NORD gratefully acknowledges Phillip A. Low, MD, Robert D. and Patricia E. Kern Professor of Neurology, Mayo Clinic College of Medicine, for assistance in the preparation of this report.
Orthostatic hypotension (OH) is a common condition characterized as a drop in blood pressure that occurs when a person stands up. OH can cause lightheadedness, dizziness or even causing a person to faint. Symptoms can also be subtle or absent. By definition, the drop in blood pressure must be greater than 20mm Hg of mercury in systolic BP and/or more than 10 mm of mercury in diastolic BP within 3 minutes upon standing from sitting or from a lying down face-up (supine) position. There are numerous, varied causes of OH. Neurogenic orthostatic hypotension (NOH) is a rare subtype caused by underlying neurologic disorders that affect a specific part of the autonomic nervous system. The autonomic nervous system is the part of the nervous system that regulates certain involuntary body functions such as heart rate, blood pressure, sweating, and bowel and bladder control. The treatment of OH depends upon several factors including the specific underlying cause.
In some people, there may not be any noticeable symptoms despite a sudden and extreme drop in blood pressure upon rising from a reclining position. When symptoms occur they can vary greatly in expression from one individual to another. Common symptoms can include dizziness, lightheadedness, generalized weakness, leg buckling, nausea, blurry vision, fatigue, and headaches. Additional symptoms can include chest pain (angina), head and neck pain (often affecting neck and shoulders with a coat hanger distribution), and a decline in cognitive functioning such as difficulty concentrating.
Affected individuals may experience a temporary loss of consciousness or “blackout,” a condition known as syncope. There may be a gradual build up to an episode of syncope or it can occur suddenly.
A serious complication of OH is the risk of falling, which can lead to physical damage such as a broken hip or other broken bones. The constant dropping and raising of blood pressure associated with OH has also been identified as a risk factor in the development of stroke and other cardiovascular diseases.
Symptoms of OH on standing have been aggravated by raised ambient heat, such as hot weather, hot shower, hot tub, or when an affected individual has a fever. OH is often more common and more severe in the morning. Some individuals with NOH develop postprandial hypotension, which is defined as the development or worsening of hypotension approximately 30 minutes to 2 hours after eating a meal, particularly large meals high in carbohydrates.
Some individuals with NOH may also have high blood pressure when lying down (supine hypertension). Supine hypertension complicates treatment options for affected individuals.
Orthostatic hypotension may be a temporary condition or one that occurs consistently over time (chronic). Some sources break down the causes of OH into drugs, non-neurogenic, primary neurogenic and secondary neurogenic causes. In many cases, the underlying cause of OH remains unknown or unproven (idiopathic). Most idiopathic cases are believed to have an underlying neurogenic cause.
OH can be caused by certain chemotherapy drugs which can cause an autonomic neuropathy. A common cause of OH is the decrease in volume of circulating blood (hypovolemia) resulting from excessive use of medications that increase urination and sodium loss (diuretics), or from drug therapy that widens blood vessels (vasodilators) for the treatment of high blood pressure, heart failure or chest pains (i.e., calcium blockers and nitrates). Commonly used vasodilator drugs include levodopa for Parkinson’s disease, nitroglycerine and drugs taken to treat erectile dysfunction (sildenafil, tadalafil). A variety of drugs that interfere with the autonomic nervous system’s reflexes can also cause OH, such as certain antipsychotic (i.e., phenothiazine) and antidepressant drugs. Alcohol can also cause OH.
Non-neurogenic causes can include hypovolemia, cardiac pump failure, and venous pooling. Hypovolemia can be caused by several conditions including dehydration, chronic bleeding, adrenal insufficiency, diabetes insipidus, diarrhea, and chronic vomiting.
Cardiac pump failure refers to when the heart cannot pump blood sufficiently enough to maintain blood flow to meet the demands of the body and can be associated with heart block, disorders of heart rhythm (tachyarrhythmias), narrowing (stenosis) of the main artery of the body (aorta), or a heart attack (myocardial infarction).
Venous pooling is a normal occurrence in which gravity causes blood to pool downward within the abdomen and legs upon standing. This results in reduced venous return to the heart. There are certain conditions cause excessive venous pooling. Such conditions include rising quickly after prolonged sitting or lying down (recumbency), prolonged motionless standing, fever, heat exposure, or carbohydrate heavy meals.
Primary neurogenic causes refers to individuals with an underlying primary disorder that is involved with malfunction of the autonomic nervous system such as multiple system atrophy, Parkinson’s disease, pure autonomic failure, dopamine beta-hydroxylase deficiency, Lewy body disease, familial dysautonomia, and non-diabetic autonomic neuropathy.
Secondary neurogenic causes can include spinal cord problems such as transverse myelitis or tumors of the spinal cord and various peripheral neuropathies such as amyloidosis, Guillain-Barre syndrome, diabetes mellitus, and the hereditary sensory and autonomic neuropathies. Individuals with OH due to primary or secondary neurogenic causes are referred to as having neurogenic orthostatic hypotension (NOH).
The symptoms of OH result from the failure of the body to compensate for the normal drop in blood pressure that occurs upon standing or sitting up. Upon standing, gravity causes the blood in the body to pool downward into the legs and trunk. Consequently, less blood is returned to the heart and cardiac filling pressure is reduced, resulting in diminished cardiac output. In a matter of seconds, the body goes through a normal series of involuntary responses that compensate for this drop in blood pressure. These responses are controlled by the autonomic nervous system and include signaling blood vessels to narrow so that more blood is pushed upward and signaling the heart to beat faster (increased heart rate) to pump more blood and ensure proper blood flow and pressure.
Any interruption in these involuntary processes can result in OH. For example, the baroreflex is essential in maintaining proper blood pressure and does not function properly in individuals with NOH. The baroreflex refers to specialized cells called baroreceptors that trigger the autonomic nervous system to increase levels of certain hormones called catecholamines, specifically norepinephrine. Norepinephrine is a chemical messenger that is necessary for nerves to communicate in order to trigger blood vessels to narrow to increase blood pressure upon standing (vasoconstriction). This response is known as the baroreflex. When the baroreflex is impaired the body fails to produce sufficient amounts of norepinephrine and cannot offset the drop in blood pressure that occurs upon standing, resulting in the symptoms of OH.
Not all cases of OH result from dysfunction of the autonomic nervous system. Conditions that cause hypovolemia such as dehydration cause OH because the loss of blood volume prevents the body from compensating for the decreased blood pressure that occurs upon standing. Conditions that affect the heart such as cardiac pump failure prevent the heart from pumping efficiently or rapidly enough to compensate for the drop in blood pressure that occurs upon standing.
OH is most common in the elderly, postpartum mothers, those who have been on bed rest, and teenagers, because of their large amounts of growth over a small time period. The prevalence increases with age. Institutionalized elderly have higher rates of OH than individuals who remain living in the community.
Although the symptoms are sometimes vague, OH can be diagnosed by a simple test of an individual’s blood pressure when sitting down and then immediately upon standing up. A significant fall in blood pressure during this test will indicate OH. Heart rate is also monitored in both the sitting and standing position and can aid in diagnosis. A tilt table test may also be conducted in order to assess blood pressure. In this test, a patient will lie flat on a special table or bed while connected to an electrocardiogram (ECG) and blood pressure monitors. The table then tilts to create a change in posture from lying to standing. Autonomic reflex testing provides an evaluation of autonomic reflexes including baroreflexes and determines whether the OH is neurogenic or not.
A detailed examination and assessment of the central nervous system may be performed to evaluate affected individuals for signs or symptoms of conditions associated with NOH such as Parkinson’s disease or multiple system atrophy. A thorough evaluation might involve an autonomic reflex screen (to evaluate adrenergic, sudomotor and cardiovagal function), thermoregulatory sweat test (to evaluate the distribution of anhidrosis), tests for an autonomic neuropathy (such as diabetes, amyloid, autoimmunity) and measurement of plasma norepinephrine supine and standing.
The treatment of OH can be challenging as the ultimate goal is to improve blood pressure upon standing, but this must be accomplished without excessively increasing blood pressure when lying down (supine hypertension). Supine hypertension is of particular concern in individuals with NOH.
Specific therapies depend upon the underlying cause. When OH is caused by a decrease in volume of circulating blood (hypovolemia) due to the use of certain medication(s), it is treated by adjusting the dosage or discontinuing the medication, under a doctor’s supervision. Hypovolemia also responds to an increase in salt intake. Low blood pressure resulting from extended bed rest can be corrected by allowing the affected individual to sit up each day at certain times with increasing frequency.
Some relief particularly in mild cases may be achieved by taking some simple precautions such as avoiding hot baths that lower blood pressure, avoiding long walks in hot weather, and taking medications that help raise blood pressure, strengthen bladder tone, or prevent constipation. Taking one’s time when changing positions including rising from a chair or getting up from bed can help. Elevating the head of the bed may be of benefit in some cases. Limiting alcohol intake and avoiding large carbohydrate-laden meals can help in specific cases. Exercise programs geared toward improving conditioning and strengthening the legs can be of benefit. These programs may also teach specific physical maneuvers designed to avoid OH such as toe raises, thigh contractions, leg crossing, and bending over at the waist.
Maintaining an elevated salt-intake may be prescribed, either through sodium supplements or drinks containing electrolytes. Drinking a large quantity of fluids also can aid in preventing OH episodes by preventing dehydration. Increasing fluid and salt intake are essential to help to expand blood volume. Water boluses, which involve drinking glasses of water in rapid succession, can help to expand blood volume. The specific amount reported in the medical literature varies, but is approximately two 8 ounce glasses of water.
In some cases, the legs may be fitted for elastic stocking that can help maintain blood pressure upon standing. A medical compression garment known as an abdominal binder used alone or in combination with elastic, compression stockings may provide relief of OH.
In 1996, the drug midodrine hydrochloride (ProAmatine®) was approved by the U.S. Food and Drug Administration (FDA) to treat OH by reducing the radius of blood vessels and thus, increasing blood pressure. In 2011, the FDA requested additional clinical trials to assess the efficacy of midodrine in individuals with OH.
In February of 2014, the FDA approved droxidopa (Northera®) for the treatment of adults with NOH caused by Parkinson’s disease, multiple system atrophy, pure autonomic failure, dopamine beta-hydroxylase deficiency and non-diabetic autonomic neuropathy. Northera was approved under the FDA’s accelerated approval program and has demonstrated short-term relief from the symptoms of NOH. The continued safety and effectiveness of this drug is continually being assessed.
Other medications have been used off label to treat individuals with OH including pyridostigmine. This drug acts on the sympathetic baroreflex pathway, which is active during standing. The drug can improve OH without worsening or aggravating supine hypertension. However, the effects of pyridostigmine are mild and the drug is generally used for individuals with mild cases of OH. In more severe cases, fludrocortisone (Florinef®) may be used. This drug increases blood volume and enhances the response of blood vessels to catecholamines such as norepinephrine.
Additional medications have shown some benefit in treating OH including non-steroidal anti-inflammatories (NSAIDs), caffeine, and erythropoietin. These drugs may be given alone on in combination.
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