DOI: 10.1002/ncp.

10907

INVITED REVIEW

Demystifying hyponatremia: A clinical guide to evaluation

and management

Bhavna Bhasin‐Chhabra MD1 | Vineet Veitla MD2,3 | Samuel Weinberg MD4 |

Abhilash Koratala MD2

1
Division of Nephrology, Department of
Medicine, Mayo Clinic, Scottsdale, Abstract
Arizona, USA Hyponatremia (serum sodium <135 mEq/L) is a frequent electrolyte
2
Division of Nephrology, Department of abnormality complicating the clinical care of hospitalized patients. Hypona-
Medicine, Medical College of Wisconsin,
Milwaukee, Wisconsin, USA tremia has been associated with an increased risk of mortality. Hyponatremia
3
Division of Pulmonary and Critical Care can be seen in patients with euvolemia, hypovolemia, or hypervolemia.
Medicine, Medical College of Wisconsin, Evaluation of hyponatremia relies on clinical assessment and estimation of
Milwaukee, Wisconsin, USA
serum sodium, urine electrolytes, and serum and urine osmolality in addition
4
Department of Medicine, Medical
College of Wisconsin, Milwaukee,
to other case‐specific laboratory parameters. In addition, point‐of‐care
Wisconsin, USA ultrasonography is an important adjunct to physical assessment in estimation
of volume status. Understanding the pathophysiology of the underlying
Correspondence
Bhavna Bhasin‐Chhabra, MD, process can lead to a timely diagnosis and appropriate management of
Department of Medicine, Division of hyponatremia.
Nephrology, Medical College of
Wisconsin, Milwaukee, WI 53226, USA. KEYWORDS
Email: Bhasin-Chhabra.Bhavna@mayo.edu
antidiuretic hormone, hyponatremia, point of care ultrasound, pseudohyponatremia,
sodium, vasopressin

I N T R O D U C TI O N hyponatremia,5,9 and occurrence of even mild hypona-

tremia may be associated with an increased risk of
Hyponatremia is the most frequent electrolyte abnormal- mortality after hospital discharge.10
ity, complicating the clinical care of 30%–40% of
hospitalized patients1,2 and 13%–30% of patients admitted
to the intensive care unit (ICU).3–5 The reference range of Basics of salt and water balance in
serum sodium is between 135 and 145 mEq/L, although the body
the exact range may be laboratory specific. Any decrease
in serum sodium below 135 mEq/L is considered Serum sodium concentration depends on the content of
hyponatremia. This may further be classified as acute exchangeable sodium (eNa) and exchangeable potassium
(ongoing for 48 h or less) vs chronic (ongoing for >48 h).6 (eK) relative to total body water (TBW), as described in the
Another system of classification would be labeling simplified Edelman formula: [Na] = (eNa+ + eK+)/TBW.
hyponatremia as moderate (125–129 mEq/L) or severe Hyponatremia should be considered a problem of water
(<125 mEq/L) depending on how far below the reference balance rather than salt balance in the body.11 As sodium
limit is the sodium level.7,8 The odds ratio for risk of is ion with the highest concentration in the extracellular
mortality increases incrementally based on the severity of fluid, it contributes the most to plasma osmolarity

© 2022 American Society for Parenteral and Enteral Nutrition.

Nutr. Clin. Pract. 2022;1–10. wileyonlinelibrary.com/journal/ncp | 1

2 | BHASIN‐CHHABRA ET AL.

(reported as mOsm/kg H2O), which can be measured in channels on the basolateral aspect. This process allows
the laboratory and also calculated using this formula: an otherwise impermeable membrane of the principal
2 × [Na+] (mEq/L) + serum urea nitrogen (mg/dl)/ cells to transport water efficiently into the cells and
2.8 + glucose (mg/dl)/18.12 Even though used interchange- circulation from the tubular fluid.13
ably in clinic practice, tonicity of the plasma is a different
concept that includes the concentration of effective
osmoles that cannot cross cell membranes readily and CLINICAL MANIFESTATIONS OF
contribute to hypotonicity or hypertonicity in a particular HY PON A TR EMIA
compartment (intracellular or extracellular), which can
then impact water movement into and out of the cells Hyponatremia leads to the movement of water into cells,
driven by the prevailing state of tonicity in the plasma. As causing cellular swelling. This same process in the brain
urea is freely permeable across cell membranes, it can leads to neurological manifestations of nausea, vomiting,
contribute to osmolarity but not tonicity. Thus, plasma headache, and lethargy. Chronic hyponatremia (ongoing
tonicity is obtained by deducting the value that urea lends for >48 h) is more common and may be better tolerated
to the osmolality formula above.11 than acute hyponatremia (developing in <48 h) because
the brain cells are able to lose electrolytes and amino
acids, which allows the brain to compensate somewhat
Regulation of tonicity by reducing the intracellular solute content. Acute severe
hyponatremia (sodium levels <125 mEq/L) may lead to
Tonicity is regulated by the pituitary gland and the profound neurological symptoms such as seizures,
kidney (Figure 1). The pituitary gland produces arginine cerebral edema, and coma, which will require prompt
vasopressin (AVP) in response to hypertonicity. Vaso- correction of the serum sodium levels (by 4–6 mEq/L) for
pressin is also known as antidiuretic hormone (ADH). a period of 1–2 h with hypertonic saline (3%) in the
Low plasma volume can also stimulate ADH production. critical care setting to alleviate these symptoms.6,14
A moderate to large decrease in blood pressure and the
resulting stretch of the carotid baroreceptors can also
lead to release of ADH. In the kidney, ADH acts on the Types of hyponatremia
vasopressin 2 receptors (V2 receptors) on the luminal
aspect of the principal cells in the collecting duct. This Evaluation of hyponatremia begins with obtaining serum
allows for migration and insertion of aquaporin‐2 osmolality (sOsm) in addition to urine osmolality (uOsm)
vesicles into the luminal membrane and transport of and urine electrolytes (or urine sodium [uNa]) (Figure 2).
water into the cell, which then moves into the hypertonic sOsm normally ranges between 275 and 295 mOsm/kg
medullary interstitial compartment through aquaporin of H2O.12 Hyponatremia can be classified as hypotonic

F I G U R E 1 Regulation of tonicity by the pituitary gland and kidney. AQP‐2, aquaporin‐2; ATP, adenosine triphosphate; cAMP, cyclic
adenosine monophosphate; V2R, vasopressin 2 receptor.
NUTRITION IN CLINICAL PRACTICE | 3

F I G U R E 2 Algorithm for evaluation of hyponatremia. *uOsm in states of low solute intake can be >100 mOsm/kg, depending on the
actual solute intake. **uNa can be variable with thiazide diuretic use. ADH, antidiuretic hormone; CHF, congestive heart failure;
ECV, effective circulatory volume; SIADH, syndrome of inappropriate ADH secretion; sNa, serum sodium; sOsm, serum osmolality
(in mOsm/kg H2O); uNa, urine sodium; uOsm, urine osmolality (in mOsm/kg H2O).

(sOsm <275 mOsm/kg of H2 O), isotonic (sOsm H2O) of electrolyte‐free water, leaving the individual in a
275–295 mOsm/kg of H2 O), or hypertonic (sOsm state of free water excess. This is in contrast to the
>295 mOsm/kg of H 2O). average of approximately 800 mOsm of solute per day
The next step after estimation of sOsm is obtaining generated by the kidney on a normal diet in which
the uOsm. ADH plays a critical role in urinary dilution, maximal urine dilution can allow for 16 L (800 mOsm/
which can cause the uOsm to range from a low value of 50 mOsm/kg of H2O) of free water excretion per day. The
50 mOsm/kg H2O to as high as 1200 mOsm/kg H2O. dominant mechanism underlying hypotonic hyponatre-
uOsm <100 mOsm/kg H2O is indicative of a state of mia is the impairment of urinary dilution by ADH, which
suppressed ADH, which may be physiological in condi- can be physiologically appropriate or inappropriate and
tions of excessive water ingestion, such as primary can be seen in a state of euvolemia, hypovolemia, or
polydipsia, or pathological with decreased production of hypervolemia. So the next step in assessment of
ADH in central diabetes insipidus. Solute ingestion is a hypotonic hyponatremia is an estimation of the volume
key factor in determining the excretion of free water. status. A diagnostic approach to hyponatremia and
Normal solute excretion by the kidney varies, with an etiologies of hyponatremia is described in Figure 2.
average of 800 mOsm per day.11 Decreased solute intake
may be noted in beer potomania and tea and toast diet,
and this in turn leads to low solute output by the Hypovolemic hyponatremia
kidney.15 Assuming a solute output of 200 mOsm per day
and maximal urine dilution down to 50 mOsm/kg, the Hypovolemic hyponatremia can result from increased
kidney can excrete only 4 L (200 mOsm/50 mOsm/kg volume losses from gastrointestinal tract (diarrhea or
4 | BHASIN‐CHHABRA ET AL.

vomiting) or kidney (loop diuretics, osmotic diuresis, Euvolemic hyponatremia

salt wasting from mineralocorticoid deficiency, or
cerebral salt wasting). Bicarbonaturia and ketonuria The leading etiologies for euvolemic hyponatremia are
have also been associated with increased renal sodium the syndrome of inappropriate ADH secretion (SIADH),
and water loss. Other sources such as excessive cortisol deficiency as well as severe hypothyroidism.
sweating, blood loss due to hemorrhage or third spacing SIADH is characterized by an inappropriate release of
of fluid in burns, pancreatitis, and muscle trauma can ADH in the absence of an osmotic or non‐osmotic
also induce a state of volume depletion.16 Establishing stimulus. Cortisol deficiency causes euvolemic hypona-
an accurate volume status is critical to guiding tremia and may be accompanied by hypoglycemia. In
appropriate further management directed toward the severe hypothyroidism, the decrease in cardiac output
etiology of hypovolemia. A thorough physical examina- may lead to a non‐osmotic release of ADH and fluid
tion focusing on features supportive of hypovolemia is retention.11 It is noteworthy that patients receiving
imperative. Point‐of‐care ultrasonography (POCUS) is a thiazide diuretics can appear euvolemic while being
helpful adjunct to physical examination to guide volume hyponatremic because of impaired urinary dilution.16,19
assessment in hyponatremia,17,18 and this will be
discussed later in the article.
SPECIAL C ONSIDERATIONS

Hypervolemic hyponatremia Pseudohyponatremia

Hypervolemic hyponatremia is frequently encountered Isotonic hyponatremia should raise suspicion of pseudohy-
in patients with cirrhosis, nephrotic syndrome, and ponatremia, which can be encountered owing to para-
decompensated heart failure in which there is vascular proteinemia or hyperlipidemia. The term pseudohypona-
underfilling due to reduced intravascular circulating volume tremia refers to a falsely low measurement of serum sodium
generating a state of hypoperfusion, leading to non‐osmotic levels due to expansion of the solid phase of the plasma by a
release of ADH. This in turn impairs the urinary diluting high protein level (in paraproteinemia) or lipid level
capacity, leading to hyponatremia. Urinary dilution is also (in hypertriglyceridemia and hypercholesterolemia),20,21 as
impaired in the setting of acute and chronic kidney disease is demonstrated in Figure 3. The traditional method of
because of a decreased ability to handle free water excretion measurement of serum sodium in the laboratory uses
in these cases.16 Development of hyponatremia may be an indirect potentiometry with ion‐specific electrodes. This
indicator of the severity and advanced state of the underlying involves measurement of the potential across a membrane
disease process (cirrhosis and heart failure) and has been (selective for sodium ion) when a serum sample is run. In
associated with mortality. this technique, the sample is diluted before running it.

F I G U R E 3 Demonstration of
pseudohyponatremia with an elevated protein
and lipid level. Figure created with
biorender.com
NUTRITION IN CLINICAL PRACTICE | 5

When the standard amount of diluent is added to a serum feasible.26 Patients undergoing PN may experience non‐
sample in which the solid‐phase protein or lipid content of osmotic release of ADH due to various drugs or in the
plasma is high, the result is a falsely low serum sodium presence of nausea or pain. Administration of excess
level. The true sodium level can be checked by performing fluid in a setting of ADH upregulation may explain the
direct potentiometry in the laboratory.22 Thus, a sodium observed occurrence of hyponatremia with PN. Severe
level checked on an arterial blood gas (which uses direct malnutrition, female sex, nausea or vomiting, and opiate
potentiometry) may yield the correct sodium level. use have been shown to be risk factors associated with
Another condition labeled as pseudohyponatremia development of hyponatremia in patients receiving PN,25
but more accurately defined as true dilutional hypona- whereas the sodium content of PN has not been shown to
tremia is hyperglycemia. Glucose is osmotically active be associated with hyponatremia.26
and can drive the movement of water across membranes.
Any rise in serum glucose >100 mg/dl can cause a
decrease in serum sodium by 1.6 mEq/L for every 100‐ Hyponatremia in the critically sick
mg/dl rise in serum glucose. When serum glucose level
increases beyond 400 mg/dl, this correction can be as Hyponatremia is the most frequently encountered
high as 2.4 mEq/L. Pseudohyponatremia can also be seen electrolyte disturbance in patients admitted to the ICU.
after transurethral resection of the prostate with the use Similar to other hospitalized patients, hyponatremia
of glycine‐ or sorbitol‐rich irrigation solutions, which can (even mild hyponatremia) is an independent predictor
be absorbed into the systemic circulation.23 for an increased length of stay in the ICU and increased
in‐hospital mortality.27 The risk factors for patients for
hyponatremia in the ICU include severe sepsis, pneumo-
Hyponatremia due to low solute intake nia, heart failure, cirrhosis, subarachnoid hemorrhage,
and after surgery.28 In addition to the underlying disease‐
Hyponatremia due to low solute intake includes the specific process, hyponatremia in the ICU may be
categories of tea and toast diet as well as beer potomania. aggravated by an upregulation of ADH and excessive
These processes underlying hyponatremia are indepen- administration of hypotonic fluids.29
dent of ADH activity. These dietary patterns lead to
excess free water or alcohol (in beer potomania) relative
to solute intake. With low solute (low protein and salt) SIADH
intake, the kidney is limited in its ability to optimize free
water excretion. Assessment of uOsm may show a low SIADH is characterized by a state of euvolemic hypona-
total solute excretion of 500 mOsm per day.24 It is tremia, although patients may have increased extracel-
important to remember that rapid restoration of solute lular volume. Although SIADH may be coexistent with a
intake with administration of intravenous fluids may disorder of hypovolemia or hypervolemia, fluid status
lead to overly rapid correction of serum sodium levels, must be corrected before uncovering a diagnosis of
and chronic alcoholism is a risk factor for osmotic SIADH.30 Additionally, patients should not be on diuretic
demyelination syndrome (ODS) discussed in the treat- therapy and other etiologies of euvolemic hyponatremia
ment section.23 (glucocorticoid deficiency and hypothyroidism) must be
ruled out before a diagnosis of SIADH can be ascer-
tained.31 Serum laboratory markers classically show a
Parenteral nutrition–related hypo‐osmolar hyponatremic state (serum osmolality
hyponatremia <275 mosm/kg of H2O), elevated uOsm, and elevated
urine sodium (>40 mmol/L) in addition to other
Hyponatremia is more frequently encountered in pa- supporting clinical features, which include a low plasma
tients (18%) receiving parenteral nutrition (PN) than in uric acid (<4 mg/dl) and worsening of serum sodium
other hospitalized patients, and this has been associated levels with fluid administration.32
with higher mortality.25 Some studies estimate that the SIADH has numerous etiologies and is implicated in
correction of hyponatremia by accounting for total 90% of the hyponatremia occurring after a subarachnoid
protein may yield a higher estimate of the prevalence hemorrhage and traumatic brain injury. SIADH also
of hyponatremia.26 Hospitalized patients may require PN accounts for about 80% of cases of pneumonia in which
when they need bowel rest for another clinical indication hyponatremia is seen.33 There are many classes of
(gastrointestinal malignancy, obstruction, intractable medications that have been associated with SIADH,
diarrhea, or vomiting) and enteral nutrition is not including psychiatric medications (selective serotonin
6 | BHASIN‐CHHABRA ET AL.

reuptake inhibitors and tricyclic antidepressants) and

clinical and laboratory data

some antiepileptic drugs (carbamazepine, oxcarbazepine,

Discordant or ambiguous
and valproate). Chemotherapy drugs such as vincristine,
vinblastine, cyclophosphamide, methotrexate, and cis-
platin have also been known to cause SIADH. Pain
medication such as nonsteroidal anti‐inflammatory drugs
and opioids, as well as medication in other categories
such as amiodarone and fluroquinolones, has been

Abbreviations: FoCUS, focused cardiac ultrasound; NA, not applicable; POCUS, point‐of‐care ultrasonography; VExUS, venous excess Doppler ultrasound; VTI, velocity time integral.
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
associated with SIADH too. Malignant cells can produce
ADH, most commonly in lung cancer (particularly small
cell lung cancer), squamous cell carcinoma of head and
neck, olfactory neuroblastoma, and extrapulmonary
small cell carcinomas. Any surgery or procedure can

Lung ultrasound, VExUS

FoCUS, lung ultrasound

FoCUS, lung ultrasound

FoCUS, lung ultrasound
induce SIADH. Nearly any pulmonary insult, commonly

Secondary POCUS
pneumonia, pneumothorax, respiratory failure, or atelec-

Inferior vena cava

Inferior vena cava

tasis, can result in SIADH. HIV is an infectious cause of

parameters
SIADH. Idiopathic SIADH can be diagnosed when
known causes have been ruled out.32–37 There are some

FoCUS
genetic causes of SIADH, but these would be more likely

NA
to be diagnosed during early childhood than to be
diagnosed in adulthood.38,39
Primary POCUS parameter that directly aided

Role of POCUS in hyponatremia

Summary of case studies demonstrating the role of POCUS in evaluation of hyponatremia

FoCUS (left ventricular outflow tract VTI)

As mentioned previously, assessment of extracellular

Inferior vena cava, lung ultrasound

volume status is a key component in the evaluation and
management of hyponatremia. However, it has been long
recognized that the conventional physical examination is
of limited sensitivity and specificity for this purpose. In
one study including 58 non‐edematous patients with
Inferior vena cava

serum sodium <130 mEq/L, clinical assessment correctly

in diagnosis

identified only 47% of patients with hypovolemia and

48% of patients with euvolemia, highlighting the need for
VExUS
VExUS

VExUS
VExUS

VExUS

more objective measures of volume status.40 Similar

observations have been replicated in various clinical
settings associated with volume derangements, including
heart failure, critical illness, and hemodialysis.41–43 Over
Hypervolemic, hypo‐osmolar
Hypervolemic, hypo‐osmolar

Hypervolemic, hypo‐osmolar
Hypervolemic, hypo‐osmolar
Hypervolemic, hypo‐osmolar
Hypervolemic, hypo‐osmolar
Hypovolemic, hypo‐osmolar
Hypovolemic, hypo‐osmolar

the past several years, POCUS has evolved as an

Type of hyponatremia

enhancement to physical examination in various special-

ties, including nephrology and critical care.44,45 It refers
to clinician‐performed limited ultrasound examination
intended to answer focused clinical questions. Bedside
sonographic evaluation of the pump (heart), pipes
(inferior vena cava, abdominal venous Doppler), and
the leaks (extravascular lung water, ascites) facilitates
objective assessment of fluid status in conjunction with
First author, year

clinical and laboratory data.46 For example, uNa can be

17
Chatterjee, 2022
Koratala, 202247

50
18

low in patients with hypovolemia or hypervolemia as

48

Koratala, 2021
Samant, 2021

52
Varudo, 2022

51
Saqib, 202249

Singh, 2019

well as in those with low effective circulating volume,

Evins, 2020
TABLE 1

such as vasodilatory/high‐output state (cirrhosis). In

such cases, being able to estimate stroke volume and
identify the presence or absence of venous congestion at
NUTRITION IN CLINICAL PRACTICE | 7

F I G U R E 4 Overview of the common sonographic findings in hypovolemia, hypervolemia, and vasodilatory states. These clinical
entities are dynamic in nature and can be seen in the same patient during the course of therapy. D, hepatic diastolic wave; HV, hepatic vein;
LV, left ventricle; PV, portal vein; RAP, right atrial pressure; RV, renal parenchymal vein; RV, right ventricle; S, hepatic systolic wave;
VExUS, venous excess Doppler ultrasound.

the bedside, using POCUS, guides appropriate manage- slower correction of serum sodium is required. There is
ment, thus minimizing empiric interventions. Moreover, evidence to support that a rate of correction of 4–6 mmol/
solely relying on physical findings such as pedal edema, 1 L/24 h is both safe and effective and leaves room for
skin turgor, and even lung crackles may lead to incorrect error in the event of an inadvertent rapid correction of
diagnosis.17,18 Table 1 summarizes case studies in which hyponatremia that which puts the individual patient at
POCUS aided in clinical decision making in patients with high risk for ODS.7,30 This is caused by the inability of the
hyponatremia. Interestingly, there was a discordance brain to restore the solutes that were lost earlier in the
between clinical and/or laboratory parameters in all the development of hyponatremia, and this leads to central
cases, prompting POCUS evaluation to discern volume pontine myelinolysis and extrapontine myelinolysis54 and
status. Whereas the detailed description of individual is typically diagnosed by magnetic resonance imaging of
sonographic parameters is beyond the scope of this the brain. ODS may be asymptomatic or present with
manuscript, common findings in major phenotypes of neurologic manifestations of paraparesis or quadriparesis,
volume alterations in patients with hyponatremia are confusion, dysarthria, and ataxia.55,56 Serum sodium levels
concisely presented in Figure 4. <105 mEq/L, alcohol use disorder, malnutrition, liver
disease, and hypokalemia have been reported to be
associated with a higher risk of ODS.23,56 Despite close
T R E A T M E N T OF H Y P O N A T R E M I A monitoring of serum sodium, if there is a rapid correction
of serum sodium levels beyond goal range during a 24‐h
Treatment of hyponatremia is based on the acuity of onset period, attempts at returning the serum sodium level to
(acute vs chronic) and severity of hyponatremia and target range rely on administration of hypotonic fluids—
symptoms at presentation. When a patient with hypona- for example, 5% dextrose in water—as well as intravenous
tremia presents with severe neurological symptoms, such desmopressin to augment free water resorption in the
as seizures or changes in mental status leading to distal tubules.30,31
encephalopathy or coma, an increase in serum sodium In addition to safe correction of serum sodium levels,
by 4–6 mEq/L by administration of hypertonic saline is treatment of hyponatremia is directed toward the
warranted, typically with administration of 100‐ml underlying pathology. Primary polydipsia requires a
doses.7,30,53 In patients without severe neurologic symp- strict fluid restriction and, ideally, psychiatric manage-
toms from hyponatremia and chronic hyponatremia, a ment of the underling mental illness that typically
8 | BHASIN‐CHHABRA ET AL.

accompanies primary polydipsia. Those with low solute underlying pathology, whether it be removal of offending
intake owing to a tea and toast diet or beer potomania medication, resolution of pneumonia, treatment of
require augmentation of solute intake. Fluids should be malignancy, and so on.31 In the setting of SIADH,
administered with caution because these patients are at normal saline should be avoided, as it can worsen the
risk for rapid correction of serum sodium.57 A long‐term hyponatremia. If fluid administration is needed, 3%
change in the patient's diet, nutrition counseling, and/or hypertonic saline should be given. With SIADH, an
reduction of beer consumption is required to avoid repeat estimated 1 ml/kg of hypertonic saline will increase the
episodes of hyponatremia. Patients diagnosed with serum sodium by about 1 mEq/L.11,35 The other causes of
hypovolemic hyponatremia need careful fluid resuscita- euvolemic hyponatremia should be corrected by treating
tion with normal saline and close monitoring of serum the underlying etiology—for example, proper correction
sodium levels to keep sodium correction within goal of thyroid hormone in hypothyroidism or supplementa-
range. Those with cerebral salt wasting may require more tion of glucocorticoids in adrenal insufficiency.31 Proper
sodium supplementation than patients with other causes diagnosis of hyponatremia is required to provide timely
of hypovolemic hyponatremia.31 Patients with hypervo- and effective treatment with careful monitoring of
lemic hyponatremia, regardless of etiology, require a sodium levels to avoid the risk of rapid correction
reduction in TBW. Typically, the most effective method is and ODS.
diuresis, although strict free water and salt restriction is
the usual recommended initial treatment.58,59 Chronic A U T H O R C O N TR I B U T I O N S
diuretic and other disease‐specific, evidence‐based thera- Bhavna Bhasin‐Chhabra and Abhilash Koratala concep-
pies are required to reduce the risk of chronic tualized the article and contributed to the writing and
hyponatremia in conditions such as heart failure and editing of the manuscript, figures, and tables. Vineet
cirrhosis. Another class of drugs called vaptans Veitla and Samuel Weinberg contributed to the writing of
(described in the next paragraph) have also been used the manuscript.
to promote aquaresis by increasing free water
excretion.60 C O NF L I C T O F I N T E R E S T
With SIADH as the etiology of hyponatremia, the None declared.
initial treatment is typically fluid restriction. The amount
of fluid restriction that can be used with success in ORC ID
hyponatremia depends on the ratio of urinary sodium Bhavna Bhasin‐Chhabra http://orcid.org/0000-0003-
and potassium to serum sodium levels. If this ratio is 1199-7822
<0.5, a fluid restriction of 1.0 L may be imposed. If the
ratio is 0.5–1, a fluid restriction of 500 ml per day can be REFER ENCES
considered, whereas fluid restriction is unlikely to be 1. Buffington MA, Abreo K. Hyponatremia: a review. J Intensive
effective if this ratio is >1.0.11,61,62 If fluid restriction fails Care Med. 2016;31(4):223‐236. doi:10.1177/0885066614566794
to correct hyponatremia, the next step is to consider salt 2. Upadhyay A, Jaber BL, Madias NE. Incidence and prevalence
tablets and additional pharmacotherapy. Salt tablets are of hyponatremia. Am J Med. 2006;119(7 suppl 1):S30‐S35.
doi:10.1016/j.amjmed.2006.05.005
widely used to increase solute delivery and increase free
3. Vandergheynst F, Sakr Y, Felleiter P, et al. Incidence and
water excretion. Oral urea can be given to increase free
prognosis of dysnatraemia in critically ill patients: analysis of a
water excretion, as well as reduce urine sodium large prevalence study. Eur J Clin Invest. 2013;43(9):933‐948.
excretion.7,11 Another therapeutic option, although less doi:10.1111/eci.12123
preferred, is the use of demeclocycline. The administra- 4. DeVita MV, Gardenswartz MH, Konecky A, Zabetakis PM.
tion of demeclocycline can cause a nephrogenic diabetes Incidence and etiology of hyponatremia in an intensive care
insipidus, reducing urine osmolarity. However, this unit. Clin Nephrol. 1990;34(4):163‐166.
comes with an attendant risk of acute kidney injury.63 5. Funk GC, Lindner G, Druml W, et al. Incidence and prognosis
Finally, vaptans can be used. This is a class of medication of dysnatremias present on ICU admission. Intensive Care
Med. 2010;36(2):304‐311. doi:10.1007/s00134-009-1692-0
that blocks the AVP V2 receptor, promotes aquaresis,
6. Sterns RH. Treatment of severe hyponatremia. Clin J Am Soc
and increases free water excretion. Tolvaptan is an oral
Nephrol. 2018;13(4):641‐649. doi:10.2215/CJN.10440917
V2 receptor antagonist that has been used in clinical 7. Hoorn EJ, Zietse R. Diagnosis and treatment of hyponatremia:
practice but is an expensive option for treatment of compilation of the guidelines. J Am Soc Nephrol. 2017;28(5):
SIADH‐related hyponatremia. It should be used while 1340‐1349. doi:10.1681/ASN.2016101139
working in collaboration with an experienced nephrolo- 8. Ball SG, Iqbal Z. Diagnosis and treatment of hyponatraemia.
gist so as to avoid adverse events.11,61 The definitive Best Pract Res Clin Endocrinol Metab. 2016;30(2):161‐173.
treatment of hyponatremia is correction of the doi:10.1016/j.beem.2015.12.001
NUTRITION IN CLINICAL PRACTICE | 9

9. Stelfox HT, Ahmed SB, Khandwala F, Zygun D, Shahpori R, 26. Gómez‐Hoyos E, Fernández‐Peña S, Cuesta M, et al. Hypona-
Laupland K. The epidemiology of intensive care unit‐ tremia in patients receiving parenteral nutrition: the impor-
acquired hyponatraemia and hypernatraemia in medical‐ tance of correcting serum sodium for total proteins. The role
surgical intensive care units. Crit Care. 2008;12(6):R162. of the composition of parenteral nutrition in the development
doi:10.1186/cc7162 of hyponatremia. Eur J Clin Nutr. 2018;72(3):446‐451. doi:10.
10. Waikar SS, Mount DB, Curhan GC. Mortality after hospital- 1038/s41430-017-0026-5
ization with mild, moderate, and severe hyponatremia. Am 27. Rafat C, Flamant M, Gaudry S, Vidal‐Petiot E, Ricard JD,
J Med. 2009;122(9):857‐865. doi:10.1016/j.amjmed.2009.01.027 Dreyfuss D. Hyponatremia in the intensive care unit: how to
11. Seay NW, Lehrich RW, Greenberg A. Diagnosis and manage- avoid a Zugzwang situation. Ann Intensive Care. 2015;5(1):39.
ment of disorders of body tonicity‐hyponatremia and hyper- doi:10.1186/s13613-015-0066-8
natremia: core curriculum 2020. Am J Kidney Dis. 2020;75(2): 28. Padhi R, Panda BN, Jagati S, Patra SC. Hyponatremia in
272‐286. doi:10.1053/j.ajkd.2019.07.014 critically ill patients. Indian J Crit Care Med. 2014;18(2):83‐87.
12. Rasouli M. Basic concepts and practical equations on doi:10.4103/0972-5229.126077
osmolality: biochemical approach. Clin Biochem. 2016;49(12): 29. Rosner MH, Ronco C. Dysnatremias in the intensive care unit.
936‐941. doi:10.1016/j.clinbiochem.2016.06.001 Contrib Nephrol. 2010;165:292‐298. doi:10.1159/000313769
13. Bankir L, Bichet DG, Morgenthaler NG. Vasopressin: physiol- 30. Verbalis JG, Goldsmith SR, Greenberg A, et al. Diagnosis,
ogy, assessment and osmosensation. J Intern Med. 2017;282(4): evaluation, and treatment of hyponatremia: expert panel
284‐297. doi:10.1111/joim.12645 recommendations. Am J Med. 2013;126(10 suppl 1):S1‐S42.
14. Rondon‐Berrios H, Agaba EI, Tzamaloukas AH. Hyponatre- doi:10.1016/j.amjmed.2013.07.006
mia: pathophysiology, classification, manifestations and man- 31. Arampatzis S, Frauchiger B, Fiedler GM, et al. Characteristics,
agement. Int Urol Nephrol. 2014;46(11):2153‐2165. doi:10. symptoms, and outcome of severe dysnatremias present on
1007/s11255-014-0839-2 hospital admission. Am J Med. 2012;125(11):1125.e1‐1125.e7.
15. Berl T. Impact of solute intake on urine flow and water doi:10.1016/j.amjmed.2012.04.041
excretion. J Am Soc Nephrol. 2008;19(6):1076‐1078. doi:10. 32. Ellison DH, Berl T. Clinical practice. The syndrome of
1681/ASN.2007091042 inappropriate antidiuresis. N Engl J Med. 2007;356(20):
16. Adrogue HJ, Madias NE. Hyponatremia. N Engl J Med. 2064‐2072. doi:10.1056/NEJMcp066837
2000;342(21):1581‐1589. doi:10.1056/NEJM200005253422107 33. Cuesta M, Thompson CJ. The syndrome of inappropriate
17. Chatterjee T, Koratala A. Point of care cardiac ultrasound in antidiuresis (SIAD). Best Pract Res Clin Endocrinol Metab.
the management of hyponatremia: an enhancement to 2016;30(2):175‐187. doi:10.1016/j.beem.2016.02.009
physical examination. CEN Case Rep. 2022;11(1):6‐10. doi:10. 34. Spasovski G, Vanholder R, Allolio B, et al. Clinical practice
1007/s13730-021-00623-9 guideline on diagnosis and treatment of hyponatraemia.
18. Samant S, Koratala A. Point‐of‐care Doppler ultrasound Nephrol Dial Transplant. 2014;29(suppl 2):i1‐i39. doi:10.
in the management of hyponatremia: another string to 1093/ndt/gfu040
nephrologists' Bow. Clin Case Rep. 2021;9(8):e04687. doi:10. 35. Sahay M, Sahay R. Hyponatremia: a practical approach.
1002/ccr3.4687 Indian J Endocrinol Metab. 2014;18(6):760‐771. doi:10.4103/
19. Filippone EJ, Ruzieh M, Foy A. Thiazide‐associated hypona- 2230-8210.141320
tremia: clinical manifestations and pathophysiology. Am 36. Yoo M, Bediako EO, Akca O. Syndrome of inappropriate
J Kidney Dis. 2020;75(2):256‐264. doi:10.1053/j.ajkd.2019. antidiuretic hormone (SIADH) secretion caused by squamous
07.011 cell carcinoma of the nasopharynx: case report. Clin Exp
20. Dawson A, Kanukuntla A, Kata P, Ali R, Cheriyath P. Otorhinolaryngol. 2008;1(2):110‐112. doi:10.3342/ceo.2008.1.
Pseudohyponatremia leading to a fatal outcome in a patient 2.110
with familial hypertriglyceridemia. Cureus. 2021;13(8):e17066. 37. Berniker AV, Abdulrahman AA, Teytelboym OM,
doi:10.7759/cureus.17066 Galindo LM, Mackey JE. Extrapulmonary small cell carci-
21. Girot H, Dehais M, Fraissinet F, Wils J, Brunel V. Atypical noma: imaging features with radiologic‐pathologic correlation.
pseudohyponatremia. Clin Chem. 2018;64(2):414‐415. doi:10. Radiographics. 2015;35(1):152‐163. doi:10.1148/rg.351140050
1373/clinchem.2017.276501 38. Feldman BJ, Rosenthal SM, Vargas GA, et al. Nephrogenic
22. Dhatt G, Talor Z, Kazory A. Direct ion‐selective electrode syndrome of inappropriate antidiuresis. N Engl J Med.
method is useful in diagnosis of pseudohyponatremia. 2005;352(18):1884‐1890. doi:10.1056/NEJMoa042743
J Emerg Med. 2012;43(2):348‐349. doi:10.1016/j.jemermed. 39. Ranieri M, Tamma G, Pellegrino T, et al. Gain‐of‐function
2011.07.021 mutations of the V2 vasopressin receptor in nephrogenic
23. Henry DA. In the clinic: hyponatremia. Ann Intern Med. syndrome of inappropriate antidiuresis (NSIAD): a cell‐based
2015;163(3):ITC1‐ITC19. doi:10.7326/AITC201508040 assay to assess constitutive water reabsorption. Pflugers Arch.
24. Yeates KE, Singer M, Morton AR. Salt and water: a simple 2019;471(10):1291‐1304. doi:10.1007/s00424-019-02307-x
approach to hyponatremia. CMAJ. 2004;170(3):365‐369. 40. Chung HM, Kluge R, Schrier RW, Anderson RJ. Clinical
25. Gómez‐Hoyos E, Buigues AO, Ballesteros Pomar MD, et al. assessment of extracellular fluid volume in hyponatremia. Am
Development of hyponatremia in non‐critical patients receiv- J Med. 1987;83(5):905‐908. doi:10.1016/0002-9343(87)90649-8
ing total parenteral nutrition: a prospective, multicenter study. 41. Stevenson LW, Perloff JK. The limited reliability of physical
Clin Nutr. 2019;38(6):2639‐2644. doi:10.1016/j.clnu.2018. signs for estimating hemodynamics in chronic heart failure.
11.014 JAMA. 1989;261(6):884‐888.
10 | BHASIN‐CHHABRA ET AL.

42. Cox EGM, Koster G, Baron A, et al. Should the ultrasound 54. Lambeck J, Hieber M, Dressing A, Niesen WD. Central
probe replace your stethoscope? a SICS‐I sub‐study comparing pontine myelinosis and osmotic demyelination syndrome.
lung ultrasound and pulmonary auscultation in the critically Dtsch Arztebl Int. 2019;116(35‐36):600‐606. doi:10.3238/
ill. Crit Care. 2020;24(1):14. doi:10.1186/s13054-019-2719-8 arztebl.2019.0600
43. Torino C, Gargani L, Sicari R, et al. The agreement between 55. Jahan M, Sharma S, Rehmani R. Osmotic demyelination
auscultation and lung ultrasound in hemodialysis patients: the syndrome despite appropriate hyponatremia correction.
LUST study. Clin J Am Soc Nephrol. 2016;11(11):2005‐2011. Cureus. 2020;12(5):e8209. doi:10.7759/cureus.8209
doi:10.2215/CJN.03890416 56. Tandukar S, Sterns RH, Rondon‐Berrios H. Osmotic demyeli-
44. Koratala A, Olaoye OA, Bhasin‐Chhabra B, Kazory A. nation syndrome following correction of hyponatremia by ≤10
A blueprint for an integrated point‐of‐care ultrasound mEq/L per day. Kidney360. 2021;2(9):1415‐1423. doi:10.34067/
curriculum for nephrology trainees. Kidney360. 2021;2(10): KID.0004402021
1669‐1676. doi:10.34067/KID.0005082021 57. Lodhi MU, Saleem TS, Kuzel AR, et al. “Beer Potomania”—a
45. Kirkpatrick JN, Grimm R, Johri AM, et al. Recommendations syndrome of severe hyponatremia with unique patho-
for echocardiography laboratories Participating in Cardiac physiology: case studies and literature review. Cureus.
Point of Care Cardiac Ultrasound (POCUS) and critical care 2017;9(12):e2000. doi:10.7759/cureus.2000
echocardiography training: report from the American Society 58. Nagler EV, Vanmassenhove J, van der Veer SN, et al.
of Echocardiography. J Am Soc Echocardiogr. 2020;33(4): Diagnosis and treatment of hyponatremia: a systematic review
409‐422. doi:10.1016/j.echo.2020.01.008 of clinical practice guidelines and consensus statements. BMC
46. Koratala A, Kazory A. Point of care ultrasonography for Med. 2014;12:1. doi:10.1186/s12916-014-0231-1
objective assessment of heart failure: integration of cardiac, 59. Bernardi M, Zaccherini G. Approach and management of
vascular, and extravascular determinants of volume status. dysnatremias in cirrhosis. Hepatol Int. 2018;12(6):487‐499.
Cardiorenal Med. 2021;11(1):5‐17. doi:10.1159/000510732 doi:10.1007/s12072-018-9894-6
47. Koratala A, Ronco C, Kazory A. Multi‐organ point‐of‐care 60. Vinod P, Krishnappa V, Chauvin AM, Khare A, Raina R.
ultrasound in acute kidney injury. Blood Purif. Accepted Cardiorenal syndrome: role of arginine vasopressin and
manuscript. Published online March 18, 2022. doi:10.1159/ vaptans in heart failure. Cardiol Res. 2017;8(3):87‐95. doi:10.
000522652 14740/cr553w
48. Varudo R, Pimenta I, Blanco JB, Gonzalez FA. Use of Venous 61. Workeneh BT, Jhaveri KD, Rondon‐Berrios H. Hyponatremia
Excess UltraSound (VExUS) score in hyponatraemia manage- in the cancer patient. Kidney Int. 2020;98(4):870‐882. doi:10.
ment in critically ill patient. BMJ Case Rep. 1016/j.kint.2020.05.015
2022;15(2):e246995. doi:10.1136/bcr-2021-246995 62. Grant P, Ayuk J, Bouloux PM, et al. The diagnosis and
49. Saqib M, Capelli G, Koratala A. Utility of nephrologist‐ management of inpatient hyponatraemia and SIADH. Eur
performed point of care ultrasonography in the evaluation of J Clin Invest. 2015;45(8):888‐894. doi:10.1111/eci.12465
hyponatremia. POCUS J. 2022;7(kidney):11‐13. 63. Miell J, Dhanjal P, Jamookeeah C. Evidence for the use of
50. Koratala A, Sturgill D. Point‐of‐care venous Doppler ultra- demeclocycline in the treatment of hyponatraemia secondary
sound in the management of heart failure and hyponatremia. to SIADH: a systematic review. Int J Clin Pract. 2015;69(12):
Clin Nephrol. 2021;96(1):63‐66. doi:10.5414/CN110388 1396‐1417. doi:10.1111/ijcp.12713
51. Evins C, Rao A. Point‐of‐care ultrasound to evaluate volume
status in severe hyponatremia. BMJ Case Rep.
2020;13(6):e235304. doi:10.1136/bcr-2020-235304
52. Singh G, Rachoin JS, Chien C, Patel S. The use of portal vein How to cite this article: Bhasin‐Chhabra B,
pulsatility to differentiate hypervolemic and hypovolemic
Veitla V, Weinberg S, Koratala A. Demystifying
hyponatremia. Case Rep Crit Care. 2019;2019:9591823.
doi:10.1155/2019/9591823
hyponatremia: A clinical guide to evaluation and
53. Spasovski G, Vanholder R, Allolio B, et al. Clinical practice management. Nutr Clin Pract. 2022;1‐10.
guideline on diagnosis and treatment of hyponatraemia. Eur doi:10.1002/ncp.10907
J Endocrinol. 2014;170(3):G1‐G47. doi:10.1530/EJE-13-1020