How to treat orthostatic hypotension?

Treatment of Orthostatic Hypotension

Start with non-pharmacological measures for all patients, then add midodrine 2.5-5 mg three times daily (last dose before 6 PM) as first-line pharmacological therapy if symptoms persist, followed by fludrocortisone 0.05-0.1 mg daily if midodrine alone is insufficient. 1

Initial Assessment and Reversible Causes

• Immediately review and discontinue or switch all blood pressure-lowering medications that worsen orthostatic hypotension, including ACE inhibitors, calcium channel blockers, and especially diuretics—switching to alternative therapy is essential, not dose reduction. 1
• Evaluate for drug-induced autonomic failure (the most frequent cause), volume depletion, neurogenic causes, and endocrine disorders. 1
• Measure blood pressure after 5 minutes of lying/sitting, then at 1 and 3 minutes after standing to confirm the diagnosis (drop of ≥20 mmHg systolic or ≥10 mmHg diastolic). 1

Non-Pharmacological Management (Implement First for All Patients)

Fluid and Salt Optimization:

• Increase fluid intake to 2-3 liters daily unless contraindicated by heart failure. 1
• Increase salt intake to 6-9 grams daily (approximately 1-2 teaspoons of table salt) if not 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

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
• Advise gradual staged movements with postural changes. 1

Dietary Modifications:

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

Exercise:

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

Pharmacological Management (When Non-Pharmacological Measures Fail)

First-Line: Midodrine

• Midodrine has the strongest evidence base among pressor agents, with three randomized placebo-controlled trials demonstrating efficacy. 1
• Start at 2.5-5 mg three times daily, with the last dose at least 3-4 hours before bedtime (no later than 6 PM) to prevent supine hypertension. 1, 2
• Mechanism: Alpha-1 adrenergic agonist that increases vascular tone through arteriolar and venous constriction. 1, 2
• Effect: Increases standing systolic BP by 15-30 mmHg for 2-3 hours after dosing. 1, 2
• FDA-approved specifically for symptomatic orthostatic hypotension. 2
• Critical precaution: Use with caution in older males due to potential urinary retention from alpha-adrenergic effects on the bladder neck. 2

Second-Line: Fludrocortisone (Add if Midodrine Insufficient)

• Start at 0.05-0.1 mg once daily, titrate individually to 0.1-0.3 mg daily (maximum 1.0 mg daily). 1
• Mechanism: Mineralocorticoid that increases plasma volume 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—only very low-certainty evidence from small, short-term trials. 1, 3

Alternative First-Line: Droxidopa

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

Refractory Cases: Pyridostigmine

• Consider for patients refractory to midodrine and fludrocortisone, with a favorable side effect profile compared to alternatives. 1
• Supported by 2017 ACC/AHA/HRS guidelines for neurogenic orthostatic hypotension. 1
• 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

Special Populations

Patients with Concurrent Hypertension:

• Consider long-acting dihydropyridine calcium channel blockers or RAS inhibitors as first-line antihypertensive therapy. 1

Diabetic Patients:

• Assess for cardiovascular autonomic neuropathy. 1
• Consider α-lipoic acid for painful diabetic neuropathy, potentially beneficial for autonomic function. 1

Patients on Hemodialysis:

• Midodrine is removed by dialysis—adjust timing accordingly. 2

Patients with Renal Impairment:

• Start midodrine at 2.5 mg due to renal elimination of the active metabolite desglymidodrine. 2

Patients with Hepatic Impairment:

• Use midodrine with caution as the liver has a role in metabolism. 2

Treatment Goals and Monitoring

Primary Goal:

• The therapeutic objective is minimizing postural symptoms and improving functional capacity, NOT restoring normotension—aggressive blood pressure targets may worsen supine hypertension. 1

Monitoring Protocol:

• Measure blood pressure after 5 minutes lying/sitting, then at 1 and 3 minutes after standing. 1
• Early review at 24-48 hours after medication initiation. 1
• Intermediate follow-up at 1-2 weeks to assess standing heart rate, blood pressure, and symptom improvement. 1
• Monitor for supine hypertension development, which can cause end-organ damage—this is the most important limiting factor. 1
• Check electrolytes periodically with fludrocortisone due to potassium wasting. 1

Discontinuation Criteria:

• Continue midodrine only for patients who report significant symptomatic improvement after initiation. 2

Critical Pitfalls to Avoid

• Never simply reduce the dose of BP-lowering medications—switch to alternative therapy or discontinue entirely. 1
• Avoid combining multiple vasoconstrictors without careful blood pressure monitoring. 1
• Do not take midodrine after 6 PM or if the patient will be supine for any length of time. 1, 2
• Avoid midodrine with MAO inhibitors or linezolid. 2
• Caution when combining midodrine with cardiac glycosides (may precipitate bradycardia, AV block, or arrhythmia), other drugs that increase blood pressure (phenylephrine, pseudoephedrine, ephedrine, dihydroergotamine, thyroid hormones, droxidopa), or agents that reduce heart rate. 2
• Alpha-adrenergic blocking agents (prazosin, terazosin, doxazosin) antagonize midodrine's effects. 2
• Balance treatment benefits against supine hypertension risk—supine BP >200 mmHg systolic occurred in 22% of patients on 10 mg midodrine and 45% on 20 mg. 2