Is Florinef (fludrocortisone) effective for treating syncope related to orthostatic hypotension?

Fludrocortisone for Syncope Related to Orthostatic Hypotension

Fludrocortisone can be beneficial in patients with syncope due to neurogenic orthostatic hypotension, with a recommended dosage of 0.1-0.3 mg once daily. 1

Mechanism and Efficacy

• Fludrocortisone is a mineralocorticoid that stimulates renal sodium retention and expands fluid volume, which helps counteract the blood pressure drop that occurs when standing 1
• Evidence supporting fludrocortisone comes from small observational studies and one double-blind trial in 60 patients, showing hemodynamic benefit and symptom improvement 1
• In patients with neurogenic orthostatic hypotension, fludrocortisone can effectively minimize orthostatic symptoms and increase orthostatic blood pressure 2

Treatment Algorithm for Orthostatic Hypotension

First-line non-pharmacological measures:

• Adequate hydration and salt intake (targeting 2-3 L of fluids per day and 10 g of NaCl) 1
• Physical counterpressure maneuvers (leg crossing, squatting) for patients with warning symptoms 1
• Compression garments (abdominal binders or thigh-high compression stockings) 1
• Sleeping with head of bed elevated (10°) to maintain favorable fluid distribution 1

Pharmacological treatment when non-pharmacological measures are insufficient:

1. Fludrocortisone (0.1-0.3 mg once daily) 1
2. Midodrine (5-20 mg, three times daily) 1
3. Droxidopa for neurogenic orthostatic hypotension 1
4. Consider pyridostigmine for refractory cases 1
5. Consider octreotide for refractory postprandial hypotension 1

Special Considerations and Cautions

• Supine hypertension may be a limiting factor for fludrocortisone use; when present, other medications should be considered first 1
• Common side effects include edema, hypokalemia, and headache 1
• More serious adverse reactions such as adrenal suppression and immunosuppression can occur with doses >0.3 mg daily 1
• Fludrocortisone is poorly tolerated in the long term in older patients, with approximately 33% discontinuing treatment (mean of 5 months) due to hypertension, cardiac failure, depression, or edema 3
• Always eliminate offending medications that may cause or worsen orthostatic hypotension before initiating treatment 1

Evidence Quality and Limitations

• The 2017 ACC/AHA/HRS guidelines give fludrocortisone a Class IIa recommendation with Level C-LD evidence for neurogenic orthostatic hypotension 1
• A 2021 Cochrane review found very low-certainty evidence about the effects of fludrocortisone on blood pressure, orthostatic symptoms, or adverse events 4
• Most studies are small, short-term, and examine fludrocortisone in specific conditions (diabetes, Parkinson's disease) 4
• There is limited information on long-term treatment efficacy and safety 4

Combination Therapy

• The combination of head-up tilt sleeping and fludrocortisone has shown to be particularly effective in minimizing orthostatic symptoms 2
• In cases where fludrocortisone alone is insufficient, adding sympathetic vasoconstrictor drugs like midodrine may provide additional benefit 1
• For refractory cases, referral to specialized centers for evaluation and treatment of autonomic failure should be considered 1