Orthostatic hypotension is defined as a sudden drop in blood pressure upon standing from a sitting or supine position. Clinically, this is diagnosed by a sustained reduction in systolic blood pressure of at least 20 mmHg or diastolic blood pressure of 10 mmHg within three minutes of standing after being supine for five minutes or at a 60-degree angle on the tilt table. This sudden drop in blood pressure is usually secondary to failure of autonomic reflex, volume depletion, or adverse reaction to medication. Symptoms on presentation are commonly related to cerebral hypoperfusion, but patients can also be asymptomatic. There also is a high rate of morbidity and mortality related to this disease process due to frequent falls, which can lead to multiple hospital admissions. 
Orthostatic hypotension can be caused by both neurogenic and non-neurogenic etiologies and can also be related to medication. Neurogenic orthostatic hypotension is characterized by autonomic instability secondary to neuropathic disease, neurodegenerative disease, or aging. Neuropathic diseases include diabetes, cholinergic receptor autoantibodies, and familial dysautonomia. Neurodegenerative diseases include Parkinson disease, multiple-system atrophy, and pure autonomic failure. Non-neurogenic orthostatic hypotension is most commonly due to volume depletion. One must also consider medication induced orthostatic hypotension particularly in the case of polypharmacy in the elderly.
According to the literature, orthostatic hypotension is most prevalent in patients age 65 years or older, in part due to impaired baroreceptor sensitivity. The prevalence can be as high as 18.2% within that age range. Patients with cardiovascular disease such as aortic stenosis, pericarditis/myocarditis or arrhythmias are also at increased risk for orthostatic hypotension. It can also occur in younger and middle-age patients, who, in the absence of volume depletion, usually have a chronic autonomic failure.
There is pooling of approximately 300 mL to 800 mL of blood in the lower extremities secondary to gravitational forces immediately upon standing from a supine position. This results in decreased venous return to the heart, and as a result, there is a decrease in cardiac output as defined by the Frank Starling Curve. The human body normally compensates with an increase in sympathetic tone and a decrease in vagal tone, known as the baroreceptor reflex. This increase in sympathetic outflow raises peripheral vascular resistance, which subsequently increases venous return and cardiac output, thereby limiting the fall in blood pressure. When patients lack this compensatory mechanism, they present with symptoms of orthostatic hypotension.
The diagnosis of orthostatic hypotension is based entirely on a detailed history and physical exam. The physical exam must include orthostatic vital signs. All patients should be screened with orthostatic vitals, particularly in the case of the elderly. This is a simple and easy test that is often forgotten in the clinical setting.
Patients often present with generalized symptoms of lightheadedness, dizziness, or syncope and less commonly with leg buckling, headache, or chest pain. It is important to determine preceding events or precipitating events and look at the medication list. One must perform a detailed cardiovascular and neurologic exam to rule out a cardiogenic origin of the symptoms. In the elderly, it is also important to rule out neurogenic causes as well as hypovolemia secondary to diuretics, blood loss, or vomiting, and polypharmacy. Particularly in the case of syncope, it is important to rule out other common causes such as seizure and neurocardiogenic syncope (vasovagal syncope).
The initial evaluation of these patients requires a thorough medication reconciliation. Medications including vasodilators, diuretics, antidepressants, antipsychotics and dopaminergic drugs commonly precipitate orthostatic hypotension. Patients with no obvious cause should have a thorough cardiac evaluation beginning with an ECG as well as a laboratory evaluation to look for findings of anemia, dehydration, diabetes, alcoholism, or heart failure. One must also consider neurodegenerative disease, which is primarily diagnosed by history and physical exam.
It is essential to obtain orthostatic vital signs to make an orthostatic hypotension diagnosis. Allow the patient to rest supine while obtaining the blood pressure and heart rate. After five minutes of lying supine, the patient should be asked to stand quietly for two to five minutes, and vital signs should be taken again. If there is a 20 mmHg drop in systolic blood pressure or a 10 mmHg drop in diastolic blood pressure, one can make the diagnosis of orthostatic hypotension.
The etiology determines the management of these patients. The treatment goal is to relieve symptoms and prevent associated morbidity. According to the literature, asymptomatic patients are left alone except for patients with Parkinson disease. These patients should be screened as they have associated impairments in their quality of life, as well as higher risk of falls. For patients with a medication-related disease, it is important to remove the offending agent and optimize the patient's medication regimen. Many patients require a multidisciplinary approach to address underlying diabetes, hypertension, Parkinson's disease and other comorbidities. Patients that are suffering from dehydration require timely volume resuscitation.
Patients with neurogenic etiology should be counseled on lower extremity stockings, abdominal binders, adequate hydration, salt intake, and fall prevention. Nonpharmacologic measures are generally sufficient. Pharmacologic treatment should be implemented after a nonpharmacologic intervention has failed to relieve symptoms. According to the literature, fludrocortisone and midodrine remain first-line medications, but many other pharmacologic therapies can be used, including pyridostigmine. Fludrocortisone is an aldosterone analogue; midodrine is an alpha-1 agonist and pyridostigmine is an acetylcholinesterase inhibitor. All of these medications work through different mechanisms in order to increase vascular tone. In a recent study, midodrine was shown to be more efficacious than pyridostigmine with regards to symptomatic relief. 
Approximately 50% of patients with neurogenic orthostatic hypotension suffer from supine hypertension. This association is due to side effects from anti-hypertensive medications as well as the common autonomic dysfunction seen in these patients due to comorbid conditions, such as diabetes mellitus. There is currently no approved anti-hypertensive medication that selectively targets the supine position. This complicates treatment because supine hypertension in patients with autonomic failure can result in end organ damage. The treatment approach for these patients is currently being studied and might be an outlet for individualized based medicine in the future.
The management of orthostatic hypotension is best done with a multidisciplinary team that includes an endocrinologist, internist, primary care provider, neurologist, and nurse practitioner. The etiology determines the management of these patients. The treatment goal is to relieve symptoms and prevent associated morbidity. According to the literature, asymptomatic patients are left alone except for patients with Parkinson disease. These patients should be screened as they have associated impairments in their quality of life, as well as a higher risk of falls. For patients with a medication-related disease, it is important to remove the offending agent and optimize the patient's medication regimen. Many patients require a multidisciplinary approach to address underlying diabetes, hypertension, Parkinson's disease and other comorbidities. Patients that are suffering from dehydration require timely volume resuscitation. Overall, the prognosis of asymptomatic patients is excellent but those with symptoms tend to have a poor quality of life. (Level V)
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