surgery

Grand Rounds September 11, 2026: Embedded Trials in a Learning Health System: A Hospital Policy of Tranexamic Acid to Reduce Transfusion in Major Noncardiac Surgery (Ryan Zarychanski, MD, MSc, FRCPC, FCAHS)

Posted on by Sophia Ramirez

Speaker

Ryan Zarychanski, MD, MSc, FRCPC, FCAHS
Professor of Medicine (Hematology and Critical Care), Pharmacy, and Community Health Sciences
Tier 1 Canada Research Chair in Clinical Trials
Max Rady College of Medicine | University of Manitoba
Hematologist and Senior Scientist
CancerCare Manitoba and Research Institute
Scientific Director
George and Fay Yee Centre for Healthcare Innovation & Aurora Clinical Research

Keywords

Infusion; Surgery; Tranexamic Acid; Noncardiac Surgery

Key Points

  • Tranexamic acid (TXA) is an inexpensive, widely available resource with an established safety profile. Evidence shows that the use of TXA during cardiac surgeries reduces the rate of blood transfusion – an expensive procedure involving a limited resource.
  • The TRACTION trial sought to assess the use of TXA in non-cardiac surgery through a multicenter randomized controlled trial with 2 co-primary outcomes: the proportion of patients who received a blood transfusion and the rate of venous thromboembolism (VTE) within 90 days of the surgery.
  • Patients undergoing surgeries with over 5% risk of transfusion were eligible. Ultimately, 8,400 patients were enrolled across 10 sites in Canada. The study team utilized a cluster-randomized embedded design; each site was randomized to either placebo or TXA every 4 weeks.
  • TXA reduced the rate of transfusion during non-cardiac surgeries, with 7.4% of patients in the intervention arm versus 9.8% in the control arm. Thrombotic event rates were equivalent between the 2 groups. Novel methods like the cluster-randomized embedded design, risk-adapted consent, and electronic data capture increased efficiency and substantially reduced the cost of the trial.

Discussion Themes

Years of preparatory studies, statistical modeling, and navigating complex provincial and governmental data-sharing agreements were required before trial launch.

A decision not to include pregnant women in the trial was driven by hospital leadership's risk aversion and liability concerns rather than regulatory or IRB refusals.

A strict 1% non-inferiority margin for thrombotic safety was established through direct consultation with patient groups and clinicians.

Grand Rounds February 27, 2026: Optimal Transfusion Strategy in High Cardiac Risk Patients After Major Surgery: Results of the TOP Trial (Panos Kougias, MD, MSc; Sherene Sharath, PhD, MPH)

Posted on by Sophia Ramirez

Speakers

Panos Kougias, MD, MSc
Professor and Chair
Department of Surgery, SUNY Downstate Health Sciences University

Sherene Sharath, PhD, MPH
Assistant Professor
Department of Surgery, SUNY Downstate Health Sciences University

Keywords

Blood Transfusion; Surgery; Cardiology; Cardiac Outcomes

Key Points

  • Postoperative anemia is common after major operations. While the current guidelines recommend transfusion for hemoglobin (Hb) below 7 g/dL, the safety of this restrictive strategy is unclear – particularly after major operations and in high cardiac risk patients.
  • The study team sought to evaluate whether a more liberal transfusion strategy reduces the risk of mortality or major ischemic events in high cardiac risk patients undergoing major operations. They randomized eligible veterans from 16 VA medical centers to receive transfusion at either Hb<10 g/dL (the “liberal” arm) or Hb<7 g/dL (the “restrictive” arm).
  • They found that the rates of mortality and major ischemic events were similar between the groups. While the rates of most secondary outcomes were also similar, a composite outcome of heart failure and arrhythmias was more frequent in the restrictive arm.
  • The study team noted that a one-size-fits-all approach may not be applicable for transfusion strategies. Potential cardiac-outcome related benefits should be explored in future trials.

Discussion Themes

In the weighting of composite outcomes, the analysis treated all events (e.g., death vs. minor complications) as having equal clinical severity. This may have reduced the trial’s statistical power.

The actual event rate (10%) was much lower than the anticipated 30%. The study team attributed this to improved perioperative care and better cardiovascular outcomes over the last decade compared to the historical data used for initial calculations.

Communicating nuanced findings may require some extra legwork; clinicians often struggle to interpret results that are not clear-cut “wins” or “losses.”

Grand Rounds November 22, 2024: Tranexamic Acid Versus Placebo to Reduce Perioperative Blood Transfusion in Patients Undergoing Liver Resection: HeLiX Trial (Paul J. Karanicolas, MD, PhD, FRCSC)

Posted on by Sophia Ramirez

Speaker

Paul J. Karanicolas, MD, PhD, FRCSC
Associate Professor of Emergency Medicine and Epidemiology
The Edmond Odette Cancer Centre @ Sunnybrook Health Sciences Centre
Professor of Surgery
University of Toronto

Keywords

Liver Cancer; Liver Resection; Blood Transfusions

Key Points

  • Liver resection is a major operation. Though it’s become safer over the past several decades, it requires blood transfusion in 20-40% of patients. Bleeding and blood transfusion are associated with substantial post-operative morbidity and an increase in mortality, re-operation, and re-admission rates.
  • A 2012 meta-analysis found that tranexamic acid (TXA) use in surgery was associated with lower blood transfusion rates. However, most of the trials included in the analysis involved cardiac and orthopedic surgery. There was limited evidence to suggest that TXA offered similar protective effects for liver resection patients.
  • The research team designed a pragmatic trial of adult patients undergoing cancer-related liver resection. Their primary outcome was the receipt of blood transfusion over the first seven days during or following surgery.
  • They randomized 1,384 participants to either a TXA arm or a placebo arm over eight years. They found that administration of TXA had no impact on blood transfusion, interoperative bleeding, or total blood loss; however, it increased the incidence of any surgical complications and major adverse events, with a possible increase in venous thromboembolism (VTE).
  • These findings were discordant with most existing evidence. Possible explanations included chance (unlikely, given the narrow confidence interval); a differing mechanism of bleeding in liver resection patients; and a difference in the dose or timing of TXA (also unlikely).
  • Based on this trial, the study team concluded that 1) TXA does not reduce blood transfusion or bleeding in patients undergoing liver resection; 2) TXA increases adverse events in this context with a signal towards increased VTE; and 3) TXA should not be used routinely in patients undergoing liver resection.
  • More work is necessary to determine whether TXA is beneficial and safe in other types of major oncologic surgery.

Discussion Themes

After some debate, the research team designed their trial to include all liver resection patients as opposed to only patients receiving major liver resections. Only 1/3 of patients have a major operation, and all liver resection patients have at least a 15% risk for bleeding and blood transfusion.

They landed on receipt of blood transfusion as the primary outcome because of the strong association between transfusion and other patient-important outcomes and due to the limited nature of blood transfusions as a resource.

Dr. Karanicolas reflected that the team should have collected adverse events data differently, grouping the complications into more meaningful categories; currently, they are limited in their ability to interpret the complications data.

The study team intentionally did not build an efficacy stopping rule into the trial due to concerns about bias. Having seen the trial through to the end, they had stronger evidence when they arrived at their surprising conclusion.