Syncope (fainting) is a common although disturbing experience. It is the sudden transient loss of consciousness with loss of postural tone caused by impaired blood flow to the central nervous system. Recovery is usually spontaneous when lying down. Syncope may occur even while lying down or standing upright and under a wide variety of conditions. It may be due to medication, cardiac disease (usually arrhythmia), or severe impairment of cardiac blood flow by mechanical pump failure or obstruction. It may be due to transient impairment of central nervous system function as in a transient ischemic attack TIA, but this is less common. Although convulsive like movements may occur during fainting, it is distinct from a seizure disorder.
Cardiac syncope is often quite serious and should be regarded as life threatening. When specific cardiac disease is found, it is treated specifically. However, the large majority of exercise related syncope cases are non cardiogenic in origin, at least for children and adolescents.
Approximately 90% of syncope in children is either neurocardiogenic (also known as vasovagal syncope) or unexplained. Often the unexplained variety is reclassified as neurocardiogenic once tilt table testing has been performed. Neurocardiogenic is the current term for fainting mediated through a combination of inappropriate vascular (blood vessel) and heart rate control. Almost all of neurocardiogenic syncope in children can be deemed vasovagal (‘vaso’ denoting widening of blood vessels, and ‘vagal’ slowing of the heart rate through stimulation of the vagus nerve). On the other hand, adult syncope is much more likely to be cardiogenic, about 50% of the time. Since vasovagal syncope almost always occurs in the upright position, which may sometimes include sitting, it is regarded as a form of orthostatic intolerance.
Orthostatic intolerance can be defined as the development of symptoms during upright standing relieved by recumbency. Most of us have experienced some lightheadedness at one time or another when rising suddenly. A little further loss of blood pressure and fainting would occur. Many patients have no intercurrent illness, meaning that between faints they are well.
However, chronic orthostatic intolerance also occurs and may be confused with syncope because chronic illness can be punctuated by acute fainting episodes. Defining symptoms of chronic orthostatic intolerance include dizziness in all patients with a high incidence of altered vision (blurred, ‘white outs’, ‘black outs’), fatigue, nausea and palpitations. A large fraction of patients also experience headache, tremulousness, difficulty breathing or swallowing, sweating, pallor, and other vasomotor symptoms.
Standing up requires rapid and effective circulatory and neurologic compensation in order to maintain blood pressure and consciousness. The primary defense against blood pooling in the lower extremities is leg muscle contraction which propels venous blood back to the heart. The muscle pump is also partly defeated during quiet standing and is nearly completely defeated while standing without motion. The second line of defense against orthostatic intolerance is neurovascular adjustment which includes rapid vasoconstriction which limits blood flow to the extremities and other organs.
While systolic blood pressure normally does not fall and diastolic blood pressure often rises, cardiac output decreases an estimated 25% due to impaired heart filling which is only partially offset by an increase in heart rate. There is even a normal decrease in cerebral blood flow because cerebrovascular autoregulatory mechanisms at their limit.
Patterns of orthostatic intolerance are best defined by an orthostatic stress test. Due to the difficulty of monitoring patients by simple means, the standard of orthostatic assessment is the head up tilt table test. This device consists of a table driven by an electrical motor with a supportive footboard enabling positioning of a patient at varying angles of upright tilt. Following a resting period, the patients are placed upright and their response over a period of tilt is assessed. This is usually anywhere between 30 to 45 minutes. At a minimum, blood pressure and continuous electrocardiography are assessed.
The central purpose of a tilt table test is to reproduce symptoms of orthostatic intolerance in a setting in which blood pressure, heart rate and blood flow can be assessed. Most often there is correlation with changing physiological signs, but the definition of orthostatic intolerance requires symptoms. Thus for example the incidence of false positive faints during head up tilt is high. If the complaining symptoms are not reproduced but the patient has a simple faint, the test is judged as negative.
The normal response to head up tilt is a modest increase in heart rate (10 to 20 beats/min) without a fall in systolic blood pressure. Abnormal tilt test responses can be used to categorize patterns of orthostatic intolerance. The overall patient assessment of chronicity and severity of impairment should be combined with these data to reach any conclusion concerning the nature of orthostatic intolerance in a particular patient. In addition to the normal pattern, three typical patterns of orthostatic intolerance are depicted in the figure, which shows the systolic blood pressure and heart rate in patients during tilt.
Classic simple faint (Vasovagal Syncope)
Typically patients easily tolerate the early parts of tilt with little change in blood pressure or sensation. Following a variable period of time i.e. on the order of 7 to 20 minutes, patients develop orthostatic symptoms of nausea, dizziness, heat, heavy breathing, and sweatiness associated most commonly with a small initial slow fall in blood pressure. In short order there is an abrupt drop in blood pressure and heart rate. The early fall in blood pressure is coincident with a decrease in vasoconstriction (the peripheral arteries vasodilate) which normally occurs as part of the neurovascular compensation required to maintain blood pressure with orthostasis. Blood pressure and heart rate may plummet precipitously, and asystole may occur. When this happens there is a rapid loss of central nervous system activity and often a dysinhibition of peripheral neurologic responses resulting in muscular movements mimicking a tonic clonic seizure. This is denoted “convulsive syncope”.
Fainting usually is short lived; upon assuming recumbence the patient usually awakes after a few seconds. But some patients do not awake immediately and prolonged sleep like states have occurred. A patient persistently maintained upright in a severe simple faint can potentially die. Patients should be placed supine or allowed to fall to a recumbent position. Recumbence invariably resolves all symptoms and signs.
There are several theories as to the mechanisms for the vasovagal faint, best left for discussion elsewhere. Without a clear mechanism there is no clear treatment. Moreover, many patients with infrequent simple faints, who do not injure themselves and who do not have convulsive syncope, may require no specific therapy above training in aversive maneuvers. The simplest of these maneuvers is lying down although leg crossing, bending at the waist, squatting and other maneuvers may also be effective.
In terms of medication, often beta1 blockade works well. Other possible medications include fludrocortisone (florinef), which retains sodium and water at the expense of small potassium wasting and has little if any corticosteroid side effects. In addition to its other actions, florinef may aid in sensitizing alpha receptors and blocking vasodilation. A new, direct acting alpha1 agonist, midodrine (proamatine) has been used to good effect in many patients with assorted forms of orthostatic intolerance. Other agents have included alpha2 adrenergic agents (both clonidine and its obverse yohimbine) which have been used in select patients. Recently, selective serotonin reuptake inhibitors (SSRI) have been used to good effect in a variety of orthostatic disabilities. These seem to interfere with hypotensive responses at a central level.
Dysautonomic Orthostatic Intolerance
Included in this group are patients with true “orthostatic hypotension” defined by the American Autonomic Society to be a persistent fall in systolic blood pressure of >25 mm Hg within 3 minutes of assuming the upright position. This group harbors patients with autonomic failure. Autonomic failure includes primary forms such as primary autonomic failure and multiple system atrophy, and more common secondary forms occurring with Parkinson’s disease and diabetes.
Dysautonomia may also be drug induced. Pediatric causes are rare and include familial dysautonomia. Acute forms may occur during infectious and inflammatory diseases or be related to peripheral nerve disease, e.g. Guillian Barre syndrome.
Using standard tests of circulatory autonomic function such as timed breathing and the quantitative Valsalva maneuver patients show signs of circulatory autonomic dysfunction. Also other manifestations of dysautonomia are present including pupillary, gastrointestinal, and sweating abnormalities. Neurological damage such as occurs in cerebral palsy, trauma, etc may result in some autonomic dysfunction in addition to other neurologic disability. Blood pressure falls while there is no significant change in heart rate throughout the course of the tilt. The appropriate response of the arterial baroreflex to hypotension is increased heart rate, which fails to occur in these illnesses. Patients may be so brittle that they are hypertensive (high blood pressure) lying down, hypotensive upright, and lose consciousness due to overzealous venous pooling in the splenic tissues after every heavy meal.
Specific therapy for chronic disease is largely experimental and acute therapy for acute illness remains specific for the specific disease.
Chronic Orthostatic Intolerance and the Postural Orthostatic Tachycardia Syndrome
The orthostatic tachycardia syndrome is a disabling disease state described at least since 1940 and is the most common reason for referral for orthostatic intolerance in adults. It is an emerging form of orthostatic intolerance in children. Patients have day to day disability, a feature not shared with those with simple faint. With some exception, traditional tests of autonomic function are normal in these patients. The understanding of its pathophysiology remains incomplete.
The central physical finding is upright tachycardia although hypotension and resting tachycardia may also be present. An operational definition of the syndrome (also denoted by the acronym POTS for postural orthostatic tachycardia syndrome) includes symptoms of orthostatic intolerance associated with an increase in heart rate from the supine to upright position of more than 30 beats per minute or to a heart rate greater than 120 beats per minute within 10 minutes of head up tilt.
Hypotension may follow or occur with tachycardia. Often it is delayed beyond the onset of the symptoms and of the tachycardia, and therefore only shows up during the artificially sustained orthostasis enforced during head up tilt.
Onset of symptoms often follows an infectious disease and may be related to inflammatory mediators. POTS physiology underlies orthostatic intolerance in the large majority of adolescents with the chronic fatigue syndrome (CFS). POTS is common, affecting an undisclosed number of patients mostly in the age range of 12 to 50 years, mostly female (approximately 80%). There is an as yet undetermined but increasing prevalence in children and adolescents. Patients with the syndrome display an unusual amount of pooling in the lower extremities often associated with acrocyanosis.
Conventional medicine uses some of the medications mentioned in the vasovagal section. Of these florinef and midodrine seem to be most effective with an emerging use of SSRI’s. Beta blockers and clonidine are rarely tolerated and may point to a very different origin for Chronic Orthostatic Intolerance from syncope.