Washing red blood cells and platelets transfused in cardiac surgery reduces postoperative inflammation and number of transfusions: results of a prospective, randomized, controlled clinical trial

Abstract

Objectives: Children undergoing cardiac surgery with cardiopulmonary bypass are susceptible to additional inflammatory and immunogenic insults from blood transfusions. We hypothesize that washing red blood cells and platelets transfused to these patients will reduce postoperative transfusion-related immune modulation and inflammation.

Design: Prospective, randomized, controlled clinical trial.

Setting: University hospital pediatric cardiac intensive care unit.

Patients: Children from birth to 17 yrs undergoing cardiac surgery with cardiopulmonary bypass.

Interventions: Children were randomized to an unwashed or washed red blood cells and platelet transfusion protocol for their surgery and postoperative care. All blood was leuko-reduced, irradiated, and ABO identical. Plasma was obtained for laboratory analysis preoperatively, immediately, and 6 and 12 hrs after cardiopulmonary bypass. Primary outcome was the 12-hr postcardiopulmonary bypass interleukin-6-to-interleukin-10 ratio. Secondary measures were interleukin levels, C-reactive protein, and clinical outcomes.

Measurements and main results: One hundred sixty-two subjects were studied, 81 per group. Thirty-four subjects (17 per group) did not receive any blood transfusions. Storage duration of blood products was similar between groups. Among transfused subjects, the 12-hr interleukin ratio was significantly lower in the washed group (3.8 vs. 4.8; p = .04) secondary to lower interleukin-6 levels (after cardiopulmonary bypass: 65 vs.100 pg/mL, p = .06; 6 hrs: 89 vs.152 pg/mL, p = .02; 12 hrs: 84 vs.122 pg/mL, p = .09). Postoperative C-reactive protein was lower in subjects receiving washed blood (38 vs. 43 mg/L; p = .03). There was a numerical, but not statistically significant, decrease in total blood product transfusions (203 vs. 260) and mortality (2 vs. 6 deaths) in the washed group compared to the unwashed group.

Conclusions: Washed blood transfusions in cardiac surgery reduced inflammatory biomarkers, number of transfusions, donor exposures, and were associated with a nonsignificant trend toward reduced mortality. A larger study powered to test for clinical outcomes is needed to determine whether these laboratory findings are clinically significant.

Trial registration: ClinicalTrials.gov NCT00693498.

CONSORT Flow Diagram

Figure 1

Between group comparison of IL-6:IL-10 ratio in transfused subjects. Shown are box plots for the median (middle of the box) and 75^th percentile (upper edge of each box) of each distribution, with outliers beyond the 95^% confidence intervals shown as individual points. The lower end of the box (the 25^th percentile) often falls below zero, and thus is not visible in some cases. For the pre-op and post-op values, the median is zero and is superimposed on the x axis and thus no box is shown. P values are shown for individual comparison of the distributions for the washed and unwashed transfusion recipients. Only at 12 hours post-op is there a striking difference between the washed and unwashed arms, with many more high outliers in the unwashed group.

Figure 2

Between group comparison of IL-6 levels in transfused subjects. Shown are box plots for the median (middle of the box) and 75^th percentile (upper edge of each box) of each distribution, with outliers beyond the 95^% confidence intervals shown as individual points. For the pre-op values, the median is zero and superimposed on the x axis and thus no box is shown. The lower end of the box (the 25^th percentile) often falls below zero, and thus is not visible in some cases. P values are shown for individual comparison of the distributions for the washed and unwashed transfusion recipients. Only at 6 hours post-op is there a striking difference between the washed and unwashed arms, with many more high outliers and a higher median level in the unwashed group.

Figure 3

Between group comparison of C-reactive protein in transfused subjects. Shown are box plots for the median (middle of the box) and 75^th percentile (upper edge of each box) of each distribution, with outliers beyond the 95^% confidence intervals shown as individual points. The lower end of the box (the 25^th percentile) often falls below zero, and thus is not visible in some cases. For the pre-op values, the median is zero and is superimposed on the x axis and thus no box is shown. P values are shown for individual comparison of the distributions for the washed and unwashed transfusion recipients. Only on day 1 post-op is there a striking difference between the washed and unwashed arms, with many more high outliers in the unwashed group.

Figure 4

Association of IL-6 and survival in transfused subjects. Bar charts displaying the mean and 95% upper confidence interval for each group are shown. Patients in the unwashed group had higher mean levels of IL-6 at 6 hours as shown in Figure 2, this difference being primarily due to the very high 6 hour IL-6 levels in the six patients in the unwashed arm that died.