What is the treatment for a patient presenting with orthostatic hypotension?

Treatment of Orthostatic Hypotension

Begin by immediately discontinuing or switching—not just reducing the dose of—any blood pressure-lowering medications that worsen orthostatic hypotension, as drug-induced autonomic failure is the most frequent cause. 1, 2

Initial Management: Identify and Remove Causative Factors

• Medication review is the critical first step: Diuretics, vasodilators (including nitrates), ACE inhibitors, calcium channel blockers, alpha-adrenergic blockers, and psychotropic medications are the most common culprits. 1, 2
• Switch to alternative antihypertensive therapy (such as long-acting dihydropyridine calcium channel blockers or RAS inhibitors if hypertension control is still needed), rather than simply reducing doses. 1
• Discontinue alcohol, as it causes both autonomic neuropathy and central volume depletion. 1
• Assess for volume depletion, blood loss, and endocrine disorders as reversible causes. 1

Non-Pharmacological Treatment (Implement for ALL Patients)

These measures must be implemented before or alongside pharmacological therapy:

• Fluid and salt intake: Increase fluid intake to 2-3 liters daily and salt consumption to 6-9 grams daily (approximately 1-2 teaspoons of table salt), unless contraindicated by heart failure. 1, 3
• Physical counter-maneuvers: Teach leg crossing, squatting, stooping, and muscle tensing during symptomatic episodes—particularly effective in patients under 60 years with prodromal symptoms. 1, 3
• Compression garments: Use waist-high compression stockings (30-40 mmHg) and abdominal binders to reduce venous pooling. 1, 3
• Elevate head of bed: Raise the head of the bed by 10 degrees during sleep to prevent nocturnal polyuria, maintain favorable fluid distribution, and ameliorate supine hypertension. 1, 3
• Dietary modifications: Eat smaller, more frequent meals to reduce post-prandial hypotension. 1
• Gradual positional changes: Advise staged movements when changing posture. 1
• Acute water ingestion: Drink ≥480 mL of water for temporary relief, with peak effect at 30 minutes. 1

Pharmacological Treatment (When Non-Pharmacological Measures Are Insufficient)

First-Line Medication: Midodrine

Midodrine has the strongest evidence base among pressor agents, with three randomized placebo-controlled trials demonstrating efficacy. 1, 4

• Dosing: Start at 2.5-5 mg three times daily; titrate up to 10 mg three times daily based on response. 1, 3, 4
• Mechanism: Alpha-1 adrenergic agonist that increases vascular tone through arteriolar and venous constriction, elevating standing systolic BP by 15-30 mmHg for 2-3 hours. 1, 2
• Critical timing: The last dose must be taken at least 3-4 hours before bedtime (not after 6 PM) to prevent supine hypertension during sleep. 1, 3, 4
• FDA indication: Approved specifically for symptomatic orthostatic hypotension in patients whose lives are considerably impaired despite standard clinical care. 4

Second-Line or Combination Therapy: Fludrocortisone

• Dosing: Start at 0.05-0.1 mg once daily; 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—complementary to midodrine's mechanism. 1
• When to add: If midodrine alone provides insufficient symptom control, add fludrocortisone for combination therapy. 1, 5
• Contraindications: Avoid in patients with active heart failure, significant cardiac dysfunction, severe renal disease, or pre-existing supine hypertension. 1
• Monitoring requirements: Check for supine hypertension (most important limiting factor), hypokalemia, congestive heart failure, and peripheral edema; monitor electrolytes periodically. 1

Alternative First-Line Option: Droxidopa

• FDA-approved and particularly effective for neurogenic orthostatic hypotension in Parkinson's disease, pure autonomic failure, and multiple system atrophy. 1, 2
• May reduce falls in these populations. 1

Refractory Cases: Pyridostigmine

• Consider for elderly patients refractory to other treatments, with fewer side effects than alternatives like fludrocortisone. 1
• Supported by 2017 ACC/AHA/HRS guidelines for neurogenic orthostatic hypotension unresponsive to first-line agents. 1

Treatment Goals and Monitoring

The therapeutic objective is minimizing postural symptoms and improving functional capacity—NOT restoring normotension. 1, 3

• Aggressive blood pressure targets may worsen supine hypertension, which can cause left ventricular hypertrophy, stroke, and sudden death. 2
• Measurement protocol: Measure BP after 5 minutes lying/sitting, then at 1 and 3 minutes after standing. 6, 1
• Follow-up timing: Reassess within 1-2 weeks after medication changes; monitor for both symptomatic improvement and development of supine hypertension. 1
• Continue midodrine only if patients report significant symptomatic improvement. 4

Critical Pitfalls to Avoid

• Do not simply reduce the dose of offending medications—switch to alternative therapy instead. 1
• Do not administer midodrine after 6 PM, as this causes supine hypertension during sleep. 1, 4
• Do not use fludrocortisone in patients with heart failure or supine hypertension. 1
• Do not combine multiple vasoconstrictors without careful BP monitoring, as this increases supine hypertension risk. 3, 4
• Do not overlook volume depletion as a contributing factor before starting pressor agents. 1
• Cardiac pacing is NOT recommended for orthostatic hypotension with bradycardia unless there is documented intrinsic sinus node dysfunction independent of postural changes. 3

Special Populations

• Patients with both hypertension and orthostatic hypotension: Prefer long-acting dihydropyridine calcium channel blockers or RAS inhibitors as first-line antihypertensive therapy. 1
• Diabetic patients: Assess for cardiovascular autonomic neuropathy; optimize glucose control to prevent progression. 1, 2
• Patients with renal impairment: Start midodrine at 2.5 mg and use with caution, as desglymidodrine is eliminated via the kidneys. 4