However, Cerebral Salt Wasting is an Additional (Although Less Common) Etiology of Hyponatremia in Patients with Central Nervous System Disease (Especially in Patients with Subarachnoid Hemorrhage)
Common Neurologic Etiology of Cerebral Salt Wasting
In Patients with Subarachnoid Hemorrhage-Associated Hyponatremia, SIADH Accounts for Approximately 69% of Cases of Hyponatremia, as Compared to Cerebral Salt Wasting Which Accounts for Only 7% of Cases of Hyponatremia (Clin Endocrinol-Oxf, 2006) [MEDLINE]
In Patients with Subarachnoid Hemorrhage, Hyponatremia Occurs in 49% of Cases (J Clin Endocrinol Metab, 2014) [MEDLINE]
In This Study, Hyponatremia was Attributable to SIADH in 71% of Cases, to Glucocorticoid Deficiency in 8% of Cases, and to Cerebral Salt Wasting in None of the Cases
All Patients in the Study were Serially Evaluated for Volume Status, Plasma Cortisol, Arginine Vasopressin, and Brain Natriuretic Peptide
Brain Natriuretic Peptide Decreases Autonomic Outflow Via Effects on the Brainstem (Am J Physiol, 1991) [MEDLINE] (NEJM, 1998) [MEDLINE]
Disruption of Neural Input to the Kidney
Sympathetic Nervous System Enhances Proximal Tubular Sodium, Water, and Uric Acid Reabsorption
Sympathetic Nervous System Enhances Renin Release
Consequently, Impaired Sympathetic Neural Output Results in Increased Sodum/Water/Uric Acid Loss in the Urine, as Well as Impaired Renin-Aldosterone Release
The Failure of Aldosterone to Increase in Response to Hypovolemia Explains the Absence of Potassium Wasting (Despite an Increase in Distal Sodium Delivery)
Diagnostic Strategies to Differentiate Cerebral Salt Wasting from Syndrome of Inappropriate Antidiuretic Hormone Secretion
Cerebral Salt Wasting and the Syndrome of Inappropriate Antidiuretic Hormone Secretion Share the Following Clinical Features
Hyponatremia with Increased ADH Release and Inappropriately Increased Urine Osmolality
Hyponatremia Would Normally Inhibit ADH Release
The Increased ADH Release is an Appropriate Response in Cerebral Salt Wasting, But is an Inappropriate Response in SIADH
Increased Urine Sodium (Usually >40 mEq/L)
In Cerebral Salt Wasting, This is Due to Renal Salt Wasting
In SIADH, This is Due to Volume Expansion
Decreased Serum Uric Acid Due to Decreased Urinary Uric Acid Excretion
In Cerebral Salt Wasting, This is Likely Due to BNP
In SIADH, This is Likely Due to Volume Expansion and a Direct Effect of ADH on the V1 Receptor (Am J Kidney Dis, 1992) [MEDLINE]
Cerebral Salt Wasting from Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) are Distinguished by the Following Clinical Features
In Cerebral Salt Wasting, Clinical Hypovolemia is Present
In SIADH, Extracellular Fluid Volume is Normal-Slightly Increased
Trial of Isotonic Normal Saline
In Theory, a Trial of Isotonic/Normal Saline Might Help Differentiate Cerebral Salt Wasting from Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) for the Following Reasons
Restoration of Euvolemia in Cerebral Salt Wasting Should Remove the Stimulus for Antidiuretic Hormone Release, Resulting in a Dilute Urine and Correction of the Hyponatremia (Curr Opin Nephrol Hypertens, 2020) [MEDLINE]
However, This Has Not Been Documented to Occur in Cerebral Salt Wasting
Also, a Lack of Urinary Dilution Does Not Necessarily Preclude the Diagnosis of Cerebral Salt Wasting, Since Patients with Subarachnoid Hemorrhage May Also Have SIADH
In Contrast, Isotonic/Normal Saline Often Worsens the Hyponatremia in SIADH, as the Salt is Excreted and Some of the Water is Retained
For This Reason, a Trial of Isotonic/Normal Saline is Discouraged as a Means to Differentiate These Clinical Syndromes
Other Diagnostic Strategies
While Difficult to Perform, Evidence of Net Negative Sodium Balance Prior to Therapy is Also Consistent with the Diagnosis of Cerebral Salt Wasting
Calculation of the Sodium Intake Includes that Obtained by Both Oral/Intravenous Routes (Including Sodium supplements, Food, etc), While Sodium Excretion Involves Frequent Measurement of Urine Sodium Concentrations and Measurement of Urine Volume
Presence of Hypovolemia Distinguishes Cerebral Salt Wasting from Syndrome of inappropriate Antidiuretic Hormone Secretion (SIADH), Where the Patient is Typically Euvolemic or Modestly Hypervolemic (see Syndrome of Inappropriate Antidiuretic Hormone Secretion)
Clinical
Extracellular Fluid Depletion with Hypotension, Decreased Skin Turgor, and/or Polycythemia
Fluid Restriction is Contraindicated (Especially in the Setting of Subarachnoid Hemorrhage (SAH)
While Fluid Restriction is the Usual First-Line Therapy in the Treatment of SIADH, it is Contraindicated in the Treatment of Cerebral Salt Wasting in Association with Subarachnoid Hemorrhage
Fluid Restriction May Worsen the Hypovolemia, Cause Hypotension, and Increase the Risk of Cerebral Infarction
Some Experts Suggest that the Distinction Between Cerebral Salt Wasting and SIADH in Patients with an Active Intracranial Disease Process is Not Necessary, Since the Patient Will Be Treated with Hypertonic (3%) Saline in Both Cases to Increase the Serum Sodium and Avoid a Decrease in Extracellular Fluid Volume (J Am Soc Nephrol, 2008) [MEDLINE]
Hypertonic Saline will increase the serum sodium concentration in patients with both Cerebral Salt Wasting and SIADH
For patients with documented Cerebral Salt Wasting, salt tablets can be administered once the patients are able to take oral medications. Salt tablets may also be effective in patients with SIADH
May Also Be Used (Arch Dis Child, 2001) [MEDLINE] (Pediatr Neurosurg, 2001) [MEDLINE] (Pediatrics, 2006) [MEDLINE] (JAMA Neurol, 2018) [MEDLINE]
Prognosis
Resolution Usually Occurs within 3-4 wks (Nephrol Dial Transplant, 2000) [MEDLINE]
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