Phlebotomy resulting in controlled hypovolemia to prevent blood loss in major hepatic resections (PRICE-2): study protocol for a phase 3 randomized controlled trial
Guillaume Martel,
Tori Lenet,
Christopher Wherrett,
François-Martin Carrier,
Leah Monette,
Aklile Workneh,
Karine Brousseau,
Monique Ruel,
Michaël Chassé,
Yves Collin,
Franck Vandenbroucke-Menu,
Élodie Hamel-Perreault,
Michel-Antoine Perreault,
Jeieung Park,
Shirley Lim,
Véronique Maltais,
Philemon Leung,
Richard W. D. Gilbert,
Maja Segedi,
Jad Abou-Khalil,
Kimberly A. Bertens,
Fady K. Balaa,
Tim Ramsay,
Dean A. Fergusson
Affiliations
Guillaume Martel
Liver and Pancreas Unit, Department of Surgery, The Ottawa Hospital– General Campus, University of Ottawa
Tori Lenet
Liver and Pancreas Unit, Department of Surgery, The Ottawa Hospital– General Campus, University of Ottawa
Christopher Wherrett
Departments of Anesthesiology and Pain Medicine, The Ottawa Hospital, University of Ottawa
François-Martin Carrier
Department of Anesthesiology, Centre Hospitalier de l’Université de Montréal, Université de Montréal
Leah Monette
Liver and Pancreas Unit, Department of Surgery, The Ottawa Hospital– General Campus, University of Ottawa
Aklile Workneh
Liver and Pancreas Unit, Department of Surgery, The Ottawa Hospital– General Campus, University of Ottawa
Karine Brousseau
Liver and Pancreas Unit, Department of Surgery, The Ottawa Hospital– General Campus, University of Ottawa
Monique Ruel
Department of Anesthesiology, Centre Hospitalier de l’Université de Montréal, Université de Montréal
Michaël Chassé
Department of Medicine, Critical Care Division, Centre Hospitalier de l’Université de Montréal, Université de Montréal
Yves Collin
Division of General Surgery, Department of Surgery, Centre Hospitalier Universitaire de Sherbrooke
Franck Vandenbroucke-Menu
Hepato-Pancreato-Biliary and Liver Transplantation Surgery Unit, Department of Surgery - Centre Hospitalier de l’Université de Montréal
Élodie Hamel-Perreault
Departement of Anesthesiology, Centre Hospitalier Universitaire de Sherbrooke
Michel-Antoine Perreault
Departement of Anesthesiology, Centre Hospitalier Universitaire de Sherbrooke
Jeieung Park
Department of Anesthesiology and Perioperative Care, Vancouver General Hospital, University of British Columbia
Shirley Lim
Department of Anesthesiology and Perioperative Care, Vancouver General Hospital, University of British Columbia
Véronique Maltais
Department of Surgery, Vancouver General Hospital, University of British Columbia
Philemon Leung
Department of Surgery, Vancouver General Hospital, University of British Columbia
Richard W. D. Gilbert
Department of Surgery, Vancouver General Hospital, University of British Columbia
Maja Segedi
Department of Surgery, Vancouver General Hospital, University of British Columbia
Jad Abou-Khalil
Liver and Pancreas Unit, Department of Surgery, The Ottawa Hospital– General Campus, University of Ottawa
Kimberly A. Bertens
Liver and Pancreas Unit, Department of Surgery, The Ottawa Hospital– General Campus, University of Ottawa
Fady K. Balaa
Liver and Pancreas Unit, Department of Surgery, The Ottawa Hospital– General Campus, University of Ottawa
Tim Ramsay
Clinical Epidemiology Program, Ottawa Hospital Research Institute
Dean A. Fergusson
Clinical Epidemiology Program, Ottawa Hospital Research Institute
Abstract Introduction Blood loss and red blood cell (RBC) transfusion in liver surgery are areas of concern for surgeons, anesthesiologists, and patients alike. While various methods are employed to reduce surgical blood loss, the evidence base surrounding each intervention is limited. Hypovolemic phlebotomy, the removal of whole blood from the patient without volume replacement during liver transection, has been strongly associated with decreased bleeding and RBC transfusion in observational studies. This trial aims to investigate whether hypovolemic phlebotomy is superior to usual care in reducing RBC transfusions in liver resection. Methods This study is a double-blind multicenter randomized controlled trial. Adult patients undergoing major hepatic resections for any indication will be randomly allocated in a 1:1 ratio to either hypovolemic phlebotomy and usual care or usual care alone. Exclusion criteria will be minor resections, preoperative hemoglobin <100g/L, renal insufficiency, and other contraindication to hypovolemic phlebotomy. The primary outcome will be the proportion of patients receiving at least one allogeneic RBC transfusion unit within 30 days of the onset of surgery. Secondary outcomes will include transfusion of other allogeneic blood products, blood loss, morbidity, mortality, and intraoperative physiologic parameters. The surgical team will be blinded to the intervention. Randomization will occur on the morning of surgery. The sample size will comprise 440 patients. Enrolment will occur at four Canadian academic liver surgery centers over a 4-year period. Ethics approval will be obtained at participating sites before enrolment. Discussion The results of this randomized control trial will provide high-quality evidence regarding the use of hypovolemic phlebotomy in major liver resection and its effects on RBC transfusion. If proven to be effective, this intervention could become standard of care in liver operations internationally and become incorporated within perioperative patient blood management programs. Trial registration ClinicalTrials.gov NCT03651154 . Registered on August 29 2018.
