What are the diagnosis and management of orthostatic hypotension?

From the Guidelines

Postural hypotension (orthostatic hypotension) is diagnosed when there is a drop in blood pressure of at least 20 mmHg systolic or 10 mmHg diastolic within 3 minutes of standing from a sitting or lying position, accompanied by symptoms like dizziness, lightheadedness, or syncope, as defined in the 2018 European Heart Journal guidelines 1.

Diagnosis and Management

Diagnosis requires blood pressure measurements in both positions and a thorough medical history to identify underlying causes such as dehydration, medication side effects, or neurological disorders. Management begins with non-pharmacological approaches including:

• Gradual position changes
• Adequate hydration (2-3 liters of fluid daily)
• Increased salt intake (unless contraindicated)
• Compression stockings
• Avoiding triggers like hot environments or large meals If these measures are insufficient, medications may be necessary.

Pharmacological Options

First-line pharmacological options include:

• Fludrocortisone (starting at 0.1 mg daily, maximum 0.3 mg daily), which increases sodium retention and blood volume
• Midodrine (2.5-10 mg three times daily), an alpha-1 agonist that increases vascular tone For neurogenic orthostatic hypotension, droxidopa (100-600 mg three times daily) may be effective, as approved by the FDA and mentioned in the 2021 Diabetes Care standards 1.

Adjusting Medications and Monitoring

Medications should be adjusted based on symptom response and blood pressure monitoring. Underlying causes should always be addressed when possible, including adjustment of medications that may be contributing to hypotension, such as antihypertensives, antidepressants, or diuretics, as noted in the 2018 European Heart Journal guidelines 1 and the 2020 Diabetes Care standards 1. Regular follow-up is essential to assess treatment efficacy and adjust management strategies as needed.

From the FDA Drug Label

Midodrine hydrochloride tablets are indicated for the treatment of symptomatic orthostatic hypotension (OH) Because midodrine hydrochloride tablets can cause marked elevation of supine blood pressure (BP>200 mmHg systolic), it should be used in patients whose lives are considerably impaired despite standard clinical care, including non-pharmacologic treatment (such as support stockings), fluid expansion, and lifestyle alterations

The diagnosis of postural hypotension is not directly addressed in the provided drug labels. However, the management of symptomatic orthostatic hypotension (OH) is indicated for midodrine hydrochloride tablets. Key points for management include:

• Midodrine should be used in patients whose lives are considerably impaired despite standard clinical care, including:
  • Non-pharmacologic treatment (such as support stockings)
  • Fluid expansion
  • Lifestyle alterations
• Midodrine hydrochloride tablets should be continued only for patients who report significant symptomatic improvement 2
• The mechanism of action of midodrine is via activation of the alpha-adrenergic receptors of the arteriolar and venous vasculature, producing an increase in vascular tone and elevation of blood pressure 2

From the Research

Diagnosis of Postural Hypotension

• Postural hypotension is defined as a reduction of at least 20 mm Hg in systolic blood pressure or at least a 10 mm Hg decrease in diastolic blood pressure upon assumption of the upright posture 3
• The diagnosis of postural hypotension can be made by measuring blood pressure in the supine and standing positions 3

Management of Postural Hypotension

• Nonpharmacologic measures are the first line of treatment, including increasing fluid and salt intake, avoiding large carbohydrate-rich meals, and maintaining adequate hydration 3, 4
• Pharmacologic treatment can be used if nonpharmacologic measures are insufficient, with fludrocortisone, midodrine, and pyridostigmine being commonly used agents 3, 5, 6, 4
• The goal of treatment is to make the patient as ambulatory and symptom-free as possible without causing supine hypertension 3
• Midodrine and droxidopa have the most evidence for increasing blood pressure and alleviating symptoms, while pyridostigmine and fludrocortisone can be used in patients who fail to respond to these agents 4
• Combination therapy with midodrine and pyridostigmine may also be effective in improving orthostatic blood pressure drop and ameliorating symptoms 6

Treatment Options

• Fludrocortisone: a mineralocorticoid that increases blood volume and blood pressure, considered first- or second-line pharmacological therapy for orthostatic hypotension 5, 7
• Midodrine: an alpha-adrenergic agonist that increases blood pressure, effective in improving orthostatic blood pressure drop and ameliorating symptoms 6, 4
• Pyridostigmine: an acetylcholinesterase inhibitor that increases blood pressure, can be used in combination with midodrine or as an alternative therapy 6, 4
• Droxidopa: a synthetic precursor of norepinephrine that increases blood pressure, has evidence for increasing blood pressure and alleviating symptoms 4