Projects

HEMOTION Trial: HEMOglobin transfusion threshold in Traumatic brain Injury OptimizatioN

Principal Investigator(s) Turgeon, Alexis
Lauzier, Francois
Fergusson, Dean
Co-investigator(s) the HEMOTION Trial investigators
Research Coordinator(s) Clayton, Lucy

HEMOTION Trial: HEMOglobin transfusion threshold in Traumatic brain Injury OptimizatioN

BACKGROUND

In Canada, trauma causes more than 15,000 deaths every year. Most deaths are related to traumatic brain injury (TBI). Although the management of TBI patients has improved, mortality remains unacceptably high (20 to 50%), and half of survivors are left with major functional impairment. Current guidelines for the management of TBI are based on limited evidence and practice is highly variable, including strategies to improve brain oxygen delivery such as blood transfusion. Most critically ill patients with TBI will develop anemia, which may decrease oxygen delivered to a fragile traumatized brain. While clinical practice is moving towards transfusing patients at low hemoglobin (Hgb) levels, experts have expressed concerns regarding restrictive strategies and the low level of evidence on which they are based. Indeed, there is concern that anemia might adversely affect clinical outcomes in TBI.

THE PROBLEM

Current guidelines for the management of TBI are based on limited evidence and practices are highly variable, including for strategies to improve brain oxygen delivery such as blood transfusion. However, most critically ill patients sustaining traumatic brain injury will develop anemia over their hospital stay. Hemoglobin being responsible for oxygen delivery to tissues, anemia may thus generate decreased oxygen delivered to end organs, and more so to a fragile traumatized brain. Evidence-base practice for red blood cell (RBC) transfusions is thus a core topic in trauma, but more so in TBI.

While clinical practice is moving towards restrictive transfusion strategies (transfusion threshold at low hemoglobin levels) for most trauma patients in the intensive care unit, many experts have expressed concerns regarding optimal RBC transfusion strategies in patients with TBI, emphasizing on the low level of evidence driving clinical practice. Indeed, concerns that low hemoglobin levels in the context of traumatic brain injuries (TBI) might unfavorably affect clinical outcomes have been expressed. RBC transfusions to reach satisfying hemoglobin levels are thus advocated by some to increase cerebral oxygen delivery.

Thus, evidence-based driven data on what transfusion strategy to adopt in patients with TBI is unclear, as well as when benefits outweigh the risks associated with this intervention. The scientific community has expressed the critical need for rigorous studies and high-quality data on RBC transfusion in this population. We developed a research program to evaluate optimal transfusion strategies in patients with TBI. Our findings will allow for both optimal usage of a scarce resource and the proper understanding of the brain’s blood requirements in this vulnerable population.

STUDY  HYPOTHESIS

We hypothesize that, among critically ill adult patients with TBI, a liberal RBC transfusion strategy (triggered by Hgb ≤100g/L) improves long-term functional outcomes compared to a restrictive strategy (triggered by Hgb ≤70g/L).

THE PROPOSED TRIAL

We will conduct a multicentre pragmatic open blinded-endpoint (PROBE) randomized trial critically ill patients with TBI. Our primary objective is to evaluate the effect of RBC transfusion on neurological functional outcome (Glasgow Outcome Scale extended) at 6 months. Our secondary objectives are to evaluate overall functional outcome (Functional Independence Measure [FIM]), quality of life, psychological outcomes and mortality at 6 months. Critically ill adult patients with moderate or severe TBI will be randomized into a liberal or a restrictive RBC transfusion strategy when reaching an Hgb ≤100g/L. Randomization will be stratified by centre and by TBI severity. Additional RBC transfusions will be given if the Hgb level remains below the threshold of the treatment group. The allocated transfusion strategy will be applied from the time of randomization to death or discharge from the intensive care unit. Data collection will be done prospectively by experienced research personnel. Methods to minimize biases and ensure feasibility have been put in place.

EXPERTISE

A large group co-investigators with different key expertise, along with partners (patient representatives, stakeholders, policy makers, scientific community representatives, research networks) have contributed to the conception and the development of the trial and committed to substantial in-kind funding. This team, and our experience with previous large multicenter studies in TBI and in transfusion ensure the feasibility of the HEMOTION trial.

CONTRIBUTION TO EXISTING KNOWLEDGE

If our hypothesis is verified, the superiority of a liberal strategy compared to a restrictive one will improve long-term outcomes for the most vulnerable trauma patients group. Conversely, an absence of benefit of a liberal strategy will favour the adoption of a restrictive strategy given the transfusion costs and resources spent. From the patient’s perspective, regardless of the findings, our results will determine the most effective RBC transfusion management strategy to ensure the provision of high quality of care through the best available evidence.

FUNDING

Canadian Institutes of Health Research

CENTRES

  • CHU de Québec – Université Laval (Hôpital de l’Enfant-Jésus) (Québec, Québec)
  • Hôpital du Sacré-Coeur de Montréal (Montréal, Québec)
  • Centre Hospitalier Universitaire de Sherbrooke (Sherbrooke, Québec)
  • Sunnybrook Health Sciences Center (Toronto, Ontario)
  • St-Michael’s Hospital (Toronto, Ontario)
  • Hamilton Health Sciences Center (Hamilton, Ontario)
  • London Health Sciences Center (London, Ontario)
  • Montreal General Hospital (Montréal, Québec)
  • Winnipeg Health Sciences Center (Winnipeg, Manitoba)
  • Foothills Health Sciences Center (Calgary, Alberta)
  • CIUSSS de la Mauricie-et-Centre-du-Québec (Trois-Rivières, Québec)
  • Ottawa Hospital – Civic Campus (Ottawa, Ontario)
  • Kingston General Hospital (Kingston, Ontario)
  • Vancouver General Hospital (Vancouver, British Columbia)
  • Royal Jubilee Hospital (Victoria, British Columbia)
  • Queen Elizabeth II Health Sciences Centre (Halifax, Nova Scotia)
  • Royal Alexandra Site (Edmonton, Alberta)

 

  • Western General Hospital, Edinburgh (United Kingdom)
  • St Mary’s Hospital, London (United Kingdom)
  • Salford Royal Hospital, Salford (United Kingdom)
  • James Cook Hospital, Middlesbrough (United Kingdom)
  • The University of Nottingham Hospital, Nottingham (United Kingdom)
  • King’s College Hospital, London (United Kingdom)
  • University Hospital of Wales, Cardiff (United Kingdom)