Orthostatic Hypotension

Aka: Orthostatic Hypotension, Postural Hypotension, Orthostatic Blood Pressure, Orthostasis, Orthostatic Syncope, Postural Blood Pressure, Postural Pulse, Shellong Test, Postprandial hypotension

1. See Also
   1. Medication Causes of Orthostatic Hypotension
   2. Dizziness
2. Definitions
   1. Orthostatic Hypotension
      1. Blood Pressure drop on standing of >20 mmHg systolic or 10 mHg diastolic
      2. Occurs within 3 minutes of standing from supine (or at 60 degrees on Tilt Table testing)
   2. Orthostatic Heart Rate
      1. Heart Rate increase on standing from supine of 30 beats per minute
      2. Occurs within 3 minutes of standing from supine
      3. Expected compensatory response that is lacking in neurogenic Orthostatic Hypotension
   3. Postprandial hypotension
      1. Systolic Blood Pressure drop >20 mmHg from baseline >100 mmHg within 2 hours of a meal
3. Epidemiology
   1. Orthostatic Hypotension Prevalence increases with age and debility
      1. Middle Age: 5%
      2. Age > 60 years: 20%
      3. Nursing Home: 50%
      4. Geriatric medical ward: 68%
   2. Orthostatic Hypotension related hospital admissions (U.S., 2007)
      1. All adults: 36 per 100,000
      2. Adults>75 years: 233 per 100,000
4. Physiology
   1. Event: Rising from lying to standing position
      1. Intravascular volume redistributes and 300 to 800 ml of blood pools in legs (and splanchnic circulation)
      2. Results in decreased venous return and decreased Cardiac Output
   2. Physiologic response
      1. Lower extremity Muscle Contraction compresses veins
      2. Autonomic response
         1. Baroreceptors sense change in Blood Pressure
            1. Carotid Sinuses (carotid arteries, via Glossopharyngeal Nerve)
            2. Aortic Baroreceptors (aortic arch, via Vagus Nerve)
         2. Sympathetic Nervous System response
            1. Increases vascular tone (Peripheral Vascular Resistance)
            2. Increases Heart Rate and cardiac contractility
      3. Orthostatic Hypotension causes
         1. Inadequate autonomic response (neurogenic) OR
         2. Insufficient intravascular volume or circulation (nonneurogenic)
   3. Modifiers
      1. Age
         1. Baroreceptor sensitivity decreases resulting in a delayed autonomic response
         2. Affects 20% in age > 60 years (but only 5% in middle aged adults, see above)
      2. Decreased Blood Volume or Dehydration
         1. Baroreceptors trigger increased renin and Vasopressin
         2. Results in increased Sodium and water reabsorption
      3. Postprandial hypotension
         1. Systolic Blood Pressure drop >20 mmHg from baseline >100 mmHg within 2 hours of a meal
         2. More common in comorbid Diabetes Mellitus, other neurologic disorders and Hypertension
         3. Associated with higher risk of Syncope, increased coronary events and mortality
5. Risk Factors
   1. Older adults (esp. age >70 years)
   2. Polypharmacy
      1. See Medication Causes of Orthostatic Hypotension
   3. Peripheral Neuropathy
      1. Diabetic Neuropathy (most common)
      2. Amyloidosis
      3. HIV Infection
   4. Neurodegenerative disorders
      1. Lewy Body Dementia
      2. Multiple System Atrophy
      3. Parkinsonism
      4. Pure autonomic failure
6. Symptoms
   1. May be asymptomatic
   2. Symptoms occur on standing from supine (or seated position) and are relieved on returning to supine position
      1. Symptoms are a result of transient Hypotension causing decreased end organ perfusion
   3. Dizziness or light headedness
   4. Chest Pain or Palpitations
   5. Orthostatic Syncope
   6. Nausea
   7. Pallor
   8. Weakness or Fatigue
   9. Dyspnea
   10. Blurred or dimmed Vision
   11. Neck or Shoulder Pain
7. Exam
   1. See Head-Up Tilt Table Test
   2. Orthostatic Blood Pressure and Pulse (Shellong Test)
      1. Technique
         1. Supine Blood Pressure and pulse after lying for 5 minutes
         2. Standing Blood Pressure, pulse after 3 minutes standing, from supine position
      2. Interpretation
         1. Orthostatic Hypotension is present if Blood Pressure drops >=20 mmHg systolic or 10 mmHg diastolic
            1. In supine Hypertension, use systolic BP drop >=30 mmHg for diagnosis (see below)
         2. Heart Rate increase >30 bpm on standing from supine is suggestive of Orthostasis
            1. Compensatory Heart Rate is present in nonneurogenic Orthostasis (e.g. Dehydration)
            2. Compensatory Heart Rate is ABSENT in neurogenic Orthostasis (defective autonomic response)
            3. Heart Rate increases without BP drop in Postural Orthostatic Tachycardia Syndrome (POTS)
   3. Supine Hypertension
      1. Systolic BP >140 mmHg or Diastolic BP >90 mmHg after 5 minutes in supine position
      2. If supine Hypertension is present, use systolic BP drop >=30 mmHg for Orthostatic Hypotension diagnosis
      3. Supine Hypertension affects >50% of patients with neurogenic Orthostatic Hypotension
         1. Often worsened with antihypertensive medications
   4. Response to 15 second Valsalva Maneuver
      1. Normally Blood Pressure falls, then rises over baseline
      2. Abnormal if Blood Pressure does not overshoot baseline
   5. Pulse variation on deep breathing (sinus Arrhythmia)
      1. Normal response
         1. Tachycardia on inspiration
         2. Bradycardia on expiration
      2. Abnormal if <9 beat/min difference during cycle
8. Efficacy: Orthostatic Blood Pressure and Pulse as a Hydration Marker
   1. Orthostatic Vital Signs have low utility and other measures should be used to assess volume status
      1. Swaminathan In Herbert (2013) EM: Rap 13(11): 6-7
   2. Orthostatic Blood Pressure and pulse are poor indicators of Hypovolemia in Hemorrhage and Dehydration
      1. McGee (1999) JAMA 281(11): 1022-9 [PubMed]
      2. Johnson (1995) Acad Emerg Med 2(8):692-7 [PubMed]
   3. Orthostasis is present in as many as 20-50% of those over age 65 years (and typically asymptomatic)
      1. Rutan (1992) Hypertension 19(6 pt 1): 508-19 [PubMed]
      2. Ooi (1997) JAMA 277(16):1299-304 [PubMed]
9. Causes: Neurogenic
   1. Background
      1. Inadequate autonomic response to standing from supine
      2. Compensatory Heart Rate response to standing is typically ABSENT
      3. May be associated with neurologic deficits (e.g. Parkinsonism, Dementia, Ataxia)
      4. May be associated with autonomic failure symptoms (e.g. Postprandial hypotension, morning symptoms)
      5. Associated with supine Hypertension in >50% of cases (see exam above)
   2. Trauma or mass
      1. Spinal cord injury
      2. Traumatic Brain Injury
      3. Syringomyelia
   3. Infectious and Inflammatory
      1. Tabes Dorsalis
      2. Human Immunodeficiency Virus (HIV)
   4. Autonomic alpha-synucleinopathy
      1. Lewy Body Dementia
      2. Multiple System Atrophy
      3. Parkinsonism
      4. Pure Autonomic Failure
   5. Peripheral Autonomic Disorders
      1. Diabetic Neuropathy
      2. Amyloidosis
      3. Alcohol Abuse
      4. Vitamin B12 Deficiency (Pernicious Anemia)
      5. Postprandial hypotension (occurs within 2 hours of a meal)
   6. Carotid Sinus Hypersensitivity
      1. Cardioinhibitory Syncope
      2. Vasodepressor Syncope
   7. Miscellaneous
      1. Guillain-Barre Syndrome
      2. Post-sympathectomy
      3. Idiopathic Orthostatic Hypotension
      4. Shy-Drager Syndrome
10. Causes: Nonneurogenic
    1. Background
       1. Inadequate cardiovascular response to standing from supine
       2. Compensatory Heart Rate response to standing is typically PRESENT (Heart Rate increases)
          1. Expect Heart Rate increase of at least 0.5 bpm per mmHg decrease in systolic Blood Pressure
          2. Norcliffe-Kaufmann (2018) Ann Neurol 83(3): 522-31 [PubMed]
    2. Medications
       1. See Medication Causes of Orthostatic Hypotension
    3. Cardiogenic
       1. Myocardial Infarction
       2. Arrhythmia
       3. Aortic Stenosis
       4. Myocarditis
       5. Pericarditis
       6. Bradycardia
       7. Congestive Heart Failure
    4. Hypovolemia (Tachycardia present, most common)
       1. Dehydration
       2. Hemorrhage
       3. Sepsis (Distributive Shock)
       4. Anemia
       5. Burn Injury
       6. Adrenal Insufficiency
       7. Diabetes Insipidus
       8. Hyperglycemia
       9. Straining
          1. Heavy lifting
          2. Urinating (Micturition Syncope)
    5. Venous pooling
       1. Venous Insufficiency
       2. Prolonged bed rest
       3. Strenuous Exercise
       4. Fever
       5. Sepsis
       6. Heat exposure
       7. Alcohol Intoxication
       8. Pregnancy or postpartum
    6. Miscellaneous causes
       1. Aging (esp. age >70 years)
       2. Hypokalemia
       3. Hypothyroidism
11. Differential Diagnosis
    1. See Hypotension
    2. See Syncope
    3. Postural Orthostatic Tachycardia Syndrome (POTS)
       1. Symptoms of Orthostasis with Tachycardia, but insignificant Hypotension
    4. Orthostatic Intolerance
       1. Symptoms of Orthostasis that make upright Posture difficult to maintain
12. Labs
    1. Basic metabolic panel (Electrolytes, Renal Function tests, Serum Glucose)
    2. Complete Blood Count
    3. Serum Vitamin B12
    4. Electrocardiogram (EKG)
    5. Thyroid Stimulating Hormone (TSH)
    6. Consider morning Cortisol level
    7. Consider Holter Monitor if unexplained symptoms
13. Imaging
    1. Head CT or Head MRI
    2. Echocardiogram
14. Evaluation
    1. See Head-Up Tilt Table Test
    2. Consider intravascular volume replacement (IV Fluids) in nonneurogenic Orthostasis
    3. Consider causes above (including Medication Causes of Orthostatic Hypotension)
    4. Evaluate for supine Hypertension (see above)
       1. Consider 24 hour Ambulatory Blood Pressure Monitoring in supine Hypertension
15. Complications
    1. Orthostatic Syncope
    2. Orthostatic Hypotension is associated with increased cardiovascular risks and mortality
       1. Increased risks of Myocardial Infarction and Congestive Heart Failure
       2. Increased fall risk
       3. Increased mortality
       4. Ricci (2015) Eur Heart J 36(25): 1609-17 [PubMed]
       5. Federowski (2010) Eur Heart J 31(1): 85-91 [PubMed]
16. Management
    1. General goals
       1. Reduce symptoms and improve quality of life
       2. Interventions are not intended to normalize Blood Pressure to a specific number
    2. Avoid medications related to Orthostasis (e.g. Opioids, psychoactive agents, Anticholinergic Medications)
       1. See Medication Causes of Orthostatic Hypotension
       2. Decrease dose or change medication to one less likey to cause Orthostatic Hypotension
          1. Consider stopping Tricyclic Antidepressants, Antipsychotics
       3. Consider nighttime dosing of antihypertensives
    3. Treat underlying causes
       1. Correct Anemia
       2. Correct Vitamin B12 Deficiency
       3. Correct Hypothyroidism
       4. Correct Electrolyte abnormalities (e.g. Hypokalemia)
       5. Optimize Blood Sugar management in Diabetes Mellitus (see Diabetic Neuropathy)
    4. Modify diet
       1. Increase salt
          1. Maintain at least 2 to 3 grams Sodium daily
          2. Consider supplement up to 1-2 grams extra-per day (avoid in CHF, Edematous States)
          3. Target 24 hour urinary Sodium >170 mmol Sodium in 24 hours
       2. Increase water intake (>64 ounces or >2 Liters daily)
          1. Target >1500 ml Urine Output daily
       3. Avoid Alcohol
       4. Eat smaller, more frequent meals (avoid large carbohydrate rich meals)
          1. Reduces risk of Postprandial hypotension
          2. Postprandial hypotension may also respond to Acarbose (Alpha-glucosidase Inhibitor)
    5. Modify activity
       1. Avoid excessive heat exposure
       2. General activity and Exercise should be encouraged
          1. However, avoid Exercise with frequent position changes or very strenuous Exercise
       3. Sleep with head of bed slightly elevated to 30 to 45 degrees
          1. Variable evidence
       4. Rise from bed slowly allowing for equilibration
       5. Avoid standing for long periods of time
       6. Isometric Exercises
          1. Work arms, legs and abdominal Muscles (e.g. toe raises, thigh contractions, forward flexion at waist)
       7. While standing, move frequently and stand with crossed legs (consider leaning forward)
       8. Squatting will also help maintain upright Posture
       9. Avoid work with arms above Shoulder height
       10. Dorsiflex feet several times before standing
       11. Consider graded Compression Stockings (30 to 40 mmHg)
    6. Consider medication therapy (esp. for neurologic causes)
       1. Review precautions before using
       2. Consult specialty care (e.g. neurology, cardiology)
       3. Fludrocortisone (Florinef)
          1. Synthetic Mineralocorticoid that increases Sodium and water retention
          2. Also increases vascular alpha-Adrenergic Receptor sensitivity resulting in Vasoconstriction
          3. Precaution
             1. Monitor for Hypokalemia
             2. Risk of Congestive Heart Failure exacerbation
             3. Risk of longterm Left Ventricular Hypertrophy and Renal Failure
          4. Start at 0.1 mg daily, titrate weekly by 0.1 mg to maximum of 1mg daily
          5. Target
             1. Improved symptoms
             2. Significant Edema
             3. Weight gain > 3.6 kg
       4. Midodrine (ProAmitine)
          1. Limit to specialist use (FDA recommends removing from market due to lack efficacy)
          2. Short acting alpha-1 Adrenergic Agonist results in Vasoconstriction (increased Peripheral Vascular Resistance)
          3. Increases Blood Pressure for 2-3 hours
          4. Risk of supine Hypertension (take at least 3-5 hours before bedtime)
          5. Contraindicated in Coronary Artery Disease, Hyperthyroidism, Acute Renal Failure
          6. Start at 2.5 three times daily, titrate weekly by 2.5 mg to maximum dose of 10 mg three times daily
       5. Northera (droxidopa)
          1. Very expensive ($7800/month) compared to other agents listed above (e.g. Fludrocortisone is $35/month)
          2. Short-acting Norepinephrine precursor that like Midodrine increases Peripheral Vascular Resistance
          3. Similar risks to Midodrine
          4. Start at 100 mg orally three times daily and titrate up to maximum of 600 mg orally three times daily
    7. Other adjunctive medications
       1. Pyridostigmine (Mestinon)
          1. Start at 30 mg bid to tid and titrate to symptom control or up to 60 mg three times daily
       2. Atomoxetine (Strattera)
          1. Dosing: 18 mg orally once daily
17. References
    1. (2017) Presc Lett 24(2): 10
    2. Engstrom (1997) Am Fam Physician 56(5):1378-84 [PubMed]
    3. Kim (2022) Am Fam Physician 105(1): 39-49 [PubMed]
    4. Lanier (2011) Am Fam Physician 84(5): 527-36 [PubMed]
    5. Low (2015) J Clin Neurol 11(3):220-6 +PMID:26174784 [PubMed]
    6. Mathias (1995) Neurology 45:S6-11 [PubMed]