How should orthostatic (postural) hypotension be managed?

Management of Orthostatic Hypotension

Orthostatic hypotension should be managed with a stepwise approach beginning with medication review and discontinuation of offending agents, followed by non-pharmacologic measures (fluid/salt intake, compression garments, physical counter-maneuvers), and finally pharmacologic therapy with midodrine or fludrocortisone when symptoms persist despite conservative measures. 1

Diagnostic Confirmation

Before initiating treatment, confirm the diagnosis by measuring blood pressure after 5 minutes of supine or seated rest, then at 1 minute and 3 minutes after standing. 1, 2 A drop of ≥20 mmHg systolic or ≥10 mmHg diastolic defines orthostatic hypotension. 1, 3 Document accompanying symptoms (dizziness, lightheadedness, near-syncope) that correlate with postural changes. 1

Step 1: Identify and Eliminate Causative Medications

The most frequent cause of orthostatic hypotension is drug-induced autonomic failure, making medication review the critical first step. 1

High-Priority Medications to Discontinue or Switch:

• Alpha-1 blockers (doxazosin, prazosin, terazosin, tamsulosin) are the most problematic agents and should be discontinued completely rather than dose-reduced. 1, 4
• Centrally-acting antihypertensives (clonidine, methyldopa, guanfacine) must be tapered gradually to avoid rebound hypertension, then switched to alternatives. 1, 4
• Diuretics are among the most frequent culprits, particularly in elderly patients where they cause volume depletion even when ineffective for blood pressure control. 1, 4
• Vasodilators (hydralazine, minoxidil) should be switched to alternative antihypertensive classes. 4

Preferred Alternative Antihypertensive Agents:

When blood pressure control is still required, switch to long-acting dihydropyridine calcium channel blockers (e.g., amlodipine) or RAS inhibitors (ACE inhibitors/ARBs) as first-line agents, as these have minimal impact on orthostatic blood pressure. 1, 4 Do not simply reduce the dose of offending medications—complete substitution is required. 1

Step 2: Non-Pharmacologic Interventions

These measures form the foundation of treatment and should be implemented in all patients, regardless of whether pharmacologic therapy is added. 1, 2

Volume Expansion:

• Increase fluid intake to 2–3 liters daily unless contraindicated by heart failure. 1, 2
• Increase dietary sodium to 6–9 grams daily unless contraindicated by heart failure or uncontrolled hypertension. 1, 2
• Acute water ingestion of ≥480 mL provides temporary relief with peak effect at 30 minutes, useful before standing activities. 1

Physical Counter-Maneuvers:

• Teach leg crossing, squatting, stooping, and muscle tensing during symptomatic episodes—these are particularly effective in patients under 60 years with prodromal symptoms. 1, 2
• Advise gradual positional changes: sit on the bedside for 2–3 minutes before standing, avoid prolonged standing. 1

Compression Garments:

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

Positional Strategies:

• Elevate the head of the bed by approximately 10 degrees to prevent nocturnal polyuria, maintain favorable fluid distribution, and ameliorate nocturnal hypertension. 1

Dietary Modifications:

• Eat smaller, more frequent meals to reduce post-prandial hypotension. 1

Physical Conditioning:

• Encourage regular physical activity and exercise to avoid deconditioning, which worsens orthostatic intolerance. 1

Step 3: Pharmacologic Therapy

Pharmacologic treatment should be initiated when non-pharmacologic measures fail to adequately control symptoms, with the therapeutic goal of minimizing postural symptoms rather than restoring normotension. 1, 2

First-Line Pharmacologic Options:

Midodrine (Preferred First-Line Agent):

Midodrine has the strongest evidence base among pressor agents, supported by three randomized placebo-controlled trials demonstrating efficacy. 1, 2

• Starting dose: 2.5–5 mg three times daily (first dose before arising). 1, 2
• Titration: Increase individually up to 10 mg three times daily based on response. 1, 2
• 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, 2
• Mechanism: Alpha-1 adrenergic agonist causing peripheral vasoconstriction; increases standing systolic BP by 15–30 mmHg for 2–3 hours. 1
• Monitoring: Watch for supine hypertension, urinary retention (especially in men on alpha-blockers for BPH), and bradycardia when combined with beta-blockers or digoxin. 1

Fludrocortisone (Alternative or Add-On First-Line Agent):

Fludrocortisone is equally appropriate as initial therapy, particularly when volume expansion is needed. 1, 2

• Starting dose: 0.05–0.1 mg once daily. 1, 2
• Titration: Increase to 0.1–0.3 mg daily based on response. 1, 2
• Mechanism: Mineralocorticoid that expands plasma volume through sodium retention and vessel wall effects. 1
• Monitoring: Check for supine hypertension, hypokalemia (monitor electrolytes periodically), congestive heart failure, and peripheral edema. 1, 2
• Contraindications: Active heart failure, severe renal disease, pre-existing supine hypertension. 1

Combination Therapy for Inadequate Response:

When monotherapy with midodrine or fludrocortisone does not achieve adequate symptom control, combining the two agents is recommended because they act via complementary mechanisms (alpha-1 adrenergic vasoconstriction versus mineralocorticoid-mediated volume expansion). 1, 2

Second-Line Pharmacologic Options:

Droxidopa:

Droxidopa is FDA-approved for neurogenic orthostatic hypotension and is particularly effective in Parkinson's disease, pure autonomic failure, and multiple system atrophy. 1, 2, 5

• Dosing: Titrate to effect; typical maintenance doses range from 100–600 mg three times daily. 5
• Evidence: In clinical trials, droxidopa showed a statistically significant 0.9-unit decrease in dizziness scores at Week 1 versus placebo (P=0.028), though the effect did not persist beyond Week 1 in some studies. 5
• Important caveat: Effectiveness beyond 2 weeks is uncertain; patients should be evaluated periodically to determine whether droxidopa continues to provide benefit. 5
• Drug interaction: Concomitant carbidopa therapy (in Parkinson's patients) may diminish droxidopa's effectiveness by inhibiting peripheral conversion to norepinephrine. 1

Pyridostigmine (For Refractory Cases):

Pyridostigmine is beneficial for refractory orthostatic hypotension, particularly in elderly patients who have not responded to midodrine and fludrocortisone, and when supine hypertension is a concern. 1, 2

• Dosing: 60 mg orally three times daily. 1
• Mechanism: Acetylcholinesterase inhibitor that enhances ganglionic sympathetic transmission; does not worsen supine blood pressure. 1
• Advantage: Does not cause fluid retention or supine hypertension, making it safer in patients with cardiac dysfunction. 1
• Side effects: Nausea, vomiting, abdominal cramping, sweating, salivation, urinary incontinence (generally manageable). 1

Treatment Goals and Monitoring

The primary therapeutic goal is to minimize postural symptoms and improve functional capacity, NOT to restore normotension. 1, 2 Attempting to normalize standing blood pressure often leads to dangerous supine hypertension. 1

Monitoring Protocol:

• At each follow-up visit: Measure both supine (after 5 minutes rest) and standing blood pressure (at 1 and 3 minutes after standing). 1, 2
• Reassess within 1–2 weeks after medication changes to evaluate efficacy and detect supine hypertension. 1
• When using fludrocortisone: Check electrolytes, BUN, and creatinine periodically due to mineralocorticoid effects. 1

Balancing Supine Hypertension:

All pressor agents (midodrine, droxidopa, fludrocortisone) can precipitate supine hypertension, which can cause end-organ damage. 1, 2 The risk must be balanced against the benefit of reducing orthostatic symptoms and fall risk. 1 Head-of-bed elevation and timing the last dose of midodrine at least 4 hours before bedtime are critical strategies. 1

Special Populations

Diabetic Patients:

• Assess for cardiovascular autonomic neuropathy (CAN) in diabetic patients over 50 years with orthostatic hypotension, as this represents advanced autonomic failure and confers additional mortality risk. 1
• Consider alpha-lipoic acid for painful diabetic neuropathy and potentially beneficial effects on autonomic function. 1

Elderly and Frail Patients:

• For patients aged ≥85 years with moderate-to-severe frailty: Defer blood pressure treatment until office BP ≥140/90 mmHg, and adopt an "as low as reasonably achievable" (ALARA) target rather than strict 130/80 mmHg goals. 1
• When antihypertensive therapy is required: Preferentially use long-acting dihydropyridine calcium channel blockers or RAS inhibitors as first-line agents. 1, 4

Common Pitfalls to Avoid

• Do not simply reduce the dose of offending medications—switch to alternative agents with minimal orthostatic impact. 1
• Do not administer midodrine after 6 PM to avoid nocturnal supine hypertension. 1
• Do not use fludrocortisone in patients with heart failure or supine hypertension. 1
• Do not combine multiple vasodilating agents (ACE inhibitors + calcium channel blockers + diuretics) without careful monitoring. 1
• Do not overlook volume depletion as a contributing factor—assess fluid intake, recent illness, and diuretic use. 1
• Do not withhold ACE inhibitors or ARBs from patients with heart failure, post-MI, diabetes, or chronic kidney disease solely because of orthostatic hypotension—start at low doses with gradual titration and close monitoring. 4