What is the role of Fludrocortisone in Subarachnoid Hemorrhage (SAH)?

From the Guidelines

Fludrocortisone is recommended for the management of cerebral salt wasting (CSW) in patients with subarachnoid hemorrhage (SAH), as it has been shown to reduce excess sodium excretion, urine volume, hyponatremia, and intravenous fluid use during acute aSAH 1. The typical dosage is 0.1-0.4 mg orally once or twice daily, with treatment usually continuing for 1-2 weeks or until resolution of hyponatremia. Start with 0.1 mg twice daily and titrate based on serum sodium levels and volume status. Fludrocortisone works by enhancing sodium reabsorption in the kidneys through its mineralocorticoid activity, helping to counteract the excessive sodium loss that occurs in CSW following SAH. This treatment should be accompanied by adequate fluid intake and sodium supplementation as needed. Monitor serum electrolytes, especially potassium, as hypokalemia is a common side effect. Blood pressure should also be regularly checked as fludrocortisone can cause hypertension. Discontinue gradually rather than abruptly when the patient's sodium levels stabilize. Fludrocortisone is particularly useful in SAH patients because it addresses the underlying pathophysiology of CSW, which is characterized by inappropriate natriuresis and volume depletion, distinguishing it from SIADH which requires fluid restriction instead. Some key points to consider when using fludrocortisone in SAH patients include:

• The use of fludrocortisone acetate and hypertonic saline is reasonable for correcting hyponatremia 1
• Monitoring volume status in certain patients with recent SAH using some combination of central venous pressure, pulmonary artery wedge pressure, fluid balance, and body weight is reasonable, as is treatment of volume contraction with isotonic fluids 1
• Administration of large volumes of hypotonic fluids and intravascular volume contraction should generally be avoided after SAH 1

From the FDA Drug Label

CLINICAL PHARMACOLOGY Corticosteroids are thought to act at least in part, by controlling the rate of synthesis of proteins. Although there are a number of instances in which the synthesis of specific proteins is known to be induced by corticosteroids, the links between the initial actions of the hormones and the final metabolic effects have not been completely elucidated The physiologic action of fludrocortisone acetate is similar to that of hydrocortisone. However, the effects of fludrocortisone acetate, particularly on electrolyte balance, but also on carbohydrate metabolism, are considerably heightened and prolonged Mineralocorticoids act on the distal tubules of the kidney to enhance the reabsorption of sodium ions from the tubular fluid into the plasma; they increase the urinary excretion of both potassium and hydrogen ions The consequence of these three primary effects together with similar actions on cation transport in other tissues appear to account for the entire spectrum of physiological activities that are characteristic of mineralocorticoids. In small oral doses, fludrocortisone acetate produces marked sodium retention and increased urinary potassium excretion It also causes a rise in blood pressure, apparently because of these effects on electrolyte levels. In larger doses, fludrocortisone acetate inhibits endogenous adrenal cortical secretion, thymic activity, and pituitary corticotropin excretion; promotes the deposition of liver glycogen; and, unless protein intake is adequate, induces negative nitrogen balance. The approximate plasma half-life of fludrocortisone (fluorohydrocortisone) is 3. 5 hours or more and the biological half-life is 18 to 36 hours.

The FDA drug label does not answer the question.

From the Research

Fludrocortisone in Subarachnoid Hemorrhage (SAH)

• Fludrocortisone is a mineralocorticoid that facilitates retention of sodium and water, and has been studied as a potential treatment for cerebral salt wasting in patients with aneurysmal subarachnoid hemorrhage (SAH) 2, 3, 4.
• A retrospective study published in 2023 found that fludrocortisone was associated with decreased urine output and subsequently, decreased volume intake, to maintain euvolemia in patients with aneurysmal subarachnoid hemorrhage and cerebral salt wasting 2.
• Another study published in 1997 suggested that fludrocortisone may help maintain plasma volume in patients with SAH, but larger controlled trials are needed to ascertain the impact of fludrocortisone on prevention of cerebral ischemia in patients with SAH 3.
• A study published in 2013 found that early inhibition of natriuresis with fludrocortisone acetate before the occurrence of hyponatremia prevented symptomatic cerebral vasospasm after aneurysmal SAH 4.

Management of SAH

• The management of SAH includes admission of patients to high-volume centers, expeditious identification and treatment of the bleeding source, management of patients in a neurocritical care unit with enteral nimodipine, blood pressure control, euvolemia, and close monitoring for neurologic and medical complications 5, 6.
• Treatment of symptomatic cerebral vasospasm/delayed cerebral ischemia with induced hypertension and endovascular therapies is also recommended 5, 6.
• The use of fludrocortisone in the management of SAH is not universally recommended, and its effectiveness in preventing cerebral ischemia is still uncertain 3, 4.