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Pediatrics: General Medicine > Endocrinology
Cerebral Salt-Wasting Syndrome
Article Last Updated: Sep 18, 2006
AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: James Springate, MD, Professor, Department of Pediatrics, State University of New York at Buffalo
James Springate is a member of the following medical societies: American Academy of Pediatrics, American Physiological Society, American Society of Pediatric Nephrology, and Society for Pediatric Research
Editors: Erawati V Bawle, MD, FAAP, FACMG, Director, Division of Genetic and Metabolic Disorders, Department of Pediatrics, Children's Hospital of Michigan; Professor (Clinician-Educator), Wayne State University School of Medicine; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Barry B Bercu, MD, Professor, Departments of Pediatrics, Molecular Pharmacology and Physiology, University of South Florida College of Medicine, All Children's Hospital; Merrily P M Poth, MD, Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences; George P Chrousos, MD, FAAP, MACP, MACE, Professor and Chair, Department of Pediatrics, Athens University Medical School
Author and Editor Disclosure
Synonyms and related keywords:
cerebral salt-wasting syndrome, CSWS, intracranial disease, salt wasting, renal salt wasting, natriuresis, hyponatremic dehydration
Background
First described by Peters et al in 1950, cerebral salt-wasting syndrome (CSWS) is defined by the development of excessive natriuresis and subsequent hyponatremic dehydration in patients with intracranial disease. Differentiation of this disorder from the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), another common cause of hyponatremia in this setting, is critical to prescribing appropriate therapy.
Pathophysiology
The exact mechanism underlying renal salt wasting in this syndrome remains unclear. One hypothesis is that an exaggerated renal pressure–natriuresis response caused by increased activity of the sympathetic nervous system and dopamine release is responsible for urinary sodium loss. Another hypothesis involves release of natriuretic factors, possibly including brain natriuretic peptide, C-type natriuretic peptide or an oubainlike peptide, by the injured brain. Kojima et al have recently described an animal model of CSWS that may allow better clarification of CSWS pathophysiology.
Frequency
United States
Exact incidence data for this disorder are not available. Approximately 60% of children with brain injuries or tumors develop hyponatremia during their hospital course. Some experts suggest that CSWS is responsible for hyponatremia at least as often as SIADH, particularly in neurosurgical patients.
Mortality/Morbidity
CSWS usually appears in the first week after brain injury and spontaneously resolves in 2-4 weeks. Death and complication rates for this syndrome are not available. Failure to distinguish CSWS from SIADH as the cause of hyponatremia will lead to improper therapy (ie, fluid restriction), thereby exacerbating intravascular volume depletion and potentially jeopardizing cerebral perfusion.
Age
CSWS can occur at any age. Published reports include patients aged 6 months to 65 years.
History
- Hyponatremia
- As the decline in serum sodium concentration reduces serum osmolality, a tonicity gradient develops across the blood-brain barrier that causes cerebral edema.
- Symptoms include lethargy, agitation, headache, altered consciousness, seizures, and coma.
- Severity of symptoms typically reflects the magnitude and rapidity of the decrease in serum sodium concentration.
- Intravascular volume depletion: Historical features suggesting hypovolemia include thirst, abrupt weight loss, decreasing urinary frequency, and negative fluid balance.
Physical
- Physical signs include those associated with severe hyponatremia or intravascular volume depletion. Hyponatremia can be indicated by acute central nervous system (CNS) dysfunction such as altered mental status, seizures, and coma.
- Unfortunately, no single physical finding can accurately and reproducibly measure effective circulating volume. Commonly used signs of hypovolemia include orthostatic tachycardia or hypotension, increased capillary refill time, increased skin turgor, dry mucous membranes, and sunken anterior fontanel. These signs usually appear only when the degree of dehydration is moderate to severe.
Causes
- CSWS occurs in the setting of acute CNS disease. Conditions include the following:
- Head injury
- Brain tumor
- Intracranial surgery
- Stroke
- Intracerebral hemorrhage
- Tuberculous meningitis
- Craniosynostosis repair
Hyponatremia
Syndrome of Inappropriate Antidiuretic Hormone Secretion
Lab Studies
- Serum sodium concentration: Patients with untreated CSWS are often hyponatremic.
- Serum osmolality: If measured serum osmolality exceeds twice the serum sodium concentration and azotemia is not present, suspect hyperglycemia or mannitol as the cause of hyponatremia.
- Serum uric acid concentrations are often low in SIADH but can be normal in CSWS.
- Urine output: Urine is dilute and flow rate is often high in CSWS but is usually very concentrated, and flow rate is low, in SIADH.
- Urine sodium concentrations are typically elevated in both SIADH and CSWS (>40 mEq/L). However, urinary sodium excretion (urine sodium concentration [mEq/L] X urine volume [L/24 h]) is substantially higher than sodium intake in CSWS but generally equals sodium intake in SIADH. Therefore, net sodium balance (intake minus output) is negative in CSWS.
- Fractional excretion of uric acid
- Fractional excretion of uric acid (FEUA) is defined as the percentage of urate filtered by glomeruli that is excreted in urine. It is calculated by dividing the product of (urinary uric acid [mg/mL] X serum creatinine [mg/mL]) by the product of (serum uric acid [mg/mL] X urine creatinine [mg/mL]) and multiplying the result by 100%.
- Normal values are less than 10%. Patients with either CSWS or SIADH have elevated FEUA. However, after correction of hyponatremia, FEUA normalizes in SIADH but remains elevated in CSWS. Maesaka et al have proposed that FEUA can be used to distinguish between CSWS and SIADH in cases in which the clinical picture is unclear.
Medical Care
- Evaluation and treatment typically occurs in the inpatient setting because most patients are seriously ill with acute CNS disease.
- Management centers on correction of intravascular volume depletion and hyponatremia as well as replacement of ongoing urinary sodium loss with intravenous isotonic or hypertonic saline solutions.
- Once the patient is stabilized, enteral salt supplementation can be considered.
Drug Category: Mineralocorticoids
Some clinicians have reported a favorable response to mineralocorticoid therapy in CSWS. Acts on fluid and electrolyte balance. These agents enhance sodium reabsorption in the kidney by direct action on renal tubule cell, resulting in expanded extracellular fluid volume. They increase renal excretion of potassium and hydrogen ion.
| Drug Name | Fludrocortisone (Florinef) |
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| Description | Promotes increased reabsorption of sodium and loss of potassium renal distal tubules. |
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| Adult Dose | 0.05-0.2 mg/d PO |
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| Pediatric Dose | Administer as in adults |
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| Contraindications | Documented hypersensitivity; congestive heart failure; systemic fungal infections |
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| Interactions | Barbiturates, phenytoin, and rifampin can increase hepatic metabolism of fludrocortisone diminishing its effect; fludrocortisone-induced hypokalemia can enhance digoxin toxicity |
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| Pregnancy | C - Safety for use during pregnancy has not been established.
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| Precautions | Adverse effects include hypertension, edema, congestive heart failure, and hypokalemic alkalosis; dose should be carefully titrated to level of patient tolerance and effectiveness; monitor for dizziness, severe or continuing headaches, swelling feet or lower legs, or unusual weight gain; administer with food to minimize GI adverse effects |
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Further Inpatient Care
- Children with CSWS usually are hospitalized for management of their underlying CNS disease.
- Ongoing monitoring of body weight, fluid balance, and serum sodium concentration is essential during the hospital course.
Further Outpatient Care
- Patients whose neurologic insult has improved and who demonstrate normal intravascular volume and serum sodium concentrations on enteral salt supplements and/or fludrocortisone can be closely observed as outpatients until CSWS resolves.
In/Out Patient Meds
- Medications include sodium chloride tablets or solution (adjust based on serum and urine sodium levels) and fludrocortisone.
Complications
- Symptomatic hyponatremia
- Dehydration
Prognosis
- CSWS usually develops in the first week following a brain insult. Its duration is usually brief (spontaneously resolves in 2-4 weeks), although it can last for several months.
Medical/Legal Pitfalls
- Failure to distinguish CSWS from SIADH in a hyponatremic patient with brain injury will lead to inappropriate therapy and potentially exacerbate intravascular volume depletion.
| Media file 1:
Possible mechanisms for cerebral salt-wasting syndrome. The injured brain may release natriuretic proteins that act directly on the kidney. In addition, cerebral injury may increase sympathetic nervous system activity, elevating renal perfusion pressure and releasing dopamine. |
 |  View Full Size Image | |
Media type: Graph
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Cerebral Salt-Wasting Syndrome excerpt Article Last Updated: Sep 18, 2006
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