Background
Many advantages of intraoperative cell salvage (ICS) as an alternative to allogeneic (donated) blood transfusion (ABT) were confirmed, including a potential reduction in adverse outcomes, and improved immune competence (1-3). Remaining obstacles include: 1) the risk of systemic bacteraemia in the presence of bacterial contamination from the surgical field and 2) the potential risk of systemic cancer cell dissemination during surgery for malignant tumours (4).
Aim
The C-I-ICS study, aims to assess whether ICS (processing and filtering) could reduce the risks of cancer cell and bacterial dissemination into the patient’s circulation, when used during curative pelvic exenteration surgery.
Objectives
To analyse blood samples collected during various stages of ICS (from collection, through processing and LDF filtering), and time points during pelvic exenteration surgery; and consider the presence and potential to reduce cancer cells (adenocarcinoma), and bacterial contamination within salvaged blood.
Hypothesis
We hypothesise that ICS processing (especially in combination with a leukodepletion filter (LDF)) during pelvic exenteration surgery, would significantly reduce adenocarcinoma cells and bacterial contamination.
Methods
The C-I-ICS study is a prospective observational pilot trial (n=20), during pelvic exenteration surgery, at the RBWH. The study team will collect seven study samples from each patient, at various stages of the ICS process (i.e., collected, processed, and filtered) and at various peri-operative time points (i.e., before, after two hours and after four hours of ICS). Expert collaboration (UQCCR, USC and RBWH) will enable patient recruitment and salvaged sample collection by an experienced exemplar ICS team and a 2-step analysis approach (i.e., firstly a ThinPrep™ CytoLyt™ Solution test and analysis of adenocarcinoma cell count using flow cytometry and blood cultures to assess bacterial contamination). Importantly multiple confounding factors present in transfusion research will be considered; with senior biostatistical support.
Significance
Intraoperative haemorrhage during pelvic exenteration surgery can be sudden, rapid and catastrophic, often requiring massive blood product transfusion; a recent audit at the RBWH (2015-2019; n=69) confirmed a mean intraoperative blood loss of > 3000mL and mean packed red blood cell (pRBC) requirement of 6 units per patient (unpublished data, used with permission here). Authors within this grant application recently (2022) published an in-depth literature review (book chapter) considering clinical outcomes after many surgeries where ICS was previously deemed unsafe. During many of these procedures ICS (compared to ABT) did not increase clinical cancer recurrence or infection risks. However, despite this evidence, clinicians remain cautious and mostly avoid ICS during procedures with perceived cancer and bacterial contamination risks. It is now essential to develop technology and define areas (e.g., surgical sub-specialties and relevant cancer cells etc.) where ICS use could potentially be safe. Therefore, robust research into laboratory methods, and precise ICS technique (e.g., LDF technology) as proposed in this study, could provide more clarity, from a scientific / laboratory science point of view, to potentially encourage ICS use. The use of ICS during procedures with major haemorrhage is feasible and beneficial but avoided due to perceived cancer and infection risks. We recently confirmed that 10.8% (119/1176, 2022) of cancer procedures at the RBWH, where ICS is avoided due to these perceived risks, require transfusion. Results from this pilot study will be used to refine methods, and to gather information to support a larger future clinical trial.
Likely benefits of the research
The expected benefits to the community and the potential opportunity to use ICS in Australia is substantial, considering that each year; a) >630,000 units of packed red blood cells are issued, b) fresh blood expenditure exceed $620.7m, with an average annual growth of 6.6%. An estimated 1,300 surgical patients at the RBWH require blood transfusion each year.
References
1. Roets M, Sturgess DJ, Wyssusek K, van Zundert AA: Intraoperative cell salvage: A technology built upon the failures, fads and fashions of blood transfusion. Anaesthesia and Intensive Care 2019; 47: 17-30
2. Roets M, Sturgess DJ, Obeysekera MP, Tran TV, Wyssusek KH, Punnasseril JEJ, da Silva D, van Zundert A, Perros AJ, Tung JP: Intraoperative Cell Salvage as an Alternative to Allogeneic (Donated) Blood Transfusion: A Prospective Observational Evaluation of the Immune Response Profile. Cell Transplantation (Cell Transplant) 2020; 29: 0963689720966265.
3. Carless PA, Henry DA, Moxey AJ, O'Connell D, Brown T, Fergusson DA: Cell salvage for minimising perioperative allogeneic blood transfusion. Cochrane Database of Systematic Reviews 2010; Apr 14: Cd001888.
4. DeAndrade D, Waters JH, Triulzi DJ, Alarcon L, Wisniewski MK, Dyga R, Yazer MH: Very low rate of patient‐related adverse events associated with the use of intraoperative cell salvage. Transfusion 2016; 56: 2768-2772
Dr Michelle Roets, Dr Angela Tognolini, Dr Craig Harris, Dr Mahendra Singh,
Royal Brisbane and Women’s Hospital, Queensland
Dr Melinda Dean, University of the Sunshine Coast, Queensland
Associate Professor Peter Simpson, Dr Andrew Dalley,
University of Queensland Centre for Clinical Research
Associate Professor David Sturgess, Surgical Treatment and Rehabilitation Service, Brisbane.
The project was awarded A$66,231 funding through the ANZCA research grants program for 2024.