Orthostatic hypotension
Synonyms and keywords: Postural hypotension; orthostatic intolerance; head rush; dizzy spell

# Overview
Orthostatic hypotension or postural hypotension is defined as a reduction of systolic blood pressure of at least 20 mm Hg or 10 mm Hg in diastolic blood pressure within 3 minutes of standing. A similar fall during head-up tilt test at 60 degrees also defines orthostatic hypotension. Orthostatic hypotension may be asymptomatic or may cause symptoms of lightheadedness, dizziness, blurred vision or cognitive impairment. It may have acute or chronic causes. Management of orthostatic hypotension may be challenging, in particular in patients with orthostatic hypotension and concomitant supine hypertension. 

# Classification
- Based on the underlying pathophysiology correlated to a postural drop in blood pressure, orthostatic hypotension can be classified into:
Initial orthostatic hypotension (iOH)
- It is most common in healthy adolescents
- It is demarcated as a brief BP decrease of >40 mmHg systolic or >20 mmHg diastolic with symptomatic cerebral hypoperfusion within five to fifteen seconds after standing, typically resolved by twenty seconds.
Neurogenic orthostatic hypotension (nOH)
- In Neurogenic orthostatic hypotension, the sympathetic noradrenergic nerves continually fail to facilitate the reflexive cardiovascular responses essential to sustain blood pressure in response to orthostatic stress.
- It is described as a constant BP decrease of >20 mmHg systolic or >10 mmHg diastolic, without or with symptoms, within three minutes of head-up tilt or standing.
Delayed orthostatic hypotension (dOH)
- Delayed orthostatic hypotension (dOH) is demarcated as a fall in blood pressure that accomplishes neurogenic orthostatic hypotension criteria but ensues after three minutes.
Neurally mediated syncope (vOH)
- It is also recognized as vasodepressor or vasovagal syncope, it involves a  paroxysmal extraction of sympathetic vasopressor tone, frequently during prolonged standing, in patients with an effective autonomic nervous system.
Cardiovascular orthostatic hypotension (cOH)
- Cardiovascular orthostatic hypotension occurs from intravascular hypovolemia or reduced cardiac output along with compensatory tachycardia.
Orthostatic pseudohypotension (pOH)
- It is stated as apparent orthostatic hypotension when baseline supine blood pressure is raised, which may be due to a short time at rest to create a valid baseline, related recumbent hypertension, or fluctuation of baseline blood pressure with labile hypertension 

# Pathophysiology
- In the standing position, 500 to 1000 mL of blood pools in the lower extremities and splanchnic circulation, causing a rapid decline in venous return to the heart.
- Decreased ventricular filling pressures lower cardiac output and systemic blood pressure. 
- Baroreceptors located mainly in the aorta and carotid arteries are very sensitive to fluctuations in blood pressure. A fall in blood pressure decreases the stretching of baroreceptors, thus decreasing their firing. The decreased firing of baroreceptors increases sympathetic and decreases parasympathetic outflow.
- This compensatory reflex increases heart rate, contractility and peripheral vascular resistance (i.e., both arteriolar and venous vasoconstriction). These changes result in increased venous return and increased cardiac output, and limit the decline in blood pressure. This compensatory reflex is known as baroreflex.
- Any disruption in this pathway can cause a significant decline in blood pressure upon standing (i.e., orthostatic hypotension), causing symptoms of cerebral hypoperfusion including nausea, dizziness, headache, lightheadedness, blurred vision, and impaired cognition.
- Although many pathologic causes may alter this normal physiologic response to standing, the most common pathophysiologic mechanisms include:
Autonomic dysfunction affecting the baroreflex (i.e. baroreflex dysfunction)
Volume depletion
Adverse effects of certain medications
- Autonomic dysfunction affecting the baroreflex (i.e. baroreflex dysfunction)
- Volume depletion
- Adverse effects of certain medications

# Causes
Common causes of orthostsic hypotension include: 

# Differentiating Orthostatic Hypotension from Other Diseases
Orthostatic hypotension must be differentiated from neurogenic syncope, cardiogenic syncope, situational syncope, multiple system atrophy with orthostatic hypotension, neurally mediated hypotension, postural orthostatic tachycardia syndrome (POTS) and vasovagal syncope 

# Epidemiology and Demographics
Incidence
- The approximation of orthostatic hypotensionassociated hospitalization is 36 per 100,000 adults, and the rate can be as high as 233 per 100,000 patients >75 years of age. 
Prevalence
- The overall prevalence of orthostatic hypotension depends on age as it increases with age in the general population.
- The prevalence ranges from 5% in patients 70 years of age.
- It is ~20% in >65-year-old patients. 
Age
- Orthostatic Hypotension is commonly seen in individuals older than 50 years of age.
Gender
- Orthostatic hypotension affects men and women equally.

# Risk Factors
Common risk factors in the development of orthostatic hypotension include: 
- Age (>65)
- Medications
- Autonomic neuropathies, such asParkinson's disease, diabetes
- Volume depletion
- Postpartum period
- Prolong bedrest.

# Screening
- Orthostatic hypotension screening consists of blood pressure measurements in supine (or sitting) and standing position during clinical consultations. 

# Natural History, Complications, and Prognosis

### Natural History
- The symptoms of orthostatic hypotension mainly develop in the elderly, and start with generalized symptoms of dizziness, lightheadedness, or syncope and less frequently with headache, leg buckling, or chest pain 

### Complications
Common complications of orthostatic hypotension  include: 
- Symptomatic orthostatic hypotension may cause falling.  
The risk of recurrent falls is particularly higher in frail, older adults.
- The risk of recurrent falls is particularly higher in frail, older adults.
- According to various studies, orthostatic hypotension may be a risk factor for:      
Cardiovascular and all-cause mortality
Cardiovascular events
Congestive heart failure
Atrial fibrillation
Cognitive decline or dementia
Anxiety, depression, and impaired quality of life
- Cardiovascular and all-cause mortality
- Cardiovascular events
- Congestive heart failure
- Atrial fibrillation
- Cognitive decline or dementia
- Anxiety, depression, and impaired quality of life

### Prognosis
- Depending on the underlying cause of orthostatic hypotension, the prognosis may vary.

# Diagnosis

## Diagnostic study of choice
- Orthostatic vitals are the best diagnostic tests that are simple and easy to perform in a clinical setting. 
- Blood pressure and heart rate should be measured within 2-5 minutes of standing after a 5-minute period of supine rest.
- Orthostatic hypotension is diagnosed when there is:
At least a 20 mmHg decline in systolic blood pressure
At least 10 mmHg decline in diastolic blood pressure
- At least a 20 mmHg decline in systolic blood pressure
- At least 10 mmHg decline in diastolic blood pressure
- The absence of the normal rise in heart rate on standing is a diagnostic clue to the presence of autonomic dysfunction; however, an increased heart rate cannot exclude autonomic failure.

## History and Symptoms
- When evaluating a patient with orthostatic hypotension, the following features in history may provide a clue to the diagnosis: 
- Use of certain medications known to cause orthostatic hypotension.
- Recent history of volume depletion (such as fever, fluid restriction, vomiting, diarrhea, hemorrhage)
- Medical history of common diseases causing orthostatic hypotension, such as congestive heart failure, diabetes, Parkinson's disease, malignancies.
- History of alcohol consumption
- Particular attention should be made to the presence of neurologic symptoms (e.g., parkinsonism, ataxia, peripheral neuropathy) or symptoms of autonomic dysfunction (e.g. abnormal pupillary response, chronic constipation, erectile dysfunction, urinary incontinence)
- Symptoms of orthostatic hypotension are prominent immediately upon standing, might improve in sitting position, and disappear in the supine position (i.e., postural symptoms). 
- Symptoms may also be seen in association with meals, exercise, and prolonged standing
- Symptoms are due to cerebral hypoperfusion
- Symptoms usually last for few minutes
- The most common symptoms are lightheadedness and dizziness upon standing.
- Other symptoms include:
- Generalized weakness
- Headache
- Blurred or dimmed vision (possibly to the point of momentary blindness)
- Fatigue
- Cognitive impairment
- Loss of consciousness (syncope) may be seen in severe cases

## Physical Examination
Common physical examination findings of orthostatic hypotension include checking the blood pressure, pulse, and symptoms while having the patient in the standing and sitting position. 

## Laboratory Findings
There are no diagnostic laboratory findings associated with orthostatic hypotension. While the definitive diagnosis of orthostatic hypotension is made clinically, other tests contribute to understanding the risks of disease and may provide clues to the selection of treatment options. 
These tests include those that access the underlying cause that may be altered in patients suffering from orthostatic hypotension.
- CBC
- Basic metabolic panel
- Serum electrolytes
- Blood Glucose
- Creatinine
- TSH

## Electrocardiogram
An ECG may be helpful in the diagnosis of cardiovascular causes of orthostatic hypotension.

## X-ray
There are no x-ray findings associated with orthostatic hypotension.

## Echocardiography
Echocardiography may be helpful in the diagnosis of orthostatic hypotension. Findings on an echocardiography diagnostic of orthostatic hypotension include cardiac structural changes such as left ventricular hypertrophy, development of diastolic dysfunction, and decreased right chamber volume. 

## CT scan
A CT scan may be helpful in the diagnosis of orthostatic hypotension. Findings on a CT scan diagnostic of orthostatic hypotension include the presence of a cerebral tumor or communicating hydrocephalus. 

## MRI
A brain MRI may be helpful in the diagnosis of orthostatic hypotension. Findings on a MRI suggestive of orthostatic hypotension include:
- Neurodegenerative disorder
- Stroke

## Other Imaging Findings
There are no other diagnostic studies associated with orthostatic hypotension.

## Other Diagnostic Studies
There are no other diagnostic studies associated with orthostatic hypotension.

# Treatment
- Asymptomatic hypotension is a common finding in practice and does not require any treatment.
- There is no specific target blood pressure goals in the management of orthostatic hypotension.
- However, management is targeted to alleviate symptoms, prevention of future falls, and excessive supine hypertension.
- Management of orthostatic hypotension can be categorized into lifestyle modifications and medical therapy.
- Education of the patient and non-pharmacological treatments are the cornerstone of treatment of orthostatic hypotension.

## Non-Pharmacological Therapy
- Education of the patient and non-pharmacological treatments are the cornerstone of treatment of orthostatic hypotension.
- Cessation of orthostatic hypotension inducing drugs such as anti-hypertensivess in patients with a mean blood pressure below target value is recommended.
- Avoidance of certain factors that aggravate hypotension such as heat, and alcohol intake.
- Consumption of large meals induces splanchnic vasodilation thereby resulting in hypotension postprandially.
Fractionated meals are recommended in patients with postprandial symptoms.
- Fractionated meals are recommended in patients with postprandial symptoms.

## Medical Therapy
- Pharmacological: Some drugs that are used in the treatment of orthostatic hypotension include fludrocortisone (Florinef), erythropoietin, midodrine and Pyridostigmine bromide (Mestinon) 

## Initial Therapy
- Preferred regimen (1): Fludrocortisone acetate at a dose of 0.1 mg per day, administered in the morning, which can eventually be increased up to 0.3 mg per day.
Considered first-line regimen for hypotension in the absence of heart failure and supine hypertension
- Considered first-line regimen for hypotension in the absence of heart failure and supine hypertension
- Preferred regimen (2): Midodrine 2.5 to 10 mg three times a day.
Max dose should not exceed 40 mg/day.
- Max dose should not exceed 40 mg/day.
- Preferred regimen (2): Droxidopa starts at 100 mg and escalates to 600 mg three times per day.
Patients should not take droxidopa within four to five hours of bedtime in order to limit supine hypertension.
- Patients should not take droxidopa within four to five hours of bedtime in order to limit supine hypertension.

## Second-line Therapy
- Preferred regimen (1): Erythropoietin is administered SC or IV at doses between 25 to 75 units/kg three times a week.
- Preferred regimen (1): Methylxanthine caffeine  100 to 250 mg three times a day with meals.
- Preferred regimen (1): Pyridostigmine initiated at a dose of 30 mg three times daily, up to a maximum dose of 90 mg three times daily.
- Preferred regimen (1): Non-steroidal anti-inflammatory drugs are rarely effective as monotherapy
They can supplement treatment with fludrocortisone or a sympathomimetic agent.
- They can supplement treatment with fludrocortisone or a sympathomimetic agent.

## Third-line Therapy
- Preferred regimen (1): Atomoxetine
- Preferred regimen (1): Vasopressin analogs (desmopressin (DDAVP))
- Preferred regimen (1): Yohimbine a single dose of yohimbine (5.4 mg).
Yohimbine has limited availability in the United States.
- Yohimbine has limited availability in the United States.
- Preferred regimen (1): Somatostatin subcutaneous doses range from 25 to 200 mcg.
- Preferred regimen (1): Ergotamine-caffeine (1 mg/100 mg) up to twice-daily dosing in patients with orthostatic hypotension.
- Preferred regimen (1): Metoclopramide and domperidone

## Primary Prevention
Effective measures for the primary prevention of orthostatic hypotension include:
ABCDEF method
- A.     Abdominal compression: Wear an abdominal binder when out of bed
- B.	A bolus of water/elevate bed: On bad days, drink two 8-ounce glasses of cold water prior to prolonged standing and sleep with the head of the bed raised about 4 inches
- C.	Counter-maneuvers:  While standing, contract the lower abdominal muscles for about 30 seconds
- D.	Drugs: Midodrine, Pyridostigmine, or Fludrocortisone can be used to elevate blood pressure (acknowledge any medications currently taken that can lower blood pressure)
- E.	Education & Exercise: Note any symptoms that indicate a fall in blood pressure while standing, recognize conditions that lower blood pressure (i.e. heavy metals, temperature changes, exercise, change in position)
- F.	Fluids: Stay hydrated