Neurogenic Orthostatic Hypotension (nOH)

What is nOH?

Neurogenic orthostatic hypotension (nOH) is a condition in which the autonomic system, which controls the automatic functions of the body, loses the ability to properly regulate blood pressure as one moves from sitting or lying down to standing, or when one changes positions quickly. As a result, patients with NOH suffer sudden and dangerous drops in blood pressure. Doctors define nOH as a >20mm Hg drop in systolic blood pressure – the upper number of the blood pressure ratio – or a >10mm Hg decrease in the diastolic pressure – the lower number of the blood pressure ratio – within 3 minutes of standing up from sitting or lying down. (9) Other everyday activities that elicit an increase in blood pressure, such as digestion of food, lifting heavy objects, and defecating can also bring on an episode of nOH.

The main symptoms of nOH include dizziness and visual disturbances. Fatigue, cognitive impairment, blurry vision, and difficulty breathing also occur as part of this condition. Symptoms may occur more often or more severely early in the morning, in hot weather, after large meals, or from prolonged standing. (1) nOH is common in MSA, affecting about 75% of patients. (1) By comparison, up to 58% of Parkinson’s disease patients and 10% to 30% of the aging population at large experience orthostatic hypotension. (1)

Non-Pharmacological Treatment Options

Lifestyle Changes

Numerous non-drug methods may help prevent or manage nOH symptoms. Patients experiencing nOH may find that lifestyle changes such as moving more slowly and carefully than they are accustomed to so as to prevent rapid changes in position, eating smaller meals, and avoiding exposure to extremes of temperature, such as going from indoor air conditioning to the outdoors on a hot day, may be in order. Rearranging activities for afternoons rather than mornings, when nOH symptoms are more pronounced, may result in fewer episodes of nOH. Heavy lifting should also be avoided. (2)

Compression Stockings

Preventing blood from pooling in the legs when one stands up can keep blood pressure from falling. Compression stockings and other compression garments provide a mechanical boost to make up for the lack of autonomic control in such situations. Valuable knowledge about this method for treating nOH comes from research conducted by the aerospace industry. OH affects astronauts who have recently spent time in space, where their bodies adapt to diminished gravity by decreasing blood volume. As a result, they experience a period of OH upon their return to earth. One study showed that inflatable compression suits and specially designed compression garments increase astronauts’ blood pressure and improve their ability to perform tilt tests without experiencing OH. Commercially available, custom-fit, graded compression stockings known as Jobst stockings, which have higher pressure at the ankles tapering to lower pressure around the top of the thigh, and some compression garments that include the abdomen, also perform well at preventing lightheadedness or faintness, a condition known as presyncope. (4) (5) These garments offer the added advantage of being non-inflatable.

Hydration

Drinking water, which raises blood pressure by increasing blood volume, has been found to be a particularly effective means of managing nOH. Pre-emptive water intake may increase blood pressure more than can be achieved pharmacologically. (6) Increases of over 40mm Hg in systolic pressure have been observed within 20 minutes of rapidly drinking 480 mL or about 16 fluid ounces. Of note, plain water, as opposed to other watery fluids, seems to be a key component of this method for MSA patients. In an experiment in which clear soup was used in place of water, results were not favorable for the participants with MSA who underwent a tilt test after consuming 450 mL of clear soup. (7) Similarly, sugary drinks have the opposite effect, lowering blood pressure instead of raising it. (8)

Salt and Kidney Function

Eating a high-salt diet is an effective way to raise your blood pressure and is recommended for patients with nOH provided there is no history of kidney disease. Check with your doctor before implementing any dietary change.

Neurogenic orthostatic hypotension causes the kidneys to function differently in ways that perpetuate nOH while you are sleeping or are lying down. At such times, blood return from the lower half of the body increases, stimulating the kidneys to filter the blood at a higher rate. To offset the increased blood volume they must filter, the kidneys secrete sodium, promoting loss of water, which contributes to low blood volume, worsening nOH symptoms.

Elevation of Head of Bed

Raising the head of the bed by 10 to 30 degrees while sleeping can raise the standing blood pressure and help offset the low blood pressure effects of NOH. Patients may need to do this regularly for a few weeks before seeing noticeable benefits. (9)

Leg Crossing

Crossing the legs can help with OH by decreasing circulation to the legs, thereby maintaining higher blood volume and blood pressure in the head. (11) One study found that leg crossing while standing increased average arterial blood pressure in patients with either pure autonomic failure or MSA by an average of 24%, resulting in improved blood flow and oxygenation to the brain and less risk of dizziness, falling, and other complications of OH. (12) Contracting the leg, buttocks, and abdominal muscles while using the leg crossing method can help maintain blood flow in the legs while still increasing blood supply to the head. (13) (14)

Reducing Medications

Dopamine drugs for Parkinson’s symptoms and medication for high blood pressure may worsen OH symptoms and may require patients to reduce or discontinue those medications in order to effectively manage OH. (9)

Pharmacological Treatment Options

Medication therapy for nOH is highly individualized. As opposed to bringing blood pressure up to normal values, which may not be realistic or necessary, the goal is to arrive at the proper drug and dosage level that most effectively manages your NOH symptoms. (15)

Adrenal-Supportive Drugs

Fludrocortisone

One of the mainstay medicines for nOH is fludrocortisone, trade name Florinef. This drug is a synthetic adrenal corticosteroid hormone that increases blood volume and blood pressure by making the body retain sodium, thus increasing water retention. Fludrocortisone also makes cells more sensitive to adrenaline, a hormone that causes blood vessels to contract, reducing blood flow to the kidneys and slowing the production of urine. (16) However, fludrocortisone’s blood pressure-raising effects can cause blood pressure to become elevated while the patient is lying down, a complication that can potentially lead to congestive heart failure. This and other drugs that promote adrenal hormone activity should be taken 30 to 45 minutes before activity rather than on a fixed schedule. Potential side effects of fludrocortisone include difficulty sleeping, dizziness, headache, sweating, indigestion, and nervousness. (17)

Midodrine

Midodrine, trade names Amatine and Gutron, elevates blood pressure by making arteries and veins more sensitive to adrenaline, which causes blood vessels to contract. In a review of research studies conducted on midodrine, researchers found that it increased standing systolic blood pressure by an average of 21.5 mm Hg. (18) Study participants reported significant improvement in their symptoms. Potential side effects of midodrine include difficulty initiating urination, urinary urgency, elevated blood pressure when lying down, itchy scalp, and goosebumps on the skin. Midodrine can also cause blurred vision, dizziness, fainting, headache, and pounding in the ears. (19)

Droxidopa

Droxidopa, trade name Northera, a newer drug for managing nOH, is a chemical that the body converts to two neurotransmitters: norepinephrine and adrenaline. This versatility allows droxidopa to work within the brain, where it acts on the blood pressure-regulating center, and the body, where it influences the heart, blood vessels, and other organs to increase standing blood pressure. (20)

A clinical trial that included patients with MSA and pure autonomic failure found that droxidopa improved nOH symptoms in 78% of participants and completely eliminated symptoms in 44% of participants. (21) Drops in supine-to-standing blood pressure improved by 40%. In another study, symptoms such as dizziness, lightheadedness, and blurred vision also improved. Additionally, droxidopa did not cause an increase in supine blood pressure. It has been in use for other indications since 1989 and has been proven highly safe with few side effects. While a small percentage of patients have experienced serious adverse events while taking droxidopa, including breathing difficulty and fainting, these instances may have been related to disease severity, as opposed to side effects caused by droxidopa. (22)

Yohimbine

Yohimbine is an herb which stimulates production of adrenaline and activates adrenaline receptors and has been shown to prevent blood pressure from dropping upon standing from lying down by more than 10 mmHg. (25) Potential side effects of yohimbine include racing or irregular heartbeat, anxiety, tremor, and confusion. Allergic reaction to yohimbine may cause swelling of the throat and difficulty breathing.

Atomoxetine

Atomoxetine, trade name Strattera, helps keep adrenaline in circulation. It is particularly useful if, as for most MSA patients, nOH stems from degeneration of blood pressure control centers in the brain but adrenaline receptors throughout the body remain intact. (23) Potential side effects of atomoxetine include acid indigestion, cough, urinary retention, urinary incontinence, constipation, nausea, chest tightness, difficulty sleeping, and fatigue. (28)

Pyridostigmine

Pyridostigmine, trade name Regonol, is a drug which inhibits the breakdown of acetylcholine, the main neurotransmitter of the autonomic nervous system. By doing so, it stimulates the adrenal glands to release adrenaline. Pyridostigmine produces a significant increase in standing blood pressure. It also helps avoid the problem of elevated supine blood pressure by promoting adrenaline production only during times of activity and not when one is sedentary. However, pyridostigmine has been found to be less effective in severe forms of nOH. (23) In a comparison study of yohimbine with pyridostigmine in patients with MSA, Parkinson’s Disease, PAF, and severe autonomic failure, yohimbine raised standing blood pressure by an average of 11 mm Hg and reduced nOH symptoms, while pyridostigmine raised blood pressure by an average of 0.6 mm Hg with no improvement in symptoms. (27) Potential side effects of pyridostigmine include extreme muscle weakness and twitching, slurred speech, vision problems, severe vomiting or diarrhea, anxiety, and seizure. (24)

Rasagiline

Rasagiline, trade name Azilect, an antidepressant sometimes used to treat Parkinson’s symptoms, has been studied and found to have no effect for those with nOH and MSA. (34)

Brain Neurotransmitter Activation

Ergotamine, derived from the ergot fungus, resembles several neurotransmitters, including epinephrine, serotonin, and dopamine in structure. Ergotamine has been used alone or in combination with caffeine to increase blood pressure and improve nOH symptoms. However, ability of the body to absorb and utilize ergotamine varies from person to person. Also, ergotamine may not be safe for patients with heart disease. (23)

Anti-Anemia

Patients with severe autonomic failure often develop a mild form of anemia due to impaired red blood cell production. Treating anemia with a hormone called recombinant erythropoietin can increase blood volume and blood pressure, reducing nOH symptoms. Disadvantages of recombinant erythropoietin are that it must be delivered by injection 3 times per week and is costly.

An alternative to recombinant erythropoietin is the drug desmopressin or DDAVP, a synthetic form of the blood pressure-raising hormone vasopressin. Desmopressin is injected at bedtime and is safe to use for patients with elevated supine blood pressure. However, this medication can cause low sodium levels. (23)

Other Drugs and Supplements

Octreotide, trade name Sandostatin, is a drug that mimics somatostatin, a brain hormone that controls secretion of growth hormone from the pituitary gland. Octreotide has demonstrated superior ability to raise blood pressure by constricting veins and offers similar effectiveness to midodrine for improving prolonged standing ability. Octreotide can be used in conjunction with midodrine; however, it must be injected. Potential side effects of octreotide include abdominal pain, blurred vision, constipation, depression, dizziness, fainting, increased urination, fatigue, and difficulty breathing.

A review of previous studies found that the drugs indomethacin, a nonsteroidal anti-inflammatory agent, and the supplement potassium chloride raise blood pressure, on average more than 10 mm Hg. (25) Potential side effects of indomethacin may include acid indigestion, nausea, vomiting, and diarrhea. Potassium chloride side effects may include nausea, vomiting, and diarrhea as well. (32)

Patients have also reported improvement in symptoms with a combination of the herbs camphor and hawthorn berry. (25) The herbal combination has been tested in clinical trials and found effective for some patients with nOH. These substances are generally considered safe and well-tolerated, (31) though some patients experience fatigue, nausea, or sweating from taking hawthorn berry. (33)