“Blood loss is a major concern in liver surgery. Taking out half a litre of blood right before major liver surgery is the best thing we’ve found so far for reducing blood loss and transfusions,” said Dr. Guillaume MartelRemoving 10 per cent of a patient’s blood before major liver surgery and giving it back afterwards reduced transfusions by half, according to a large clinical trial published in The Lancet Gastroenterology & Hepatology. Known as hypovolemic phlebotomy, this practice could save one in every 11 patients having this surgery from needing a transfusion.
“Blood loss is a major concern in liver surgery. Taking out half a litre of blood right before major liver surgery is the best thing we’ve found so far for reducing blood loss and transfusions,” said co-lead author Dr. Guillaume Martel, a surgeon and scientist who holds the Arnie Vered Family Chair in Hepato-Pancreato-Biliary Research at The Ottawa Hospital and University of Ottawa. “It works by lowering the blood pressure in the liver. It’s safe, simple, inexpensive, and should be considered for any liver surgery with a high risk of bleeding.”
Between a quarter to a third of people having major liver surgery will need a transfusion. Cancer is the most common reason for these surgeries and having a transfusion during or shortly after surgery is possibly associated with a higher risk of the cancer coming back.
“Now that we’ve proven removing blood before liver surgery reduces transfusions, we’re spreading the word and teaching our colleagues how to do it,” said co-lead author Dr. François Martin Carrier, an anesthesiologist and critical care medicine specialist at le Centre Hospitalier de l’Université de Montréal who holds the Héma-Québec – Bayer Chair in Transfusion Medicine at Université de Montréal. “Providers find it simple after they’ve done it once, and the impact on surgery is dramatic. It’s now standard of care in the four hospitals that were part of the trial, and other hospitals around the world should start to adopt it after learning of our results.”
Practice-changing trial largest of its kind
In the largest trial of its kind, 446 people having major liver surgery were recruited at four Canadian hospitals between 2018 and 2023 (The Ottawa Hospital, le Centre Hospitalier de l’Université de Montréal, le Centre Hospitalier Universitaire de Sherbrooke, and Vancouver General Hospital).
Once under anesthetic, patients were randomly assigned to receive either hypovolemic phlebotomy or usual care. Only the anesthesiologist knew which patients were in which group.
For patients in the hypovolemic phlebotomy group, the anesthesiologist removed the equivalent of one blood donation (about 450 mL) into a blood bag before surgery. If the patient needed blood during surgery, their blood was used first. Otherwise, it was re-infused before they woke up.
According to hospital blood bank data and patient medical records, 7.6 per cent of those who received hypovolemic phlebotomy (17 of 223) had blood transfusions in the 30 days after surgery compared to 16.1 per cent (36 of 223) of those who received usual care. Hypovolemic phlebotomy caused no more complications than usual care.
Surgeons also said hypovolemic phlebotomy made the surgery easier to do, because there was less blood obscuring the places they needed to cut. Median estimated blood loss was 670 mL with hypovolemic phlebotomy compared to 800 mL with usual care.
“I’m so glad I was picked, and I’m glad it will help other people,” says participant
"You’re told before surgery that the liver is so full of blood vessels that there are risks of major bleeding. I thought it was great that researchers were trying things to reduce those risks," said participant Rowan Ladd.Rowan Ladd was 44 when she had colon cancer surgery on Christmas Eve 2020. Two years later, the cancer had spread to her liver and she needed another surgery, this time on her liver.
“I signed up for every study I was offered. If I’m going into liver surgery, then why not? I’m a big proponent of research,” says the Ottawa mother of two. “I was interested in this study in particular because they had great results in the pilot trial. You’re told before surgery that the liver is so full of blood vessels that there are risks of major bleeding. I thought it was great that researchers were trying things to reduce those risks.”
During her liver surgery in October 2022, Rowan was randomly selected to have hypovolemic phlebotomy. She found out which group she was in after the surgery. She did not need a blood transfusion. After four days in hospital, she was back home. Two years later, she remains cancer-free.
“I looked at this surgery like it saved my life. I stopped working, I relaxed, I took care of myself. I was unlucky to get cancer, but it woke me up. Now I live life and I really enjoy it where before I was just existing,” she says. “Being part of this trial was a really positive experience, and the team was wonderful. I’m so glad I was picked, and I’m glad it will help other people.”
Saving blood for those who need it most
One blood transfusion in Canada costs at least $500 CAD, mainly in human resources. The blood bags and tubes used for hypovolemic phlebotomy cost less than $30 CAD.
“Blood transfusions can save lives, but if you don’t need one to save your life then it’s better to avoid it. Blood is a precious and limited resource that we need to preserve as much as possible for those who need it most,” said senior author Dr. Dean Fergusson, Deputy Scientific Director, Clinical Research and senior scientist at The Ottawa Hospital and professor at the University of Ottawa.
Dr. Martel’s team previously tested the safety and feasibility of hypovolemic phlebotomy in major liver surgery in a phase 1 trial at The Ottawa Hospital. The procedure is now being tested in liver transplantation, and there may be future interest in testing it for other surgeries with significant blood loss.
Full reference: Hypovolemic phlebotomy in hepatic resections at higher risk of blood loss: a randomized controlled trial (PRICE-2). Guillaume Martel, François Martin Carrier, Christopher Wherrett, Tori Lenet, Katlin Mallette, Karine Brousseau, Leah Monette, Aklile Workneh Monique Ruel, Elham Sabri, Heather Maddison, Melanie Tokessym, Patrick B. Y. Wong, Professor Franck Vandenbroucke-Menu, Luc Massicotte, Michaël Chassé, Yves Collin, Michel-Antoine Perrault, Élodie Hamel-Perreault, Jeieung Park, Shirley Lim, Véronique Maltais, Philemon Leung, Richard W. D. Gilberta, Maja Segedi, Jad Abou Khalil, Kimberly A. Bertens, Fady K. Balaa, Timothy Ramsay, Alan Tinmouth, Dean A. Fergusson. The Lancet Gastroenterology & Hepatology. December 9, 2024.
Core resources: Ottawa Methods Centre
Funding: This study was funded by the Canadian Institutes of Health Research.
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