Pre-operative anaemia, red blood cell transfusion and mortality after cardiac surgery: a Netherlands Heart Registration mediation analysis

Introduction: Pre-operative anaemia is an established risk factor for mortality after cardiac surgery. The extent to which this risk is mediated by complications related to red blood cell transfusion remains uncertain, particularly across different age groups. Methods: This nationwide cohort study included adult cardiac surgery patients from the Netherlands Heart Registration. Pre-operative anaemia was defined according to World Health Organization criteria and red blood cell transfusion as any red blood cell transfusion during hospital stay. The main study endpoint was 120-day mortality. We used multivariable logistic regression to quantify the associations between pre-operative anaemia, red blood cell transfusion and 120-day mortality. Subsequently, a mediation analysis was conducted to quantify how much of the effect of pre-operative anaemia on postoperative mortality is because of red blood cell transfusion. Results: Of 71,053 patients, 14,452 (20.3%) had pre-operative anaemia. Of these, 7621 (52.7%) received red blood cell transfusion during hospital stay, compared with 9930 (17.5%) of patients without anaemia (p < 0.001). Observed 120-day mortality was 612 (4.2%) and 901 (1.6%), respectively. In multivariable regression analysis, pre-operative anaemia remained independently associated with postoperative mortality (adjusted odds ratio 1.66, 95%CI 1.47–1.87), with consistent effects across age groups. Mediation analysis showed that red blood cell transfusion accounted for 58.9% (95%CI 41.3–76.5%) of the association between pre-operative anaemia and 120-day mortality. The proportion mediated was larger in patients aged ≥ 70 years (77.3%, 95%CI 43.1–100%) compared with younger patients (39.3%, 95%CI 21.4–57.2%). Discussion: A substantial part of the association between pre-operative anaemia and mortality after cardiac surgery is mediated by red blood cell transfusion during hospital stay. The mediating role of red blood cell transfusion was more pronounced in older patients.