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Orthostatic or postural hypotension (OH) is arbitrarily defined as either a 20 mm Hg fall in systolic blood pressure or a 10 mm Hg fall in diastolic blood pressure on assuming an upright posture from a supine position. OH implies abnormal blood pressure homeostasis and is a frequent observation with advancing age. Prevalence of postural hypotension varies between 4% and 33% among community-living older persons depending on the methodology used. Higher prevalence and larger falls in systolic blood pressure have been reported with increasing age and often signify general physical frailty. Prevalence of OH in the older-aged community-dwelling adults is 30% and increases to more than 50% in hospitalized geriatric patients making its diagnosis highly relevant. OH is an important cause of syncope, accounting for 14% of all diagnosed cases in a large series. In a tertiary referral clinic dealing with unexplained syncope, dizziness and falls, 32% of patients over age 65 had orthostatic hypotension as a possible attributable cause of symptoms.
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A recent population-based study which employed beat-to-beat measurement of orthostatic blood pressure demonstrated a significant age gradient for abnormalities in orthostatic blood pressure such that in 7% of 50- to 55-year-olds, systolic and diastolic blood pressure failed to stabilize by 2 minutes after standing compared with 41% of those 80 years old and older. Failure of stabilization was associated with falls, depression, and global cognitive impairment.
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The heart rate and blood pressure responses to orthostasis occur in three phases: (1) an initial heart rate rise and blood pressure drop, (2) an early phase of stabilization, and (3) a phase of prolonged stabilization. All three phases are influenced by aging. The maximum rise in heart rate and the ratio between the maximum and the minimum heart rate in the initial phase decline with age, implying a relatively fixed heart rate irrespective of posture. Despite a blunted heart rate response, blood pressure and cardiac output are adequately maintained on standing in active, healthy, well-hydrated, and normotensive older persons because of decreased vasodilatation and reduced venous pooling during the initial phases and increased peripheral vascular resistance after prolonged standing. However, in older persons with hypertension, cardiovascular disease or receiving vasoactive drugs, these circulatory compensatory adjustments to orthostatic stress are disturbed, rendering them vulnerable to develop postural hypotension. More recent research suggests that the velocity of the initial orthostatc heart rate response at 10 and 20 seconds predicts mortality and morbidity.
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This age-related gradient may reflect autonomic dysfunction, increased arterial stiffness, and muscle pump defects. Traditionally, OH is defined as a reduction in systolic BP of at least 20 mm Hg or in diastolic BP of at least 10 mm Hg within 3 minutes of standing. Orthostatic intolerance (OI) refers to symptoms and signs with upright posture due to circulatory abnormality. Syndromes of OI that may cause syncope include initial OH where symptoms of light-headedness/dizziness or visual disturbance are experienced seconds after standing; classic OH where dizziness, presyncope, fatigue, weakness, palpitations, visual and hearing disturbances are experienced; delayed OH where there is a prolonged prodrome frequently followed by rapid syncope; delayed OH and reflex syncope where a prolonged prodrome is always followed by syncope; reflex syncope triggered by standing where there is classic prodrome and triggers always followed by syncope; and postural orthostatic tachycardia syndrome where there is symptomatic HR increase and instability of BP without syncope. Many older patients with OH also have postprandial hypotension. Causes of OH include volume depletion or disturbance of the autonomic nervous system resulting in failure in vasoconstrictor compensatory mechanisms induced by upright posture.
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Hypertension further increases the risk of hypotension by impairing baroreflex sensitivity and reducing ventricular compliance. Hypertension increases the risk of cerebral ischemia from sudden declines in blood pressure. Older persons with hypertension are more vulnerable to cerebral ischemic symptoms even with modest and short-term postural hypotension, because the threshold for cerebral autoregulation is altered by prolonged elevation of blood pressure. In addition, antihypertensive agents may impair cardiovascular reflexes and further increase the risk of orthostatic hypotension.
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Drugs (see Table 51-3) are important causes of OH. Ideally establishing a causal relationship between a drug and OH requires identification of the culprit medicine, abolition of symptoms by withdrawal of the drug, and rechallenge with the drug to reproduce symptoms and signs. Rechallenge is often omitted in clinical practice in view of the potential serious consequences. In the presence of polypharmacy, which is common in the older person, it becomes difficult to identify a single culprit drug because of the synergistic effect of different drugs and drug interactions. Thus all drugs should be considered as possible contributors to orthostasis.
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A number of nonneurogenic conditions are also associated with postural hypotension. These conditions include myocarditis, atrial myxoma, aortic stenosis, constrictive pericarditis, hemorrhage, diarrhea, vomiting, ileostomy, burns, hemodialysis, salt-loosing nephropathy, diabetes insipidus, adrenal insufficiency, fever, and extensive varicose veins. Volume depletion for any reason is often a common sole, or contributing, cause of postural hypotension, and, in turn, syncope.
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Primary Autonomic Failure Syndromes
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Three distinct clinical entities—namely pure autonomic failure (PAF), multiple system atrophy (MSA) or Shy-Drager syndrome (SDS), and autonomic failure associated with idiopathic Parkinson disease (IPD)—are associated with orthostatic hypotension. PAF, the least common condition and a relatively benign entity, was previously known as idiopathic orthostatic hypotension. This condition presents with orthostatic hypotension, defective sweating, erectile dysfunction, and bowel disturbances. No other neurologic deficits are evident and resting plasma norepinephrine levels are low. MSA is the most common among these syndromes and has the poorest prognosis. Clinical manifestations include features of dysautonomia and motor disturbances due to striatonigral degeneration, cerebellar atrophy, or pyramidal lesions. Additional neurologic deficits include muscle atrophy, distal sensorimotor neuropathy, pupillary abnormalities, restriction of ocular movements, disturbances in rhythm and control of breathing, life-threatening laryngeal stridor, and bladder disturbances. Psychiatric manifestations and cognitive defects are usually absent. Resting plasma norepinephrine levels are usually within the normal range, but fail to rise on standing or tilting.
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The prevalence of orthostatic hypotension in Parkinson disease rises with advancing years and with the number of medications prescribed. Cognitive impairment, in particular abnormal attention and executive function, is more common in Parkinson disease with orthostatic hypotension suggesting a possible causal association with hypotension including watershed hypoperfusion and infarction. Orthostatic hypotension in Parkinson disease can be due to autonomic failure and/or side effects of antiparkinsonian medications.
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Secondary Autonomic Dysfunction
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Autonomic nervous system involvement is seen in several systemic diseases. A large number of neurologic disorders are also complicated by autonomic dysfunction which may involve several organs leading to a variety of symptoms in addition to orthostatic hypotension including anhidrosis, constipation, diarrhea, erectile dysfunction, urinary retention, urinary incontinence, stridor, apneic episodes, and Horner syndrome. Among the most serious and prevalent conditions associated with an orthostasis due to autonomic dysfunction are diabetes, multiple sclerosis, brainstem lesions, compressive and noncompressive spinal cord lesions, demyelinating polyneuropathies (Guillain-Barre syndrome), chronic renal failure, chronic liver disease, and connective tissue disorders.
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The clinical manifestations of orthostatic hypotension are due to hypoperfusion of the brain and other organs. Depending on the degree of fall in blood pressure and cerebral hypoperfusion, symptoms can vary from dizziness to syncope associated with a variety of visual defects, from blurred vision to blackout. Other reported ischemic symptoms of orthostatic hypotension are nonspecific lethargy and weakness, suboccipital and paravertebral muscle pain, low backache, calf claudication, and angina. Several precipitating factors for orthostatic hypotension have been identified including speed of positional change, prolonged recumbency, warm environment, raised intrathoracic pressure (coughing, defecation, micturition, physical exertion), and vasoactive drugs.
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The diagnosis of orthostatic hypotension involves a demonstration of a postural fall in blood pressure after active standing. Reproducibility of orthostatic hypotension depends on the time of measurement and on autonomic function. The diagnosis may be missed on casual measurement during the afternoon. The procedure should be repeated during the morning after first maintaining supine posture for at least 10 minutes. Sphygmomanometer measurement will detect hypotension which is sustained. Phasic blood pressure measurements are more sensitive for detection of transient falls in blood pressure. Where possible these methods should be employed. Active standing is more appropriate than head-up tilt because the former more readily represents the physiologic α-adrenergic–mediated vasodilation due to calf muscle activation. Once a diagnosis of postural hypotension is made, the evaluation involves identifying the cause or causes of orthostasis mentioned earlier.
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The goal of therapy for symptomatic orthostatic hypotension is to improve cerebral perfusion. There are several nonpharmacologic interventions that should be tried in the first instance. These interventions include patient education regarding avoidance of precipitating factors for low blood pressure, maintaining adequate volume status, and application of graduated pressure from an abdominal support garment or from stockings (Table 51-5). Medications known to contribute to postural hypotension should be eliminated or reduced. There are reports to suggest benefit from implantation of cardiac pacemakers, in a small number of patients, by increasing heart rate during postural change. However, the benefits of tachypacing on cardiac output in patients with maximal vasodilatation are short lived, probably because venous pooling and vasodilation dominate. A large number of drugs have been used to raise blood pressure in orthostatic hypotension, including fludrocortisone, midodrine, ephedrine, desmopressin (DDAVP), octeotride, erythropoeitin, and nonsteroidal anti-inflammatory agents. Fludrocortisone (9α-fluorohydrocortisone), in a dose of 0.1 to 0.2 mg, causes volume expansion, reduces natriuresis, and sensitizes α-adrenoceptors to norepinephrine. In older people, the drug can be poorly tolerated in high doses and for long periods. Adverse effects include hypertension, cardiac failure, depression, edema, and hypokalemia. Midodrine is a directly acting sympathomimetic vasoconstrictor of resistance vessels. Treatment is started at a dose of 2.5 mg three times daily and requires gradual titration to a maximum dose of 30 mg/day. Adverse effects include hypertension, pilomotor erection, gastrointestinal symptoms, and central nervous system toxicity. Side effects are usually controlled by dose reduction. Midodrine can be used in combination with low-dose fludrocortisone with good effect. DDAVP has potent antidiuretic and mild pressor effects. Intranasal doses of 5 to 40 μg at bedtime are useful. The main side effects are hyponatremia and water retention. This agent can also be combined with fludrocortisone with synergistic effect. The drug treatment for orthostatic hypotension in older persons requires frequent monitoring for supine hypertension, electrolyte imbalance, and congestive heart failure. One option for treating supine hypertension which is most prominent at night is to apply a nitroglycerine patch after going to bed, remove it in the morning, and take midrodrine with or without fludrocortisone 20 minutes before rising. This is effective provided that the older person remains in bed throughout the night. Nocturia is therefore an important consideration. In order to identify these coexistent diurnal BP variations of supine hypertension and morning orthostasis, 24-hour ambulatory BP monitoring is the preferred investigation. Postprandial hypotension, due to splanchnic vascular pooling often coexists with orthostatic hypotension in older patients.
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