What are the causes and treatments of orthostatic hypotension?

Root Causes and Treatment of Orthostatic Hypotension

Root Causes of Orthostatic Hypotension

Orthostatic hypotension is primarily caused by medication side effects, autonomic dysfunction, and volume depletion, with treatment focused on addressing the underlying cause and implementing both non-pharmacological and pharmacological interventions to improve symptoms and quality of life.

• Drug-induced autonomic failure is the most frequent cause of orthostatic hypotension, with diuretics and vasodilators being the most important culprits 1
• Alcohol can cause orthostatic intolerance through both direct acute actions on the central nervous system and central volume depletion 1
• Primary autonomic failure conditions such as Parkinson's disease and multiple system atrophy can cause orthostatic hypotension 2
• Diabetic autonomic neuropathy is a secondary autonomic dysfunction that commonly leads to orthostatic hypotension 2
• Neurodegenerative disorders can cause orthostatic hypotension through autonomic dysfunction 2
• Volume depletion from dehydration or blood loss can lead to orthostatic hypotension 3

Non-Pharmacological Treatment

• Discontinuation or modification of culprit medications is the first-line approach to managing orthostatic hypotension 1, 2
• Patient education on gradual positional changes and avoiding precipitating factors is crucial for management 1, 2
• Physical countermeasures such as leg crossing, stooping, squatting, and tensing muscles can help manage symptoms 1, 4
• Increased fluid and salt intake (if not contraindicated) helps maintain central volume 1, 4
• Elastic garments over the legs and abdomen can reduce venous pooling 1, 4
• Head-up bed position during sleep helps prevent supine hypertension 1, 4
• Smaller, more frequent meals can reduce post-prandial hypotension 1, 4
• Physical activity and exercise should be encouraged to avoid deconditioning, which worsens orthostatic intolerance 1

Pharmacological Treatment

First-Line Medications

• Midodrine is an FDA-approved peripheral selective α1-adrenergic agonist that exerts a pressor effect through arteriolar and venous constriction 1, 5

  • Dosing should be individually tailored up to 10 mg 2-4 times daily, with the first dose taken before arising 1
  • The last daily dose should be taken 3-4 hours before bedtime to minimize nighttime supine hypertension 5
  • Monitor for adverse effects including pilomotor reactions, pruritus, supine hypertension, bradycardia, and urinary retention 1, 5

• Fludrocortisone (9-α-fluorohydrocortisone) acts through sodium retention and vessel wall effects 1, 4

  • Initial dose should be 0.05-0.1 mg daily with individual titration to 0.1-0.3 mg daily 1, 4
  • Monitor for adverse effects including supine hypertension, hypokalemia, congestive heart failure, and peripheral edema 1, 4

• Droxidopa is FDA-approved for the treatment of orthostatic hypotension 1, 4

Second-Line Medications and Adjuncts

• Erythropoietin can be considered for patients with anemia and severe autonomic neuropathy 1
• Desmopressin acetate may correct nocturnal polyuria and morning orthostatic hypotension 1
• Shorter-acting antihypertensives at bedtime (guanfacine, clonidine, isradipine, or short-acting β-blockers) may help manage supine hypertension 1

Special Considerations

• Treatment goals should focus on minimizing postural symptoms rather than restoring normotension 1
• Balance the benefits of increasing standing blood pressure against the risk of worsening supine hypertension 1, 2
• Combination therapy with midodrine and fludrocortisone may be considered for non-responders to monotherapy 4
• Regular monitoring for adverse effects, especially supine hypertension with pressor agents and electrolyte abnormalities with fludrocortisone, is essential 4, 5
• Avoid medications that can exacerbate orthostatic hypotension when possible, including psychotropic drugs, diuretics, and α-adrenoreceptor antagonists 1

Treatment Algorithm

1. Identify and address reversible causes:

   • Discontinue or modify culprit medications 1
   • Correct volume depletion 1
   • Treat underlying conditions 2

2. Implement non-pharmacological measures:

   • Patient education on gradual position changes 1
   • Physical countermeasures 1, 4
   • Increased fluid and salt intake if not contraindicated 1, 4
   • Compression garments 1, 4
   • Head-up bed position 1, 4

3. If symptoms persist, initiate pharmacological therapy:

   • Start with midodrine (2.5-5 mg three times daily, titrate as needed) 1, 5
   • OR fludrocortisone (0.05-0.1 mg daily, titrate as needed) 1, 4
   • Consider droxidopa for neurogenic orthostatic hypotension 1

4. For inadequate response to monotherapy:

   • Consider combination therapy with midodrine and fludrocortisone 4
   • Add adjunctive medications as needed 1, 4

5. Monitor and adjust therapy:

   • Regular assessment of symptom improvement 5
   • Monitor for supine hypertension 1, 5
   • Adjust timing and dosing of medications to minimize adverse effects 4, 5