How to manage orthostatic hypotension?

Management of Orthostatic Hypotension

Begin 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

• Measure blood pressure after 5 minutes of lying/sitting, then at 1 and 3 minutes after standing to confirm the diagnosis (≥20 mmHg systolic or ≥10 mmHg diastolic drop). 1
• Immediately review all medications and discontinue or switch offending agents: diuretics, vasodilators (ACE inhibitors, ARBs, calcium channel blockers), alpha-1 blockers, tricyclic antidepressants, and phenothiazines. 1
• Assess for volume depletion, anemia, endocrine disorders (adrenal insufficiency, hypothyroidism), and cardiovascular autonomic neuropathy (especially in diabetic patients). 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:

• Fluid and salt expansion: Increase fluid intake to 2-3 liters daily and salt intake to 6-10 grams daily (approximately 1-2 teaspoons of table salt), unless contraindicated by heart failure. 1, 2
• Acute water bolus: Drink ≥480 mL of cool water rapidly for temporary relief, with peak effect at 30 minutes—particularly effective for post-prandial hypotension. 1, 2
• Physical counter-maneuvers: Teach leg crossing, squatting, stooping, and muscle tensing during symptomatic episodes; these are particularly effective in patients under 60 years with prodromal symptoms. 1, 2
• Compression garments: Use waist-high compression stockings (30-40 mmHg) and abdominal binders to reduce venous pooling in the splanchnic and lower extremity circulation. 1, 2
• Head-up bed tilt: Elevate the head of the bed by 10 degrees during sleep to prevent nocturnal polyuria, maintain favorable fluid distribution, and ameliorate supine hypertension. 1, 2
• Dietary modifications: Eat smaller, more frequent meals to reduce post-prandial hypotension. 1
• Exercise: Encourage physical activity to avoid deconditioning, which worsens orthostatic intolerance. 1

Pharmacological Management (When Non-Pharmacological Measures Fail)

First-Line Agent: Midodrine

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

• Mechanism: Alpha-1 adrenergic agonist that increases vascular tone through arteriolar and venous constriction without direct cardiac or CNS effects. 3
• Dosing: Start at 2.5-5 mg three times daily, titrate up to 10 mg three times daily based on response. 1, 3
• Effect: Increases standing systolic blood pressure by 15-30 mmHg for 2-3 hours after dosing. 1, 3
• Critical timing: The last dose must be taken at least 3-4 hours before bedtime (not after 6 PM) to prevent supine hypertension during sleep. 1, 4
• Monitoring: Check supine blood pressure regularly to detect treatment-induced supine hypertension. 1
• Caution: May cause slight vagal-mediated heart rate slowing; use cautiously with cardiac glycosides, beta-blockers, or other agents that reduce heart rate. 3

Second-Line or Combination Agent: Fludrocortisone

• Mechanism: Mineralocorticoid that increases plasma volume through sodium retention and vessel wall effects. 1
• Dosing: Start at 0.05-0.1 mg once daily, titrate to 0.1-0.3 mg daily (maximum 1.0 mg daily). 1
• Combination therapy: For non-responders to midodrine monotherapy, add fludrocortisone as the mechanisms are complementary (midodrine increases vascular tone, fludrocortisone expands volume). 1
• Monitoring: Check electrolytes periodically for hypokalemia; monitor for supine hypertension, congestive heart failure, and peripheral edema. 1
• Contraindications: Avoid in patients with active heart failure, severe renal disease, or pre-existing supine hypertension. 1

Alternative Agents for Specific Situations

• Droxidopa: FDA-approved for neurogenic orthostatic hypotension, particularly effective in Parkinson's disease, pure autonomic failure, and multiple system atrophy; may reduce falls. 1
• Pyridostigmine: Consider for refractory neurogenic orthostatic hypotension in elderly patients who have not responded to other treatments; has a favorable side effect profile compared to fludrocortisone. 1
• Octreotide: May be considered for severe post-prandial hypotension. 2
• Desmopressin: May correct nocturnal polyuria and morning orthostatic hypotension. 1, 2

Treatment Goals and Monitoring

The therapeutic objective is minimizing postural symptoms and improving functional capacity, NOT restoring normotension. 1, 4

• Aggressive blood pressure targets may worsen supine hypertension and cause end-organ damage. 1
• Measure orthostatic vital signs at each follow-up visit. 1
• Reassess within 1-2 weeks after medication initiation or changes. 1, 4
• Balance the benefits of increasing standing blood pressure against the risk of supine hypertension. 1

Special Populations

Patients with Hypertension and Orthostatic Hypotension

• Switch to preferred agents: Use long-acting dihydropyridine calcium channel blockers (e.g., amlodipine) or RAS inhibitors as first-line therapy for hypertension in these patients. 1
• Avoid: Do not combine multiple vasodilating agents (ACE inhibitors + calcium channel blockers + diuretics) without careful monitoring. 1
• Timing strategy: Consider shorter-acting antihypertensives at bedtime to manage supine hypertension while allowing lower blood pressure during the day. 1

Diabetic Patients

• Assess for cardiovascular autonomic neuropathy. 1
• Consider alpha-lipoic acid for painful diabetic neuropathy, which may also benefit autonomic function. 1

Patients on Hemodialysis

• Midodrine is removed by dialysis; timing of doses relative to dialysis sessions requires adjustment. 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 overlook volume depletion as a contributing factor. 1
• Do not confine patients to bed while using pressor agents—this only increases supine blood pressure and worsens pressure diuresis. 5
• Beta-blockers are not effective and may aggravate bradycardia in cardioinhibitory cases. 1
• 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. 4