During our randomized controlled study, we did not find a statistically significant difference in the number of syncope or pre-syncope events between the water and control arms of our study. The statistical power of the study to detect minor effects of water was limited due to a lower than anticipated syncope/pre-syncope incidence of 1.7% among adolescent donors in the Eastern Cape in South Africa, which is lower than reported in other adolescent donor populations. Furthermore, we noted a 7-fold lower risk of syncope and pre-syncope among our black adolescent donors as compared to the white adolescent donors. These data led us to conclude that there would be little operational or clinical benefit in introducing water preloading for adolescent donors in the South African setting.
Newman et al demonstrated in 2007 that preloading young donors with 473ml of water reduced syncope and pre-syncope reactions by 21%. Subsequently, a study in Japan showed that preloading at risk donors with a drink, may reduce the number of syncope/pre-syncope events in that group.17
Tomasulo et al also indicated that introducing water preloading in combination with other interventions, may reduce syncope/pre-syncope.16
More recently a small study in Ohio, USA, showed that consumption of 500ml water may reduce syncope and pre-syncope15
It is not certain why our study showed different results. First, our study was not powered to detect a 20% reduction, so we might have missed a small effect of water loading. Second, the lower than anticipated overall number of syncope and pre-syncope events we observed suggest population differences in susceptibility to syncope, perhaps explained by the relatively large number of black donors in our sample. Having fewer “at risk” donors, would not only reduce the number of events, but possibly diminish the effect of interventions aimed at reducing the risk.
The significantly lower than expected overall syncope and pre-syncope events among our scholars was surprising when compared to that noted in other studies18
, and the generally higher incidence of complications and deferrals in younger compared to older donors.8–10,18–19
In 2006, Eder et al8
, found that 10.7% of American Red Cross donors aged 16 to 17-years, and 8.3% of those aged 18 to 19 years experienced adverse events compared to 2.8% of those aged 20 and older. In a study of faint and prefaint reactions at 16 United Blood Services Centers, donors 17 to 18 years old had a reaction rate of 39.6/1,000 donation and an adjusted odds ratio of 2.75 for faint and prefaint reactions as compared to their 25 to 65 year old counterparts. Analysis of our unadjusted data demonstrated an almost linear reduction in syncope and pre-syncope with increasing age, but this effect was blunted after adjusting for gender, race and donation history.
It has been shown that donors who suffer adverse events have significantly lower return rates,12,13
with syncope and pre-syncope type symptoms having the biggest negative effect.12
In fact, those who do suffer adverse events may not donate again for as long as 5–6 years.20
Conversely, those who return soon after their first donation, were more likely to become habitual donors.21
Furthermore, very young donors have been shown to have higher return rates as long as their first donation experience was adverse event free.22
Finding interventions to minimize syncope and pre-syncope events is of great importance, but unfortunately, we confirmed that giving South African adolescent donors water to drink just prior to donating, will not reduce the number of vasovagal events in any meaningful manner. On the positive side, our lower than anticipated syncope/pre-syncope incidence suggests that this reaction should have less overall impact on donor return.
The relatively high proportion of Black (25%) and Coloured (15%) donors among our study group allowed for further interpretation of the syncope and pre-syncope events among the various race groups in the Eastern Cape. The black donors had 5 to 7 times fewer syncope and pre-syncope events than the white donors. The New York Blood Center reviewed the syncope and pre-syncope reactions among first time teenaged donors and found an overall syncope/pre-syncope reaction rate of 8.2% but a 1.3% rate among African-American high school students.18
Wiltbank et al demonstrated similar findings11
. Additionally, we demonstrated that the odds of syncope/pre-syncope events among coloured donors were intermediate between those of blacks and whites. Even though this was not statistically significant, it is in keeping with the theory that there is a genetic factor that offers donors of African origin protection against syncope and pre-syncope. Recently, Hinds et al, showed greater orthostatic tolerance among young black versus white females and noted greater sympathetic response to orthostatic challenges in the former group23
. This echoes work done by others24–26
and is in keeping with unpublished observations from other African blood transfusion services of very low syncope and pre-syncope events among African donors (personal communication, Dr P. Knox, 2011).
Similar to other studies, we noted that the female adolescent donors had a two-fold higher number of syncope and pre-syncope events compared to the males9,11,18
. However, the absolute incidence of events among the females was lower in our trial than other published studies. Others have noted that this higher faint rate is likely, at least in part, to be related to the proportionally smaller blood volume in female donors. Unfortunately, body weight was not recorded during this study.
Our study had several strengths. Study participants were blinded as they were not aware of the purpose of the intervention. Additionally, the intervention was well defined and delivered under controlled circumstances, with the students receiving the water at the time of being registered. The lag time between being registered and starting the donation process would range between 10 and 30 minutes. Seasonal effects were minimized by completing the entire study within one month. The outcome was also well-defined, well-known event with which the observers are familiar. As a result, we are of the opinion that the effects of observer bias and placebo effect were kept to the minimum.
Our study had some limitations. Initially, we used the syncope/pre-syncope event rate reported in the Wiltbank11
study to calculate our sample size, but with our rate being significantly lower, our study may not have been powered to detect minor differences in syncope and pre-syncope rates between the two arms. We calculate that with the available sample size, our study would have been sufficiently powered to detect only a 69% relative or 1.1% absolute decrease (i.e. 0.5% in the water arm and 1.6% in the control arm). For our study to have been robustly powered at 80 percent, we would have required a sample size of 2907 donors per arm to detect a 50% reduction (0.8% decrease), or 21,760 donors per arm to detect a 20% reduction (0.32% decrease). Although a study of 6000 might be feasible in the future, it is unlikely that a study of 43,000 high school donors will ever be accomplished.
As it was not possible to randomize the participants by individual, we had to apply randomisation by school and the “no water” arm ended with more male and black donors compared to the “water” arm. We attempted to correct for this imbalance by using multivariable logistic regression, but residual confounding could have affected our results. Finally, there may have been under-reporting of minor pre-syncope events but presumably this would have been similar in both arms of the study.
In conclusion, although we showed no benefit of pre-donation water administration in preventing syncope and pre-syncope symptoms, we were able to establish the incidence of syncope/pre-syncope rates for adolescent donors in the Eastern Cape, as well as variation by age, race and gender. We showed similar variation in syncope/pre-syncopel reactions within these subgroups as reported by other authors, but the overall incidence of reactions was much lower than in the USA. Thus, population differences in reaction rates illustrate the need for international blood services to conduct local research before implementing changes based upon findings from other countries. Finally, the experience gained with this study has resulted in improved processes for reporting and recording donor adverse events within the South African National Blood Service, paving the way for more detailed analysis of donor reactions within South Africa.