Report of the Workshop on Diffusion of ECMO Technology Extracorporeal Membrane Oxygenation Sponsored by: National Institute of Child Health and Human Development, NIH Office of Medical Applications of Research, NIH National Institute of Neurological Disorders and Stroke, NIH National Heart, Lung, and Blood Institute, NIH Agency for Health Care Policy and Research Federal Drug Administration May 31,1990—June 1,1990 Rockville, Maryland Edited by: Linda L. Wright, M.D. Pregnancy and Perinatology Branch Center for Research for Mothers and Children National Institute of Child Health and Human Development, NIH U.S. Department of Health and Human Services Public Health Service National Institutes of Health National Institute of Child Health and Human Development NIH Publication No. 93-3399 January 1993
Participants Planning Committee
John H. Ferguson, M.D. (Co-Chairman) Director, Office of Medical Applications of Research National Institutes of HealthElsa Bray (OMAR) Charlotte S. Catz, M.D. (NICHD) Dorothy Gail, Ph.D. (NHLBI) Gil Hill, M.S. (NICHD) Deborah G. Hirtz, M.D. (NINDS) | George A. Little, M.D. (Co-Chairman) Chairman, Department of Maternal and Child Health Dartmouth-Hitchcock Medical CenterJennifer Mayfield, M.D. (AHCPR) George C. Murray, Ph.D. (FDA) Philip H. Sheridan, M.D. (NINDS) Linda L. Wright, M.D. (NICHD) Sumner Yaffe, M.D. (NICHD) |
Invited Participants
Robert M. Arensman, M.D. (Chicago) Roberta A. Ballard, M.D. (San Francisco) Robert H. Bartlett, M.D. (Ann Arbor) Mary Anne Berberich, Ph.D. (Bethesda) Alfred Brann, M.D. (Atlanta) F. J. Brinley, Jr., M.D., Ph.D. (Bethesda) L. Joseph Butterfield, M.D. (Denver) J. Devn Cornish, M.D. (San Diego) Robert A. deLemos, M.D. (San Antonio) James Dillard, (Rockville) Joseph S. Drage, M.D. (Bethesda) Jonas Ellenberg, Ph.D. (Bethesda) Michael F. Epstein, M.D. (Boston) Philippe Evrard, M.D. (Belgium/Bethesda) Peggy C. Ferry, M.D. (Tucson) Craig Fleming, M.D. (Hanover) Roger K. Freeman, M.D. (Long Beach) Lawrence M. Gartner, M.D. (Chicago) Penny Glass, Ph.D. (Washington) Jan Goddard-Finegold, M.D. (Houston) William H. Hall (OMAR) Ann Lennarson Greer, Ph.D. (Milwaukee) Ian Gross, M.D. (New Haven) Terry A. Huriburt Ill, M.D. (Hanover) L. Stanley James, M.D. (New York) | Arnold D. Kaluzny, Ph.D. (Chapel Hill) Martin Keszler, M.D. (Washington) Lorraine V. Klerman, Ph.D. (New Haven) Theodore Kolobow, Ph.D. (Bethesda) Alfred N. Krauss, M.D. (New York) Jerold F. Lucey, M.D. (Burlington) Susan K. McCune, M.D. (Bethesda) Gerald B. Merenstein, M.D. (Denver) Valerie Mike, Ph.D. (New York) George C. Murray, Ph.D. (Rockville) Karin B. Nelson, M.D. (Bethesda) Michael R. Neuman, M.D., Ph.D. (Cleveland) Seymour Perry, M.D. (Washington) Charles R. Rosenfeld, M.D. (Dallas) Alan L. Sandler, D.D.S. (Bethesda) Rachel Schwartz, M.P.H. (Providence) P. Pearl O’Rourke, M.D. (Seattle) Billie Lou Short, M.D. (Washington) Hal C. Sox, Jr., M.D. (Hanover) Giovanna M. Spinella, M.D. (Bethesda) Charles Stolar, M.D. (New York) Robert Vannucci, M.D. (Hershey) Richard B. Warnecke, Ph.D. (Chicago) Alison Wichman, M.D. (Bethesda) David D. Wirtschafter, M.D. (Pasadena) |
Contents Participants Summary with Policy and Research Recommendations Diffusion of Medical Technology: The Case of ECMO Ann Lennarson Greer, Ph.D. Extracorporeal Life Support State-of-the-Art 1990 Robert H. Bartlett, M.D. Charles Stolar, M.D. Neonatal Problems Treated with ECMO: Pathology, Prevention, Alternative Therapies L. Stanley James, M.D. Jen-Tien Wung, M.D. Neurological Outcome After Extracorporeal Membrane Oxygenation Therapy in the Newborn Jan Goddard-Fine gold, M.D. Extracorporeal Membrane Oxygenation Versus Conventional Medical Therapy for Management of Persistent Pulmonary Hypertension of the Neonate: A Decision Analysis Craig Fleming, M.D. Terry A. Huribut, M.D. Harold C. Sox, M.D. Extracorporeal Membrane Oxygenation: Cost, Organization, and Policy Considerations Rachel M. Schwartz, MR H. Katherine K. Willrich, BA. David E. Gagnon, M.RH. Summary with Policy and Research Recommendations Introduction This workshop, which was initiated by the National Institute of Child Health and Human Development (NICHD), is the result of the combined efforts of the NICHD, the Office of Medical Applications of Research (OMAR), the National Institute of Neurological Disorders and Stroke (NINDS), the National Heart, Lung, and Blood Institute (NHLBI), the Food and Drug Administration (FDA), and the Agency for Health Care Policy and Research (AHCPR). A planning committee commissioned background papers which were circulated to the invited participants prior to the meeting. Presentation and discussion of the papers was followed by working groups which met to define policy and research recommendations in the areas of prevention and therapeutic alternatives, identification of populations to benefit from ECMO, research needs, and policy concerns. Recommendations of the working groups were reviewed in plenary session. The resulting Summary with Policy and Research Recommendations is presented below, followed by the commissioned papers. Extracorporeal Membrane Oxygenation (ECMO) is a new, highly invasive therapy that is being investigated and utilized in newborn infants with cardiorespiratory failure. The apparent increasing use of this technology, especially in new patient populations, as well as concerns about long-term outcome stimulated an invitational forum sponsored by multiple U.S. Government agencies. The specific focus of the forum was diffusion of ECMO technology. Development and use of this technology in newborns is relatively well defined and documented. The literature includes reports on technical details and clinical application up to and including recent controlled trials. An organization, ELSO, or Extracorporeal Life Support Organization, was formally established in 1989 by investigators and clinicians who previously had been involved in regular meetings and the sharing of information and establishment of guidelines. A patient registry supported by federal and private funds has been maintained. Current State of Knowledge Concerning Populations to Benefit and Indications for Use Certain patients with a high risk of morbidity and mortality are appropriate candidates for ECMO when pulmonary function and other studies suggest that mechanical ventilation will be unsuccessful or cause undue harm. ECMO should no longer be considered an extraordinary or rescue therapy for moribund infants over 2 kilograms. Early consultation with ECMO units concerning infants within defined weight and disease categories is encouraged to facilitate timely, safe transfer. Term and Near Term Newborns Infants born at greater than 35 weeks gestation with the following disease states should be considered candidates: Meconium Aspiration Syndrome (MAS) and Persistent Pulmonary Hypertension of the Newborn (PPHN)—A small portion of babies with clinical manifestations of MAS and PPNN may not respond to conventional therapy. Initial stabilization and a trial of conventional therapy should be instituted before consideration of ECMO. Congenital Diaphragmatic Hernia (CDH)— Mechanical ventilation, general physiologic support, and early surgical repair remain the current standard of care for CDH. ECMO may improve survival in infants with CDH who have continued respiratory failure after repair. Given the increased vulnerability of the congenitally hypoplastic lung to mechanical ventilation, institution of ECMO should be considered earlier in these infants than in infants with PPNN. However, ECMO is not appropriate for infants with severe pulmonary hypoplasia. Delayed repair following stabilization (which may include ECMO) is currently under study and is not at present a preferred treatment. Sepsis—ECMO is appropriate for a limited number of infants with respiratory failure due to sepsis who do not respond to other therapy. However, studies of children with multiple organ failure (including respiratory) secondary to sepsis, who are treated with ECMO, reveal higher morbidity and mortality compared to other groups treated with ECMO. The indication for ECMO in this group requires further research. Respiratory Distress Syndrome (RDS)— Apparent RDS in infants of greater than 2 kilograms birthweight appears in a small number of infants and may include other entitles as yet poorly defined. ECMO is appropriate when optimal ventilatory management fails. Preterm Infants ECMO is not appropriate for infants under 2 kilograms and 36 weeks gestation except under carefully controlled research protocols. Postneonatal Pediatric Patients Respiratory Failure—ECMO is currently being used as rescue therapy for severe respiratory failure in pediatric patients (1 month to 16 years) in a small number of centers. There is an urgent need to define mortality and morbidity risks as well as natural history in this diverse diagnostic group. It should not be assumed that the favorable results of treatment achieved with ECMO with certain term newborn problems can be transferred to those of the older patient. Any use should be considered experimental and should be undertaken with Institutional Review Board (IRB) approval in pediatric intensive care units by experienced pediatric intensivists and ECMO teams with careful data collection and reporting. Cardiac Support—ECMO is also being used as an adjunct to cardiac surgery in a small number of centers. As in pediatric respiratory failure, these early trials should be done with IRB approval in pediatric intensive care units, by experienced intensivists and ECMO teams, following protocols with careful data collection and reporting. Patients with Irreversible and Hopeless Conditions ECMO is a temporizing and not a corrective intervention. Repair and recovery is necessary for patients to benefit. There may be some infants with irreversible organ dysfunction or damage with no hope of correction who may be appropriately excluded from ECMO treatment. Each institution should establish a mechanism of review for such infants. Prevention and Therapeutic Alternatives The number of centers that offer ECMO treatment has increased dramatically, however, alternative therapies and prevention have not been adequately explored. There is a serious lack of knowledge regarding epidemiologic factors that influence the requirement for ECMO therapy. The actual incidence of conditions treated with ECMO, such as PPHN, is not well documented. Furthermore, inter-institutional differences in ECMO utilization are substantial and the relative effectiveness of alternatives versus ECMO is unclear. In the ECMO registry, inborn patients represent only 7 percent of the population receiving ECMO treatment, suggesting that management of outborn patients before they are referred is a major factor determining the requirement for ECMO treatment. Studies of obstetric and/or neonatal care practices that either prevent or increase the use of ECMO therapy are needed. It is well known that a substantial portion of babies referred for ECMO do not receive the treatment. The ECMO registry might serve as a valuable resource to identify perinatal care practices that influence or determine need. Examples of practices that some feel differ extensively include early recognition and intervention when meconium is present at birth, use of tolazoline, and ventilatory management including the extent of over ventilation. Particular note should be made of the deficit of information regarding the importance of ventilatory care practices. Retrospective evidence suggests that the mode of ventilation may modify or predispose to a need for subsequent ECMO therapy in infants who develop progressive lung disease. High levels of oxygen alone may result in lung damage; furthermore, the definition of an "acceptable" low level of arterial oxygen (PaO2) varies considerably between institutions. A concept has emerged in recent years that a lower PaO2 than previously accepted might be indicated. Education and prevention strategies should be developed based upon epidemiologic information about current practices and their impact on the need for ECMO. It is not yet known whether the use of ECMO can be reduced through education of physicians, nurses, and others concerned with the care of critically ill neonates, but the effort should be undertaken. Based on present knowledge and understanding of the use of ECMO and the infants needing this mode of treatment, the following summary statements regarding prevention and therapies were derived: - Educational needs of pertinent individuals (physicians, nurses, respiratory therapists) should be determined from practice and epidemiologic studies. Efforts directed toward modifying care practices of the at-risk fetus, the newborn, and the ill newborn should be undertaken. This pertains especially to the physicians responsible for care of the newborn in the delivery room and the physician responsible for management of the infant on a ventilator.
- Continued use and improvement of presently available alternative therapies should be pursued. The use of ECMO for infants who do not meet the presently-accepted criteria for term or near-term infants mentioned above must be considered clinical research and take place only with consideration of alternatives and within appropriately designed trials. Research should continue to determine if there are additional alternatives to ECMO therapy.
Research The increasing use of ECMO especially in new patient populations creates an urgent need for further research. Clinical studies are needed to determine when ECMO is the most appropriate treatment alternative and what technical improvements are safe and feasible. The short-term and long-term effects of ECMO on the nervous system, pulmonary system, cardiac system, and the blood in all age groups must be further defined. Quality of life as well as specific biologic parameters should be studied. The Ideal Prospective Randomized Controlled Clinical Trial The baby at risk for severe neonatal cardiopulmonary problems should be identified before or shortly after birth. The decision to enroll an ill neonate should be made within hours after birth with random assignment to one of several alternative therapeutic interventions. In parallel, the patient should be matched both to a control baby with similar problems of less severity that does not meet study entrance criteria and to a healthy matched control baby. Preintervention parameters should be measured to survey organ dysfunction resulting from the underlying disease process itself. Subsequently, appropriate parameters should be measured during the time of therapeutic intervention. Short-term outcomes (hours to weeks), intermediate outcomes (months), and long-term outcomes (years) should be determined. The idealized times, mentioned above, for the collection of data from patients to be enrolled in a prospective randomized controlled clinical trial are illustrated in Figure 1. Because of rapidly-changing technological improvements, it is necessary to accrue patients over a limited time period. Multi-center collaboration to ensure adequate patient entry is necessary. A severity and/or prognosis index is needed to ensure balanced risk among the alternative treatment arms.
 Figure 1. Idealized time course for a prospective controlled randomized clinical time. Note: All therapeutic intervention groups and control groops have the same parameters measured before, during, and after the possible intervention period. Table 1: Parameters and Techniques to Determine Organ Function During Animal Model and clinical Studies | Animal model Studies | Clinical studies | | Neurologic | 1. Perfusion/hemodynamics (Doppler) 2. Electrophysiologic (FEG, EP’s) 3. Non-invasive imaging (NMR, NIRS, US) 4. Metabolic (NMR, NIRS) 5. Behavior assessment 6. Neuropathology
| 1. Perfusion/hemodynamics (Doppler) 2. Electrophysiologic (FEG, EP’s) 3. Non-invasive imaging (NMR, NIRS, US) 4. Metabolic (NMR, NIRS) 5. Neurodevelopmental assessment 6. Neuropathology
| | | | | Pulmonary | | | | 1. Pulmonary vascular resistance control -----mediators –anatomy of development mechanics of hyperactivity 2. Surfactant dynamics
| 1. ABG 2. Pulmonary function tests (PFT’s) 3. Surfactant dynamics 4. Pulmonary pathology 5. Long-term PFT’s
| | | | | Cardiac | 1. Myocardial oxygen consumption 2. Coronary artery flow
| 1. Ventricular function (echocardiography) 2. NMR 3. Cardiac pathology
| | | | | Blood | 1. Impact of biomaterials on cellular elements and vasoactive substances 2. Impact of circuity on cellular elements
| 1. Coagulation parameters 2. CBC 3. Vasoactive substances
|
Abbreviations: ABG-aterial blood gases, CBC-complete blood count, EEG-electroencephalography, EPS-evoked potentials, NIRS-near infrared spectroscopy, NMR-nuclear magnetic resonance, PFTs-pulmonary function tests, US-ultrasound. Assessment of Expanded Clinical Indications ECMO may eventually prove to be an appropriate therapy for certain premature neonates, but the risks for this population appear greater and the benefits less certain at this time. Any application of ECMO to the premature neonatal population should be limited to strict clinical research protocols. ECMO following cardiac surgery is currently in use in some centers and requires careful evaluation by clinical research protocols to determine who should be a postsurgical candidate for ECMO and to determine risk versus benefit. Role of Animal Studies Animal studies will be necessary to answer certain key questions relevant to clinical studies. Research with animal models to define the pathogenesis and treatment of such pulmonary vascular disorders as persistent pulmonary hypertension could lead to increased prevention and less need for ECMO or its alternatives. A better understanding of the optimal timing for initiation and discontinuation of ECMO may be derived from animal research. ECMO could possibly be used to simulate the process of in utero hypoxia-ischemia in an animal research model, thereby permitting serial observations and elucidation of pathogenesis. Specific Studies of Organ Function and Dysfunction Table 1 lists the key organ systems affected both by the underlying diseases leading to cardiopulmonary failure and by the therapeutic intervention. The critical parameters and techniques used to assess organ function in the clinical situation and in animal models are outlined. With new and promising techniques rapidly becoming available, it will be possible to assess pulmonary, cardiac, blood, and neurologic parameters before, during, and after the ECMO procedure. Neurologic status is a crucial outcome measure for assessing the long-term functional results of therapeutic intervention. Comprehensive neurologic and developmental assessments by age-appropriate evaluative instruments are needed. Information from neuroimaging, cerebral hemodynamic, neurophysiologic, and neurochemical studies are required before, during, and after the intervention so that outcomes may be related to specific events either preceding or during treatment. Cardiopulmonary studies require ongoing monitoring of pulmonary function tests, arterial blood gases, and myocardial physiology. Factors controlling pulmonary vascular resistance (systemic mediators, hyperreactivity mechanisms, and changing surfactant dynamics) are of particular interest. Research concerning the effects of intervention on ventricular function and coronary artery flow are also crucial. Both cellular and plasma blood components can be affected by the ECMO apparatus. Such blood changes (cells, vasoactive substances, and coagulation factors) can have a major impact on systemic physiology. Studies to Improve ECMO Technology A number of improvements in ECMO technology are under development. Veno-venous catheterization would be a less invasive technique compared to veno-arterial catheterization. Carotid reanastomosis may prove to be possible. The use of anticoagulative circuits may eliminate the need for systemic heparinization with its accompanying risks. Circuit control and monitoring systems when combined with measurement of critical clinical parameters may increase the precision and delicacy of the intervention. The use of biomaterials as components of the ECMO system would be expected to significantly reduce complications of hypersensitivity or embolization. Careful evaluation of the immediate efficacy and safety, as well as the long-term outcome of these various modifications will be necessary. Studies to Improve Alternative Therapies Alternative treatments for cardiopulmonary failure in the neonate are currently being explored. These include the use of surfactant, high-frequency ventilation, negative-pressure ventilation, liquid ventilation, and nitric oxide. A spectrum of "conservative" or "conventional" ventilatory assistance interventions, which are either already in use or are being developed, require controlled trials to determine their relative effectiveness. Outcome Analysis (Follow-up Studies) All studies require rigorous delineation of outcome analysis. The short-term outcomes include death, neurologic function (including EEG, neuroimaging, and clinical parameters), and cardiorespiratory function as defined by physiologic parameters. The long-term outcomes include death, health status (disease, disability, morbidity), and both global and system-specific functional status (psychomotor development, quality of life, and social adaptive functioning). Long-term outcomes also should be analyzed with respect to total health care utilization and cost. The ultimate goal would be to analyze specific factors present before or during the ECMO procedure with regard to possible relationship to specific functional deficits detected at follow-up. It is essential to follow children long enough (school age or beyond) to assess motor performance and higher critical functions, including right versus left hemisphere cognitive processes. Contacts between physicians and parents established at the beginning of ECMO therapy should be maintained to facilitate study. Policy Considerations Influencing the Diffusion of ECMO ECMO is a relatively new technology, so it is not surprising that few, if any, policies currently influence its use at existing centers or its spread to other facilities. Even technologies with longer histories have few formal policies governing their use. Decisions about who will perform medical and surgical procedures and where they will be performed are often under the control of hospitals and other health care facilities, as well as being strongly influenced by the organizations that pay for such procedures. Professional organizations, accrediting bodies, the Federal Food and Drug Administration, and state regulatory agencies also establish policies. To make ECMO available to those infants who would benefit from it, and in the most cost effective manner, the development of three types of policies is recommended: - Those that would promote effective and efficient use of existing ECMO centers and avoid inefficient and expensive proliferation.
- Those that would monitor the quanity and quality of ECMO treatment.
- Those that would encourage long-term studies.
To promote effective and efficient use of existing ECMO centers and avoid inefficient and expensive proliferation, the following should be implemented: - Planning at the state and regional levels. This should include obtaining epidemiologic information that can be used to forecast the need for ECMO in various geographic areas.
- Development of guidelines for ECMO centers. Such guidelines should include staffing needs, minimum number of cases per year, acceptance criteria, data to be collected and submitted to the registry, quality criteria, and other aspects of care. (For the present, such guidelines should be limited to the use of ECMO with neonates.) Expansion of the technology for the treatment of pediatric or adult patients would necessitate the development of additional guidelines. Several organizations should be involved in the development of additional guidelines. The Extracorporeal Life Support Organization (ELSO) has already developed guidelines and the Committee on the Fetus and Newborn of the AMerican Academy of Pediatrics (AAP) has issued "Recommendations on ECMO" (Pediatrics 85:618-619, 1990.) These groups should be encouraged to remain active in guideline development. The Agency for Health Care Policy and Research (AHCPR) now has a mandate to develop practice guidelines; although its work to date has been primarily in relation to practices supported by Medicare, it should be expanding to tother fields in the near future. The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) should be asked to become involved in accreditation of ECMO centers (see next bulleted section).
- Development of an accreditation procedure. ECMO centers should be accredited, or licensed, or designated. Models for such accreditation are those currently used by the 10 American College of Surgeons (ACS) for Cancer and Trauma Centers. The JCAHOmight be asked to form and ad hoc ECMO Accreditation Task Force, which shouldinclude representatives from groups such as ELSO, AAP and ACS. Other groups that might be involved in the process are federal and state rate-setting agencies and state maternal and child health agencies because of their concern for children with special health care needs.
- Encouragement of the developement of hospital "strategic alliances." Hospitals can work together to promote efficient utilization of existing centers through regional cooperation. Alliances have the potential to stabilize referrals, secure economy of scale, and promote continuing education of staff. This model of collaboration already exists in the Community Clinical Oncology Program.
- Development of funding policies that encourage use of existing ECMO centers and discourage inappropriate proliferation. Medicaid and other third-party payers should provide reimbursement for ECMO treatment outside of the state in which the infant resides and for transportation to and from ECMO regional centers.
To monitor the quality and quantity of ECMO treatment, the following recommendations concerning data and case registration are made: - Continuation and improvement of the existing ELSO case registry-The case registry should be used as a management and research tool in order to determine efficacy and effectiveness. It should be able to indicate quality problems such as institutions that treat too few infants or have high failure rates. It should be used to help defelop long-term outcome studies.
Formation of an advisory board—This board should develop a list of data elements and undertake other relevant tasks, such as the development of procedures and incentives for establishing and maintaining data quality. Development of a permanent funding base— Funding of the registry should be the ultimate responsibility of participating ECMO centers. The Federal Government and foundations have assisted with initial efforts and should continue in the short term. Participation in the registry should be required for accreditation. The registry should be used to monitor the relevance of guidelines.
Diffusion of Medical Technology: The Case of ECMO Ann Lennarson Greer, Ph.D. University of Wisconsin—Milwaukee Abstract This overview distills accepted diffusion theory and the author’s ongoing research to outline factors and dynamics which come into play around high-cost, high-risk, highly-complex technologies like Extracorporeal Membrane Oxygenation (ECMO). Three themes are developed. The first is the need to understand adoption of new technology as a social process wherein a consensus for change develops among local medical colleagues who communicate directly with one another in a situation of common circumstances, pressures, and experience. The second concerns the fact of medical technologies such as ECMO diffusing into practice even as they continue to change and develop. With such dynamic technologies, the state-of-the-art is as much a consequence of practice as of science. The third theme concerns the fact that hospital technology adoptions engage multiple interests, decision-makers, and criteria for adoption. The assessments of doctors are combined with those of businessmen and organizational planners in a dynamic local process which drives adoption and use. There is a brief discussion of the difficulties of using guidelines to affect this process. The Diffusion of Dynamic Technology The diffusion of an innovation is a highly social process. The spread of even a simple technology, a new drug for example, is characterized by many interpersonal contacts and differentiated social roles—change agents, idea champions, early and late adopters, and opinion leaders.1’2 Except for quacks and cranks and geniuses recognizable only after the fact, innovation is adopted not by isolated individuals alone with their journals but by networks of people who adopt more or less as a body, following a change in the local consensus about what one should do and be seen doing. Initial awareness of an innovation may come through reading but one-on-one activities—observation, trial, and social reinforcement—are usually necessary to adoption. The spread of a technical innovation is not so different from the spread of a new dance step. Most want to be neither first nor last, perform badly, or look like a fool. The desire for consensus is most understandable. Research findings and their application are rarely clear-cut. In our studies, doctors have shown themselves to be skeptical of their professional literature. (It could easily lead you to foolishness.) They cite the over-optimism of scientists and developers in interpreting early findings, the frequent inconsistency of published results, and the coming and going of touted procedures. In addition to confusion over results actually achieved at research sites, local physicians have many uncertainties regarding their personal ability and the ability of their colleagues to achieve benefits in their practices. They fault the medical literature for omitting details of application and report skepticism regarding the application of findings to their own patients and institutions. Personal contacts made at professional meetings or instructional seminars permit resolution of some difficulties but uncertainties ordinarily slow adoption until time and local opinion support (or may even seem to demand) behavioral change.3’4’5 In shaping the local consensus, opinion leaders are key actors. Found in all groups, opinion leaders are respected by their local colleagues both for their competence and for their commitment to the welfare of the group. Colleagues trust that they will know what a new thing is about, what it means to the group, and that they will not steer associates wrong. Their acceptance of an innovation portends adoption by other members of their social network. Assessing new technology in its relation to local circumstances may be difficult. Allen contrasts the acceptance of scientific findings with the introduction of new technology. Scientists share a universal language and common criteria for judgement. Technology is local, defined by local goals, problems, people, facilities, equipment, systems, and values.6 Appraising the implications of a new technology may then presuppose its prior local demonstration. When this is the case, successful introduction requires a local innovator, a technical person who is able to adapt the technology to the specific situation. This innovator’s activities may, in turn, affect the technology’s ongoing development, creating a dynamic interaction between concept and practice. The difficulties of application compound when the technology is itself a complex mix of human as well as technical components. The potential for interpersonal problems can lead to another role which is associated with successful implementations. This is the advocate, or idea champion. Internal to the adopting group or organization, this champion becomes committed to an innovation’s acceptance. The idea champion keeps the idea alive through the innumerable organizational, financial, and political hazards which beset any undertaking that has the potential to absorb scarce resources or alter personal relationships. Both the technical innovator and the idea champion must be in a position to devote time to the tasks of reconciling technology and local circumstance. Rogers has used the term "re-invention," to indicate the degree to which an innovation is changed by adopters in the process of adopton and implementation.2 Not only may the tool be changed, the technology may be used by different personnel, combined with other technologies in new ways, or used for purposes other than those originally intended. In this process of trial and modification, ambiguities are removed and possibilities are revealed or restricted. In the case of dynamic technologies, what diffuses is not so much a prepackaged product as a concept that is specified as it is applied. ECMO does not appear to be an exception. ECMO offers a high tech, high cost, labor and equipment-intensive rescue for newborns suffering from intractable respiratory failure. External cardiopulmonary support is provided to the infant by a modified heart-lung machine so that the damaged lung may rest. It is a technically high-risk procedure which ordinarily includes ligation of the right carotid artery and jugular vein through which the support system has been connected. Claims of remarkable results by developers have generated controversy in the literature over 1) the design of evaluations which have, for the most part, lacked a true control group7 and 2) the baseline predictions of mortality against which the survival of ECMO babies is so startling. Some writers have suggested that the high mortality associated with pre-ECMO management of candidate babies may have been iatrogenic.8,9 The technology itself is changing rapidly. Even as the University of Michigan developers of ECMO are proposing a new means of cannulation to avoid permanent ligation of the carotid artery, other surgeons in other locations are reconstructing the artery.10, 11 Independent teams are varying other components also, such as the time during which infants are maintained on ECMO.11 Conditions for expanding the indications for ECMO are being discussed as are possible new uses. Donn reports optimism that new technical developments will open the procedure to premature infants and prove useful in preserving transplant organs or as "a temporizing device for cardiac surgery."10 He reports that the development of expertise in ECMO centers has made possible the application of technologies other than that which organized the teams. Some ECMO programs are able to treat up to one-half the babies referred for ECMO with conventional methods.10 ECMO team members are drawn from several specialties and tasks are performed by members of more than one specialty with the key supervisor, for example, being sometimes a pediatric intensivist, sometimes a neonatologist, and sometimes a pediatric cardiac surgeon. This might suggest an early division of opinion as to whether childrens’ hospitals or neonatal intensive care units (NICUs) attached to large obstetric units are to be preferred locations for ECMO technology. Finally, experience with a wide variety of technologies from ultrasound to lasers shows how quickly new technologies jump the boundaries of their originating specialties when medical tinkerers see them in action. With dynamic medical technologies, the experience of early (and not so early) adopters may be considered part of a technology’s development. These technologies develop as they diffuse with adopters’ activities complementing or diverging from the work of the initial developers, whose work may also be ongoing. This process of adaptation may seem to develop or to betray the original innovation. It leads to inconsistencies in results and in the published literature and to variations in local practice. Different versions in different hands provide different localities with differing experiences which may lead to inappropriate curtailment of use in one community and to excessive optimism in another. While highly significant in affecting local assessment, diverse experiences may or not make it to the published literature and may or may not be considered to contribute. Patients will have been selected differently, procedures will have been performed differently, outcome measures will be inconsistent, and few will have adequate controls. Multiple Vantage Points for Adoption Decisions If it is difficult to develop useful guidelines for medical doctors considering adoption or use of dynamic medical technologies, it is much more difficult to guide adoption when a variety of non-medical concerns and pressures come into play as they do in the operation of contemporary hospitals.12’13 While it is tempting to focus on medical criteria, other decision criteria may constrain or impel adoption and use. Indeed, our data indicates that medical doctors are less involved in hospital decisions than a decade ago and medical criteria are less influential.14 Three types of assessments affect the adoption of hospital-based technologies such as ECMO. These are summarized in Table 1. Medical criteria are applied by doctors, both those who will apply ECMO and those who will refer patients for it. But these decision-makers confront two types of organizational decision-makers who draw their decision criteria from the fiscal/ managerial and strategic planning domains. Medical Assessments Affecting Adoption by Physician Users In many studies certain attributes of innovations have been observed to affect physician adoption of a new technology. Among those commonly identified are: relative advantage over previous methods, risk, compatibility with adopters’ values, understandability, and complexity of use.2,3 Each of these attributes is actually a subjective judgement made by a potential adopter who perceives risk and complexity in relation to personal skill and experience, advantage in relation to failure or success with alternative methods, and complexity in relation to professional backup and organizational capabilities. Given the many questions that are likely to be unanswered in the literature and the difficulty of integrating change into one’s practice, the most common result is to "wait and see"—where the findings of the literature will settle, what models will become available, how one’s local colleague’s will respond, where and when the local consensus will gel. ECMO belongs to a small category of desperation technologies that may attract unusually positive assessment since they offer hope where there was no hope. Relative advantage is calculated against death; calculations of risk may also seem niggling. The absence of scientific data on long-term outcomes leaves physicians without the ability to include in their assessment important aspects of risk, benefit, and compatibility with values. In the absence of comprehensive outcome data, application is likely to emphasize (1) short-term goals, (2) theoretical plausibility of benefit, and (3) one’s level of satisfaction with alternative treatments. Despite the compelling thrust toward diffusion provided by desperation technologies, adoption remains problematic. Most physicians are very concerned about their ability to perform morally and proficiently within professional guidelines. Application of a technology may involve pain, expense, and anguish for patient and family. Two attributes of innovations that are commonly associated with adoption are firsthand observability of benefits and potential for hands-on trial. Opportunities for observation and training may be initially limited to those offered by developers. Accordingly, they may vary, although many innovators are also energetic educators who open their units to interested colleagues to observe and learn. Well into the diffusion of surgical procedures, it appears that existing sites of activity are the most important dispensers of education and trial. The personal experience acquired at such sites is often a motivator to further action but it may also highlight dangers, such as a high complication rate in the learning stage, or difficulties, such as those encountered in mounting a new program. Manufacturers have long been attuned to the need to hand carry reassuring information to potential but skeptical users of their products, and to reduce those barriers over which they have some control, such as providing staff training, technical backup, or a period of equipment trial. | Table 1: Types of Hospital Technology Assessments | | Dimension | Medical-individualistic | Fiscal-managerial | Strategic-institutional | | Prominent actors | Physicians, primarily specialists | Chief executives, fiscal officers, employed department heads, hospital-based physicians | Governing boards and chief executives | | Espoused ideologies and values | Maximizing patients welfare, avoiding risk | Rationality, predictability, financial viability, "profitability" | Formulating and realizing viable institutional missions, securing and protecting future options. | | Bases of influence | Professional training, clinical experiences, colleagues’ respect | Reputation for financial, computational, and marketing ability | Authority, credibility, and charisma | | Typical structuring of decisions | Professional collegia, medical staff committees | Embodied in standardized procedures and analytical programs | Long-range planning and policymaking bodies | | Typical decision processes | Assessing clinical effects consensually, tempered by norms of professional deference | Conducting cost-benefit analyses, discounted cash flows, etc. | Forecasting impending threats and opportunities, constructing alternative scenarios | | Information gathering and utilization | Information obtained, personal experience, professional media, and short courses of developers/advocates | Systematic search, quantitative evaluation | Information gleaned from diffuse sources combined and extrapolated holistically |
Medical Assessments Affecting Decisions of Referring Physicians Physicians who refer patients to specialized facilities also grapple with assessment of benefit and risk but from a somewhat different perspective. These physicians are less likely to be abreast of specific findings concerning the procedure and do not expect to make a final determination on appropriate application. They are likely to become aware of new modalities such as ECMO through a personal contact with a person who is familiar with the technique. Physicians affiliated with the hospital offering a new treatment are likely to produce the first referrals. Referrals from neighboring institutions are likely to be next. Most often these will be stimulated by contacts that referring physicians have with the local innovators or from contacts that these physicians have with other physicians who are aware of the option—rotating residents, circuit-riding colleagues who practice at multiple hospitals, or newly affiliated physicians. This process of information diffusion may be speeded by continuing education or marketing activities of the sponsors or the sponsoring hospital, local professional associations, manufacturers, or medical schools. Referring physicians will weigh problems of patient transfer against possible benefit. Referral for a life-saving technique is likely to be appealing, although enthusiasm for referral is often tempered by the physician’s general dislike of transporting patients to another institution. They dislike the hazards and inconvenience associated with referral and may perceive the potential to lose a patient to physicians at the referral center. The more referrals from a specific hospital to a referral center expand, the more physicians at the former seem willing to consider local development of the program. This possibility seems reduced to the extent that ECMO is a self-limiting procedure offered at specialized children’s hospitals, although it is possible to imagine that neonatologists at a non-ECMO center might fear loss of referrals to a NICU having the ECMO backup. As a technology such as ECMO is refined, indications are expanded and additional uses are contemplated (e.g., ECMO as a backup for surgery vexed by respiratory failure), the arguments for additional programs may grow. Fiscal and Managerial Considerations Affecting Adoption Current payment strategies that fix the amount that will be paid for procedures, either annual patient care or specific diagnoses, were intended to make adoption of expensive but seldom-used technologies unattractive because they are unprofitable. The acceleration of the hospital "arms race" that has accompanied implementation of competitive policies suggest that they do not work in the way intended.15 In response to the new payment policies, the ranks of financial, marketing, and quality control workers in hospitals have swollen. These specialists provide expert analyses of the fiscal and managerial aspects of the organization that affect the bottom line, including technology. These staffs work with such aspects of the organization as management of volume, billing, patient mix, contracts for services, and position in the capital market. They suggest means to maximize and regularize income and control expenditures in ways that accommodate the fixed payments that hospitals have agreed to accept. Toward this end, they combine cost-control and marketing strategies, trying both to hold down costs and increase patient revenues. Such financial calculations are supposed to favor economies of scale and the avoidance of activities where insufficient volume produces high "per unit" costs. However, for each strategy of curtailment there appear to be alternatives, such as increasing volume and providing as many services as possible internally. It has been suggested that administrators of hospitals containing ECMO units may encourage an expansion of indications for its use in the interest of achieving financial solvency for the unit.10 Similarly, in my area, HMO’s have reportedly questioned the need to refer babies out of a prepaid neonatal center to an ECMO center where additional costs must be paid. In advising the development of new programs such as ECMO, fiscal and managerial staff are asked to calculate the period required for "payback," given start-up costs, payments, and projected volume. However, an unfavorable calculation is more likely to restrain low visibility expenditures—routine equipment purchases, staffing, or research—than those with high visibility or potential visibility. Even under rate review, hospitals’ cost-reducing strategies in the area of technology were directed primarily to second pieces of equipment and replacement of equipment, not to new introductions.16 Under market competition, there is increased pressure to direct funds to areas that enhance the hospital’s visibility, market share, or potential to tap new markets. Strategic Planning Considerations Affecting Assessment In recent years, the importance of strategic plans to hospital management has steadily increased.17 The competitive pressures of policies introduced since 1984 have accented the importance of targeting development to achieve desired position in the marketplace. "Markets" may be diagnoses that are favorably reimbursed under DRG’s, or populations that are well-insured, and one market may be perceived as connected to another. Financial and managerial calculations are advisory to strategic planning, which focuses heavily on the image that the hospital wishes to convey. How costly will it be to convey the desired image of a hospital as better or at least as good as competitors? What is the cost of increasing market share, capturing new markets, or securing future options? Money may have to be saved somewhere in the hospital, but it will not be in areas targeted as strategically important, given concern with image, payment, demographics, or interrelationships with other services. In these cases, the issue is not the balance sheet, but survival viewed strategically. Strategic planning may dictate the development of ECMO programs, irrespective of potential financial losses. In my area, cardiac surgery offers a prior example. Hospitals have continued to introduce new programs in spite of a dense supply. Administrators argue that heart surgery is a necessary backup to angioplasty and therefore to cardiology, and because "ambulances will bypass a hospital that does not have heart surgery." They closely watch outward referrals with dismay, often envisioning a domino effect. For similar reasons, it has been difficult to sustain the regionalization that once characterized neonatal intensive care. Obstetrical care is dispersed among hospitals which, if it can be avoided, do not want to refer mothers to regional centers from which they may not return. As one neonatologist told us: "I mean the perinatologist [at a regional center] has to work hard to tell the [referred] mother ‘I’ve taken care of you during this high risk delivery. Now you go back to your regular obstetrician in the suburbs. Okay?’ The hospital in the suburbs has to work hard to have itself identified as being still the place that is going to provide medical care for that family and not have the mother say, ‘God, when I have been really sick and I had that real bad baby and I went into the hospital in the middle of the city at the medical center, I had such great care. God, if anybody in my family ever gets sick again, we’re going right back there." Hospital administrators routinely cite outward referrals in their arguments for the adoption of a new technology or service. ECMO seems susceptible to such pressures, especially since the existence of superior neonatal intensive care is often advertised as a reason that prospective mothers should choose a hospital’s obstetrical unit. Obstetrical care, in turn, is viewed as the entry point for families to life-long hospital care and an important element in the full-service package sought by HMO’s. When are medical, fiscal/managerial or strategic criteria important? How do the decision-makers who employ them exert their influence? What concordance among decision-makers is necessary for a chosen policy to be realized? To inform answers to these questions, the next section will be devoted to developing a brief prototype of adoption dynamics. This simplified representation contains characteristic elements that we have encountered repeatedly across diverse technologies. Prototype Adoption Although information on a new technology may be appearing and being noted by local physician communities, active local consideration awaits the emergence of a local medical innovator. This first adopter affiliates with a developing technology, perhaps early enough to be a major contributor, or somewhat later in its evolution. This local innovator is linked from past training or experience to national or regional pioneers of the technique, or now becomes so linked. When the demands of the technology require large expense or organizational adjustment, the innovator is successful to the extent that an idea champion is engaged. This is frequently a hospital administrator who seizes upon the idea of securing a new market or positioning the hospital for future gains. The hospital board is persuaded of the importance of the new development. The program is organized. The innovator addresses technical problems and trains colleagues and staff, while the administrator addresses problems of finance, recruitment, turf, and securing a referral base for the procedure The existence of the program alters the local environment. Potential new adopters and referrals surface as the new activity (1) generates visible applicable clinical evidence; (2) opens opportunities for training of both residents and existing specialists; (3) attracts attention of media and patients, thus generating publicity and patient inquiries; (4) focuses attention on merits of the development (wise or unwise, wisely located or misplaced); (5) spotlights the behavior and referrals of physicians in relevant specialties (Do they perform? Refer locally? Refer to more distant sites?); and (6) provides ammunition to equipment or other salesmen who will manipulate the appearance of consensus and rapid diffusion in the hopes of expanding utilization. All of this speeds the need of pertinent specialists to develop a professional opinion, potentially speeding the development of a consensus for change. The larger community of physicians is affected by (1) a surge of information following local adoption (brochures, lectures, demonstrations, referral solicitations) from the provider hospital, manufacturers, newspaper reports, continuing medical education, and gossip; (2) circulating individuals who are aware of the new activity; and (3) patient inquiries stemming from newspaper stories or contacts with early patients or their families. This turbulence in the local arena demands a response and raise a suspicion on the part of physicians and hospitals that patient choices of physician and hospital may be affected by this. Hospital administrators are aroused as the lead hospital markets the new technology to potential patients as a mark of superiority and to HMO’s as a reason to become a member health care provider. Administrators of rival hospitals perceive the new technology as a threat to their own high technology image, to viability of their own competing units, and possibly thus to the whole of the hospital. They begin to monitor outward referrals, inquiries from patients and HMO’s, outward transfer of prospectively budgeted funds, image benefit to other institutions, and the overall effect of the development on competitive relationships with rival hospitals. They consider their own position in terms of advantages to be gained from offering the technology and the chances of capturing existing or future market share. If the development is viewed as a serious threat or serious opportunity, hospital executives may encourage physicians interested in performing the procedure or begin recruitment of physicians with needed skills and interest. The Role of Guidelines Information circulates as this drama plays, but seems not to be master of the forces at work. My own studies of the diffusion of innovation began in 1975, when open heart surgery could be observed in its still early stages in my city of Milwaukee. In one of the first half dozen interviews of what now approaches 800, a local heart surgeon, Dr. Derwood Lepley, pressed into my hands the 1972 report of the Committee on Coronary Artery Surgery of the Intersocietal Commission for Heart Disease Resources. The Intersocietal Commission had as its sponsors virtually every professional society and government institute bearing any relation to heart, surgery, or hospitals. The report was entitled "Optimal Resources for Coronary Artery Surgery." The committee had been chaired by Dr. Lepley. The report specified the qualifications and numbers of personnel that the procedure required, the necessary equipment, relationship to diagnostic facilities, and the minimum volume of procedures. Committee members felt so strongly about the need for teams performing the surgery to commit themselves to research that they devoted almost one-third of the 14-page report to criteria for assessing the results of surgery, including three pages devoted to diagrams directing autopsy. Already in 1975, Dr. Lepley was grieving over the disregard of the guidelines. He and other early developers interviewed by us in longitudinal personal interviews were to lament the role of money and other forces in driving a different diffusion pattern than that advised by the committee and to decry their successors’ lack of interest in research. I recalled those early days when I read the statement of the Committee on Fetus and Newborns of the American Academy of Pediatrics and pondered the fate of that document and the deliberations of the NIH workshop reported in this publication. Where do such guidelines fit into diffusion? Apparently statements are noted by recipients but not acted upon 18,19,20,21 In the following paragraphs I briefly consider the potential for guidelines to influence the categories of decision-makers that I have identified in this paper. Medical Decision-makers: Adopters Medical innovators, including early adopters, are likely to reject guidelines that are inconsistent with their own assessments of a technology. They embrace as goals the improvement of equipment, technique, knowledge, and results. They are aware of the changes that they and others have introduced and tend to dismiss contrary results, including controlled trials, as inapplicable because dated. Negative results from other teams are often attributed to incompetent performance of the technique. Innovators frequently disavow irresponsible diffusion of a new technology but contribute to it through their own demonstration and training, which provides the pool of professionals available to launch new initiatives. Medical Decision-makers: Referrers Education directed to individual physicians does not have a robust effect unless reinforced by local peers whose agreement may be quickened by pressures from patients, local media, manufacturers’ representatives, and health care administrators. Potential referring physicians may be advised to evaluate ECMO facilities for desired characteristics but by the time they are considering a potential referral, they will probably have it associated in their minds with particular places and individuals known to them for this or other reasons. Since referring doctors do not decide appropriate application, additional information provided to them (if it has an effect) will likely stimulate referrals to ECMO teams for evaluation. Fiscal and Managerial Decision-makers In a situation of multiple payers, the opportunity to use payment to enforce guidelines seems limited. Fiscal incentives have proven effective enablers of expansion but poor vehicles of restraint. Competition among insurers has all but guaranteed coverage of high profile services atleast for certain groups. Competition among hospitals all but guarantees the pervasive development of these services at the expense of other services if need be. Payment decisions not in accord with local professional and public opinion present themselves not as the basis for a hospital’s strategic plan but as obstacles to be surmounted in the interest of implementing it. Strategic-Institutional Decision-makers It is not clear at this time what potential ECMO has to be perceived by the public as a life-saving technique that should be offered by all excellent hospitals. Should it develop this image, it could be the sort of technology which is very hard to contain. Lack of sufficient volume for multiple programs is not necessarily a deterrent and may merely feed competitive rivalry to attract physicians with strong reputations or referral networks or to absorb losses as a cost of doing business. A hospital’s strategic plan rests, finally, on the best guesses of administrators and boards of directors about future hospital care—the services which successful hospitals will offer and the ways they will be provided, including the standards which will be demanded by doctors and the public. Unless strategic decision-makers associate practice guidelines with operating or symbolic values as significant as the hospital’s technology profile, they will be accorded minimal weight. Conclusion With dynamic technologies, those evolving as they diffuse, overall patterns of adoption and use of technology reflect a myriad of local decisions. These, in turn, reflect a variety of local considerations, both medical and non-medical. For many reasons guidelines which are externally developed may appear inapplicable and thus fail to achieve their desired results. Local social processes have shown themselves time and again to support their own versions of moral behavior, including sabotage of externally-imposed directives. In the United States, it is now unfashionable to ask physicians to shape the conduct of medical practice, except at the individual level. Nor have physicians come forth. The current system provides no consistent forum for local discussion of medical standards or priorities and no place for local physicians to participate meaningfully in the allocation of resources. Just as the adoption and use of innovation hinge on the action of local professionals, so may the restraint of innovation. Lest vitality and compassion be lost in the pursuit of rational medical behavior, local physicians need mechanisms for response which are as dynamic as the innovations. Acknowledgments This research is supported by the Agency for Health Care Policy and Research (Grant #RO1 HS 06065-01) which also supported the collection of baseline data (#1 RO1 HS 03238-01A1). References Coleman JS, Katz, Menzel H: Medical Innovatiom: A Duffusion Study lndianapolis Bobbs-Merrill, 1966. Rogers EM: Diffusion of Innovations. New York, Free Press, 1983. Greer AL: Medical Technology Assessment, adoption, and utilization. J of Medical Systems 5:129-145, 1981. Greer AL: The state of the art vs. the state of the scinece: Diffusion of medical technology into practice. Int J. of Technology Assessment in Health Care 4:5-26, 1988 Allen TJ: The role of person-to-person communications in the transter of technological knowledge. IN: Roberts EB, Levy RI, Finkelstein SN et al. Biomedical Innovation. Cambrioge, MA. MIT Press, 34-39, 1981. Paneth N, Wallenstein S: Extracorporeal membrane oxygenation and the play the winner rule. Pediatrics 76:622-623, 1985. Wung J-T, James LS, Kilohevsky JE: Management of infants with severe respiratory failutre and persistence of the fetal circulation, without hyperventilation. Pediatrics 76:488-494, 1985. Dworefz AR, Moys FR, Sabo B et al.: Survival of infants with persistent pulmonary hypertension without extracorporeal membrance oxygenation. Pediatrics 84:1-6, 1989. Donn SM: ECMO indications and complications. Hospital Practice 25:143-157, 1990. Personal communications, 1990. Greer AL: Adoption of medical technology: The hospital’s three decision systems. Int. J of Technology Assessment in Health Care 1:669-680, 1985 Fennell ML, Warnecke RB: The Diffusion of Medical Innovations: An Applied Network Analysis. New York, Pienum, 1-8, 1988 Greer AL, Greer S: Medical Technology Decisions in Hospitals: Changes Since 1980. Final Report for Grant #R01 Hs 06054. The Agency for Health Care Policy and Research, Rockville, MD, 1991. Greer AL, Greer S: Some consequences of market forces in U.S. hospitals: Lessons for the new Look NHS?" Health Services Management, forthcoming 1990. Wagner JL, Krieger MJ, Lee RH et al: A Study of the Impact of Reimbursement Strategies on the Diffusion of Medical Technologies. Washington D.C., Urban Institute, 1982. Luke RD, Begun JW: The Management of Strategy, IN: Shortell SM, Kaluzny AD, Health Care Management: A Text in Organization Theory and Behavior, New York, John Wiley 463-487, 1988. Kosecoff J. Kanouse DC, Rogers WH et al.: Effects of the National Institutes of Health consensus development program on physician practice. JAMA 258:2708-13, 1987. Greer AL: The two coltures of bio-medicine: Can there be consensus? JAMA 258:2739-40, 1987. Lomas J, Anderson GM, Pierre KD et al.: Do practice guidelines guide practice? The effect of a consensus statement on the practice of physicians. N Engl J Med 321:1306-11, 1989. Lomas J. Words without action? The production, dissemination and impact of consensus recommendations. IN: Omenn GS (ed). Annual Review of Public Health 12:41-65, 1991. Extracorporeal Life Support: State-of-the-Art 1990 Robert H. Bartlett, M.D. and Charles Stolar, M.D. University of Michigan Medical Center and Columbia Presbyterian Medical Center Introduction The apparatus and techniques of extracorporeal circulation are routinely used for a few hours to permit surgery on the heart. With several modifications, extracorporeal circulation can be used for days or weeks to support the life of patients with severe cardiac or pulmonary failure. The procedure involves cannulation of major vessels without thoracotomy, carefully titrated partial anticoagulation with heparin, and continuous high-flow extracorporeal circulation through a membrane lung. Depending on the cannulation and application, this procedure has been called extracorporeal life support (ECLS), extracorporeal CO2 removal (ECCOR), extracorporeal heart assist, extracorporeal lung assist, and extracorporeal membrane oxygenation (ECMO). In this report the abbreviations ECLS and ECMO are used interchangably. ECLS is not a therapy, but a mechanical support system which allows time for the damaged heart or lungs to heal in a milieu of normal perfusion and gas exchange, while "resting" the damaged organs from the effects of mechanical ventilation and inotropic drugs. In the last decade ECLS has grown rapidly from a research protocol to clinical practice. It has been the most successful in neonatal respiratory failure and is now considered standard therapy for full-term infants with severe respiratory failure. It is the only method of mechanical cardiac support in children. It is a reasonable (albeit extraordinary) approach to the management of severe respiratory failure in children and adults. Over 3,000 infant cases have been treated in the United States1 There are more than 60 neonatal centers offering ECLS as standard treatment.2 Currently the treatment is used for moribund infants with 83 percent survival overall and 95 percent survival in the most experienced centers: The incidence of pulmonary or neurologic handicap (approximately 20 percent)3 is lower than that of other neonatal intensive care unit (ICU) graduates.4 Two prospective randomized studies have demonstrated the effectiveness of ECLS in newborn infants,5,6 and two studies have documented an overall decrease in hospitalization and expense in neonate.7,8 Thus, although ECLS is the ultimate example of high-tech, labor and resource-intensive, expensive, invasive procedures, it routinely results in healthy children at less cost, resource utilization, and morbidity than the previous conventional treatment. (We wish this were true for liver and bone marrow transplantation or cancer chemotherapy.) A study group of active centers was organized in 1989—the Extracorporeal Life Support Organization (ELSO). The results of ventilator and pharmacologic management in neonatal respiratory failure are excellent. Only a few neonates managed primarily at major centers fail to respond to treatment. There may be several deaths in any year if there are many cases of diaphragmatic hernia and neonatal sepsis. There may be none at all if only meconium aspiration and persistent fetal circulation are treated. Nonetheless, there are still approximately 3,000 deaths from respiratory failure in full-term infants each year in the United States. Almost all of these deaths are preventable. Why does extracorporeal support result in routine recovery of infants who are moribund with acute respiratory failure? Certainly there is nothing therapeutic about anticoagulation and extracorporeal circulation. Lung recovery must result from "resting" the lung from high pressure and high oxygen concentration. Simply by sustaining the life of the infant through a few days (which usually includes total lack of lung function) recovery of aeration, pulmonary blood flow and ultimate survival almost always results. This should suggest to us that there is something about the ventilator or pharmacologic management of this small group of full-term infants that contributes to pulmonary dysfunction. Obviously, a change in treatment aimed at preventing progression to severe respiratory failure would be better than treating established respiratory failure with ECMO. Because most of the clinical application of ECMO is currently in newborn infants, this description and discussion will refer primarily to that group of patients. The basic principles of extracorporeal circulation, gas exchange, and systemic oxygen delivery apply to patients of all sizes and ages. ECLS Technology The circuit includes a servo-regulated roller pump, membrane lung, heat exchanger, tubing, and connectors (Figure 1). Right atrial blood is drained via a right internal jugular vein cannula to a small distensible bladder. A microswitch on the bladder automatically regulates the roller pump, controlling blood flow based on venous drainage and preventing air embolism. Blood passes through the pump and is perfused through a membrane lung. The size of the artificial lung is selected to provide total cardiopulmonary support, even though partial support will be adequate for most patients. Routine blood flow rates are 100–150 cc/kg/mm in neonates. As the blood is oxygenated, CO2 and water vapor are removed into the gas phase of the artificial lung. Blood then flows through a heat exchanger and back into the patient. In venoarterial circulation, the blood is perfused through the right carotid artery cannula into the aortic arch. In venovenous circulation blood is returned to the venous circulation.
 Figure 1. Diagram of a typical neonatal ECMO circuit. Venoarterial bypass is represented. Permission to reprint by Mosby Year Book, Inc. New York.39 Cannulation is performed at the bedside in the ICU with an operating room team present. The internal diameter of the venous catheter is the limiting factor which determines maximal flow. The diameter of the arterial catheter determines pressure in the circuit. Once on ECMO support, paralyzing agents, vasoactive drugs, and other infusions are generally discontinued. Ventilator settings are adjusted to minimal levels to allow "lung rest." Typical neonatal settings are: pressure limit 20 cm H20, positive end-expiratory pressure of 4cm H20, rate 10/mm, and FiO2 0.3. The patient is usually awake and alert. During venoarterial bypass, blood flow is maintained at a level sufficient to keep the venous saturation at approximately 75 percent. Venous saturation is continuously monitored by a fiberoptic catheter in the venous line. A normal venous saturation insures that the combined oxygen delivery from the patient’s cardiopulmonary system and the circuit is adequate for oxygen consumption requirements. A continuous non-invasive arterial oxygen saturation monitor is placed on the patient in an area of postductal blood flow distribution. With this monitoring available, arterial blood gases need only be drawn occasionally once the patient is stable. The arterial saturation is maintained at 95 percent and is manipulated by adjusting the extracorporeal blood flow rate. The PCO2 is maintained between 35 and 50 and is inversely proportional to the flow rate of gas ventilating the membrane lung. During venovenous bypass, blood is recirculated to and from the right atrium, so that the mixed venous blood is typically 85–90 percent saturated. If the lung is not working at all the arterial blood will have the same saturation. As lung function improves there will be a step-up between right atrial and arterial blood. Although venovenous support results in lower arterial P02, systemic oxygen delivery is sustained by increased cardiac output, and the overall ability to provide lung rest and ultimate survival is the same as in venoarterial bypass. The use of venovenous bypass in the neonate avoids ligation of the carotid artery. Heparin is infused continuously at 30–60 units/kg/hr. The level of anticoagulation is monitored hourly by the whole blood activated clotting time (ACT). The heparin dose is adjusted to maintain the ACT between 200 and 220 seconds (normal is approximately 100 seconds). There is a fall in platelet count at the onset of bypass; platelet consumption continues during ECMO. In infants, platelet transfusions are required to maintain a level greater than 75,000. The hematocrit is maintained between 45 to 50 percent and occasional red blood cell transfusion is required. In general, hemolysis is minimal and free serum hemoglobin 300 40 levels are usually <30 mg/dl during ECMO (normal <5 mg/dl). Antibiotics and parenteral nutrition are routine; diuretics are given if the patient is edematous. The extracorporeal flow is gradually decreased when the native lung function increases. When the flow is approximately 20 cc/kg/mm a trial off the bypass at low ventilator settings is attempted. If tolerated for a 1-3 hour period, the cannulae are removed. Patients often are weaned from the ventilator and extubated over the subsequent 24-48 hours. Management of a typical case is shown in Figure 2. Figure 2. Ventilator settings and clinical events during a typical neonatal ECMO case. Permission to reprint by Mosby Year Book, Inc., Chicago, IL. In: Ravitch (ed.): Pediatric Surgery, 4th edition, 1986, pp. 74—77. ECLS has become routine practice in the last several years because of the standardized system and approach, and because of the development of a new group of health care professionals—the ECLS clinical specialist. The need for ECLS specialists arose because the current systems require continuous attendance for monitoring and management, coagulation control, and management of emergencies. Specialists may have been trained in medicine, nursing, respiratory therapy, or perfusion. Extensive didactic, laboratory, and bedside experience is required, because even individuals from these various professions do not have the backgrounds necessary for ECLS management. The ECLS specialist team is essential for making the technique work, but it is also the most expensive component of extracorporeal life support. The Development of Prolonged Extracorporeal Circulation Between 1955 and 1970 hundreds of bioengineering and laboratory studies brought prolonged extracorporeal circulation from theory to clinical application. These studies are described in detail elsewhere.11,12,13,14 The first attempts at prolonged extracorporeal circulation in humans were by Callaghan,15 Dennis,16 and others. The first attempts at respiratory support in infants were reported by Rashkind,17 Dorson,18 and White.19 The first successful adult case was reported by Hill, O’Brien, and others in 1972.20 Reports of several other successful cases soon followed.21 22,23 In 1974 the Lung Division of the National Heart and Lung Institute proposed a multicenter, prospective, randomized study of ECMO in adult respiratory failure. This study began in 1975, which was a pivotal year for extracorporeal support. In 1975 a meeting was held outside of Copenhagen which included most of the researchers on prolonged extracorporeal support; the proceedings were reported in a benchmark publication.24 The plans for the NIH adult ECMO study were reported and reviewed at that meeting. Four different membrane oxygenators were manufactured and used in 1975, the Kolobow Sci-Med, the LandJ -Edwards, the Pierce-GE, and the Bramson (the Food and Drug Administration did not become involved with devices until 1976). The first successful treatment of a newborn infant with ECMO was done in May 1975 and reported at the Copenhagen meeting. Adult Respiratory Failure The NIH-sponsored study of ECMO in adult patients was completed in 1979 and reported in 1980. 25 Other related studies of pathology findings and the epidemiology of respiratory failure26 in the study centers were reported. The study had a major influence on later prospective randomized controlled studies in neonates, so it will be described in some detail. This was the first attempt at a prospective, randomized study of a life-support technique in which the end point was death. There were many problems with the study; nine centers were involved, some of which had no prior experience with ECMO before their first study patient. The logistics of consent to the study tended to exclude the best-risk and worst-risk patients. A nationwide epidemic of influenza pneumonia occurred in 1976, and these patients dominated the trial. Bleeding complications were major, with average blood loss exceeding 2 L per day.28 Although the purpose of ECMO is lung rest, many of the patients remained on high ventilator settings.28 The study was planned for 300 patients, but it was terminated after 92 patients were entered because the survival in both control and ECMO group was less than 10 percent and it seemed unlikely that the results would be any different after 300 patients. The cause of death was related to technical complications in a significant number of patients, but extensive and apparently irreversible fibrosis was uniformly found at autopsy, indicating that the major problem was not the technology but the underlying parenchymal lung disease.26 As a result of this study, clinical research on ECMO in adult patients essentially stopped in 1979. Since that time only occasional cases have been reported in the United States, and the study of extracorporeal support in adults occurs primarily in Europe. Evolution of the Concept of Extracorporeal CO2 Removal Luciano Gattinoni worked with Kolobow at the National Institutes of Health, learning the techniques of extracorporeal support in sheep. He returned to Milan, Italy, with these hypotheses: (1) The purpose of ventilation is to excrete CO2; oxygenation can be achieved by inflation and airway oxygenation alone. Progressive lung injury in adult respiratory distress syndrome is caused in part by ventilator-induced high pressure injury of the most normal alveoli. When functional residual capacity is severely decreased, the remaining alveoli can be overinflated if high tidal volumes are used, leading quickly to alveolar injury and fibrosis. An extracorporeal support system should eliminate the need for high airway pressure and high FiO2, although this was not always done in the NIH-sponsored ECMO study. (2) If the emphasis is on CO2 removal to eliminate the need for high pressure ventilation, this could be accomplished with venovenous access, using relatively low flow and large membrane-oxygenator surface area. This system would allow for normal pulmonary blood flow, even if the lung is severely injured with large amounts of transpulmonary shunting. The venoarterial bypass used in the NIH ECMO study caused decreased pulmonary blood flow which might have contributed to microthrombosis or inhibition of lung healing. Gattinoni and his colleagues used these principles in venovenous extracorporeal gas exchange in a variety of adult patients selected by the same criteria used for the NIH ECMO study. In 1986 they reported 21 survivors in 43 patients (49 percent).29 These results were corroborated by Lennartz and colleagues in Marburg, Germany,30 Falke in Dusseldorf,31 Bindslev32 in Stockholm, and Todd in Toronto.33 Similar results were reported by Morioka of Kumamoto, Japan.34 All of these investigators reported their results at a European communities conference held at Marburg, Germany in 1988.35 Neonatal Respiratory Failure Bartlett, Gazzaniga, and their colleagues at the University of California, Irvine, treated the first successful neonatal ECMO patient36 (named by the nurses, Esperanza-Hope).37 This was soon followed by other successful neonatal cases.28 By mid-1980 they had treated 40 newborn cases with 22 survivors.39 The technique for newborn infants was fairly standardized, including venoarterial access via the right internal jugular vein and right carotid artery, heparin titration based on whole blood activated clotting times, "lung rest" at low ventilator settings, and recognition of persistent pulmonary hypertension as the primary underlying pathophysiology. In 1979 the first neonatal ECMO seminar was held at the University of California, Irvine, demonstrating the circuit, the technology, and the concept of the ECMO team, and specialists. This led to the development of ECMO research teams in Richmond, Pittsburgh, and Detroit. In 1980 the neonatal ECMO project moved from the University of California, Irvine, to the University of Michigan and experience gradually increased from a few cases each year to a few cases each month. Representatives of other centers attended the annual seminar, and some established ECMO teams—all with a standardized system and protocol. By the end of 1986 715 newborn cases had been treated in 18 centers40 with excellent survival results reported from each center.41,42,43,44 By the end of 1989 over 3,500 cases had been treated in 64 centers. The growth of neonatal ECMO centers and cases is documented in Figure 3. The sequence of events which controlled the diffusion of this technology are discussed in detail elsewhere in this symposium. With the technique standardized and an experienced team trained, the Michigan group carried out a prospective randomized study in newborn infants between 1982 and 1984.45 They used a statistical technique called randomized play-the-winner, in which assignment to one treatment or the other is randomized, but influenced by all the previous patients in the study.45 Statistical significance is reached when there is a significantly larger group of patients in one arm of the study compared to the other. This resulted in the unusual groupings of one control patient (who died) and 11 ECMO patients (all of whom survived). This proved that the results with ECMO were better than conventional therapy, but the study was treated with skepticism. The most articulate of the critics, Ware and Epstein,49 undertook to design a prospective randomized study of ECMO in neonatal respiratory failure, but soon encountered the same problems of ethics and logistics. They solved this problem by using a similar adaptive statistical design. Four of 10 control conventional ventilation patients died and 1 of 38 ECMO patients died. This second prospective randomized study was reported in 1989.6 It should be noted that it is most unusual for a new technology to be tested by two separate prospective randomized controlled trials of life support systems in which the endpoint is death. These are, in fact, only the second and third such studies reported (the first was the adult NIH study referred to earlier). The ethical and logistical problems encountered when designing a prospective randomized study of a life-support technique in children are particularly difficult; this difficulty is compounded when it is known that at least 90 percent of the children given the experimental treatment will survive. During the adult ECMO study this problem and several other problems of study design were identified. All of these problems were addressed in the design of the neonatal studies. Aside from a general increase in survival of patients considered to be moribund, the application of ECMO has had an impact on some specific neonatal conditions. Congenital diaphragmatic hernia symptomatic in the first day of life has carried a 50 percent mortality risk for the last 40 years. ECMO is used for those infants who are dying from pulmonary failure—the survival rate ranges from 60-90 percent in various centers. This has changed the natural history of diaphragmatic hernia from 50 percent mortality to 25 percent mortality, as documented in one recent study.47 Neonatal sepsis was thought to be a contraindication to ECMO in 1982. Septic patients are now treated routinely with 80-90 percent survival. Use of ECMO for premature infants less than 35 weeks gestational age was tabled in 1983 because of high incidence of intracranial bleeding in those patients. Now, with improved techniques of anticoagulation and management of intracranial venous and arterial pressure, research has resumed on respiratory failure in premature infants. The early results are very promising. The follow-up on the first 72 neonatal survivors ranged from 3 months to 11 years.10 Ten children (14 percent) were lost to follow-up. Forty-five (63 percent) were normal or near-normal. Twelve (17 percent) had neurologic dysfunction and/or developmental delay. These results are similar to the findings of Towne,45 Krummel,49 and others who noted normal mental function in 70-80 percent of the patients in their studies. Additionally, all these results are comparable to the 77 percent normal mental ability noted in the 3-year follow-up of patients treated with conventional mechanical ventilation therapy. This suggests that neurologic damage is secondary to events that precede the onset of ECMO. Eight of the first 72 neonatal ECMO survivors (10 percent) had residual lung disease when discharged from the hospital.10 The bronchopulmonary dysplasia (BPD) resolved in two patients. This compares with a 0-35 percent incidence of BPD in survivors of conventional therapy. This increased survival in high risk neonates with relatively low morbidity is gratifying. However, ECMO also appears to have economic advantages as noted in a study by Pearson and Short.7 The average daily ECMO charge was approximately $4,000, almost $2,000 more than the daily charge for conventional therapy patients. However, the number of hospital days was substantially reduced in the ECMO patients (21 vs. 37.4 days). The total hospitalization charge of survivors in the ECMO group was 43 percent less than that of survivors among the conventional mechanical-ventilation therapy patients. A recent prospective, randomized study comparing cost effectiveness and morbidity of conventional ventilation to that with ECMO was recently conducted at the University of Michigan.8 ECMO patients had shorter hospitalization and less morbidity without increased hospital charges. Present Status of ECLS Patient Selection: Mortality Criteria, Indications, and Contraindications ECMO is indicated when conventional management fails and the risk of morbidity or mortality is high. In respiratory failure the mortality risk is estimated by measuring the extent of pulmonary dysfunction and the level of ventilator support required to sustain gas exchange. In the neonate the underlying pathophysiology is usually pulmonary arterial vasospasm resulting in pulmonary hypertension and right-to-left shunting through the ductus arteriosus or foramen ovale (persistent fetal circulation syndrome, PFC). This is true regardless of the primary diagnosis. Because of this pathophysiologic syndrome, the degree of vasospasm and right-to-left shunting is reflected in postductal hypoxia despite high FiO2. In most neonatal centers PFC is treated by hyperventilation to induce alkalosis and relax the vasospasm. Compliance is usually decreased so that FiO2 and airway pressure are indirect measures of the degree of pulmonary dysfunction. These factors have been combined into measurements to estimate the severity of pulmonary dysfunction in the alveolar-arterial oxygen gradient (AaDO3) or the oxygenation index (OI). The normal AaDO2 is approximately 50 torr. When the AaDO2 is consistently higher than 600-620, despite optimal treatment, the mortality risk is 80-90 percent. The OI is calculated as mean airway pressure x FiO2 x 100/postductal PaO2. An oxygenation index consistently greater than 40 is generally associated with 80 percent or greater mortality risk. The usefulness of these measurements in any neonatal center is dependent upon the method and philosophy of ventilatory management. Each center must determine the mortality risk in that center using AaDO2, OI, or some other objective measurement. Relative contraindications to ECMO in newborn infants are prematurity less than 35 weeks gestational age, preexisting intracranial bleeding or other major neurologic injury, or mechanical ventilation longer than 10 days. The incidence of severe bronchopulmonary dysplasia is high in children who have been ventilated with high pressures for a few days, and is prohibitively high in infants who have been ventilated more than 10 days. Intracranial bleeding may be exacerbated by anticoagulation, so ECMO is generally avoided in babies with ultrasound evidence of intracranial bleeding. However, the risk of extending a bleed can be minimized by decreasing the heparin dose and increasing the platelet count. Grade Ill or IV hemorrhage is a definite contraindication, but many experienced centers are now using ECMO for infants with Grade I and questionable Grade II intracerebral hemorrhage. During the early development of neonatal ECMO, we realized that the incidence of intracranial bleeding was very high in premature infants (less than 35 weeks gestational age).51 Consequently, EGA less than 35 weeks became a contraindication in 1985, just before the rapid growth of cases and centers. Management of anticoagulation and blood flow has improved considerably, and the risk of bleeding is now decreased. The University of Michigan team recently used ECMO for two premature infants without complications. If this experience continues, prematurity will no longer be a relative contraindication. Results Between 1980 and 1989, 3,528 infants were registered in the Neonatal ECMO Registry of the Extracorporeal Life Support Organization. The patients were treated in 58 centers in the United States and 7 abroad (Table 1). The first 715 cases (1973-1986) from 18 centers were discussed in the first Registry report.40 The three years of 1987-1989 showed a 261 percent increase in ECMO centers and a 393 percent increase in treated infants. Although there was rapid increase in the aggregate and annual numbers of infants treated through 1988, the annual totals for 1988 and 1989 are the same (Figure 3). Similarly, the annual rate at which new ECMO centers have opened was greatest in 1987 and is less for 1988 and 1989 (Figure 4). The number of infants treated at any one ECMO center ranged from 2 to 100; the average annual number of ECMO cases was 12 per center per year. Almost all infants treated with ECMO were referred from a Level Ill neonatal intensive care unit specifically for respiratory management; 93 percent of the patients were outborn and only 7 percent inborn. Table 1: Centers Contributing Cases to the Neonatal ECMO Registry (1990) Children’s Hospital of Alabama, Birmingham, Alabama St. Vincent’s Hospital, Birmingham, Alabama Phoenix Children’s Hospital, Phoenix, Arizona St. Joseph’s Hospital and Medical Center, Phoenix, Arizona Arkansas Children’s Hospital, Little Rock, Arkansas Children’s Hospital of Los Angeles, Los Angeles, California Children’s Hospital of Oakland, Oakland, California Children’s Hospital of Orange County, Orange, California Huntington Memorial Hospital, Pasadena, California San Diego Regional ECMO Program, San Diego, California Sutter Memorial Hospital, Sacramento, California Stanford University Hospital, Stanford, California UCLA Medical Center, Los Angeles, California University of California, San Francisco, California Children’s Hospital, Denver, Colorado Children’s National Medical Center, Washington, D.C. Georgetown University Hospital, Washington, D.C. Miami Children’s Hospital, Miami, Florida University of Florida, Gainesville, Florida Arnold Palmer Hospital, Orlando, Florida Medical College of Georgia, Augusta, Georgia St. Luke’s Hospital, Boise, Idaho
| Children’s Memorial Hospital, Chicago, Illinois Cook County Hospital, Chicago, Illinois Lutheran General Hospital, Park Ridge, Illinois St. Francis Medical Center, Peoria, Illinois James Whitcomb Riley Hospital, Indianapolis, Indiana Kosair Children’s Hospital, Louisville, Kentucky Ochsner Foundation Hospital, New Orleans, Louisiana Boston Children’s Hospital, Boston, Massachusetts Massachusetts General Hospital, Boston, Massachusetts Johns Hopkins University, Baltimore, Maryland Children’s Hospital of Michigan, Detroit, Michigan University of Michigan Medical Center, Ann Arbor, Michigan Minnesota Regional ECMO Program, Minneapolis, Minnesota Cardinal Glennon Children’s Hospital, St. Louis, Missouri The Children’s Mercy Hospital, Kansas City, Missouri St. Louis Children’s Hospital, St. Louis, Missouri University of Nebraska Medical Center, Omaha, Nebraska The Babies Hospital, New York City, New York Charlotte Memorial Hospital, Charlotte, North Carolina Children’s Hospital Medical Center, Cincinnati, Ohio Miami Valley Hospital, Dayton, Ohio Rainbow Babies and Children’s Hospital, Cleveland, Ohio Children’s Hospital, Columbus, Ohio
| Eastern Oklahoma Perinatal Center, Tulsa, Oklahoma Emanuel Hospital and Health Center, Portland, Oregon Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania Thomas Jefferson University Hospital, Philadelphia, Pennsylvania Medical University of South Carolina, Charleston, South Carolina University of South Carolina, Columbia, South Carolina John Sealy Hospital, Galveston, Texas Texas Tech University, Lubbock, Texas Wilford Hall Medical Center, Lackland Air Force Base, Texas Presbyterian Hospital of Dallas, Dallas, Texas Primary Children’s Medical Center, Salt Lake City, Utah Medical College of Virginia, Richmond, Virginia Children’s Hospital and Medical Center, Seattle, Washington Children’s Hospital of Wisconsin, Milwaukee, Wisconsin Assistance Publique Hospitauz de Paris, Paris, France Hospital Trousseau, Paris, France Kumamoto University Medical School, Kumamoto, Japan Central Hospital, Kasugai, Aichi, Japan Karolinska Institutet, Stockholm, Sweden Universitäts-Kinderklinik Mannheim, West Germany
Royal Alexandra Children’s Pavillion, Edmonton, Alberta, Canada |
ECMO Patient Description The primary diagnoses for the group were meconium aspiration—39 percent; congenital diaphragmatic hernia—16 percent; respiratory distress syndrome—15 percent; persistent pulmonary hypertension of the newborn—13 percent; sepsis—12 percent; cardiac support—2 percent; and other—2 percent (Table 2). The distribution of diagnoses by year is shown in Figure 5. Although meconium aspiration syndrome predominates in all years, it has decreased from 47 percent of all ECMO cases in i985 to 37 percent in 1989 (p < .05). Over the same period of time there was an increase in the numbers being treated for sepsis (7 percent to 15 percent). The most common secondary diagnosis was PPHN (64 percent), followed by air leak syndrome (19 percent). 
Figure 3. Neonatal ECMO cases and outcome during the development and clinical application stages.
Figure 4. Neonatal ECMO centers/year. Sixty percent were boys. Racial background, method of delivery, and payor status were incompletely reported. Mean 1-and 5-minute APGAR scores were 5.2 ± 3.8 and 7.2 ± 3.5 respectively. Mean birth weight was 3.2 " 0.6 kg and mean gestational age was 39 ± 2.4 weeks. The infants were 51.7 ± 48.6 hours old when ECMO was initiated and the mean duration of ECMO was 128.3± 111.6 hours. ECMO Criteria Criteria for instituting ECMO changed and evolved during the 10 years of this report. The goal of all selection criteria was to identify infants with a greater than 80 percent likelihood of mortality. The selection criteria were high (Table 3): - alveolar-arterial oxygen gradient for 6-8 hours or more (22 percent)
- oxygenation index (18 percent)
- acute deterioration (14 percent)
- failure of maximal therapy (34 percent)
- barotrauma (1 percent)
- cardiac arrest (1 percent)
- no entry criteria indicated (10 percent)
The following occur just prior to ECMO (pre- or post-ductal not specified): - Arterial blood gas measurements
pH=7.39 ± .20 PCO2=41.3 ± 23.8 torr P02 =41.0 ± 32.3 torr HCO3=22.6 ± 7.0 MEq/L Sa02=70.6 ± 23.6%
- Ventilator settings
rate/min=96.4 ± 71.6 FiO2=1.0 ± .06 peak inspiratory pressure=45.9 ± 10.9 cm H20 positive end-expiratory pressure=4.3 ± 2.8 cm H20 mean airway pressure=19.7 ± 4.8 cm H20

Figure 5. Diagnoses per year (Neonatal ECMO Regis |