Cardiopulmonary Bypass: Past, Present, and Future

Physiologists interested in studying organ function first described extracorporeal perfusion in the 1800s.1,2 Reports of artificial heart and lung systems appeared in the literature many decades before early clinical applications of CPB in the 1950s.3–6 The person most often associated with bringing CPB to clinical reality through ingenious design and meticulous experiment was Dr. John H. Gibbon, Jr. After witnessing a patient die of massive pulmonary embolism, he developed a complicated film-type oxygenator using finger cot pumps. With this apparatus, he performed numerous experiments in which the pulmonary arteries of cats were able to be totally occluded for more than 30 minutes followed by survival. In reporting these results, Dr. Gibbon suggested three possible uses for extracorporeal circulation: first, temporary cardiorespiratory support to allow the heart and lungs to recover function; second, pulmonary embolectomy; and third, mitral valve repair.7 He was remarkably prescient in these predictions, because all three applications have become widely used in the last 50 years. Other workers besides Dr. Gibbon recognized that a temporary substitute for cardiopulmonary function would allow cardiac surgery to be safely performed. Clarence Dennis8 and C. Walton Lillehei9 at the University of Minnesota, Forest Dodrill10 in Detroit, Sigmund Wesolowski,11 Willis Potts,12 and James Helmsworth13 elsewhere in the United States, William Mustard14 in Canada, and J. Jongbloed,15 Viking Björk,16 Denis Melrose17 and Achille Dogliotti18 in Europe all reported mechanical means of support of the circulation. Intensive laboratory study preceded the first few clinical applications, and an abundant literature exists describing these early attempts. In 1953, Bernard Miller, a coworker of Gibbon, would write, “The ultimate purpose of an extracorporeal circuit embodying an artificial heart, or an artificial heart and lung, is to provide a bloodless field within the cardiac chambers during definitive surgical procedures.”19 This statement succinctly summarized the fundamental purpose of CPB then and remains valid to the present. The first successful open-heart surgical procedure in which CPB was used occurred in May 1953 when Dr. Gibbon closed an atrial septal defect in an 18 year-old girl in Philadelphia.20 This seminal case was preceded and followed by many failures, and use of CPB was not assured. Out of 18 documented attempts to use CPB for cardiac surgery between 1951 and 1953, only the one patient reported by Dr. Gibbon survived.21 Machines of this era were custom-built, had reusable components that needed to be cleaned and sterilized before use, and all circuits required large volumes of donor blood for priming and operation. Remarkably, many of these early machines were completely automatic as the developers sought total control over venous, recirculation, and arterial blood flow, gas exchange, and maintenance of the patient’s blood volume and pressures. Largely as a result of Lillehei’s success with cross-circulation in 1954–1955,22 workers continued to develop CPB and apply it clinically. A major breakthrough occurred at the University of Minnesota when Richard DeWall, working in Lillehei’s laboratory, developed a reliable disposable bubble oxygenator constructed from Mayon tubing as used in the food industry.23 Concurrently, John Kirklin at the Mayo Clinic refined the original Gibbon-IBM machine and achieved many successes, primarily for closure of ventricular septal defects.24 The DeWall-Lillehei bubble oxygenator concept was first marketed by Baxter-Travenol as the plastic sheet bubble oxygenator in 1957.25 With the accrual of more clinical experience, principles of conduct of CPB were established regarding acceptable blood flow rates, blood gas and acid-base management, priming solutions, and methods of cannulation.26 Hypothermia alone had been used for early cardiac surgery without CPB, but by the late 1950s, it was coupled with extracorporeal perfusion and found to be another powerful tool for the cardiac surgeon.27 The decade of the 1960s witnessed debate over the merits of the reusable disc oxygenator, as advocated by Robert Gross,28 in contrast to the ever more popular disposable bubble oxygenator. In 1966, Donald Bentley, an engineer in California, developed and marketed the first disposable bubble oxygenator to incorporate a heat exchanger; it was called the Bentley Temptrol™.29 Valve replacement and repair of congenital cardiac defects predominated early cardiac surgery, but in this decade the first reports of coronary artery bypass surgery appeared.30 Hemodilution perfusion, or the purposeful lowering of the patient’s hematocrit by use of crystalloid prime alone for CPB, became accepted as a viable technique.31 Whereas physicians were the first to operate the CPB apparatus, the perfusion profession had its beginnings with the formation of the American Society of Extra-Corporeal Technology (AmSECT) in 1964. Figure 1 shows the tremendous growth in the number of open-heart facilities in the United States beginning in 1955. Only two centers in the world in 1955 offered open-heart surgery, one in Minneapolis at the University of Minnesota and the other just 90 miles away at the Mayo Clinic in Rochester, Minnesota. In 1960, there were approximately 200 facilities; by 1970 there were nearly 500; and, by 2002, the number of facilities had doubled once again to approximately 1000. It is estimated that in the year 2000 one million CPB cases were performed worldwide.Figure 1.: Open Heart Surgery—Facilities by Decade (USA). Graph depicting growth in number of hospitals performing cardiac surgery beginning in 1955. NOTE: Dotted line indicates lack of American Hospital Association data between the years 1955 and 1970. In 1960 it is estimated there were approximately 200 programs in the USA.In the 1970s, the medical device industry delivered a wide array of CPB disposables. There were more choices of bubble oxygenators, reservoirs, filters, and pumps. With the growing number of open-heart surgical cases, there became an increasing awareness of patient injuries associated with CPB. These injuries were most often manifested as transient kidney, lung, or brain dysfunction immediately following surgery. The device industry once again delivered by providing bubble oxygenators with lower gas-to-blood flow ratios, many arterial filter designs, and more efficient heat exchangers. The CPB system in most hospitals was now entirely disposable. Membrane oxygenators, which were initially thought to be the proper approach for CPB, were a hard sell with clinicians and were not readily accepted. Objections included larger priming volumes, more complex set up and operating procedures, and limited gas exchange that required sizing the oxygenator to the patient’s weight. The Travenol Teflo™ microporous Teflon membrane oxygenator was introduced in 197232 and was the first to gain an appreciable case experience by the late 1970s. However, in many comparison studies, a membrane oxygenator for routine CPB was found not to offer significant advantages over a bubble oxygenator.33–35 The decade of the 1980s saw major advances in myocardial preservation techniques. Hyperkalemic, hypothermic crystalloid cardioplegia was first used widely, and its controlled administration became part of the CPB system. Better management of systemic anticoagulation evolved. The major emphasis for those involved in open-heart surgery in this decade was trying to keep pace with the ever-increasing volume of coronary artery bypass operations. The roller pump had been a key component of CPB since Gibbon’s early reports,4,36 but an alternative in the form of a disposable centrifugal pump became increasingly used clinically.37 The United States Food and Drug Administration commissioned a study38 on the safety of CPB in the early 1980s, and subsequent surveys by several groups39–42 further quantified the relative risks of CPB. These reports led to further improvements in devices and practice. Membrane oxygenators realized their promise of three decades earlier and were finally accepted by clinicians. Figure 2 shows the number of CPB cases in the United States each year from 1980 to 1998 along with type of oxygenator used. The crossover year was 1985 in which one-half of all cases were performed with a bubble oxygenator and one-half with a membrane type. The number of cases during these years annually rose from 175,000 in 1980 to approximately 475,000 by 1998.Figure 2.: Oxygenator Use in the United States (1980–1998). Graph depicting growth in number of procedures by year (bars) and type of oxygenator (squares = bubble, circles = membrane). Whereas bubble oxygenators were used predominantly in the early 1980s, by 1985 membrane oxygenators accounted for one-half of all procedures. Membrane oxygenator use grew steadily in the 1990s as bubble oxygenators fell into disuse.In the 1990s, the bubble oxygenator was relegated to an item of historical interest only as membrane oxygenators were universally used for CPB. Incremental refinements in technology and practice continued. For example, myocardial protection was perfected with blood cardioplegia and antegrade and retrograde delivery from the CPB circuit. Avoidance of blood transfusion became a goal in most centers as CPB priming volumes were reduced further. The equipment was more reliable, and better monitoring of CPB became standard. Online sensors to continuously display blood gas and chemistry values permitted more precise management of CPB. Blood damage and an awareness of the whole body inflammatory response to CPB led to use of heparin-coated circuits. Surgeons also recognized some of the disadvantages of routine hypothermia to 24 or 28°C, so CPB to more moderate temperatures of 32–35°C became popular. For pediatric perfusion, more choices for equipment finally became available from industry. State-of-the-art CPB today includes a pre-assembled, surface-coated, low-prime circuit consisting of a microporous hollow fiber membrane oxygenator, a centrifugal pump for systemic blood flow, a tangential-entry screen arterial line filter, and routine use of hemofiltration to remove excess fluid and/or cell salvage for washing cardiotomy-suctioned blood before transfusion. Vacuum-assisted venous drainage is also used in some centers to allow smaller thoracic incisions and smaller venous cannulae and tubing, thus replacing simple gravity siphon drainage. There is now a wide variety of safety devices with servoregulation incorporated onto the CPB circuit, such as multiple air bubble detectors, level and pressure sensors, and ever more sophisticated online sensors. As for the future, there is always some risk in making predictions. For example, Robert Gross, one of the best-known cardiac surgeons in the 1950s, made a thoroughly convincing pronouncement in 1959 by stating, “I have little doubt that bubble oxygenators will largely fall into discard.” His view, which was published in The New England Journal of Medicine,43 was followed by the immense popularity of the bubble oxygenator for the next 20 years that probably did more to promote the rapid growth of open-heart surgery worldwide than any other single technology. The CPB circuit of the future will be more compact as the system is moved closer to the patient in an effort to reduce priming volumes even further. Components will be fully integrated; one manufacturer’s device now has a built-in centrifugal pump as part of the oxygenator/heat exchanger with integral filter as one disposable unit. The quest for biocompatibility to minimize blood damage and the systemic inflammatory response will continue, but will not make significant progress until blood flow perturbations in the CPB circuit are minimized. Servo-regulation to the degree used on the early CPB machines will continue to be a goal, but will most likely depend upon acceptance by clinicians that such automation is truly better and safer for patient management. Cost considerations will also figure into any wide adoption of servo-regulated circuitry. Finally, there will be a move towards standardization of the CPB circuit, which will also help reduce costs. Figure 3 shows trends in the number of CPB cases annually since 1999 and projected until the year 2008. There are also bars showing the number of off-pump coronary artery bypass (OPCAB) cases in which CPB is not used. There has clearly been a decline in the number of CPB cases in the United States to approximately 350,000 in 2003 and 2004 from a high of nearly 500,000 in 1999. This downward trend is projected to continue in the coming years. After a slight recent decline in the number of OPCAB cases, industry projections predict a new technology within two years that will make this type of operation more acceptable to surgeons. It is acknowledged that the decline in the overall number of CPB cases has also been profoundly affected by use of coronary stents by interventional cardiologists.Figure 3.: Current and Future Trends in CPB. Graph depicting decline in number of CPB procedures beginning in 1999 and projected until year 2008 (striped bars). Solid bars depict modest growth in number of off-pump coronary artery bypass (OPCAB) procedures in which CPB is not used.Having briefly reviewed 50 years of CPB, what else can be said about this spectacular development of artificial organ technology? There have been important spin-off technologies. First, emergency cardiopulmonary support was first described in the early 1960s44 and consisted of use of conventional CPB. This application evolved into systems that could be implemented for circulatory support in a matter of minutes anywhere in the hospital.45 The first ventricular assist system was a heart-lung machine.46 The centrifugal pump was originally envisioned as an artificial heart and was used widely in the 1980s for prolonged ventricular support. Extracorporeal membrane oxygenation (ECMO) most certainly had its genesis in CPB,47 and the systems that were developed in the mid-1980s and are widely used today consist of conventional CPB devices simply adapted and used long-term. Left- and right-heart bypass are infrequently used, but, once again, are useful adjuncts for the surgeon faced with difficult patient pathology. Cell salvage and increasing applications of blood processing technologies also had their origins in the open-heart surgical suite. In summary, when considering 50 years of CPB, we recognize the extraordinary accomplishments of early workers to develop CPB as an adjunct to cardiac surgery. We marvel at current levels of reliability and safety of CPB equipment. We note with some concern the decrease in use of CPB for coronary bypass operations in the future.

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