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Specifically, the relative risk of being observed to experience a VVR in donors who water loaded was 0.79 (95% CI, 0.70-0.89). However, three of the five trials were assessed by Fisher and colleagues of having a high risk of selection bias due to the methods of randomisation employed. When these trials were removed from the metaanalysis, the effect of pre-donation water loading on VVRs was no longer significant, suggesting a negligible decrease in relative risk of observed VVRs among those who water loaded in comparison to those who did not. Where severity of reaction was assessed through ratings on the BDRI, pre-donation water loading significantly reduced the severity of vasovagal symptoms selfreported by donors in comparison to donors who had not water loaded (Hanson and France 2004; France et al. 2010). A recent study not included in the Fisher and colleagues (2016) meta-analysis reported significantly lower odds of a phlebotomist-registered VVRs among those who drank 500mL of fluid approximately 9 minutes before phlebotomy compared to those assigned to the ‘usual practice’ control arm (OR, 0.74; 95% CI, 0.55-0.99) (Morand et al. 2016). Drawing on research conducted in non-blood donation settings that found beneficial effects of dietary sodium in increasing plasma volume and orthostatic tolerance in dehydrated athletes (Wieling et al. 2011a), Morand and colleagues (2016) also evaluated the impact of consuming 500mL of an isotonic drink before phlebotomy. No differences were found in the rate of on-site reactions between those who This article is protected by copyright. All rights reserved. 12 consumed water and those who consumed the isotonic drink. However, follow up calls to donors revealed that consumption of the isotonic drink was related to significantly lower odds of reporting having experienced a reaction offsite in 48 hours post donation than those in the ‘usual practice’ control condition (OR, 0.62; 95% CI, 0.40-0.98). While such a reduction is highly desirable, particularly as offsite reactions can result in the most severe injuries to donors (Newman and Graves 2001), more research is needed to determine the efficacy of isotonic drinks in reducing offsite VVRs. Further, more research is needed to determine the optimal method (e.g., timing and volume of fluid to be consumed) and how effective water loading technique is in reducing phlebotomist-registered VVRs. In the same meta-analysis, Fisher and colleagues (2016) also considered the evidence for the efficacy of AMT, another physiological intervention. AMT involves donors engaging in repeated contraction of leg and abdomen muscles in order to increase blood pressure. Eight trials were considered which compared AMT to no-treatment control conditions. In these, no significant differences were observed in the relative risk of rate of chair reclines, heart rate, systolic blood pressure, diastolic blood pressure, and registered VVRs by phlebotomists between the AMT condition and the no-treatment control condition. AMT did, however, impact the severity of donor’s self-reported vasovagal symptoms. In three trials, reporting log-transformed BDRI scores, donors who used AMT reported significantly lower severity scores compared to those who did not (Ditto et al. 2003a; Ditto and France 2006a; Ditto et al. 2007). However, significant variability in the instructions used to prompt AMT was observed between the studies. For example, in one This article is protected by copyright. All rights reserved. 13 study, participants were instructed to lift one leg at a time for 10 seconds (France et al. 2010) whilst in another, participants were asked to engage in repeated, 5-second cycles of tensing the major muscle groups in their arms and legs (Ditto et al. 2003b; Ditto et al. 2007). Two trials evaluating the impact of combining both AMT and pre-donation water loading reported a significantly lower relative risk of phlebotomist-registered VVRs and lower donor self-reported symptom severity in donors who received the combined intervention compared to the no treatment control group (France et al. 2010; Morand et al. 2016). However, again, the precise instructions given to donors to prompt AMT differed greatly between the two studies making comparison of the trials difficult. The absence of a standardised AMT instruction in the blood donation context coupled with the variability observed in outcomes of trials of this technique suggests a need for further research to determine the effectiveness of AMT as an intervention. Further, research is also required to determine the efficacy of AMT in conjunction with predonation water loading. Along with pre-donation water loading and AMT, the efficacy of another physiological intervention to increase donor blood pressure – the consumption of caffeine – has been evaluated. In a small randomised trial with high risk donors (62 young females with a sensitivity to blood or injury stimuli), 125 or 250 mg of caffeine administered prior to blood donation resulted in significantly lower number of chair reclines, reduced self-reported VVR symptoms, and greater increases in blood pressure in comparison to those in a no caffeine placebo control group (Sauer and France 1999). No significant differences were observed between the three groups in reduction of preThis article is protected by copyright. All rights reserved. 14

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