CME

Managing hyponatremia in adults

Darla Moran, PA-C, MPAS, RD; Carissa Fronk, PA-C, MPAS; Ellen Mandel, DMH, MPA, PA-C, RD

ABSTRACT
Hyponatremia can be challenging to manage, especially in
older adults. Acute severe hyponatremia can cause significant
morbidity and mortality, but too-rapid reversal of chronic
hyponatremia can cause serious neurologic issues or death.
This article reviews the causes, presentations, and management
of hyponatremia in adults.
Keywords: hyponatremia, older adults, acute, chronic,
long-term care, syndrome of inappropriate antidiuretic
hormone

Learning objectives
Identify the major causes of hyponatremia in adults.
Differentiate the clinical presentation of acute and chronic
hyponatremia.
Create treatment plans for various types of hyponatremia in
adults, including older adults.

CAROL AND MIKE WERNER / PHOTOTAKE

T
he diagnosis and management of hyponatremia,
especially in older adults, can be a challenge for
clinicians.1,2 Hyponatremia is the most common
electrolyte imbalance, occurring in 15% to 30% of hos-
pitalized patients, 11% of older ambulatory care patients,
5.3% of hospitalized older adults, and 18% of long-term
care residents.2-8 Patients presenting with hyponatremia
tend to be over age 80 years, female, and living in long-
term care.2 Some patients experience mild effects while
others reach potentially fatal states.9 Hyponatremia has
been linked to higher mortality, longer hospital stays, and tions, diagnostic tools, and treatment options. Clinicians
higher healthcare costs.10,11 also should have a realistic awareness of the gravity of this
Although acute severe hyponatremia may lead to sig- condition so they can develop effective care plans to cau-
nificant morbidity and mortality, too-rapid correction of tiously reverse hyponatremia in older adults.9
chronic hyponatremia may result in serious neurologic Because older adults are more likely to develop hypona-
issues or death.3,12 As a result, clinicians need a solid under- tremia and more likely to die from it than younger adults,
standing of the various causes of hyponatremia, presenta- this article highlights the causes and pathophysiology of
hyponatremia in older adults.

Darla Moran and Carissa Fronk are recent graduates of the PA
program at Pace University-Lenox Hill Hospital in New York, N.Y. Ellen
Mandel is a clinical professor in the PA program at Pace University.
The authors have disclosed no potential conflicts of interest, financial
or otherwise.
DOI: 10.1097/01.JAA.0000444730.86174.e8
Copyright 2014 American Academy of Physician Assistants
CAUSES
Many factors can cause a patients serum sodium to drop
below the normal range of 135 to 145 mEq/L.13 Dysna-
tremias are particularly common in older adults in part
due to the normal aging process, which alters patients
ability to maintain water and sodium homeostasis.2,7

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CME

Patients with hypervolemic hyponatremia may have a

Key points history of liver and kidney failure, and the physical exam-
Hyponatremia is the most common electrolyte imbalance ination may reveal jugular venous distension, peripheral
in older adults. Causes in older adults include changes edema, and pulmonary congestion.7,10,16 If the patient is
in the aging kidney, hormonal changes related to aging, not taking diuretics, the fractional excretion of sodium
medications, low dietary sodium intake, and idiopathic (FENa) can be calculated; the result should be less than
SIADH. 1% if the patient has cardiac failure or cirrhosis, and greater
Acute severe hyponatremia can cause significant morbidity than 1% in patients with acute kidney injury or chronic
and mortality, but too-rapid reversal of hyponatremia can kidney disease.7
cause serious neurologic issues or death.
Patients with euvolemic hyponatremia have total body
Hypotonic hyponatremia, the most common form, occurs sodium close to normal without extracellular fluid volume
when patients have excess free water relative to serum
abnormalities such as edema, ascites, pulmonary congestion,
sodium levels.
or pleural effusion.7,10,16 With euvolemic hyponatremia,
Treatment includes IV administration of hypertonic saline clinicians must rule out hypothyroidism, hypopituitarism,
and treating underlying conditions, while taking into
pharmacologic stimulation of ADH (Table 1), severe emo-
account the patients volume status.
tional and physical stress including psychosis, anesthesia,
and surgery before considering a diagnosis of SIADH.
Laboratory studies to evaluate SIADH include thyroid
Significant renal, cardiac, and hepatic dysfunction, com- stimulating hormone (TSH) and cortisol response to adre-
mon in older adults, are the greatest risk factors for devel- nocorticotropic hormone (ACTH).7
oping hyponatremia due to the nonosmotic release of Patients with SIADH generally have low urine output
antidiuretic hormone (ADH, also called vasopressin).4 In (for example, 500 mL/24 hours) with a concomitant
fact, nonosmotic release of ADH is the cause in more than increase in urine sodium concentration.7 For a diagnosis
95% of inpatients and long-term care residents diagnosed of SIADH, the patient must be euvolemic, with a urine
with hyponatremia. In addition, various medications com- osmolality greater than 100 mOsm/kg and low serum
monly prescribed to older adults decrease the ability to osmolality.17 The patient also should be evaluated for
concentrate urine or can induce syndrome of inappropri- pulmonary, nervous system, vascular, and neoplastic con-
ate secretion of antidiuretic hormone (SIADH), ultimately ditions, which are responsible for more than 90% of cases
leading to drug-induced hyponatremia (Table 1).2,7,14 of SIADH.7,10
Older adults who are immobile also may have a con- Hyponatremia can present with varied tonicity:
comitant increase in total body water with lower serum Hypertonic hyponatremia occurs when another osmole,
sodium. Some of the many other causes include postop- such as glucose, draws water into the intravascular space,
erative complications, acute illness, hypocortisolism, and diluting the serum sodium content. This type of hypona-
hypothyroidism.2,15 tremia can occur in patients with hyperglycemia and after
mannitol or contrast media administration.4,8,10,18
TABLE 1. Drugs that can induce hyponatremia2,7,18 Isotonic hyponatremia, also known as pseudohypona-
tremia, is a rare finding often resulting from hyperlipidemia
Drugs or drug classes in italics may induce SIADH. or hyperproteinemia causing an artificially low serum
Acetaminophen Morphine and opioid derivatives sodium due to a dilutional effect.4,10,18 In such cases the
Amiloride Nicotine plasma may be isotonic or hypertonic to the intracellular
Amiodarone NSAIDs fluid, but neither results in intracellular fluid shifts and will
Antidepressants Proton pump inhibitors
not result in adverse reactions.4
Antiepileptics Prostaglandin-synthesis
Hypotonic hyponatremia is the most common of the
Antipsychotics inhibitors
Barbiturates Phenothiazines hyponatremias, occurring when the patient has excess free
Bromocriptine Theophylline water relative to serum sodium levels.3,18 Common causes
Carbamazepine Thiazides of hypotonic hyponatremia are listed in Table 2.
Chlorpropamide Tolbutamide Hypotonic hyponatremia can be further subdivided based
Ciprofloxacin Tricyclic antidepressants on the patients volume level, and many causes of hypo-
Clofibrate Trimethoprim-sulfamethoxazole natremia can be categorized by volume status.
Cyclophosphamide Venlafaxine Euvolemic hyponatremia is most common due to the
Desmopressin Vincristine abundance of disease states presenting with concomitant
Indapamide Vinblastine SIADH.3,5 This type of hypotonic hyponatremia is charac-
IV Immunoglobulin
terized by an increase in total body water with no concurrent
Loop diuretics
change to serum sodium levels. SIADH, the most common
Lorcainide
cause of hyponatremia, is more common in older adults.17

24 www.JAAPA.com Volume 27 Number 4 April 2014

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 Managing hyponatremia in adults

Hypervolemic hyponatremia results when both total

TABLE 2. Causes of hypotonic hyponatremia3,10,14,15,21
body water and sodium retention are increased with over-
all water retention exceeding sodium retention. EuvolemicSIADH, diabetes insipidus, CNS disorders,
Hypovolemic hyponatremia is defined as sodium loss drug induced, adrenal insufficiency, pulmonary diseases,
that far surpasses water loss in spite of both water and hypothyroidism, primary polydipsia, beer potomania, very
sodium levels decreasing.3,10,18-20 low protein diet

Hypervolemicheart failure, nephrotic syndrome, renal

PATHOPHYSIOLOGY AND RISK FACTORS
failure, Cushing syndrome, saline infusions
The principal mechanisms of water and sodium homeo-
stasis in the body are controlled by hypothalamic osmo- HypovolemicGI losses such as from vomiting, diarrhea,
receptors, which regulate the secretion of ADH and or GI suction; renal losses from diuretic therapy, cerebral
perception of thirst.2,5,21 When osmoreceptors sense slight salt wasting, or mineralocorticoid deficiency; third-spacing
increases in plasma tonicity, ADH is released from the from burns, bowel obstruction, or pancreatitis; sweating
posterior pituitary, causing increased
kidney tubule permeability, increased
water reabsorption, and formation
of more concentrated urine.2
In older adults, osmoreceptors
are hypersensitive compared with
younger adults, as shown by hyper-
tonic fluid administration and water
deprivation tests.5 The same phenom-
enon can be observed by administer-
ing metoclopramide to stimulate
vasopressin, resulting in significantly
higher ADH release in older adults.5
Hypersensitivity of these mechanisms
along with increased time to excrete
excess water predispose older adults
to hyponatremia.5
Structural changes in the aging kid-
ney also can contribute to the devel-
opment of hyponatremia. These
changes include glomerular sclerosis
of the superficial cortex, tubular
atrophy, interstitial fibrosis, and
hyalinosis of the arterioles. This
leads to functional declines including
decreases in glomerular filtration rate
(GFR), creatinine clearance, renal
plasma flow, and the ability to dilute
and concentrate filtrate.2,22 Normally,
older adults are able to compensate
for these changes and sustain a nor-
NUCLEUS MEDICAL ART, INC / PHOTOTAKE

mal balance of electrolytes. However,

illness or injury may potentiate loss
of electrolyte homeostasis and lead
to dysnatremias and volume dys-
regulation.2
Hormonal changes with aging
result in decreased renin and renin
activity, decreased aldosterone, and
may contribute to heightened excre-
tion of sodium into the urine, espe-
cially in patients with hypovolemia.2 FIGURE 1. Severe acute hyponatremia and the brain

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CME
Natural age-related changes also occur in atrial natriuretic
hormone secretion and the renin-angiotensin-aldosterone
system (RAAS). These changes alter homeostatic regulation
of fluid balance and may lead to hyponatremia.5
Risk factors for hyponatremia in older adults include
administration of hypotonic fluid, low dietary sodium
intake, low-sodium enteral nutrition formulas for primary
nutrition, previous brain injury, age, and idiopathic SIADH.
Whites and Hispanics appear to be at higher risk than
African Americans.5 Thiazide diuretics and selective sero-
tonin reuptake inhibitors are more likely to cause hypo-
natremia in older adults than in younger adults.2 Clinicians
must take steps to avoid promoting hyponatremia in older
adults because of these structural and functional altera-
tions, comorbid conditions, and medications that can lead
to fluid and sodium dysregulation.
CLINICAL PRESENTATION
Patients may present with varying signs and symptoms,
including headache, muscle weakness, nausea, vomiting,
lethargy, disorientation, depressed reflexes, or seizures.1
The severity depends on many factors, including the dura-
tion of the condition, serum sodium levels, and the acute
or chronic nature of onset.23,24
The symptoms of mild-to-moderate hyponatremia
lethargy, weakness, irritability, nausea, abdominal pain,
confusion, and tachypneaalso may be characteristic of
hypothyroidism, hypoglycemia, viral or psychiatric illness,
and various other electrolyte imbalances. Patients with
more severe hyponatremia may present with a head injury
resulting from a fall or seizure. Head injury secondary to
a fall also may be characteristic of nonhyponatremia-
related seizures, stroke, polysubstance abuse, and cardiac
emergencies.10
Acute hypotonic hyponatremia This electrolyte imbal-
ance arises in less than 48 hours.24 Common symptoms
include mental status changes (confusion, lethargy, and
irritability), anorexia, and nausea.7 The rapid change in
sodium levels may cause cerebral edema and intracranial
hypertension (Figure 1), which can quickly progress to
brainstem herniation, seizure, coma, and respiratory
arrest.9,24 In very severe cases (serum sodium less than
125 mEq/L), patients may suffer permanent neurologic
damage, coma, or death.1 Cerebral edema, if present, is
visible on CT and MRI. Acute hyponatremia is a medical
emergency and must be corrected promptly to avoid
irreversible consequences.25 Within a few hours of onset,
brain volume begins adaptation via excretion of intracel-
lular and extracellular solutes to stimulate water loss and
decrease brain swelling.24 Within 2 days, intracranial
pressure can essentially stabilize. Although brain adapta-
tion helps reduce symptoms of hyponatremia, it also
greatly increases the patients risk for osmotic demyelin-
ation.9 Prompt and appropriate treatment is essential to
prevent further neurologic damage.
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Chronic hyponatremia This type of hyponatremia has
a gradual onset (over more than 48 hours), and occurs
when the brain volume is able to adapt with concomitant
fluid loss; brain volume is near-normal in spite of the
significant decrease in serum sodium levels.23,24 Modest
symptoms were thought to be the only manifestation of
chronic hyponatremia.16 However, recent insight into
older adults has revealed that manifestations of chronic
hyponatremia may include gait instability leading to
increased falls and fractures, as well as attention difficul-
ties.15,16,23,24,26-28 Osteoporosis has also been linked to
chronic hyponatremia because patients with chronic
hyponatremia mobilize bone matrix sodium stores at
an increased rate and also have heightened osteoclast
activity. 15,16,23,24 Chronic hyponatremia can lead to
increased osteoporosis and fractures and increased
patient morbidity and mortality.15,23,24
MORTALITY
Hospitalized patients with hyponatremia have a 50%
greater risk of death than normonatremic patients; older
adults with hyponatremia have a doubled risk of death
compared with normonatremic older adults.2,29-31 Studies
evaluating mortality in patients with various severities of
hyponatremia found an overall increase in mortality regard-
less of degree of severity, and increased mortality especially
in patients with multiple underlying illnesses.2,29-31 Hypo-
natremia is also a marker in heart, liver, and kidney disease
or injury, as well as brain tumors, brain hemorrhages, and
malignancy.31 Waikar and Chawla found that underlying
illness contributed more to mortality than the severity of
hyponatremia; Whelan adjusted for such factors and still
found hyponatremia independently and significantly asso-
ciated with mortality.30-32
DIAGNOSIS
Obtain a thorough history and physical examination,
assessing the patients medications, neurologic state,
and extracellular fluid volume status. These objective
methods may add insight into volume status to help
better classify the suspected hyponatremia. For exam-
ple, patients with hypovolemic hyponatremia may
present with vomiting, diarrhea, diuretic use, hypergly-
cemia with glucosuria, increased thirst, weight loss,
orthostatic hypotension, tachycardia, dry mucous mem-
branes, decreased skin turgor, and decreased capillary
refill.10,16
To differentiate GI and renal losses, calculate the patients
FENa, the ratio between sodium excreted via urine and
the amount of sodium filtered and reabsorbed by the kid-
ney. The calculation is based on the concentrations of
sodium and creatinine in the blood and urine.33 The values
needed are serum sodium (PNa), urine sodium (UNa), serum
creatinine (PCr), and urine creatinine (UCr), and the formula
is FENa = ((UNa x PCr)/(PNa x UCr) x 100.34
Volume 27 Number 4 April 2014

TABLE 3. Diagnostic studies and laboratory tests
useful in diagnosing hyponatremia9,12,35,36,42,43
Urine osmolality can help clinicians differentiate between
impaired excretion of water versus normal but excessive
water excretion as in polydipsia.
Serum osmolality measures the bodys electrolyte-water
balance and can differentiate between true and pseudo-
hyponatremia.
Urinary sodium concentration can help differentiate
hypovolemic hyponatremia from hyponatremia secondary
to SIADH.
CBC count with differential, basic metabolic panel, and
renal and liver function tests can help identify comorbidi-
ties and their potential causes.
TSH and cortisol response to ACTH can evaluate for
SIADH as a potential cause of hyponatremia.
Serum uric acid and urea concentrations can identify
hypouricemia associated with SIADH.
A brain CT or MRI and chest radiographs may reveal
cerebral edema, demyelination, pulmonary congestion as
a potential cause of SIADH, or cerebral salt wasting.
In patients with GI losses from vomiting and diarrhea,
the FENa should be within normal limits and less than
1%. In patients with renal losses, such as from diuretics,
glucosuria, and bicarbonaturia, the FENa will be greater
than 1%.7 Clinical presentation should always be taken
into account when examining FENa.
Patients with hyponatremia should undergo a full labo-
ratory workup to identify potential causes of the disorder,
differentiate between types of hyponatremia, and inves-
tigate other comorbidities. Urine osmolality, serum osmo-
lality, and urine sodium concentrations are the three
cornerstone tests that help to differentiate between causes
of the electrolyte disorder (Table 3).35,36
Confirmed normal or elevated serum osmolality sug-
gests the presence of another osmole, aside from sodium,
that draws water out of the cells and into the intravas-
cular space. Most commonly, low serum osmolality is
found on laboratory analysis, and in that case, the next
step is urinalysis, to determine urine osmolality and
whether the patients renal function is intact. Maximally
dilute urine (less than 100 mOsm/L) indicates normal
kidney function and may suggest primary polydipsia or
low solute intake; excessively concentrated urine (more
than 200 mOsm/L) indicates some impairment of renal
filtration or dilution as in SIADH or cerebral salt wast-
ing (urinary sodium concentrations greater than 40
mEq/L).16,37 These diagnostic tests will guide later treat-
ment because management is based on the apparent cause
of hyponatremia.
Evidence of osmotic demyelination is not usually vis-
ible on CT or MRI until 6 to 10 days after clinical
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Managing hyponatremia in adults
TABLE 4. Initial treatment of hyponatremia based on
patient volume status4,12,44
Euvolemic
Restrict fluids
Prescribe loop diuretics and saline infusions to replace
urinary sodium losses
Prescribe demeclocycline and vasopressin receptor
antagonists
Enhance solute intake if patient has poor nutritional
status
Discontinue medications associated with SIADH
Treat underlying conditions associated with SIADH
Treat endocrinopathies (for example, hypothyroidism)
Hypervolemic
Restrict fluids and sodium
Prescribe loop diuretics
Treat underlying conditions
Hypovolemic
Prescribe IV isotonic saline
Discontinue diuretics
Replace mineralocorticoid deficiencies.
symptoms appear.7,25 Uric acid generally rises with volume
depletion and is low in SIADH.3 Arterial sodium can be
measured with a blood gas device to rule out suspected
pseudohyponatremia.4 To aid in determining the cause
of hyponatremia, assess serum osmolality as promptly
as possible.
TREATMENT
Management depends on the patients clinical presentation
(including volume status and severity of symptoms) and
the cause of the electrolyte imbalance.4,10,19 Because hypo-
natremia is potentially fatal, prompt intervention is impor-
tant. The appropriate rate of correction depends on whether
the patient has acute or chronic hyponatremia.4,7,12 Next,
assess the patients volume status to determine the appro-
priate correction strategy (Table 4).4,7
Acute hyponatremia Acute onset of symptomatic hypo-
natremia can be a medical emergency leading to cerebral
edema, brain herniation, and cardiopulmonary arrest, and
requires rapid correction with 3% hypertonic saline.7 If
the patient is hypervolemic because of heart failure or
underlying cardiovascular disease, also administer a loop
diuretic to avoid volume overload.4,7,10 Closely monitor
patients receiving hypertonic saline for extracellular volume
status, neurologic symptoms, and serum sodium trends to
avoid rapid overcorrection.4,7
Once the patients severe signs and symptoms have
resolved, discontinue 3% hypertonic saline, reassess
www.JAAPA.com 27
CME
volume status, and tailor treatment based on the patients
volume status and cause of the hyponatremia (Table 4).4
Chronic hyponatremia Patients with chronic hypona-
tremia are unlikely to present with serious signs and
symptoms. If they do, carefully tailor sodium correction
to reverse serious signs and symptoms only and avoid
overcorrection.4 Too-rapid correction of chronic hypo-
natremia with hypertonic saline can cause excessive loss
of intracellular water, cell shrinkage, and osmotic demy-
elination syndrome (damage to the myelin sheaths cover-
ing axons of the brainstem, which can lead to permanent
neurologic damage).1,4,7 Patients with osmotic demyelin-
ation syndrome may show improved mental status initially,
accompanied by neurologic declines, paresis, flaccid
paralysis, dysarthria, dysphagia, hypotension, and pos-
sible death.4 Patients who are malnourished; abuse alco-
hol; have hypokalemia, burns, or advanced liver disease;
and older women on thiazide diuretics have much lower
thresholds for osmotic demyelination and should be cor-
rected much more slowly.3,4,7
Patients with chronic hyponatremia who do not display
serious signs and symptoms do not need immediate treat-
ment to correct serum sodium, but may be mildly symp-
tomatic, putting them at increased risk for falls and devel-
opment of osteoporosis.4,15,27 Fluid restriction is the treat-
ment of choice; instruct patients not to take in more fluid
than they excrete in urine and insensible losses.3,4,13,38 Water
excretion can be calculated from solute intake and urine
osmolarity.4
Other chronically hyponatremic patients have shown
asymptomatic sodium levels as low as 115 to 120 mEq/L
due to cerebral adaptation. In such cases, consider revers-
ible causes of excess water (such as continuous maintenance
fluid infusions or excess oral fluid intake) and eliminate
them when possible.4
If the timing of hyponatremia development is unknown,
clinicians should assume the hyponatremia is chronic and
should apply conservative measures, avoiding too-rapid
correction to prevent osmotic demyelination.4,9 Patients
presenting with severe neurologic signs and symptoms
require immediate increases in serum sodium, whether
hyponatremia is acute or chronic.4,20 When the patients
neurologic symptoms improve, treatment can be adjusted
depending on how long the hyponatremia is thought to
have been present. In nonemergent cases, initial treatment
should be based on volume status (Table 4).4,12
RATE OF CORRECTION
A patients serum sodium level should be increased by no
more than 10 to 12 mmol/L in the first 24 hours and then
by no more than 18 mmol/L in the first 48 hours of ther-
apy.3,4,7,12 Rates of correction should be even lower in
patients with chronic hyponatremia and signs or symptoms
of cerebral edema. Terminating fluids before the serum
sodium has increased 10 to 12 mmol/L in the first 24 hours
28 www.JAAPA.com
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is also important because the sodium level can continue
to rise after fluids have been discontinued.4
As emphasized previously, great care must be taken to
avoid overcorrection. If overcorrection results, discontinue
all sodium-containing therapies and immediately admin-
ister IV D5W.10 Although more research is needed about
using desmopressin to manage sodium overcorrection, this
drug may be given for prevention and reversal of serum
sodium overcorrection.4,39 Desmopressin decreases sodium
by 2 to 9 mmol/L without serious adverse reactions and
can be given alone or with D5W.
EMERGING THERAPIES:
VASOPRESSIN ANTAGONISTS
Vasopressin antagonists are fairly new drugs that inhibit
the V1A, V1B, or V2 subtypes of vasopressin receptors
and block ADH action.40 Vasopressin antagonists are
indicated for use in patients with severe hyponatremia
(serum sodium less than 125 mEq/L) or in those with less
severe hyponatremia who are symptomatic and ineffec-
tively treated with fluid restriction.41 Based on recent
studies, therapy with vasopressin antagonists appears
promising; however, further recommendations are neces-
sary to ensure that they can be used safely to correct
hyponatremia.3,4,7,38,40 Concerns about vasopressin antag-
onists include their high cost, the adverse reaction of
increased thirst, and whether they can be used safely in
patients with cirrhosis-related ascites.4,7,40
Because of the limited experience in using vasopressin
antagonists to treat signs and symptoms of cerebral edema
in patients with hyponatremia, 3% hypertonic saline
remains the gold standard for treatment.
CONCLUSION
Hyponatremia is a complex condition that demands
a systematic approach to diagnosis and management.23
In older adults, hyponatremia is one of the most com-
mon electrolyte imbalances and is associated with
increased mortality.11 Careful attention to common
causes, clinical presentation, laboratory diagnosis, and
appropriate treatment will help practitioners safely
reverse this potentially life-threatening condition. The
primary treatment for hyponatremia is to identify and
correct underlying causes and, if necessary, correct
sodium imbalances slowly to lessen the chance of
neurologic disease. Vasopressin antagonists have
emerged as promising new treatments that may improve
outcomes.29 JAAPA
Earn Category I CME Credit by reading both CME articles in this issue,
reviewing the post-test, then taking the online test at http://cme.aapa.
org. Successful completion is defined as a cumulative score of at least
70% correct. This material has been reviewed and is approved for 1
hour of clinical Category I (Preapproved) CME credit by the AAPA. The
term of approval is for 1 year from the publication date of April 2014.
Volume 27 Number 4 April 2014

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