 Abstract | | |
Vasovagal syncope (VVS) in donors is a transient loss of consciousness due to short-term global cerebral hypoperfusion, which has a rapid onset and has complete spontaneous recovery. VVS may be triggered by pain, fear, anxiety, or emotional upset and loss of blood perse. It is an exaggeration of an adaptive response meant to assist in reducing the amount of bleeding/loss of blood. The four major components necessary for rapid cardiovascular adjustments to supine or upright posture, otherwise called orthostasis, are the autonomic nervous system, adequate blood volume, and intact skeletal and respiratory muscle pumps. The taxing of these autoregulatory mechanisms and their inability to compensate sufficiently results in VVS. VVR episodes can be described in 3 phases; Presyncope, Syncope, and Postsyncope. The actual syncope generally lasts for <15 s, comprising staring, muscle jerks, eye deviation/rolling, sometimes incontinence, loss of consciousness, gasping, snoring, apnea, inability to move/react, etc., The postsyncopal phase is the longest, which is generally manifested as fatigue. Keywords: Blood donation, emotional syncope, pathophysiology, vasovagal syncope
How to cite this URL:
Basavarajegowda A, Nalini Y C. Syncopal reactions in blood donors: Pathophysiology, clinical course, and features. Asian J Transfus Sci [Epub ahead of print] [cited 2023 Mar 23]. Available from: https://www.ajts.org/preprintarticle.asp?id=356870 |
| Introduction | |  |
Vasovagal syncope (VVS) in donors is a transient loss of consciousness due to short-term global cerebral hypoperfusion, which has a rapid onset and has complete spontaneous recovery.[1] The term “vaso” refers to vasodilation and “vagal” for vagus stimulation. This is also called neurovasogenic or reflex syncope. VVS may be triggered by anxiety, fear, pain, or emotional upset, although a specific precipitating factor cannot be identified frequently.[2] The vasovagal reaction is an exaggeration of an adaptive response meant to assist in hemostasis, i.e. the body reflexively lowers blood pressure (BP) and heart rate to reduce the amount of bleeding/loss of blood.
The graph in [Figure 1] shows the fainting rates across the time course of whole blood donation. The overall vasovagal syncopal rate is about 0.3%. There is a very low risk of reaction from time of arrival to donation up to needle insertion. The complete donation typically takes 7–10 min. During the first 4 min of the introduction of the needle, the reaction rates remain low. This increases towards the end of donation with a sharp peak around the time of removal of the needle. This coincides with the completion of removal of the blood volume, which is now extracorporeal. After the removal, donors are allowed to rest on the couch for another couple of minutes (typically 3–5 min) before standing up. Up to 40% of reactions are known to happen during this period.[3]
After standing up from the donation couch, a small increased rate attributed to initial orthostatic hypotension combined with vasovagal reflex is noticed. This period in the refreshment area is wherein 50% of syncopes are observed in blood donation.
After leaving the donor room a slightly <10% syncopes are noted as long as 4–6 h after donation. However, there is always an underestimation of reactions in this period as they are generally underreported or have no active follow-up. However, these are very important as the injury rate is very high when these reactions happen off-site of donation compared to those happening on site. Somehow off-site reactions are known to be more common in females.
| Etiology and Risk Factors | | |
The various period-specific causes and risk factors for VVR during blood donation are shown in [Figure 2].[3],[4],[5] The various risk factors have been reviewed elaboratively in Thijsen et al. Genetic link for the syndrome is also sought with genomic analysis demonstrating some variations in families with a high burden of reflex syncope.[6] A “low systolic BP phenotype” has been described by the European Society of Cardiology ESC 2018, indicating susceptibility to VVS. People with VVS have shown a lower-than-expected increase in BP with age.[7] | Figure 2: The period-specific causes and risk factors for VVR during the process of blood donation. EBV= Estimated blood volume
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| Mechanisms and Pathophysiology | | |
To understand the pathophysiology of vasovagal reaction, it is essential to understand the physiological mechanisms involved in short-term BP regulation. Short term regulatory responses of BP are basically of 3 types:
- Baroreceptors response
- Chemoreceptor response
- CNS ischemic response.
Chemoreceptors (peripheral and central) are activated when the chemical composition of blood is altered, like changes in blood pH, arterial oxygen, and carbon dioxide concentration, to bring homeostasis through a negative feedback mechanism.[8] Central nervous system ischemic response comes into play when mean arterial pressure drops below 60 mm Hg. It is the last mechanism of the body to bring back homeostasis through intense vasoconstriction.[9] Since the chemical composition of blood is not altered, nor is this kind of severe drop in arterial pressure not seen in VVS or orthostatic hypotension, these defense mechanisms do not come into action and will not be discussed further.
Of these, the baroreceptor response is the most crucial reflex as it acts swiftly to bring out the desired changes in BP. BP in the body can rise or fall below the normal range of <120, 80 systolic, and diastolic pressure, respectively. Baroreceptors detect this change in BP, and the message is conveyed to the cardiovascular control centers situated in the medulla via the afferent nerves. In response to the stimulation, the medullary centers bring out corrective changes in the cardiovascular system (innervation to the heart and blood vessel) via the efferent nerve, bringing back the BP within the normal range. This pathway is summarized in [Table 1]. The types of baroreceptors and their location are summarized in [Figure 3].
Baroreceptors are stretch receptors or mechanoreceptors located in the dilated sinus; these are coiled nerve endings located in the adventitia of carotid and aortic arteries that are high-pressure areas of circulation. They respond to BP changes between 70 and 150 mm Hg by altered discharge frequency. The glossopharyngeal nerve innervates carotid baroreceptors, and vagus nerves innervate aortic baroreceptors. The afferent nerves from the baroreceptors are called buffer nerves as they try to reduce the impact of altered BP on the organs by immediately stimulating short-term regulatory mechanisms within seconds. The efferent nerve is mainly via the vagus nerve.[10]
What does the center do to bring back homeostasis?
The baroreceptors on stimulation via the afferent fibers glossopharyngeal and vagus nerve reach the medulla. The medulla consists of the caudal ventral lateral medulla (CVLM) and rostral lateral medulla (RVLM). The afferent fibers then release excitatory neurotransmitters (glutamate) to excite the neurons in the nucleus tractus solitarious (NTS). These NTS neurons then excite the CVLM. CVLM on excitation release on inhibitory neurotransmitter: Gamma-aminobutyric acid (GABA) into RVLM to reduce the firing rate. Excitatory projections also extend from NTS to the vagal nuclei (nucleus ambiguus and dorsal motor nucleus). So, increased stimulation of baroreceptors discharge inhibits the tonic discharge of sympathetic nerves and excites the heart's vagal innervation, resulting in effector response of vasodilation, venodilation, hypotension, bradycardia, and decrease in cardiac output.
Decrease stimulation of baroreceptors is generally seen when a sudden drop in BP decreases the release of excitatory neurotransmitters (glutamate) in NTS. Decrease stimulation of CVLM, resulting in decreased inhibition of RVLM through GABA. Since RVLM is the primary source of excitatory input to sympathetic nerves controlling vasculature, resulting in vasoconstriction, hypertension, increase in cardiac output, and tachycardia.[11]
 | Figure 4: Rapid negative feedback mechanism (homeostatic pathway) following blood pressure drops
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Gravity exerts significant effects on central venous pressure (CVP) and venous return. When a person is supine, systemic blood vessels are positioned near the hydrostatic level of the heart, which results in uniform distribution of the blood volume between the major compartments of the body such as head, legs, abdomen, and thorax. In the supine position, CVP is 2 mm Hg, and venous pressure in the legs is 4–6 mm Hg. When there is a change of position from supine to standing posture, gravity acts on the vascular volume, causing blood to accumulate in the lower extremities. As venous compliance is much more than arterial compliance, the shift in blood volume to the legs increases their venous pressure and volume. This venous pooling in the lower limb results in decreased venous return, stroke volume, cardiac output, and BP.[12] Rapid negative feedback mechanism (Homeostatic pathway) when BP drops is summarized in [Figure 4].
Emotional syncope
The corticothalamic centers involved in emotional triggers project onto nucleus ambiguus/dorsal vagal nucleus, which induce vagal stimulation, and rostroventral medulla.
| Orthostatic Regulation | | |
The four major components necessary for rapid cardiovascular adjustments to supine or upright posture, otherwise called orthostasis, are adequate blood volume, autonomic nervous system, and intact skeletal and respiratory muscle pumps. In the earlier section, we have seen the role of the autonomic nervous system in cardiovascular adjustments to hypotension. We need to learn about two crucial pumps that are skeletal and respiratory and their role in maintaining venous return and stroke volume before we begin to understand what orthostatic hypotension is.
Skeletal muscle pump
Veins in the lower limbs consist of a one-way valve that permits blood flow in one direction towards the heart, as depicted in [Figure 5]. Deep veins in the lower limbs are surrounded by large groups of muscle that compress the veins when the muscles contract. The compression produced by muscle contraction increases the pressure within the veins, which results in the opening of downstream valves and closure of upstream valves resulting in a pumping mechanism. Thus, muscles' rhythmic contraction helps counteract gravitational forces when a person stands up by facilitating venous return and lowering venous and capillary pressures in the feet and lower limb.
Respiratory pump
High right atrial pressure decreases venous return, whereas low right atrial pressure facilitates venous return. As right atrial pressure falls during inspiration, the pressure gradient for venous return to the heart is increased. During expiration, the opposite occurs, although the net effect of respiration is that the increased rate and depth of ventilation facilitate the venous return, thereby increasing stroke volume and cardiac output.[13]
On change of posture from supine to standing, we know that there is a drop in BP which gets corrected by baroreceptor response, but that does not happen, and If systemic arterial pressure falls by more than 20 mmHg upon standing, this is termed orthostatic or postural hypotension. When this occurs, cerebral perfusion may fall, and a person may become “light-headed” and experience a transient loss of consciousness (syncope) and is usually relieved by changing from upright to supine posture.
| Vasovagal Reflex and Syncope | | |
The VVS can be subdivided into “Orthostatic” and “Emotional” phases. Orthostatic is the most common [Table 2]. The mechanism culminating in VVS is shown in the algorithm in [Figure 6]. | Figure 6: Flow chart explaining the mechanism of vasovagal syncope. SNS: Sympathetic nervous system, PNS: Parasympathetic nervous system, NA: Nucleus ambiguus, DVN: Dorsal vagal nuclei, MAP: Mean arterial pressure, NTS: Nucleus tractus solitarius, CVLM: Caudal ventrolateral medulla, RVLM: Rostro ventrolateral medulla, SA NODE: Sinoatrial node, VMC: Vasomotor center
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Input from higher cortical regions can alter autonomic function. For example, sudden fear or emotion can sometimes cause vagal activation leading to bradycardia, withdrawal of sympathetic vascular tone, and fainting (VVS). The mechanisms responsible for vasovagal response are complex with both depression of cardiac output (cardio inhibition) and decrease in vascular tone (vaso depression). The vasovagal reaction is an exaggeration of an adaptive response meant to attain hemostasis. The body responds to blood loss/trauma by lowering BP and heart rate to reduce the blood loss. As we have seen baroreceptor reflex as an afferent arc, center and efferent arc, let us understand VVS on the same lines. The afferent limb of the vasovagal reflex arc begins with a trigger. The trigger may be emotional stress or pain and is often challenging to identify. This trigger, along with central hypovolemia, increases cardiac contractility, which triggers the mechanoreceptors in the ventricles, sending a signal through the vagus nerve to the central nervous system.[6]
The increased parasympathetic activity of the heart results in a decrease in heart rate, and decreased sympathetic activity reduces the vasoconstrictor tone in the arteries. This results in decreased preload, venous return, stroke volume. Since there is a drop in heart rate and circulating blood volume, the mean arterial pressure drops. Cerebral autoregulation (the innate ability of the brain to maintain perfusion despite a drop in mean arterial pressure) comes into the picture to preserve cerebral blood flow. However, if the drop in mean arterial pressure is below the organ's ability to auto-regulate, the person develops syncope.
About 500 ml of blood pools in an average adult's lower limbs (downward pooling) when he rises from a supine position (within 10 s). In addition to about 500 ml of blood lost in donation, this doubles the orthostatic stress taxing the vasoconstrictor reserve, leading to a drop in BP resulting in fainting. Also to be noted is that the donor is not completely supine on the blood donation couch.[2]
The vasovagal syncope
VVR episodes can be described in three phases; presyncope, syncope, and postsyncope. The various signs and symptoms noted in these phases are summarized in [Table 3].
Presyncope
The prodromal symptoms or presyncopal symptoms start 30–60 s before syncope. Nausea, sweating, and light-headedness are the three most consistent symptoms of presyncope. All signs and symptoms result from autonomic activation, both sympathetic and parasympathetic, with the retina and brain hypoperfusion. If the fall in arterial BP is slow enough, the donors perceive symptoms.[3]
Sweating happens as a result of sympathetic stimulation followed by increased release of adrenaline from the adrenal medulla. Sinus tachycardia is noted if the donor is standing.
Facial pallor, the first sign, occurs due to vasoconstriction (sympathetic) and reduced BP or blood flow. Increased vasopressin due to hypotension leads to vasoconstriction. The subcutaneous tissue and fat, generally mild carotene/yellowish-white, become visible when the vasoconstriction leads to reduced blood flow to the dermis and, hence, pallor.
Pupillary dilation happens due to sympathetic activation and adrenaline with inhibition of parasympathetic (pupillary constriction). Maximum pupillary dilation happens just before Loss of Consciousness (LOC).
An increase in depth of breathing is a reflex response to increase venous return and forego abdominal pump (BP increases during a heavy sigh). Head drop is due to loss of muscle tone.
A yawn is a reflex comprising of the simultaneous inhalation of air followed by an exhalation of breath. When one's blood contains increased carbon dioxide, a yawn provides a prolonged expulsion followed by oxygen influx. Yawning helps increase a person's alertness. Yawning is the body's way of controlling brain temperature by cooling down the brain; the pressure of the brain is increased by an influx of air caused by increased cranial space.[14]
Syncope
Abrupt onset syncope is induced by a long cardiac standstill or prolonged deep fall in arterial pressure. Steep fall in arterial pressure happens on standing up (>10 mm Hg). The timeline course of syncopal signs and events is depicted in [Figure 7]. These are the typical signs elicited by hypoperfusion of the brain. Eye-opening with deviation is typical of the onset of loss of consciousness. Some donors close their eyes on their own when this sequence of events happens. Loss of muscle tone is common, but muscle stiffening can occur. Incontinence, generally urine and rarely stools, can happen because of the loss of sphincter tone due to cerebral hypoperfusion. The donor may turn blue in prolonged apnea.[15],[16]
Postsyncope
A distinction can be made between signs and symptoms that occur in the first few seconds of recovery and those that last for several minutes following recovery. The early events are an occurrence of flush in the face and upper thorax, rapid recovery of consciousness, and a few seconds of amazement and incomprehension (5–10 s). After 20–30 s of abrupt onset syncope, the donors are usually well oriented and capable of performing purposeful movements. The after-effects are pallor, sweating, fatigue, nausea, and prolonged post faint hypotension (rarely). Recovery of BP is generally rapid. Prolonged postfaint hypotension is defined as the persistence of systolic BP <85 mmHg in a supine position beyond 2 min. A pronounced sense of weakness after recovery and a tendency for recurrence on rising are characteristic of VVR.[17],[18]
Grading of vasovagal reactions
The vasovagal reactions have been graded as mild, moderate, and severe. The mild grade is assigned for presyncope vasovagal reactions such as pallor, sweating, anxiety; moderate grade, for those with hypotension, vomiting, and transient loss of consciousness (few seconds); and severe grade for loss of consciousness associated with other signs and symptoms such as recurrent vomiting, prolonged pulse and/or BP recovery times (>15 min), incontinence, and convulsions.[19],[20]
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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Correspondence Address:
YC Nalini,
Department of Physiology, Mahatma Gandhi Medical College and Research Institute, Pondicherry
India
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/ajts.ajts_167_21
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
[Table 1], [Table 2], [Table 3] |
