The dose-effect relationship between red blood cell transfusion volume and adverse events in pediatric cardiac surgery.

Background: Pediatric cardiac surgery requiring cardiopulmonary bypass (CPB) is associated with high transfusion rates. While transfusions increase risks of adverse events, existing evidence cannot differentiate whether risks arise from transfusion itself or cumulative volumes. This study aims to explore the relationship between intra-operative transfusion volume and adverse outcomes, exploring whether transfusion volume has a linear or threshold effect on adverse outcomes. Methods: This retrospective cohort study included pediatric patients (≤14 years old) undergoing cardiac surgery with CPB, categorized by intra-operative red blood cell (RBC) volume transfused: 0, 0.1-22.2 mL/kg, 22.3-27.0 mL/kg, 27.1-34.5 mL/kg and >34.5 mL/kg. Outcomes included prolonged mechanical ventilation (MV), acute kidney injury (AKI), severe AKI and composite complications (chest drainage >10 mL/kg/d, culture-confirmed pulmonary infection, extracorporeal membrane oxygenation (ECMO) implantation, and in-hospital mortality). Multivariable logistic regression was used to analyze the relationship between intra-operative RBC transfusion volume and outcomes. Results: A total of 19,081 children were included, of whom 44.5% received RBC transfusion during surgery. Among these, 10.7% received 0.1-22.2 mL/kg, 11.3% received 22.3-27.0 mL/kg, 11.3% received 27.1-34.5 mL/kg and 11.0% received >34.5 mL/kg RBC transfusion. Higher RBC transfusion volumes correlated with certain adverse events. However, after adjustment for potential confounders, no consistent linear dose-effect relationship was observed. Instead, a threshold-effect association was identified. Compared with no transfusion, RBC transfusion >34.5 mL/kg was associated with increased risks of prolonged MV [odds ratio (OR): 3.45, 95% confidence interval (CI): 2.78-4.28; P<0.001], AKI (OR: 1.21, 95% CI: 1.01-1.44; P=0.04), and composite complications (OR: 2.30, 95% CI: 1.54-3.43; P<0.001), whereas low-volume transfusion was inversely associated with composite complications (0.1-22.2 mL/kg: OR, 0.36; 95% CI: 0.17-0.76; P=0.007), prolonged MV (0.1-22.2 mL/kg: OR, 0.55; 95% CI: 0.40-0.77; P=0.001; 22.3-27.0 mL/kg: OR, 0.64; 95% CI: 0.48-0.85; P=0.002), and AKI (0.1-22.2 mL/kg: OR, 0.81; 95% CI: 0.68-0.95; P=0.01). Conclusions: In this large cohort of pediatric patients undergoing surgery for congenital heart disease (CHD), there was a threshold effect between intraoperative RBC transfusion volume and adverse outcomes. Besides, low-volume transfusion was inversely associated with these outcomes. These findings highlight the importance of evaluating RBC transfusion using weight-adjusted volume and suggest that an optimal transfusion range may exist in pediatric cardiac surgery.