Syncope prevention in blood donors: when to do what?

Syncope (fainting) or near-syncope is a major adverse reaction among blood donors that usually occurs during or in close temporal proximity to whole blood donation.1 Not only can syncope cause injuries in donors, its occurrence also decreases the likelihood of subsequent donations.2 Although a great deal of effort has been applied to the prevention of syncope in donors, the best strategies for reducing the incidence of syncopal reactions remain uncertain. One key reason for this dilemma may be lack of a clear understanding of the pathophysiology underlying syncope during as well as after blood donation. In this issue of TRANSFUSION, Morand et al.3 report a large, randomized controlled trial of two different mechanisms to prevent syncope during and after whole blood donation. The authors found that drinking 500 mL of water or isotonic drink before the donation was useful in preventing (pre)syncopal reactions in donors, whereas isotonic drinks had the advantage of preventing delayed reactions and fatigue after the donation. Conversely, the effect of light muscle-tensing exercise was short term, only significantly reducing syncope-type reactions during the blood collection period, but not after the donation. These observations are important and have essential clinical implications. Although the intervention implemented by the investigators is reasonable, it perhaps could be even better designed, and the outcomes might well then have been further improved if more specific pathophysiology-based approaches had been selected. Approximately 40% of syncopal reactions occur in the process of blood donation/collection.1, 3 Donors are typically in the recumbent or semirecumbent position, although reductions in central blood volume are not substantial during this period. Both psychological (e.g., fear of needles, pain, and blood) and physiological factors contribute to syncopal reactions in donors, and the former are primary during this early time period. Indeed, a recent study showed that fear was the strongest predictor of syncopal reaction during blood collection; furthermore, when fear was present in the prediction models, many of the previously reported predictors of reactions, such as age, sex, donor status, and estimated blood volume, were no longer significant.4 Although the links from psychological input to autonomic circulatory control are unknown, syncopal reactions in the course of blood collection may be triggered by “threatening” or “emotional” stimuli, and the afferent neural signals may originate from higher cortical sites rather than peripheral sites (i.e., pain receptors).5, 6 Syncope during this period is a neurally mediated reflex reaction, namely, sympathetic withdrawal, increased vagal tone, or both. Based on conventional wisdom, loss of sympathetic tone7-11 with relaxation of vascular resistance12-15 is thought to play a major role in neurally mediated syncope, although we have found that there is large individual variability in the response of vasomotor sympathetic activity before (pre)syncope in healthy humans.16 Previous microneurographic studies demonstrated that, in patients with phobia to blood/injury, an inhibition of sympathetic nerve activity is part of an autonomic response to arousal stimuli, the strength of which reflects a fear-related, subjective factor.17 It also was found that the number of bursts inhibited was positively correlated with syncopal episodes in phobic patients, suggesting that the exaggerated sympathetic inhibition may be a counterpart of their exaggerated fear of injury: the stronger the fear, the more pronounced the inhibition.17 In addition, signs and symptoms of increased vagal tone (e.g., pallor, sweating, nausea, etc.) also are commonly observed before the onset of syncope during this period. The majority of syncopal reactions (about 60%) occur after blood donation, either on-site or off-site, when donors are ambulating (usually in the upright posture).1, 3 Donors are in the hypovolemic state during this period. Circulating or intravascular blood volume has a profound effect on arterial pressure maintenance during orthostasis in humans.18, 19 Individuals with a reduced intravascular volume exhibit subnormal (decreased) cardiac filling pressure, stroke volume, and cardiac output, and their capacity to buffer orthostatic reductions in central blood volume is limited.18 Under such conditions, if neural (through sympathetic adrenergic vasoconstriction) and/or renal-adrenal (through salt and water retention, volume expansion, and angiotensin II-mediated vasoconstriction) reflex responses to orthostasis are inadequate or inappropriate, then syncope ensues.20 Syncope during this period may not be so much neurally mediated but, rather, is driven primarily by orthostatic central hypovolemia. Indeed, syncope or orthostatic intolerance is more common in astronauts returning to Earth after spaceflight,21, 22 in healthy people after a period of head-down bed rest (i.e., simulated microgravity exposure),23 after acute dehydration24 or in the heat (reversed with volume expansion via dextran infusion),25 and in patients who have the postural orthostatic tachycardia syndrome (also called chronic orthostatic intolerance, in which patients are unable to stand or remain upright for prolonged periods of time because of intolerable palpitations, light-headedness, weakness, and near-fainting),26 when circulating blood volume is reduced and orthostatic central hypovolemia becomes more apparent. Clarifying the pathophysiology of syncope during and after blood donation should guide the best or most appropriate intervention strategies to effectively prevent adverse reactions. As mentioned above, syncope in the process of blood collection appears to be attributed primarily to sympathetic inhibition elicited by fearful stimuli, whereas blood volume reduction is minimally important. Therefore, the light muscle-tensing exercise implemented by Morand and colleagues3 has little possibility to substantially alter central blood volume and is more likely to act as a distraction to fear. Indeed, among people who are afraid of needles and blood draws, learning a muscle-tensing exercise has been found to help reduce syncopal symptoms during blood collection and increase the rate of subsequent donations,27 partly through reducing anxiety.28 Perhaps by superimposing the exercise pressor reflex,29 which causes sympathetic activation and vagal withdrawal, such an intervention would be expected to oppose a neurally mediated reflex syncope. It is highly likely that an even simpler type of exercise, such as squeezing a rubber ball using either static or rhythmic contraction, would be equally or perhaps more effective for this purpose. The authors acknowledge this concept indirectly by referring to the Dutch leg-crossing maneuver (crossing one foot in front of the other and squeezing the thighs and gluteal muscles together),30, 31 which is very potent at restoring venous return in the upright position. So the most effective strategy would be static handgrip (using a rubber ball) during the donation, and then teaching the donors to employ the leg-crossing maneuver,30, 31 or even “cough cardiopulmonary resuscitation”32, 33 if they get dizzy in the 48 hours after donation, when orthostatic pooling of blood below the heart becomes the dominant pathophysiology. In terms of the drinking component, for healthy people, drinking water has no significant impact on arterial pressure34; thus, the benefit of drinking before the donation would be minimal. Trying to hydrate an individual who is effectively euhydrated is relatively ineffective (there is a whole literature on the efforts to induce “hyperhydration” in euhydrated individuals, generally athletes35). The time to drink should be after the donation has started or even after it has finished, when volume-regulatory mechanisms are upregulated and primed to retain the fluid.36 Certainly there is also an extensive literature on rehydration solutions, which should contain glucose as well as salt to take advantage of the glucose-sodium transporter (which is why it is so effective and life-saving in diarrheal syndromes like cholera). So, just putting some salt in a bottle of mineral water should not be expected to have much of an effect and is not likely to be optimal. Glucose/salt rehydration solution taken during or soon after donation, plus “salty snacks” eaten in the immediate donation period would be the best way to combat the late pathophysiology, which is not so much neurally mediated as primarily driven by orthostatic central hypovolemia. Figure 1 depicts the proposed pathophysiology-based, period-specific interventions to prevent syncopal reactions in blood donors. Certainly the effectiveness of these strategies needs to be verified in large, randomized clinical trials in the future. Morand and colleagues deserve congratulations for testing a specific intervention to reduce syncope from blood donation. We look forward to refinement of their approach, which we suspect will even further reduce the frequency of such reactions and improve the safety of blood donation. Proposed pathophysiology-based, period-specific interventions to prevent syncopal reactions in blood donors. CPR = cardiopulmonary resuscitation; LOC = loss of consciousness. The authors have disclosed no conflicts of interest. Qi Fu, MD, PhDBenjamin D. Levine, MD e-mail: BenjaminLevine@TexasHealth.