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Syndrome of Inappropriate Release of Antidiuretic Hormone
Definition
Hyponatremia is defined as a serum sodium level less
than 135mmol/L1. Syndrome of inappropriate release of
antidiuretic hormone (SIADH) is a disorder of sodium and
water balance presented with euvolemic hyponatremia
and impaired urinary dilution in the absence of renal
disease or any identifiable non-osmotic stimulus known to
release antidiuretic hormone (ADH)2.
Epidemiology
Hyponatremia is common in hospitalized patients.
Approximately 15 to 20 percent of patients developed mild
hyponatremia and 3 to 5 percent of patients developed
severe hyponatremia. SIADH is the most common cause
of hyponatremia2,3. Elderly persons, especially women
are more susceptible to hyponatremia because of a
decrease in total body water and hormonal changes4.
Pathophysiology
Antidiuretic hormone or arginine vasopressin (AVP)
binds to the AVP V2 receptors on the kidney collecting
tubules causing synthesis and insertion of water channels
(aquaporin-2) along the luminal surface. Insertion of
aquaporins promotes free water reabsorption from the
renal tubules4.
AVP secretion is triggered by the osmotic and non-
osmotic stimuli. Osmotic receptors are located on the
anterior hypothalamus. These receptors monitor the
serum osmolality. Small (1-2%) increases in plasma
osmolality are sufficient to stimulate the osmoreceptors
and trigger the secretion of AVP 4. If serum osmolality is
less than 275mOsm/kg, AVP secretion is suppressed.
However, when serum osmolality is greater than
285mOsm/kg, AVP starts to release. A non-osmotic
stimulus includes hypovolemia, stress, nausea, vomiting,
drugs, hypoglycaemia, and/or pain4.
Syndrome of inappropriate release of antidiuretic
hormone is resulted from inappropriate release of AVP
and excessive fluid intake. Patients with SIADH may have
“inappropriate thirst” due to the lowering of osmolality
threshold for thirst5,6,7.
Causes of SIADH include tumors such as small cell
lung carcinoma, pancreatic carcinoma, and lymphoma;
central nervous system disorders such as multiple
sclerosis, Guillain Barrè syndrome, hydrocephalus, and
cerebrovascular diseases; drugs such as serotionin
reuptake Inhibitors, carbamazepine, oxcarbazepine,
vincristine, cyclophosphamide; and pulmonary diseases
such as tuberculosis, pneumonia, acute respiratory
failure. Other causes include acquired immunodeficiency
syndrome, strenuous exercise, and hyperglycemia 2, 8-11.
Manifestations
Presentation of SIADH is primarily related to the
severity and duration of hyponatremia. Patients with
chronic and mild hyponatremia may be asymptomatic
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because of the slow process that allows the brain cells to
adapt to the lower serum osmolality4,12.
In mild hyponatremia, the most common symptoms are
headache, nausea, fatigue, anorexia, difficulty
concentrating, impaired memory, muscle cramps,
weakness, dysgeusia (change in the sense of taste) and
lethargy. When hyponatremia becomes more severe,
neurological signs such as confusion, hallucinations,
seizures, and delirium occur. If serum sodium falls below
115mmol/L coma, respiratory arrest, and death can
result4,13.
Diagnostic Tests
Diagnosis of SIADH is dependent on patient
presentation, physical examination, and laboratory results
(see below table). Other tests include water load test,
fractional excretion of sodium and saline infusion
study1,4,14.
Laboratory tests include both serum and urine tests
(see below table).
Table: Diagnostic criteria for SIADH4,13.
Essential · Serum osmolality <275 mOsm/kg
features · Urine osmolality >100 mOsm/kg
· Urine sodium >40 mmol/L
· No recent use of diuretic agents
· Clinical euvolemia
· Normal thyroid and adrenal function
Supplementary · Serum uric acid <4mg/mL
features · BUN <10 mg/mL
· Fractional sodium excretion >1%
· Failure to correct hyponatremia after
0.9% saline infusion
· Elevated serum AVP levels
· Abnormal water load test result
Treatment Options
Management for patients with SIADH includes
elimination of the underlying causes and correcting the
electrolyte imbalance. When selecting interventions to
correct hyponatremia, the severity and duration of
hyponatremia and the symptoms of patients should be
considered4.
If patients develop symptoms of acute hyponatremia
(hyponatremia developed within 48 hours), the goal is to
raise serum sodium level by 1-2mmol/L/H. Hypertonic
sodium chloride (3%) is commonly used to correct
hyponatremia13,15. Correction of sodium in the first 48
hours should be gradual. In the first 24 hours, serum
sodium correction should be less than 8 to 10mmol/L, and
in the first 48 hours serum sodium correction should be
between 18 to 25mmol/L. In clinical practice, the most
commonly used calculation for 3% hypertonic saline
infusion rate is 1 ml/kg/h. This will increase serum sodium
level by 1 mmol/L/h2,14. Administration of furosemide to
promote water excretion is also recommended16.
 During treatment, serum sodium should not be raised
greater than 12mmol/L/day. Monitor for symptoms of
central pontine and extrapontine myelinolysis. These
include tremors, incontinence, hypereflexia, mutism or
dysarthria, dysphagia, cranial nerve palsies, seizures,
spastic quadriparesis, pseudobulbar palsy, and/or locked-
in syndrome4,17.
Isotonic (0.9%) saline may be administered when
patients have mild and asymptomatic hyponatremia.
However, if patients have severe and acute
hyponatremia, isotonic saline should be avoided because
patients with SIADH will excrete most of the sodium in
the saline solution and retain the water component
resulting in worsened hyponatremia4.
Fluid restriction is usually the first treatment for
SIADH. Most often, total fluid intake is limited to 0.8L to
1L/day or daily urine output minus 500mL4,7.
In the acute phase of treatment, serum electrolyte
levels should be assessed every 2 to 4 hours to avoid
over correction4.
A newer drug group known as the Vaptans
(Conivaptan and Tolvaptan) has been used in SIADH.
Vaptans are V receptors antagonists (blockers). When V 2
receptors are blocked, it inhibits the action of AVP and
prevents free water reabsorption. Vaptans do not affect or
increase the excretion of urine solutes such as sodium or
potassium18.
Urea is the major osmotic constituent of urine,
administering urea orally can act as osmotic dieresis
because it increases the renal filtrate osmolality. Urea
also promotes reabsorption of sodium in the ascending
limb of the loop of Henle and reduces sodium excretion 12.
However, the bitter taste of urea keeps some patient
away from using this option7.
Nursing Implications
Monitor patients’ vital sign closely for any hypotensive
effects if patients are on Conivaptan.
If patients are receiving intravenous infusion of
hypertonic (3%) sodium chloride, assess the intravenous
insertion site regularly, hypertonic saline may cause
irritation and phlebitis13.
Patients with SIADH may have “inappropriate
thirst”.
This change may cause patient to be non-compliant with
fluid restrictions. Explain to the patient the rationale for
fluid restriction and encourage patients to adhere to the
fluid intake restriction5,6,7. Provide hard candy or ice
chips
to ameliorate the “thirsty” feeling14.
Maintain a strict fluid intake and output record and
monitor daily body weights19. When patients are on fluid
restrictions, calculate the total fluid intake carefully. All
types of fluid intakes such as intravenous fluid,
medication, oral fluid intake, and tube feeding formula
should be included. Note that when patients are on tube
feeding formulas, some feeding formulas have different
dry weights. Please consult the manufacturer’s manual
for the exact fluid volume or use the calculator on the
www.neuro4nurses.com website to calculate the oral fluid
allowed when patients are on tube feeding formulas.
Consult a registered dietitian when a more concentrated
feeding formula is required.
Reference
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hyponatremic patient: A systemtic approach to laboratory diagnosis.
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(2011). The syndrome of inappropriate antidiuresis:
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©
2014
Disclaimer: The author neither represents nor guarantees that the
practices described herein, if followed, ensure safe and effective patient
care. The authors further assume no responsibility or liability in
connection with any information or recommendations contained in this
article. The recommendations and instructions in this article are based
on the knowledge and practice in neuroscience as of the date of
publication. These recommendation and instructions are subject to
change based on the availability of new scientific information.