<span class="paragraphSection"><div class="boxTitle">Abstract</div><strong>Background.</strong> Experimental studies suggest that mechanical cell washing to remove pro-inflammatory components that accumulate in the supernatant of stored donor red blood cells (RBCs) might reduce inflammation and organ injury in transfused patients.<strong>Methods.</strong> Cardiac surgery patients at increased risk of large-volume RBC transfusion were eligible. Participants were randomized to receive either mechanically washed allogenic RBCs or standard care RBCs. The primary outcome was serum interleukin-8 measured at baseline and at four postsurgery time points. A mechanism substudy evaluated the effects of washing on stored RBCs <span style="font-style:italic;">in vitro</span> and on markers of platelet, leucocyte, and endothelial activation in trial subjects.<strong>Results.</strong> Sixty adult cardiac surgery patients at three UK cardiac centres were enrolled between September 2013 and March 2015. Subjects received a median of 3.5 (interquartile range 2–5.5) RBC units, stored for a mean of 21 (<span style="text-transform:lowercase;font-variant:small-caps;">sd</span> 5.2) days, within 48 h of surgery. Mechanical washing reduced concentrations of RBC-derived microvesicles but increased cell-free haemoglobin concentrations in RBC supernatant relative to standard care RBC supernatant. There was no difference between groups with respect to perioperative serum interleukin-8 values [adjusted mean difference 0.239 (95% confidence intervals −0.231, 0.709), <span style="font-style:italic;">P</span>=0.318] or concentrations of plasma RBC microvesicles, platelet and leucocyte activation, plasma cell-free haemoglobin, endothelial activation, or biomarkers of heart, lung, or kidney injury.<strong>Conclusions.</strong> These results do not support a hypothesis that allogenic red blood cell washing has clinical benefits in cardiac surgery.<strong>Clinical trial registration.</strong> ISRCTN 27076315.</span>
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