Efficacy of acute normovolemic hemodilution in adult cardiac surgery in reducing the need for allogenic red cell transfusion: A systematic review and updated meta-analysis of randomized controlled trials.

Abstract

Abstract Introduction: Allogeneic red blood cell transfusions during cardiac surgery increase risks of immunologic reactions, infections, and transfusion-related complications. Acute normovolemic hemodilution (ANH) is a blood conservation technique used in cardiac surgery to reduce allogeneic transfusions and associated risks. However, its efficacy remains uncertain, particularly with contemporary advanced intraoperative blood management strategies. This systematic review and meta-analysis aim to evaluate ANH's impact on transfusion requirements and perioperative outcomes in adult cardiac surgery. Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines. A literature search was performed across PubMed, Scopus, Embase, and Google Scholar databases up to July 2025, comparing outcomes between Acute Normovolemic Hemodilution (ANH) and standard care in adult cardiac surgery. Data were analyzed using RevMan 5.4.1. Risk ratios (RRs) and mean differences were calculated using Mantel-Haenszel and inverse variance methods. Fixed and random effects models were selected based on study characteristics. Statistical significance was determined at p< 0.05. The risk of bias was assessed using RoB 2.0. Results: Twelve randomized controlled trials (RCTs) encompassing 3,216 patients were included in the analysis. Of these, 1,599 patients were allocated to the ANH group, while 1,617 patients were assigned to usual care. The ANH group exhibited a significantly lower likelihood of receiving allogeneic red blood cell (RBC) transfusions (32.20%) compared to the usual care group (38.09%), corresponding to a RR reduction of 21% (RR = 0.79; 95% confidence interval [CI]: 0.64-0.98; I² = 81%). ANH was associated with a reduction in postoperative blood loss via chest drains (mean difference -14.92 mL, 95% CI: -29.87 to 0.04; p = 0.05), approaching statistical significance. The proportion of ANH patients receiving fresh frozen plasma (FFP) transfusions was 21.38% compared to 24.57% in the non-ANH group (RR: 0.70; 95% CI: 0.44–1.13; I² = 70%), showing a trend favoring ANH without statistical significance. Platelet transfusion rates showed a non-significant preference for the ANH group (7.47% ANH vs. 7.60% usual care, 17 studies, RR 1.00; CI: 0.76 to 1.31). Mortality rates were lower in the ANH group (1.47%) compared to usual care (2.03%), though not statistically significant (p = 0.47; RR 1.75; 95% CI: 0.42-1.34; I² = 0%). Bleeding complications occurred in 3.97% of ANH patients versus 2.89% in controls (RR 1.37; 95% CI: 0.93-2.02; I² = 0%), showing a numerically higher rate without statistical significance. Discussion: Our meta-analysis of 12 RCTs, including 3,216 patients, shows a significant reduction in allogeneic red blood cell transfusions due to ANH. This intervention is associated with decreased postoperative chest tube drainage rates, suggesting enhanced blood preservation. The effect is attributed to red blood cell dilution during surgery, which reduces intraoperative blood loss and donor transfusion needs. However, ANH's impact on FFP or plasma transfusion rates, mortality, and bleeding rates was statistically insignificant between groups. This variation may stem from multiple factors affecting coagulation and hemostasis beyond the procedure. Focusing on trials conducted post year 2000, we emphasize contemporary, evidence-based medicine to establish protocols, addressing current needs with advanced cardiopulmonary bypass machines and diverse interventional options. Despite large trials, heterogeneity in outcomes persists, and long-term follow-up data remain insufficient. Future research should prioritize multicenter studies to identify populations deriving the most benefit, including those with anemia or perioperative anemia. Overall, ANH is a valuable addition to blood conservation strategies during cardiac surgeries, though it is more effective when integrated with other evidence-based practices.