Key message
We found 19 studies that compared different ways of doing red blood cell transfusion in newborns and children requiring heart surgery for congenital heart disease (heart problems they were born with). However, we are unable to reach any reliable conclusions based on this evidence. More studies are required.
What is congenital heart disease?
Congenital heart disease is any problem with the heart's development that a person is born with. It means the heart has not formed properly. It affects between four and nine children out of every 1000 live births. In most cases, surgery is needed to allow a child to live and grow healthily. Adults often need surgery for congenital heart conditions.
Why is it important to manage blood transfusions during cardiac surgery?
Patients often need transfusions of red blood cells either before, during or after heart surgery. Most patients will have the surgery using a cardiopulmonary bypass (CPB) machine, which acts as their heart and lungs during the operation. More patients survive heart surgery now than in the past, and the aim is to make surgery even safer. Some research suggests that red blood cell transfusions may make people more ill. If so, it would be better to avoid unnecessary transfusions.
What did we want to find out?
We wanted to find out how the management of red blood cell transfusions affects patient outcomes after heart surgery. Do red blood cell transfusions have an impact on short-term and longer-term survival, serious side effects (e.g. stroke, kidney failure, infection, clots, bleeding) and the length of time patients stay in the intensive care unit and in hospital after their operation?
What did we do?
We searched medical databases for relevant studies. We looked for the most reliable type of studies, which are known as randomised controlled trials ('trials'). We compared and summarised the results of the trials and rated our confidence in the evidence, based on factors like their methods and the number of people involved.
What did we find?
We found 19 trials involving 1606 children. There were no trials involving adults. The trials examined eight treatments. We selected six comparisons as the key results. These are listed below. In the full review, we also present results for two other comparisons, which tested treatments that are now in common use.
1. Five trials compared giving a red blood cell transfusion only when the levels of haemoglobin in the blood fall below a certain concentration (a 'restrictive' versus a 'liberal' transfusion trigger). It is unclear if using a restrictive transfusion trigger has an effect on how many children die, develop severe side effects or develop an infection.
2. Five trials compared washing or not washing the red blood cells added to the heart-lung machine. We do not know if washing the red blood cells has an effect on how many children die, develop severe side effects or infection, or how long children stay in the intensive care unit.
3. Two trials compared adding or omitting red cell transfusions into the fluid in the cardiopulmonary bypass machine. We do not know if not using blood in the heart-lung machine has any effect on how long children stay on a ventilator, or how long they stay in the intensive care unit.
4. Two trials compared filtering the blood going through the heart-lung bypass machine fluid to reduce high levels of minerals/salts and inflammation, which is sometimes a problem in transfused blood, versus not filtering it. It is unclear whether filtering the blood in the heart-lung bypass machine has any effect on how many children die. Filtering may slightly reduce the time children spend on a ventilator, and may slightly reduce how long they stay in the intensive care unit.
5. One trial looked at using the child's own blood in the heart-lung machine instead of a blood transfusion. The study did not give results on serious harmful events or how many children died. It is unclear if using the child's own blood in the heart-lung machine instead of a transfusion has any effect on the time children spend on a ventilator or the time they spend in the intensive care unit.
6. One trial compared using very new blood compared with older blood to try to reduce harmful effects of older blood. This trial did not test the aspects we were interested in.
What are the limitations of the evidence?
The trials were small and measured many different aspects of red blood cell transfusion management in different children having heart surgery, so it is difficult to draw accurate conclusions about the benefits or risks of red blood cell transfusion. More research is needed to allow accurate conclusions to be drawn.
How up-to-date is the evidence?
We found all the published studies on this topic up to 2 January 2024. We also found all the trials that are in progress or due to be started soon.
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.
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.