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Syndrome of Inappropriate Release of Antidiuretic Hormone
Definition because of the slow process that allows the brain cells to
Hyponatremia is defined as a serum sodium level less adapt to the lower serum osmolality4,12.
than 135mmol/L1. Syndrome of inappropriate release of In mild hyponatremia, the most common symptoms are
antidiuretic hormone (SIADH) is a disorder of sodium and headache, nausea, fatigue, anorexia, difficulty
water balance presented with euvolemic hyponatremia concentrating, impaired memory, muscle cramps,
and impaired urinary dilution in the absence of renal weakness, dysgeusia (change in the sense of taste) and
disease or any identifiable non-osmotic stimulus known to lethargy. When hyponatremia becomes more severe,
release antidiuretic hormone (ADH)2. neurological signs such as confusion, hallucinations,
seizures, and delirium occur. If serum sodium falls below
Epidemiology 115mmol/L coma, respiratory arrest, and death can
Hyponatremia is common in hospitalized patients. result4,13.
Approximately 15 to 20 percent of patients developed mild
hyponatremia and 3 to 5 percent of patients developed Diagnostic Tests
severe hyponatremia. SIADH is the most common cause Diagnosis of SIADH is dependent on patient
of hyponatremia2,3. Elderly persons, especially women presentation, physical examination, and laboratory results
are more susceptible to hyponatremia because of a (see below table). Other tests include water load test,
decrease in total body water and hormonal changes4. fractional excretion of sodium and saline infusion
study1,4,14.
Pathophysiology Laboratory tests include both serum and urine tests
Antidiuretic hormone or arginine vasopressin (AVP) (see below table).
binds to the AVP V2 receptors on the kidney collecting
tubules causing synthesis and insertion of water channels Table: Diagnostic criteria for SIADH4,13.
(aquaporin-2) along the luminal surface. Insertion of
aquaporins promotes free water reabsorption from the Essential · Serum osmolality <275 mOsm/kg
renal tubules4. features · Urine osmolality >100 mOsm/kg
AVP secretion is triggered by the osmotic and non- · Urine sodium >40 mmol/L
osmotic stimuli. Osmotic receptors are located on the · No recent use of diuretic agents
anterior hypothalamus. These receptors monitor the · Clinical euvolemia
serum osmolality. Small (1-2%) increases in plasma · Normal thyroid and adrenal function
osmolality are sufficient to stimulate the osmoreceptors Supplementary · Serum uric acid <4mg/mL
and trigger the secretion of AVP 4. If serum osmolality is features · BUN <10 mg/mL
less than 275mOsm/kg, AVP secretion is suppressed. · Fractional sodium excretion >1%
However, when serum osmolality is greater than · Failure to correct hyponatremia after
285mOsm/kg, AVP starts to release. A non-osmotic 0.9% saline infusion
stimulus includes hypovolemia, stress, nausea, vomiting, · Elevated serum AVP levels
drugs, hypoglycaemia, and/or pain4. · Abnormal water load test result
Syndrome of inappropriate release of antidiuretic
hormone is resulted from inappropriate release of AVP Treatment Options
and excessive fluid intake. Patients with SIADH may have Management for patients with SIADH includes
“inappropriate thirst” due to the lowering of osmolality elimination of the underlying causes and correcting the
threshold for thirst5,6,7. electrolyte imbalance. When selecting interventions to
Causes of SIADH include tumors such as small cell correct hyponatremia, the severity and duration of
lung carcinoma, pancreatic carcinoma, and lymphoma; hyponatremia and the symptoms of patients should be
central nervous system disorders such as multiple considered4.
sclerosis, Guillain Barrè syndrome, hydrocephalus, and If patients develop symptoms of acute hyponatremia
cerebrovascular diseases; drugs such as serotionin (hyponatremia developed within 48 hours), the goal is to
reuptake Inhibitors, carbamazepine, oxcarbazepine, raise serum sodium level by 1-2mmol/L/H. Hypertonic
vincristine, cyclophosphamide; and pulmonary diseases sodium chloride (3%) is commonly used to correct
such as tuberculosis, pneumonia, acute respiratory hyponatremia13,15. Correction of sodium in the first 48
failure. Other causes include acquired immunodeficiency hours should be gradual. In the first 24 hours, serum
syndrome, strenuous exercise, and hyperglycemia 2, 8-11. sodium correction should be less than 8 to 10mmol/L, and
in the first 48 hours serum sodium correction should be
Manifestations between 18 to 25mmol/L. In clinical practice, the most
Presentation of SIADH is primarily related to the commonly used calculation for 3% hypertonic saline
severity and duration of hyponatremia. Patients with infusion rate is 1 ml/kg/h. This will increase serum sodium
chronic and mild hyponatremia may be asymptomatic 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 Reference
greater than 12mmol/L/day. Monitor for symptoms of 1) Milionis, H.J., Liamis, G.L., & Elisaf, M.S. (2002). The
central pontine and extrapontine myelinolysis. These hyponatremic patient: A systemtic approach to laboratory diagnosis.
Canadian Medical Association Journal, 166, 1056-1062.
include tremors, incontinence, hypereflexia, mutism or
2) Esposito, P., Piotti, G., Bianzina, S., Maliul, Y., & Canton, A.D.
dysarthria, dysphagia, cranial nerve palsies, seizures, (2011). The syndrome of inappropriate antidiuresis:
spastic quadriparesis, pseudobulbar palsy, and/or locked- Pathophysiology, clinical management and new therapeutic options.
in syndrome4,17. Nephron Clinical Practice, 119, c62-c73.
3) Verbalis, J.G. (1993). Hyponatremia: Epidemiology,
Isotonic (0.9%) saline may be administered when pathophysiology, and therapy. Current Opinion in Nephrology and
patients have mild and asymptomatic hyponatremia. Hypertension, 2,
However, if patients have severe and acute 636-652.
hyponatremia, isotonic saline should be avoided because 4) Janicic, N., & Verbalis, J.G. (2003). Evaluation and
patients with SIADH will excrete most of the sodium in management of hypo-osmolality in hospitalized patients.
Endocrinology and Metabolism Clinics of North America, 32, 459-
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resulting in worsened hyponatremia4. 5) Crawford, A., & Harris, H. (2012). SIADH: Fluid out of
Fluid restriction is usually the first treatment for balance.
SIADH. Most often, total fluid intake is limited to 0.8L to Nursing, 42, 50-58.
1L/day or daily urine output minus 500mL4,7. 6) Smith, D., Moore, K., Tormey, W., Baylis, P.H., & Thompson,
C.J. (2004). Downward reseeting of the osmotic threshold for thirst
In the acute phase of treatment, serum electrolyte in patients with SIADH. American Journal of Physiology,
levels should be assessed every 2 to 4 hours to avoid Endocrinology, and Metabolism, 287, E1019-E1023.
over correction4. 7) Zietse, R., van der Lubbe, N., & Hoorn, E.J. (2009). Current
and future treatment options in SIADH. Nephrology, Dialysis, and
A newer drug group known as the Vaptans Transplantation (NDT Plus), 2(Suppl 3), iii12-iii19.
(Conivaptan and Tolvaptan) has been used in SIADH. 8) Anderson, R.J., Chung, H.M., Kluge, R., & Schrier, R.W.
Vaptans are V receptors antagonists (blockers). When V 2 (1985). Hyponatremia: A prospective analysis of its epidemiology
receptors are blocked, it inhibits the action of AVP and and the pathogenic role of vasopressin. Annals of Internal
Medicine, 102,
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increase the excretion of urine solutes such as sodium or 9) Castillo, J.J., Vincent, M., & Hustice, E. (2012). Diagnosis and
potassium18. management of hyponatremia in cancer patients. The Oncologist,
17, 756-765.
Urea is the major osmotic constituent of urine,
10) Paydas, S., Araz, F., & Balal, M. (2008). SIADH induced by
administering urea orally can act as osmotic dieresis amiodarone in a patient with heart failure. Internation Journal of
because it increases the renal filtrate osmolality. Urea Clinical Practice, 62, 337.
also promotes reabsorption of sodium in the ascending 11) Reddy, P., & Mooradian, A.D. (2009). Diagnosis and
limb of the loop of Henle and reduces sodium excretion 12. management of hyponatremia in hospitalized patients. The
International Journal of Clinical Practice, 63, 1494-1508.
However, the bitter taste of urea keeps some patient
12) Pierrakos, C., Taccone, F.S., Decaux, G., Vincent, J.L., &
away from using this option7. Brimioulle, S. (2012). Urea for treatment of acute SIADH in patients
with subarachnoid hemorrhage: A single-center experience. Annals
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If patients are receiving intravenous infusion of 14) Verbalis, J.G., Goldsmith, S.R., Greenberg, A., Schrier, R.W.,
hypertonic (3%) sodium chloride, assess the intravenous & Sterns, R.H. (2007). Hyponatremia treatment guidelines 2007:
Expert panel recommendations. The American Journal of Medicine,
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irritation and phlebitis13. 15) Berl, T. (2007). The Adrogue-Madias formula revisited.
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thirst”. 16) Adrogué, H.J., & Madias, N.E. (2000). Hyponatremia. The
New England Journal of Medicine,342, 1581-1589.
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fluid restriction and encourage patients to adhere to the 18) Peri, A. (2013). The use of vaptans in clinical endocrinology.
fluid intake restriction5,6,7. Provide hard candy or ice Journal of Clinical ERndocrinology and Metabolism, 98, 1321-1332.
chips 19) Langfeldt, L.A. & Cooley, M.E. (2003). Syndrome of
inappropriate antidiuretuic hormone secretion in malignancy:
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Maintain a strict fluid intake and output record and of Oncology Nursing, 7, 425-430.
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 2014
for the exact fluid volume or use the calculator on the Disclaimer: The author neither represents nor guarantees that the
www.neuro4nurses.com website to calculate the oral fluid practices described herein, if followed, ensure safe and effective patient
allowed when patients are on tube feeding formulas. care. The authors further assume no responsibility or liability in
Consult a registered dietitian when a more concentrated connection with any information or recommendations contained in this
article. The recommendations and instructions in this article are based
feeding formula is required. 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.