The human body is approximately 60% water, which is contained within two major compartments, the extracellular fluid and the intracellular fluid (Guyton & Hall, 2000). The fluid inside the cells is called intracellular fluid; the extracellular fluid is found outside the cells, in the plasma and the interstitial fluid. Most of the body’s fluids are intracellular fluids.
Dissolved as ions or solutes in the water are electrolytes, which are separated by a cell membrane; this helps keep the ions in their appropriate compartment. Intracellular ions consist mostly of potassium and phosphate ions, with lesser amounts of magnesium and sulfate ions; these ions are found to a lesser extent in the extracellular fluid. The chief ions of the extracellular fluid are sodium and chloride (Guyton & Hall, 2000). The number of solutes dissolved in water is termed osmoles, and the osmolarity of a solution is based on the number of solutes in the solution.
The body has a variety of homeostatic mechanisms to maintain a balance between the cellular compartments. Thirst is a major mechanism of fluid intake. Fluids and electrolytes are lost through the skin, lungs, renal system, and gastrointestinal tract. The cells regulate water passage across the cell membrane to maintain isotonicity between the intracellular and extracellular fluids (Guyton & Hall, 2000). Osmosis is the process by which water moves. If one compartment has too much or too little of an ion concentration, water moves between compartments to restore balance.
The kidneys regulate the amount of water and solutes in the body. When the body has too little water, the posterior pituitary gland secretes and releases antidiuretic hormone (ADH), which allows the kidneys to reabsorb water; when the body has too much water, ADH release stops, and the kidneys excrete the excess water. Water and sodium ions have a close alliance, therefore if the amount of water is reduced, the sodium concentration increases; ADH is released and causes more water to be reabsorbed by the kidneys and less water to be excreted (Guyton & Hall, 2000).
In SIADH, the body secretes ADH (also known as vasopressin) inappropriately from the hypothalamus, resulting in water reabsorption by the kidneys and increased body water with increased intracellular and extracellular water (Flounders, 2003). The excess water dilutes the sodium in the extracellular compartment, causing hyposmolarity and movement of water into the intracellular compartment. As a result, the patient has a fluid volume excess intracellularly and a low solute (sodium) concentration extracellularly (Flounders, 2003).
In summary, ADH secretion results in increased water absorption by the kidneys, causing hypervolemia and dilutional hyponatremia. Therefore some signs of hypervolemia are seen, including weight gain, normal or elevated blood pressure, and changes in mental status (Trimarchi, 2006). However, heart failure, edema, and ascites are not normally seen (Flounders, 2003), because most of the water is intracellular.
EPIDEMIOLOGY AND ETIOLOGY
Although frequently a paraneoplastic syndrome, SIADH has both malignant and nonmalignant causes. The most common malignant causes are small cell lung cancer (SCLC), followed by GI and GU cancers. Approximately 3% to 15% of patients with SCLC develop SIADH (Lokich, 1982). SCLC cells produce ectopic ADH, resulting in SIADH (Gandhi & Johnson, 2006). Two alkylating agents, ifosfamide and cyclophosphamide, are associated with SIADH, as are carboplatin (Yokoyama et al., 2005; Chu & DeVita, 2004), cisplatin (Yamamoto et al., 2005; Chu & DeVita, 2004), and the monoclonal antibody alemtuzumab (Kunz & Bannerji, 2005). SIADH has numerous causes and risk factors (Box 47-1). Antidepressants, especially the selective serotonin reuptake inhibitors (SSRIs), and anticonvulsants are also known causes (Table 47-1).
BOX 47-1
PARTIAL RISK PROFILE FOR SIADH
Malignant Conditions
• Lung cancers
• Small cell
• Non-small cell
• Gastrointestinal cancers
• Duodenal
• Pancreas
• Colon
• Carcinoid
• Esophageal
• Genitourinary cancers
• Ovarian
• Bladder
• Ureter
• Prostate
• Other cancers
• Brain, brain metastases, carcinomatous meningitis, neuroblastoma
• Breast
• Sarcomas
• Lymphomas and leukemias
• Other small cell tumors
• Mesothelioma
• Thymoma
• Head and neck
Nonmalignant Conditions
• Central nervous system
• Head trauma
• Infection
• Meningitis
• Encephalitis
• Intracranial bleeding
• Abscess
• CVA
• Polydipsia
• Pulmonary
• Pneumonia
• Abscess
• Tuberculosis
• Asthma
• Infections
• Pneumothorax
• Respiratory failure
• Peripheral neuropathy
• Infections
• AIDS
• Hypotension, dehydration
• Severe pain
• Pain from abdominal or chest surgery
• Pituitary surgery
• Smoking
• Emotional stress
• Hemorrhage
• Medications
• Antineoplastics:
• Ifosfamide
• Cyclophosphamide
• Vincristine
• Vinblastine
• Cisplatin
• Carboplatin
• Melphalan
• Monoclonal antibody:
• Alemtuzumab
• Narcotics and acetaminophen
• Non-steroidal anti-inflammatory agents
• Anesthetic agents
• Anticonvulsants (Table 47-1)
• Antidepressants
• Barbiturates
• Selective serotonin reuptake inhibitors (Table 47-1)
• Antipsychotics
• Diuretics
• Oral hypoglycemics
• Chemotherapy-induced nausea
• Exogenous hormones
• Nicotine, cigarette smoking
Data from Kraft, M. D., Btaiche, I. F., & Sacks, G. S., et al. (2005). Treatment of electrolyte disorders in adult patients in the intensive care unit. American Journal of Health-System Pharmacy, 62:1663-1682; Robertson, G. L. (2005). Disorders of the neurohypophysis. In D. L. Kasper, E. Braunwald, & A. S. Fauci, et al. (Eds.), Harrison’s principles of internal medicine (pp. 2097-2104). (16th ed). New York: McGraw-Hill; Poe, C. M., & Taylor, L. M. (1989). Syndrome of inappropriate antidiuretic hormone: Assessment and nursing implications. Oncology Nursing Forum, 16:373-381; Keenan, A. M. M. (1999). Syndrome of inappropriate antidiuretic hormone in malignancy. Seminars in Oncology Nursing, 15:160-167; Richerson, M. T. (2004). Electrolyte imbalances. In C. H. Yarbro, M. H. Frogge, & M. Goodman (Eds.), Cancer symptom management (pp.440-453). (3rd ed.). Sudbury, MA: Jones & Bartlett; Flounders, J. A. (2003). Syndrome of inappropriate antidiuretic hormone. Oncology Nursing Forum, 30(3):E63-E68. Retrieved May 25, 2006, from http://www.ons.org/publications/journals/ONF/Volume30/Issue3/pdf/381.pdf; and Rose, B. D. (2006). Causes of the SIADH. UpToDate. Retrieved May 24, 2006, from http://www.uptodateonline.com.
| Generic Name | Trade Name | Medication Category | Reference |
|---|---|---|---|
| Carbamazepine | Tegretol | Anticonvulsant | Llinares-Tello et al., 2005 |
| Levetiracetam | Keppra | Anticonvulsant | Nasrallah & Silver, 2005 |
| Amitriptyline | Apo-amitriptyline | SSRI | Miehle et al., 2005 |
| Citalopram hydrochloride | Celexa | SSRI | Miehle et al., 2005 |
| Duloxetine | Cymbalta | SSRI | Maramattom, 2006 |
| Escitalopram oxalate | Lexapro | SSRI | Miehle et al., 2005 |
| Fluoxetine hydrochloride | Prozac | SSRI | Maramattom, 2006 |
| Paroxetine mesylate | Paxil | SSRI | Alvarez Perez et al., 2004 |
RISK PROFILE
• Age: Older adults and children are more prone to developing symptoms (Berl & Verbalis, 2004). The prevalence of hyponatremia in elderly individuals living in long-term care facilities in Taipei was reported as 31.3% (Chen et al., 2006), and abnormal sodium levels are commonly found in elderly patients (Tareen et al., 2005; Kugler & Hustead, 2000).
• Female gender: Menstruating patients have a greater risk of SIADH-related neurotoxicity (Ayus et al., 1992).
• Chemotherapy: Treatment with ifosfamide, cyclophosphamide, carboplatin, or cisplatin.
• Monoclonal antibody: Alemtuzumab (Campath) can induce SIADH (Kunz & Bannerji, 2005).
• Bone marrow transplantation: The prevalence of SIADH in post stem cell transplant (SCT) patients is 11.4%. SIADH is a common complication, especially in children under 4 years of age and after SCT from an HLA-mismatched donor (Kobayashi et al., 2004). SIADH precedes varicella-zoster virus reactivation months after autologous stem cell transplantation for leukemia (Vinzio et al., 2005).
• Rate and severity of reduced extracellular osmolality (Berl & Verbalis, 2004):
• The faster the onset of low osmolality, the greater the risk of neurologic symptoms (Berl & Verbalis, 2004).
• The lower the serum osmolality, the greater the risk of neurologic symptoms (Berl & Verbalis, 2004).
• Medications: Use of Ecstasy, treatment with SSRIs or anticonvulsants.
• Cytomegalovirus (CMV) associated with acute pandysautonomia has been reported (Sato et al., 2004).
PROGNOSIS
For patients with cancer and SIADH, the mortality rate ranges from 5% to 55% (Berl, 1990; Sterns, 1987; Arieff et al., 1976). SIADH is a poor prognostic factor and is associated with advanced disease (Berl & Verbalis, 2004).
PROFESSIONAL ASSESSMENT CRITERIA (PAC)
SIADH is frequently detected through diagnostic studies in patients with few symptoms. A high degree of suspicion is required by the health care provider.
1. Laboratory values (Gobel, 2005; Richerson, 2004; Flounders, 2003;): The serum sodium level cannot be used as the sole test to diagnose SIADH; hyposmolality must also be present (Flounders, 2003). Lab values should be assessed daily.
• Low serum sodium level (less than 130 to 134 mEq/L).
• Serum hyposmolality (less than 275 to 280 mOsm/kg).
• Urine hyperosmolality (greater than 300 to 330 mOsm/kg).
• High urine sodium level (greater than 20 to 25 mEq/L).
• Urine specific gravity greater than 1.015.
• Decreased serum values for BUN, creatinine, uric acid, and electrolytes.
• Normal thyroid, adrenal, cardiac, liver, and kidney function.
• Normal blood glucose (Robertson, 2005).
2. Clinical manifestations (signs and symptoms) and patient assessment of signs and symptoms (Table 47-2). The development of clinical signs and symptoms is related to how quickly the serum sodium falls and how low it falls in relation to the reduced osmolality of the extracellular fluid (Berl & Verbalis, 2004; Keenan, 1999). Most clinical manifestations are related to the brain; neurologic function is affected by the excess amount of water in the brain cells, which causes these cells to swell (intracellular fluid expansion). Extracellular fluid excess typically is not seen, therefore patients do not usually develop peripheral edema or heart failure from fluid overload (Flounders, 2003).
| Severity | |||
|---|---|---|---|
| Mild | Moderate | Severe | |
| Serum sodium level (mEq/L) | 125-134 | 115-124 | < 115 |
| Clinical manifestations | No symptoms (possible) Dysgeusia (unpleasant sweet taste) | Dysgeusia (unpleasant sweet taste) | Dysgeusia (unpleasant sweet taste) |
| Neurologic | Headache Mild changes in mental status, such as confusion, trouble concentrating, disorientation, sleepiness
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