What are the treatment options for postural hypotension?

Treatment of Postural Hypotension

Initial Management: Eliminate Offending Medications First

The most critical first step is to discontinue or switch medications that worsen orthostatic hypotension—particularly diuretics, vasodilators, and alpha-blockers—rather than simply reducing doses. 1 Drug-induced autonomic failure is the most frequent cause of orthostatic hypotension, and elimination of the offending agent is the principal treatment strategy. 2

• For patients requiring ongoing antihypertensive therapy, switch to long-acting dihydropyridine calcium channel blockers (such as amlodipine) or RAS inhibitors as first-line agents. 1
• Avoid RAS blockers in patients with isolated orthostatic hypotension due to vasodilatory effects that exacerbate postural blood pressure drops. 1
• Alcohol should be avoided as it induces both autonomic neuropathy and central volume depletion. 2

Non-Pharmacological Interventions (Implement Before Medications)

All patients should begin with non-pharmacological measures, which form the foundation of treatment. 1, 3

Volume Expansion Strategies

• Increase fluid intake to 2-3 liters daily unless contraindicated by heart failure. 1, 3
• Increase salt consumption to 6-10 grams daily (approximately 1-2 teaspoons of table salt) if not contraindicated. 1, 3
• Acute water ingestion of ≥480 mL provides temporary relief with peak effect at 30 minutes—plain water is more effective than salt water for acute blood pressure elevation. 1, 3

Postural and Mechanical Interventions

• Elevate the head of bed by 10 degrees during sleep to prevent nocturnal polyuria, maintain favorable fluid distribution, and reduce supine hypertension. 1, 3
• Use waist-high compression stockings (30-40 mmHg) and abdominal binders to reduce venous pooling. 1
• Teach physical counter-pressure maneuvers: 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

Dietary Modifications

• Eat smaller, more frequent meals to reduce post-prandial hypotension. 1, 3
• Encourage physical activity and exercise to avoid deconditioning, which exacerbates orthostatic intolerance. 1

First-Line Pharmacological Treatment: Midodrine

When non-pharmacological measures fail, midodrine is the first-line pharmacological agent with the strongest evidence base among pressor agents for orthostatic hypotension. 1, 3

Dosing and Administration

• Start at 2.5-5 mg three times daily, titrate individually up to 10 mg three times daily based on response. 1, 3
• Critical timing: The last dose must be taken at least 3-4 hours before bedtime (not later than 6 PM) to prevent supine hypertension during sleep. 1
• Expected effect: Increases standing systolic BP by 15-30 mmHg for 2-3 hours after dosing. 1

Mechanism and Evidence

• Midodrine is an alpha-1 adrenergic agonist that increases vascular tone through arteriolar and venous constriction. 1, 3
• Three randomized placebo-controlled trials demonstrate efficacy at doses ranging from 5-20 mg three times daily. 1
• FDA-approved for symptomatic orthostatic hypotension, though clinical benefits (improved ability to perform life activities) are based on surrogate markers. 4

Precautions

• Use with caution in older males due to potential urinary outflow issues. 1
• Monitor for supine hypertension (BP >200 mmHg systolic). 4

Second-Line Pharmacological Treatment: Fludrocortisone

If midodrine alone provides insufficient symptom control, add fludrocortisone or use it as monotherapy if midodrine is contraindicated. 1, 3

Dosing and Titration

• Start at 0.05-0.1 mg once daily, titrate individually to 0.1-0.3 mg daily (maximum 1.0 mg daily). 1, 3
• An alternative approach uses a 0.2 mg loading dose followed by 0.1 mg daily maintenance. 1

Mechanism and Rationale

• Fludrocortisone is a mineralocorticoid that increases plasma volume through sodium retention and has direct vessel wall effects. 1, 3
• Acts through a different mechanism than midodrine (volume expansion vs. vasoconstriction), making combination therapy complementary rather than redundant. 1

Contraindications and Monitoring

• Avoid in active heart failure, significant cardiac dysfunction, pre-existing supine hypertension, or severe renal disease where sodium retention would be harmful. 1
• Monitor for supine hypertension (most important limiting factor), hypokalemia, congestive heart failure, and peripheral edema. 1
• Check electrolytes, BUN, and creatinine periodically due to mineralocorticoid effects causing potassium wasting. 1
• Use with caution in patients with low serum albumin due to risk of ankle edema. 5

Third-Line and Refractory Options

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 these populations. 1

Pyridostigmine

• Beneficial for refractory orthostatic hypotension in elderly patients who have not responded to other treatments. 1
• Class IIa recommendation from ACC/AHA/HRS guidelines for neurogenic orthostatic hypotension refractory to other treatments. 1
• Favorable side effect profile compared to alternatives like fludrocortisone, though common side effects include nausea, vomiting, abdominal cramping, sweating, salivation, and urinary incontinence. 1

Combination Therapy

• For non-responders to monotherapy, consider combining midodrine and fludrocortisone. 1
• Ensure adequate salt (6-10 g daily) and fluid (2-3 L daily) intake as adjunctive measures unless contraindicated by heart failure. 1

Treatment Goals and Monitoring

The therapeutic objective is minimizing postural symptoms and improving functional capacity, not restoring normotension. 1, 3

Diagnostic Confirmation

• Measure blood pressure after 5 minutes of sitting/lying, then at 1 and/or 3 minutes after standing to document orthostatic changes. 1, 3
• Orthostatic hypotension is defined as a reduction of systolic BP ≥20 mmHg or diastolic BP ≥10 mmHg within 3 minutes of standing. 3

Follow-up and Safety Monitoring

• Reassess the patient within 1-2 weeks after medication changes. 1
• Monitor orthostatic vital signs at each follow-up visit. 1
• Monitor for supine hypertension development, which can cause end-organ damage—this is the critical balancing act in treatment. 1, 3
• Balance the benefits of increasing standing blood pressure against the risk of worsening supine hypertension. 1

Special Populations

Diabetic Patients

• Assess for cardiovascular autonomic neuropathy in diabetic patients presenting with orthostatic hypotension, as symptoms are often rare despite significant blood pressure drops. 3
• Consider alpha-lipoic acid for painful diabetic neuropathy and potentially beneficial effects on autonomic function. 1

Hemodialysis Patients

• Longer weekly treatment time (5 hours per session, 3 times per week) causes less hypotension during dialysis and less postdialysis postural hypotension compared to shorter sessions. 3

Critical Pitfalls to Avoid

• Do not simply reduce the dose of offending medications—switch to alternative therapy. 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
• Do not overlook volume depletion as a contributing factor. 1
• Beta-adrenergic blocking drugs are not effective and may aggravate bradycardia in cardioinhibitory cases. 2