Continuing Education Activity

Cerebral salt wasting (CSW) is a potential cause of hyponatremia in the setting of disease of the central nervous system (CNS). Cerebral salt wasting is characterized by hyponatremia with elevated urine sodium and hypovolemia. In the current literature, professionals debate if cerebral salt wasting is a distinct condition or a special form of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). This activity describes the cause and pathophysiology of cerebral salt wasting syndrome and highlights the role of the interprofessional team in its management.

Objectives:

• Describe the pathophysiology of cerebral salt wasting syndrome.
• Review the history of cerebral salt wasting syndrome.
• Summarize the evaluation of a patient with cerebral salt wasting syndrome.
• Explain the importance of improving care coordination among interprofessional team members to improve outcomes for patients affected by cerebral salt wasting syndrome.

Introduction

Cerebral salt wasting (CSW) is a potential cause of hyponatremia in the setting of disease of the central nervous system (CNS). Cerebral salt wasting is characterized by hyponatremia with elevated urine sodium and hypovolemia. In the current literature, professionals debate if cerebral salt wasting is a distinct condition or a special form of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). It is important to distinguish between cerebral salt wasting and SIADH as the 2 are treated with opposite treatment strategies. For cerebral salt wasting the patient is given fluids and sodium supplementation. For SIADH the patient is fluid restricted. Cerebral salt wasting tends to resolve within weeks to months after onset but can remain a chronic issue. Leading theories for the pathophysiology of cerebral salt wasting include the release of brain natriuretic peptide (BNP) or damage to the hypothalamus with subsequent disorder sympathetic system.[1]

Etiology

The etiology of cerebral salt wasting (CSW) is not completely understood. Cerebral salt wasting is most commonly seen after a central nervous system insult. The most commonly described precipitating insult is aneurysmal subarachnoid hemorrhage. Why cerebral salt wasting occurs more frequently after aneurysmal subarachnoid hemorrhage versus traumatic subarachnoid hemorrhage or other CNS insult is not well defined. Why cerebral salt wasting is uncommon after other injuries or diseases is also not well defined.

Epidemiology

Since cerebral salt wasting (CSW) is still a debated condition, its exact incidence and prevalence may be hard to pin down. Cerebral salt wasting is most commonly seen after aneurysmal subarachnoid hemorrhage but can be seen after other insults to the central nervous system. Other conditions in which cerebral salt wasting has been reported include: after surgery for a pituitary tumor or acoustic neuroma or calvarial remodeling, glioma, infections including tuberculous meningitis and viral meningitis, metastatic carcinoma, and cranial trauma.

Some have calculated that cerebral salt wasting accounts for up to one-quarter of severe hyponatremia after aneurysmal subarachnoid hemorrhage. The incidence of cerebral salt wasting for other CNS insults is mostly reported as case reports. The incidence and prevalence of cerebral salt wasting outside of patients with CNS insult are not reliably reported.

Pathophysiology

The true etiology of cerebral salt wasting (CSW) remains an area of debate and research. As noted, some argue cerebral salt wasting does not exist and is a form of SIADH.

There are two current theories for the etiology of cerebral salt wasting: the effect of a circulating factor or sympathetic nervous system dysfunction.

Some research points to the brain releasing brain natriuretic peptide (BNP) after injury, which then enters systemic circulation through a disrupted blood-brain barrier. The BNP acts on the collecting ducts of the renal tubules to inhibit sodium reabsorption as well as decrease the release of renin.

The second theory suggests that an injured sympathetic nervous system can no longer promote sodium reabsorption and stimulate renin release due to injury to the hypothalamus. The exact mechanism of cerebral salt wasting remains open to debate.

History and Physical

The most common presenting story for cerebral salt wasting is hyponatremia after aneurysmal subarachnoid hemorrhage.[2] A few days after the hemorrhage the patient’s serum sodium begins to drop while the urine sodium increases. The patient’s fluid status also decreases, and the patient becomes hyponatremia and hypovolemic.  With treatment, the cerebral salt wasting resolves within a few weeks to months, and long-term treatment is not commonly required.

Cerebral salt wasting has also been reported after surgery of the central nervous system including pituitary surgery, vestibular schwannoma resection, and calvarial remodeling. Additionally, cerebral salt wasting has been seen after a head injury, intracranial malignancy, and central nervous system (CNS) infections.

Evaluation

It is critically important to distinguish cerebral salt wasting (CSW) from the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) as the treatments are opposite. Evaluation for cerebral salt wasting begins with a basic metabolic panel (BMP) to identify the hyponatremia (serum sodium less than 135 meq/L). Urine studies are commonly checked for urine sodium and osmolality. Urine sodium is typically elevated above 40 meq/L. Urine osmolality is elevated above 100 mosmol/kg. The patient must also have signs or symptoms of hypovolemia such as hypotension, decreased central venous pressure, lack of skin turgor, or elevated hematocrit.

Syndrome of inappropriate secretion of antidiuretic of hormone (SIADH) will have a similar laboratory picture as cerebral salt wasting with hyponatremia and increased urine sodium. However, with SIADH, the patient is euvolemic to hypervolemic from the retained free water as compared to the hypovolemic picture of cerebral salt wasting.[3][4]

Other potential causes of hyponatremia should also be sought including polydipsia, renal disease, use of diuretics, heart failure, hypothyroidism, heart failure, malignancies, hormone deficiency, and pseudohyponatremia. Many times cerebral salt wasting becomes a diagnosis of exclusion after labs reveal serum hyponatremia with increased urine sodium levels.

Treatment / Management

The treatment of cerebral salt wasting (CSW) and syndrome of inappropriate secretion of antidiuretic of hormone (SIADH) is very different, so it is critical to have the correct diagnosis prior to initiating treatment.

As cerebral salt wasting typically occurs after aneurysmal subarachnoid hemorrhage, the first treatment strategies are targeted at treating the underlying subarachnoid hemorrhage and aneurysm or another CNS insult. This treatment is covered in the StatPearls article on acute subarachnoid hemorrhage. Secondly, the patient must be volume repleted while treating the hyponatremia. Typically, the patient is started on isotonic saline for mild to moderate cases of hyponatremia of cerebral salt wasting. The isotonic fluid provides the fluid for the hypovolemic patient as well as helps to restore the body's sodium stores. For moderate to severe cases of hyponatremia, more aggressive sodium replenishment may be required with either hypertonic saline such as 3% hypertonic saline and/or salt tabs (1 to 2 grams up to three times daily) as well as limiting free water intake. Some have advocated for the use of fludrocortisone as well for the treatment of cerebral salt wasting.[4]

When correcting the hyponatremia, the serum sodium should be monitored frequently. Overcorrection of the serum sodium can lead to hypernatremia which can cause muscle twitching, lethargy, seizure, and death. Additionally, hyponatremia should not be corrected too quickly. There is the risk of central pontine myelinolysis if the hyponatremia is corrected too quickly, especially for long-standing hyponatremia. Most experts recommend correcting no more than 10 meq/L/24 hours or 1 meq/L every 2 hours. 

The most important issue is to distinguish between cerebral salt wasting and syndrome of inappropriate secretion of antidiuretic of hormone (SIADH) as they are treated with opposite approaches. In cases of SIADH, the treatment is typically fluid restriction, hypertonic saline, demeclocycline, and/or furosemide.  If the patient truly has cerebral salt wasting, they are hypovolemic, and the SIADH treatment modalities would be detrimental by exacerbating the hypovolemia.[5][6][7]

Differential Diagnosis

It is critical to distinguish between cerebral salt wasting and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Both conditions are characterized by hyponatremia with elevated urine sodium, concentrated urine, and no edema. The key distinguishing factor is that in cerebral salt wasting the patient is hypovolemic versus in SIADH the patient is euvolemic to hypervolemic.[3] The differential of the etiology of CSW is:

• Head injury
• Brain tumor
• Stroke
• Intracranial surgery
• Intracerebral hemorrhage
• Craniosynostosis repair
• Tuberculous meningitis

Enhancing Healthcare Team Outcomes

Cerebral salt wasting often occurs after significant CNS pathology such as aneurysmal subarachnoid hemorrhage. Care for such patients must be coordinated between multiple specialties as the treatment of cerebral salt wasting may include additional fluid volume which can exacerbate issues including cerebral edema, pulmonary edema, heart failure, and renal dysfunction. Additional attention should be paid to the carrier fluids for the other medications and to avoid infusing too much free water to the patient. Patients can require continued management of their hyponatremia for weeks to months or more after the original insult. During treatment, the patient's GCS and neurological exam must be continually assessed. The outcomes for most patients with cerebral salt wasting not due to a subarachnoid hemorrhage are good. However, some patients may continue to have mild neurological deficits despite optimal treatment.[8][9]

Outcomes can be improved with the participation of an interprofessional team. Primary care providers, emergency department physicians, neurologists, neurosurgeons, specialty care nurses, and pharmacists can all be involved. Critical care and neuroscience nurses caring out treatments, monitor patients, provide education to patients and their families, and provide updates on the patient's condition to the team. Pharmacists assist the team by reviewing medications prescribed and drug-drug interactions that can exacerbate the condition, and reporting to the clinician team if any therapy changes are necessary. [Level 5]