What is the mechanism of action (MOA) of vasovagal syncope?

Mechanism of Action of Vasovagal Syncope

Vasovagal syncope occurs when an inappropriate autonomic reflex causes simultaneous peripheral vasodilation and bradycardia, leading to systemic hypotension and global cerebral hypoperfusion that results in transient loss of consciousness. 1

Core Pathophysiologic Mechanism

The fundamental problem is a sudden failure of autonomic regulatory mechanisms to maintain adequate blood pressure and cerebral perfusion 2. This involves two key components:

Vasodepressor Component

• Inappropriate peripheral vasodilation causes blood vessels throughout the body to dilate excessively, reducing total peripheral vascular resistance 1, 3
• Blood pools in the lower extremities and splanchnic circulation, decreasing venous return to the heart 3
• This reduces cardiac output despite circulatory demands 1

Cardioinhibitory Component

• Reflex bradycardia occurs when the brain sends inappropriate signals to the heart, instructing it to slow down or even temporarily stop beating 3
• This further compounds the drop in cardiac output 1
• The relative contribution of vasodilation versus bradycardia varies considerably between individuals and even between episodes in the same patient 1

The Reflex Arc

The vasovagal response represents a triggered reflex with afferent, central, and efferent pathways 4:

• Afferent signals originate from ventricular mechanoreceptors that become activated when venous return drops abruptly during orthostatic stress 1, 5
• Central processing occurs in the brainstem, where autonomic centers misinterpret these signals 4
• Efferent output includes increased parasympathetic activity (causing bradycardia) and decreased sympathetic vasoconstrictor outflow (causing vasodilation) 4

Critical Threshold for Loss of Consciousness

Cerebral blood flow must be reduced by approximately 35% or completely disrupted for 5-10 seconds to cause syncope 1. Tilt-table studies demonstrate that systolic blood pressure typically falls to 60 mmHg or lower when syncope occurs 1. The brain, located at the top of the body, is the most vulnerable organ when blood pressure drops due to gravitational effects 3.

Common Triggers That Activate the Reflex

The vasovagal reflex can be triggered by multiple mechanisms 1, 5:

Emotional/Psychological Triggers

• Fear, pain, blood phobia, or medical instrumentation (venipuncture, injections) 1, 6
• These activate neural pathways that initiate the inappropriate reflex 5

Orthostatic Stress

• Prolonged standing reduces central blood volume and activates ventricular mechanoreceptors 5
• Hot, confining environments exacerbate this effect 1

Situational Triggers

• Gastrointestinal stimulation (swallowing, defecation, visceral pain) 1
• Micturition (especially post-micturition) 1
• Coughing or sneezing 1, 5
• Post-exercise or post-prandial states 1

Prodromal Symptoms and Their Mechanism

Warning symptoms occur in approximately two-thirds of cases and result from marginal cerebral perfusion before complete loss of consciousness 1, 3:

• Lightheadedness, dizziness, and visual changes (blurred or tunnel vision) reflect early cerebral hypoperfusion 1, 6
• Nausea, vomiting, diaphoresis, pallor, and warmth represent autonomic nervous system activation 1, 3, 6
• These prodromal symptoms typically last only seconds, providing a brief window for intervention 1

Recovery Phase

Loss of consciousness is typically brief, usually lasting less than 20 seconds to one minute 3, 6. Recovery is rapid and complete once the person assumes a horizontal position, which eliminates the gravitational challenge and allows blood to return to the brain 3. Patients return spontaneously to baseline without therapeutic intervention and do not experience prolonged confusion, distinguishing vasovagal syncope from seizures 1.

Important Clinical Pitfalls

• Myoclonic jerks may occur in up to 90% of vasovagal episodes, which can be mistaken for seizure activity 6
• Older adults often have atypical presentations with short or absent prodrome and may have amnesia for loss of consciousness, leading to misdiagnosis as falls 5, 7
• The reflex represents either a hypersensitive autonomic system that over-responds to stimuli or a hyposensitive system unable to maintain steady-state adaptation 3
• Volume depletion from any cause (dehydration, blood loss, vomiting) exacerbates susceptibility to vasovagal syncope 1, 3