Since the early days of transplant medicine, the parallel practice of organ preservation branched off into a separate science and field of research. The primary goal of mechanical perfusion and oxygenation is to protect organs from the consequences of hypoxia for as long as possible until transplantation can occur.

Cooling is an obvious method to reduce metabolic demand. The ability to apply appropriate cold temperature ex vivo, in ways that could be readily reversed, has led to considerable research and development. Now, flush cooling and ice storage with synthetic preservation solutions have become the most widely used method and have allowed for cost-effective, multiple retrievals from a single donor. 

For years, static cold storage has dominated clinical preservation practices, but currently, there is growing interest in more dynamic strategies that implement perfusion. Although this method is by no means new, current interest is driven by changing donor demographics, new potential clinical applications, and the need to utilize all available organs for transplantation to meet rising demand.

Perfusion Based Organ Preservation Research

Organ preservation, using continuous mechanical perfusion with blood-based or bloodless perfusates has been an active field of research for years. Beyond simply extending its viability beyond 24 hours (the standard for cold-storage techniques), the research reveals other benefits that perfusion methods might offer.

One recent study out of the Department of Surgery and Transplantation, Swiss Hepato-Pancreato-Biliary (HPB) Center, University Hospital Zurich, Zurich, Switzerland reveals that integrated mechanical perfusion and oxygenation can preserve injured human livers for one week.

Study Design 

Given that organs can usually be delivered within 24 hours to the operating table, what are the advantages of preserving them for longer time frames? The authors of the Zurich study highlight there is a high reject rate due to damage or injury. However, if the body parts could be kept viable and nursed to recovery, they could potentially increase the pool of donors.

The study included the development of specialized perfusion and oxygenation equipment equipped with intravascular pressure and blood gas tension monitoring in addition to a dialysis unit for physiologic electrolyte balance and removal of metabolic waste products from the blood. 

An algorithm was used to automatically adjust the dialysate flow, controlling the concentration of red blood cells (hematocrit) based on continuous measurements. Automated insulin and glucagon administration was used to maintain physiological blood glucose levels (targeted range of 3.5–6.5 mmol l−1).

To simulate diaphragmatic liver movement in the ex vivo system, they were placed on a silicone mat. An inflatable balloon was positioned beneath the mat and connected to an air oscillator to induce movement that mimics diaphragm motion which in turn helps prevent pressure necrosis.

Mechanical perfusion: Study Results & Potential Clinical Applications

After seven-day perfusion, six of the human livers showed preserved function as indicated by bile production, coagulation factor synthesis, maintained cellular energy (ATP), and an intact structure.

As the authors state, with additional research, multiple potential benefits could be realized with extended organ perfusion technology, such as:

  • Repair of damaged or diseased organs to be transplanted later.
  • Graft immunogenicity modification to induce tolerance. 
  • Treatment of tumors with chemotherapeutic agents that are too toxic for systemic use.
  • Safe transport over long distances to improve global sharing.
  • Liver regeneration, divided into segments to regrow ex vivo. Such an approach could double or even triple availability. 
  • Partial grafts for auto-transplantation in patients with liver cancer, obviating the need for immune suppression.

Article References:

Organ Preservation into the 2020s: The Era of Dynamic Intervention

https://www.karger.com/Article/FullText/499610#ref19

An integrated perfusion machine preserves injured human livers for 1 week

https://www.nature.com/articles/s41587-019-0374-x

The fundamental purpose of qualitative research is to understand better why a particular group behaves as it does. The numbers produced by quantitative research only scratch the surface of these types of questions, being more about learning which sub-groups are essential and how much they may vary in behaviors and responses. In comparison, qualitative research is much better at getting at the ‘hows’ and ‘whys’ that are so important to in-depth knowledge.

First, you select a particular population to study. It can be any group with some level of shared experience. Second, you need to collect some free-form data from (or about) a representative sample of that population. Third, you want to record any potentially relevant information about the sources of that data: age, ethnicity, sex, previous ailments – you name it. Fourth, it is time to highlight the most relevant sections of that qualitative data, have a preliminary perhaps coding each excerpt for the degree to which it supports or refutes a particular theme. These themes can be questions you now want to investigate upfront or questions that the excerpts themselves suggest during your study. This step will be based mainly on the project’s research methodology. If any CCS perfusionists are interested in formulating a study or wish to discuss examining a specific study group, please reach out to Professor Gunaydin or me at any time.

We thought this week’s topic would cover our recent pediatric study and publication, and we hope you enjoy the reading. A STRUCTURED BLOOD CONSERVATION PROGRAM IN PEDIATRIC CARDIAC SURGERY: More Is Better”

Background: The limitation of alternative transfusion practices in infants increases the benefits of blood conservation. We analyzed the efficacy of a structured program to reduce transfusions and transfusion-associated complications in cardiac surgery

Methods: Our pediatric surgery database was reviewed retrospectively, comparing outcomes from two different time periods, after the implementation of an effective blood conservation program beginning in March 2014.  A total of 214 infants (8.1±3.4 months) who underwent biventricular repair utilizing CPB (Group1-Blood conservation) were studied in 12 months (March 2014-February 2015) after the implementation of the new program and compared with 250 infants (7.91±3.2 months) (Group 2-Control-No blood conservation) of the previous 12-month period (March 2013-February 2014).

Results: The proportion of patients transfused with red blood cells was 75.2% (N=188) in the control group and reduced by 16.4% in the study group (58.8%- 126 patients, p <0.01). The mean number of transfusions was 1.25 ± 0.5 units per patient in the control group and decreased to 0.7 ± 0.5 units per patient after the start of the program (P = 0.035). Cerebral oximetry demonstrated better follow-up during the operative period confirming less hemodilution in Group 1. Respiratory support, inotropic need, and ICU stay were significantly better in the study group.

Conclusion: These findings, in addition to attendant risks and side effects of blood transfusion and the rising cost of safer blood products, justify blood conservation in pediatric cardiac operations. Circuit miniaturization, ultrafiltration, and reduced postoperative bleeding, presumably secondary to higher fibrinogen and other coagulation factor levels, contributed to this outcome.

Kevin McCusker Ph.D., MSc., CCP
Assistant Professor of Surgery
New York Medical College
Valhalla, New York 10575                                                          

Serdar Gunaydin M.D., Ph.D.
Professor of Surgery
University of Health Sciences
Ankara, Turkey