What are the treatment options for Orthostatic Hypotension?

Treatment of Orthostatic Hypotension

Begin with non-pharmacological interventions in all patients, and add midodrine as first-line pharmacological therapy when lifestyle measures fail to adequately control symptoms, with the goal of minimizing postural symptoms rather than normalizing blood pressure. 1

Initial Assessment and Reversible Causes

• Immediately review and discontinue or switch medications that worsen orthostatic hypotension—particularly diuretics, vasodilators, ACE inhibitors, and alpha-blockers—as drug-induced autonomic failure is the most frequent cause. 1 Switching to alternative therapy is essential, not simply dose reduction. 1

• Evaluate for volume depletion, endocrine disorders (hypothyroidism, adrenal insufficiency), and cardiovascular causes before initiating treatment. 1

• Avoid alcohol, as it causes both direct autonomic neuropathy and central volume depletion. 1

• Confirm diagnosis by measuring blood pressure after 5 minutes of lying/sitting, then at 1 and 3 minutes after standing. 1, 2

Non-Pharmacological Management (First-Line for All Patients)

Fluid and Salt Expansion:

• Increase fluid intake to 2-3 liters daily unless contraindicated by heart failure. 1, 2
• Increase salt intake to 6-9 grams daily (approximately 1-2 teaspoons of table salt) if not contraindicated. 1, 2
• Acute water ingestion of ≥480 mL provides temporary relief with peak effect at 30 minutes. 1

Physical Countermaneuvers:

• Teach leg crossing, squatting, stooping, and muscle tensing during symptomatic episodes—particularly effective in patients under 60 years with prodromal symptoms. 1, 2
• These maneuvers increase venous return and can abort symptoms before syncope occurs. 1

Compression Garments:

• Use waist-high compression stockings (30-40 mmHg) and abdominal binders to reduce venous pooling. 1, 2

Postural Modifications:

• Elevate the head of the bed by 10 degrees during sleep to prevent nocturnal polyuria, maintain favorable fluid distribution, and ameliorate supine hypertension. 1, 2
• Teach gradual staged movements with postural changes. 1

Dietary Modifications:

• Recommend smaller, more frequent meals to reduce post-prandial hypotension. 1, 2
• Encourage physical activity and exercise to avoid deconditioning, which worsens orthostatic intolerance. 1

Pharmacological Management (When Non-Pharmacological Measures Fail)

First-Line: Midodrine

Midodrine has the strongest evidence base among pressor agents, with three randomized placebo-controlled trials demonstrating efficacy. 1, 3

• Starting dose: 2.5-5 mg three times daily. 1, 2, 3
• Mechanism: Alpha-1 adrenergic agonist that increases vascular tone through arteriolar and venous constriction. 1, 2
• Effect: Increases standing systolic blood pressure by 15-30 mmHg for 2-3 hours. 1
• Titration: Individually tailor up to 10 mg two to four times daily based on response. 1

Critical Timing Restriction:

• The last dose must be taken at least 3-4 hours before bedtime (not after 6 PM) to prevent supine hypertension during sleep. 1, 2, 3

Monitoring:

• Monitor for supine hypertension (the most important limiting factor)—symptoms include cardiac awareness, pounding in ears, headache, and blurred vision. 2, 3
• May cause slight vagal-mediated heart rate slowing, but benefits usually outweigh this concern. 2, 3
• Use cautiously with cardiac glycosides, beta blockers, or other agents that reduce heart rate. 3

Contraindications and Cautions:

• Avoid concomitant use with other vasoconstrictors (phenylephrine, pseudoephedrine, ephedrine, dihydroergotamine) without careful blood pressure monitoring. 3
• Use with caution in patients with urinary retention, diabetes, renal impairment (start at 2.5 mg), or hepatic impairment. 3

Second-Line: Fludrocortisone

Add fludrocortisone if midodrine alone provides insufficient symptom control, or use as monotherapy if midodrine is contraindicated. 1, 2

• Starting dose: 0.05-0.1 mg once daily. 1, 2
• Titration: Individually titrate to 0.1-0.3 mg daily (maximum 1.0 mg daily). 1
• Mechanism: Mineralocorticoid that increases plasma volume through sodium retention and vessel wall effects. 1, 2

Monitoring Requirements:

• Monitor for supine hypertension (most important limiting factor). 1, 2
• Check electrolytes periodically for hypokalemia due to mineralocorticoid effects. 1, 2
• Monitor for congestive heart failure and peripheral edema. 1, 2

Contraindications:

• Avoid in patients with active heart failure, significant cardiac dysfunction, pre-existing supine hypertension, or severe renal disease where sodium retention would be harmful. 1

Combination Therapy

• For non-responders to monotherapy, consider combining midodrine and fludrocortisone, as they work through complementary mechanisms (alpha-1 adrenergic stimulation versus sodium retention). 1
• Ensure adequate salt (6-10 g daily) and fluid (2-3 L daily) intake as adjunctive measures when using either agent. 1

Alternative Agents

Droxidopa:

• FDA-approved for neurogenic orthostatic hypotension, particularly effective in Parkinson's disease, pure autonomic failure, and multiple system atrophy. 1
• May reduce falls in these populations. 1

Pyridostigmine:

• Beneficial for refractory orthostatic hypotension in elderly patients who have not responded to other treatments. 1
• Favorable side effect profile compared to alternatives like fludrocortisone. 1
• Common side effects include nausea, vomiting, abdominal cramping, sweating, salivation, and urinary incontinence. 1

Special Populations

Patients with Hypertension and Orthostatic Hypotension:

• Switch to long-acting dihydropyridine calcium channel blockers (e.g., amlodipine) or RAS inhibitors as first-line therapy for hypertension. 1
• Avoid combining multiple vasodilating agents (ACE inhibitors + calcium channel blockers + diuretics) without careful monitoring. 1

Diabetic Patients:

• Assess for cardiovascular autonomic neuropathy. 1
• Do not overlook volume depletion as a contributing factor. 1

Treatment Goals and Monitoring

The therapeutic objective is minimizing postural symptoms and improving functional capacity, NOT restoring normotension. 1, 2, 4

• Aggressive blood pressure targets may worsen supine hypertension and cause end-organ damage. 1, 2
• Balance the benefits of increasing standing blood pressure against the risk of worsening supine hypertension. 1, 2

Follow-up Schedule:

• Early review at 24-48 hours after medication initiation. 2
• Reassess within 1-2 weeks after medication changes. 1, 2
• Monitor orthostatic vital signs at each follow-up visit. 1
• Continue treatment only for patients who report significant symptomatic improvement. 3

Critical Pitfalls to Avoid

• Do not simply reduce the dose of offending medications—switch to alternative therapy. 1
• Do not administer midodrine after 6 PM. 1, 2
• Do not use fludrocortisone in patients with heart failure or supine hypertension. 1
• Do not combine multiple vasoconstrictors without careful blood pressure monitoring. 2, 3
• Cardiac pacing is NOT recommended for orthostatic hypotension with bradycardia unless there is documented intrinsic sinus node dysfunction causing symptomatic bradyarrhythmias independent of postural changes. 2
• Beta-adrenergic blocking drugs are not effective and may aggravate bradycardia in cardioinhibitory cases. 1