How do you manage a patient with orthostatic hypotension?

Management of Orthostatic Hypotension

Start with non-pharmacological interventions immediately, and if symptoms persist after 1-2 weeks, initiate midodrine as first-line pharmacological therapy, with fludrocortisone as an alternative or addition for refractory cases. 1

Confirm the Diagnosis

• Measure blood pressure after 5 minutes of lying or sitting, then at 1 and 3 minutes after standing—a drop of ≥20 mmHg systolic or ≥10 mmHg diastolic confirms orthostatic hypotension. 1, 2
• Document symptoms during testing: dizziness, lightheadedness, blurred vision, weakness, or syncope indicate symptomatic orthostatic hypotension requiring treatment. 3, 4

Identify and Address Reversible Causes First

Drug-induced autonomic failure is the most frequent cause of orthostatic hypotension—review all medications immediately. 1

• Discontinue or switch (not just reduce the dose) medications that worsen orthostatic hypotension: 1

  • Diuretics (most common culprit) 1
  • Alpha-1 blockers (doxazosin, prazosin, terazosin, tamsulosin) 1
  • Vasodilators (hydralazine, minoxidil) 1
  • Centrally acting agents (clonidine, methyldopa) 1
  • Beta-blockers (unless compelling indication exists) 1

• Switch to alternative antihypertensive therapy if blood pressure control is needed: 1

  • Long-acting dihydropyridine calcium channel blockers (amlodipine) are preferred first-line agents 1
  • RAS inhibitors (ACE inhibitors or ARBs) are acceptable alternatives 1

• Assess for volume depletion from dehydration, blood loss, or inadequate fluid intake. 1, 3

• Avoid alcohol, which causes both autonomic neuropathy and central volume depletion. 1

Non-Pharmacological Management (Implement for ALL Patients)

These interventions should be started immediately and continued even if pharmacological therapy is added. 1

Fluid and Salt Management

• 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—use liberalized dietary sodium rather than salt tablets to minimize gastrointestinal side effects. 1, 5
• 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—these maneuvers are particularly effective in patients under 60 years with prodromal symptoms. 1
• Instruct on gradual staged movements with postural changes to prevent sudden blood pressure drops. 1

Compression Garments

• Apply waist-high compression stockings (30-40 mmHg) and abdominal binders to reduce venous pooling in lower extremities. 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
• Recommend smaller, more frequent meals to reduce post-prandial hypotension. 1
• Encourage physical activity and exercise to avoid deconditioning, which worsens orthostatic intolerance. 1
• Avoid prolonged standing, hot environments, and large meals. 1

Pharmacological Management (When Non-Pharmacological Measures Fail)

The therapeutic goal is minimizing postural symptoms and improving functional capacity, NOT restoring normotension. 1, 6

First-Line: Midodrine

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

• Starting dose: 2.5-5 mg orally three times daily 1, 6
• Mechanism: Alpha-1 adrenergic agonist that increases standing systolic BP by 15-30 mmHg for 2-3 hours 1, 6
• Titration: Individually tailor up to 10 mg three times daily based on response 1

Critical timing considerations: 1, 6

• Take first dose in the morning before rising 1
• Avoid doses after 6 PM to prevent supine hypertension during sleep 1, 6
• Last dose must be at least 3-4 hours before bedtime 1

Monitoring requirements: 1, 6

• Monitor supine blood pressure regularly—supine hypertension is the most important limiting factor 1
• Use with caution in older males due to potential urinary retention (alpha-adrenergic effects on bladder neck) 6
• Avoid concomitant use with other vasoconstrictors (phenylephrine, pseudoephedrine, ephedrine) 6

Second-Line or Alternative: Fludrocortisone

• Starting dose: 0.05-0.1 mg once daily 1
• Titration: Individually adjust to 0.1-0.3 mg daily based on response (maximum 1.0 mg daily) 1
• Mechanism: Mineralocorticoid that acts through sodium retention and vessel wall effects 1

Contraindications: 1

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

Monitoring requirements: 1

• Check electrolytes periodically—mineralocorticoid effects cause potassium wasting 1
• Monitor for supine hypertension, hypokalemia, congestive heart failure, and peripheral edema 1
• Ensure adequate salt intake (6-9 g daily) as adjunctive measure 1

Evidence quality note: Fludrocortisone has only very low-certainty evidence from small, short-term trials, but remains widely used in clinical practice. 1

Combination Therapy for Refractory Cases

• For non-responders to monotherapy, consider combining midodrine and fludrocortisone—they work through different mechanisms (alpha-1 adrenergic stimulation vs. sodium retention). 1
• When adding fludrocortisone to midodrine, start with the lowest dose (0.05-0.1 mg daily) and monitor closely for supine hypertension. 1

Third-Line: Droxidopa

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

Refractory Cases: Pyridostigmine

Pyridostigmine is beneficial for elderly patients with refractory orthostatic hypotension who have not responded to first-line treatments, with a favorable side effect profile. 1

• Indication: Neurogenic orthostatic hypotension refractory to midodrine and fludrocortisone 1
• Starting dose: 60 mg orally three times daily (maximum 600 mg daily) 1
• Mechanism: Acetylcholinesterase inhibitor that enhances ganglionic sympathetic transmission 1
• Advantage: Does not worsen supine hypertension—preferred when supine hypertension is a concern 1
• Side effects: Nausea, vomiting, abdominal cramping, sweating, salivation, urinary incontinence (generally manageable) 1

Monitoring and Follow-Up

• Reassess within 1-2 weeks after initiating treatment or medication changes. 1
• Measure orthostatic vital signs at each visit using the standardized protocol (5 minutes lying/sitting, then 1 and 3 minutes standing). 1
• Monitor both standing and supine blood pressure to detect treatment-induced supine hypertension. 1
• Balance the risk of falls and injury from orthostatic hypotension against the risk of supine hypertension from treatment. 1

Critical Pitfalls to Avoid

• Do not simply reduce the dose of offending medications—switch to alternative therapy instead. 1
• 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
• Asymptomatic orthostatic hypotension during hypertension treatment should not trigger automatic down-titration of therapy—intensive blood pressure lowering may actually reduce the risk of orthostatic hypotension by improving baroreflex function. 7
• Do not overlook volume depletion as a contributing factor. 1

Special Considerations

Patients with Concurrent Hypertension and Orthostatic Hypotension

• Long-acting dihydropyridine calcium channel blockers or RAS inhibitors are first-line therapy. 1
• Avoid alpha-1 blockers, which are explicitly associated with orthostatic hypotension in older adults. 1

Older Adults (≥85 years) with Frailty

• Defer blood pressure-lowering treatment until office BP ≥140/90 mmHg in patients with pre-treatment symptomatic orthostatic hypotension, moderate-to-severe frailty, or limited life expectancy. 1
• Target "as low as reasonably achievable" (ALARA principle) rather than strict 130/80 mmHg. 1

Diabetic Patients

• Assess for cardiovascular autonomic neuropathy. 1
• Consider alpha-lipoic acid for painful diabetic neuropathy, which may be beneficial for autonomic function. 1