Perspective

Hypertonic Saline for Hyponatremia: Meeting Goals and

Avoiding Harm
Helbert Rondon-Berrios and Richard H. Sterns

Hypertonic saline has been used for the treatment of hyponatremia for nearly a century. There Complete author and article
is now general consensus that hypertonic saline should be used in patients with hyponatremia information provided before
references.
associated with moderate or severe symptoms to prevent neurological complications. However,
much less agreement exists among experts regarding other aspects of its use. Should hy- Correspondence to
pertonic saline be administered as a bolus injection or continuous infusion? What is the R.H. Sterns (richard.
sterns@rochesterregional.
appropriate dose? Is a central venous line necessary? Should desmopressin be used
org)
concomitantly and for how long? This article considers these important questions, briefly ex-
plores the historical origins of hypertonic saline use for hyponatremia, and reviews recent Am J Kidney Dis. XX(XX):1-
7. Published online month
evidence behind its indications, dosing, administration modality and route, combined use with
xx, xxxx.
desmopressin to prevent rapid correction of serum sodium, and other considerations such as
the need and degree for fluid restriction. The authors conclude by offering some practical doi: 10.1053/
j.ajkd.2021.07.020
recommendations for the use of hypertonic saline.
© 2021 by the National
Kidney Foundation, Inc.

Introduction (Table 1).14,15 Both adopted minor modifications of the

Nearly a century after hypertonic saline was first suggested
as a treatment for acute water intoxication,1 we still don’t
know exactly how to use the drug. When is it indicated?
How much should be given? At what rate? By what route?
How can complications best be avoided? In this perspec-
tive we consider these questions, revisiting the various
answers that have been proposed over time and the evi-
dence supporting them.
Therapeutic Goals
For many years, a brief, rapid infusion of 100 to 300 mL
of hypertonic saline, as first described by Helwig et al2 in
1938, was standard treatment for what later came to be
known as acute symptomatic hyponatremia.3 Years later,
clinical practice began to stray from the Helwig regimen.
In the 1980s, most nephrology experts agreed with a
regimen first proposed by Ayus et al4 of rapidly infusing
hypertonic saline to raise the serum sodium (SNa) by 2
mEq/L/h until a “safe” level was achieved, somewhere
between 120 and 130 mEq/L.5
Evidence that posttherapeutic neurological sequelae
(dubbed the osmotic demyelination syndrome or ODS) could
complicate such therapy6,7 was initially viewed with skepti-
cism.4,5,8 As more cases of ODS were reported, some after
correction by only 9 to 10 mEq/L in 24 hours,9-11 expert
opinion began to shift.11 In 2000, a highly cited review in the
New England Journal of Medicine concluded that small increases in
SNa (3-7 mEq/L) were sufficient to reduce symptoms and
stop seizures and that correction should not exceed 8 mEq/L
in 24 hours.12 Experience in normonatremic neurosurgical
patients has shown this to be enough to markedly reduce
intracranial pressure and reverse impending herniation.13
Subsequently, guidelines published by panels of experts in
the United States and Europe made similar recommendations
original Helwig treatment for severe hyponatremic
symptoms—100 or 150 mL bolus infusions of NaCl 3%,
repeated if necessary—aiming at a 4 to 6 mEq/L increase in
SNa. Without fully abandoning rapid attainment of a “safe”
SNa as the eventual goal, Moritz and Ayus also recommended
small volume bolus infusions for relief of symptoms.16
Therapeutic Limits
Even among former skeptics, there is now general agree-
ment that excessive correction can trigger demyelination
of the brain. However, differences remain in the published
estimates of how much correction is “too much” and on
measures that should be taken to avoid overcorrection
(Table 2). For those believing the main priority is to
prevent seizures and respiratory arrest by reaching a “safe”
SNa > 120 mEq/L (or higher), the proposed limits are
permissive, and demyelination is deemed unlikely if
correction is <25 mEq/L in 48 hours and normonatremia
or hypernatremia are avoided.17,18 For those stressing
avoidance of iatrogenic harm and lack of evidence that
urgent correction by >4 to 6 mEq/L is ever necessary, the
proposed limits have been more strict: as low as 6 to 8
mEq/L per day,11,12,19 especially for patients with condi-
tions placing them at higher risk of injury from over-
correction (alcohol use disorder, advanced liver disease,
hypokalemia, malnutrition, or a SNa ≤ 105 mEq/L).15
Experts recommending even stricter limits emphasize
that these are rates to avoid rather than goals of therapy.
For patients at high risk of developing ODS, daily correc-
tion by 4 to 6 mEq/L has been recommended.15
Inadvertent Overcorrection
Many causes of hyponatremia are reversible, and once the
cause (eg, hypovolemia, medications, cortisol deficiency)

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 Rondon-Berrios and Sterns

Table 1. Indications, Dosing, and Goals of Correction for Bolus Injection of Hypertonic Saline per Current Guidelines
Indication Dose Goal
2013 American Expert Panel Recommendations15
Seizures or coma, regardless of known NaCl 3% 100 mL IV bolus (over 10 Correct SNa by 4 to 6 mEq/L
chronicity min) up to 3 times as needed within first hour
High risk of herniation (intracranial pathology or NaCl 3% 100 mL IV bolus (over 10 Correct SNa by 4 to 6 mEq/L
increased intracranial pressure; acute min) up to 3 times as needed within first hour
hyponatremiaa with headache, vomiting, or
confusion)
Acute hyponatremia with mild to moderate NaCl 3% in a continuous IV infusion at Correct SNa by 4 to 6 mEq/L
symptomsb a rate of 0.5 to 2 mL/kg/h within 6 hours
2014 European Clinical Practice Guidelines14
Severe symptoms of hyponatremia (ie, vomiting, NaCl 3% 150 mL IV bolus (over 20 Correct SNa by 5 mEq/L within
cardiorespiratory distress, abnormal and deep min) 2 times and then repeat twice or first hour
somnolence, seizures, or coma) until SNa goal is achieved
Moderate symptoms of hyponatremia (ie, NaCl 3% 150 mL IV bolus (over 20 Correct SNa by 5 mEq/L within
nausea without vomiting, confusion, or min) once first 24 hours
headaches)
Abbreviations: IV, intravenous, SNa, serum sodium.
a
The American Expert Panel defined acute hyponatremia as known duration <24-48 hours (eg, postoperative hyponatremia) or self-induced water intoxication (eg, due to
schizophrenia, endurance exercise, or use of 3,4-methylenedioxy-methamphetamine [Ecstasy]).
b
The American Expert Panel did not specifically define “mild to moderate symptoms” but implied these to be symptoms attributed to hyponatremia that are less severe than
those mandating urgent correction within 1 hour.

has been resolved, spontaneous excretion of dilute urine Recent Studies

can potentially raise the SNa by >2 mEq/L/h, exceeding
Opinions on how best to treat hyponatremia far exceed the
therapeutic limits within a few hours.20 A 1990 review
data available to support them. In the past 5 years, 6
suggested exogenous desmopressin to prevent excessively
studies have helped narrow this gap by comparing out-
rapid correction should a water diuresis emerge.21
comes with various therapeutic regimens.
Subsequently, several investigators described their
experience with desmopressin using 3 different strategies
(Table 3): (1) proactive (in anticipation of water diuresis), Hypertonic Saline Bolus Versus Continuous
(2) reactive (in response to water diuresis and impending Infusion
overcorrection), and (3) rescue (after overcorrection had For hyponatremic patients with worrisome symptoms, the
already occurred).22-24 Proactive desmopressin has even American Expert Panel Recommendations15 and European
been used in patients with a SNa well below 100 mEq/L; Clinical Practice Guidelines14 both endorse a bolus of NaCl
although a so-called safe SNa above 120 mEq/L was not 3% to achieve a rapid increase in SNa of approximately 5
reached for days, recovery was uneventful.25-27 mEq/L; however, their dosing strategies differ (Table 1).
Garrahy et al28 prospectively assessed clinical and
Table 2. Proposed Serum Sodium Correction Limits biochemical outcomes after treatment based on US
Limit, mEq/L guidelines (100 mL bolus, repeated, if necessary, up to 2
Study Year 24 Hour 48 Hour 72 Hour
more times). Chifu et al29 reported their experience with
treatment based on European guidelines (150 mL bolus,
Norenberg et al47 1982 — — 20
with a second bolus for patients with severe symptoms).
Sterns et al7 1986 12 — —
Ayus et al17 1987 — 25 —
Baek et al31 conducted a multi-center randomized trial
Sterns et al48 1994 12 18 —
comparing repeated bolus to continuous infusion of NaCl
Oh et al11 1995 8 — — 3%.
Laureno and Karp49 1997 10 — — The study by Garrahy et al28 is most illuminating
Adrogu e and Madias12 2000 8 — — because all patients had the syndrome of inappropriate
Moritz and Ayus18 2003 — 15 to 20 — antidiuresis (SIAD) and were given hypertonic saline for
Verbalis et al50 2007 10 18 — confusion, coma, seizures, or documented cerebral ede-
Sterns et al51 2009 10 18 20 ma—symptoms considered severe by both US and Euro-
Adrogu e and Madias19 2012 6 to 8a — — pean guidelines. In response to the publication of the US
Verbalis et al15 2013 8 to10b 16 to 18b — guidelines, the investigators had changed their standard
Spasovski et al14 2014 10 18 — hypertonic saline protocol—continuous infusion, begin-
High risk of osmotic demyelination syndrome (ODS) includes patients with serum ning at 20 mL/h, with subsequent dose adjustments every
sodium ≤ 105 mEq/L, hypokalemia, alcohol use disorder, malnutrition, or advanced 2 hours to achieve correction by 8 to 12 mEq/L in 24
liver disease.
a
6 mEq/L per day for patients at high risk of ODS. hours—to 100 mL bolus given over 15 minutes to achieve
b
8 mEq/L per day for patients at high risk of ODS. correction by 4 to 6 mEq/L in 6 hours. The modification

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Rondon-Berrios and Sterns
Table 3. Strategies to Prevent and Treat Overly Rapid Correction of Hyponatremia Using Desmopressin
Strategy Indications
Proactive Start immediately when SNa < 120 mEq/L and:
• High risk for rapid correctiona and/or
• High risk for ODSb
Reactive Worrisome SNa trajectory:
• SNa goal of 6 mEq/L in a 24-h period has been
achieved and/or
• UOP > 1 mL/kg/h
Rescue Overly rapid correction of hyponatremia has already
occurred:
• Increase in SNa ≥ 8 mEq/L in any 24-h period
Abbreviations: D5W, destrose 5% in water; IV, intravenous; SC, subcutaneous; SIAD, syndrome of inappropriate antidiuresis; SNa, serum sodium; UOP, urine output.
a
Low solute intake, hypovolemia, adrenal insufficiency, transient SIAD, thiazide diuretics, desmopressin, or vasopressin antagonists.
b
Alcohol use disorder, hypokalemia, liver disease, malnutrition, or SNa ≤ 105 mEq/L.
c
Self-induced water intoxication or acute postoperative hyponatremia (risk that SNa will fall due to delayed absorption of ingested water or excretion of hypertonic urine).
allowed them to prospectively compare outcomes in 22
patients treated by bolus to retrospective data from 28
patients given continuous infusions. The bolus regimen
raised SNa significantly more rapidly at 6 hours: median of
6 (range, 2-11) versus 3 (range, 1-4) mEq/L (P <
0.0001). There also was a concomitant, significant
improvement at 6 hours in the Glasgow Coma Scale:
median of 3 (range, 1 to 6) versus 1 (range, −2 to 2) (P <
0.0001). The median SNa was similar at 24 hours in the
groups, but frequent electrolyte monitoring and judicious
intervention was necessary to prevent overcorrection with
bolus therapy; a third saline bolus was associated with a
greater requirement for infusion of dextrose 5% in water
(D5W) and/or desmopressin to prevent overcorrection
(odds ratio [OR], 24 [95% CI, 2.1-322]; P = 0.006). There
were no cases of ODS in either group.
The retrospective study by Chifu et al29 reported high
rates of overcorrection after a 150-mL bolus of NaCl 3%
per the European guidelines in 36 patients with symp-
tomatic hyponatremia, most commonly diuretic induced.
Overcorrection was defined as an increase in SNa of >10
mEq/L within 24 hours of admission and >8 mEq/L
during each of the subsequent 24 hours until the SNa
was ≥130 mEq/L. Although a second 150-mL bolus, rec-
ommended by the guidelines for patients with severe
symptoms, was not given, the SNa was relowered after the
first 150-mL bolus in 10 patients (28%) with D5W (n =
3), desmopressin (n = 2), or both (n = 5); despite these
interventions, overcorrection occurred in 6. ODS was
suspected in 1 patient with a SNa of 115 mEq/L due to
secondary adrenal insufficiency. The patient recovered
completely, and magnetic resonance imaging of the brain
was not done. The investigators found lower rates of
overcorrection in the controls who were treated without
hypertonic saline. However, these findings are uninter-
pretable because the controls had a much higher baseline
SNa.
Baek et al31 conducted the SALSA trial, the only ran-
domized controlled trial to compare hypertonic saline by
bolus (n = 72) with continuous infusion (n = 73). Only 7
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Description
Desmopressin 2-4 μg IV/SC every 6-8 h and
NaCl 3% 100 mL bolus for seizures, coma, or rapidly
falling SNac or
NaCl 3% 1-1.5 mL/kg IV over 6 h (to increase SNa by
≈ 1 mEq/L every 6 h)
Desmopressin 2-4 μg IV/SC every 6-8 h
Desmopressin 2-4 μg IV/SC every 6-8 h and
D5W 3 mL/kg/h IV (to decrease SNa by ≈ 1 mEq/L/h)
until SNa is below the correction limit
of 145 patients met the criteria of the American Expert
Panel for bolus dosing (2 with seizures and 5 with stupor).
Most met the European criteria (nausea, headache, and
vomiting), but none had acute postoperative or self-
induced water intoxication, where such symptoms sug-
gest cerebral edema.32 Some participants reported malaise
and weakness only. In addition to a lower threshold for
starting therapy, both study arms (2 mL/kg bolus every 6
hours vs continuous infusion at 0.5 mL/kg/h) were more
aggressive than either US or European guidelines recom-
mend. Rather than stopping after a 5 mEq/L increase in
SNa, hypertonic saline was continued for up to 48 hours
until symptom resolution or a SNa increase near the
study’s definition of overcorrection (>12 or >18 mEq/L
within 24 or 48 hours, respectively). As a result, relow-
ering therapy with D5W and/or desmopressin was often
required (41.4% for bolus and 57.1% for continuous
infusion). As expected, at 1 hour, correction after a bolus
was greater because 5 times as much hypertonic saline had
been given. At other time points, there were no significant
differences in outcomes, including rates of overcorrection
(despite the bolus regimen providing two-thirds of the
volume provided by continuous infusion). No cases of
ODS were identified, but few patients were at serious risk
of this complication (the mean SNa was 118 mEq/L, no
patient had liver disease, and only 5 had alcohol use
disorder).
Hypertonic Saline Dosing for Continuous Infusion
A variety of formulas have been proposed to estimate SNa
change for a given volume of fluid (eg, NaCl 3%)
administered.12 These are simply mathematical manipu-
lations of the Edelman equation33 and are often inaccurate
in predicting SNa changes.34 A recent analysis of the
Adrogue-Madias (A-M) formula showed that estimated
changes in SNa are not linearly scalable.35
One of the major drawbacks of many formulas is that
they assume a closed compartment, ignoring urinary
electrolyte and water losses. A retrospective analysis of 62
adults given NaCl 3% for SNa < 120 mEq/L found SNa
3

increases predicted by the A-M formula were too low in
74.2%, sometimes by a factor of 5.20 Other formulas36,37
account for urinary losses but presume constant parame-
ters; in reality, urine composition frequently changes
during therapy.34 A retrospective study of 31 patients
compared predicted and actual SNa using 4 formulas.38
The root-mean-square error or average error was 4.79-
6.37 mEq/L for all studied formulas, suggesting they are
too inaccurate for prognostication.
Hypertonic Saline Route of Administration
Some hospitals only allow administration of NaCl 3%
through a central vein, a potential barrier to its use. This
misconception originated from a study comparing pe-
ripheral venous infusions of amino acids for parenteral
nutrition to nonnitrogen solutions (eg, dextrose 5% in
NaCl 0.9%).39 Amino acid solutions with osmolarity >
600 mOsm/L infused for 35.2 ± 19.9 hours had twice the
risk for phlebitis associated with nonnitrogen solutions.
These findings were conflated to apply to NaCl 3% (os-
molarity 1,027 mOsm/L), which was not studied. As of
May 2021, a review of Baxter’s global pharmacovigilance
database looking for adverse events related to NaCl 3% and
5% showed no reports of sclerosis of the vein, 2 reports of
infusion site reaction, and 1 report of extravasation, all
from medical/scientific literature.40 In 2 of the studies
cited in this article,28,31 a total of 228 patients received
NaCl 3% through a peripheral vein, and there were only 2
reported cases of phlebitis. These findings are consistent
with other published experience.41,42
Hypertonic Saline in Combination With
Desmopressin to Avoid Overcorrection
Three studies, all retrospective, compared overcorrection
rates in patients treated with hypertonic saline for hypo-
natremia with or without desmopressin.30,43,44 All suffer
from the same flaw: desmopressin did not always follow a
true “proactive” approach, and desmopressin was pre-
scribed at the provider’s discretion, not always for
accepted indications. Two studies included patients with
SNa > 120 mEq/L,30,44 a level unlikely to spontaneously
correct by >18 mEq/L in 48 hours (because endogenous
vasopressin terminates a water diuresis once SNa reaches
135 mEq/L). In one of these studies,30 the SNa was as high
as 125 mEq/L, a level unlikely to correct by >10 mEq/L.
As originally described, proactive desmopressin was
combined with concurrently infused hypertonic saline.26
However, not all patients assigned to “proactive” groups
in these studies received hypertonic saline; presumably in
some, desmopressin’s effect was allowed to wear off
before giving the next dose, a modification of the reactive
approach.
In the largest of these studies, MacMillan and Cav-
alcanti44 reviewed 1,450 admitted patients whose SNa
was <123 mEq/L, including 254 (17.5%) who were given
desmopressin. Paradoxically, although desmopressin
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Rondon-Berrios and Sterns
slowed the rate of rise of SNa, overcorrection was signif-
icantly more common with desmopressin than without it
(29.1% vs 15.5% corrected by >12 mEq/L in any 24-hour
period, P < 0.001; 13.5% vs 7.7% corrected by >18 mEq/L
in any 48-hour period, P = 0.005; 70.1% vs 35.1% cor-
rected by >8 mEq/L in any 24-hour period, P < 0.001).
However, desmopressin-treated patients had a lower me-
dian SNa (116 [interquartile range (IQR), 7] vs 120 [IQR,
4] mEq/L, P < 0.001); in most cases, desmopressin was
given after correction limits had already been exceeded. A
proactive strategy was used in only 28 cases, primarily for
hyponatremia caused by thiazides (28.6%), hypovolemia
(21.4%), and SIAD (14.3%). The proactive strategy had
lower rates of overcorrection than the reactive strategy,
used in 174 patients (3.6% vs 16.7% corrected by >12
mEq/L in 24 hours, 3.6% vs 8.6% corrected by >18 mEq/
L in 48 hours, and 21.4% vs 70.7% corrected by >8 mEq/
L/d), but the statistical significance of these differences
was not reported. Proactive use of desmopressin was also
associated with a longer length of stay; however none of
the 28 proactively treated patients received concurrent
NaCl 3%. Four of 1,450 patients in this series developed
ODS; all had predisposing factors (alcohol use disorder,
advanced liver disease, malnutrition, or hypokalemia) and
a presenting SNa of ≤115 mEq/L, below the median SNa
of the entire cohort.
In the MacMillan and Cavalcanti study, very few patients
were given hypertonic saline. Tran et al30 only studied
patients given NaCl 3%. The outcomes in the 80 patients
with SNa ≤ 125 mEq/L managed without desmopressin
were compared with the 32 patients treated with combi-
nations of 3% saline and either proactive (n = 20) or
reactive (n = 12) desmopressin; 46.9% of desmopressin-
treated patients were euvolemic (etiology not specified),
and 46.9% were hypovolemic.
Most patients treated with a proactive strategy received
desmopressin every 6 to 8 hours. Desmopressin therapy
did not significantly reduce the incidence of overcorrection
(defined as a SNa increase of either >10 mEq/L in any 24-
hour period or ≥18 mEq/L in any 48-hour period), but it
did significantly prolong the duration of NaCl 3% infusion.
However, the initial SNa, before starting NaCl 3%, was not
used to calculate the correction rates, potentially under-
estimating the true incidence of overcorrection. The SNa at
initiation of NaCl 3% was significantly lower in the des-
mopressin group (116 [IQR, 112-118] vs 117.5 [IQR,
114-121] mEq/L; P = 0.035), and the SNa in the proactive
desmopressin group was not reported.
Jingushi et al43 limited their study to patients with
SNa < 115 mEq/L, a level much more prone to over-
correction; they compared 47 patients treated with
intranasal desmopressin (which had been adopted as a
standard protocol) with 17 patients treated without
desmopressin. Of the desmopressin-treated patients, 51%
had SIAD, 26% were polydipsic, and 11% were hypo-
volemic. Fewer patients in the desmopressin group were
corrected by >8 mEq/L in the first 24 hours (32% vs
Rondon-Berrios and Sterns

59%, P < 0.039), and a dose-response analysis indicated a Table 4. Advantage and Disadvantages of the Use of
positive association between cumulative 24-hour des- Hypertonic Saline Bolus Injection Versus Continuous Infusion
mopressin dose and correction by <8 mEq/L at 24 hours for the Management of Hyponatremia
(P = 0.003). Mode of
Administration Advantages Disadvantages
Bolus injection of Rapid attainment Fixed dose;
Conclusions and Recommendations hypertonic saline of goals and rapid overcorrection
reduction of common,
The Helwig intervention has stood the test of time. There intracranial especially after
are pros—and cons—to bolus injections versus continuous pressure repeated doses
infusion of hypertonic saline in the management of Continuous Rate can be Slow attainment of
hyponatremia (Table 4). Hyponatremic patients with infusion of adjusted frequently goals and slower
impending herniation, active seizures, impaired con- hypertonic saline to achieve desired reduction of
goals while intracranial
sciousness, or delirium should be treated with one or two avoiding pressure
100-mL boluses of NaCl 3%, each given over 10 minutes, overcorrection
or a single 150-mL infusion infused in a peripheral vein
over 30 minutes. Increasing the SNa by a few milli-
equivalents per liter within minutes rather than hours
makes both physiological and common sense and is now chronic hyponatremia with a baseline SNa < 120 mEq/L, a
supported by compelling experience. high risk for rapid correction and/or ODS (Table 3). We
However, despite claims to the contrary, bolus admin- continue desmopressin in patients with diabetes insipidus
istration of hypertonic saline is not less likely than who become hyponatremic while taking the drug,
continuous infusion to result in overcorrection of hypo- regardless of the severity of hyponatremia. We do not
natremia. Overcorrection was shown to be particularly recommend desmopressin for self-induced water intoxi-
common after a third 100-mL bolus in the Garrahy study, cation due to psychosis or if a water diuresis is unlikely to
and it is likely to be common after the second 150-mL develop (eg, hyponatremia caused by heart failure or
bolus recommended by the European guidelines. A third cirrhosis or longstanding SIAD). If the symptoms are se-
bolus should be reserved for active seizures or continuing vere, desmopressin can be combined with a bolus of NaCl
signs of herniation. We need better evidence that bolus 3%. To successfully avoid overcorrection, we continue
infusions are necessary in patients with nonspecific desmopressin at 6 to 8 hour intervals until the SNa reaches
symptoms like nausea and vomiting. 125 to 130 mEq/L, infusing NaCl 3% concurrently to
Even small volumes of hypertonic saline can provoke ensure correction by 4 to 6 mEq/L per day. Before stop-
water diuresis in patients with hypovolemia or low solute ping desmopressin, the previous day’s correction should
intake; to avoid this complication, we favor concurrent be assessed to be sure that the 48-hour limit is not
administration of desmopressin. We discourage formulas exceeded. Patients should be fluid restricted during des-
to guide the dosing of NaCl 3% because these are inac- mopressin use (eg, <800 mL/d) to prevent exacerbation of
curate,38 and we prefer frequent SNa determinations. hyponatremia.
When NaCl 3% is given by continuous infusion, we begin Proactive desmopressin may prolong the hospital stay;
at 1 to 1.5 mL/kg every 6 hours (eg, for an 80-kg person, however, we believe this is a small price to pay to prevent
80 × 1.5 = 120 mL infused over 6 hours, at 20 mL/h) and ODS, a potentially devastating neurological complication.
adjust the dose based on SNa measurements obtained every The regimen requires monitoring SNa at frequent intervals
4 to 6 hours. Potassium supplementation should be and a prompt response to results. For some hospitals, a
considered when correcting SNa with NaCl 3%. Potassium step-down unit will suffice.
is osmotically equivalent to sodium (1 mEq of concen- We need more data on when and how to use desmo-
trated potassium chloride is roughly equivalent to 2 mL of pressin with hypertonic saline. To be meaningful, the
NaCl 3%), and correction of hypokalemia can increase studies should employ standardized protocols and should
SNa.45 be limited to patients with SNa < 115 mEq/L, excluding
Even without hypertonic saline, patients with severe patients whose underlying condition makes overcorrection
chronic hyponatremia are at risk of neurological injury unlikely.
from excessive correction. For patients at added risk of
ODS (SNa ≤ 105 mEq/L, alcohol use disorder, hypokale-
Article Information
mia, malnutrition, or liver disease), correction by >8
mEq/L in 24 hours should be avoided,46 although Authors’ Full Names and Academic Degrees: Helbert Rondon-
Berrios, MD, MS, and Richard H. Sterns, MD.
adherence to this limit is difficult. The studies that have
addressed the proactive approach have had significant Authors’ Affiliations: Renal-Electrolyte Division, Department of
Medicine, School of Medicine, University of Pittsburgh, Pittsburgh,
methodological limitations, so no firm conclusion can be Pennsylvania (HR-B); Rochester General Hospital and School of
drawn from them. However, we favor proactive desmo- Medicine and Dentistry, University of Rochester, Rochester, New
pressin (2 to 4 μg intravenously or subcutaneously) for York (RHS).

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Address for Correspondence: Richard H. Sterns, MD, Rochester
General Hospital, 1425 Portland Ave, Rochester, NY 14621.
Email: richard.sterns@rochesterregional.org
Support: None.
Financial Disclosure: Dr Rondon-Berrios is funded by exploratory/
developmental research grant R21DK122023 from the National
Institute of Diabetes and Digestive and Kidney Diseases of the
National Institutes of Health. Dr Sterns declares that he has no
relevant financial interests.
Peer Review: Received May 30, 2021. Evaluated by 2 external peer
reviewers, with direct editorial input from an Associate Editor and a
Deputy Editor. Accepted in revised form July 25, 2021.
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