Objective Children undergoing cardiac surgery with cardiopulmonary bypass (CPB) are susceptible to additional inflammatory and immunogenic insults from blood transfusions. We hypothesize that washing red blood cells (RBC) and platelets transfused to these patients will reduce post-operative 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 years old undergoing cardiac surgery with CPB. Interventions Children were randomized to an unwashed or washed RBC and platelet transfusion protocol for their surgery and postoperative care. All blood was leukoreduced, irradiated, and ABO identical. Plasma was obtained for laboratory analysis: pre-op, immediately, six and 12 hours after CPB. Primary outcome was the 12-hour post-CPB interleukin (IL)-6: IL-10 ratio. Secondary measures were IL levels, C-reactive protein (CRP), and clinical outcomes. Measurements and main results 162 subjects were studied, 81 per group. 34 subjects (17 per group) did not receive any blood transfusions. Storage duration of blood products was similar between groups. Among transfused subjects, the 12-hour IL ratio was significantly lower in the washed group (3.8 v. 4.8; p=0.04) secondary to lower IL-6 levels (post-CPB: 65 v.100 pg/ml; p = 0.06; 6 hour: 89 v.152 pg/ml; p = 0.02; 12-hour: 84 v.122 pg/ml; p = 0.09). Post-operative CRP was lower in subjects receiving washed blood (38 v. 43 mg/L; p = 0.03). There was a numerical, but not statistically significant decrease in total blood product transfusions (203 v. 260) and mortality (2 v. 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 non-significant trend towards reduced mortality. A larger study powered to test for clinical outcomes is needed to determine whether these laboratory findings are clinically significant.
Background Infants and children undergoing open heart surgery routinely require multiple red blood cell (RBC) transfusions. Children receiving greater numbers of RBC transfusions have increased post-operative complications and mortality. Longer RBC storage age is also associated with increased morbidity and mortality in critically ill children. Whether the association of increased transfusions and worse outcomes can be ameliorated by use of fresh RBCs in pediatric cardiac surgery for congenital heart disease is unknown. Methods 128 consecutively transfused children undergoing repair or palliation of congenital heart disease with cardiopulmonary bypass who were participating in a randomized trial of washed v. standard RBC transfusions were evaluated for an association of RBC storage age and clinical outcomes. To avoid confounding with dose of transfusions and timing of infection versus timing of transfusion, a subgroup analysis of patients only transfused 1–2 units on the day of surgery was performed. Results Mortality was low (4.9%) with no association between RBC storage duration and survival. The post-operative infection rate was significantly higher in children receiving the oldest blood (25–38 days) compared to those receiving the freshest RBCs (7–15 days); (34% v. 7%; p = 0.004). Subgroup analysis of subjects receiving only 1–2 RBC transfusions on the day of surgery (n=74) also demonstrates a greater incidence of infections in subjects receiving the oldest RBC units [0 of 33 (0%) with 7–15 day storage, 1 of 21 (5%) with 16–24 day storage and 4 of 20 (20%) with 25–38 day storage; (p=0.01)]. In multivariate analysis, RBC storage age and corticosteroid administration were the only predictors of post-operative infection. Washing the oldest RBCs (>27 days) was associated with a higher infection rate and increased morbidity compared with unwashed RBCs. Discussion Longer RBC storage duration was associated with increased postoperative nosocomial infections. This association may be secondary in part, to the large doses of stored RBCs transfused, from single donor units. Washing the oldest RBCs was associated with increased morbidity, possibly from increased destruction of older, more fragile erythrocytes incurred by washing procedures. Additional studies examining the effect of RBC storage age on post-operative infection rate in pediatric cardiac surgery are warranted.
We examined the efficacy of epidural butorphanol to either prevent or relieve pruritus associated with epidural morphine infusion in children. Forty-six children were randomized to receive either epidural morphine (M) or epidural M with butorphanol (B) for postoperative analgesia. They received bupivacaine and either M 50 microg.kg-1 or the same dose of M plus B 10 microg.kg-1. Following surgery, a continuous infusion of 0.1% bupivacaine with either M 20 microg.ml-1 or M 20 microg.ml-1 + B 4 microg.ml-1 was given at a rate of 0.3 ml.kg-1.h-1. Pain scores and pruritus scores were recorded every 4 h during epidural infusion. Subjects with a pruritus score=2 received diphenhydramine 0.5 mg.kg-1 i.v. and were switched to an alternate epidural infusion; subjects receiving M (group M) were switched to M+B while subjects receiving M+B (group B) were switched to hydromorphone (H) 4 microg.ml-1. There was no difference in the initial incidence of pruritus (group M 11/18; group B 13/28). No subject in group M required a second change of epidural infusion because of continued pruritus after being switched to M+B; five of 13 subjects in group B continued to experience pruritus after being switched to H and required a second change of epidural infusion or an alternate analgesic modality (P=0.038). The median pruritus score in the first 24 h after changing epidural infusions was 0 in subjects in group MDelta (changed from M to M+B) and 1 in subjects in group BDelta (changed from M+B to H; P=0.012). While the median sedation score in the first 24 h was 1 in both groups, there was a greater incidence of sedation scores of 2 in group B than group M (28% vs 12.3%; P=0.021). B 10 microg.kg-1 was not effective in preventing pruritus associated with bolus epidural administration of M 50 microg.kg-1 in children. B 1.2 microg.kg-1. h-1 was effective in relieving pruritus associated with continuous epidural infusion of M 6 microg.kg-1.h-1.
The duration of cortical isoelectric states seems related to neurodevelopmental outcomes. Strategies using continuous EEG monitoring to minimize isoelectric states may be useful during complex congenital heart surgery.
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