Review

2022 Dec 29. [Epub ahead of print]

https://doi.org/10.3904/kjim.2022.346

Evaluation and management of hypernatremia in

adults: clinical perspectives
Giae Yun1,*, Seon Ha Baek2,*, and Sejoong Kim1,3,4

1
Department of Internal Medicine, Hypernatremia is an occasionally encountered electrolyte disorder, which may lead to
Seoul National University Bundang
Hospital, Seongnam; 2Department of
fatal consequences under improper management. Hypernatremia is a disorder of the
Internal Medicine, Hallym University homeostatic status regarding body water and sodium contents. This imbalance is the
Dongtan Sacred Heart Hospital, basis for the diagnostic approach to hypernatremia. We summarize the eight diagnostic
Hwaseong; 3Artificial Intelligence in
Healthcare, Seoul National University steps of the traditional approach and introduce new biomarkers: exclude pseudohyper-
Bundang Hospital, Seongnam; natremia, confirm glucose-corrected sodium concentrations, determine the extracellular
4
Department of Internal Medicine, volume status, measure urine sodium levels, measure urine volume and osmolality, check
Seoul National University College of
Medicine, Seoul, Korea ongoing urinary electrolyte free water clearance, determine arginine vasopressin/copeptin
levels, and assess other electrolyte disorders. Moreover, we suggest six steps to manage
Received : November 7, 2022 hypernatremia by replacing water deficits, ongoing water losses, and insensible water
Accepted : November 29, 2022 losses: identify underlying causes, distinguish between acute and chronic hypernatremia,
determine the amount and rate of water administration, select the type of replacement
Correspondence to
Sejoong Kim, M.D. solution, adjust the treatment schedule, and consider additional therapy for diabetes in-
Division of Nephrology, Department sipidus. Physicians may apply some of these steps to all patients with hypernatremia, and
of Internal Medicine, Seoul National can also adapt the regimens for specific causes or situations.
University Bundang Hospital, 82
Gumi-ro 173beon-gil, Bundang-gu,
Seongnam 13620, Korea Keywords: Correction; Evaluation; Hypernatremia; Sodium; Treatment
Tel: +82-31-787-7088
Fax: +82-31-787-4052
E-mail: sejoong@snubh.org
https://orcid.org/0000-0002-7238-
9962

*These authors contributed equally

to this work.

Introduction ment, hypernatremia is rare with a prevalence of 0.2% to

1.0%, this prevalence is about 10 times higher at 2% to 6%
Hypernatremia is defined as serum sodium (sNa) concentra- in critically ill patients, whereas it is about 10% in intensive
tion exceeding 145 mmol/L and reflects serum hyperosmo- care units [4,9-11].
lality, which is an occasionally encountered electrolyte disor- In patients with acute hypernatremia, the morbidity and
der in hospitalized patients, especially in elderly and critically mortality rates are exceedingly high [10,12]. Several stud-
ill patients [1-3]. The prevalence of hypernatremia varies ies have shown that the mortality of hypernatremia varies
widely depending on various clinical settings [4,5]. The prev- from 10% to 75% [1,10,12,13]. In studies with adult pa-
alence among hospitalized patients has been reported to be tient populations, sNa concentrations above 160 mmol/L
between 0.5% and 5.0% [2,6-8]; in the emergency depart- (severe hypernatremia) are associated with a 75% mortality

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 The Korean Journal of Internal Medicine. 2022 Dec 29. [Epub ahead of print]

rate [3,12,14]. Neonatal hypernatremia is a potentially le- content, which can result from a net water loss or hyper-
thal condition, and children with acute hypernatremia have tonic sodium gain [12,25,27]. Because plasma sodium is a
a 10% to 70% mortality rate [13,15-17]. Similar to hypona- solute unable to permeate cell membranes, it contributes
tremia [18-22], hypernatremia can be life-threatening [1], so to tonicity and induces the movement of water across cell
it needs to be diagnosed and managed promptly based on membranes [1,12,28]. Therefore, hypernatremia induces
practice guidelines. hypertonicity and always causes, at least, transient cellular
dehydration [1,12,28]. Sustained hypertonicity caused by
chronic hypernatremia promotes the accumulation of or-
Pathophysiology of Hypernatremia ganic osmolytes (e.g., glutamate, taurine, and myo-inositol)
and these adaptive changes thereby pull water into the cells
The human body maintains a normal osmolality between and restore the cell volume [12,13,28,29]. Therefore, chron-
280 and 295 mOsm/kg by water homeostasis, which is ic hypernatremia is much less likely to provoke neurologic
mediated by arginine vasopressin (AVP) secretion, thirst-in- symptoms [12,28]. However, adaptive changes to chronic
duced water ingestion, and the renal water transport in hypernatremia induce delayed clearance of osmolytes from
response to AVP [1,2,23-25]. Abnormalities in water ho- the cell compared to rapid loss of potassium and sodium
meostasis (defects in one or more of these physiological during cerebral swelling [12,28]. Thus, rehydration to rap-
mechanisms) are manifested as disorders in the sNa concen- idly correct chronic hypernatremia induces cerebral edema,
tration―hypernatremia or hyponatremia [1,2,13,24-27]. seizures, and coma [1,12,28].
An impairment in the urine-diluting capacity or excess water
intake leads to hyponatremia [25]. By contrast, hypernatre-
mia is caused by a defect in the ability to concentrate urine Clinical manifestations
or insufficient water intake [25]. Hypernatremia usually re-
sults from a deficit of water in relation to the body’s sodium Signs and symptoms of hypernatremia are predominantly

Table 1. Signs and symptoms of hypernatremia

Characteristics of hypernatremia Symptoms related to the characteristics of hypernatremia
Cognitive dysfunction and symptoms associated with neuronal cell Lethargy
shrinkage Obtundation (depression on sensorium)
Confusion
Abnormal speech
Irritability
Seizures (unusual in adults)
Nystagmus
Myoclonic jerks
Muscle spasticity (unusual in adults)
Focal neurologic deficits
Nausea or vomiting
Dehydration or clinical signs of volume depletion Orthostatic blood pressure changes
Tachycardia
Oliguria
Dry oral mucosa
Abnormal skin turgor
Dry axillae
Intense thirst
Other clinical findings Weight loss
Generalized weakness
Fever
Labored respiration

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Yun G, et al. Management of hypernatremia in adults

related to disturbances of the central nervous system due to Therefore, hypernatremia should be further classified to
brain cell shrinkage and are prominent when the increase provide evaluation and treatment directions (Table 2) [3,38].
in sNa concentration is large or occurs rapidly [13,28]. Hypernatremia is divided into acute (within 48 hours) and
Manifestations of hypernatremia vary from thirst, weak- chronic (more than 48 hours or unknown time of initiation)
ness, neuromuscular excitability, hyperreflexia, and lethar- hypernatremia [13,24,39].
gy to confusion, seizure, or coma (Table 1) [2,3,13,18,30]. Because sustained hypernatremia can occur only when
Acute hypernatremia (within 48 hours) causes abrupt brain thirst perception or water access is impaired, the groups
cell shrinkage that can result in vascular rupture, cerebral at highest risk are patients with altered mental status, in-
bleeding, subarachnoid hemorrhage, or even death; these tubated patients, infants, and elderly persons [12,15,27]. In
vascular complications are mostly encountered in pediatric geriatric and intensive care patients, hypernatremia is asso-
and neonatal patients [1,12,13]. The loss of consciousness ciated with (1) the inability to maintain an adequate volume
level is associated with the severity of hypernatremia [3]. Pa- balance (e.g., in physically or mentally impaired patients);
tients with chronic hypernatremia (more than 48 hours or (2) the need for parenteral nutrition (e.g., patients in inten-
unknown time of initiation) are less likely to develop severe sive care units or nursing homes); and (3) an impaired thirst
neurologic symptoms due to adaptive responses generating perception, which may be caused by the age-dependent
osmolytes [12,29]. However, adaptive changes to chronic degeneration of osmoreceptors in the brain stem [1,12,40].
hypernatremia may lead to the development of cerebral Hypernatremia is generally caused by combined water
edema and seizures during overly rapid rehydration (over- and electrolyte deficit, with losses of free water in excess of
correction of plasma Na+ by ≥ 12 mmol/L or ≥ 0.5 mmol/L/ Na+ [12,25,27]. This imbalance can result from (1) net water
hr), especially in infants [28,31-33]. In critically ill adults, loss, which can either be pure water (absence of a sodium
however, recent evidence does not indicate that rapid cor- deficit) or hypotonic fluid (presence of a sodium deficit) loss,
rection of hypernatremia is associated with increased mor- or (2) gain of hypertonic sodium [4]. Most cases of hyperna-
tality, seizure, or cerebral edema; therefore, if overcorrec- tremia are caused by net water loss, which can result from
tion of hypernatremia occurs, hypernatremia does not need renal and non-renal routes (insensible or gastrointestinal
to be reinduced [31,34]. By contrast, several adult studies water loss) [20]. Common causes of renal water loss include
have demonstrated that higher mortality results from exces- osmotic diuresis secondary to hyperglycemia, excessive
sively slow correction rates [11,35,36]. urea, postobstructive diuresis, or mannitol administration,
all of which share an increase in urinary solute excretion and
urine osmolality (Uosm) [1,26,41-43]. Hypernatremia due to
Classification and etiology of hyper- water diuresis develops in central or nephrogenic diabetes
natremia insipidus [12]. Less frequently, hypertonic sodium gain usu-
ally results from clinical interventions or accidental sodium
Hypernatremia is not a disease but rather a pathophysio- loading. The etiology of hypernatremia is summarized in
logic process indicating disturbed water balance [20,37]. Table 3 and Fig. 1 [12].

Table 2. Classifications of hypernatremia

Criteria Classification Value
Absolute serum sodium concentration Mild 146–150 mmol/L
Moderate 151–155 mmol/L
Severe > 155 mmol/L [38]
Extreme > 190 mmol/L [3]
Time of development (cutoff 48 hours) Acute vs. Chronic
Clinical assessment of volume status Hypovolemic
Euvolemic
Hypervolemic

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 The Korean Journal of Internal Medicine. 2022 Dec 29. [Epub ahead of print]

Table 3. Cause of hypernatremia

1. Net water loss
1) Euvolemia (pure water loss = water deficit)
↓↓total body water, total body Na+ unchanged
Extrarenal losses
Respiratory (tachycardia)
Dermal (sweating, fever)
Renal losses
Central diabetes insipidus (neurogenic)
Post-traumatic
Caused by tumors, cysts, histiocytosis, tuberculosis, sarcoidosis
Idiopathic
Caused by aneurysms, meningitis, encephalitis, Guillain-Barré syndrome
Caused by ethanol ingestion (transient)
Nephrogenic diabetes insipidus
Congenital
Acquired
Caused by renal disease (e.g., medullary cystic disease)
Caused by hypercalcemia or hypokalemia
Caused by drugs (lithium, demeclocycline, foscarnet, methoxyflurane, amphotericin B, vasopressin V2 receptor antagonists)
Other
Inability to gain access to fluids
Hypodipsia or adipsia
Reset osmostat (essential hypernatremia)
2) Hypovolemia (hypotonic fluid loss = combined water and sodium deficit)
↓↓total body water, ↓total body Na+
Extrarenal losses
Gastrointestinal losses
Vomiting
Nasogastric drainage
Enterocutaneous fistula
Diarrhea
Use of osmotic cathartic agents (e.g., lactulose)
Dermal (cutaneous causes)
Burns
Excessive sweating
Renal losses
Osmotic diuresis (mannitol, glucose, urea)
Loop diuretics
Postobstructive diuresis
Polyuric phase of acute tubular necrosis
Intrinsic renal disease
Others

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Yun G, et al. Management of hypernatremia in adults

Table 3. Continued
2. Hypertonic sodium gain (hypervolemia)
variable total body water (↓/unchanged/↑), ↑↑total body Na+
Hypertonic saline (e.g, 3% normal saline) or NaHCO3 administration
Infants or comatose patients receiving hypertonic feeding
Ingestion of sodium chloride
Ingestion of seawater
Sodium chloride-rich emetics
Hypertonic saline enemas
Intrauterine injection of hypertonic saline
Hypertonic sodium chloride infusion
Hypertonic dialysis
Primary hyperaldosteronism
Cushing’s syndrome
Mineralocorticoid excess

Hypernatremia

Exclude pseudohypernatremia and calculate corrected sNa

Assess volume status

(ECF volume)

Not increased Increased

Hypovolemia Euvolemia Hypervolemia

TBW ↓↓ TBW ↓ TBW ↑

TBNa+ ↓ TBNa+ ↔ TBNa+ ↑↑

U[Na+] > 20 mmol/L U[Na+] < 20 mmol/L U[Na+] variable U[Na+] > 20 mmol/L

Renal losses Extrarenal losses Renal losses Extrarenal losses Sodium gains
: Uosm high : Uosm high : Uosm low : Uosm high : Uosm high

• Osmotic or loop diuretics • Excess sweating • DI • Insensible losses • Primary

• Post obstruction • Burns • Respiratory • Hyperaldosteronism
• Intrinsic renal disease • Diarrhea • Dermal • Cushing’s syndrome
• Fistulas • Hypodipsia • Hypertonic dialysis
• Hypertonic sodium
• Bicarbonate
• NaCl tablets

Figure 1. Diagnostic approach to hypernatremia. sNa, serum sodium; ECF, extracellular fluid; TBW, total body water; TBNa+, total body
sodium; U[Na+], urine sodium concentration; Uosm, urine osmolality; DI, diabetes insipidus; NaCl, sodium chloride.

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 The Korean Journal of Internal Medicine. 2022 Dec 29. [Epub ahead of print]

Diagnostic approach to hypernatremia EIGHT DIAGNOSTIC STEPS OF HYPERNA-

TREMIA
Comprehensive consideration of clinical history, physical ex-
amination, and laboratory findings helps to determine the Hypernatremia can be divided into three different subgroups
cause of hypernatremia (Fig. 1) [13,44]. The history should based on the extracellular fluid volume [2]. Using a urinary
focus on predisposing factors including impaired mental marker (Uosm, urine electrolyte, or urine electrolyte-free
states, physical handicaps, and postoperative state; the pres- water clearance [EFWC]), the physician can determine the
ence or absence of thirst; diuresis/oliguria; and non-renal underlying cause of hypernatremia and adjust the treatment
sources of water loss, such as diarrhea, fever, and infection accordingly [2,46-48].
[13,39]. The physical examination should include a detailed
neurologic evaluation and an assessment of the extracellu- 1. First, exclude pseudohypernatremia
lar fluid volume; reduced jugular venous pressure and or- Pseudohypernatremia is defined as spuriously increased
thostatic hypotension are symptoms of hypovolemia, which plasma sodium (> 145 mmol/L) due to decreased plasma
indicates a considerable water deficit or an electrolyte and protein or lipid concentration [49,50]. There are two meth-
water deficiency [2,13]. Accurate documentation of daily ods of measuring sodium concentration with an ion-selec-
fluid input and urine output is also critical for diagnosing tive electrode (ISE) using either an undiluted sample (direct
and managing hypernatremia (Table 1) [37]. Patients with ISE) or a diluted sample (indirect ISE) [2,51]. Because spuri-
hypernatremia can be categorized into one of the following ous sodium concentrations occur mainly in indirect ISE anal-
three groups depending on their volume status [2]. yses, direct ISE has been proposed as the preferred method
in clinical settings characterized by abnormal protein or lipid
Hypovolemic hypernatremia (combined water concentration, particularly in critically ill patients [50,51]. In
and sodium deficit) patients with suspected pseudohypernatremia, measuring
Hypovolemic hypernatremia is a condition when a patient serum osmolality with an osmometer or sodium concentra-
loses both water and sodium; however, the water loss is tions with a direct potentiometer can reflect the true sNa
comparatively more substantial [13]. Signs and symptoms levels [2,50].
of hypovolemia, such as low blood pressure, tachycardia,
dry mucous membranes, abnormal skin turgor, orthostatic 2. Second, in patients with hyperglycemia, sNa concentra-
hypotension, weight loss, prerenal acute renal failure, met- tions should be corrected for glucose based on Eqs. (1)
abolic alkalosis, hemoconcentration resulting in elevated and (2) [6,51,52].
hematocrit or serum protein, or decreased jugular venous • Hillier et al. [53] (1999): Corrected Na level =
pressure (< 5 cmH2O), are present [2,13]. Na + 0.024 × [serum glucose (mg/dL) − 100] Eq. (1)
• Katz [54] (1973): Corrected Na level =
Euvolemic hypernatremia (water deficit) Na + 0.016 × [serum glucose (mg/dL) − 100] Eq. (2)
Patients with euvolemic hypernatremia may undergo renal
or non-renal water loss without any sodium loss [2,13]. Nei- 3. Third, determine whether the extracellular volume is
ther hypo- nor hypervolemia is apparent in the examination hypovolemic, euvolemic, or hypervolemic using the his-
[13]. tory and physical examinations, as described above

Hypervolemic hypernatremia (hypertonic 4. Fourth, measure urine sodium

sodium gain) Patients with volume depletion exhibit decreased sodium
Patients with hypervolemic hypernatremia show signs of excretion in the urine (< 20 mmol/L) [2,55]. Although hy-
volume overload such as peripheral or pulmonary edema povolemia may be present, a concentrating defect and an
[2]. Some of these patients have comorbidities such as liv- elevated urine sodium concentration (> 20 mmol/L) might
er dysfunction, renal dysfunction, or hypoalbuminemia that be observed in case of osmotic diuresis, the use of diuretics,
are likely to contribute to salt retention [13,45]. postobstructive nephropathy, or the recovery phase from
acute tubular necrosis [27,41,56].

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Yun G, et al. Management of hypernatremia in adults

5. Fifth, measure urine volume (UV) and Uosm al and stimulated levels of AVP or copeptin, a peptide co-se-
A Uosm < 300 mOsm/kg and polyuria (> 3 L/day or > 40 creted with AVP in the setting of hypertonicity, are required
mL/kg/day) suggest the presence of diabetes insipidus [2,56- for adequate differentiation between polyuria-polydipsia
58]. Administration of exogenous AVP (typically its pharma- syndrome, which includes primary polydipsia, as well as cen-
cological analog desmopressin acetate [DDAVP]) enables tral and nephrogenic diabetes insipidus [24,65,66]. By defi-
the distinction between central and nephrogenic diabetes nition, patients with baseline hypernatremia are hypertonic,
insipidus, which is associated with at least a 50% increase with an adequate stimulus for AVP secretion by the poste-
in Uosm along with a significant decrease in UV in central rior pituitary [20,59,67]. Basal AVP or copeptin concentra-
diabetes insipidus, whereas no change is seen in nephro- tions in the serum are elevated in hypernatremic patients
genic diabetes insipidus [9,28,59]. If Uosm is between 300 with nephrogenic diabetes insipidus [27,66,68-70]. Their
and 800 mOsm/kg, this may reflect partial diabetes insipi- low Uosm will also fail to respond to DDAVP, increasing
dus (central or nephrogenic), central diabetes insipidus with by < 50% or < 150 mOsm/kg from baseline; patients with
volume depletion, or a process of osmotic diuresis [13,60]. central diabetes insipidus will respond to DDAVP stimulation
The measurement of total solute excretion is helpful in this with a reduction in AVP or copeptin levels [68-70]. The level
situation [2,13]. of circulating basal and stimulated AVP or copeptin will help
• Total solute excretion distinguish the underlying etiology (central and nephrogen-
= Uosm × 24 hr UV (L) Eq. (3) ic diabetes insipidus, primary polydipsia) [27,62,68-70]. Pa-
Excessive excretion of sodium chloride, mannitol, glucose, tients may have a partial response to DDAVP, with a > 50%
or urea, with a daily solute excretion of > 750–1,000 mOsm/ rise in Uosm that nevertheless fails to achieve 800 mOsm/
day (> 15 mOsm/kg body water/day), might result in an os- kg [60,65]. AVP is not routinely measured in clinical practice
motic diuresis [13,61]. A Uosm > 800 mOsm/kg indicates due to preanalytic instability [71-73]. Copeptin has become
either primary hypodipsia, excessive non-renal water loss, or a surrogate marker for AVP concentration, has advantag-
saline overload [1,2,13]. In this case, the non-renal source es over AVP regarding stability, and can be measured with
(gastrointestinal tract, respiratory tract, or skin) of water loss commercially available assays with high-standard technical
may be the primary reason for the development of hyper- performance [62,68-70].
natremia [13]. The appropriate response to hypernatremia
and hyperosmolality is an increase in circulating AVP and 8. Eighth, check concomitant electrolyte disorders (serum
the excretion of low volumes (< 500 mL/day) of maximally potassium and calcium)
concentrated urine (Uosm > 800 mOsm/kg) [62]. Hypokalemia (serum potassium level < 3.0 mmol/L) [74]
or hypercalcemia (serum calcium concentration > 11 mg/dL
6. Sixth, in patients with hypernatremia due to renal wa- or 2.75 mmol/L) [75] may induce an impairment of kidney
ter loss, check ongoing urinary EFWC calculated based concentrating ability via decreased collecting tubule respon-
on Eq. (4). siveness to vasopressin, resulting in polyuria, nephrogen-
• Urine EFWC = UV × [1 – (UNa + UK) / SNa] Eq. (4) ic diabetes insipidus, and development of hypernatremia
(UNa, urine sodium; UK, urine potassium) [9,27,61].
EFWC can differentiate between renal or extrarenal water
losses [2,63,64]. Therefore, a substantially increased positive
value indicates increased renal water losses due to osmot- Treatment of hypernatremia
ic diuresis, furosemide administration, renal failure, or dia-
betes insipidus, whereas a value near zero or even (rarely) Management of hypernatremia requires two approaches:
negative suggests gastrointestinal or insensible water losses (1) identifying and resolving the underlying cause and (2)
[42,63,64]. correcting the established hypertonicity (hyperosmolarity)
considering the severity of neurologic symptoms, onset time
7. Seventh, check AVP or copeptin levels in patients with (acute vs. chronic), and volume status [1,13]. A stepwise ap-
hypotonic polyuria proach is summarized in the following points (Fig. 2).
A water deprivation test along with the evaluation of bas-

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 The Korean Journal of Internal Medicine. 2022 Dec 29. [Epub ahead of print]

1. First, identify the underlying cause and initiate treat- natremia (within 48 hours) due to sodium loading, a more
ment accordingly aggressive rapid correction of plasma sodium (falling by 1–2
Identifying the underlying cause of hypernatremia and mmol/L/hr for the first 6–8 hours, restoring a sNa concentra-
initiating treatment is important to prevent further water tion of 145 mmol/L within 24 hours) improves the prognosis
loss or hypertonic sodium gain [13,76]. Management of the without increasing the risk of cerebral edema [1,9,13,28].
predisposing factors may include stopping offending medi- However, patients with hypernatremia of longer (> 48
cation (lactulose, diuretics, or drugs associated with nephro- hours) or unknown duration should be corrected at a rate
genic diabetes insipidus) and gastrointestinal fluid losses of < 0.5 mmol/hr (12 mmol/L/day) based on data in pedi-
(vomiting or diarrhea); controlling fever, hyperglycemia, and atric patients (particularly infants) who have no neurologic
glycosuria; relieving urinary obstruction; treating hypercal- sequelae [1,9,32,33,78]. However, several studies in adults
cemia and hypokalemia; and withdrawing hypertonic tube have reported that rapid correction rates (> 0.5 mmol/L/hr)
feeds [1,13,27,77]. are not associated with a high risk of mortality and neu-
rologic damage [31,34], whereas higher mortality results
2. Second, assess the severity of symptoms and decide from excessively slow correction rates (< 0.25 mmol/L/hr,
whether the hypernatremia is acute or chronic 6 mmol/L/day) [11,31,35]. However, if the target rate is
The rate of sNa lowering should be estimated based main- inadvertently exceeded, therapeutic re-raising of the sNa
ly on the severity of neurologic symptoms and the duration concentration is not recommended [36]. For this reason, an
of hypernatremia [1,2,12,27]. In acute symptomatic hyper- ongoing study whose results will be available within 3 years

Hypernatremia

Acute (< 48 hours) Chronic (> 48 hours or unknown)

Onset?

Rapid correction Slow correction

Decrease in [Na+] 1-2 mmol/L/hr, Decrease in [Na+] < 0.5 mmol/L/hr

Target goal of sodium: 145 mmol/L within 24 hours Target goal of sodium: 6-11 mmol/L/day

Assess volume status

Hypovolemia Euvolemia Hypervolemia

Correction of volume deficit Correction of water deficit Removal of sodium

• ‌Initial fluid resuscitation with balanced crystalloid • ‌Calculate water deficit • Discontinue
‌ offending agents
(normal saline or lactated Ringer’s) until hypovole- • ‌Administer 0.45% saline, 5% dextrose, or oral hydra- • Free
‌ water replacement (intravenous 5% dextrose) +
mia improves tion to replace the water deficit and ongoing losses loop diuretics
• ‌Treatment of the underlying cause of losses (insulin, • ‌In central DI with severe losses: desmopressin • Hemodialysis
‌ as needed for renal failure
relief of obstruction, removal of osmotic diuretics,
etc.)

Correction of water deficit Long-term therapy

• Calculate water deficit • Central DI

• Administer 0.45% saline, 5% dextrose, or oral hydra- • Nephrogenic DI: discontinue offending agents and
tion to replace the water deficit and ongoing losses begin thiazide, amiloride, or NSAID

Figure 2. Treatment of hypernatremia. DI, diabetes insipidus; NSAID, nonsteroidal anti-inflammatory drug.

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Yun G, et al. Management of hypernatremia in adults

examines the effects of a sNa target correction rate of 6 to deficit or simplified fluid repletion regimen + insensible
11 mmol/L/day during the first 24 hours for the treatment loss + renal/extrarenal ongoing loss Eq. (7)
of hypernatremia [31]. 'Ongoing losses' are classified into renal and non-renal
losses. In patients with hypernatremia due to urinary losses,
3. Third, determine the required amount and rate of wa- the amount of ongoing water loss (urine EFWC) can be cal-
ter administration culated using Eq. (8) [64,83,84].
Estimate the 'water deficit' using Eq. (5) or (6) or devise a • Urine EFWC = UV × [1 − (UNa + UK) / SNa] Eq. (8)
fluid repletion regimen (I or II) as outlined below. However, Eq. (8) is limited and impractical to make pro-
•W  ater deficit = total body water (TBW; L) spective decisions because of the need to measure 24-hour
× (sNa / 140 − 1) Eq. (5) UV and complicated calculations [85]. A study suggested
For example, a female patient who weighs 60 kg and has a predictive guide of water restriction based on a simple
a sNa concentration of 166 mmol/L has a water deficit of approach of the urine/plasma electrolyte ratio derived from
0.5 × 60 [(166/140) − 1] = 5.6 L. With a simplified calcu- EFWC in patients with chronic hyponatremia [85]. An on-
lation, TBW is generally estimated to be 60% of the body going study in which the urine/plasma electrolyte ratio is
weight for men and 50% for women, and 5% is deducted applied to the treatment of hypernatremia and the results
for elderly patients [12,60]. In water-depleted hypernatre- regarding the usefulness of this parameter should be avail-
mic patients, lower values are usually applied (for men and able in the future [31].
women, 50% and 40% of the lean body weight, respec- In contrast to ongoing urinary losses, measuring ongo-
tively) [2]. To get the plasma sodium concentration back to ing water losses in the stool (as in patients with diarrhea) is
140 mmol/L, use Eq. (5) to calculate how much positive wa- usually impractical and not routinely performed [9]. In such
ter balance is needed [2,12] and administer the estimated patients, the simplest approach is to initiate therapy without
amount of water over 48 to 72 hours (2 to 3 days) [27]. accounting for ongoing free water losses, monitor the sNa
• Change in serum Na+ concentration, and increase the rate of fluid administration
= [(infusate Na+ + infusate K+) − sNa] if it is not falling at the desired rate [63,86].
/ (TBW + 1) Eq. (6) Extracellular fluid volume depletion or hypokalemia are
The formula in Eq. (6) proposed by Adrogue-Madias can common co-morbidities in patients with hypernatremia
be used in patients with hypernatremia to estimate the ef- [2,13]. Because volume depletion and hypokalemia can
fect of 1 L of any infusate on the patient’s sNa concentra- worsen hypernatremia, they should be included in the pro-
tion [79,80]. However, Eq. (6) did not accurately predict the vided 'maintenance fluid' or corrected by oral ingestion
changes in sNa levels in a group of patients with hyperna- [2,47,87,88]. Sodium or potassium can be added to the in-
tremia, severe extracellular volume depletion, and markedly travenous fluid as necessary to simultaneously correct the
reduced renal function [2,81]. water and electrolyte deficits [83,89]. However, the sodium
The following initial fixed-dose regimens have been sug- and potassium content of the replacement fluid decreases
gested. the amount of free water being supplied [87,90]. Using two
(I) Initial fixed-dose regimen with 5% dextrose water, in- intravenous solutions―one for free water and the other
travenously at a rate of 1.35 mL/kg/hr [28]. for sodium with or without potassium as an iso-osmotic
(II) Initial fixed-dose regimen with 5% dextrose water, in- solution―instead of combining water and sodium (with or
travenously at a rate of 3 mL/kg/hr. The rationale is without potassium) into one solution is an alternative [88].
that every 1 mmol/L decrease in the sNa concentration
requires 3 mL/kg of electrolyte-free water [82]. 4. Fourth, select the type of replacement solution
When administering the calculated amount of water A proper intravenous solution should be selected de-
based on Eq. (5) or (6) (intravenously, as dextrose in water, pending on the history, blood pressure, or volume status
or orally if the patient can drink) or by initial fixed-dose reg- as shown in Fig. 2 [12,88]. It may be appropriate to initially
imens (I or II), additional insensible loss, ongoing renal or treat the patient with hypotonic fluids including 5% dex-
extrarenal losses must be considered in the calculation [12]. trose, 0.2% or 0.45% sodium chloride (1/4 or 1/2 normal
• Total infused amount of water/day = calculated water saline) [13,91]. Notably, if a hypotonic saline solution is to

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 The Korean Journal of Internal Medicine. 2022 Dec 29. [Epub ahead of print]

be given, the amount of free water in the solution should Conclusions

be estimated [60]. In case of shock or hypotension, 0.9%
normal saline or balanced crystalloid should be used for re- Hypernatremia is attributed to a deficit of water, which can
suscitation regardless of the sNa level until the restoration result from a net water loss or hypertonic sodium gain. The
of volume has been reached [13,25,88,92]. In patients with detailed evaluation of the etiologies and proper choice of
volume overload (hypervolemic hypernatremia), the free type and rate of intravenous solution during the treatment
water deficit can be replaced with 5% dextrose in water, of hypernatremia is crucial since under- or overcorrection of
and diuretics should be administered to promote sodium hypernatremia is associated with increased morbidity and
excretion and maintain a negative fluid balance [9,89]. mortality.

5. Fifth, adjust the treatment schedule Conflict of interest

For the safety and successful management of patients No potential conflict of interest relevant to this article was
with hypernatremia, the treatment must be adjusted appro- reported.
priately, and repeated measurements of sNa are necessary
[36,46,93]. Acknowledgments
The research was supported by a grant No. 2021R1C1C
6. Sixth, consider additional therapy for diabetes insipidus 1008966 from the National Research Foundation of Korea.
Patients with central diabetes insipidus are treated with
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