Perfusion Technology Research Articles

Are Perfusion Technology and Perfusionists Ready for Quality Reporting Employing Six-Sigma Performance Measurement?

Are Perfusion Technology and Perfusionists Ready for Quality Reporting Employing Six-Sigma Performance Measurement?

Expanding the role of perfusionists in the era of new treatment options for cardiovascular disease.

Treatment for cardiovascular disease has dramatically changed the surgical patient population over the past 10 years. Advances in medical management and interventional cardiovascular procedures have delayed surgery in many adults, and the surgical pool has begun to decrease despite an aging population. This affects perfusionists in terms of new psychological and technical challenges, and has serious consequences and implications for the future of the profession. This study will review the changing patterns of diagnosis and treatment of cardiovascular disease in the USA over the past 10 years by examining the annual surgical procedure rates and correlating them with the number of practicing perfusionists and new student graduates. The purpose of this review is to project the future employment opportunities for perfusionists. The second part of the paper will look at the alternative roles perfusionists have expanded into as a result of changes in the treatment of cardiovascular disease. The results of an e-mail survey of perfusionists will be presented to identify new applications of perfusion technology.

After biocompatibility and advances in perfusion techniques and technologies

After biocompatibility and advances in perfusion techniques and technologies

The evolution of cardiopulmonary bypass: lessons to be learned.

John Gibbon conceived cardiopulmonary bypass (CPB) and performed the first intracardiac repair using extracorporeal perfusion in 1953. This achievement stimulated rapid development of the knowledge base and equipment necessary for accurate diagnoses and successful intracardiac operations. In the early 60s increasing evidence indicated that exposure of blood to nonendothelial cell surfaces produced bleeding and thrombotic complications and a massive inflammatory response. Early efforts to discover a synthetic, nonthrombogenic surface gave way to efforts to control the 'whole-body inflammatory response' by pharmacological means. These efforts are ongoing; progress is slow; and heparin is still required for most applications of extracorporeal perfusion technology. Nevertheless, CPB now enables over one million cardiac surgical operations each year. Future progress and the development of artificial internal organs that process blood depend upon control of the blood-surface interface without anticoagulants.

Successful extracorporeal porcine liver perfusion for 72 hr.

Improvements in extracorporeal perfusion technology and the production of transgenic pigs resistant to hyperacute rejection have stimulated several groups to re-explore the possibility of supporting patients in hepatic failure with extracorporeal porcine livers. The success of organ transplantation has also stimulated interest in using extracorporeal perfusion as a means of organ preservation and resuscitation of organs from marginal donors. The present study describes a method by which livers can be maintained in a viable condition for a minimum of 72 hr of normothermic, extracorporeal perfusion. Five extracorporeal porcine liver perfusions were performed, each with a duration of 72 hr. Hepatectomy was performed, followed by cold preservation, cannulation of vessels, and initiation of perfusion with normothermic, oxygenated porcine blood. Organ viability was assessed by metabolic, synthetic, hemodynamic, and histologic parameters. After 72 hr of normothermic, extracorporeal perfusion, the isolated livers demonstrated maintenance of normal physiological levels of pH and electrolytes. Continued hepatic protein synthesis (complement and factor V) was maintained throughout the perfusion. Hemodynamic parameters remained within normal physiological range. Histology demonstrated good preservation of the liver with no overall architectural change. It is possible to maintain a liver in a viable condition for a minimum of 72 hr of extracorporeal perfusion. This technique has been developed primarily as a preclinical model of extracorporeal liver support with the intention of proceeding to a clinical trial in patients with fulminant liver failure. However, it also has potential applications in organ preservation or resuscitation before transplantation and in the experimental study of isolated liver physiology.

“Change in the wind”: report from the 2000 Thoracic Surgery Directors Association Retreat on Thoracic Surgery Graduate Medical Education

In October, 1999, the American Board of Thoracic Surgery (ABTS) resolved that “the ABTS change current policy regarding American Board of Surgery (ABS) certification so that at a point in the future, yet to be determined, ABS certification will become optional.” This position was taken by the ABTS after exhaustive study and debate of the relevant issues and of evolving data pertinent to Thoracic Surgery Graduate Medical Education (TSGME), a topic of three major conferences in the last decade 1 and of the addresses of seven thoracic societal presidents, four of them in the last 6 years. Among the most provocative points that were considered by the Board were: (1) The vast expansion of fundamental knowledge and of operative approaches to cardiothoracic diseases currently required to educate the TS resident in a time-frame essentially unchanged since formal education in TS began in 1928; (2) a total duration of medical school and of GME that obligates the thoracic surgeon entering practice to be older, as compared to peers in other professions, and to be constrained by greater indebtedness; (3) a disturbingly diminished pool of applicants to TS residencies, with fewer US medical graduates applying than residency positions to fill; and (4) diminishing funding for TSGME occurring concomitantly with increasing financial burdens on academic thoracic surgery programs. The specific intent of the ABTS was to facilitate change if change were to be the desire of thoracic surgery educators and of the other parties in organized thoracic surgery vested with interest in, and responsibility for, the process and product of TSGME.

Noninvasive Diagnostic Testing of Coronary Artery Disease in Women

Noninvasive diagnostic testing of coronary artery disease (CAD) is widely recognized as an area that is less studied and less accurate with regard to women than to men. Accurate and safe diagnostic testing constitutes the crucial link between early detection and optimal management of CAD. Many noninvasive diagnostic modalities are available to the clinician, including traditional electrocardiography, the relatively novel imaging of echocardiography, the emerging nuclear perfusion technology of electron beam computed tomography, exercise testing, and pharmacologic testing. The most accurate and cost-effective diagnostic method for patients depends on the patients' pretest likelihood of the disease as determined by factors such as sex, age, and cardiovascular risk factors. Noninvasive tests are most useful in the diagnosis of CAD in patients with intermediate pretest likelihood of CAD. Patients with low pretest likelihood of CAD with normal electrocardiograms may benefit from noninvasive tests or a watchful waiting strategy. Patients with a high pretest likelihood of CAD may benefit greatly from direct referral to coronary angiography. Among the noninvasive diagnostic methods, exercise electrocardiography is the most studied and least accurate with regard to women patients. Electrocardiography improves in accuracy when combined with imaging techniques such as echocardiography or nuclear single photon emission computed tomography. Combining data from all studies has shown that exercise echocardiography yields the highest diagnostic accuracy in women among all of the exercise stress tests. Patients who are unable to achieve maximal exercise capacity may undergo pharmacologic testing using dipyridamole or adenosine radionuclide perfusion or dobutamine echocardiography. Recent development of electron beam computed tomography accurately detects coronary artery calcium but has not been validated yet as a standard diagnostic test for CAD.

CARDIOPULMONARY AND CEREBRAL RESUSCITATION

The future of cardiopulmonary resuscitation lies in new technologies for monitoring and generating vital organ perfusion during cardiac arrest and the post-resuscitation phase and in pharmacologic agents that will enhance ROSC and reverse ischemia-reperfusion injury. ROSC is the first step toward survival, so interventions that improve ROSC deserve further investigation. Long-term survival with good neurologic recovery is the critical endpoint. Interventions recommended for clinical practice must therefore demonstrate improved long-term survival. The resources required to provide many of the interventions discussed in this article, principally invasive perfusion technologies, cannot be justified unless there is clear benefit. The allocation of such resources to provide intensive resuscitation and post-resuscitation support will need to be addressed from medical and societal viewpoints.

Minimally invasive cardiac operation: adapting cardioprotective strategies

Background. Minimally invasive heart operation differs from traditional cardiac operations through the omission of a sternotomy, cardiopulmonary bypass, or both. Current concerns with minimally invasive operation include: operative safety, learning curve, operative times, arrest times, and adequacy of myocardial protection. While many of the protective strategies used for traditional procedures may be applied to minimally invasive cardiac operations, the safe applications of minimally invasive operations require unique techniques of myocardial protection.Methods and Results. Omission of extracorporeal perfusion may benefit patients through attenuation of systemic inflammatory response, decrement in neurologic insults, and reduced bleeding complications. As a counterbalance, surgeons must consider long-term operative quality and level of myocardial protection provided during beating heart coronary operation. Current issues that must be addressed include: pharmacologic management, coronary collateralization and ischemic preconditioning, the utility of intraluminal coronary shunts, and technical adequacy of the anastomosis. Nonsternotomy cardiopulmonary bypass methods utilize alternative incisions and “port-access” technology, and may render more rapid patient recovery including: decreased pain, shortened hospital stay, and more rapid return to work. Altered strategies of myocardial protection in a closed chest environment must address: method of cannulation, technique of aortic occlusion, rapidity and maintenance of cardiac arrest, and cardiac de-airing techniques.Conclusions. Previous obstacles to minimally invasive cardiac operations included limitations in operative exposure, inadequate perfusion technology, and inability to provide myocardial protection. Recent advances in videoscopic visualization and evolving mechanisms of myocardial protection may justify the expanding application of minimally invasive techniques.

Perfusion Education in the United States at the Turn of the Century

The challenges facing institutions charged with the delivery of health care have also affected the delivery of education in the health sciences. In the 30 years since the establishment of a process for formalized perfusion education, significant changes have shaped how the fundamentals of perfusion sciences are learned. The establishment and maintenance of a profession can only be secured through the creation of standards that guide educational facilities in the delivery of formalized instruction in a discipline. Perfusion education programs continue to meet these standards but are doing so at a time where resources continue to dwindle and quantitative assessment of manpower issues are fuzzy, at best. The peak of perfusion education programs occurred in 1994, and 5 years later only 25 programs were still accredited by the Committee on Accreditation of Allied Health Programs (CAAHEP). In the past decade, only one new education program has sought accreditation from CAAHEP. There were 41% fewer graduates in the United States in 1998 than in 1992, which follows a 6-year trend in declining numbers of individuals entering the field of perfusion. Individual programs are challenged by the reordering of university and community hospital structures, which often results in critical reviews of resource allocation to perfusion programs. The health of the perfusion profession remains deeply tied to the success of perfusion education programs. Likewise, the health of these programs can only be assured by means of continued solicitation of support and guidance from practitioners who serve as stewards of perfusion technology.

Short-term neuropsychologic differences after normothermic versus hypothermic cardiopulmonary bypass

Short-term neuropsychologic differences after normothermic versus hypothermic cardiopulmonary bypass

Port-access cardiac operations with cardioplegic arrest

A less invasive approach to cardiac surgery has been propelled by recent advances in video-assisted surgery. Previous obstacles to minimally invasive cardiac operations with cardioplegic arrest included limitations in operative exposure, inadequate perfusion technology, and inability to provide myocardial protection. Port-access technology allows endovascular aortic occlusion, cardioplegia delivery, and left ventricular decompression. The endoaortic clamp is a triple-lumen catheter with an inflatable balloon at its distal end. Antegrade cardioplegia is delivered through a central lumen, which also acts as an aortic root vent, a second lumen is used as an aortic root pressure monitor, and a third lumen is used for balloon inflation to provide aortic occlusion. Experimental and clinical studies have demonstrated the feasibility of port-access coronary artery bypass grafting and port-access mitral valve procedures. Endovascular cardiopulmonary bypass using the endoaortic clamp was effective in achieving cardiac arrest and myocardial protection to allow internal mammary artery to coronary artery anastomosis in a still and bloodless field. Intracardiac procedures, such as mitral valve replacement or repair, have been successfully performed clinically. The port-access system effectively achieves cardiopulmonary bypass and cardioplegic arrest, thereby enabling the surgeon to perform cardiac procedures in a minimally invasive fashion. This system provides for endovascular aortic occlusion, cardioplegia delivery, and left ventricular decompression.

Perfusion therapy to reduce myocardial ischemia en route to emergency coronary artery bypass grafting for failed percutaneous transluminal coronary angioplasty.

Despite improvements in operator technique, catheter technology, and the development of new devices, emergency coronary artery bypass grafting (CABG) is still required in 1%-4% of attempted catheter based revascularization procedures. Patients who require such emergency CABG after failed percutaneous transluminal coronary angioplasty (PTCA) have worse acute outcomes than those undergoing elective CABG, with a higher incidence of Q wave myocardial infarction (MI) and a higher operative mortality. In patients with otherwise refractory abrupt closure, maintenance of antegrade coronary blood flow using perfusion catheters lessens the incidence of Q wave MI and lowers peak creatinine phosphokinase. Direct maintenance of coronary flow thus appears to provide more definitive control of myocardial ischemia than purely adjunctive measures, such as intra-aortic balloon pumping, cardiopulmonary support, or coronary sinus retroperfusion. Although the recent introduction of coronary stents holds great promise for definitive percutaneous reversal of abrupt closure and a dramatic decrease in the incidence of emergency CABG for failed PTCA, maintenance of antegrade flow via perfusion technology remains the cornerstone of management in reducing the perioperative mortality and morbidity of patients who still require emergency bypass surgery after failed PTCA.

Future paradigm for autologous bone marrow transplantation: tumor purging and ex vivo production of normal stem and progenitor cells.

A major concern in autologous bone marrow transplantation (ABMT) is the possible contamination of the graft with tumor cells. Transplantation of malignant cells, along with normal hematopoietic stem and progenitor cells, may contribute to relapse of disease. Therefore, a growing strategy is to subject autologous marrow to some type of purging procedure to eliminate tumor cells selectively. Transplantation of purged marrow, however, often results in a delayed engraftment associated with (specific or nonspecific) loss of normal stem and progenitor cells during manipulations related to the purging process. A new and burgeoning field in the area of clinical bone marrow transplantation is the ex vivo production of stem and progenitor cells. Several advantages accrue to this strategy. First, this technology makes it possible to expand the stem and progenitor cell population of a small volume of bone marrow or mobilized peripheral blood (MPB), thus lessening the initial tumor burden to be purged. Secondly, ex vivo marrow or MPB expansion may overcome the significant problem of delayed engraftment by rebuilding the numbers of normal stem and progenitor cells necessary for both early and durable engraftment. To accomplish these and other objectives, an automated and closed, clinical-scale bioreactor system, based on continuous perfusion technology, is being developed and will soon enter clinical trials.

Reoperation, Emergency and Urgent Open Cardiac Surgery in Jehovah's Witnesses

Progressive advances in perfusion technology and perioperative supportive management have made it possible for members of the Jehovah's Witnesses religious group to undergo open cardiac operations with remarkable safety. However, hospital mortality remains high in (1) patients requiring reoperation (in whom both technical and bleeding problems tend to be more frequent) and (2) patients with significantly compromised cardiac performance requiring urgent or emergency operation. Employing a number of perioperative measures designed to minimize blood loss and maintain hematocrit levels (including use of the recently available recombinant human erythropoietin in two patients whose cases are reported herein), 13 reoperations and five urgent or emergency operations were performed. The one death in the entire series occurred in a patient (reoperation group) who died of a cerebrovascular accident of presumed embolic etiology, having undergone combined debridement of a stenotic heavily calcified aortic valve and a second coronary artery revascularization procedure. None of the patients required surgical exploration for bleeding. We suggest that currently available methodology permits Jehovah's Witnesses to undergo reoperation, emergency surgery, or urgent open cardiac operation at a level of risk not dissimilar to that seen in patients who permit use of homologous blood and products in their treatment.

Motivating Adult Learners with Effective feedback

Although students are ultimately responsible for their own motivation, instructors can use techniques of goalsetting and clear, constructive negative and positive feedback to give learners an accurate sense of their own competence and to help stimulate them to reach their full potential. Many perfusion technology instructors fail to use these techniques effectively. Clinical objectives are devised in such a way to make it immediately clear whether the student’s performance measures up. The learner, the instructor or both can develop these job-oriented objectives. Some believe that feedback is the number one motivator of people. Negative and positive feedback techniques and ways to defuse defensiveness are discussed. Feedback should be objective, timely, accurate and based on first-hand data. Feedback should be focused on the behavior, not the person. “Gunnysacking,” “pimping” and other destructive feedback should be avoided because evidence suggests that it de-motivates adult learners. Any emotional response on the part of the instructor should be communicated in an “I message.” Feedback provided to students should deal with specific behaviors, not generalizations. Self-assessment and life-long learning skills can be fostered in learners by asking them to appraise their own performance and suggest ways they think such performance might be improved.

Safety and economic aspects of continuous mammalian cell culture

Mammalian cell cultures are the most appropriate host cells for recombinant DNA derived products if complex protein structures have to be synthesized in their native form. Due to their physiological behaviour they grow either adherent or in suspension. For the attachment of adherent cells, microcarriers or wire springs can be applied to increase the internal surface of the bioreactor. Both systems provide a simplified media exchange but, however, show some limitations in scale up. In contrast, suspension culture systems as homogeneous systems independent of any carrier have not shown any limitation in scale up. Because most cell lines which are of commercial interest grow in suspension, this technology is best advanced and used in batch and continuous mode. Although mammalian cell cultures are sensitive to hydrodynamic shear forces, technologies for deep tank production are developed which allow stirrer tip speed of up to 1.5 m s −I sufficient for oxygen uptake, suspension of cells and homogeneous supply with nutrients. For long term bioprocesses without selection pressure it has to be considered that transformed cell lines might show genetic instability due to their variations of chromosomes. In addition, sterile technology becomes an important factor in long term bioprocesses. The decision as to which cell culture system should be chosen, whether batch or continuous processes should be applied essentially is based on the capital investment, the amount of material to be produced, genetic stability of the production cell line, reliability of sterile technology and the flexibility required in the production plant. Under the assumption that 20 kg of a protein have to be produced per year and the same product concentrations in the harvest fluid are reached in the batch process and for instance in the chemostat, it can be considered that the capital investment for one 10,000 1 batch process and a 2 X 2,000 1 continuous process, necessary to produce the amount of material, is comparable. Risk of microbial contamination or technical failure can be considered to be fairly low in the batch process. The economic risk for long term bioprocess in the chemostat can be expected to be medium and high in the perfusion system which is in the large scale not technically fully satisfactory. In addition, due to the longer down time period after contaminations and the start up of the continuous process, the annual yield of the batch process can be considered to be higher. To match the capacity of the batch process at equal capital investment either the flow rate or the product concentration has to be increased and this is only possible in a perfusion system with cell retention. Due to the long bioprocess period the continuous process is less flexible and can only handle a low number of products per year. Compared to the batch process, as long as the formulated bulks derived from different harvests of one bioprocess run meet the specification, they can be combined with other formulated bulks of the same bioprocess run or from a different bioprocess run. The necessary time required for process development and validation of the continuous process will be prolonged in the continuous process compared to the batch process. To ensure constant product quality the Master Cell Bank and the Master Working Cell Bank have to be characterized according to their identity, purity, safety and their genetic stability and productivity within and beyond the fixed bioprocess period. However, in both cases, the bioprocess has to be validated for constant productivity, product quality and viable cell count from harvest to harvest and bioprocess run to bioprocess run. In conclusion, continuous processes only can compete with batch processes at identical capital investments if higher cell densities and product concentrations in the harvest fluid are achieved. This will be possible if perfusion technology can be further developed to larger scales.

The Development of a Perfusion Educational Program

(J. fxtra-Corpor. Technol. 19[2] p. 216–220 Summer 1987). The development of a School of Perfusion Technology starts with a purpose statement that defines the need for such a program and the role of the school within the professional community. After defining the purpose for such an educational program, a task analysis provides the program description of a perfusionist, which later is used to develop the curriculum. A goal analysis details what the student and program will achieve at completion. A statement of the professional and educational philosophy along with the program objective complete the basic foundation. Level of sponsorship of the program determines the duration of education, physical resources, budgetary support, clinical availability and instructional faculty. A target population study forms the basis to define the applicant traits desirable for the program. All of the above data are combined to generate an application process and to begin to create the curriculum. Specific subject matter is listed to include all pertinent and ancillary topics along with the approximate time required to cover each topic. Classes are developed from the topic list, with material coordinated to provide an overlap of knowledge between classes. Statement of course goals and objectives defines the learning expectation while the examination evaluates student knowledge. Clinical rotations provide the opportunity for practical application of the scientific principles learned in the didactic portion of the education. Pre and post clinical evaluations are essential toward determining student’s strengths and weaknesses, in order to validate his or her knowledge in the clinical practice. This form of education mandates a single instructor per student and continual vigilance. An outcome analysis is generated after graduation with employer feedback and peer review of the graduate perfusionist. From this analysis the program goals and objectives are tested, and program re-evaluation begins.

Trends in the Training of Cardiopulmonary Perfusionists

While the most significant developments in perfusion technology have occurred in the past twenty-five to thirty years, interest in extracorporeal circulation was evident as early as the 18th Century. In this article (1) early developments in the field up to the first use of a heart-lung machine by Gibbon are traced; (2) development of accreditation and certification processes is described; (3) data on the current and continued need for perfusionists in the U.S. are presented; and (4) the Baylor College of Medicine baccalaureate program in perfusion is described. One conclusion drawn from information on the need for perfusionists and from information concerning extent of perfusion education is that perfusionists could work more effectively with surgeons than is presently the case if they are more broadly trained and, consequently, delegated greater responsibilities in and out of the operating room.

Developing a Perfusion Technology Curriculum Using the DACUM Process

The DACUM process was used to develop a curriculum for a Perfusion Technology Bachelor of Science Program at Indiana University School of Medicine, Division of Allied Health Sciences. DACUM, an acronym for developing a curriculum, is a brainstorming process for defining a job in terms of the skills necessary to perform it daily. As a result of the DACUM process, general areas of competence are identified and subdivided into specific skills. Once the necessary skills are identified, courses are designed to teach the skills.