Neurogenic orthostatic hypotension: the very basics

The diagnosis of orthostatic hypotension (OH) requires blood pressure (BP) readings while supine and upright, either during active standing or during a tilt-table test, to determine the presence of a sustained orthostatic fall of at least 20 mmHg systolic or 10 mmHg diastolic BP. BP and heart rate should be measured after the patient has been supine for several minutes and after standing still (or passively tilted) for 1–3 min. The changes in heart rate on standing help to determine whether the OH is neurogenic in origin. In patients with neurogenic OH (nOH) the increase in heart rate upon standing up is usually\20 bpm. Marked increases in heart rate suggest that the OH is non-neurogenic (Table 1).


Diagnosis
The diagnosis of orthostatic hypotension (OH) requires blood pressure (BP) readings while supine and upright, either during active standing or during a tilt-table test, to determine the presence of a sustained orthostatic fall of at least 20 mmHg systolic or 10 mmHg diastolic BP. BP and heart rate should be measured after the patient has been supine for several minutes and after standing still (or passively tilted) for 1-3 min. The changes in heart rate on standing help to determine whether the OH is neurogenic in origin. In patients with neurogenic OH (nOH) the increase in heart rate upon standing up is usually \20 bpm. Marked increases in heart rate suggest that the OH is non-neurogenic (Table 1).

Symptomatic or asymptomatic
Patients with nOH may or may not have symptoms. Symptoms of nOH typically disappear after the patient resumes the sitting or lying position because cerebral blood flow is restored to levels above the lower limit of autoregulatory capacity (Fig. 1). The chronic nature of nOH allows remarkable adaptive changes in cerebral autoregulatory mechanisms. Indeed, patients with nOH are frequently able to tolerate wide swings in BPs and often remain conscious at pressures that would otherwise induce syncope in healthy subjects [2,5].

Ambulatory blood pressure monitoring
Ambulatory blood pressure monitoring (ABPM) is useful for the diagnosis of nOH in patients who do not have a fall in BP during an office visit, and to identify postprandial hypotension and nocturnal hypertension [3] (Fig. 2).

Management
The goal of treatment is not to normalize standing BP, but to reduce symptom burden, and to improve quality of life. The steps in management include: (1) correcting aggravating factors, (2) implementing non-pharmacological measures, and (3) drug therapies (Fig. 3).

Non-pharmacologic management
Non-pharmacologic management is vital and often underestimated to ameliorate the symptoms and severity of neurogenic orthostatic hypotenion (nOH). Patients and their families or caregivers should understand the basics of nOH pathophysiology and the importance of nonpharmacologic methods. In many situations, educational materials may be helpful for both the patient and the caregiver ( Table 2). Physical inactivity and prolonged bed rest are common in patients with nOH. This leads to cardiovascular deconditioning further worsening the fall in BP and increasing symptoms leading to a vicious cycle (Fig. 4).

Pharmacologic treatments
The selection of one drug over the other is related not only to the severity of the patient's symptoms, but also, in certain situations, based on the clinician's preference and experience with a certain drug ( Table 3).

Treatment of supine hypertension associated with neurogenic orthostatic hypotension
Hypertension in the supine occurs in *50% of patients with nOH. There are no controlled clinical trials on its treatments. In patients with nOH experiencing supine hypertension [systolic blood pressure (BP) of 160-180 mmHg or diastolic BP of 90-100 mmHg], there is agreement that sleeping with the head of the bed raised at least 30°-45°should be recommended. If patients are experiencing sustained severe supine hypertension (systolic BP of[180 mmHg or diastolic BP of [110 mmHg) even after sleeping in the semi-sitting position, some experts advocate using short-acting an anti-  Upon awakening the next morning, his orthostatic hypotension is worse due to volume depletion overnight. This recording emphasizes the need to sleep with the head of the bed raised 30°-45°and to avoid high-calorie meals and alcohol during daytime hypertensive agent before bedtime (Table 4). This remains controversial and clinicians must be aware that pharmacological treatment for supine hypertension increases the risk of worsening hypotension and falls when the patient gets up at night or in the early morning. Fig. 4 The vicious cycle of physical deconditioning. Modified from [4]. Because patients with neurogenic orthostatic hypotension (nOH) have intolerable symptoms when standing they avoid moving; lack of physical activity results in striated and cardiac muscle atrophy, which further impairs cardiovascular control. This, in turn, further increases the orthostatic fall in blood pressure, worsening symptoms in a perpetual cycle. Improving symptoms can break this cycle Fig. 3 Treatment algorithm in patients with neurogenic orthostatic hypotension. Modified from [4]. Removal of aggravating factors and initiation of non-pharmacological measures must always predate pharmacological agents Table 2 Recommendations of non-pharmacologic treatments for neurogenic orthostatic hypotension Reproduced from [1] Treatment Notes

Educate patients and their caregivers
Includes education on understanding orthostatic intolerance; avoiding prolonged standing, immobilization, or prolonged diurnal recumbence; as well as rising gradually from supine and sitting positions, especially in the morning, after meals, and after urination/defecation Change diet Eat smaller, rather than large, and more frequent meals. With nOH, sympathetic vasoconstrictor nerve activity is deficient and many patients become severely hypotensive within 2 h of eating. In patients with postprandial hypotension, smaller and more frequent meals are recommended Avoid increased core body temperature Elevation in body temperature causes peripheral vasodilation. Patients with nOH should avoid situations that could increase core body temperature, such as excessive high-intensity exercise; exercise when ambient temperature and humidity are high; utilization of hot-tubs, spas, or saunas; prolonged hot showers, etc. Avoidance of physical deconditioning Lower body strength training and moderate, non-strenuous activities may be incorporated into standard treatment for patients with nOH Use head-up position while sleeping Use of head of the bed elevation up to 30 degrees during sleep. This may reduce nocturia, volume depletion, and supine hypertension Increase hydration Increased fluid intake, including rapid water bolus intake if needed, can potentially combat acute nOH symptoms. Volume expansion requires up to 64 oz of water daily. Proper hydration can produce both acute and long-lasting significant clinical benefits to patients with nOH Increase salt intake For the patient with nOH, it is recommended that they add up to 1-2 teaspoons (2.3-4.6 g) of salt per day to their normal diet. However, increasing salt intake should be used with caution in patients with heart and kidney failure Use compression garments These provide a reduction of peripheral pooling in the lower limbs and splanchnic region. Compression of 30-40 mmHg is required to improve venous return and provide a meaningful blood pressure impact. Abdominal binders offer an effective alternative Treat anemia and vitamin deficiencies Anemia leads to decreased blood viscosity and oxygen-carrying capacity and may worsen symptoms of nOH. Vitamin B12 deficiency (\250 pg/mL with elevated methylmalonic acid levels) may also unmask or exacerbate symptoms of nOH  No controlled trials have been performed. The risk-benefit ratio should be individually assessed a Short-acting antihypertensives should be administered at bedtime only, not during daytime hours. Many medications have twice or three times/day as recommended dosing and patients may inadvertently start taking these medications during daytime hours and worsen symptoms of nOH b The use of clonidine carries a risk of a severe hypotension in the morning as well as rebound hypertension