What is the treatment for severe orthostasis?

Treatment of Severe Orthostatic Hypotension

For severe orthostatic hypotension, initiate midodrine 2.5-5 mg three times daily as first-line pharmacological therapy after implementing non-pharmacological measures, with the last dose at least 3-4 hours before bedtime to prevent supine hypertension. 1, 2

Immediate First Steps

Discontinue or switch culprit medications immediately - do not simply reduce doses. 1 The most common offenders include:

• Diuretics (most important cause of drug-induced orthostatic hypotension) 1
• ACE inhibitors and calcium channel blockers 1
• Alpha-blockers and vasodilators 3

Non-Pharmacological Management (Must Be Implemented First)

These interventions should begin immediately and continue alongside any pharmacological therapy:

Fluid and salt expansion (Class I recommendation):

• Increase fluid intake to 2-3 liters daily unless contraindicated by heart failure 3, 1
• Increase salt intake to 6-10 grams daily (approximately 1-2 teaspoons of table salt) 3, 1
• Acute water ingestion of ≥480 mL provides temporary relief with peak effect at 30 minutes 1

Compression garments:

• Use waist-high compression stockings (30-40 mmHg) and abdominal binders to reduce venous pooling 1
• Abdominal compression is particularly effective and may provide benefit even if full lower body compression is not tolerated 4

Physical counterpressure maneuvers:

• Teach leg crossing, squatting, stooping, and muscle tensing during symptomatic episodes 3, 1
• These are particularly effective in patients under 60 years with prodromal symptoms 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 3, 1
• Implement gradual staged movements with postural changes 1

Dietary modifications:

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

First-Line Pharmacological Treatment

Midodrine is the first-line agent with the strongest evidence base (three randomized placebo-controlled trials): 3, 1, 2

• Start at 2.5-5 mg three times daily 1, 2
• Increases standing systolic BP by 15-30 mmHg for 2-3 hours 1, 2
• Mechanism: alpha-1 adrenergic agonist causing arteriolar and venous constriction 1, 2
• Critical timing: last dose must be at least 3-4 hours before bedtime to prevent supine hypertension 1
• FDA-approved specifically for symptomatic orthostatic hypotension 2

Second-Line and Combination Therapy

If midodrine provides insufficient symptom control, add fludrocortisone:

• Start at 0.05-0.1 mg once daily 3, 1
• Titrate individually up to 0.1-0.3 mg daily 1
• Mechanism: mineralocorticoid that stimulates renal sodium retention and expands plasma volume 3, 1
• Monitor for hypokalemia, supine hypertension, congestive heart failure, and peripheral edema 1

Alternative or adjunctive agents:

• Droxidopa: FDA-approved, particularly effective for neurogenic orthostatic hypotension in Parkinson's disease, pure autonomic failure, and multiple system atrophy 1
• Pyridostigmine: beneficial for refractory cases in elderly patients with fewer side effects than alternatives, particularly when other treatments have failed 1

Critical Monitoring Requirements

Treatment goal: minimize postural symptoms and improve functional capacity, NOT restore normotension 1

Blood pressure monitoring protocol:

• Measure BP after 5 minutes lying/sitting, then at 1 and 3 minutes after standing 1
• Monitor for supine hypertension development (the most important limiting factor) 1
• Early review at 24-48 hours after medication initiation 1
• Intermediate follow-up at 1-2 weeks 1

Laboratory monitoring:

• Check electrolytes periodically when using fludrocortisone due to potassium wasting 1

Common Pitfalls to Avoid

Do not use cardiac pacing for orthostatic hypotension unless there is documented intrinsic sinus node dysfunction causing symptomatic bradyarrhythmias independent of postural changes - pacing has not been rigorously studied for orthostatic hypotension and is not considered of treatment value. 3

Avoid combining multiple vasoconstrictors without careful blood pressure monitoring to prevent severe supine hypertension. 1

Do not use beta-blockers - they are not indicated for reflex syncope or orthostatic hypotension. 3

Balance treatment benefits against supine hypertension risk - aggressive blood pressure targets may worsen supine hypertension and cause end-organ damage. 1

Contraindications for fludrocortisone:

• Active heart failure or significant cardiac dysfunction 1
• Pre-existing supine hypertension 1
• Severe renal disease where sodium retention would be harmful 1

Evidence Quality Note

The indication for midodrine is based on its effect on 1-minute standing systolic blood pressure (a surrogate marker), and clinical benefits such as improved ability to perform life activities have not been fully established in long-term studies. 2 However, it remains the best-studied and most effective pharmacological option available. 3, 1