Orthostatic Intolerance

Orthostatic intolerance encompasses disorders of blood flow, heart rate, and blood pressure (BP) regulation that are most easily demonstrable during orthostatic stress yet are present in all positions. Improved understanding of changes in these parameters is the result of the recently popularized head-up tilt test. Three easily definable entities of orthostatic intolerance include vasovagal syncope, orthostatic hypotension, and postural orthostatic tachycardia syndrome (POTS).

Vasovagal Syncope

Vasovagal syncope (also called simple fainting or neurocardiogenic or neurally mediated syncope) is the most common type of syncope in otherwise healthy children and adolescents. This syncope is uncommon before 10 to 12 years of age but quite prevalent in adolescent girls. It is characterized by a prodrome (warning symptoms and signs) lasting a few seconds to 1 minute; the prodrome may include dizziness, nausea, pallor, diaphoresis, palpitation, blurred vision, headache, or hyperventilation. The prodrome is followed by loss of consciousness and muscle tone. The patient usually falls without injury, the unconsciousness does not last more than 1 minute, and the patient gradually awakens. The syncope may occur after rising in the morning; after taking a morning shower; or in association with prolonged standing, anxiety or fright, pain, blood drawing or the sight of blood, fasting, hot and humid conditions, or crowded places. It may occur after prolonged exercise (if it is stopped suddenly).

The pathophysiology of vasovagal syncope is not completely understood. The following is a popular hypothesis (although dismissed by some). In normal individuals, an erect posture without movement shifts blood to the lower extremities and pelvis and causes a decrease in venous return, thus decreasing stroke volume and BP. This reduced filling of the ventricle places less stretch on the mechanoreceptor (i.e., C fibers) and causes a decrease in afferent neural output to the brain stem, reflecting hypotension. This decline in neural traffic from the mechanoreceptors and a decreased arterial pressure elicit an increase in sympathetic output, resulting in an increase in heart rate and peripheral vasoconstriction to restore BP to the normal range. Thus, the normal responses to the assumption of an upright posture are a reduced cardiac output (by 25%), an increase in heart rate, an unchanged or slightly diminished systolic pressure ( Fig. 31-1 ), and an increase in diastolic pressure to ensure coronary artery perfusion. Cerebral blood flow decreases by approximately 6% with cerebrovascular autoregulation functioning near its maximal limit.

Schematic drawing of changes in heart rate (HR) and blood pressure (BP) observed during the head-up tilt test. Thin arrows mark the start of orthostatic stress. Large unfilled arrows indicate the appearance of symptoms with changes seen in HR and BP. In normal individuals, the HR increases slightly with no change or a slight reduction in BP. In patients with vasovagal syncope, both the HR and BP drop precipitously with the appearance of symptoms. Postural hypotension is characterized by a drop in BP by 10 to 15 mm Hg as symptoms appear within 3 minutes of standing. Postural hypotension may not occur in the presence of good hydration. In POTS, the HR increases significantly by more than 30 beats/min (or the HR is 120 beats/min or higher) with development of symptoms within 10 minutes of standing. POTS, postural orthostatic tachycardia syndrome.

In susceptible individuals, however, a sudden decrease in venous return to the ventricle produces a large increase in the force of ventricular contraction; this causes activation of the left ventricular mechanoreceptors, which normally respond only to stretch ( Fig. 31-2 ). The resulting paroxysmal increase in neural traffic to the brain stem somehow mimics the conditions seen in hypertension and thereby produces a paradoxical withdrawal of sympathetic activity and vagal activation. Withdrawal of sympathetic activity leads to a peripheral vasodilatation, hypotension, and bradycardia. Vagal activation results in bradycardia (see Fig. 31-2 ). Characteristically, the reduction of BP and especially the heart rate are severe enough to decrease cerebral perfusion, resulting in either presyncope or syncope (with loss of consciousness). Vasovagal syncope always occurs while the patient is in a standing position. Hypovolemia (or dehydration) is often a predisposing factor. “Stress” may also be a possible predisposing factor in the pathogenesis of syncope. With respect to the pharmacologic approach to prevent vasovagal syncope, α-adrenergic agonists, beta-blockers, serotonin reuptake inhibitors, anticholinergic muscarinic blockers, and volume expansion have been used successfully, and their presumed points of action are shown Figure 31-2 .

Proposed pathophysiology of neurocardiogenic syncope. Presumed points of action of various pharmacologic agents are also shown by open arrows. LV, left ventricular.

Modified from Ross BA, Saul JP: Management of vasovagal syncope: pharmacologic, nonpharmacologic, or pacing. In Walsh EP, Saul JP, Triedman JK (eds): Cardiac Arrhythmias in Children and Young Adults with Congenital Heart Disease. Philadelphia, Lippincott Williams and Wilkins, 2001.

History is most important in establishing the diagnosis of vasovagal syncope. Tilt testing of various protocols is useful in diagnosing vasovagal syncope, but it has not been well standardized, and its specificity and reproducibility are questionable.

Placing the patient in a supine position until the circulatory crisis resolves may be all that is indicated. If the patient feels the prodrome to a faint, he or she should be told to lie down with the feet raised above the chest; this usually aborts the syncope. Success in preventing syncope has been reported with medications, such as fludrocortisone (Florinef), beta-blockers, pseudoephedrine, and others (see Management section below).

Orthostatic Hypotension (Dysautonomia)

The normal response to standing is reflex arterial and venous constriction and a slight increase in heart rate. In orthostatic hypotension, the normal adrenergic vasoconstriction of the arterioles and veins in the upright position is absent or inadequate, resulting in hypotension without a reflex increase in heart rate (see Fig. 31-1 ). In contrast to the prodrome seen with vasovagal syncope, in orthostatic hypotension, patients experience only lightheadedness. Orthostatic hypotension is usually related to medication (see later discussion) or dehydration, but it can be precipitated by prolonged bed rest, prolonged standing, and conditions that decrease the circulating blood volume (e.g., bleeding, dehydration). Drugs that interfere with the sympathetic vasomotor response (e.g., calcium channel blockers, antihypertensive drugs, vasodilators, phenothiazines) and diuretics may exacerbate orthostatic hypotension. Dysautonomia may also be seen during an acute infectious disease or in peripheral neuropathies such as Guillain-Barré syndrome.

In patients suspected of having orthostatic hypotension, BP should be measured in the supine and standing positions. The American Autonomic Society has defined orthostatic hypotension as a persistent fall in systolic/diastolic pressure of more than 20/10 mm Hg within 3 minutes of assuming the upright position without moving the arms or legs with no increase in the heart rate but without fainting. Orthostatic hypotension may only be demonstrable in the presence of dehydration. In a well-hydrated state when the individual is seen in an office setting, orthostatic hypotension may not occur. Patients with orthostatic hypotension also have a positive tilt test result but do not display the autonomic nervous system signs of vasovagal syncope, such as pallor, diaphoresis, and hyperventilation.

The same management as that given for vasovagal syncope is sometimes successful. Elastic stockings, a high-salt diet, sympathomimetic amines, and corticosteroids have been used with varying degrees of success. The patient should be told to move to an upright position slowly.

Postural Orthostatic Tachycardia Syndrome

This relatively new syndrome is a form of orthostatic intolerance that is most often observed in young women. Venous pooling associated with assuming a standing position predominantly affects the lower extremities. This leads to a reduced venous return, a resulting increase in sympathetic discharge, and a significant degree of tachycardia. An increased level of adrenomedullin, a potent vasodilator with natriuretic and diuretic effects, has been observed in some children with the syndrome, possibly as a result of endothelial dysfunction ( Zhang et al, 2012 ).

Patients with POTS experience difficulties with daily routines such as housework, shopping, eating, attending work or school, and complaints of chronic fatigue. Children (and adults) with the syndrome often have symptoms of syncope, dizziness, chest discomfort or pain, headache, palpitation, nausea, fatigue, and exercise intolerance. This may be related to chronic fatigue syndrome and may be misdiagnosed as having panic attacks or chronic anxiety. The general physical examination is often unrevealing.

For the diagnosis of POTS, heart rate and BP are measured in the supine, sitting, and standing positions. POTS is defined as the development of orthostatic symptoms that are associated with at least a 30-beat/min increase in heart rate (or a heart rate of ≥120 beats/min) that occurs within the first 10 minutes of standing or upright tilt. An exaggerated increase in heart rate is often accompanied by hypotension in association with the symptoms described above (see Fig. 31-1 ). Occasional patients develop swelling of the dependent lower extremities with purplish discoloration of the dorsum of the foot and ankle. Tilt table testing is often useful as a standardized measure of response to postural change.

The same approaches of management as vasovagal syncope are used with varying level of success. One should check if any medications the patient may be taking could be contributing to the problem (e.g., vasodilators, tricyclic antidepressants, monoamine oxidase inhibitors, or alcohol). The patient is advised to avoid extreme heat and dehydration and to increase salt and fluid intake. Pharmacologic agents such as fludrocortisone, midodrine (a peripheral vasoconstrictor, at a dose of 5–10 mg three times a day), or venlafaxine (a selective serotonin reuptake inhibitor) are useful in many patients.

Exercise-Related Syncope

Sudden unconsciousness that occurs during or after strenuous physical activities or sports may signal an organic cause such as cardiopulmonary diseases, including cardiac arrhythmia. However, in most cases, exercise-related syncope is not an indicator of serious underlying cardiopulmonary or metabolic disease. It occurs more often because of a combination of venous pooling in vasodilated leg muscles, inadequate hydration, and high ambient temperature. Hyperventilation with hypocapnia (with tingling or numbness of extremities) secondary to strenuous activities may also cause syncope. To prevent venous pooling, athletes should keep moving after running competitions.

Rare Causes of Syncope

Micturition syncope is a rare form of orthostatic hypotension. In this condition, rapid bladder decompression results in decreased total peripheral vascular resistance with splanchnic stasis and reduced venous return to the heart, resulting in postural hypotension.

Cough syncope occurs after paroxysmal nocturnal coughing in children with asthma. The patient’s face become plethoric and cyanotic, and the child perspires, becomes agitated, and is frightened. Loss of consciousness is associated with muscle contractions lasting for several seconds. Urinary incontinence is frequent. Consciousness is regained within a few minutes. Paroxysmal coughing produces a marked increase in intrapleural pressure with a reduced venous return and reduced cardiac output, resulting in altered cerebral blood flow and loss of consciousness. Treatment is aimed at preventing bronchoconstriction with aggressive asthma treatment plans