Istanbul Symposiums on Pediatric Extracorporeal Life Support Systems and Pediatric Cardiopulmonary Bypass 2011-2015

Istanbul Symposiums on Pediatric Extracorporeal Life Support Systems and Pediatric Cardiopulmonary Bypass 2011-2015

Content 1. Istanbul Symposiums on Pediatric Extracorporeal Life Support Systems 2. Istanbul Symposium on Neonatal and Pediatric Cardiopulmonary Bypass Procedures 3. Eighth Istanbul Symposium on Pediatric Extracorporeal Life Support Systems and Pediatric Cardiopulmonary Perfusion 4. A Multidisciplinary Approach to Expand the Use of Pediatric ECLS Systems in Turkey 5. Congenital heart surgery in Turkey: today and tomorrow 6. Recommendations for the selection of techniques and components used in congenital heart surgery in Turkey 7. Updates on extracorporeal life support in the world and challenges in Turkey 8. 2011 YILINDAKİ YENİ ECLS SİSTEMLER 9. A multidisciplinary approach to expand the use of pediatric ECLS systems in Turkey 10. Perfusion Practices and Education of Perfusionists for Open Heart Surgery in Turkey Current Practices and Future Suggestions

aor_1368 983..988 Artificial Organs 35(11):983 988, Wiley Periodicals, Inc. 2011, Copyright the Authors Artificial Organs 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc. Guest Editorial Istanbul Symposiums on Pediatric Extracorporeal Life Support Systems The most recent and rapid changes in pediatric extracorporeal life support systems (ECLS) and cardiopulmonary bypass (CPB) procedures are remarkable in terms of not only the development of significantly improved circuit components but also new techniques that reduce morbidity and mortality in pediatric cardiac patients, particularly neonates and infants (1 14). The objective of this editorial is to present the outcomes of the two most recent ECLS symposiums held at the Swiss Hotel and the Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital (IMAEH) in Istanbul, Turkey on June 26, 2011 and July 23, 2011, respectively. The main goal of these two symposiums was to share the most recent advances in a custom-made ECLS system that was developed at the Pediatric Cardiovascular Research Center at Penn State Hershey College of Medicine and Penn State Hershey Children s Hospital, Hershey, PA, USA with invited clinicians around the Republic of Turkey. The custom ECLS system has many advantages including significantly less priming volume (<190 ml), less priming and setup time (<10 min), continuous monitoring no longer being required, and a reasonable disposal cost (<$2500) compared with conventional systems (15). Scientific committee members were composed of both local and international faculty members with multidisciplinary backgrounds and included pediatric heart surgeons, cardiologists, perfusionists, a pediatric critical care nurse educator, and a scientist. The format of both symposiums included not only invited lectures but also hands-on wet lab training sessions. FIRST SYMPOSIUM The first symposium was held at the Swiss Hotel following the regular sessions of the Third Scientific Meeting of the World Society for Pediatric and Congenital Heart Surgery, June 23 26, 2011, in Istanbul, Turkey (Fig. 1). Dr. Ündar opened the symposium doi:10.1111/j.1525-1594.2011.01368.x with his talk describing the custom-made Penn State Hershey ECLS system and the scientific rationale for selecting its specific components. Next, pediatric and adult ECLS systems were set up by two perfusionists, Perihan Yivli from the IMAEH and Ali Ekber Cicek from American Hospital, both from Istanbul. Following 2 h of hands-on training and wet labs, Dr. Ündar then presented the latest 2011 results of new research projects including brain protection during CPB, pulsatile versus nonpulsatile perfusion, selection of neonatal/pediatric oxygenators with and without integrated arterial filters, stolen blood flow via arterial purge line, and the evaluation of cardioplegia systems, with all experiments having been conducted at the Pediatric Cardiovascular Research Center in Hershey (16 22). SECOND SYMPOSIUM The second symposium opened with welcoming remarks by Dr. Ihsan Bakir, founder and president of the IMAEH. Dr. Linda Pauliks, a pediatric cardiologist, and Bonnie Weaver, a nurse educator, both from Penn State Hershey, presented two lectures each discussing their most recent results regarding several topics including ultrasound guidance of mechanical circulatory support, the role of echocardiography in the team approach to managing pediatric heart surgery patients, different scenarios at the pediatric intensive care unit during ECLS, and the education and training of pediatric intensive care nurses (Figs. 2 and 3). In addition, step-by-step demonstrations of the Maquet pediatric and adult ECLS systems were presented by Perihan Yivli and Ali Ekber Cicek, respectively (Figs. 4 and 5). During the second symposium, additional wet labs were carried out and specifically included the Terumo system 1 (Capiox FX-05 oxygenator, CDI 500, Terumo Corporation, Tokyo, Japan, modified ultrafiltration and cardioplegia system by Halime Erkan), the Medos ECLS system designed by Selma Ilgun and Ramazan Bacaksiz, and near-infrared spectroscopy during pediatric CPB by Dr. Sertac Haydin. 983-1 -

984 GUEST EDITORIAL FIG. 1. Participants of the First ECLS Symposium at the Swiss Hotel on June 26, 2011. Sixty-eight clinicians (pediatric heart surgeons, cardiologists, anesthesiologists, nurses, perfusionists, biomedical engineers, and scientists) from 30 centers and 114 clinicians from 26 centers participated in the first and second symposiums, respectively. At both symposiums, each participant received the Seventh International Conference proceedings, a 2011 research update that included 27 of the most recent peer-reviewed articles, along with a conference certificate (23,24). In addition, a conference booklet containing the two most recent articles on ECLS systems (translated to Turkish by Prof. Agirbasli) and a third article regarding the education of perfusionists in Turkey were both given to those in attendance (25). Written on the back cover of the booklet is the Graduate Student Oath of Penn State University that pledges a commitment to scientific integrity, professionalism, and scholarship (both in English and in Turkish). Simultaneous translation from English to Turkish and vice versa was also provided at the second event. The second ECLS symposium was recorded and uploaded to the IMAEH Website (http://www.imaeh.gov.tr) Both events were invitation only with no registration fee requested from any of the participants. All international faculty members from Penn State Hershey visited local hospitals (IMAEH by L.P., B.W, and A.Ü.; Baskent University Hospital by L.P., B.W, FIG. 2. Linda Pauliks, MD, MPH. Artif Organs, Vol. 35, No. 11, 2011-2 -

GUEST EDITORIAL 985 FIG. 3. Bonnie Weaver, RN, MSN, CCRN. FIG. 4. Perihan Yivli giving a demonstration of the pediatric ECLS circuit. FIG. 5. Ali Ekber Cicek giving a demonstration of the adult ECLS circuit. Artif Organs, Vol. 35, No. 11, 2011-3 -

986 GUEST EDITORIAL FIG. 6. Dr. Ihsan Bakir, president and founder of the IMAEH, presents the plaque to Dr. Ündar. and A.Ü.; Kartal Kosuyolu Training and Research Hospital by A.Ü.) to share their experiences with their colleagues. FINANCIAL SUPPORT Maquet (Istanbul, Turkey) not only gave substantial financial support but also arranged the preparation of the conference facility, audio/ visual equipment and pump consoles for the first event at the Swiss Hotel. Medos (Atsbiomedikal, Ankara), Covidien (Istanbul), Medtronic, and Terumo-Vascomed (Istanbul) were exhibitors for the second event. IMAEH, International Society for Pediatric Mechanical Cardiopulmonary Support, Penn State Hershey College of Medicine, and Penn State Hershey Children s Hospital all supported this event scientifically as well as financially. CONCLUSIONS The latest ECLS technology and outcomes were shared with a total of 182 clinicians from 44 centers located throughout Turkey in two symposiums. All participants had an opportunity to have hands-on training with several different ECLS systems. FIG. 7. Organizing committee (in part) at the end of the Second ECLS Symposium on July 23, 2011 (left to right: Bonnie Weaver, Linda Pauliks, Riza Turköz, Akif Ündar, Sertaç Haydin, Ender Ödemiş, Ali Ekber Cicek, Perihan Yivli, and Ersin Erek). Artif Organs, Vol. 35, No. 11, 2011-4 -

GUEST EDITORIAL 987 Participants have shown a sincere appreciation of the new ECLS systems and a willingness to adopt the systems themselves. Based on the feedback of dozens of participants, the scientific committee decided to continue Istanbul symposiums every summer with special focus topics on pediatric mechanical circulatory support systems and pediatric CPB procedures. Acknowledgments: Dr. Ündar is very appreciative after receiving a plaque for his contributions to pediatric cardiovascular health in Turkey from Dr. Ihsan Bakir, President & Founder of the IMAEH (Fig. 6). Dr. Ündar would also like to extend thanks to all local organizers, exhibitors, and wet lab instructors, in particular Dr. Sertac Haydin and Perihan Yivli for spending a significant amount of their time organizing both events. Special thanks from local faculty go to Dr. Linda Pauliks and Bonnie Weaver for their invaluable time and support and for not only giving the lectures but also visiting local hospitals to share their experience (Fig. 7). *Akif Ündar, PhD, Sertaç Haydin, MD, Perihan Yivli, RN, CCP, *Bonnie Weaver, RN, MSN,*Linda Pauliks, MD, MPH, Ali Ekber Cicek, CCP, BS, Ersin Erek, MD, Ahmet Saşmazel, MD, **Mehmet A. Ağirbaşli, MD, Tijen Alkan-Bozkaya, MD, Atif Akçevin, MD, and Ihsan Bakir, MD *Penn State Hershey Pediatric Cardiovascular Research Center Department of Pediatrics Surgery and Bioengineering Penn State Hershey College of Medicine Penn State Hershey Children s Hospital Hershey, PA, USA Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital Istanbul, Turkey Istanbul Bilim University Florence Nightingale Hospital & American Hospital Istanbul, Turkey Dr. Siyami Ersek Thoracic and Cardiovascular Surgery Training and Research Hospital Istanbul, Turkey **Marmara University Department of Cardiology Istanbul, Turkey E-mail: aundar@psu.edu REFERENCES 1. Ündar A. Penn State Hershey Pediatric Cardiovascular Research Center: 2011 update [invited editorial]. Artif Organs 2011;35:358 60. 2. Palanzo D, Qiu F, Baer L, Clark JB, Myers JL, Ündar A. Evolution of the extracorporeal life support circuitry. Artif Organs 2010;34:869 73. 3. Vasavada R, Qiu F, Ündar A. Current status of pediatric/ neonatal extracorporeal life support: clinical outcomes, circuit evolution, and translational research. Perfusion 2011;26:294 301. 4. Khan S, Vasavada R, Qiu F, Kunselman A, Ündar A. Extracorporeal life support systems: alternative vs. conventional circuits. Perfusion 2011;26:191 8. 5. Qiu F, Talor J, Zahn J, et al. Translational research in pediatric extracorporeal life support systems and cardiopulmonary bypass procedures: 2011 update. World J Pediatr Congenit Heart Surg 2011;2:476 81. 6. Qiu F, Clark JB, Kunselman AR, Ündar A, Myers JL. Hemodynamic evaluation of arterial and venous cannulae in a simulated neonatal ECLS circuit. Perfusion 2011;26:276 83. 7. Reed-Thurston D, Shenberger J, Qiu F, Ündar A. Neonatal extracorporeal life support: will the newest technology reduce morbidity? Artif Organs 2011;35:989 96. 8. Qiu F, Lu CK, Palanzo D, Baer L, Myers JL, Ündar A. Hemodynamic evaluation of the Avalon Elite Bi-Caval Lumen cannulae. Artif Organs 2011;35:1048 51. 9. Guan Y, Su X, McCoach R, Kunselman A, El-Banayosy A, Ündar A. Mechanical performance comparison between RotaFlow and CentriMag centrifugal pumps in an adult ECLS model. Perfusion 2010;25:71 6. 10. Clark JB, Guan Y, McCoach R, Kunselman AR, Myers JL, Ündar A. An investigational study of minimum rotational pump speed to avoid retrograde flow in three centrifugal pumps in a pediatric extracorporeal life support model. Perfusion 2011;26:185 90. 11. Qiu F, Khan S, Talor J, Kunselman A, Ündar A. Evaluation of two pediatric polymethyl pentene membrane oxygenators with pulsatile and nonpulsatile perfusion. Perfusion 2011;26: 229 38. 12. Agirbaşli M, Nguyen M, Win K, et al. Inflammatory and hemostatic response to cardiopulmonary bypass in pediatric population: feasibility of seriological testing of multiple biomarkers. Artif Organs 2010;34:987 95. 13. Akçevin A, Alkan-Bozkaya T, Qiu F, Ündar A. Evaluation of perfusion modes on vital organ recovery and thyroid hormone homeostasis in pediatric patients undergoing cardiopulmonary bypass. Artif Organs 2010;34:879 84. 14. Su XW, Guan Y, Barnes M, Clark JB, Myers JL, Ündar A. Improved cerebral oxygen saturation and blood flow pulsatility with pulsatile perfusion during pediatric cardiopulmonary bypass. Pediatr Res 2011;70:181 5. 15. McCoach R, Weaver B, Carney E, et al. Pediatric extracorporeal life support systems: education and training at Penn State Hershey Children s Hospital. Artif Organs 2010;34: 1023 6. 16. Clark JB, Barnes ML, Myers JL, Ündar A. Multimodality neuromonitoring for pediatric cardiac surgery: our approach and a critical appraisal of the available evidence [invited review]. World J Pediatr Congenit Heart Surg 2011 (in press). 17. Qiu F, Guan Y, Su XW. Kunselman AR, Ündar A. Evaluation of neonatal membrane oxygenators with respect to gaseous microemboli capture and transmembrane pressure gradients. Artif Organs 2010;34:923 9. 18. Yee S, Qiu F, Su XW, et al. Evaluation of HL-20 roller pump and RotaFlow centrifugal pump on perfusion quality and gaseous microemboli delivery. Artif Organs 2010;34:937 43. Artif Organs, Vol. 35, No. 11, 2011-5 -

988 GUEST EDITORIAL 19. Palanzo D, Guan Y, Wan C, et al. Air-handling capabilities of blood cardioplegia delivery systems in a simulated pediatric model. Artif Organs 2010;34:950 4. 20. Qiu F, Peng S, Kunselman AR, Ündar A. Evaluation of Capiox FX05 oxygenator with an integrated arterial filter on trapping gaseous microemboli and pressure drop with open and closed purge line. Artif Organs 2010;34:1053 7. 21. Clark JB, Qui F, Guan Y, Woitas KR, Myers JL, Ündar A. Microemboli detection and classification during pediatric cardiopulmonary bypass. World J Pediatr Congenit Heart Surg 2011;2:111 4. 22. Su X, Ündar A. Brain protection during pediatric cardiopulmonary bypass. Artif Organs 2010;34:E91 102. 23. Ündar A, ed. The Proceedings of the Seventh International Conference on Pediatric Mechanical Circulatory Support Systems and Pediatric Cardiopulmonary Perfusion. Hershey, PA: Penn State Hershey College of Medicine Press, 2011;7:1 121. 24. Ündar A, ed. The Proceedings of the Penn State Hershey Pediatric Cardiovascular Research Center: 2011 Update. Hershey, PA: Penn State Hershey College of Medicine Press, 2011;1:1 218. 25. Ündar A, Cicek A, Akcevin A, Sarioglu T. Perfusion practices and education of perfusionists for open-heart surgery in Turkey. Turk J Thorac Cardiovasc Surg 2005;13: 123 6. Artif Organs, Vol. 35, No. 11, 2011-6 -

bs_bs_banner aor_1455 463..466 2012, Copyright the Authors Artificial Organs 2012, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc. Guest Editorial Istanbul Symposium on Neonatal and Pediatric Cardiopulmonary Bypass Procedures Last summer, after organizing two Istanbul symposiums on pediatric extracorporeal life support systems, the third one was held on December 17, 2011 at the American Hospital in Istanbul, Turkey (1). The main topic of the third symposium was minimizing adverse effects of cardiopulmonary bypass procedures in neonates and pediatric cardiac patients. The objective of this editorial is to present the outcomes of the third symposium and suggest more topics for future symposiums in 2012. The third symposium is dedicated to honor Prof. Dr. Aydın Aytaç for his lifelong contributions as a pioneering surgeon and educator of the development of pediatric cardiac surgery in Turkey (Fig. 1) (2 6). Special topics After the welcoming remarks by Atıf Akçevin and Akif Ündar, cochairs of the symposium, Prof. Dr. Ali Ihsan Dokucu, the Health Director of Istanbul, made the opening speech (Fig. 2). After the introduction of the development of pediatric cardiac surgery in Turkey by Prof. Dr.Tayyar Sarıoğlu, who is one of the most senior members of the Turkish pediatric cardiac surgery community, 16 invited speakers presented a variety of topics and covered most of the special areas for neonatal and pediatric cardiopulmonary bypass (CPB) in an intense 1-day scientific program. In addition to local invited speakers, clinicians and scientists from aboard (Chris Chin and Huriyet Ersayin-Kantas from London, UK; Thomas Markmann from Germany; and Kerem Pekkan, David Palanzo, and Akif Ündar from the US) participated and shared the latest techniques and circuits for pediatric cardiac surgery. Special topics included challenges of neonatal CPB circuitry and techniques, feasibility of serological testing of multiple biomarkers, impact of pulsatile flow on vital organ recovery, ABC s of neonatal cardiac anesthesia, cerebral protection and neuromonitoring, detection and classification of microemboli, team approach to minimize injury, new pediatric ventricular assist device (Rotassist 2.8), bioengineering and hemodynamic design of the aortic cannula for CPB, and establishing a national pediatric cardiovascular research center in Turkey. Wet labs Three special neonatal and pediatric CPB circuits were brought from the UK and the US for wet labs (Fig. 3). This gave the participants an opportunity for hands-on experience with different neonatal CPB circuits used abroad. Huriyet Ersayin-Kantas, FCCP, and David Palanzo, CCP, were the instructors for doi:10.1111/j.1525-1594.2012.01455.x FIG. 1. Aydın Aytaç, MD. Artificial Organs 2012, 36(5):463 466-7 -

464 GUEST EDITORIAL A B FIG. 4. Panel discussion (from left to right: Sertaç Haydin, Rıza Türköz, David Palanzo, Huriyet Ersayin-Kantas, Tayyar Sarıoğlu, Atıf Akçevin, Chris Chin). these special wet labs. In addition, there were exhibits by several manufacturers displaying their newest products. The exposure to these products and circuits was well received and should be continued in future symposiums. FIG. 2. (A) Ali Ihsan Dokucu, the Health Director of Istanbul, and (B) Atıf Akçevin, MD, Local Chair of the Symposium. Participants Unlike the first two symposiums, the third one was by invitation only (because of limited seating space), and over 130 clinicians (pediatric heart surgeons, cardiologists, anesthesiologists, intensivists, neurologists, perfusionists, nurses, and scientists) from 30 different pediatric cardiac centers all around Turkey participated in this event (Figs. 4 and 5). In addition to a conference program, a book entitled A Life Dedicated to Heart by Prof. Dr. Aydın Aytaç and a copy of the November 2011 issue of Artificial Organs were delivered to all participants free of charge. There were no registration fees to attend this event as was the same for the previous two events. Simultaneous translation from English to Turkish and vice versa was also provided at the third event. FIG. 3. Penn State Hershey Neonatal CPB circuitry (by David Palanzo, CCP). Scientific and financial support The International Society for Pediatric Mechanical Cardiopulmonary Support; Penn State Hershey College of Medicine, Penn State Hershey Children s Hospital; Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Turkey; Istanbul Bilim University; Dr. Siyami Ersek Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Turkey; Marmara University, Department of Cardiology, Artif Organs, Vol. 36, No. 5, 2012-8 -

GUEST EDITORIAL 465 A Istanbul, Turkey; Baskent University Istanbul, Acıbadem Bakırköy Hospital, and Acıbadem University all supported this event scientifically. Covidien, Ares Medical (CasMed), Vascomed Medical (Terumo), ATS Biomedical (Medos), Medicall Biomedical (Medtronic), Bicakcilar (Sorin), and Maquet were exhibitors for the third event. To balance the budget, Dr. Ündar has financially supported this event using his personal funds as he did for the past two ECLS symposiums. Special thanks go to the American Hospital, Istanbul, for not only allowing organization of the symposium in their outstanding conference facilities, but also for providing the lunch and coffee breaks throughout the entire day. B Symposium evaluations Participants have requested to grade not only the scientific program including the quality of the lectures, invited speakers, and topics, but also the quality of registration as well as catering. Uniformly, participants enjoyed all of this scientific activity and graded to excellent in all categories except that a few speakers went over their allotted time so the entire program had to be extended in the morning sessions. We will make sure that this will not happen at the fourth symposium in 2012. All invited lecturers also enjoyed a Gala Dinner at the end of the night which took place at the University of Istanbul faculty dinner facility next to the Bosphorus with a remarkable view between Asia and Europe (Fig. 5C). C FIG. 5. (A C) Participants and the Faculty Gala Dinner of the Third Istanbul Symposium at the American Hospital, Istanbul on December 17, 2011. CONCLUSIONS The latest technology and techniques about neonatal and pediatric cardiopulmonary bypass have been discussed with local clinicians as we did with ECLS last summer (7,8). Several clinical protocols by the invited speakers have been shared and discussed thoroughly with the participants. Overall, all three symposiums have reached their objectives and generated a significant number of collaborations among local participants as well as other collaborations with investigators who live abroad (1,7,8). Future topics such as pediatric CPB, mechanical circulatory support, and extracorporeal life support systems were suggested and will be included in 2012 symposiums. Acknowledgments: The organizers would like to thank Erdal Aksoy, the Medical Director of the American Hospital, and Seda Özbucak, Head of Public Relations of the Hospital, for all their support to organize this event. *Akif Ündar, PhD, Tijen Alkan-Bozkaya, MD, *David Palanzo, CCP, Huriyet Ersayin-Kantas, Artif Organs, Vol. 36, No. 5, 2012-9 -

466 GUEST EDITORIAL FCCP, Chris Chin, MD, Ender Ödemiş, MD, ** Kerem Pekkan, PhD, Mehmet A. Ağirbaşli, MD, Ayda Türköz, MD, Rıza Türköz, MD, Sertaç Haydin, MD, Ersin Erek, MD, Yusuf K. Yalçınbaş, MD, ***Ahmet Şaşmazel, MD, ***Ali Rıza Karacı, MD, Halime Erkan, RN, Ali Ekber Çicek, BS, İhsan Bakır, MD, Tayyar Sarıoğlu, MD, Atıf Akçevin, MD, and Aydın Aytaç, MD *Professor of Pediatrics, Surgery, and Bioengineering Penn State Hershey Pediatric Cardiovascular Research Center Department of Pediatrics, Surgery and Bioengineering Penn State Hershey College of Medicine Penn State Hershey Children s Hospital Hershey, PA, USA Department of Cardiovascular Surgery Istanbul Bilim University Istanbul, Turkey Guy s and St Thomas NHS Foundation Trust Pediatric Perfusion London, UK Guy s and St Thomas NHS Foundation Trust Pediatric Anesthesia London, UK Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital Istanbul, Turkey **Department of Biomedical Engineering Carnegie Mellon University Pittsburgh, PA, USA Department of Cardiology Istanbul, Turkey Department of Cardiology Marmara University Istanbul, Turkey Departments of Cardiovascular Surgery and Anesthesiology Başkent University Istanbul, Turkey Department of Cardiovascular Surgery Acıbadem Bakırköy Hospital Istanbul, Turkey ***Dr. Siyami Ersek Thoracic and Cardiovascular Surgery Training and Research Hospital Istanbul, Turkey Department of Cardiovascular Surgery Amerikan Hospital Istanbul, Turkey Department of Cardiovascular Surgery Acıbadem University Istanbul, Turkey E-mail: aundar@psu.edu REFERENCES 1. Ündar A, Sertaç Haydin S, Yivli P, et al. Istanbul symposiums on pediatric extracorporeal life support systems. Artif Organs 2011;35:983 8. 2. Shellito JG, Buck BH, Carreau EP, Robinson RH, Aytac A. The use of citrated blood in extracorporeal circulation. Am Surg 1959;25:796 800. 3. Aytaç A, Tuncali T. The use of temporary external pacemaker to control surgically produced complete atrioventricular block during open heart surgery. Turk J Pediatr 1967;9:65 70. 4. Aytac A, Tuncali T. Direct communication of a pulmonary artery with the left atrium. First reported case of all four pulmonary veins entering the communication. J Thorac Cardiovasc Surg 1967;54:553 6. 5. Saylam A, Ikizler C, Yurdakul Y, Aytaç A. Trilogy of Fallot: analysis of 10 cases undergone open heart surgery. Turk J Pediatr 1973;15:147 56. 6. Saylam A, Tuncali T, Ikizler C, Aytaç A. Aorto-right ventricular tunnel: a new concept in congenital cardiac malformations. Ann Thorac Surg 1974;18:634 7. 7. Ündar A, Bakır I, Haydin S, et al. Congenital heart surgery in Turkey: today and tomorrow. Turk J Thorac Cardiovasc Surg 2012;(in press). 8. Ündar A, Haydin S, Erek E, et al. Recommendations for techniques and components selection during congenital heart surgery in Turkey. Turk J Thorac Cardiovasc Surg 2012;(in press). Artif Organs, Vol. 36, No. 5, 2012-10 -

bs_bs_banner Copyright 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc. Invited Editorial Eighth Istanbul Symposium on Pediatric Extracorporeal Life Support Systems and Pediatric Cardiopulmonary Perfusion To improve the outcomes of pediatric extracorporeal life support (ECLS) and cardiopulmonary bypass (CPB) procedures in Turkey, we have established a series of conferences, called Istanbul Symposiums. Since the first symposium in June of 2011, we have organized seven additional symposiums in Istanbul (1 3). The objective of this editorial is to share the latest results on pediatric ECLS and CPB patients with the Artificial Organs community. The eighth Istanbul Symposium was held at the Medipol University on January 10, 2015. A multidisciplinary faculty including pediatric heart surgeons, pediatric intensivists, perfusionists, cardiologists, anesthesiologists, and scientists were invited to share their latest results (Fig. 1). The symposium was opened with welcoming remarks by Dr. Halil Turkoglu, the head of the cardiovascular surgery department at Medipol University, Istanbul, Turkey (Fig. 2). Dr. Akif Ündar presented his lecture about the basic principles of scientific research and the impact of the Istanbul Symposiums on pediatric ECLS and CPB patients in Turkey, along with future suggestions and recommendations (Fig. 3) (4 6). There were three specific panels at the eighth symposium: 1 Pediatric ECLS: 2015 update; 2 Latest developments on pediatric cardiac surgery and pediatric CPB procedures; 3 Role of perfusionists during ECLS and CPB along with hands-on wet-labs. FIRST PANEL ON PEDIATRIC ECLS: 2015 UPDATE The historical development as well as the current ECLS practice in Turkey was discussed by Dr. Atif Akcevin. doi:10.1111/aor.12512 ECLS experience at IMAEH Dr. Sertaç Haydin presented their results and experience related to the management of complications in extracorporeal membrane oxygenation (ECMO) implementation at Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital (IMAEH). Seventy patients underwent ECMO support between March 2011 and January 2015 in this particular hospital. They changed their ECLS system from Medos Deltastream DP2 (Medos Medizintechnik AG, Stolberg, Germany) to Medos Deltastream DP3 (Medos Medizintechnik AG) after November 2012, and DP3 was used in a consecutive series of 45 patients (4.6% of all children undergoing congenital heart surgery during the same period). Their ECLS circuit consisted of a Deltastream DP3 diagonal pump head, a Hilite (Medos Medizintechnik AG) polymethylpentene diffusion membrane oxygenator, and Rheoparin (Medos Medizintechnik AG) coated tubing for both arterial and venous lines (Fig. 4). The Deltastream DP3 System can provide both nonpulsatile and pulsatile flow for pediatric ECLS. ECLS with the DP3 was performed in 45 patients. The median age and weight of the patients were 60 days (range 2 2920 days) and 3.7 kg (range 2.6 20 kg), respectively. Hemorrhage was the most common complication in patients who had successful weaning, whereas renal failure was the most common complication in unsuccessful weaning. Median ECMO duration was 5.6 days (range 4 41). ECMO was successfully discontinued (children survived and were able to maintain adequate hemodynamics more than 24 h following ECLS termination) in 31 (68.8%) patients. Nineteen (42.2%) patients survived to hospital discharge. Twelve patients (26.6%) died after successful weaning. During the study period, 13 patients received extracorporeal cardiopulmonary resuscitation (ECPR) for refractory cardiac arrest unresponsive to conventional cardiopulmonary resuscitation measures. Artificial Organs 2015, 39(5):E49 E55-11 -

E50 INVITED EDITORIAL FIG. 1. Prof. Dr. Akcevin s welcoming remarks. Successful weaning in this group was 53.8%, which compared favorably to a survival rate of 75% in non- ECPR patients. As a result of the shift to use DP3, revised ECMO protocol, and increased ECMO experience, significant improvement was observed in IMAEH clinical results. While the weaning success rate was 36% and the survival rate 20% before November 2012, 68.8% of patients were weaned, and 42.2% survived after this time. None of the patients experienced a mechanical component failure associated with the duration of ECLS. During the IMAEH study, the DP3 system could be used without any complications for up to 30 days. ECLS Experience at Medipol University Dr. Arda Ozyuksel reported their initial experience with using the CPB membrane oxygenators in the ECMO setup in a subset of patients because of reimbursement problems related to the national healthcare system (7). They connected a RotaFlow centrifugal pump (Maquet Cardiopulmonary AG, Hirrlingen, Germany) to a Capiox FX05 or Baby RX05 CPB membrane oxygenator (Terumo Inc., Tokyo, Japan) and primed the system without heparin administration. They implemented eight oxygenators in five infants without leak or hemolysis. The replaced oxygenators were used for 81, 99, and FIG. 2. Prof. Dr. Halil Türkoğlu and Prof. Dr. Atıf Akçevin, Co-Chairs of the Eighth Istanbul Symposium. Artif Organs, Vol. 39, No. 5, 2015-12 -

INVITED EDITORIAL E51 FIG. 3. Prof. Dr. Akif Ündar s opening lecture. 76 h, respectively. According to the January 2015 Extracorporeal Life Support Organization (ELSO) summary, the overall average run time for the cardiac ECMO implementation in the newborn and infantile periods were 146.1 ± 15.1 and 146.2 ± 20.3 h, FIG. 4. ECLS experience at IMAEH. respectively (8). Therefore, this system including a CPB oxygenator (instead of a ECLS) and a centrifugal pump can be an alternative circuit in case of reimbursement difficulties or the lack of availability of polymethylpentene oxygenators as also seen in the United States (9). However, there are several limitations of this alternative circuit, including risk of more microemboli delivery to the patient due to more frequent change of oxygenators, and more circuit setup time required rather than using a ready-to-plug-in circuitry. During the discussion section of Dr. Ozyuksel s presentation, Dr. Ündar also pointed out that the cost of pediatric and adult ECLS disposables in Turkey is two to three times more expensive compared with the same manufacturers in the United States (10). ECLS experience at Hacettepe University Dr. Murat Tanyildiz shared the latest ECMO experience of the Hacettepe Ihsan Dogramaci Children s Hospital which is one of the most prestigious children s hospitals in Turkey. The first ECMO was done here in the pediatric intensive care unit in 2013 as an ECPR. ECMO was implemented in 10 patients since 2013 (Fig. 5). Median age was 32 months of age (range 6 months to 14 years). Median ECMO duration time was 6 days (range 7 h to 29 days). ECMO was implemented in six cases after cardiac surgery. The most commonly observed complication was bleeding (50%) along with heparin-induced thrombocytopenia (HIT) (40%). Overall survival rate was 60%, which is one of the highest survival rates compared with the other pediatric intensive care units in Turkey (1). Artif Organs, Vol. 39, No. 5, 2015-13 -

E52 INVITED EDITORIAL FIG. 5. ECLS experience at Hacettepe University. Outcomes of ECLS patients in Turkey The above institutions (IMAEH, Medipol Hospital, and Hacettepe University) are the leading ECLS centers in Turkey. Their ECLS outcomes are comparable with the most recent International ELSO Registry report (8). Based on the most recent January 2015 international summary, neonatal cardiac patients (n = 5810) survival to discharge rate is 41% while pediatric cardiac patients (n = 7314) survival has increased to 50%. However, most of other centers ECLS outcomes in Turkey may not be as good as the above centers as previously reported (1). Current ventilator strategies during ECMO Following Dr. Tanyildiz s excellent lecture, Dr. Ayda Turkoz discussed the mechanical ventilator strategies during ECMO. Current evidence suggests that recent mechanical ventilation strategies improve survival in ECMO patients (11). Before the initiation of the mechanical ventilation, the ventilation parameters should be set by considering the alveolar strain, atelectrauma, and the applications which can limit and/or prevent overdistension. First, the tidal volume should be decreased to 6 ml/kg in protective (lung recruitment) strategy and to 4 ml/kg for ultraprotective ventilation strategy (lung rest) (11). In low tidal volume strategies, plateau pressure should be set at 20 cm H 2O. However, it is recommended to apply a moderately high level of positive end-expiratory pressure (PEEP) ( 10 cm H 2O) during low tidal volume ventilation in order to prevent alveolar collapse and nitrogen accumulation. Moderately high PEEP levels could be dangerous in patients with heart failure and acute respiratory distress syndrome on veno-venous ECMO, and could exacerbate right ventricular dysfunction and delay heart recovery (12,13). In order to decrease pulmonary oxygen toxicity, the fraction of the inspired oxygen at the ventilator should also be reduced to the minimal value to keep arterial saturation at >85%. The respiratory rate should be reduced depending on the tidal volume and ECMO gas flow settings. In pediatric patients, the tidal volume level and physiological PEEP titration should be monitored with transpulmonary pressure and tissue oxygenation. Further advanced studies are required to determine whether the use of noninvasive ECMO with awake mechanical ventilation leads to better outcomes instead of employing invasive lung recruitment and lung rest controlled mode of mechanical ventilation strategy (12,13). PANEL ON PEDIATRIC CARDIAC SURGERY AND PEDIATRIC CPB PROCEDURES Dr. Halil Turkoglu shared his experiences regarding the historical development of cardiac surgery along with the CPB procedures in Turkey. Dr. Ece Salihoglu discussed the recent updates on myocardial protection strategies in patients undergoing congenital cardiac surgery. Although a different management strategy is deemed necessary in pediatric cardiac surgery, most of the centers implemented myocardial protection methods with regard to their experience derived from adult cardiac surgery in the past. Normothermic CPB is not a routinely used technique in the era of congenital heart surgery; however, mild hypothermia is frequently used in simple procedures. Normothermic or hypothermic blood cardioplegia is the most frequent administration method in order to arrest the heart. However, in complex cardiac surgeries, a single or double-dose Artif Organs, Vol. 39, No. 5, 2015-14 -

INVITED EDITORIAL E53 administration of Del Nido (Compass-Baxter Healthcare Inc., Edison, NJ, USA) or HTK- Custodiol (Koehler Chemi, Alsbach-Haenlien, Germany) cardioplegia solutions provide a better myocardial protection along with a blood-free exposure of the cardiac chambers (14 16). The Del Nido cardioplegia protocol is not extensively used in Turkey, probably due to lack of regular procurement of the ingredients and proper delivery equipment. However, after a long period of experience in transplantation surgery, HTK-Custodiol solution has gained popularity in myocardial protection of the patients undergoing congenital cardiac surgery. The inevitable advantages of single or double-dose administration of these solutions include better myocardial protection along with a bloodless surgical exposure; however, increased familiarity of the surgical team and decreased costs of the solutions are mandatory in order to set a routine-based algorithm. During the afternoon session, Dr. Alican Hatemi gave a speech on systemic inflammation during CPB. Following the general overview of CPB-induced systemic inflammation, the content was focused on Blood-Surface Interactions and Aggregation of Serum Proteins during Extracorporeal Circulation. Based on the preliminary data of their research investigating the cause of the biochemical, immunologic, and clinical differences between phosphoryl choline-coated and conventional/noncoated extracorporeal circulation systems, Dr. Hatemi s group shifted their research through the etiology of these differences, by analyzing the protein aggregates on the extracorporeal circulation systems. Prominent protein bands present on the phosphoryl cholinecoated lines but missing on the noncoated tubings were visualized and they were excised from the SDS- PAGE (Bio-Rad Laboratories, Hercules, CA, USA) electrophoresis gels, then were extracted and identified by MALDI-TOF (AB Sciex, Framingham, MA, USA) with Mascot software (Matrix Science Inc., Boston, MA, USA) Swissport database (17). These preliminary data will be used for subsequent research activities on the development of modified extracorporeal circulation systems, aiming to reduce CPB induced inflammatory response. Dr. Alkan-Bozkaya gave a lecture about the biomarkers used as early predictors for organ damage after cardiac surgery in pediatric population and she also mentioned their experience with the combined clinical application of routinely performed patient monitorization techniques in their cardiac surgery center at Medipol University (18). International congenital cardiac surgery patients in Turkey Dr. Salihoglu gave an informative speech about the cardiac surgery candidates admitted from foreign countries to congenital heart surgery centers. The contract-based patient admission program was initiated in 2009 with foreign congenital cardiac surgery candidates in Turkey. More than 6000 patients have been operated in eight cardiac surgery centers since this agreement was signed. The overall mortality is reported to be 1.7 to 5% (personal communication with all eight centers by Dr. Salihoglu). Eighty-five percent of the patients were admitted from Middle East countries, 10% from North Africa and Libya, and the rest of them from middle-europe and Turkic Republics. The majority of the patients received healthcare with regard to the agreements signed with the Ministry of Health in the above-mentioned countries. These patients need detailed organization in terms of preoperative evaluation and accommodation along with their relatives, as well as postoperative discharge and follow-up. Moreover, infectious diseases that prohibit a fast-track surgical treatment are frequent in this patient population. There are basically two types of patients in this population: infants and children with congenital heart diseases, and adults with acquired cardiovascular diseases. Most of the patients in these population have congenital heart diseases; however, unusually late presentations such as tetralogy of Fallot in the fourth decade might be encountered. Unfortunately, some of these patients have significant adverse effects of the long-lasting morphological cardiac abnormalities, especially irreversible pulmonary hypertension and resultant Eisenmenger s Syndrome. Chromosomal abnormalities, congenital diseases other than the cardiovascular system, malnutrition, and chronic infections are common problems among these patients. The most common diagnosis among the adult patients are ischemic heart diseases and valvular pathologies; however, significant comorbidities such as uncontrolled diabetes mellitus, chronic renal failure, peripheral arterial disease, chronic obstructive pulmonary disease, congestive heart failure associated with diminished ventricular function, and obesity are encountered as well. In the last decade, Turkey has become an important destination for foreign cardiac surgery candidates, with increased experience of the cardiac centers related to preoperative evaluation of the diseases, management of the comorbidities, effective planning of the surgical treatment, and a well-scheduled follow-up program. Artif Organs, Vol. 39, No. 5, 2015-15 -

E54 INVITED EDITORIAL Biomedical engineering During the meeting, Dr. Kerem Pekkan, the principal investigator of a recently established bioengineering research laboratory at Koc University, presented their current work dedicated to congenital heart disease patients and pediatric cardiovascular engineering. The Pekkan laboratory is supported by the European Research Council and European Molecular Biology Organization (EMBO) and National Science Foundation that houses state-ofthe-art experimental and computational infrastructure for conducting multidisciplinary research that is valuable for clinicians, with the objective of improving the health and quality of life of children who suffer. Current research activities of this laboratory are: embryonic cardiovascular mechanics (19); pediatric and adult congenital heart diseases (20,21); reproductive biomechanics and cardiovascular maternal health (22); and bio-inspired engineering analysis and design (23). ROLE OF PERFUSIONISTS DURING ECLS AND CPB ALONG WITH HANDS-ON WET-LABS The last panel of the symposium was about the role of perfusionists during ECLS and CPB along with hands-on wet-labs. Perfusionist Halime Erkan from IMAEH presented their pediatric CPB protocol (24 26). Since 2010, 1500 congenital cardiac cases were performed at the IMAEH. Capiox FX05 oxygenators with integrated arterial filters were used during this time period. Before 2014, the main strategy for pediatric CPB was moderate to deep hypothermia, then it was changed to normothermic CPB. Their group started to use cold crystalloid cardioplegia (Custodiol) instead of cold blood in the second half of 2014, and they also added pulsatile flow to these changes. Inotrope doses decreased dramatically following this protocol. Cardiac recovery following cross-clamp release improved and the need for ultrafiltration during or after CPB decreased. Perioperative and postoperative course has become more straightforward. It is likely that a better pediatric CPB strategy is possible with normothermic pulsatile flow by using a pediatric oxygenator with an integrated arterial filter. This could benefit by the addition of Custodiol in terms of decreasing myocardial edema and providing a clear surgical field. Perfusionist Aydin Kahraman from Medipol University gave a speech on common complications encountered during the implementation of ECMO, primarily focusing on the air embolism arising from the equipment. Perfusionist Sibel Aydin from Kartal Kosuyolu Thoracic and Cardiovascular Surgery Training and Research Hospital also shared the most recent ECLS results in pediatric patients (1). Poster presentations were moderated by Drs. Alkan-Bozkaya and Ersoy. At the end of the meeting, a practical approach for the setting and priming of the pediatric ECMO system was implemented at the wet-labs for perfusionists. A multimedia DVD including the ECMO circuit setup and priming, along with several recent ECLS publications was also shared with all participants at the eighth symposium. Artificial Organs Based on Dr. Malchesky s recent editorial entitled Artificial organ technologies around the world, Turkish cardiovascular clinicians and scientists submitted articles to Artificial Organs as first authors between 2004 and 2013 more than most countries (27). In fact, Turkey was listed as seventh (after USA, Japan, China, Germany, Korea, and Italy) out of 57 countries. In a separate study, Dr. Altan Onat from Istanbul University pointed out that Artificial Organs is the #10 most frequently published journal by Turkish cardiovascular clinicians in 2013 (28). CONCLUSIONS During the past 3.5 years, outcomes of pediatric CPB and ECLS patients were improved by a multidisciplinary team approach in Turkey. In particular, a few ECLS centers now have similar survival rates with the ELSO centers. More clinicians prefer evidence-based approach for selecting the CPB and ECLS disposables and techniques for their patients ever than before. Artificial Organs is one of the leading journals for cardiovascular clinicians and scientists in Turkey as well. Istanbul symposiums will continue to train more young clinicians and scientists for pediatric cardiovascular research in Turkey. *Tijen Alkan-Bozkaya, MD, *Arda Özyüksel, MD, *Ece Salihoğlu, MD, Sertaç Haydın, MD, Murat Tanyıldız, MD, Kerem Pekkan, PhD, **Alican Hatemi, MD, PhD, Ayda Türköz, MD, Halime Erkan, CCP, Sibel Aydın, CCP, *Aydın Kahraman, CCP, *Alper Savaş, CCP, *Cihangir Ersoy, MD *Halil Türkoğlu, MD Akif Ündar, PhD, and *Atıf Akçevin, MD *Department of Cardiovascular Surgery, Medipol University; Department of Pediatric Cardiovascular Artif Organs, Vol. 39, No. 5, 2015-16 -

INVITED EDITORIAL E55 Surgery, Istanbul Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital; Department of Bioengineering, Koc University; Department of Pediatric Cardiovascular Surgery, Kartal Kosuyolu Thoracic and Cardiovascular Surgery Training and Research Hospital; **Department of Cardiovascular Surgery, Institute of Cardiology, Istanbul University; Department of Anesthesiology, Baskent University, Istanbul; Department of Pediatrics, Hacettepe University, Ankara, Turkey; and Department of Pediatrics, Surgery and Bioengineering, Penn State College of Medicine, Penn State Hershey Pediatric Cardiovascular Research Center, Penn State Hershey Children s Hospital, 500 University Drive, PO Box 850, Hershey, PA 17033-0850, USA E-mail: aundar@psu.edu REFERENCES 1. Onan IS, Haydin S, Ündar A, et al. A multi-disciplinary approach to expand the use of pediatric ECLS systems in Turkey. Artif Organs 2015;39:7 13. 2. Ündar A, Alkan-Bozkaya T, Palanzo D, et al. 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Correlation between cerebral-renal near-infrared spectroscopy and ipsilateral renal perfusion parameters as clinical outcome predictors after open heart surgery in neonates and infants. Artif Organs 2015;39:53 8. 19. Kowalski WJ, Pekkan K, Tinney JP, Keller BB. Investigating developmental cardiovascular biomechanics and the origins of congenital heart defects. Front Physiol 2014;5:408. doi:10.3389/ fphys.2014.00408. 20. Albal PG, Menon PG, Kowalski W, et al. Novel fenestration designs for controlled venous flow shunting in failing Fontans with systemic venous hypertension. Artif Organs 2013;37:66 75. 21. Menon PG, Yoshida M, Pekkan K. Presurgical evaluation of Fontan connection options for patients with apicocaval juxtaposition using computational fluid dynamics. Artif Organs 2013;37:E1 8. 22. Yigit M, Kowalski W, Hutchon D, et al. Transition from fetal to neonatal circulation: modeling the effect of umbilical cord clamping. J Biomech 2015; doi:10.1016/j.jbiomech.2015.02.040. [Epub ahead of print] 23. Piskin S, Undar A, Pekkan K. Neonatal cardiopulmonary bypass hemodynamics with detailed Circle of Willis anatomy. Artif Organs 2015;39:in press. 24. Onan IS, Yivli P, Erkan H, et al. Perfusion practices and education of perfusionists for open heart surgery in Turkey current practices and future suggestions. Artif Organs 2012;36:492 5. 25. Haydin S, Onan B, Onan IS, et al. Cerebral perfusion during cardiopulmonary bypass in children: correlations between Near Infrared Spectoscopy (NIRS), temperature, lactate, pump flow and blood pressure. Artif Organs 2013;37:87 91. 26. Onan IS, Erek E, Haydin S, et al. Clinical outcome of patients in a start-up congenital heart surgery program in Turkey. Artif Organs 2013;37:E18 23. 27. Machesky PS. Artificial organ techologies around the globe. Artif Organs 2014;38:99 100. 28. Onat A. Cardiovascular publications in 2013 in Turkey advanced in quantity alone. Turk Kardiyol Dern Ars 2014;42:403 9. 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