Wilkinson Kirstin L, Kimber Catherine, Allana Alisha, Dorée Carolyn, Champaneria Rita, Brunskill Susan J, Murphy Michael F
Department of Paediatric and Adult Cardiothoracic Anaesthesia, Southampton University NHS Hospital, Southampton, UK.
Systematic Review Initiative, NHS Blood and Transplant, Oxford, UK.
Cochrane Database Syst Rev. 2025 Mar 19;3(3):CD009752. doi: 10.1002/14651858.CD009752.pub3.
Congenital heart disease is the most common neonatal congenital condition. Surgery is often necessary. Patients with congenital heart disease are potentially exposed to red cell transfusion preoperatively, intraoperatively and postoperatively when admitted for cardiac surgery. There are a number of risks associated with red cell transfusion that may increase morbidity and mortality.
To evaluate the association of red blood cell transfusion management with mortality and morbidity in people with congenital heart disease who are undergoing cardiac surgery.
We searched multiple bibliographic databases and trials registries, including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCOhost), Transfusion Evidence Library, ClinicalTrials.gov and the World Health Organization (WHO) ICTRP. The most recent search was on 2 January 2024, with no limitation by language of publication.
We included randomised controlled trials (RCTs) comparing red blood cell transfusion interventions in patients undergoing cardiac surgery for congenital heart disease. Participants of any age (neonates, paediatrics and adults) and with any type of congenital heart disease (cyanotic or acyanotic) were eligible for inclusion. No comorbidities were excluded.
Two of five (AA, CK, KW, SB, SF) review authors independently extracted data and assessed the risk of bias in the trials. We contacted study authors for additional information. Two review authors (CK, KW) used GRADE methodology to assess evidence certainty for critical outcomes and comparisons.
We identified 19 relevant trials. The trials had 1606 participants, all of whom were neonates or children. No trials were conducted in the preoperative period or with adults. The trials compared different types of red blood cell transfusions. No trial compared red blood cell transfusion versus no red blood cell transfusion. None of the trials was at low risk of bias overall. Eight trials had a high risk of bias in at least one domain, most commonly, blinding of participants and personnel. For our critical outcomes, we judged the certainty of the evidence based on GRADE criteria to be low or very low. Five trials (497 participants) compared a restrictive versus a liberal transfusion-trigger. It is very uncertain whether a restrictive transfusion-trigger has an effect on all-cause mortality in the short-term (0 to 30 days post-surgery) (risk ratio (RR) 1.12, 95% confidence interval (CI) 0.42 to 3.00; 3 RCTs, 347 participants; very low certainty evidence) or long term (31 days to two years post-surgery) (RR 0.33, 95% CI 0.01 to 7.87; 1 RCT, 60 participants; very low certainty evidence). The evidence is also very uncertain on the incidence of severe adverse cardiac events (RR 1.00, 95% CI 0.73 to 1.37; 2 RCTs, 232 participants) and infection (RR 0.81, 95% CI 0.47 to 1.39; 2 RCTs, 232 participants) (both very low certainty evidence). A restrictive transfusion-trigger may have little to no effect on the duration of mechanical ventilation (mean difference (MD) -1.65, 95% CI -3.51 to 0.2; 2 RCTs, 168 participants; low-certainty evidence) or of ICU stay (MD 0.15, 95% CI -0.72 to 1.01; 3 RCTs, 228 participants, low-certainty evidence). Five trials (231 participants) compared washed red blood cells in CPB prime versus unwashed red blood cells in CPB prime. Washing red blood cells in CPB prime may have little to no effect on all-cause mortality in the short term (0 to 30 days post-surgery) (RR 0.25, 95% CI 0.03 to 2.18; 2 RCTs, 144 participants) or long term (31 days to 2 years post-surgery) (RR 0.50, 95% CI 0.05 to 5.38; 1 RCT, 128 participants) (both low-certainty evidence). The evidence is very uncertain about the effect of washed CPB prime on severe cardiac adverse events (RR 0.88, 95% CI 0.47 to 1.64), infection (RR 1.00, 95% CI 0.50 to 1.99) and duration of ICU stay (MD -0.3, 95% CI -4.32 to 3.72) (1 RCT, 128 participants; very low certainty evidence). Two trials (76 participants) compared crystalloid (bloodless) CPB prime versus red-blood-cell-containing CPB prime. It is very uncertain whether bloodless prime has an effect on the duration of mechanical ventilation (median 8.0 hours, interquartile range (IQR) 6.8 to 9.0 hours versus median 7.0 hours, IQR 6.0 to 8.0 hours; 1 RCT, 40 participants) or duration of ICU stay (median 23.0 hours, IQR 21.8 to 41.5 hours versus median 23.5 hours, IQR 21.0 to 29.0 hours; 1 RCT, 40 participants) (both very low certainty evidence). Two trials (160 participants) compared ultrafiltration of CPB prime versus no ultrafiltration. It is very uncertain whether ultrafiltration of CPB prime has an effect on all-cause mortality in the short term (0 to 30 days post-surgery) (RR not estimable; 1 RCT, 50 participants; very low certainty evidence). Ultrafiltration may reduce the duration of mechanical ventilation (MD -16.00, 95% CI -25.00 to -7.00) and the duration of ICU stay (MD -0.6, 95% CI -0.84 to -0.36) (1 RCT, 50 participants; low-certainty evidence). One trial (59 participants) compared retrograde autologous CPB prime versus standard CPB prime. It is very uncertain whether retrograde autologous CPB prime has an effect on the duration of mechanical ventilation (MD 0.02, 95% CI -0.03 to 0.07) or duration of ICU stay (MD 0, 95% CI -0.01 to 0.01) (1 RCT, 59 participants; very low certainty evidence). One trial (178 participants) compared 'fresh' (not near expiry date) versus 'old' (near expiry date) red blood cell transfusion but did not report on our outcomes.
AUTHORS' CONCLUSIONS: No randomised controlled trial compared red blood cell transfusion against no red blood cell transfusion in people with congential heart disease undergoing cardiac surgery. There are only small, heterogeneous trials in children that compare different forms of red blood cell transfusion, and there are no trials at all in adults. There is therefore insufficient evidence to accurately assess the association of red blood cell transfusion with the morbidity and mortality of patients with congenital heart disease undergoing cardiac surgery. It is possible that trial outcomes are affected by the presence or absence of cyanosis, so this should be considered in future trial design. Further adequately powered, high-quality trials in both children and adults are required.
先天性心脏病是最常见的新生儿先天性疾病。通常需要进行手术。先天性心脏病患者在接受心脏手术时，术前、术中和术后都可能接受红细胞输血。红细胞输血存在多种风险，可能会增加发病率和死亡率。
评估红细胞输血管理与接受心脏手术的先天性心脏病患者的死亡率和发病率之间的关联。
我们检索了多个文献数据库和试验注册库，包括Cochrane对照试验中心注册库（CENTRAL）、MEDLINE（Ovid）、Embase（Ovid）、护理学与健康领域数据库（CINAHL，EBSCOhost）、输血证据库、ClinicalTrials.gov和世界卫生组织（WHO）国际临床试验注册平台（ICTRP）。最近一次检索是在2024年1月2日，不受出版物语言限制。
我们纳入了比较先天性心脏病心脏手术患者红细胞输血干预措施的随机对照试验（RCT）。任何年龄（新生儿、儿童和成人）以及任何类型先天性心脏病（青紫型或非青紫型）的参与者均符合纳入标准。不排除合并症。
五名综述作者中的两名（AA、CK、KW、SB、SF）独立提取数据并评估试验中的偏倚风险。我们与研究作者联系以获取更多信息。两名综述作者（CK、KW）使用GRADE方法评估关键结局和比较的证据确定性。
我们确定了19项相关试验。这些试验共有1606名参与者，均为新生儿或儿童。没有在术前阶段或针对成人进行的试验。试验比较了不同类型的红细胞输血。没有试验比较红细胞输血与不输血。总体而言，没有一项试验的偏倚风险较低。八项试验在至少一个领域存在高偏倚风险，最常见的是参与者和工作人员的盲法。对于我们的关键结局，根据GRADE标准，我们判断证据的确定性为低或非常低。五项试验（497名参与者）比较了限制性输血触发与宽松性输血触发。非常不确定限制性输血触发在短期（术后0至30天）对全因死亡率是否有影响（风险比（RR）1.12，95%置信区间（CI）0.42至3.00；3项RCT，347名参与者；非常低确定性证据）或长期（术后31天至两年）（RR 0.33，95%CI 0.01至7.87；1项RCT，60名参与者；非常低确定性证据）。关于严重心脏不良事件的发生率（RR 1.00，95%CI 0.73至1.37；2项RCT，232名参与者）和感染（RR 0.81，95%CI 0.47至1.39；2项RCT，232名参与者）的证据也非常不确定（两者均为非常低确定性证据）。限制性输血触发可能对机械通气时间（平均差（MD）-1.65，95%CI -3.51至0.2；2项RCT，168名参与者；低确定性证据）或重症监护病房（ICU）住院时间（MD 0.15，95%CI -0.72至1.01；3项RCT，228名参与者，低确定性证据）影响很小或没有影响。五项试验（231名参与者）比较了体外循环预充液中洗涤红细胞与未洗涤红细胞。体外循环预充液中洗涤红细胞在短期（术后0至30天）对全因死亡率可能影响很小或没有影响（RR 0.25，95%CI 0.03至2.18；2项RCT，144名参与者）或长期（术后31天至2年）（RR 0.50，95%CI 0.05至5.38；1项RCT，128名参与者）（两者均为低确定性证据）。关于洗涤后的体外循环预充液对严重心脏不良事件（RR 0.88，95%CI 0.47至1.
