What is the appropriate management of orthostatic hypotension?

Management of Orthostatic Hypotension

Begin by identifying and eliminating reversible causes—particularly medications—then implement non-pharmacological measures, and only add pharmacological therapy when symptoms persist despite these interventions. 1

Diagnostic Confirmation

• Measure blood pressure after 5 minutes of lying or sitting, then at 1 and 3 minutes after standing 1, 2
• Orthostatic hypotension is defined as a sustained decrease in systolic BP ≥20 mmHg or diastolic BP ≥10 mmHg within 3 minutes of standing 2, 3
• In patients with supine hypertension, use a systolic BP drop ≥30 mmHg as the diagnostic threshold 2
• Assess for neurogenic versus non-neurogenic causes by observing heart rate response: neurogenic orthostatic hypotension shows a blunted heart rate increase (usually <10 bpm) 2

Step 1: Identify and Eliminate Reversible Causes

Drug-induced autonomic failure is the most frequent cause of orthostatic hypotension—discontinue or switch offending medications rather than simply reducing doses. 1, 2

High-Priority Medications to Discontinue:

• Alpha-1 blockers (doxazosin, prazosin, terazosin, tamsulosin) are the most problematic agents and should be stopped immediately 1, 4
• Diuretics and vasodilators are the most important culprits causing drug-induced orthostatic hypotension 1, 2
• Centrally-acting agents (clonidine, methyldopa) should be discontinued 1, 4
• Beta-blockers should be avoided unless compelling indications exist 1, 4
• Avoid combining multiple vasodilating agents (ACE inhibitors + calcium channel blockers + diuretics) 1

Preferred Antihypertensive Alternatives:

• Long-acting dihydropyridine calcium channel blockers (amlodipine) or RAS inhibitors (ACE inhibitors/ARBs) are first-line agents with minimal impact on orthostatic blood pressure 1, 4
• These agents are particularly appropriate for elderly or frail patients requiring continued antihypertensive therapy 4

Other Reversible Causes:

• Assess for volume depletion, acute blood loss, or hypovolemia 1, 2
• Discontinue alcohol, which causes both autonomic neuropathy and central volume depletion 1

Step 2: Non-Pharmacological Management (First-Line for All Patients)

Non-pharmacological measures are the cornerstone of management and must be implemented before or alongside any pharmacological therapy. 1, 5

Fluid and Salt Intake:

• Increase fluid intake to 2-3 liters daily (unless contraindicated by heart failure) 1
• Increase salt intake to 6-9 grams daily (unless contraindicated) 1
• Acute water ingestion of ≥480 mL provides temporary relief with peak effect at 30 minutes 1

Physical Counter-Maneuvers:

• Teach leg crossing, squatting, stooping, and muscle tensing during symptomatic episodes—particularly effective in patients under 60 years with prodromal symptoms 1
• Implement gradual staged movements with postural changes 1

Compression Garments:

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

Positional Strategies:

• Elevate the head of the bed by 10 degrees during sleep to prevent nocturnal polyuria, maintain favorable fluid distribution, and ameliorate nocturnal hypertension 1

Dietary Modifications:

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

Physical Activity:

• Encourage regular physical activity and exercise to avoid deconditioning, which worsens orthostatic intolerance 1

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

The therapeutic goal is minimizing postural symptoms and improving functional capacity, NOT restoring normotension. 1, 2

First-Line Pharmacological Options:

Midodrine (Preferred First-Line Agent)

• Midodrine has the strongest evidence base among pressor agents, with three randomized placebo-controlled trials demonstrating efficacy 1, 6
• Start at 2.5-5 mg three times daily, titrate up to 10 mg three times daily based on response 1, 6
• Increases standing systolic BP by 15-30 mmHg for 2-3 hours 1
• 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
• FDA-approved for symptomatic orthostatic hypotension 6
• Monitor for supine hypertension (BP >200 mmHg systolic is possible) 6

Fludrocortisone (Alternative or Adjunctive First-Line)

• Start at 0.05-0.1 mg once daily, titrate to 0.1-0.3 mg daily (maximum 1.0 mg daily) 1, 2
• Acts through sodium retention and vessel wall effects 1
• Contraindications: Active heart failure, significant cardiac dysfunction, severe renal disease, or pre-existing supine hypertension 1
• Monitor for supine hypertension (most important limiting factor), hypokalemia, congestive heart failure, and peripheral edema 1
• Evidence quality is limited, with only very low-certainty evidence from small, short-term trials 1
• Fludrocortisone is associated with adverse events including renal and cardiac failure and increased risk of all-cause hospitalization 5

Droxidopa (Particularly for Neurogenic Orthostatic Hypotension)

• FDA-approved for neurogenic orthostatic hypotension due to Parkinson's disease, pure autonomic failure, and multiple system atrophy 1, 7
• Demonstrated statistically significant mean 0.9 unit decrease in dizziness at Week 1 versus placebo (P=0.028), but effect did not persist beyond Week 1 7
• Effectiveness beyond 2 weeks is uncertain; patients should be evaluated periodically to determine whether droxidopa is continuing to provide benefit 7
• May reduce falls in neurogenic orthostatic hypotension 1

Combination Therapy for Refractory Cases:

• For non-responders to monotherapy, combine midodrine with fludrocortisone, as they act via complementary mechanisms (vascular constriction plus sodium retention) 1
• Ensure adequate salt (6-10 grams daily) and fluid (2-3 liters daily) intake as adjunctive measures 1

Second-Line Options for Refractory Cases:

Pyridostigmine

• Preferred agent when supine hypertension is a concern because it does not worsen supine BP 1
• Start at 60 mg orally three times daily (maximum 600 mg daily) 1
• Works by inhibiting acetylcholinesterase, enhancing ganglionic sympathetic transmission 1
• Does not cause fluid retention, making it safer in patients with underlying cardiac dysfunction 1
• Common side effects: nausea, vomiting, abdominal cramping, sweating, salivation, urinary incontinence 1
• Supported by 2017 ACC/AHA/HRS guidelines for neurogenic orthostatic hypotension refractory to other treatments 1

Monitoring and Follow-Up

• Measure both supine and standing BP at each visit to detect treatment-induced supine hypertension 1
• Reassess patients within 1-2 weeks after medication changes 1, 2
• Check electrolytes, BUN, and creatinine if fludrocortisone is used 1
• Monitor orthostatic vital signs at each follow-up visit 1
• Balance the risk of falls and injury from postural hypotension against cardiovascular protection 1

Special Populations

Elderly and Frail Patients:

• Defer blood pressure-lowering treatment in patients ≥85 years with orthostatic hypotension, moderate-to-severe frailty, or limited life expectancy until BP is >140/90 mmHg 1
• Asymptomatic orthostatic hypotension during hypertension treatment should not trigger automatic down-titration, as intensive BP lowering may actually reduce the risk of orthostatic hypotension by improving baroreflex function 1

Diabetic Patients:

• In patients with diabetes aged >50 years, orthostatic hypotension warrants evaluation for cardiovascular autonomic neuropathy (CAN) using cardiac autonomic reflex tests (CARTs) 1
• CAN is a Level A evidence risk marker for all-cause mortality 1
• Routine screening for CAN (including orthostatic vital signs and CARTs) is advised for all diabetic patients over 50 years, even when asymptomatic 1

Common Pitfalls to Avoid

• Do not simply reduce the dose of offending medications—switch to alternative agents 1, 2
• Do not administer midodrine after 6 PM 1
• Do not use fludrocortisone in patients with heart failure or supine hypertension 1
• Do not overlook volume depletion as a contributing factor 1
• Do not combine multiple vasodilating agents without careful monitoring 1
• Do not withhold ACE inhibitors from patients who would benefit (heart failure, post-MI, diabetes, chronic kidney disease) simply because they have orthostatic hypotension 4