How is postural hypotension managed?

Management of Postural Hypotension

Begin with non-pharmacological interventions for all patients, and add midodrine as first-line pharmacological therapy if symptoms persist despite these measures, with fludrocortisone as an alternative or adjunct agent. 1, 2

Initial Assessment and Reversible Causes

• Immediately review and discontinue medications that worsen orthostatic hypotension rather than simply reducing doses—this includes diuretics, alpha-1 adrenergic blockers (prazosin, terazosin, doxazosin), ACE inhibitors, and vasodilators 1
• Measure blood pressure after 5 minutes of lying/sitting, then at 1 and 3 minutes after standing to confirm the diagnosis (drop of ≥20 mmHg systolic or ≥10 mmHg diastolic) 1, 2
• Assess for volume depletion, which is often an overlooked contributing factor 1

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

Volume expansion strategies:

• Increase fluid intake to 2-3 liters daily unless contraindicated by heart failure 1, 2
• Increase salt consumption to 6-10 grams daily (approximately 1-2 teaspoons of table salt) if not contraindicated 1, 2
• Acute water ingestion of ≥480 mL provides temporary relief with peak effect at 30 minutes—plain water is more effective than salt water 1, 2

Physical countermeasures (particularly effective in patients under 60 years with prodromal symptoms):

• Teach leg crossing, squatting, stooping, and muscle tensing during symptomatic episodes 1, 2
• These maneuvers increase venous return and can abort symptoms if applied early 1

Compression therapy:

• Use waist-high compression stockings (30-40 mmHg) and abdominal binders to reduce venous pooling 1
• Compression garments over legs and abdomen are essential adjuncts 3

Lifestyle modifications:

• Elevate the head of bed by 10 degrees during sleep to prevent nocturnal polyuria, maintain favorable fluid distribution, and reduce supine hypertension 1, 2
• Eat smaller, more frequent meals to reduce post-prandial hypotension 3, 1, 2
• Encourage physical activity and exercise to avoid deconditioning, which exacerbates orthostatic intolerance 3, 1
• Implement gradual staged movements with postural changes 1

Pharmacological Management (When Non-Pharmacological Measures Fail)

First-Line: Midodrine

Midodrine has the strongest evidence base among pressor agents for orthostatic hypotension, with three randomized placebo-controlled trials demonstrating efficacy. 1, 4

• Starting dose: 2.5-5 mg three times daily 1, 2, 4
• Mechanism: Alpha-1 adrenergic agonist that increases vascular tone through arteriolar and venous constriction 1, 2
• Expected effect: Increases standing systolic BP by 15-30 mmHg for 2-3 hours after dosing 1
• Critical timing: Administer the last dose at least 3-4 hours before bedtime (never after 6 PM) to prevent supine hypertension during sleep 1, 4
• FDA indication: Approved for symptomatic orthostatic hypotension in patients whose lives are considerably impaired despite standard clinical care 4

Important precautions for midodrine:

• Use cautiously in older males due to potential urinary retention (acts on alpha-adrenergic receptors of bladder neck) 4
• Monitor for bradycardia—discontinue if pulse slowing, increased dizziness, syncope, or cardiac awareness occurs 4
• Can cause marked elevation of supine BP (>200 mmHg systolic) 4

Second-Line: Fludrocortisone

Add fludrocortisone if midodrine alone provides insufficient symptom control, or use as an alternative first-line agent. 1, 2

• Starting dose: 0.05-0.1 mg once daily 3, 1, 2
• Titration: Individually adjust to 0.1-0.3 mg daily (maximum 1.0 mg daily) 3, 1
• Mechanism: Mineralocorticoid that increases plasma volume through sodium retention and has direct vessel wall effects 3, 1, 2

Monitoring requirements for fludrocortisone:

• Check for supine hypertension (the most important limiting factor) 1
• Monitor electrolytes periodically for hypokalemia due to mineralocorticoid effects 3, 1
• Assess for peripheral edema and signs of congestive heart failure 3, 1

Contraindications:

• 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 evidence for fludrocortisone is limited, with only very low-certainty evidence from small, short-term trials 1, 5

Third-Line: Droxidopa

• FDA-approved for neurogenic orthostatic hypotension, particularly effective in Parkinson disease, pure autonomic failure, and multiple system atrophy 3, 1
• May reduce falls in these populations 1

Refractory Cases: Pyridostigmine

• Consider pyridostigmine for refractory orthostatic hypotension in elderly patients who have not responded to other treatments 1
• Has a favorable side effect profile compared to alternatives like fludrocortisone 1
• Common side effects include nausea, vomiting, abdominal cramping, sweating, salivation, and urinary incontinence 1

Treatment Goals and Monitoring

The therapeutic objective is minimizing postural symptoms and improving functional capacity, NOT restoring normotension. 3, 1, 2

• Measure orthostatic vital signs at each follow-up visit 1
• Reassess within 1-2 weeks after medication changes 1
• Monitor for supine hypertension development, which can cause end-organ damage 1, 2
• Continue midodrine only for patients who report significant symptomatic improvement 4

Special Populations

Diabetic patients:

• Assess for cardiovascular autonomic neuropathy, as symptoms are often rare despite significant blood pressure drops 2
• Use midodrine cautiously in diabetic patients 4
• Consider alpha-lipoic acid for painful diabetic neuropathy, which may also benefit autonomic function 1

Patients with concurrent hypertension:

• Switch to long-acting dihydropyridine calcium channel blockers (e.g., amlodipine) or RAS inhibitors as first-line antihypertensive agents 1, 2
• Avoid combining multiple vasodilating agents (ACE inhibitors + calcium channel blockers + diuretics) without careful monitoring 1
• Consider shorter-acting antihypertensives at bedtime (guanfacine, clonidine, isradipine, atenolol, metoprolol tartrate, or enalapril) to manage supine hypertension 3, 1

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 to prevent nocturnal supine hypertension 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 combine multiple vasodilating agents without careful monitoring 1
• Avoid medications that can exacerbate orthostatic hypotension: psychotropic drugs, diuretics, alpha-adrenoreceptor antagonists, opioids, anticholinergics, tricyclic antidepressants, GLP-1 receptor agonists, and pramlintide 3, 1

Drug Interactions

• Cardiac glycosides with midodrine may enhance bradycardia, AV block, or arrhythmia 4
• Avoid MAO inhibitors or linezolid with midodrine 4
• Drugs that increase blood pressure (phenylephrine, pseudoephedrine, ephedrine, dihydroergotamine, thyroid hormones, droxidopa) increase hypertension risk with midodrine—avoid concomitant use or monitor BP closely 4
• Alpha-adrenergic blocking agents (prazosin, terazosin, doxazosin) antagonize midodrine's effects 4