Syncope is a transient, self-limited loss of consciousness due to acute global impairment of cerebral blood flow. The onset is rapid, duration brief, and recovery spontaneous and complete. Other causes of transient loss of consciousness need to be distinguished from syncope; these include seizures, vertebrobasilar ischemia, hypoxemia, and hypoglycemia. A syncopal prodrome (presyncope) is common, although loss of consciousness may occur without any warning symptoms. Typical presyncopal symptoms include dizziness, lightheadedness or faintness, weakness, fatigue, and visual and auditory disturbances. The causes of syncope can be divided into three general categories: (1) neurally mediated syncope (also called reflex or vasovagal syncope), (2) orthostatic hypotension, and (3) cardiac syncope.

Neurally mediated syncope comprises a heterogeneous group of functional disorders that are characterized by a transient change in the reflexes responsible for maintaining cardiovascular homeostasis. Episodic vasodilation (or loss of vasoconstrictor tone) and bradycardia occur in varying combinations, resulting in temporary failure of blood pressure control. In contrast, in patients with orthostatic hypotension due to autonomic failure, these cardiovascular homeostatic reflexes are chronically impaired. Cardiac syncope may be due to arrhythmias or structural cardiac diseases that cause a decrease in cardiac output. The clinical features, underlying pathophysiologic mechanisms, therapeutic interventions, and prognoses differ markedly among these three causes.

Syncope is a common presenting problem, accounting for approximately 3% of all emergency room visits and 1% of all hospital admissions. The annual cost for syncope-related hospitalization in the United States is ~$2.4 billion. Syncope has a lifetime cumulative incidence of up to 35% in the general population. The peak incidence in the young occurs between ages 10 and 30 years, with a median peak around 15 years. Neurally mediated syncope is the etiology in the vast majority of these cases. In elderly adults, there is a sharp rise in the incidence of syncope after 70 years.

In population-based studies, neurally mediated syncope is the most common cause of syncope. The incidence is slightly higher in females than males. In young subjects, there is often a family history in first-degree relatives. Cardiovascular disease due to structural disease or arrhythmias is the next most common cause in most series, particularly in emergency room settings and in older patients. Orthostatic hypotension also increases in prevalence with age because of the reduced baroreflex responsiveness, decreased cardiac compliance, and attenuation of the vestibulosympathetic reflex associated with aging. In the elderly, orthostatic hypotension is substantially more common in institutionalized (54–68%) than community-dwelling (6%) individuals, an observation most likely explained by the greater prevalence of predisposing neurologic disorders, physiologic impairment, and vasoactive medication use among institutionalized patients.

The prognosis after a single syncopal event for all age groups is generally benign. In particular, syncope of noncardiac and unexplained origin in younger individuals has an excellent prognosis; life expectancy is unaffected. By contrast, syncope due to a cardiac cause, either structural heart disease or primary arrhythmic disease, is associated with an increased risk of sudden cardiac death and mortality from other causes. Similarly, mortality rate is increased in individuals with syncope due to orthostatic hypotension related to age and the associated comorbid conditions (Table 11-1).

The upright posture imposes a unique physiologic stress upon humans; most, although not all, syncopal episodes occur from a standing position. Standing results in pooling of 500–1000 mL of blood in the lower extremities and splanchnic circulation. There is a decrease in venous return to the heart and reduced ventricular filling that result in diminished cardiac output and blood pressure. These hemodynamic changes provoke a compensatory reflex response, initiated by the baroreceptors in the carotid sinus and aortic arch, resulting in increased sympathetic outflow and decreased vagal nerve activity (Fig. 11-1). The reflex increases peripheral resistance, venous return to the heart, and cardiac output and thus limits the fall in blood pressure. If this response fails, as is the case chronically in orthostatic hypotension and transiently in neurally mediated syncope, cerebral hypoperfusion occurs.

Syncope is a consequence of global cerebral hypoperfusion and thus represents a failure of cerebral blood flow autoregulatory mechanisms. Myogenic factors, local metabolites, and to a lesser extent autonomic neurovascular control are responsible for the autoregulation of cerebral blood flow (Chap. 33). The latency of the autoregulatory response is 5–10 s. Typically cerebral blood flow ranges from 50 to 60 mL/min per 100 g brain tissue and remains relatively constant over perfusion pressures ranging from 50 to 150 mmHg. Cessation of blood flow for 6–8 s will result in loss of consciousness, while impairment of consciousness ensues when blood flow decreases to 25 mL/min per 100 g brain tissue.

From the clinical standpoint, a fall in systemic systolic blood pressure to ~50 mmHg or lower will result in syncope. A decrease in cardiac output and/or systemic vascular resistance—the determinants of blood pressure—thus underlies the pathophysiology of syncope. Common causes of impaired cardiac output include decreased effective circulating blood volume; increased thoracic pressure; massive pulmonary embolus; cardiac brady- and tachyarrhythmias; valvular heart disease; and myocardial dysfunction. Systemic vascular resistance may be decreased by central and peripheral autonomic nervous system diseases, sympatholytic medications, and transiently during neurally mediated syncope. Increased cerebral vascular resistance, most frequently due to hypocarbia induced by hyperventilation, may also contribute to the pathophysiology of syncope.

Two patterns of electroencephalographic (EEG) changes occur in syncopal subjects. The first is a “slow-flat-slow” pattern (Fig. 11-2) in which normal background activity is replaced with high-amplitude slow delta waves. This is followed by sudden flattening of the EEG—a cessation or attenuation of cortical activity—followed by the return of slow waves, and then normal activity. A second pattern, the “slow pattern,” is characterized by increasing and decreasing slow wave activity only. The EEG flattening that occurs in the slow-flat-slow pattern is a marker of more severe cerebral hypoperfusion. Despite the presence of myoclonic movements and other motor activity during some syncopal events, EEG seizure discharges are not detected.

NEURALLY MEDIATED SYNCOPE

Neurally mediated (reflex; vasovagal) syncope is the final pathway of a complex central and peripheral nervous system reflex arc. There is a sudden, transient change in autonomic efferent activity with increased parasympathetic outflow, plus sympathoinhibition (the vasodepressor response), resulting in bradycardia, vasodilation, and/or reduced vasoconstrictor tone. The resulting fall in systemic blood pressure can then reduce cerebral blood flow to below the compensatory limits of autoregulation (Fig. 11-3). In order to elicit neutrally mediated syncope, a functioning autonomic nervous system is necessary, in contrast to syncope resulting from autonomic failure (discussed below).

Multiple triggers of the afferent limb of the reflex arc can result in neutrally mediated syncope. In some situations, these can be clearly defined, e.g., the carotid sinus, the gastrointestinal tract, or the bladder. Often, however, the trigger is less easily recognized and the cause is multifactorial. Under these circumstances, it is likely that different afferent pathways converge on the central autonomic network within the medulla that integrates the neural impulses and mediates the vasodepressor-bradycardic response.