How is orthostatic hypotension managed?

Management of Orthostatic Hypotension

Start by discontinuing or switching medications that worsen orthostatic hypotension—particularly diuretics, ACE inhibitors, calcium channel blockers, and alpha-blockers—rather than simply reducing doses, as drug-induced autonomic failure is the most common cause. 1

Initial Assessment and Reversible Causes

• Confirm the diagnosis by measuring blood pressure after 5 minutes of lying/sitting, then at 1 and 3 minutes after standing; orthostatic hypotension is defined as a drop of ≥20 mmHg systolic or ≥10 mmHg diastolic. 1
• Immediately review all medications and discontinue or switch (not dose-reduce) blood pressure-lowering agents that worsen orthostatic symptoms, including ACE inhibitors, calcium channel blockers, diuretics, alpha-blockers, and vasodilators. 1
• Evaluate for volume depletion, anemia, endocrine disorders (adrenal insufficiency, hypothyroidism), and cardiovascular causes as reversible contributors. 1
• Avoid alcohol, as it causes both autonomic neuropathy and central volume depletion. 1

Non-Pharmacological Management (First-Line for All Patients)

Implement these measures before or alongside any pharmacological therapy:

• Increase fluid intake to 2-3 liters daily unless contraindicated by heart failure. 1, 2
• Increase salt intake to 6-9 grams daily (approximately 1-2 teaspoons of table salt) unless contraindicated. 1, 2
• Teach physical counter-maneuvers: leg crossing, squatting, stooping, and muscle tensing during symptomatic episodes—particularly effective in patients under 60 years with prodromal symptoms. 1
• Use compression garments: waist-high compression stockings (30-40 mmHg) and abdominal binders to reduce venous pooling. 1
• Elevate the head of the bed by 10 degrees during sleep to prevent nocturnal polyuria, maintain favorable fluid distribution, and ameliorate nocturnal hypertension. 1, 2
• Acute water ingestion of ≥480 mL can provide temporary relief with peak effect at 30 minutes—useful for rapid cool water ingestion to combat orthostatic intolerance and post-prandial hypotension. 1, 2
• Eat smaller, more frequent meals to reduce post-prandial hypotension. 1
• Encourage physical activity and exercise to avoid deconditioning, which worsens orthostatic intolerance. 1
• Teach gradual staged movements with postural changes to minimize symptoms. 1

Pharmacological Management (When Non-Pharmacological Measures Fail)

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

First-Line Pharmacological Agent: Midodrine

Midodrine has the strongest evidence base among pressor agents, with three randomized placebo-controlled trials demonstrating efficacy. 1, 3

• Starting dose: 2.5-5 mg three times daily, titrate individually up to 10 mg three times daily based on response. 1, 3
• Mechanism: Alpha-1 adrenergic agonist that increases vascular tone through arteriolar and venous constriction; increases standing systolic BP by 15-30 mmHg for 2-3 hours. 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, 3
• FDA-approved specifically for symptomatic orthostatic hypotension in patients whose lives are considerably impaired despite standard clinical care. 3
• May cause slight vagal-mediated heart rate slowing, but benefits usually outweigh this concern. 3

Second-Line or Combination Therapy: Fludrocortisone

Add fludrocortisone if midodrine alone provides insufficient symptom control, or use as monotherapy if midodrine is contraindicated. 1

• Starting dose: 0.05-0.1 mg once daily, titrate 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
• Combination therapy with midodrine and fludrocortisone is recommended for non-responders to monotherapy, as they work through complementary mechanisms (alpha-1 adrenergic stimulation vs. sodium retention). 1
• Contraindications: Active heart failure, significant cardiac dysfunction, pre-existing supine hypertension, and 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; check electrolytes, BUN, and creatinine periodically. 1
• Evidence quality is limited: Very low-certainty evidence from small, short-term trials, though observational studies suggest it may not be harmful long-term. 4

Alternative First-Line Agent: Droxidopa

• FDA-approved for neurogenic orthostatic hypotension, particularly effective in Parkinson's disease, pure autonomic failure, and multiple system atrophy; may reduce falls. 1
• Recommended as a first-line option alongside midodrine and fludrocortisone by the European Society of Cardiology. 1

Refractory Cases: Pyridostigmine

• Consider for neurogenic orthostatic hypotension refractory to other treatments, with a favorable side effect profile compared to fludrocortisone. 1
• Class IIa recommendation from the 2017 ACC/AHA/HRS guidelines for syncope due to neurogenic orthostatic hypotension. 1
• Common side effects: Nausea, vomiting, abdominal cramping, sweating, salivation, and urinary incontinence—generally manageable. 1

Additional Agents for Specific Situations

• Octreotide may be considered for post-prandial hypotension. 2
• Desmopressin may correct nocturnal polyuria and morning orthostatic hypotension. 1, 2
• Erythropoietin can be considered for patients with anemia and severe autonomic neuropathy. 1, 2

Special Considerations

Patients with Coexisting Hypertension and Orthostatic Hypotension

• Switch to long-acting dihydropyridine calcium channel blockers (e.g., amlodipine) or RAS inhibitors as first-line therapy for hypertension, as these are preferred in patients with both conditions. 1
• Do not simply reduce doses of offending medications; switch to alternative therapy. 1
• Shorter-acting antihypertensives at bedtime may help manage supine hypertension. 1

Diabetic Patients

• Assess for cardiovascular autonomic neuropathy in diabetic patients with orthostatic hypotension. 1
• Consider alpha-lipoic acid for painful diabetic neuropathy and potentially beneficial effects on autonomic function. 1

Patients on Hemodialysis

• Midodrine is removed by dialysis, so timing of doses should be adjusted accordingly. 3

Patients with Renal or Hepatic Impairment

• Start midodrine at 2.5 mg in patients with renal impairment, as desglymidodrine is eliminated via the kidneys; assess renal function prior to initiation. 3
• Use midodrine with caution in hepatic impairment, as the liver has a role in metabolism. 3

Monitoring and Follow-Up

• Monitor blood pressure after 5 minutes lying/sitting, then at 1 and 3 minutes after standing at each follow-up visit. 1
• Early review at 24-48 hours after medication initiation, with intermediate follow-up at 1-2 weeks to assess standing heart rate, blood pressure, and symptom improvement. 5
• Monitor for supine hypertension development, which can cause end-organ damage—this is the most important limiting factor in treatment. 1
• Check electrolytes periodically if using fludrocortisone due to mineralocorticoid effects causing potassium wasting. 1
• Continue midodrine only for patients who report significant symptomatic improvement, as clinical benefits (improved ability to perform life activities) are still being established in ongoing trials. 3

Critical Pitfalls to Avoid

• Do not simply reduce the dose of offending medications—switch to alternative therapy instead. 1
• Do not administer midodrine after 6 PM to prevent supine hypertension during sleep. 1, 3
• Do not use fludrocortisone in patients with heart failure or supine hypertension. 1
• Do not combine multiple vasoconstrictors without careful blood pressure monitoring, as this increases the risk of supine hypertension. 5
• Do not overlook volume depletion as a contributing factor. 1
• Do not combine multiple vasodilating agents (ACE inhibitors + calcium channel blockers + diuretics) without careful monitoring. 1
• Avoid beta-blockers, as they may be detrimental in dysautonomic syndromes and may enhance bradycardia in cardioinhibitory forms. 1, 2
• Cardiac pacing is NOT recommended for orthostatic hypotension with bradycardia unless there is documented intrinsic sinus node dysfunction causing symptomatic bradyarrhythmias independent of postural changes. 5