Reducing Red Blood Cell Transfusion Requirements for Adults Undergoing Surgical Resection of the Liver - A Quality Improvement Project

NCT07629648 | Not Yet Recruiting

• 1 other identifier: 6045703
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to determine if implementing a controlled blood removal protocol (i.e. hypovolemic phlebotomy \[HP\] where approximately 10% of the patient's blood is removed and reinfused following hepatic resection as described in the PRICE-2 clinical trial) will reduce the rate of blood transfusions in liver resection surgery at Kingston Health Sciences Centre. Our goals (not included in the PRICE-2 trial) are as follows:

• Improved monitoring of how the body responds during surgery following controlled blood removal. We will conduct blood tests to look at oxygen, carbon dioxide, lactate, and acid (pH) levels in the blood as well as urine output.
• Standardized guidelines for how fluids and blood pressure medications are used during surgery to reduce blood loss and keep hemodynamics stable.
• Monitor patients' recovery following surgery to track complications, injury to the heart, length of hospital stay, and outcomes for up to 90 days. We will also compare long-term recurrence rate of liver cancer compared to patients in the past at our site who did not receive the controlled blood removal (i.e., HP) prior to surgery.

Conditions

Hepatectomy; Blood Cells Transfusion; Phlebotomy; Transfusion Requirements; Intraoperative Bleeding; Intraoperative Monitoring

Keywords

hypovolemic phlebotomy; hepatectomy; Perioperative Care; erythrocyte transfusion; liver resection; transfusion requirements; therapeutic phlebotomy; intraoperative bleeding

Outcome Measures

Primary Outcomes (1)

• Reduction of intraoperative red blood cell (RBC) transfusion rates.

  To change intraoperative transfusion rates (representing a 38% reduction based on PRICE-2 trial) in elective hepatectomies for cancer at KHSC upon implementation of a standardized hypovolemic phlebotomy protocol. In so doing, we aim to make our local transfusion rate in line with the average transfusion rate across centers in Ontario, Canada.

  Perioperatively, from hospital admission to discharge.

Secondary Outcomes (7)

• Rate of change in pH based on serial arterial blood gases during hepatectomy.

  Intraoperatively, from induction of anesthesia to when patient is in the post-anesthetic care unit in the immediate postoperative period.

• Rate of change in PaO2 and PaCO2 (mmHg) based on serial arterial blood gases during hepatectomy.

  Intraoperatively, from induction of anesthesia to when patient is in the post-anesthetic care unit in the immediate postoperative period.

• Rate of change in serum lactate (mmol/L) based on serial arterial blood gases during hepatectomy.

  Intraoperatively, from induction of anesthesia to when patient is in the post-anesthetic care unit in the immediate postoperative period.

• Rate of change in urine output (mL) during hepatectomy.

  Intraoperatively, from induction of anesthesia to when patient is in the post-anesthetic care unit in the immediate postoperative period.

• Total dose of vasopressors (ephedrine, phenylephrine, norepinephrine, epinephrine, vasopressin) required to maintain a mean arterial pressure (MAP) target of ≥65 mmHg intraoperatively during hypovolemic phlebotomy hepatectomy.

  Intraoperatively, from induction of anesthesia to when patient is in the post-anesthetic care unit in the immediate postoperative period.

Study Arms (2)

Standardized hypovolemic phlebotomy protocol

Adult patients at KHSC who are undergoing elective liver resection will receive hypovolemic phlebotomy (HP) in addition to standard anesthetic and surgical care. Following induction of general anesthesia and before hepatic resection, 10% of estimated total blood volume (approximately 7-10 mL/kg) will be removed via central venous access or a large bore peripheral venous line. Hemodynamic changes following phlebotomy will be managed using vasopressors \[phenylephrine +/- norepinephrine at the discretion of the attending anesthesiologist(s)\] instead of routine IV crystalloid replacement. The goal is to maintain mean arterial pressure ≥65 mmHg. Serial physiologic monitoring will include arterial blood gases, lactate levels, urine output, and hemodynamic parameters at predefined timepoints (pre-phlebotomy after induction, post-phlebotomy, end of resection and in PACU). Autologous blood will be reinfused as needed if bleeding occurs prior to surgical closure (within 8 hours of collection).

Historical comparator cohort

A retrospective chart review will be conducted to assess the outcomes of previous elective liver resections prior to the introduction of hypovolemic phlebotomy at KHSC. This population will serve as a control cohort for our prospective data to document a structured hypovolemic phlebotomy approach that leads to measurable improvements in intraoperative management and perioperative outcomes. Data extracted will include demographics, indication for resection, baseline risk factors, operative variables (type and extent of resection, estimated blood loss, total fluid administered, vasopressor use including agent, dose, duration and any intraoperative transfusions of blood products). Postoperative outcomes will also be collected, including hemoglobin levels, total length of hospital stay, ICU admission (if applicable), total intraoperative blood product usage, 30- and 90- day mortality, and post-operative complications. The same exclusion criteria as the intervention group will be applied.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults aged ≥18 years undergoing elective hepatic resection at Kingston Health Sciences Centre.

You may qualify if:

• Liver resection in this study is defined according to the PRICE-2 trial, involving 3 or more liver segments, such as right posterior sectionectomy (of segments VI and VII) as well as central resections involving segments IVb and V, along with expected blood loss of \>250 mL
• in patients with known liver cirrhosis, resection of a full segment was included.

You may not qualify if:

• current cardiac condition (e.g., MI within the last 6 months, hypertrophic cardiomyopathy, severe valvular disease, or other unstable coronary syndromes)
• history of cerebrovascular disease (CVA within the past 6 months or severe carotid stenosis with more than 70% occlusion)
• history of significant peripheral vascular disease (not yet revascularized with regular/ongoing claudication)
• A current pregnancy
• A documented, patient-declared refusal to undergo phlebotomy and transfusion
• preoperative autologous blood donation
• presence of active infection
• preoperative hemoglobin \<100 g/L
• GFR \<60 mL/min
• platelets count \<100 × 109/L
• Uncorrectable coagulopathies or other decompensated cardiac or respiratory conditions that would contraindicate acute volume depletion
• undergoing emergency surgery
• planned intraoperative use of cell salvage
• inability to participate in follow up
• in the case of repeat liver resections, previous participation in the trial

Sponsors & Collaborators

• Dr. Glenio Mizubuti (MD, PhD, FRCPC): lead

Study Sites (1)

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

Location

Related Publications (8)

• Bonnet A, Gilquin N, Steer N, Gazon M, Quattrone D, Pradat P, Maynard M, Mabrut JY, Aubrun F. The use of a thromboelastometry-based algorithm reduces the need for blood product transfusion during orthotopic liver transplantation: A randomised controlled study. Eur J Anaesthesiol. 2019 Nov;36(11):825-833. doi: 10.1097/EJA.0000000000001084.

  PMID: 31567574 BACKGROUND

• Roullet S, Freyburger G, Cruc M, Quinart A, Stecken L, Audy M, Chiche L, Sztark F. Management of bleeding and transfusion during liver transplantation before and after the introduction of a rotational thromboelastometry-based algorithm. Liver Transpl. 2015 Feb;21(2):169-79. doi: 10.1002/lt.24030. Epub 2015 Jan 12.

  PMID: 25331016 BACKGROUND

• Carson JL, Guyatt G, Heddle NM, Grossman BJ, Cohn CS, Fung MK, Gernsheimer T, Holcomb JB, Kaplan LJ, Katz LM, Peterson N, Ramsey G, Rao SV, Roback JD, Shander A, Tobian AA. Clinical Practice Guidelines From the AABB: Red Blood Cell Transfusion Thresholds and Storage. JAMA. 2016 Nov 15;316(19):2025-2035. doi: 10.1001/jama.2016.9185.

  PMID: 27732721 BACKGROUND

• Bennett S, Tinmouth A, McIsaac DI, English S, Hebert PC, Karanicolas PJ, Turgeon AF, Barkun J, Pawlik TM, Fergusson D, Martel G. Ottawa Criteria for Appropriate Transfusions in Hepatectomy: Using the RAND/UCLA Appropriateness Method. Ann Surg. 2018 Apr;267(4):766-774. doi: 10.1097/SLA.0000000000002205.

  PMID: 28288056 BACKGROUND

• Callum JL, Waters JH, Shaz BH, Sloan SR, Murphy MF. The AABB recommendations for the Choosing Wisely campaign of the American Board of Internal Medicine. Transfusion. 2014 Sep;54(9):2344-52. doi: 10.1111/trf.12802. Epub 2014 Aug 6. No abstract available.

  PMID: 25100209 BACKGROUND

• Shander A, Hofmann A, Ozawa S, Theusinger OM, Gombotz H, Spahn DR. Activity-based costs of blood transfusions in surgical patients at four hospitals. Transfusion. 2010 Apr;50(4):753-65. doi: 10.1111/j.1537-2995.2009.02518.x. Epub 2009 Dec 9.

  PMID: 20003061 RESULT

• Martel G, Carrier FM, Wherrett C, Lenet T, Mallette K, Brousseau K, Monette L, Workneh A, Ruel M, Sabri E, Maddison H, Tokessy M, Wong PBY, Vandenbroucke-Menu F, Massicotte L, Chasse M, Collin Y, Perrault MA, Hamel-Perreault E, Park J, Lim S, Maltais V, Leung P, Gilbert RWD, Segedi M, Khalil JA, Bertens KA, Balaa FK, Ramsay T, Tinmouth A, Fergusson DA. Hypovolaemic phlebotomy in patients undergoing hepatic resection at higher risk of blood loss (PRICE-2): a randomised controlled trial. Lancet Gastroenterol Hepatol. 2025 Feb;10(2):114-124. doi: 10.1016/S2468-1253(24)00307-8. Epub 2024 Dec 9.

  PMID: 39667380 RESULT

• Tai YH, Wu HL, Mandell MS, Tsou MY, Chang KY. The association of allogeneic blood transfusion and the recurrence of hepatic cancer after surgical resection. Anaesthesia. 2020 Apr;75(4):464-471. doi: 10.1111/anae.14862. Epub 2019 Oct 1.

  PMID: 31573678 RESULT

MeSH Terms

Conditions

Blood Loss, Surgical

Condition Hierarchy (Ancestors)

Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intraoperative Complications

Study Officials

• Glenio Mizubuti, MD, PhD, FRCPC

  Kingston Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Glenio Mizubuti, MD, PhD, FRCPC

CONTACT

(613) 548-7827; glenio.mizubuti@kingstonhsc.ca

Anthony M. H. Ho, MD, MSc, FRCPC

CONTACT

(613) 548-7827; hoamh@hotmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor, Department of Anesthesiology & Perioperative Medicine

Study Record Dates

• First Submitted: May 25, 2026
• First Posted: June 5, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2031
• Last Updated: June 5, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)