How is orthostatic hypotension managed?

Management of Orthostatic Hypotension

Begin with immediate medication review and discontinuation of culprit drugs, followed by non-pharmacological interventions (fluid/salt expansion, compression garments, physical maneuvers), and add midodrine as first-line pharmacological therapy if symptoms persist despite these measures. 1

Initial Assessment and Reversible Causes

Medication-induced autonomic failure is the most frequent cause of orthostatic hypotension. 1 Immediately review and discontinue or switch blood pressure-lowering medications that worsen orthostatic hypotension—switching to alternative therapy is essential, not dose reduction. 1, 2

High-Risk Medications to Discontinue or Switch:

• Diuretics and vasodilators are the most important culprits causing drug-induced orthostatic hypotension 1, 3
• Alpha-1 blockers (doxazosin, prazosin, terazosin, tamsulosin) are strongly associated with orthostatic hypotension, especially in older adults 1, 3
• ACE inhibitors and calcium channel blockers should be switched to long-acting dihydropyridine CCBs or RAS inhibitors if antihypertensive therapy remains necessary 1, 3
• Centrally-acting drugs (clonidine, methyldopa) can cause orthostatic hypotension 3

Measure blood pressure after 5 minutes of sitting/lying, then at 1 and/or 3 minutes after standing to confirm diagnosis. 1

Non-Pharmacological Management (Implement First)

All patients must receive non-pharmacological interventions before or alongside pharmacological therapy. 1, 2

Fluid and Salt Expansion:

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

Physical Countermeasures:

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

Lifestyle Modifications:

• Elevate the head of bed by 10 degrees during sleep to prevent nocturnal polyuria, maintain favorable fluid distribution, and ameliorate nocturnal hypertension 1
• Eat smaller, more frequent meals to reduce post-prandial hypotension 1
• Encourage physical activity and exercise to avoid deconditioning 1
• Teach gradual staged movements with postural change 1

Pharmacological Management

Consider pharmacological treatment when non-pharmacological measures fail to adequately control symptoms. 1 The therapeutic goal is minimizing postural symptoms and improving functional capacity, NOT restoring normotension. 1

First-Line: Midodrine

Midodrine is the first-line pharmacological agent with the strongest evidence base (three randomized placebo-controlled trials) and is FDA-approved specifically for symptomatic orthostatic hypotension. 1, 4

Dosing:

• Start at 2.5-5 mg three times daily 1, 4
• The last dose must be at least 3-4 hours before bedtime to prevent supine hypertension during sleep 1, 2, 4
• Can increase 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 1, 4

Critical Monitoring:

• Monitor for supine hypertension (BP >200 mmHg systolic can occur)—this is the most important limiting factor 1, 4
• May cause slight vagal-mediated heart rate slowing 2, 4
• Avoid combining with other vasoconstrictors (phenylephrine, pseudoephedrine, ephedrine) without careful BP monitoring 1, 4

Second-Line: Fludrocortisone

Add fludrocortisone if midodrine provides insufficient symptom control. 1

Dosing:

• Start at 0.05-0.1 mg once daily 1
• Titrate individually to 0.1-0.3 mg daily 1
• Maximum dose 1.0 mg daily 1

Mechanism: Mineralocorticoid that increases plasma volume through sodium retention and vessel wall effects 1

Contraindications:

• Avoid in active heart failure or significant cardiac dysfunction 1
• Avoid in pre-existing supine hypertension 1
• Avoid in severe renal disease where sodium retention would be harmful 1

Critical Monitoring:

• Monitor for supine hypertension—the most important limiting factor 1
• Check electrolytes periodically for hypokalemia due to mineralocorticoid effects 1
• Monitor for peripheral edema and congestive heart failure 1

Alternative First-Line Options:

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

Refractory Cases:

For patients refractory to monotherapy, consider combination therapy with midodrine and fludrocortisone. 1

Pyridostigmine may be beneficial in neurogenic orthostatic hypotension refractory to other treatments, with a favorable side effect profile (does not cause fluid retention or supine hypertension). 1, 3

Special Populations

Patients with Both Hypertension and Orthostatic Hypotension:

• Long-acting dihydropyridine calcium channel blockers or RAS inhibitors are preferred first-line agents 1, 3
• These have minimal impact on orthostatic blood pressure 3

Diabetic Patients:

• Assess for cardiovascular autonomic neuropathy 1
• Consider pyridostigmine, which does not cause fluid retention or supine hypertension 3

Patients with Bradycardia:

• Cardiac pacing is NOT recommended unless there is documented intrinsic sinus node dysfunction causing symptomatic bradyarrhythmias independent of postural changes 2
• Midodrine remains first-line despite potential for slight vagal-mediated heart rate slowing—benefits of improved BP usually outweigh this concern 2

Monitoring and Follow-Up

Early review at 24-48 hours after medication initiation, with intermediate follow-up at 1-2 weeks to assess standing heart rate, blood pressure, and symptom improvement. 2

Measure blood pressure after 5 minutes lying/sitting, then at 1 and 3 minutes after standing to document orthostatic changes and monitor for supine hypertension development. 1

Continue midodrine only for patients who report significant symptomatic improvement. 4

Common Pitfalls to Avoid

• Never simply reduce the dose of culprit medications—switch to alternatives instead 1
• Never give the last dose of midodrine after 6 PM to prevent supine hypertension during sleep 1, 4
• Never aggressively target normotension—this worsens supine hypertension and increases risk of end-organ damage 1
• Never use fludrocortisone in patients with heart failure or supine hypertension 1
• Never combine multiple vasoconstrictors without careful blood pressure monitoring 1, 4