What are the best management strategies for a patient with orthostatic hypotension?

Management of Orthostatic Hypotension

Begin with immediate medication review and discontinuation of offending agents, followed by non-pharmacological measures (fluid/salt expansion, compression garments, physical countermaneuvers), and reserve pharmacological therapy with midodrine or fludrocortisone for patients whose symptoms remain considerably life-impairing despite these initial interventions. 1

Step 1: Identify and Eliminate Causative Medications

Drug-induced autonomic failure is the most frequent cause of orthostatic hypotension, making medication review the absolute first priority. 1

• Discontinue or switch (not dose-reduce) the following high-risk medications: 1, 2

  • Diuretics and vasodilators are the most important culprits 1
  • Alpha-1 blockers (doxazosin, prazosin, terazosin, tamsulosin) are strongly associated with orthostatic hypotension, especially in older adults 2
  • Centrally-acting antihypertensives (clonidine, methyldopa) 2
  • Psychotropic medications 1

• For patients requiring continued antihypertensive therapy, switch to long-acting dihydropyridine calcium channel blockers (amlodipine) or RAS inhibitors (ACE inhibitors/ARBs), which have minimal impact on orthostatic blood pressure 2

• Avoid alcohol, as it causes both direct autonomic dysfunction and volume depletion 1

Step 2: Implement Non-Pharmacological Measures

These interventions should be implemented simultaneously and are often sufficient for milder cases: 1, 3

Volume Expansion

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

Reduce Venous Pooling

• Use waist-high compression stockings (30-40 mmHg) and abdominal binders to reduce venous pooling 1
• Teach physical countermaneuvers: leg crossing, squatting, stooping, and muscle tensing during symptomatic episodes—particularly effective in patients under 60 years with prodromal symptoms 1

Postural Modifications

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

Dietary and Activity Modifications

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

Step 3: Pharmacological Treatment (When Non-Pharmacological Measures Fail)

Pharmacological treatment should only be considered when non-pharmacological measures fail to adequately control symptoms and the patient's life remains considerably impaired. 1, 4

First-Line: Midodrine

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

• Mechanism: Alpha-1 adrenergic agonist that increases vascular tone through arteriolar and venous constriction without stimulating cardiac beta-receptors 4
• Dosing: Start at 2.5-5 mg three times daily, titrate up to 10 mg three times daily based on response 1
• Effect: Increases standing systolic BP by 15-30 mmHg for 2-3 hours 1, 4
• 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
• FDA indication: Approved specifically for symptomatic orthostatic hypotension, but should be continued only for patients who report significant symptomatic improvement 4

Second-Line: Fludrocortisone

If midodrine provides insufficient symptom control, add fludrocortisone. 1

• Mechanism: Mineralocorticoid that increases plasma volume through sodium retention and vessel wall effects 1
• Dosing: Start at 0.05-0.1 mg once daily, titrate individually to 0.1-0.3 mg daily (maximum 1.0 mg daily) 1
• Monitoring requirements: 1
  • Check for supine hypertension (most important limiting factor)
  • Monitor electrolytes periodically for hypokalemia
  • Assess for peripheral edema and congestive heart failure
• Contraindications: Active heart failure, severe renal disease, pre-existing supine hypertension 1

Alternative Agents for Refractory Cases

• 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 in elderly patients with fewer side effects than alternatives, particularly in neurogenic orthostatic hypotension 1, 5
• Combination therapy: Consider midodrine plus fludrocortisone for non-responders to monotherapy 1

Step 4: Monitoring and Treatment Goals

Diagnostic Measurement

• Measure blood pressure after 5 minutes of sitting/lying, then at 1 and/or 3 minutes after standing to document orthostatic changes 1

Treatment Objectives

• The therapeutic goal is minimizing postural symptoms and improving functional capacity, NOT restoring normotension 1, 5
• Balance the benefits of increasing standing blood pressure against the risk of worsening supine hypertension 1

Follow-Up Schedule

• Reassess within 1-2 weeks after medication changes 1
• Monitor for supine hypertension development at each visit, which can cause end-organ damage 1
• Discontinue midodrine immediately if supine hypertension persists 4

Special Considerations

Patients with Concurrent Hypertension and Orthostatic Hypotension

• Use long-acting dihydropyridine calcium channel blockers or RAS inhibitors as first-line therapy 1, 2
• Switch medications that worsen orthostatic hypotension to alternatives rather than dose-reducing 1

Patients with Bradycardia

• Midodrine may cause slight vagal-mediated heart rate slowing, but benefits usually outweigh this concern 5
• Cardiac pacing is NOT recommended unless there is documented intrinsic sinus node dysfunction causing symptomatic bradyarrhythmias independent of postural changes 5

Diabetic Patients

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

Common Pitfalls to Avoid

• Do not simply reduce the dose of offending medications—switch to alternatives 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 vasoconstrictors without careful blood pressure monitoring 5
• Do not overlook volume depletion as a contributing factor 1
• Do not inappropriately withhold beneficial medications (ACE inhibitors for heart failure, post-MI, diabetes, or chronic kidney disease) simply because orthostatic hypotension is present 2