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. 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. 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 seconds 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.

The sequence of changes on the electroencephalogram of syncopal subjects during syncope comprises background slowing (often of high amplitude), followed by attenuation or cessation of cortical activity prior to return of slow waves, and then normal activity. Despite the presence of myoclonic movements and other motor activity, electroencephalographic seizure discharges are not present in syncopal subjects.

Transient loss of consciousness may be caused by trauma, intoxication, hypoglycemia, or true syncope. Syncope refers to the abrupt, transient complete loss of consciousness and postural tone due to transient global cerebral hypoperfusion, usually due to transient profound hypotension. Since such profound hypotension can be catastrophic or fatal if prolonged, syncope may portend sudden cardiac death; therefore, a careful evaluation is critical to identify and treat patients with potentially life- threatening etiologies of syncope.


Image not available. Patients with syncope should be carefully evaluated to determine if they are at risk for sudden cardiac death.


The differential diagnosis for syncope is best remembered by considering the 3 most common causes of syncope: reflex mediated syncope, cardiac syncope, and orthostatic hypotension (Figure 31-1).

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.

Mr. M is a 23-year-old medical student who had an episode of syncope this morning after entering his anatomy lab for the first time. He is quite alarmed (and embarrassed).

What is the differential diagnosis of syncope? How would you frame the differential?