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

For perfusionists, useful, relevant data is essential. Real-time data, with the capability to view and review events recorded at any time during a procedure, can be even more useful. Ideally, real-time perfusion systems capture, analyze, and report data—especially unexpected or abnormal parameters—back to a clinician, at or near the moment they occur in the patient’s body. In this way, valuable, life-saving alert systems can be developed.

Real-time alert systems are especially useful in clinical situations where a patient’s condition can change within seconds or minutes, such as during cardiopulmonary bypass (CPB) surgery. Other scenarios where physiologic conditions fluctuate and change rapidly include critical care and emergency units. Real-time clinical data obtained in all these areas can be used to improve the quality of care.

Additionally, this type of data adds substantial value to any patient’s electronic health record (EHR). By the same token, the EHR may be the vehicle upon which funding for real-time systems may be procured.  

Real-Time, Real World

How does real-time monitoring affect the quality of care? More and more ECMO teams are using real-time patient monitoring on mobile devices to effectively deliver optimal patient outcomes. Timely alerts and automatic updates to the patient’s medical record are proven to be beneficial in the support of clinical needs as ECMO therapy requires constant supervision and vigilant safeguards for long periods of time.

The average reaction time in the group using the alerts was 3.6 seconds. The average reaction time in the control group was nearly ten times longer than the group using computer-assisted, real-time data feedback.

For continuous blood gas measurement, another study revealed blood gas levels of CPB patients in the continuous monitoring group were able to be maintained in accordance with protocol a greater percentage of the time (e.g. pCO2 management was 20% versus 2% in the control group).

Electronic Health Records & Funding Real-Time Initiatives

A wide range of real-time perfusion monitoring systems exist, and they all provide interconnectivity to electronic medical (health) record (EMR or EHR) systems via WiFi, Ethernet, or other wire-based network connections. The system used in the Columbia study enables compliance alerts for parameters, such as mean arterial pressure, temperature flow, cardiac index, blood gases, saturation, Hct, PO2, and CO2.

While fidelity to electronic health records is vital in the modern age, interconnectivity can also be leveraged into funding sources.

Since 2011, the Centers for Medicare & Medicaid services established the Medicare and Medicaid EHR Incentive Programs. Stage 2 focuses “on advancing clinical processes and ensuring that the meaningful use of EHRs supports the aims and priorities of the National Quality Strategy. Stage 2 criteria encouraged the use of CEHRT for continuous quality improvement at the point of care and the exchange of information in the most structured format possible.”

In this context, real-time monitoring solutions are an attractive option to improve perfusionist performance, impact the quality of care, and modernize any health care center’s cardiopulmonary bypass-based services.

Article references:

Will Real-Time Monitoring Technology be a Game Changer for Perfusion Safety? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474898/

Real-time data acquisition and alerts may reduce reaction time and improve perfusionist performance during cardiopulmonary bypass https://journals.sagepub.com/doi/abs/10.1177/0267659114548257

Category

Improving Patient Outcomes with Better Quality Control Measures

According to a 2016 study published in Health Affairs, $15.4 billion is spent by the medical industry each year on reporting quality measures. Even with this being the case, though, current quality control measures are simply not doing enough to improve patient outcomes.

In this article, we’ll take a look at where current quality control measures are falling short and how better quality control can be used to improve the quality of care and promote better patient outcomes.

The Shortfalls of Current Quality Control Measures

As it currently stands, the medical industry’s approach to quality measurement is both expensive and time-consuming. What’s worse, though, is the fact that it delivers insufficient results. According to the same 2016 study cited above, a majority of physicians do not trust the current quality control measures and do not use those measures to guide their patient care practices.

A big part of the reason why the current quality control measures deliver insufficient data is the fact that they do not consider information such as ambulatory care, patient-reported outcome measures, and other key sources of data. The end result is a quality control system that is both expensive and time-consuming, but not one that delivers what is truly needed to improve patient outcomes via quality control measures.

How Quality Control Measures can be Improved

At this point, it is clear that new quality control measures need to be developed. Simply developing new quality control measures alone, though, is not enough. In addition to developing quality control measures that are able to capture the full scope of what needs to be measured and improved, it’s essential to also translate those new measures into better patient care. This can be done in four essential ways:

  • Introducing more quality control measures that are actually relevant and useful in a clinical setting.
  • Working to increase buy-in from physicians.
  • Investing in more tools and putting more effort into taking full advantage of quality control measures.
  • Working to demonstrate improvement in clinically relevant measures.

Developing quality control measures that are more clinically relevant is certainly a great place to start. A new set of standards for quality measures – one that actually prioritizes patient outcomes and one that delivers relevant and actionable data – needs to be developed.

Once this new set of standards is developed, increasing buy-in from physicians and encouraging them to take advantage of quality control data to improve their care is vital if better quality control measures are actually going to translate into better patient outcomes.

Developing a better set of quality control measure standards and working to get physicians on-board with these new standards will pave the way for more investment into quality control tools and more effort being placed into using quality control in order to improve a facility’s quality of care. If all of these things are down, demonstrating the effectiveness of quality control and showcasing real, quantifiable improvement will solidify this new system of quality control and reward medical facilities for their investment.

How to Begin Improving Your Facility’s Quality Control Measures

As you can see, there is much work to be done before quality control measures are able to be used to their full potential for bettering patient outcomes. If you would like to begin taking better advantage of quality measures, though, it certainly isn’t too early to start. To learn more about how we can help you leverage the latest advances in quality control measures to improve patient outcomes at your facility, feel free to contact us today.

Source:

Improving Quality Measures Can Lead to Better Outcomes: https://www.healthcatalyst.com/insights/better-quality-measures-can-improve-patient-care

Category

Utilizing qualitative research to improve clinical outcomes.

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

Category

Paving the way to improve patient safety and quality of Perfusion Services.

Kevin McCusker Ph.D., MSc, CCP, Chief Research Scientist Professor Serdar Gunaydin M.D, Ph.D.

Fundamentally, science is not a competition or a zero-sum game; it is neither a chess match nor a wrestling contest. It is an infinite-sum game from which we all benefit. The outcome of the scientific process is not up to the practitioners since reality is set by nature itself –no negotiating. Scientists aim to figure out what reality is by collecting as much evidence as we can. We argue with each other about possible interpretations when the evidence is limited, but we do so only as spectators of a show that we were never responsible for in the first place. The scientific process may remind us of Michelangelo. When asked how he produced beautiful sculptures from a featureless block of marble, he replied: “It is already there, I just have to chisel away the superfluous material.” Similarly, science uses evidence to “chisel away” the superfluous hypotheses which are ruled out by the data we acquire. When we focus our view this way, it is a work of art.

I wish to reintroduce ourselves, I am Kevin McCusker Ph.D., CCP, I have been a clinical perfusionist for 32 years, and an Assistant Professor of Surgery at New York Medical College in Valhalla, New York. My research partner for the past 25 years has been Professor Serdar Gunaydin M.D., Ph.D. who is a Cardio-Thoracic Surgeon in Ankara, Turkey. Over the past two decades, we have researched and published our findings in many areas, such as biocompatible coatings, leukocyte filtration, condensed cardiopulmonary bypass circuitry, membrane oxygenators, polymer coatings, cardioplegia solutions, fibrin sealants, and blood management techniques.

From time to time, we would like to highlight and share our recent research findings here on this webpage. This will allow us to have a forum to share our studies with everyone and also hopefully stimulate others to join us in any of our new laboratory and clinical studies.

Our latest study covers “Long Term Protective Effects of Single/Multi-dose Cardioplegic Solutions in Cell Culture Models”

Objective: Despite the popularity of single-dose cardioplegic techniques, the time window and targeted population for successful reperfusion remain unclear. We tested currently available techniques based on cell viability and integrity to demonstrate long-term cardioprotection and clarify whether these solutions were acting better on neonatal/adult endothelium or myocardium examining different cell lines.

Methods: 
Cell viability with MTT proliferation assay until 48 h and membrane integrity (LDH test) until 24 h were documented in a cell culture setting and microscopy on adult cells (HUVEC-human umbilical vein endothelium), neonatal (H9C2-cardiomyocytes) and myofibroblasts (L929). After 24-hour seeding, cells were incubated in control (Dulbecco’s Modified Eagle), St. Thomas, blood cardioplegia (4:1), Histidine-Tryptophan-Ketoglutarate (HTK) and Del Nido solutions at 34 °C for 2 h followed by an additional 6, 24, and 48 h in standard conditions (37 °C, 5% CO2). All wells were filled with related cardioplegic solutions (200 microliters). Experiments were repeated eight times.

Results: 
Cultured L929 (2×104 cells/ml), HUVEC (2×10cells/ml), and H9C2 (5×103 cells/ml) were seeded in 96-well plates for MTT analysis and in 24-well plates for Acridine-Orange (AO) and Propidium Iodide (PI) double staining microscopy. For LDH evaluation, 5×10cells/ml from each group were allowed to attach for 24 h, then exposed to cardioplegic solutions at 34°C for 2 hours, followed by 24 h incubation. When reporting viability results, levels better than control were accepted as significant since the control solution is a media for cell culture. For LDH, higher levels noted higher disintegration (Fig 1)(*: p<0.05 with respect to control).

Conclusions: 
Experimental works on cardioplegia aiming to assess cardioprotection use time-consuming and often expensive approaches that are unrealistic in clinical practice. We have focused on the direct cellular effects of different cardioplegia solutions and documented long-term effects that we believe are the most underestimated facts about cardioplegia topics in the literature.

Please feel free to reach out to Professor Gunaydin MD, Ph.D., and me, Kevin McCusker Ph.D., MSc., CCP, with any questions or ideas towards research projects.

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

Category

Scientist-Perfusionists convert scientific findings into clinically relevant applications.

Kevin McCusker Ph.D., MSc, CCP, Chief Research Scientist

Professor Serdar Gunaydin M.D, Ph.D.

Traditionally, scientists have bridged the gap between the clinic and the laboratory. Scientist-Perfusionists now hold professional degrees related to clinical care (i.e., Ph.D., CCP, RN, RRT, and MT) but spend most of their time in the clinical arena. Through our unique combination of clinical and research experience, we look for insight into the molecular discordance that underlies disease etiology. Scientists-Perfusionist convert scientific findings into clinically relevant applications and elucidate the mechanisms that cause clinical problems. A relative decline in the scientist-perfusionist population threatens cross-talk between the laboratory and clinic. Researchers are less aware of potential clinical implications for molecular discoveries and are not privy to the clinical observations and needs that fuel clinically relevant research. The flow of information between the lab and clinic slows. Professor Gunaydin and I worry that perfusionist-scientists will become scarcer in the future, restricting this information stream to a trickle. With fewer perfusionist-scientists to intercede, cultural and professional differences between perfusionists and researchers may compromise the flow of information between these worlds, widening the current rift. With these thoughts in mind, we would like to present another of our recent studies; please feel free to comment directly to us with any additional ideas or thoughts towards furthering our studies.

Protective Efficacy of Minimally Invasive Techniques on Endothelial Glycocalyx In Aortic Valve Surgery”


Objective:
The endothelial glycocalyx (EG) is fundamentally involved in numerous physiologic and pathophysiologic actions in the circulatory system. The present study aimed to compare plasma levels of syndecan-1, a biomarker of EG integrity, in patients undergoing minimally invasive aortic valve surgery compared to conventional techniques verified by cell culture.

Methods: This prospective cohort study included high-risk patients (Euroscore II >5) undergoing aortic valve surgery between January 2016 and November 2018: Group 1: Minimally Invasive Technique (N=85) and Group 2 (control) N=89. The approach was hemi-median sternotomy and single-dose cardioplegia in Group 1 and full sternotomy with intermittent crystalloid cardioplegia in control. Serum Syndecan-1 levels were measured by ELISA via arterial line before (T1) and via coronary sinus sample at the end of the cardiopulmonary bypass (CPB) (T2). A right atrial specimen is collected before and at the end of CPB in each case and processed. Cells were incubated with LPS in culture medium with 2% FCS until 24 h and were routinely grown to 80%-90% confluence.

Results: There was not a significant difference between the groups with respect to demographic data, BMI, and the change in the troponin-I levels at T1 and T2 (p = 0.162). Post­operative hemorrhage (Group 1: 260 ± 30 and 895 ± 50 mL in control; p=0.032), respiratory support duration (9.5 ± 2 /18 ± 2 h- p=0.041) and ICU stay (1.2±1 vs 2.4±1 days, p=0.045) were significantly better in the Group 1 vs control. No difference in mortality and major complications was noted. Cross clamp time was 71.4±10 in Group 1 and 85±10 min for control (p=0.042). Serum Syndecan-1 concentration is summarized in Table. Microscopic imaging confirmed the quantitative results of Syndecan-1 dying with significantly better confluences in a minimally invasive group vs. control (11650± 3400 vs16450± 3200 RFU, p=0.028).

Conclusion: Given its importance, the protection of the EG is undoubtedly a promising future target in cardiac operations. Our data underline the impact of minimally invasive techniques verified by cellular function. A possible association between elevated syndecan-1 levels and postoperative complications needs to be clarified in more extensive studies. LEGEND: Quantitative Assessment of EG shedding in groups.

Please feel free to contact Professor Gunaydin and me at any time.

 

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