
correction of serum sodium concentration (Table 1). 3. No knowledge of the groups of patients in whom
a rather rapid increase in serum sodium is
anticipated
2. No knowledge of the proper correction rate of
serum sodium The removal of the underlying cause of hyponatremia in
certain patient groups with chronic hyponatremia is followed
The proper correction rate of hyponatremia depends on the
by a brisk water diuresis and a rather rapid and considerable
severity of neurological symptoms, the rapidity of the
increase in serum sodium levels. Specifically, the restoration of
decrease in serum sodium levels (acute hyponatremia vs.
the extracellular volume in hypovolemic patients, the admin-
chronic hyponatremia >48 h), and the underlying causes.[12]
istration of hydrocortisone in patients with primary or

CONTACT Theodosios D. Filippatos filtheo@gmail.com Department of Internal Medicine, School of Medicine, University of Ioannina, 451 10 Ioannina,
Greece
© 2016 Informa UK Limited, trading as Taylor & Francis Group

Table 1. Common pitfalls in the management of patients with hyponatremia.
Pitfall
No knowledge of the proper correction rate of serum sodium
No knowledge of the groups of patients in whom a rather rapid increase in serum
sodium is anticipated
Ignorance of the underlying conditions that place patients at high risk of developing High-risk conditions
the osmotic demyelination syndrome (ODS)
Inadequate use and evaluation of formulas to predict the serum sodium changes and
to calculate the rate of infusates used for the safe correction of hyponatremia
Inappropriate approach to patients with hypovolemic hyponatremia
Inappropriate management of patients with hyponatremia due to SIADH
Inability to adjust the patients’ treatment with the use of fluid loss formula
Inappropriate use of furosemide during treatment of symptomatic patients with SIADH
Inappropriate use of vaptans
Inadequate management of patients in whom overcorrection of hyponatremia is
observed
SIADH: syndrome of inappropriate antidiuretic hormone secretion.
POSTGRADUATE MEDICINE 517
Tips to avoid
● Acute symptomatic hyponatremia: increase in serum sodium levels by 4–6 mEq/L
within the first 4–6 h, by <10 mEq/L within the first 24 h, and by <8 mEq/L/day
thereafter.
● Oligosymptomatic acute hyponatremia and chronic hyponatremia: rate of increase
of serum sodium levels <6–8 mEq/L/24 h
High-risk conditions:
● Restoration of the extracellular volume in hypovolemic patients
● Administration of hydrocortisone in patients with primary or secondary adrenal
insufficiency
● Discontinuation of the offending drugs
● Increased intake of salt and proteins in patients with decreased solute intake
● Hypokalemia
● Malnutrition
● Advanced liver disease
● Alcoholic individuals
● Patients with serum sodium ≤105 mEq/L
● Adrogue and Madias equation: projects the effect of gaining 1 L of any infusate
on the patients’ serum sodium.
● Formula of sodium deficit is useful.
● Tonicity balance approach is also useful.
● Calculation of the rate of the hypertonic saline solution needed to increase serum
sodium by 6–8 mEq/L is mandatory.
● Restoration of euvolemia with isotonic saline is indicated.
● Avoid fluid restriction.
● Overcorrection of sodium levels after the restoration of volume is anticipated and
needs special attention.
● Acute symptomatic hyponatremia: hypertonic 3% saline solution in a dose of
2 mL/kg of body weight over 10 min. The dose can be repeated after 20 min (no
more than three doses).
● Moderately severe symptoms: normal saline should be avoided. Careful adminis-
tration of hypertonic (3%) saline solution (0.5–2 mL/kg/h) is advised. Furosemide
can be carefully used to increase water losses and to treat volume overload.
● Asymptomatic patients with SIADH and chronic hyponatremia: water restriction
(500 mL below the 24-h urine volume). Calculation of the electrolyte-free water
clearance or urine/serum electrolyte ratio is mandatory.
● Chronic hyponatremia not responding to water restriction: increase in solute
intake (with salt- and protein-rich diet), urea, demeclocycline, and tolvaptan.
● Frequent determination of serum and urine electrolytes in all cases.
Fluid loss formula:
● Projects the effect of losing 1 L of any fluid (mainly urine) on the patients’ serum
sodium.
● Mandatory when ongoing fluid losses (mainly renal losses) are >1 L/day.
● Furosemide can significantly contribute to the increase in serum sodium.
concentration by increasing free water excretion. Frequent determination of
serum sodium is mandatory.
● Vaptans can be used in patients with euvolemic hyponatremia (mainly in
patients with SIADH), patients with congestive heart failure, or patients with
cirrhosis and ascites.
● Short-term use with frequent determination of serum sodium is advised.
● Long-term use in patients with irreversible euvolemic hyponatremia with distur-
bances associated with the decreased sodium level (gait disturbance and frequent
falls) not responding to fluid restriction.
● In patients with high risk of ODS in whom overcorrection of serum sodium
concentration is observed, a careful reduction of serum sodium levels (using
hypotonic saline solutions or desmopressin) should be attempted aiming to a
final increase of <6 mEq/L/day in serum sodium concentration.
518 T. D. FILIPPATOS ET AL.
secondary adrenal insufficiency, the discontinuation of diure-
tics, the abrupt decrease in water intake in patients with
polydipsia, or the increased intake of salt and proteins com-
bined with water restriction in patients with decreased solute
intake (e.g. in patients with the beer-potomania syndrome or
in elderly patients with tea and toast diet) may be followed by
an abrupt increase in serum sodium levels.[13,14,18–20]
Hence, careful monitoring of these patients with repeated
(every few hours) determination of serum sodium levels is
mandatory. It should be mentioned that large-volume polyuria
is an alarming sign indicating inappropriate correction of
hyponatremia.
4. Ignorance of the underlying conditions that place
patients at high risk of developing the ODS
Rapid correction of hyponatremia, especially in patients with
chronic (>48 h) or oligosymptomatic hyponatremia with
serum sodium concentration <120 mEq/L, puts patients at
risk for developing ODS with its devastating consequences.
Additionally, patients with hypokalemia, malnutrition, and
advanced liver disease, as well as alcoholic individuals; and
patients with serum sodium concentration ≤105 mEq/L, are
reported in literature as having high risk for developing the
ODS.[21–23] A more frequent monitoring strategy (e.g. deter-
mination of serum sodium concentration every 4–6 h) and
appropriate tailoring of the correction rate is strongly recom-
mended for patients with high risk of developing the ODS.
5. Inadequate use and evaluation of formulas to
predict the serum sodium changes and to calculate
the rate of infusates used for the safe correction of
hyponatremia
A number of formulas have been used to predict the change
of serum sodium levels during treatment and to calculate the
initial infusion rates. These formulas are useful as starting
points, but it should be mentioned that they underestimate
the rate of correction, probably because they do not take into
account the concurrent water losses (the patient is considered
as a closed system).[24,25] Hence, frequent adjustments of
therapy may be needed in order to avoid overcorrection.
According to the traditional procedure, the sodium
required to increased serum sodium levels by approximately
10 mEq/L within 24 h can be estimated by the formula of
sodium deficit [26]:
Required Naþ ¼ Total body waterΔNaþ (1)
The estimated total body water (TBW) is calculated as a
fraction of body weight; the fraction 0.6 in nonelderly men, 0.5
in elderly men and nonelderly women, and 0.45 in elderly
women has been used.[27] Thus, the amount of Na+ required
to increase serum sodium by 10 mEq/L/day in a patient with
serum sodium 110 mEq/L and TBW 42 L is 420 mEq
(42 L × 10 mEq/L). Thus, if administration of 3% saline solution
(513 mEq Na+/L) has been chosen, the needed volume of this
solution is 420 mEq/513 mEq/L = 818 mL (34 mL/h). It should
be mentioned that the increase estimated by the Equation (1)
(approximately 10 mEq/L/24 h) is rather large for most
patients. Thus, the use of this equation should be tailored to
each patient.
The Adrogue and Madias equation [28] can project the effect
of gaining 1 L of any infusate on the patients’ serum sodium:
½ðNaþ þKþ Þof the infusateðserum Naþ Þ
ΔNaþ ¼ (2)
Total body water þ 1
The administration of 1 L of hypertonic saline (513 mEq Na+/L)
in the previous patient is anticipated to increase serum sodium
levels by 9.6 mEq/L. Thus, a 10-mEq/L/day increase in serum
sodium levels can be achieved by administering 1070 mL of
the hypertonic saline solution (44 mEq/h). As it is clearly depicted
in the Adrogue–Madias equation, the potassium content of the
infusate should be taken into account in the calculation of the
projected serum sodium change. This means that the adminis-
tered potassium can increase serum sodium levels and that
correction of coexistent potassium depletion aids to the correc-
tion of hyponatremia.[29]
Finally, other authors suggested a simpler strategy to cal-
culate the rate of the administration of hypertonic saline
solution. This approach estimates an expected correction of
1 mEq/L/h for each mL/kg/h of 3% saline.[30,31]
Thus, in the previous case, the rate of infusion needed to
increase serum sodium levels by 1 mEq/L/h is as follows:
Infusion rateðmL=hÞ ¼ goal rate  body weightðkgÞ
¼ 1mEq=L=h  70kg ¼ 70mL=h (3)
It should be mentioned that frequent and repeated mea-
surement of serum sodium levels are required during the
administration of hypertonic saline.
The tonicity balance approach is a useful approach for the
understanding of sodium changes. It is based on the following
equation:
total cation content
Naþ concentration ¼ (4)
total body water
First, the patient’s total cation content is calculated with
the conversion of Equation (4):
Total cation content ¼ Serum sodium
 total body water (5)
The total cation content in the previous case is 4620 mEq
(42 L × 110 mEq/L). Next, the loss of total cations in the urine
is estimated. Ideally, 24-h urine measurements should be used
for this estimation, but a spot urine sample along with urine
volume (Vurine) produced during the administration of a cer-
tain solution can provide a rough estimate of total cation loss.
For example, the administration of 1 L NaCl 3% provides
513 mEq Na+. Let us suppose that during the administration
of this solution, a urine volume of 1 L is produced and urine
sodium and potassium concentrations of 80 and 40 mEq/L,
respectively, are measured in a spot urine sample. This means
loss of 120 mEq of total cations during the administration of
this hypertonic solution. Thus, the new total cation content is
(4620 + 513 − 120) = 5013 mEq, while no significant change in
TBW was observed (1 L − 1 L = 0). Accordingly, the new
sodium concentration will be as follows:

new total cation content 5013
New Naþ concentration ¼ ¼
new total body water 42
¼ 119:3mEq=L:
So, tonicity balance studies can explain the sodium
changes observed with the administration of certain solutions.
This approach is very helpful for understanding the pathophy-
siology of sodium changes in serum, but it is not helpful for
the prediction of serum changes.
6. Inappropriate approach to patients with
hypovolemic hyponatremia
Restoration of plasma volume with isotonic saline solution is
the treatment of choice in patients with hypovolemic hypona-
tremia. Additionally, stopping of thiazides and restoration of
the underlying volume depletion and potassium deficit can
lead to normonatremia in patients with diuretic-induced hypo-
volemic hyponatremia.[32] Special emphasis should be given
in patients with hypovolemic hyponatremia to the possibility
of an overly rapid increase in serum sodium levels when
volume depletion is restored. In this case, an abrupt decrease
in antidiuretic hormone (ADH) secretion and subsequently a
rapid increase in diuresis is observed.[25,29,33,34]
7. Inappropriate management of patients with
hyponatremia due to SIADH
(i) In patients with acute symptomatic hyponatremia
(especially in patients with severe neurologic symp-
toms such as vomiting, seizures, or coma), which is
a medical emergency, hypertonic 3% saline solution
(513 mEq Na+/L) in a dose of 100 mL over 10 min
should be used to gradually increase serum sodium
levels; if there is no clinical improvement, this dose
can be repeated after 20 min (no more than three
doses).[11] The urgent correction by 4–6 mmol/L is
usually associated with clinical improvement. In
case that the severe symptoms do not subside
despite the correction of serum sodium concentra-
tion by 5 mEq/L in the first hour, a correction rate
of 1 mEq/L/h of serum sodium levels with contin-
uous infusion of hypertonic saline until symptom
improvement has been suggested.[12] Frequent
determinations of serum sodium concentration are
advised. Even in patients with symptomatic hypo-
natremia, overcorrection of hyponatremia (increase
of >10 mEq/L/d) should be avoided.
(ii) In patients with chronic hyponatremia with moderately
severe symptoms (nausea without vomiting, confusion,
and headache [12]), normal saline should not be admi-
nistered since it can lead to even further decrease in
serum sodium levels (especially in patients with
increased urine osmolality >500 mOsm/kg). In these
patients, careful administration of hypertonic (3%) saline
solution (1 to 2 mL/kg/h) is advised in order to achieve
the desired rate of correction,[30] while furosemide can
also be used to avoid volume overload and to increase
water losses (decrease in urine osmolality; see below for
POSTGRADUATE MEDICINE 519
details). Frequent determination of serum and urine
electrolytes is necessary during treatment to avoid inap-
propriate increase in serum sodium levels.
(iii) In asymptomatic patients with SIADH and chronic
hyponatremia, water restriction (500 mL below the
24-h urine volume) is recommended.[35] However,
the effectiveness of water restriction is quite variable;
the calculation of the electrolyte-free water clearance
(Ce H2 O ) is mandatory since it can easily calculate the
ability of the kidneys to excrete water.[36] The Ce H2 O
can be easily estimated by the following equation:
 
Urine ðNaþ þ Kþ Þ
Ce H2 O ¼ Vurine  1  (6)
Serum Naþ
A negative value indicates inability of the kidneys to
excrete free water and suggests that water restriction
alone is inadequate for the patient’s management.
Alternatively, the urine/serum electrolyte ratio (in a
urine sample) is a useful marker of the ability to
excrete water [37]:
Urine ðNaþ þ Kþ Þ
Urine=serum electrolyte ratio ¼ (7)
Serum Naþ
A value of >1 suggests that fluid restriction is not able
to increase serum sodium and is not advised. In con-
trast, a value of <0.5 is indicative of a good response
to fluid restriction.
(iv) In patients with chronic hyponatremia due to SIADH in
whom water restriction is inadequate, the increase in
solute intake (with salt- and protein-rich diet), com-
bined with low-dose loop diuretics, could assist to an
increase in serum sodium levels. Alternatively, urea
(doses of 0.25–0.50 g/kg/day) may be a useful adjunct
if it is available.[12,38,39] Additionally, demeclocycline
(600–1200 mg/day in divided doses; 3 to 4 days to
achieve maximal diuretic effects are needed) or a
vasopressin receptor antagonist (vaptan) can be used
to increase serum sodium levels [11,40–42]; however,
other investigators recommend against the use of
these drugs.[12] Monitoring of serum sodium concen-
tration is advised during use of the above treatments
in order to follow the appropriate rate of correction.
8. Inability to adjust the patients’ treatment with
the use of fluid loss formula
In the setting of substantial ongoing fluid losses (>1 L/day;
mainly renal losses), the fluid loss formula should be used,
which can project the effect of losing 1 L of any fluid (mainly
urine) on the patients’ serum sodium [43,44]:
Serum Naþ  urine ðNaþ þ Kþ Þ
ΔNaþ ¼ (8)
TBW þ 1
In the previous case, the ΔNa+ for urinary volume of 1 L
with the above mentioned urine sodium and potassium con-
centration (80 and 40 mEq/L, respectively) is:
520 T. D. FILIPPATOS ET AL.
110  ð80 þ 40Þ
ΔNaþ ¼ ¼ <1meq=L
42 þ 1
Thus, in this case, urine losses do not significantly contri-
bute to the change in serum sodium levels. However, in a
patient with body weight 60 kg, serum Na+ 120 mEq/L, urine
(sodium + potassium) 40 mEq/L and urine volume 2.5 L, the
ΔNa+ would be 2.5 × 2.6 mEq/L = + 6.5 mEq/L. Thus, a rather
inappropriate sodium correction rate is anticipated if the clin-
ician does not take into account the ongoing urine losses.
It has been proposed that the Adrogue–Madias formula
(Equation (2)) should be used to calculate the initial saline
infusion rate in patients with hyponatremia. When ongoing
renal losses are substantial (urine volume >1 L), the fluid loss
formula should be used to properly adjust treatment.[45]
It should be mentioned that some authors propose an
alternative treatment algorithm for SIADH-associated hypona-
tremia. In this approach, hypertonic saline is administered
concurrently with desmopressin (1 to 2 μg parenterally every
6–8 h). The amount of hypertonic saline projected to increase
the serum sodium concentration by 6 mEq/L/24 h is calculated
based on Adrogue–Madias formula (Equation (2)). The concur-
rent administration of desmopressin aims to prevent the over-
correction that may be seen when the cause of hyponatremia
has been removed.[46] However, this ‘proactive’ approach
should be limited to experienced clinicians because the
administration of desmopressin needs much attention in
order to avoid undercorrection.
9. Inappropriate use of furosemide during
treatment of symptomatic patients with SIADH
Hypertonic saline solution (3%) is commonly used in sympto-
matic patients with SIADH. In these cases, furosemide (20–40 mg
intravenously) can also be administered to avoid circulatory over-
load. However, furosemide can contribute to the increase in
serum sodium concentration by increasing free water excretion.
For example, 1 L of hypertonic saline solution is adminis-
tered in a male patient (body weight 70 kg) with serum
sodium 110 mEq/L and urine osmolality (Uosm) 500 mOsm/
kg. It should be mentioned that Uosm is relatively stable in
SIADH patients despite any changes in water and solutes
intake.[47] Hence, since the patient exhibited extracellular
volume expansion due to ADH-mediated water retention,
this amount of infusate will be rapidly excreted with urine.
Thus, the anticipated Vurine is estimated as follows:
Solute load 1026
Vurine ¼ ¼  2L (9)
Uosm 500
Consequently, the anticipated new sodium concentration will
be (according to the previously mentioned tonicity balance
study and Equation (4)) as follows:
New total cation content
New sodium concentration ¼
New TBW
110 mEq  42L
¼ L
 112:7mEq=L
42 þ 1  2L
So, an increase in serum sodium is anticipated. If furose-
mide is administered, the Vurine will be increased, for example,
to 3.4 L associated with approximately 100 mEq additional
Na+ + K+ urine losses, and the Uosm will be reduced to
approximately 300 mOsm/kg. Thus, the new predicted sodium
concentration is as follows:
New total cation content
New sodium concentration ¼
New TBW
110 mEq  42L
¼ L
 114:4mEq=L
42 þ 1  3:4L
So, the administration of furosemide can induce a further
increase in serum sodium levels. Consequently, in some cases,
an inappropriate increase in serum sodium concentration
might be observed, and this change should be taken into
account during management of patients with hyponatremia.
The inability of isotonic saline solution to increase serum
sodium levels in patients with SIADH is easily explained with
the above calculations. Using the above equations, since the
Uosm is relatively constant at 500 mOsm/kg, the anticipated
urine volume with the use of 1 L of isotonic saline solution
(154 mEq/L) will be as follows:
Solute load 308
Vurine ðLÞ¼ ¼  0:6L
Uosm 500
Thus, administration of 1 L of isotonic saline will result in
retention of 400 mL of water. The projected new serum
sodium concentration is as follows:
New total cation content
New sodium concentration ¼
New TBW
L 42L
110 mEq
¼  109mEq=L
42 þ 0:4L
Hence, a decrease in serum sodium concentration is
anticipated.
10. Inappropriate use of vaptans
Vaptans (vasopressin receptor antagonists) are a new class of
drugs for the management of hyponatremia and are considered
by some authors as first choice drugs, especially in patients with
SIADH.[48] These drugs selectively antagonize the antidiuretic
effect of vasopressin leading to increased water diuresis (aquar-
esis).[49] These drugs can be used in patients with chronic
symptomatic euvolemic hyponatremia (mainly in patients with
SIADH) and in some countries in patients with hypervolemic
hyponatremia (mainly in patients with congestive heart failure
but also in patients with cirrhosis and ascites).[40–42,49–54]
Vaptans should be initiated in hospital environment, and gen-
erally, short-term use along with monitoring of serum sodium
and urine output is usually advised to avoid an undesirable
increase in serum sodium levels.
Treatment with tolvaptan should be initiated at a dose of 15 mg
once daily.[55,56] The dose of the drug can be increased to 30 or
60 mg/day if a <5 mEq/L increase in plasma sodium is not observed
in the previous 24 h.[11] Additionally, tolvaptan can be carefully
given for longer periods in selected patients with irreversible
euvolemic hyponatremia who cannot be managed with fluid
restriction and having disturbances that could be attributed to
the decreased sodium concentration (gait disturbance and

frequent falls). Drug-induced liver injury has been observed in
clinical trials investigating the role of long-term tolvaptan (at
higher doses than approved) in autosomal dominant polycystic
kidney disease.[57,58] Determination of liver enzymes should be
promptly performed in patients with symptoms indicating liver
injury, and the drug should be discontinued if liver injury is sus-
pected or liver enzymes are elevated more than three times the
upper limit of normal levels.[55,56,59]
Conivaptan is indicated to raise serum sodium in hospita-
lized patients with euvolemic and hypervolemic hyponatre-
mia.[60,61] Conivaptan is given intravenously as a loading
dose of 20 mg administered over 30 min, followed by contin-
uous infusion at a rate of 20 mg/24 h (which may be increased
up to 40 mg/24 h) for 2–4 days.[62] Conivaptan has not been
specifically associated with elevation of liver enzymes.
It should be pointed out that vaptans are contraindicated
in hypovolemic hyponatremia.[49]
11. Inadequate management of patients in whom
overcorrection of hyponatremia is observed
It has been shown that hypertonic saline and vaptans (con-
ivaptan) lead to a similar correction rate of serum sodium
levels in hyponatremic patients.[61] However, if hypertonic
saline has been chosen, it is prudent to measure serum
sodium concentration every few hours and adjust the rate of
infusion accordingly. In contrast, with vaptans, the maximum
change in serum sodium is observed between 8–24 h; in this
case, a significant increase in urine output is predictive of a
large increase in serum sodium levels. Thus, in patients taking
vaptans, in whom a significant increase in urine output is
observed, it is prudent to measure serum sodium concentra-
tion before the administration of the next vaptan dose.
In patients with chronic hyponatremia in whom overcorrec-
tion of sodium levels is observed, especially in those who are at
high risk for developing ODS, clinicians should take measures in
order to achieve a final <6–8 mEq/L/day increase in serum
sodium concentration.[63] If the correction is significantly
greater than the desired target, discontinuation of the hyper-
tonic saline or vaptans may be not enough to deal with the
overcorrection; in this case, a decrease in serum sodium levels
may be needed that can be achieved with the careful adminis-
tration of hypotonic saline solutions to replace ongoing water
losses (e.g. 1 L half-isotonic saline for 8 h, with repeated every
2–4 h measurement of serum sodium). Additionally, administra-
tion of desmopressin (2.4 µg/8 h parenterally) is another mod-
ality that can be useful; however, this treatment needs
experience and should be chosen if a specially trained clinician
can be consulted.[11,63,64]
12. Conclusions
Hyponatremia should be corrected at a proper rate, since both
undercorrection and overcorrection of serum sodium levels
are related to devastating consequences. Clinicians should
be aware of certain pitfalls that commonly encounter during
treatment of hyponatremia, which usually refer to the goals
and limits of the correction rate; the use of solutions, drugs, or
formulas; and the inadequate management of overcorrection.
POSTGRADUATE MEDICINE 521
The awareness for these common pitfalls may lead to better
and safer management of patients with hyponatremia.
Declaration of interests
The authors have no relevant affiliations or financial involvement with any
organization or entity with a financial interest in or financial conflict with
the subject matter or materials discussed in the manuscript. This includes
employment, consultancies, honoraria, stock ownership or options, expert
testimony, grants or patents received or pending, or royalties.
ORCID
Theodosios D. Filippatos http://orcid.org/0000-0002-1713-0923
George Liamis http://orcid.org/0000-0003-1522-8318
Moses S. Elisaf http://orcid.org/0000-0003-0505-078X
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