How should orthostatic hypotension be managed, including identification of reversible causes, non‑pharmacologic measures, and first‑line pharmacologic therapy?

Management of Orthostatic Hypotension

Orthostatic hypotension should be managed by first identifying and eliminating reversible causes (especially medications), implementing non-pharmacologic measures (increased salt/fluid intake, compression garments, physical counter-maneuvers), and when these fail, initiating midodrine as first-line pharmacologic therapy. 1

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Diagnostic Confirmation

• Measure blood pressure after 5 minutes of supine or seated rest, then at 1 minute and 3 minutes after standing 1
• Orthostatic hypotension is confirmed by a sustained drop of ≥20 mmHg systolic or ≥10 mmHg diastolic 1, 2
• The therapeutic goal is minimizing postural symptoms and improving functional capacity, NOT restoring normotension 1

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Step 1: Identify and Eliminate Reversible Causes

Medication Review (Most Common Cause)

Drug-induced autonomic failure is the most frequent cause of orthostatic hypotension 1

Discontinue or switch the following high-risk medications (do NOT simply reduce the dose): 1

• Alpha-1 blockers (doxazosin, prazosin, terazosin, tamsulosin) – most problematic in older adults 1, 3
• Diuretics – cause volume depletion and are among the most important culprits 1, 3
• Vasodilators (hydralazine, minoxidil) 1, 3
• Centrally-acting agents (clonidine, methyldopa) 3
• Beta-blockers – avoid unless compelling indication exists (heart failure, recent MI) 1, 3

Volume Depletion Assessment

• Assess for dehydration, acute blood loss, or hypovolemia as reversible contributors 4
• Alcohol causes orthostatic intolerance through direct CNS effects and central volume depletion 1

Endocrine Evaluation (Especially in Diabetics)

• In diabetic patients >50 years, evaluate for cardiovascular autonomic neuropathy (CAN) using cardiac autonomic reflex tests (CARTs) 4
• CAN is a Level A evidence risk marker for all-cause mortality 4
• Screen for adrenal insufficiency, hypothyroidism, and other endocrine disorders 4, 5

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Step 2: Non-Pharmacologic Measures (First-Line for All Patients)

Dietary Modifications

• 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
• Eat smaller, more frequent meals to reduce postprandial hypotension 1
• Acute water ingestion ≥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 <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

Exercise and Physical Activity

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

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Step 3: Pharmacologic Therapy (When Non-Pharmacologic Measures Fail)

First-Line: Midodrine

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

• Initial dose: 2.5–5 mg three times daily 1
• Titrate individually up to 10 mg three times daily based on response 1
• Last dose must be ≥4 hours before bedtime (not after 6 PM) to prevent supine hypertension during sleep 1
• Increases standing systolic BP by 15–30 mmHg for 2–3 hours 1
• Mechanism: alpha-1 adrenergic agonist causing arteriolar and venous constriction 1

Alternative First-Line: Droxidopa

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

Second-Line: Fludrocortisone

• Initial dose: 0.05–0.1 mg once daily 1
• Titrate to 0.1–0.3 mg daily (maximum 1.0 mg daily) 1
• Mechanism: mineralocorticoid that increases plasma volume through sodium retention 1
• Monitor for adverse effects: supine hypertension, hypokalemia, congestive heart failure, peripheral edema 1
• Contraindications: active heart failure, significant cardiac dysfunction, severe renal disease, pre-existing supine hypertension 1
• Evidence quality is limited (very low-certainty evidence from small, short-term trials) 1

Combination Therapy for Non-Responders

For patients with inadequate response to monotherapy, combine midodrine with fludrocortisone – they act via complementary mechanisms (vascular constriction plus sodium retention) 1, 4

Refractory Cases: Pyridostigmine

• Dose: 60 mg orally three times daily (maximum 600 mg daily) 1
• Particularly beneficial in elderly patients refractory to other treatments 1
• Preferred when supine hypertension is a concern because it does not worsen supine BP 1
• Does not cause fluid retention, making it safer in patients with cardiac dysfunction 1
• Mechanism: acetylcholinesterase inhibitor that enhances ganglionic sympathetic transmission 1
• Common side effects: nausea, vomiting, abdominal cramping, sweating, salivation, urinary incontinence 1

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Special Populations

Patients with Concurrent Hypertension and Orthostatic Hypotension

• Switch to long-acting dihydropyridine calcium channel blockers (e.g., amlodipine) or RAS inhibitors (ACE inhibitors/ARBs) as first-line antihypertensive agents 1, 3
• These have minimal impact on orthostatic blood pressure 3
• Do NOT simply reduce the dose of offending medications – switch to alternative therapy 1

Frail Elderly (≥85 Years)

• Defer antihypertensive therapy until office BP ≥140/90 mmHg in patients with pre-treatment symptomatic orthostatic hypotension, moderate-to-severe frailty, or limited life expectancy 1
• When treatment is necessary, use long-acting dihydropyridine CCBs or RAS inhibitors first-line, followed by low-dose diuretics if tolerated 1
• Target "as low as reasonably achievable" (ALARA) rather than strict 130/80 mmHg 1

Diabetic Patients

• Routine screening for orthostatic hypotension is advised for all diabetic patients >50 years, even when asymptomatic 4
• Perform CARTs to confirm CAN 4
• Consider alpha-lipoic acid for painful diabetic neuropathy and potentially beneficial autonomic function 1

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Monitoring and Follow-Up

Critical Monitoring Parameters

• Measure supine and standing BP at each visit to detect treatment-induced supine hypertension 1
• Reassess within 1–2 weeks after medication changes 1
• Check electrolytes, BUN, and creatinine if fludrocortisone is used 1
• Monitor for hypokalemia with fludrocortisone (mineralocorticoid effects cause potassium wasting) 1

Treatment Goals

• Balance increasing standing BP against the risk of worsening supine hypertension 1
• Focus on symptom reduction and improving quality of life, not normalizing BP 4

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Common Pitfalls to Avoid

• Do NOT simply reduce the dose of offending medications – switch to alternative therapy 1
• Do NOT administer midodrine after 6 PM – causes supine hypertension during sleep 1
• Do NOT use fludrocortisone in patients with heart failure or supine hypertension 1
• Do NOT combine multiple vasodilating agents (ACE inhibitors + CCBs + diuretics) without careful monitoring 1
• Do NOT overlook volume depletion as a contributing factor 1
• Do NOT withhold ACE inhibitors from patients with compelling indications (heart failure, post-MI, diabetes, CKD) simply because they have orthostatic hypotension 3
• Asymptomatic orthostatic hypotension during treatment should NOT trigger automatic down-titration of antihypertensives 1