PRICE-2: Hypovolaemic Phlebotomy Reduces Blood Transfusions After Liver Resection

Guillaume Martel, MD, MSc

Credit: The Ottawa Hospital

Hypovolaemic phlebotomy may help reduce the need for perioperative red blood cell transfusion while improving operative conditions in patients undergoing liver resection, according to findings from a recent study.¹

A multicenter, single-blind, superiority randomized controlled trial, PRICE-2 was conducted at 4 academic tertiary-care hospitals in Canada among more than 400 patients at an increased risk of blood loss undergoing liver resection. Results showed 7.6% of those who received hypovolemic phlebotomy had blood transfusions in the 30 days after surgery compared to 16.1% of those who received usual care.¹

“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,” senior author Dean Fergusson, PhD, MHA, deputy scientific director, clinical research and senior scientist at The Ottawa Hospital and a professor at the University of Ottawa, said in a press release.²

The safety and feasibility of hypovolemic phlebotomy in major liver surgery was previously tested in a phase 1 trial conducted at The Ottawa Hospital. Among 138 prospectively examined consecutive patients who had an elective liver resection and concurrent phlebotomy between 2013 and 2016, 37 underwent liver resection with phlebotomy. Results showed these patients had lower median blood loss (400 vs 700 mL; P = .0016) and a reduced perioperative transfusion rate (8.1% vs 32%; P = .0048) compared with patients who underwent liver resection without phlebotomy.²

In PRICE-2, patients at a higher risk of blood loss undergoing liver resection for any indication at The Ottawa Hospital; le Centre Hospitalier de l’Université de Montréal; le Centre Hospitalier Universitaire de Sherbrooke; and Vancouver General Hospital were randomly assigned to receive hypovolaemic phlebotomy or usual care. Surgeons, patients, and outcome assessors were masked to treatment allocation.^1,2

The primary outcome was perioperative red blood cell transfusion to 30 days post-randomization, analyzed in all randomly assigned patients who underwent liver resection.¹

Between October 1, 2018, and January 13, 2023, 486 individuals were randomly assigned to receive hypovolaemic phlebotomy (n = 245) or usual care (n = 241). Of note, 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.¹

In total, 223 patients with a mean age of 61.4 years who were predominantly (61%) male were included in the hypovolaemic phlebotomy group while 223 patients with a mean age of 62.1 years who were also predominantly (51%) male were included in the control group.¹

By 30 days following the procedure, 17 (8%) patients allocated to hypovolaemic phlebotomy and 36 (16%) patients allocated to usual care had a perioperative red blood cell transfusion (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).¹

Investigators noted 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 to 1.61), while overall complications to 30 days occurred in 135 (61%) patients allocated to hypovolaemic phlebotomy and 116 (52%) patients allocated to usual care (aRR, 1.08; 95% CI, 0.92–1.25). Of note, there was no postoperative mortality to 90 days.¹

“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 Guillaume Martel, MD, MSc, a surgeon and the Arnie Vered Family Chair in Hepato-Pancreato-Biliary Research at The Ottawa Hospital and the University of Ottawa.² “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.”

“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 François Martin Carrier, MD, MSc, an anesthesiologist and critical care medicine specialist at le Centre Hospitalier de l’Université de Montréal and the Héma-Québec – Bayer Chair in Transfusion Medicine at Université de Montréal.² “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.”

References

1. ^{Martel G, Carrier FM, Wherrett C, et al. Hypovolaemic phlebotomy in patients undergoing hepatic resection at higher risk of blood loss (PRICE-2): a randomised controlled trial. The Lancet Gastroenterology and Hepatology. doi:10.1016/S2468-1253(24)00307-8}
2. ^{The Ottawa Hospital. Blood removal before major liver surgery cuts transfusions in half. EurekAlert! December 9, 2024. Accessed December 10, 2024. https://www.eurekalert.org/news-releases/1067387}
3. ^{Rekman J, Wherrett C, Bennett S, et al. Safety and feasibility of phlebotomy with controlled hypovolemia to minimize blood loss in liver resections. Surgery. doi:10.1016/j.surg.2016.08.026.}