What is the management and treatment of orthostatic hypotension?

Complete Workup on Orthostatic Hypotension

Definition and Diagnosis

Orthostatic hypotension is defined as a decrease in systolic blood pressure ≥20 mmHg or diastolic blood pressure ≥10 mmHg within 3 minutes of standing from a supine or sitting position. 1

Diagnostic Testing

• Measure blood pressure after 5 minutes of lying/sitting, then at 1 and 3 minutes after standing 1
• If bedside testing is nondiagnostic but clinical suspicion remains high, or if the patient cannot stand safely, proceed to head-up tilt-table testing at ≥60 degrees 1, 2
• Assess for neurogenic versus non-neurogenic causes by evaluating heart rate response: neurogenic orthostatic hypotension typically shows absent compensatory tachycardia 3

Initial Evaluation for Reversible Causes

• Review all medications immediately - drug-induced autonomic failure is the most frequent cause, with diuretics and vasodilators being the primary culprits 1
• Assess for volume depletion from dehydration, blood loss, or inadequate fluid intake 1
• Evaluate for endocrine disorders (adrenal insufficiency, hypothyroidism) 1
• Screen for cardiovascular causes including cardiac insufficiency and impaired venous return 4
• In diabetic patients, assess for cardiovascular autonomic neuropathy 1
• Check renal and hepatic function before initiating pharmacotherapy 5
• Consider alcohol use, which causes orthostatic intolerance through direct CNS effects and volume depletion 1

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

Medication Adjustment

Switch (not reduce) blood pressure-lowering medications that worsen orthostatic hypotension to alternative therapy. 1 This includes:

• ACE inhibitors (e.g., perindopril) 1
• Calcium channel blockers (e.g., lercanidipine) 1
• Diuretics 1
• Alpha-adrenergic antagonists 1
• RAS blockers due to vasodilatory effects 1

Fluid and Salt Management

• Increase fluid intake to 2-3 liters daily unless contraindicated by heart failure (Class I recommendation) 1, 3
• Increase salt intake to 6-9 grams daily (approximately 1-2 teaspoons of table salt) if not contraindicated 1, 3
• Acute water ingestion of ≥480 mL provides temporary relief with peak effect at 30 minutes 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 1, 3
• Teach gradual staged movements with postural changes 1
• Avoid becoming fully supine during the day 5

Physical Counter-Maneuvers

• Teach leg crossing, squatting, stooping, and muscle tensing during symptomatic episodes - particularly effective in patients under 60 years with prodromal symptoms 1, 3
• These maneuvers should be implemented at symptom onset 1

Compression Garments

• Use waist-high compression stockings (30-40 mmHg) and abdominal binders to reduce venous pooling 1, 3
• Thigh-high compression is also effective 1

Dietary Modifications

• Eat smaller, more frequent meals to reduce post-prandial hypotension 1
• Avoid large meals that can exacerbate symptoms 1

Exercise and Activity

• Encourage physical activity and exercise to avoid deconditioning, which worsens orthostatic intolerance 1

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Pharmacological Management (When Non-Pharmacological Measures Fail)

Treatment Goals

The therapeutic objective is minimizing postural symptoms and improving functional capacity, NOT restoring normotension. 1, 3 Aggressive blood pressure targets may worsen supine hypertension 3

First-Line Pharmacological Agent: Midodrine

Midodrine is the first-line pharmacological agent with the strongest evidence base, supported by three randomized placebo-controlled trials. 1

Dosing and Administration

• Start at 2.5-5 mg three times daily 1, 3, 5
• For patients with renal impairment, start at 2.5 mg 5
• The last dose must be at least 3-4 hours before bedtime to prevent supine hypertension during sleep 1, 3, 5
• Avoid taking the last dose after 6 PM 1

Mechanism and Efficacy

• Alpha-1 adrenergic agonist that increases vascular tone through arteriolar and venous constriction 1, 3
• Can increase standing systolic BP by 15-30 mmHg for 2-3 hours 1
• FDA-approved specifically for symptomatic orthostatic hypotension 3, 5

Monitoring and Precautions

• Monitor carefully for supine and sitting hypertension at the beginning of therapy 5
• May cause slight vagal-mediated heart rate slowing, but benefits usually outweigh this concern 3
• Use cautiously with cardiac glycosides, which may enhance bradycardia, AV block, or arrhythmia 5
• Avoid concomitant use with other vasoconstrictors (phenylephrine, pseudoephedrine, ephedrine, dihydroergotamine) or monitor blood pressure closely if unavoidable 5
• Avoid MAO inhibitors or linezolid with midodrine 5
• Use with caution in patients with urinary retention, as it acts on alpha-adrenergic receptors of the bladder neck 5

Contraindications

• Patients advised to report symptoms of supine hypertension immediately (cardiac awareness, pounding in ears, headache, blurred vision) and discontinue if it persists 5
• Patients experiencing bradycardia symptoms (pulse slowing, increased dizziness, syncope) should discontinue and be re-evaluated 5

Second-Line Agent: Fludrocortisone

Add fludrocortisone if midodrine alone provides insufficient symptom control. 1

Dosing and Administration

• Start at 0.05-0.1 mg once daily 1, 3
• Titrate individually to 0.1-0.3 mg daily based on response 1
• Alternative approach: 0.2 mg loading dose followed by 0.1 mg daily maintenance 1
• Maximum recommended dose is 1.0 mg daily 1

Mechanism

• Mineralocorticoid that increases plasma volume through sodium retention and vessel wall effects 1, 3

Monitoring Requirements

• Monitor for supine hypertension - the most important limiting factor 1
• Check electrolytes periodically due to mineralocorticoid effects causing potassium wasting 1
• Monitor for hypokalemia 1
• Assess for peripheral edema and signs of congestive heart failure 1

Contraindications and Precautions

• Avoid in patients with active heart failure or significant cardiac dysfunction 1
• Avoid in patients with pre-existing supine hypertension 1
• Avoid in patients with severe renal disease where sodium retention would be harmful 1
• Use cautiously in diabetic patients and those with visual problems, as it can increase intraocular pressure and cause glaucoma 5
• Evidence quality is limited, with only very low-certainty evidence from small, short-term trials 1, 6
• Concerning long-term effects have been noted 2

Adjunctive Measures

• Increased salt intake to 6-9 g daily enhances effectiveness if not contraindicated by heart failure 1
• Compression garments reduce venous pooling and complement fludrocortisone therapy 1

Combination Therapy

• For non-responders to monotherapy, consider combination therapy with midodrine and fludrocortisone 1
• Avoid combining multiple vasoconstrictors without careful blood pressure monitoring 3

Alternative First-Line Agents

Droxidopa

• FDA-approved and particularly effective for neurogenic orthostatic hypotension in Parkinson's disease, pure autonomic failure, and multiple system atrophy 1, 3
• May reduce falls 1
• Recommended as a first-line option alongside midodrine and fludrocortisone by the European Society of Cardiology 1

Refractory Cases

Pyridostigmine

• Beneficial for refractory orthostatic hypotension in elderly patients who have not responded to other treatments 1
• Favorable side effect profile with fewer side effects than fludrocortisone 1
• Class IIa recommendation from ACC/AHA/HRS guidelines for neurogenic orthostatic hypotension refractory to other treatments 1
• Common side effects include nausea, vomiting, abdominal cramping, sweating, salivation, and urinary incontinence, which are generally manageable 1

Other Agents for Specific Situations

• 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 may help manage supine hypertension 1

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Special Populations and Considerations

Patients with Concurrent Hypertension

• Consider long-acting dihydropyridine calcium channel blockers or RAS inhibitors as first-line therapy for patients with both hypertension and orthostatic hypotension 1
• For patients aged ≥85 years with hypertension, long-acting dihydropyridine CCBs or RAS inhibitors are preferred first-line agents if antihypertensive therapy is needed 1
• Test for orthostatic hypotension before starting or intensifying any blood pressure-lowering medication in elderly patients 1

Patients with Bradycardia

• The bradycardia component suggests autonomic dysfunction where normal compensatory tachycardia is absent, or medication-induced autonomic failure 3
• 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 3
• Midodrine remains first-line despite potential for slight vagal-mediated heart rate slowing 3

Diabetic Patients

• Assess for cardiovascular autonomic neuropathy 1
• Consider alpha-lipoic acid for painful diabetic neuropathy, which may be beneficial for autonomic function 1
• Use midodrine cautiously in diabetic patients 5

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Monitoring and Follow-Up

Initial Monitoring

• Early review at 24-48 hours after medication initiation 3
• Intermediate follow-up at 1-2 weeks to assess standing heart rate, blood pressure, and symptom improvement 3
• Measure blood pressure after 5 minutes lying/sitting, then at 1 and 3 minutes after standing to document orthostatic changes 1, 3

Ongoing Monitoring

• Monitor for both symptomatic improvement and development of supine hypertension, which can cause end-organ damage 1, 3
• Balance the risk of falls and injury from postural hypotension against cardiovascular protection 1
• Continue midodrine only for patients who report significant symptomatic improvement 5

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Critical Pitfalls to Avoid

• Never simply reduce the dose of BP-lowering medications that worsen orthostatic hypotension - switch to alternative therapy 1, 3
• Never allow patients to take midodrine within 3-4 hours of bedtime due to supine hypertension risk 1, 3, 5
• Never combine multiple vasoconstrictors without careful blood pressure monitoring 3
• Never use fludrocortisone in patients with active heart failure 1
• Never pursue aggressive blood pressure normalization - the goal is symptom relief, not normal BP readings 1, 3
• Never overlook medication review - drug-induced causes are the most common and most reversible 1
• Caution patients about over-the-counter cold remedies and diet aids that can elevate blood pressure and potentiate midodrine's pressor effects 5