Safety and Efficacy of Acute Normovolemic Hemodilution in Female Patients: A Secondary Analysis of the ANH Trial.

IMPORTANCE

Female patients undergoing cardiac surgery have a higher transfusion burden, yet they remain underrepresented in randomized clinical trials. Although the ANH trial showed no significant reduction in the proportion of patients receiving allogeneic blood transfusions with acute normovolemic hemodilution, evidence regarding its efficacy and safety specifically in female patients remains limited.

OBJECTIVE

To evaluate the efficacy and safety of acute normovolemic hemodilution (ANH) compared with usual care in female patients undergoing elective cardiac surgery with cardiopulmonary bypass.

DESIGN, SETTING, AND

PARTICIPANTS

This was a post hoc secondary analysis of the multicenter, randomized ANH trial, which was conducted at 32 centers in 11 countries from April 2019 to December 2024. Of 2010 patients in the original ANH trial, 405 were women and were included in this analysis; 219 had been randomized to receive ANH and 186 to usual care. This secondary analysis was conducted from August 2025 to January 2026.

INTERVENTION: Withdrawal of at least 650 mL whole blood with crystalloids replacement and reinfusion after cardiopulmonary bypass.

MAIN OUTCOMES AND MEASURES: The primary outcome was the occurrence of at least 1 allogeneic packed red blood cell (pRBC) transfusion during the index hospitalization. Safety outcomes included intraoperative hypotension, intensive care unit (ICU) length of stay, hospital length of stay, mortality, and other perioperative complications.

RESULTS

The median (IQR) age of the participants was 62 (54-69) years. The occurrence of allogeneic pRBC transfusion was similar in the ANH and usual care groups (38.8% vs 44.6%, respectively; relative risk [RR], 0.87; 95% CI, 0.69-1.10; P = .24). Intraoperative hypotension occurred more frequently with ANH (16.0% vs 4.8% in usual care; RR, 3.30; 95% CI, 1.62-6.74; P = .02). Patients receiving ANH also had longer ICU stays (mean difference, 21.13 hours; 95% CI, 1.89-40.38; P = .03) and hospital stays (mean difference, 1.92 days; 95% CI, 0.14-3.70; P = .04). No significant differences were observed in mortality or other postoperative complications.

CONCLUSIONS AND RELEVANCE: In this post hoc secondary analysis of a randomized clinical trial, ANH was not associated with a reduction in allogeneic pRBC transfusion among women undergoing cardiac surgery and was associated with more frequent intraoperative hypotension and longer ICU and hospital stay. These exploratory findings warrant confirmation in adequately powered studies specifically designed to evaluate female patients undergoing cardiac surgery.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03913481.