Safety and Efficacy of Acute Normovolemic Hemodilution in Female Patients

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.

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Journal
JAMA Surgery
Published
2026-10-14
DOI
https://doi.org/10.1001/jamasurg.2026.4786
Primary Topic
Blood transfusion and management
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article
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article

Safety and Efficacy of Acute Normovolemic Hemodilution in Female Patients

Ambra Licia Di Prima, Giuseppe A. M. Giardina, Tiziana Bove, Cristina Arangino et al.
JAMA Surgery
Blood transfusion and management
article

Safety and Efficacy of Acute Normovolemic Hemodilution in Female Patients

Ambra Licia Di Prima, Giuseppe A. M. Giardina, Tiziana Bove, Cristina Arangino, Marco Ranucci, Nazar A. Bukamal, Fabrizio Monaco, 王黎妮, Chong Lei, Anna Mara Scandroglio, Mauro D’Amora, Greta Fano, Daniele Di Luca, Giuseppe Santarpino, Rosalba Lembo, Giovanni Landoni, Maria José Carvalho Carmona, Alessandro Putzu, Pasquale Nardelli, Lian Kah Ti, Monica Rocco, John S. McNeil, Gaia Barucco, Marina Pieri, Carolina Soledad Romero, Rosetta Lobreglio, Lisa Notarianni, Vincenzo Scuderi, Cristina Santonocito, Alessandro Oriani, Silvia Delrio, Sergey Mihailovich Efremov, Carolina Faustini, Elisa Cerchierini, Kristina Kadantseva, Maria Grazia Calabró, Mustafa Emre Gürcü, Gianluca Paternoster, Laura Pasin, Fabio Guarracino, Francesco Meroi, Alberto Zangrillo, Giacomo Senarighi, Matteo Aldo Bonizzoni, Kofi B. Vandyck, L. C. D'Oro, Marco Comis, Aldo Di Fazio, Alessandro Pruna, Michael A. Mazzeffi, Baobao Gao, Paolo Matteo Angeletti, Federico Mattia Oliva, Domenico Pontillo, Sabrina Porta, Marta Mucchetti, Chiara Gerli, Giovanna Frau, Valentina Ajello, Laura Fossati, Annalisa Franco, Ludhmila Abrahão Hajjar, Suraphong Lorsomradee, Michela Villano, Marta Veneziano, Federica Ferrod, Matteo Borrello, Sabrina Frisoli, Giovanna Bonelli, Benedetta Chiodi, Matteo Ghezzi, Noemi De Piccoli, Simone Bruno, Ekaterina Baryshnikova (360637), Federica Vignola, Valery Likhvantsev, Evgeny Fominskiy, ANH Study Group, Lihong Hou, Hui Zhang, Polina Turina, Giulia Franceschini, Valerii Subbotin, Ahmed M.G. Farag, Amir Latif Butt, Roman Osinsky, Xue Yang, Caetano Nigro Neto, Franscesco Federici
article en

Abstract

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.

JAMA Surgery
Università Cattolica del Sacro Cuore (IT), University of Rome Tor Vergata (IT), Vita-Salute San Raffaele University (IT), St Petersburg University (RU), University of Basilicata (IT), Oklahoma City University (US), Agostino Gemelli University Polyclinic (IT), University of Chieti-Pescara (IT), Moscow Clinical Scientific Center (RU), IRCCS Policlinico San Donato (IT), Ospedale San Carlo (IT), Azienda USL di Bologna (IT), V.A. Negovsky Scientific Research Institute of General Reanimatology (RU), Azienda Ospedaliera Sant'Andrea (IT), A. O. Ordine Mauriziano di Torino (IT), Policlinico Universitario di Catania (IT), IRCCS Ospedale San Raffaele (IT), Ospedali Riuniti San Giovanni di Dio e Ruggi d'Aragona (IT), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (BR), National University Hospital (SG), Meshalkin National Medical Research Center (RU), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Xijing Hospital (CN), IRCCS Humanitas Research Hospital (IT), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele (IT), Chiang Mai University (TH), University of Oklahoma Health Sciences Center (US), University of Virginia (US), Sapienza University of Rome (IT), University of Bologna (IT)
Good health and well-being
Openalex Percentile: Top 16%
Blood transfusion and management
DOISourceOpenAlex
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