Robustness of Randomized Controlled Trials Evaluating Acute Normovolemic Hemodilution as a Blood Conservation Strategy in Cardiac Surgery

Objective: To evaluate the robustness of randomized controlled trials (RCTs) investigating acute normovolemic hemodilution (ANH), a blood conservation strategy designed to reduce transfusion requirements, in cardiac surgery using the Fragility Index (FI). Although recommended in clinical guidelines, high-quality evidence supporting ANH remains limited. Design: A systematic review of RCTs. Setting: A search of PubMed/MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE databases was conducted from their inception. Participants: Adult patients undergoing cardiac surgery. Intervention: RCTs comparing ANH with standard care (without ANH) as a blood conservation strategy in adult patients undergoing cardiac surgery. The statistical robustness of RCTs was assessed using the FI, reverse FI, and Continuous FI (CFI), with higher values indicating stronger evidence. Measurements and Main Results: Twenty-eight RCTs were identified. The median sample size was 75.8 patients. On-pump coronary artery bypass grafting was the most common procedure (39.3%). The median FI for perioperative transfusion rates was higher in nonsignificant studies (p ≥ 0.05) than in significant ones (p < 0.05), suggesting weaker evidence for reducing transfusions in nonsignificant trials. Conversely, the median CFI for the number of red blood cell units transfused was higher in significant studies, supporting ANH's effectiveness in reducing transfusion requirements. Conclusion: RCTs reporting significant reductions in red blood cell transfusions with ANH exhibited greater statistical robustness, as indicated by higher FI and CFI values, compared with nonsignificant studies. The fragility of perioperative transfusion outcomes highlights the need for larger, methodologically rigorous RCTs to validate ANH's efficacy in cardiac surgery.