What is the appropriate workup and treatment for a patient presenting with orthostatic hypotension?

Orthostatic Hypotension Workup

Diagnostic Confirmation

Measure blood pressure after 5 minutes of supine rest, then at 1 minute and 3 minutes after standing, with the arm maintained at heart level throughout all measurements. 1, 2 Orthostatic hypotension is confirmed when systolic BP drops ≥20 mmHg OR diastolic BP drops ≥10 mmHg within 3 minutes of standing. 1, 2

Measurement Technique Details

• Use a validated, calibrated BP device with appropriate cuff size (bladder encircles 80% of arm circumference). 1, 2
• Supine position is more sensitive than sitting, though sitting is more practical in clinical settings. 2
• Patients should avoid caffeine, exercise, and smoking for 30 minutes before measurement. 2
• Record both systolic and diastolic BP plus heart rate at each time point. 2
• The 1-minute measurement is equally important as the 3-minute measurement for detecting early orthostatic hypotension. 1

When to Screen

• All patients over 50 years old periodically. 2
• Elderly patients (≥65 years) and diabetic patients before starting or intensifying BP-lowering medications. 1, 2
• Patients with symptoms: dizziness, lightheadedness, postural unsteadiness, fainting, blurred vision, weakness, or syncope. 2, 3
• Patients taking medications that may cause orthostatic hypotension (diuretics, vasodilators, alpha-blockers, beta-blockers, nitrates). 2
• Patients with Parkinson's disease (high risk for neurogenic orthostatic hypotension). 2

Identify Reversible Causes

The first step is evaluating for reversible causes, with medication effects and volume depletion being the most common culprits. 4

Medication Review

• Drug-induced autonomic failure is the most frequent cause of orthostatic hypotension. 4
• Discontinue or switch (not just reduce dose) medications that worsen orthostatic hypotension: 4
  • Diuretics and vasodilators (most important culprits) 4
  • Alpha-1 blockers (doxazosin, prazosin, terazosin, tamsulosin) 4
  • Centrally acting agents (clonidine, methyldopa) 4
  • Direct vasodilators (hydralazine, minoxidil) 4
  • Psychotropic drugs 4
• Avoid alcohol, which causes both autonomic neuropathy and central volume depletion. 4

Volume Status Assessment

• Evaluate for dehydration or blood loss. 4, 3
• Check for hypovolemia from any cause. 5

Underlying Medical Conditions

• Assess for cardiovascular autonomic neuropathy in diabetic patients. 4
• Evaluate for endocrine disorders (adrenal insufficiency, hypothyroidism). 4
• Consider cardiac insufficiency and impaired venous return. 5
• In older adults with autonomic dysfunction, consider cardiac amyloidosis in the differential. 4

Special Assessments

• Check for post-prandial hypotension (occurs after meals). 4, 6
• Assess for supine hypertension (common in neurogenic orthostatic hypotension). 4, 6
• Evaluate renal and hepatic function before initiating pharmacologic therapy. 7

Classification: Neurogenic vs Non-Neurogenic

Determine if orthostatic hypotension is neurogenic (autonomic failure) or non-neurogenic based on heart rate response and underlying etiology. 8, 6

• Neurogenic: Inadequate heart rate increase (<15 bpm) with standing; causes include Parkinson's disease, pure autonomic failure, multiple system atrophy, diabetic neuropathy. 4, 8
• Non-neurogenic: Appropriate heart rate increase (>15 bpm); causes include medications, volume depletion, cardiac insufficiency. 8, 5

Treatment Algorithm

Step 1: Non-Pharmacologic Management (Offer to ALL Patients)

Implement non-pharmacologic measures first, as they form the foundation of treatment regardless of severity. 4, 8

Dietary Modifications

• Increase fluid intake to 2-3 liters daily (unless contraindicated by heart failure). 4
• Increase salt intake to 6-9 grams daily (unless contraindicated). 4
• Eat smaller, more frequent meals to reduce post-prandial hypotension. 4
• Acute water ingestion ≥480 mL provides temporary relief with peak effect at 30 minutes. 4

Physical Maneuvers

• Teach leg crossing, squatting, stooping, and muscle tensing during symptomatic episodes (particularly effective in patients <60 years with prodromal symptoms). 4
• Advise gradual staged movements with postural changes. 4

Compression Garments

• Use waist-high compression stockings (30-40 mmHg) and abdominal binders to reduce venous pooling. 4

Sleep Position

• Elevate head of bed by 10 degrees during sleep to prevent nocturnal polyuria, maintain favorable fluid distribution, and ameliorate nocturnal hypertension. 4

Exercise

• Encourage physical activity and exercise to avoid deconditioning, which worsens orthostatic intolerance. 4

Step 2: Pharmacologic Treatment (When Non-Pharmacologic Measures Fail)

The therapeutic goal is minimizing postural symptoms and improving functional capacity, NOT restoring normotension. 4, 7

First-Line Medications

Midodrine has the strongest evidence base among pressor agents, with three randomized placebo-controlled trials demonstrating efficacy. 4, 7

• Midodrine: Start 2.5-5 mg three times daily, titrate up to 10 mg three times daily. 4, 7
  • Alpha-1 agonist that increases standing systolic BP by 15-30 mmHg for 2-3 hours. 4, 7
  • Critical: Last dose must be at least 3-4 hours before bedtime (not after 6 PM) to prevent supine hypertension during sleep. 4, 7
  • FDA-approved for symptomatic orthostatic hypotension. 7
  • Monitor for supine hypertension (BP >200 mmHg systolic can occur). 7

Alternative first-line options: 4

• Fludrocortisone: Start 0.05-0.1 mg daily, titrate to 0.1-0.3 mg daily (maximum 1.0 mg daily). 4

  • Acts through sodium retention and vessel wall effects. 4
  • Monitor for supine hypertension, hypokalemia, congestive heart failure, and peripheral edema. 4
  • Contraindicated in active heart failure, significant cardiac dysfunction, severe renal disease, and pre-existing supine hypertension. 4
  • Check electrolytes periodically due to potassium wasting. 4

• Droxidopa: FDA-approved, particularly effective for neurogenic orthostatic hypotension in Parkinson's disease, pure autonomic failure, and multiple system atrophy. 4

  • May reduce falls. 4

Second-Line Medication (For Refractory Cases)

Pyridostigmine is beneficial for refractory orthostatic hypotension, particularly in elderly patients with supine hypertension, as it does not worsen supine BP. 4

• Dose: 60 mg orally three times daily (maximum 600 mg daily). 4
• Mechanism: Inhibits acetylcholinesterase, enhancing ganglionic sympathetic transmission. 4
• Favorable side effect profile compared to alternatives. 4
• Common side effects: nausea, vomiting, abdominal cramping, sweating, salivation, urinary incontinence (generally manageable). 4
• Preferred when supine hypertension is a concern, as it does not cause fluid retention or worsen supine BP. 4

Combination Therapy

For non-responders to monotherapy, consider combination therapy with midodrine and fludrocortisone. 4

• These agents work through different mechanisms (alpha-1 adrenergic stimulation vs sodium retention), making them complementary. 4
• Ensure adequate salt (6-10g daily) and fluid (2-3L daily) intake as adjunctive measures. 4

Step 3: Special Considerations

Patients with Concurrent Hypertension and Orthostatic Hypotension

Switch (not just reduce) BP-lowering medications that worsen orthostatic hypotension to long-acting dihydropyridine calcium channel blockers or RAS inhibitors as first-line therapy. 4

• Avoid alpha-1 blockers, which are explicitly contraindicated. 4
• Avoid combining multiple vasodilating agents (ACE inhibitors + calcium channel blockers + diuretics) without careful monitoring. 4
• Asymptomatic orthostatic hypotension during treatment should not trigger automatic down-titration, as intensive BP lowering may actually reduce orthostatic hypotension risk by improving baroreflex function. 4

Frail Elderly (≥85 Years)

Defer BP-lowering treatment until office BP ≥140/90 mmHg in patients ≥85 years with pre-treatment symptomatic orthostatic hypotension, moderate-to-severe frailty, or limited life expectancy. 4

• Target "as low as reasonably achievable" (ALARA principle) rather than strict 130/80 mmHg. 4

Monitoring Requirements

Measure both supine and standing BP at each follow-up visit to detect treatment-induced supine hypertension. 4

• Reassess within 1-2 weeks after medication changes. 4
• Monitor orthostatic vital signs at each follow-up visit. 4
• Check electrolytes, BUN, and creatinine if using fludrocortisone. 4
• Balance benefits of increasing standing BP against risk of worsening supine hypertension. 4

Critical Pitfalls to Avoid

• Do not simply reduce the dose of offending medications—switch to alternative therapy. 4
• Do not administer midodrine after 6 PM. 4
• Do not use fludrocortisone in patients with heart failure or supine hypertension. 4
• Do not overlook volume depletion as a contributing factor. 4
• Do not measure BP only at 3 minutes—the 1-minute measurement is equally important. 1
• Do not withhold treatment based on age alone in elderly patients. 4