What are the management options for a patient with orthostatic hypotension?

Management of Orthostatic Hypotension

Begin with non-pharmacological measures as first-line therapy, and add midodrine or fludrocortisone only when lifestyle modifications fail to adequately control symptoms—the therapeutic goal is minimizing postural symptoms, not restoring normotension. 1

Initial Assessment and Reversible Causes

• Confirm orthostatic hypotension by measuring blood pressure after 5 minutes of lying/sitting, then at 1 and 3 minutes after standing (≥20 mmHg systolic or ≥10 mmHg diastolic drop confirms diagnosis) 1, 2
• Immediately discontinue or switch medications that worsen orthostatic hypotension rather than simply reducing doses—drug-induced autonomic failure is the most frequent cause of orthostatic hypotension 1, 3
• Priority medications to discontinue: diuretics, alpha-1 blockers (doxazosin, prazosin, terazosin), vasodilators, centrally-acting antihypertensives (clonidine, methyldopa), and psychotropic drugs 1, 3
• Evaluate for volume depletion, anemia, and endocrine disorders as reversible contributors 1

Non-Pharmacological Management (Implement All Simultaneously)

Volume Expansion

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

Postural Modifications

• Teach gradual staged movements with postural changes—avoid rapid standing 1, 2
• Elevate head of bed by 10 degrees during sleep to prevent nocturnal polyuria, maintain favorable fluid distribution, and reduce supine hypertension 1
• Implement physical counter-maneuvers during symptom onset: leg crossing, squatting, stooping, and muscle tensing (particularly effective in patients under 60 years with prodromal symptoms) 1

Compression Therapy

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

Dietary Modifications

• Eat smaller, more frequent meals to reduce post-prandial hypotension 4, 1

Physical Conditioning

• Encourage physical activity and exercise to avoid deconditioning, which exacerbates orthostatic intolerance 4, 1

Pharmacological Management (When Non-Pharmacological Measures Fail)

First-Line Pharmacological Agents

Midodrine (Strongest Evidence Base)

• Midodrine is the first-line pharmacological agent with FDA approval and the strongest evidence from three randomized placebo-controlled trials 1, 5
• Start at 2.5-5 mg three times daily, with first dose before arising 1, 2
• Critical timing: last dose must be taken at least 3-4 hours before bedtime (not after 6 PM) to prevent supine hypertension during sleep 1, 5
• Increases standing systolic BP by 15-30 mmHg for 2-3 hours 1, 5
• Mechanism: alpha-1 adrenergic agonist causing arteriolar and venous constriction 5
• Titrate individually up to 10 mg three times daily based on response 1

Fludrocortisone (Alternative First-Line)

• Start at 0.05-0.1 mg once daily, titrate to 0.1-0.3 mg daily (maximum 1.0 mg daily) 4, 1
• Acts through sodium retention and vessel wall effects 4, 1
• Monitor for supine hypertension (most important limiting factor), hypokalemia, congestive heart failure, and peripheral edema 4, 1
• Contraindicated in patients with active heart failure, severe renal disease, or pre-existing supine hypertension 1
• Check electrolytes, BUN, and creatinine periodically 1

Second-Line and Combination Therapy

Droxidopa

• FDA-approved for neurogenic orthostatic hypotension, particularly effective in Parkinson's disease, pure autonomic failure, and multiple system atrophy 4, 1
• May reduce falls in these populations 1

Combination Therapy

• For non-responders to monotherapy, combine midodrine and fludrocortisone (complementary mechanisms: alpha-1 stimulation plus sodium retention) 1

Pyridostigmine (Refractory Cases)

• Consider for elderly patients refractory to first-line treatments 1
• Favorable side effect profile compared to alternatives—does not cause supine hypertension or fluid retention 1, 3
• Common side effects: nausea, vomiting, abdominal cramping, sweating, salivation, urinary incontinence 1

Special Considerations for Hypertensive Patients with Orthostatic Hypotension

• Switch to long-acting dihydropyridine calcium channel blockers or RAS inhibitors as first-line antihypertensives—these have minimal impact on orthostatic blood pressure 1, 3
• Avoid beta-blockers unless compelling indications exist 1, 3
• Use shorter-acting antihypertensives at bedtime (guanfacine, clonidine, isradipine, atenolol, metoprolol tartrate, or enalapril) to manage supine hypertension 4

Critical Monitoring Parameters

• Measure blood pressure in supine, sitting, and standing positions at each follow-up visit 1, 2
• Monitor for supine hypertension development—this is the most important limiting factor and can cause end-organ damage 1, 2
• Reassess within 1-2 weeks after medication changes 1
• Continue pharmacological treatment only in patients who report significant symptomatic improvement 5

Common Pitfalls to Avoid

• Do not simply reduce doses of offending medications—switch to alternatives instead 1, 3
• Do not administer midodrine after 6 PM 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 1
• Do not aim to restore normotension—the goal is minimizing postural symptoms and improving functional capacity 1, 2