Hypovolaemic phlebotomy in patients undergoing hepatic resection at higher risk of blood loss (PRICE-2): a randomised controlled trial

Guillaume Martel¹, François Martin Carrier², Christopher Wherrett³, Tori Lenet⁴, Katlin Mallette⁵, Karine Brousseau⁴, Leah Monette⁴, Aklile Workneh⁴, Monique Ruel⁶, Elham Sabri⁷, Heather Maddison⁸, Melanie Tokessy⁸, Patrick B Y Wong³, Franck Vandenbroucke-Menu⁹, Luc Massicotte⁶, Michaël Chassé¹⁰, Yves Collin¹¹, Michel-Antoine Perrault¹², Élodie Hamel-Perreault¹², Jeieung Park¹³, Shirley Lim¹³, Véronique Maltais¹⁴, Philemon Leung¹⁴, Richard W D Gilbert¹⁵, Maja Segedi¹⁴, Jad Abou Khalil⁴, Kimberly A Bertens⁴, Fady K Balaa⁵, Timothy Ramsay⁷, Alan Tinmouth¹⁶, Dean A Fergusson¹⁶

Affiliations

¹ Department of Surgery, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada. Electronic address: gumartel@toh.ca.
² Department of Anesthesiology, Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada; Department of Medicine, Division of Critical Care Medicine, Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada.
³ Department of Anesthesiology & Pain Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada.
⁴ Department of Surgery, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
⁵ Department of Surgery, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada.
⁶ Department of Anesthesiology, Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada.
⁷ Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
⁸ Eastern Ontario Regional Laboratory Association, Ottawa, ON, Canada.
⁹ Department of Surgery, Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada.
¹⁰ Department of Medicine, Division of Critical Care Medicine, Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada.
¹¹ Department of Surgery, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada.
¹² Department of Anesthesiology, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada.
¹³ Department of Anesthesiology, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada.
¹⁴ Department of Surgery, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada.
¹⁵ Department of Surgery, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada; Department of Surgery, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada.
¹⁶ Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada; Canadian Blood Services, Ottawa, ON, Canada.

PMID: 39667380
DOI: 10.1016/S2468-1253(24)00307-8

Randomized Controlled Trial

Hypovolaemic phlebotomy in patients undergoing hepatic resection at higher risk of blood loss (PRICE-2): a randomised controlled trial

Guillaume Martel et al. Lancet Gastroenterol Hepatol. 2025 Feb.

. 2025 Feb;10(2):114-124.

doi: 10.1016/S2468-1253(24)00307-8. Epub 2024 Dec 9.

Authors

Affiliations

¹ Department of Surgery, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada. Electronic address: gumartel@toh.ca.
² Department of Anesthesiology, Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada; Department of Medicine, Division of Critical Care Medicine, Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada.
³ Department of Anesthesiology & Pain Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada.
⁴ Department of Surgery, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
⁵ Department of Surgery, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada.
⁶ Department of Anesthesiology, Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada.
⁷ Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
⁸ Eastern Ontario Regional Laboratory Association, Ottawa, ON, Canada.
⁹ Department of Surgery, Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada.
¹⁰ Department of Medicine, Division of Critical Care Medicine, Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada.
¹¹ Department of Surgery, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada.
¹² Department of Anesthesiology, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada.
¹³ Department of Anesthesiology, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada.
¹⁴ Department of Surgery, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada.
¹⁵ Department of Surgery, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada; Department of Surgery, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada.
¹⁶ Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada; Canadian Blood Services, Ottawa, ON, Canada.

PMID: 39667380
DOI: 10.1016/S2468-1253(24)00307-8

Abstract

Background: Blood loss and subsequent red blood cell transfusions are common in liver surgery. Hypovolaemic phlebotomy is associated with decreased red blood cell transfusion in observational studies. This trial aimed to investigate whether hypovolaemic phlebotomy is superior to usual care in reducing red blood cell transfusions in patients undergoing liver resection.

Methods: PRICE-2 was a multicentre, single-blind, superiority randomised controlled trial. Patients at a higher risk of blood loss undergoing liver resection for any indication at four Canadian academic tertiary-care hospitals were randomised to receive hypovolaemic phlebotomy or usual care. Hypovolaemic phlebotomy consisted of the removal of 7-10 mL/kg of whole blood, without volume replacement, before liver transection. Patients were randomised centrally using permuted blocks of randomly variable length, stratified by centre. The randomisation sequence was computer-generated by an independent statistician. Surgeons, patients, and outcome assessors were masked to treatment allocation. The primary outcome was perioperative red blood cell transfusion to 30 days post-randomisation, analysed in all randomly assigned patients who underwent liver resection. PRICE-2 trial was registered with ClinicalTrials.gov (NCT03651154) and is completed.

Findings: Between Oct 1, 2018, and Jan 13, 2023, 486 individuals were randomly assigned to receive hypovolaemic phlebotomy (n=245) or usual care (n=241). 22 individuals in the hypovolaemic phlebotomy group and 18 in the usual care group did not undergo liver resection and were thus excluded from the primary analysis population. 223 patients were included in the hypovolaemic phlebotomy group (mean age 61·4 years [SD 13·0]; 137 [61%] men) and 223 in the control group (62·1 years [12·1]; 114 [51%]). 17 (8%) of 223 patients allocated to hypovolaemic phlebotomy and 36 (16%) of 223 patients allocated to usual care had a perioperative red blood cell transfusion by 30 days (difference -8·8 percentage points [95% CI -14·8 to -2·8]; adjusted risk ratio [aRR] 0·47 [95% CI 0·27 to 0·82]). Severe complications to 30 days occurred in 37 (17%) patients allocated to hypovolaemic phlebotomy and 36 (16%) allocated to usual care (aRR 1·06 [95% CI 0·70-1·61]). Overall complications to 30 days occurred in 135 (61%) of 223 patients allocated to hypovolaemic phlebotomy and 116 (52%) of 223 patients allocated to usual care (1·08 [0·92-1·25]). There was no postoperative mortality to 90 days.

Interpretation: In patients undergoing liver resection, hypovolaemic phlebotomy reduced perioperative red blood cell transfusion and improved operative conditions, with no statistically significant increase in the incidence of complications compared with usual care. Hypovolaemic phlebotomy should be considered for routine use in patients undergoing liver resection at higher risk of bleeding.

Funding: Canadian Institutes of Health Research (PJT-156108).

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Conflict of interest statement

Declaration of interests This study was funded by a Project Grant from the Canadian Institutes of Health Research, applicable to all coauthors. GM has received research grants from the Canadian Blood Services. VM has received a speaker's honorarium from Eisai. PL has received a speaker's honorarium from Eisai, as well as a travel or conference support from the University of British Columbia. MS has received a speaker's honorarium and travel or conference support from Eisai, and holds leadership positions in the Canadian Transplant Society and the British Columbia Surgical Society Conference. AT has received research grants and speaker's honoraria from the Canadian Blood Services and is a member of an advisory board for GlaxoSmithKline. All other authors declare no competing interests.

Comment in

Hypovolaemic phlebotomy to reduce the need for perioperative transfusion: a price worth paying?
Schnitzbauer AA. Schnitzbauer AA. Lancet Gastroenterol Hepatol. 2025 Feb;10(2):96-97. doi: 10.1016/S2468-1253(24)00351-0. Epub 2024 Dec 9. Lancet Gastroenterol Hepatol. 2025. PMID: 39667381 No abstract available.

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Hypovolaemic phlebotomy in patients undergoing hepatic resection at higher risk of blood loss (PRICE-2): a randomised controlled trial

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Hypovolaemic phlebotomy in patients undergoing hepatic resection at higher risk of blood loss (PRICE-2): a randomised controlled trial

Authors

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Abstract

Conflict of interest statement

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Medical