Background

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.

Objectives

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.

Search methods

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.

Selection criteria

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.

Data collection and analysis

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.

Main results

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.