Orthostatic hypotension

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sogand Goudarzi, MD [2]; Norina Usman, M.B.B.S[3]

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 resolves 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 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

Causes

Common causes of orthostsic hypotension include:

Causes of orthostatic hypotension

Cardiac diseases

Myocardial ischemia/Myocardial infarction

Cardiac arrhythmias

Congesive heart failure

Myocarditis/pericarditis

Valvular heart diseases

Intravascular volume depletion

Anemia

Blood loss

Dehydration

Diuretics

Venous pooling/venous vasodilation

Prolonged bed rest

Pregnancy

Venous insufficiency/Varicosities

Autonomic nervous system disorders

Primary: Pure autonomic failure Multiple system atrophy

Secondary: Diabetes Amyloidosis Sarcoidosis Renal failure

Endocrine

Adrenal insufficiency

Diabetes insipidus

Hyperglycemia (acute)

Hypoaldosteronism

Hypokalemia

Hypothyroidism

Pheochromocytoma

Medications

Miscellaneous

AIDS

Anxiety or panic disorder

Eating disorders

Postprandial hypotension

Medication-induced Orthostatic Hypotension
		Vasodilation through Alpha-1 blockade	Alpha-1 blockers: Terazosin Prazosin Doxazosin Antipsychotics: Perphenazine Risperidone Thioridazine hydrochloride Clozapine zotepine Olanzapine Fluphenazine Antihistamines Antidepressants: Trazodone Tricyclic antidepressants (TCAs) Serotonin norepinephrine reuptake inhibitors (SNRIs): Venlafaxine Duloxetine Monoamine oxidase inhibitors
Vasodilation (Others)	ACE Inhibitors ARBs Dihydropyridine calcium channel blockers Hydralazine Nitrates Phosphodiesterase inhibitors: Sildenafil
Volume depletion	Diuretics: Ethacrynic Acid Hydrochlorothiazide Furosemide SGLT-2 inhibitors
Sympathetic blockade	Ganglionic blocking agents Beta Blockers: Propranolol Clonidine
Dopamin agonists and other anti-Parkinsonian medications	Dopamine agonists Bromocriptine Pramipexole Ropinirole Levodopa Monoamine oxidase inhibitors: Selegiline Rasagiline COMT inhibitors: Entacapone
Others	Alcohol Apomorphine hydrochloride Cidofovir Iloperidone Loxapine Niacin Pergolide Ritonavir Rotigotine Narcotics: Opiates: Morhine Sedative-hypnotics: Tempazepam Muscle relaxants: Tizanidine Thiothixene Tiagabine Chemotherapeutic agents: Vincristine Vinblastine

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

Disease	History and Physical Examination													Diagnostic approach
	Lightheadedness	Fatigue	Autonomic symptoms	Fever	Nausea/vomiting	Diminished Vision	Dizziness	Slurred Speech	Tachycardia	Altered mentation	Loss of Consciousness	Weakness	Neurological Deficit	Labs and CSF findings	ECG	CT/MRI	Gold standard test
Multiple system atrophy with orthostatic hypotension	+	+	+	-	-	+	+	+	-	+	-	+	+	-	-	Atrophy of brain stem and cerebellum	Clinical assessment
Neurally mediated hypotension	+	+	+	-	+	+	+	+	-	+	-	+	-	-	-	-	Clinical assessment
'Postural Orthostatic Tachycardia Syndrome (POTS)	+	+	+	-	-	-	-	-	+	-	-	-	-	-	+	-	Clinical assessment
Neurologic syncope	+	-	+	-	+	+/-	+	-	-	-	+	+/-	-	-	-	-	Clinical assessment
Cardiac syncope	+	+	+	_	+	+	+	+	+	+/-	+	+	-	-	+	-	ECG Holter monitor Echocardiography
Situational syncope	+	+	+	-	+	+	+	+/-	+/-	+/-	+	+/-	-	-	-	-	Clinical assessment syncope occurs during defecation, micturition, or coughing
Vasovagal syncope (also known as cardio-neurogenic syncope)	+	+	+	-	+	+/-	+	+	-	+	+	+/-	-	+	+	-	ECG Echocardiogram Exercise stress test

Epidemiology and Demographics

Incidence

• The approximation of orthostatic hypotension‐associated 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 <50 years of age to 30% in those >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.
• 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

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

• 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. Addressing these conditions may improve the quality of life of a patient.

• 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 decrease right chamber volume.

CT scan

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

MRI

Brain MRI may be helpful in the diagnosis of orthostatic hypotension. Findings on 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.

Drop of systolic BP > 20 mmHg (30 for hypertensive patients)

Symptomatic

Asymptomatic

Non-pharmacological treatment

Observation and follow-up

Persistance of symtoms

Pharmacological Treatment

No supine hypertension or chronic heart failure

Supine hypertension or chronic heart failure:

Fludrocortisone Midodrine

Midodrine

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 antihypertensives s in patients with mean blood pressure below target value is recommended.
• Avoidance of certain factors that aggravate hypotension such as heat, alcohol intake.
• Consumption of large meals induces splanchnic vasodilation thereby resulting in hypotension postprandially.
  • Fractionated meals are recommended in patients with postprandial symptoms.

Non-Pharmacological methods	Mechanism of alleviating hypotension	Recommendations
Elastic stockings	Reduce venous pooling in the splanchnic and mesenteric circulations.	Elastic stockings expanding up to the waist are recommended. Leg compression alone is not considered effective. Due to the minor venous capacitance of legs relative to the abdomen. Separate abdominal and leg compression is recommended to avoid patient discomfort.
Physical Maneuvers	Transiently increase venous return and peripheral vascular resistance	Contraction of a group of muscles Leg-crossing Toe raising Bending at the waist
Head up tilt sleeping	Enhance orthostatic tolerance upon the first-morning rise	Results in reduction in supine hypertension, pressure-natriuresis
Intravascular volume	Tubular loss of salt and fluid Decreased vascular tone creates relative hypovolemia	Volume expansion can alleviate symptoms even in the presence of normal intravascular volume. 2 liters of water and 6 g of salt Twenty-four-hour urine collection is helpful to guide treatment and follow-up
Intake of cold water	Increase systolic orthostatic hypotension by more than 30 mmHg Via gastropressor response	Rapid drinking of approximatively 500 mL of cold water, independent of daily water intake

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
• Preferred regimen (2): Midodrine 2.5 to 10 mg three times a 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.

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): Nonsteroidal anti-inflammatory drugs are rarely effective as monotherapy
  • They can supplement treatment with fludrocortisone or a sympathomimetic agent.

Third line Therpay

• 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.
• 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