How is orthostatic hypotension managed?

Management of Orthostatic Hypotension

Begin with non-pharmacological interventions and medication review, then add midodrine as first-line pharmacological therapy if symptoms persist, with fludrocortisone reserved for combination therapy or when midodrine is insufficient. 1

Initial Assessment and Reversible Causes

Immediately review and discontinue or switch all medications that worsen orthostatic hypotension rather than simply reducing doses—this is the most critical first step. 1, 2 The most important culprits include:

• Diuretics (the most frequent cause of drug-induced orthostatic hypotension through volume depletion) 1
• Alpha-1 blockers (doxazosin, prazosin, terazosin, tamsulosin—strongly associated with orthostatic hypotension, especially in older adults) 3
• Vasodilators (hydralazine, minoxidil) 3
• Centrally-acting agents (clonidine, methyldopa) 3

For patients requiring continued antihypertensive therapy, switch to long-acting dihydropyridine calcium channel blockers (e.g., amlodipine) or RAS inhibitors (ACE inhibitors/ARBs) as these have minimal impact on orthostatic blood pressure. 3

Evaluate for volume depletion, endocrine disorders (hypothyroidism, adrenal insufficiency), and cardiovascular autonomic neuropathy, particularly in diabetic patients. 1

Non-Pharmacological Management (Implement First for All Patients)

These interventions must be implemented before or alongside any pharmacological therapy:

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

Pharmacological Management

First-Line: Midodrine

Midodrine has the strongest evidence base among pressor agents with three randomized placebo-controlled trials demonstrating efficacy and is FDA-approved specifically for symptomatic orthostatic hypotension. 1, 4

Dosing:

• Start: 2.5-5 mg three times daily 1, 4
• Timing: Last dose must be at least 3-4 hours before bedtime (avoid dosing after 6 PM) to prevent supine hypertension during sleep 1, 4
• Effect: Increases standing systolic BP by 15-30 mmHg for 2-3 hours 1, 4

Mechanism: Alpha-1 adrenergic agonist that increases vascular tone through arteriolar and venous constriction without stimulating cardiac beta-receptors or crossing the blood-brain barrier. 4

Monitoring:

• Check supine blood pressure regularly (most important limiting factor) 1
• May cause slight vagal-mediated heart rate slowing 4
• Use with caution in patients with urinary retention, renal impairment (start at 2.5 mg), or hepatic impairment 4

Contraindications/Cautions:

• Avoid combining with other vasoconstrictors (phenylephrine, pseudoephedrine, ephedrine) without careful BP monitoring 4
• Use cautiously with cardiac glycosides, beta-blockers, or agents that reduce heart rate 4

Second-Line: Fludrocortisone

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

Dosing:

• Start: 0.05-0.1 mg once daily 1
• Titrate: 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

Monitoring:

• Supine hypertension (most important limiting factor) 1
• Electrolytes periodically (can cause hypokalemia through potassium wasting) 1
• Signs of fluid overload (peripheral edema, congestive heart failure) 1

Contraindications:

• Active heart failure or significant cardiac dysfunction 1
• Pre-existing supine hypertension 1
• Severe renal disease where sodium retention would be harmful 1

Evidence Quality: Very low-certainty evidence from small, short-term trials, though widely used in clinical practice. 5

Combination Therapy

For non-responders to monotherapy, combine midodrine and fludrocortisone with careful monitoring for supine hypertension. 1

Alternative Agents

• Droxidopa: FDA-approved, particularly effective for neurogenic orthostatic hypotension in Parkinson's disease, pure autonomic failure, and multiple system atrophy; may reduce falls 1
• Pyridostigmine: Beneficial for refractory orthostatic hypotension with favorable side effect profile (fewer side effects than fludrocortisone); does not cause fluid retention or supine hypertension 1, 3

Treatment Goals and Monitoring

The therapeutic objective is minimizing postural symptoms and improving functional capacity, NOT restoring normotension. 1, 2 Aggressive blood pressure targets may worsen supine hypertension and cause end-organ damage.

Diagnostic Testing:

• Measure BP after 5 minutes lying/sitting, then at 1 and/or 3 minutes after standing 1
• Orthostatic hypotension is defined as ≥20 mmHg systolic or ≥10 mmHg diastolic drop 1

Follow-up Schedule:

• Early review: 24-48 hours after medication initiation 2
• Intermediate follow-up: 1-2 weeks to assess standing heart rate, BP, and symptom improvement 1, 2
• Monitor orthostatic vital signs at each follow-up visit 1

Critical Pitfalls to Avoid

• Do NOT simply reduce the dose of offending medications—switch to alternatives 1, 3
• Do NOT combine multiple vasodilating agents (ACE inhibitors + calcium channel blockers + diuretics) without careful monitoring 1
• Do NOT administer midodrine after 6 PM (risk of supine hypertension during sleep) 1
• Do NOT use fludrocortisone in patients with heart failure or supine hypertension 1
• Do NOT overlook volume depletion as a contributing factor 1
• Do NOT inappropriately withhold ACE inhibitors from patients who would benefit (heart failure, post-MI, diabetes, chronic kidney disease) simply because they have orthostatic hypotension—switch to appropriate alternatives instead 3

Special Populations

Patients with both hypertension and orthostatic hypotension:

• Prefer long-acting dihydropyridine CCBs or RAS inhibitors as first-line antihypertensives 1, 3
• Test for orthostatic hypotension before starting or intensifying any BP-lowering medication 1

Diabetic patients:

• Assess for cardiovascular autonomic neuropathy 1
• Consider alpha-lipoic acid for painful diabetic neuropathy (potentially beneficial for autonomic function) 1

Elderly/frail patients (≥85 years):

• Long-acting dihydropyridine CCBs or RAS inhibitors preferred if antihypertensive therapy needed 1
• Thiazide diuretics often cause orthostatic hypotension and further reduction in renal function 3