Heterogenous treatment effects of transfusion thresholds by patient age: Post‐hoc analysis of the TRISS trial

Background Use of a lower haemoglobin (Hb) threshold to guide red blood cell (RBC) transfusion is now generally recommended in critically ill patients, but uncertainty remains regarding the optimal Hb threshold for RBC transfusion in patients of different ages. Methods We conducted a post‐hoc analysis of 998 patients with septic shock and anaemia randomised to RBC transfusion at a Hb threshold of 7 g/dl [4.3 mmol/l] vs 9 g/dl [5.6 mmol/l] in the Transfusion Requirements in Septic Shock (TRISS) trial. We assessed if there were heterogeneous effects between the allocated Hb threshold and patient age categorised and on the continuous scale. The primary outcome was 1‐year mortality; the secondary outcome was 90‐day mortality. Both outcomes were analysed using logistic regression models and in sensitivity analyses with additional adjusting for site of enrolment, presence of haematological malignancy and the Sequential Organ Failure Assessment (SOFA) score. The secondary analyses were Kaplan‐Meier curves with corresponding log‐rank tests. Results We found no heterogeneity between patient age and the allocated Hb thresholds for RBC transfusion for 1‐year mortality or 90‐day mortality in the primary analyses. The sensitivity analyses suggested heterogeneity between age groups regarding 90‐day mortality, however, this was not consistent for 1‐year mortality or when assessing age on the continuous scale. Conclusion In this post‐hoc study of ICU patients with septic shock, we found no reliable heterogeneous effects of transfusion at a Hb threshold of 7 vs 9 g/dl according to patient age on mortality. However, due to low power, this study should only be considered as hypothesis generating.