Evaluation and management of orthostatic hypotension: Limited data, limitless opportunity

Aldo J. Peixoto

doi:10.3949/ccjm.89gr.22001

Article Figures & Data

Figures

Tables

Download figure
Open in new tab
Download powerpoint
Figure 1
Diagnostic approach to orthostatic hypotension.
^a Delta HR/delta SBP ratio is the ratio of the change in heart rate divided by the change in systolic blood pressure with standing or head-up tilt. Most patients with neurogenic orthostatic hypotension have a ratio below 0.3. Most patients with a normal autonomic response have a ratio above 1.0.

Tables

Figures

View popup

TABLE 1

Relevant causes of peripheral autonomic neuropathies to help guide the diagnostic evaluation

Diabetes mellitus

Amyloidosis
AA (secondary) amyloidosis
AL (light chain, primary) amyloidosis
Transthyretin and other hereditary forms

Toxins
Heavy metals
Vincristine
Paclitaxel
Cisplatin
Thalidomide
Bortezomib

Infections
Human immunodeficiency virus
Chagas disease
Leprosy
Botulism
Diphtheria
Lyme disease
Syphilis

Autoimmune
Sjögren syndrome
Systemic lupus erythematosus
Mixed connective tissue disease
Sarcoidosis
Acute inflammatory demyelinating polyneuropathy
Chronic inflammatory demyelinating polyneuropathy

Hereditary
Hereditary peripheral and autonomic neuropathy
Fabry disease
Allgrove syndrome

Paraneoplastic

Metabolic
Renal failure
Hypothyroidism
Vitamin B₁₂ deficiency
Porphyria

View popup

TABLE 2

Key drugs used in treating orthostatic hypotension

Drug	Class	Advantages	Disadvantages	Comments
Fludrocortisone	Synthetic mineralocorticoid	Increases extracellular volume and blood pressure Increases sensitivity to catecholamines	Supine hypertension Edema Long-acting (half-life 18–36 hours)	Start at 0.1 mg daily; increase to 0.2 mg after 2 weeks Onset of action is not immediate; full effect takes several days to 1 week
Midodrine	Prodrug of desglymidodrine (a direct alpha-1 agonist)	Increases arterial and venous tone and blood pressure Short-acting (half-life 3–4 hours)	Supine hypertension Urinary retention	Start with 2.5 mg three times a day (TID) (early morning, lunchtime, late afternoon); avoid doses within 4–6 hours before bedtime Increase dose by 2.5 mg TID every 3–7 days until symptoms controlled or maximum dose of 10 mg TID reached Higher doses are approved for other indications, but there is a flat dose-response curve at doses above 10 mg
Droxidopa	Precursor of norepinephrine (after conversion by dopa decarboxylase)	Increases arterial and venous tone Short-acting (half-life 2.5 hours)	Supine hypertension	Start with 100 mg TID (early morning, lunch-time, late afternoon) Avoid doses within 4–6 hours before bedtime Increase dose by 100 mg TID every 3–7 days until symptoms controlled or maximum dose of 600 mg TID reached
Pyridostigmine	Anticholinesterase	Improves standing blood pressure without change in supine blood pressure Short-acting (half-life 3–4 hours)	Wheezing Abdominal pain Diarrhea Hyperhidrosis	Useful in patients with constipation with or without urinary hesitancy Start with a 30-mg test dose; if well tolerated, give 60 mg twice a day, increasing to TID after 1–2 weeks if tolerated Seldom used at doses > 90–120 mg TID Titrations made every 1–2 weeks
Atomoxetine	Selective norepinephrine reuptake inhibitor	Increases standing blood pressure	Supine hypertension Irritability Insomnia Aggressive behavior Suicidal ideation	Used in lower doses than for attention deficit hyperactivity disorder Start at 10 mg once daily in morning, increasing to 18 mg, then 25 mg once daily Higher doses avoided, though safe to use up to 50 mg daily Titrations made every 1–2 weeks Half-life 5 hours, active metabolites 6–8 hours