ECMO is a high technology dependent treatment modality which aims to improve survival in critically ill patients of all age groups with a calculated mortality risk of over 80%. Given the potential sequelae new monitoring techniques are needed to guide optimal oxygen delivery to the tissues.
The main aim of this ACE is to enhance the level of care of ECMO at all age groups regarding:
- patient care evaluation of morbidity and implementation in particular of optimal (evidence based) pharmacotherapy including anticoagulation management;
- targeting the microcirculation as a diagnostic and therapeutic end-point;
- develop new technology for oxygen measurements of the cellular level;
- determine early (by proxy) biomarkers for future neurodevelopment outcome;
- cost effectiveness
- Long term effects both regarding neurodevelopmental and somatic outcome
The translational research line actively uses ECMO as part of its large animal models and provides an excellent platform for translational research aiming at better understanding the relationship between ECMO, tissue oxygenation and clinical outcome. Understanding ischemia-reperfusion injury during Extra-corporeal cardiopulmonary resuscitation (collaboration between EMC, University of Freiburg and University of Kepler).
This project will assess mitochondrial oxygen in experimental models and clinical outcome. We identified the microcirculation as a prognostic factor in ECMO outcome. Current research is directed at adjunct therapeutic strategies to improve the microcirculation which is expected to improve outcome. This will be done in collaboration with Columbia University Medical Center New York (departments of Cardiology, Thoracic Surgery and Pulmonary and Critical Care Medicine).
Together with the ACE: pharmacology in vitro and in vivo studies will be performed to identify determinants of PK of individual drugs and to create evidence based pharmacotherapy guidelines. For children, the ACE has an important focus on outcome research. A multidisciplinary long-term follow-up program (including physical, developmental, pulmonary an neuropsychological assessments) is being offered to each (neonatal) ECMO-survivor.
From a translational point of view active collaboration with the neuroscience Erasmus MC division is established evaluation the effect of hypoxia/hyperoxia on hippocampal development together with optimal drug dosages to prevent ongoing damage.
This program provides for longitudinal assessments from birth to 17 years and is unique worldwide. Moreover, two randomized controlled trails are currently being performed aiming at improvement of outcome on physical endurance and on neuropsychological functioning. International collaboration is established with Great Ormond Street Hospital London and we guide the development of international recommendations for follow-up of ECMO-survivors. The ultimate aim is to come to a European standard of long term follow up using validated tests and nationwide reference values.
International collaboration is established with Great Ormond Street Hospital London and we guide the development of international recommendations for follow-up of ECMO-survivors.
We raised the so called PHOENIX initiative a collaboration with six establised international ECMO centers to solve the problems of (anti) coagulation in ECMO patients both children and adults.
To evaluate the role of eCPR Erasmus MC is guiding a Horizon2020 project called CIRDinnova.
In 2015, the ECMO center Rotterdam has been evaluated by the American Extra-corporeal Life Support Organization, and has been awarded as Gold Level of Center of Excellence. The education was awarded with a 4 out of 5. Participants of this ACE regularly serve as teachers at the PhD level at a national level and at post graduate level for teams from abroad. Moreover we provide outreach by lecturing abroad in over 9 countries around the world and occasionally using webcasts. (Prague Czech Republic 2012, GOSH London United Kingdom 2013, Denmark 2013, Children's university hospital Dublin Ireland 2015, Meyer hospital Florence Italy 2015, Cape Town South Africa 2015, Saudi Arabia 2015, Russia 2016, Cape Town South Africa 2016).
Simulation and scenario trainings are an integral part of the educational program. Moreover we continue to discuss on a case-to-case base training on the job for the first 10 patients/country. PhD students are started on extracorporeal life support during cardiopulmonary resuscitation (deriving from the international collaboration) and on anticoagulation in ECMO patients and optimal mechanical ventilation during ECMO. The ACE will participate in the national education program for fellows of Intensive Care and the new educational program of the master Clinical Technology (starting 2017) and is anticipated to provide at least one project a year for a master thesis.
ACE/ECMO has an establied role in the setup and ongoing education of ECMO programs in different foreign countries as expert reference center for training of medical and nursing teams. Within this context we provided hospitality and training for the following nations: Italy, Saudi-Arabia, Sweden, Catar, Hungery, Austria, Germany and Kuwait.
All activities are academic according to the Robijn Model and recognized as such by the Nederlandse Zorg Autoriteit (NZA). For many of the underlying diagnoses, in particular the pediatric age group we are recognized within the context of NFU approved centers of excellence (neonatal congenital anomalies, pediatric cardiac surgery).
The ELSO organization has awarded the Erasmus MC program as Center of Excellence in 2015. We have started to use ECMO on the emergency department for out-hospital cardiac arrest (OHCA) due to lung emboli. By the end of this year we will start to use ECMO in the treatment of in-hospital cardiac arrest and thereafter we will use ECMO in OHCA outside the hospital by special ECMO team. Clinical pathways are available and are multidisciplinary. Within this context the granted Horizon2020 project CIRDinnova place an important role in the evaluation of the usefullness of ECMO as part of eCPR.
The data set includes both somatic, neuropsychological and cost-effectiveness parameters and are published in peer reviewed journals, see item 6 (all top 10 publications). From birth to 17 years patients are being offered a multidisciplinary longitudinal follow-up program aiming at early detection of problems on growth and development and to offer timely intervention. The second largest group of neonatal ECMO-survivors is congenital diaphragmatic hernia (CDH). A statement paper on optimal follow up using the SCAMP methodology is published in Pediatric Research (2018) guiding future development of evidence based long term follow up.
This patient group is part of the NFU Center of Excellence of Congenital Anatomical Malformations and will be involved in the Value Based Health Care Program. The results of two RCT's that are currently being performed on improvement of exercise endurance and working memory training. The results of these RCT's will be used to offer evidence-based care. These are published in two thesis projects (Raisa Schiller, cum laude may 2018) and (Leontien Duister-Toussiant, spring 2019).
Societal Relevance to Research, Education and Patient Care
The pharmacology research (connected to ACE Pharmacology); the coagulation studies (connected to the ACE Hemostasis) and long term follow up (connected to the ACE AAA) have resulted in international standardization in therapies and evaluation. Member of the ACE was chair of the working group ECMO of National Intensive Care Society, which developed national guidelines for institutions considering treating ECMO patients (adults only). The Erasmus MC is now part of the juries of international evaluation of ECMO centers of excellence international. A structure for evaluation has been set up together with Erasmus MC both in de US as well as in Europe.
These guidelines recently have been approved. Members of the ACE are actively being involved in patient support groups for CDH in the Netherlands. Internationally, the members contribute in writing book chapters on ECMO outcome (including the Red Book on ECMO, published by ELSO) and are involved in development of international ELSO guidelines on long-term follow-up of neonatal an pediatric ECMO-survivors. Furthermore, members of ACE contribute to postgraduate educational activities and international conferences.
Members of the ACE will be member of the working group EMCO and VAD of Scientific Standardization Subcommittee Pediatric/Neonatal Thrombosis and Hemostasis of International Society of Thrombosis and Hemostasis (pediatric patients): development of guidelines and research initiatives.
Viability of Research, Education and Patient Care
Dr. A. Top. finished her Thesis: Microcirculation in Critically ill children (mainly ECMO patients) in 2011. Thereafter, she occupied a position as pediatric intensivist in the University of Cambridge (UK). All PhD students have following the finalization of their thesis obtained a certified training position in specialties as pediatrics and anesthesiology.
Dr. A. Zwiers received the second prize of the Dutch Pediatric Association of the young investigators award and an award of the Dutch Kidney Foundations of her scientific work followed by a training position in anesthesia.
In April 2018 a celebration symposium was organized based on 25 years of ECMO in Erasmus MC with international speakers to guide the future and show our patient and research infrastructure.
On a more experimental note we will explore in our newly established Laboratory of Experimental Intensive Care Medicine methodologies to set up a rat model of cardiogenic and septic shock with VV or VA ECMO support guided by Prof. Can Ince.
Key and relevant publications of the last five years
- Cammen van der-Zijp van MH, Gischler SJ, Hop WC, Jongste JC de, Tibboel D. Deterioration of exercise capacity after neonatal extracorporeal membrane oxygenation. European Respiratory Journal 2011;38:1098-1104 IF 5.922 5-year 6.218 Ranking Respiratory System 4/46 Q1 Top 10
- Madderom M, Reuser JJ, Utens EM, Rosmalen J van, Raets M, Govaert P, Steiner K, Gischler SJ, Tibboel D, Heijst AF van, IJsselstijn H. Neurodevelopmental, educational and behavioral outcome at 8 years after neonatal ECMO: a nationwide multicenter study. Intensive Care Medicine 2013;39:1584-1593 IF 5.258 5-Year IF 5.036 Critical Care Medicine 4/27 Q1 Top 10
- Madderom M, Toussaint L, Cammen-van Zijp M, Gischler S, Wijnen R, Tibboel D, IJsselstijn H. Congenital diaphragmatic hernia with(out) ECMO: impaired development at 8 years. Archives of Disease in Childhood Fetal and Neonatal Edition 2013;98:F316-F322 IF 3.451 5-Year IF 3.517 Pediatrics 8/122 Q1 Top 10
- van der Cammen-van Zijp MH, Janssen AJ, Raets MM, van Rosmalen J, Govaert P, Steiner K, Gischler SJ, Tibboel D, van Heijst AF, IJsselstijn H. Motor performance after neonatal extracorporeal membrane oxygenation: a longitudinal evaluation. Pediatrics 2014 Aug;134(2):e427-35. IF 5.297 Journal Ranking: Pediatrics 2/117 Q1 top-10
- Zwiers AJ, Cransberg K, van Rosmalen J, Wildschut ED, Tibboel D, de Wildt SN. Loop diuretics are an independent risk factor for acute kidney injury in children on extracorporeal membrane oxygenation with pre-emptive continuous hemofiltration. Intensive Care Med 2014 Apr;40(4):627-628. IF 5.544 Journal Ranking: Critical Care Medicine 4/27 Q1 top-10
- Zwiers AJ, IJsselstijn H, van Rosmalen J, Gischler SJ, de Wildt SN, Tibboel D, Cransberg K. CKD and Hypertension during Long-Term Follow-Up in Children and Adolescents Previously Treated with Extracorporeal Membrane Oxygenation. Clin J Am Soc Nephrol. 2014 Dec 5;9(12):2070-8.IF 5.250 Journal Ranking: Urology & Nephrology 6/77 Q1 top-10
- Toussaint LC, van der Cammen-van Zijp MH, Janssen AJ, Tibboel D, van Heijst AF, IJsselstijn H. Perceived Motor Competence Differs From Actual Performance in 8-Year-Old Neonatal ECMO Survivors. Pediatrics.2016 Mar;137(3):1-9. doi: 10.1542/peds.2015-2724. IF 5.196 3/120 Q1 top 10
- Spoel M, Laas R, Gischler SJ, Hop WJC, Tibboel D, Jongste JC de, IJsselstijn H. Diagnosis-related deterioration of lung function after extracorporeal membrane oxygenation. European Respiratory Journal 2012;40:1531-1537IF 5.895 5-Year IF 5.879 Respiratory System 3/48 Q1 Top 10
- Reis Miranda D, van Thiel R, Brodie D, Bakker J, Right ventricular unloading of venovenous extra-corporeal membreane oxygenation. Am J Respir Crit Care Med 2015;191:346-348 IPF: 13.1
- Harms FA, Bodmer SI, Raat NJ, Mik EG. Non-invasive monitoring of mitochondrial oxygenation and respiration in critical illness using a novel technique. Crit Care. 2015 Sep 22
- MacLaren G, Fortenberry J, Tibboel D, Laussen PC. Pediatr Crit Care Med. 2017 Universal Follow-Up After Extracorporeal Membrane Oxygenation: Baby Steps Toward Establishing an International Standard of Care. Nov;18(11):1070-1072.
- Snoek KG, Greenough A, van Rosmalen J, Capolupo I, Schaible T, Ali K, Wijnen RM, Tibboel D.Congenital Diaphragmatic Hernia: 10-Year Evaluation of Survival, Extracorporeal Membrane Oxygenation, and Foetoscopic Endotracheal Occlusion in Four High-Volume Centres. Neonatology. 2018;113(1):63-68.
- Leeuwen L, Mous DS, van Rosmalen J, Olieman JF, Andriessen L, Gischler SJ, Joosten KFM, Wijnen RMH, Tibboel D, IJsselstijn H, Spoel M. Congenital Diaphragmatic Hernia and Growth to 12 Years. Pediatrics. 2017 Aug;140(2). pii: e20163659.
- Schiller RM, IJsselstijn H, Madderom MJ, Rietman AB, Smits M, van Heijst AFJ, Tibboel D, White T, Muetzel RL. Neurobiologic Correlates of Attention and Memory Deficits Following Critical Illness in Early Life. Crit Care Med. 2017 Oct;45(10):1742-1750.
- Snoek KG, Peters NCJ, van Rosmalen J, van Heijst AFJ, Eggink AJ, Sikkel E, Wijnen RM, IJsselstijn H, Cohen-Overbeek TE, Tibboel D. The validity of the observed-to-expected lung-to-head ratio in congenital diaphragmatic hernia in an era of standardized neonatal treatment; a multicenter study. Prenat Diagn. 2017 Jul;37(7):658-665.
- Leeuwen L, van Heijst AFJ, van Rosmalen J, de Rijke YB, Beurskens LWJE, Tibboel D, van den Akker ELT, IJsselstijn H. Changes in thyroid hormone concentrations during neonatal extracorporeal membrane oxygenation. J Perinatol. 2017 Aug;37(8):906-910.
- Kleiber N, Mathôt RAA, Ahsman MJ, Wildschut ED, Tibboel D, de Wildt SN. Population pharmacokinetics of intravenous clonidine for sedation during paediatric extracorporeal membrane oxygenation and continuous venovenous hemofiltration. Br J Clin Pharmacol. 2017 Jun;83(6):1227-1239.
- Schiller RM, Madderom MJ, Reuser JJ, Steiner K, Gischler SJ, Tibboel D, van Heijst AF, IJsselstijn H. Neuropsychological Follow-up After Neonatal ECMO. Pediatrics. 2016 Nov;138(5). pii: e20161313. Epub 2016 Oct 6.
- Houmes RJ, Ten Kate CA, Wildschut ED, Verdijk RM, Wijnen RM, de Blaauw I, Tibboel D, van Heijst AF. Risk and relevance of open lung biopsy in pediatric ECMO patients: the Dutch experience. J Pediatr Surg. 2017 Mar;52(3):405-409.
- Schiller RM, van den Bosch GE, Muetzel RL, Smits M, Dudink J, Tibboel D, Ijsselstijn H, White T. Neonatal critical illness and development: white matter and hippocampus alterations in school-age neonatal extracorporeal membrane oxygenation survivors. Dev Med Child Neurol. 2017 Mar;59(3):304-310.
- Leeuwen L, van Heijst AF, Vijfhuize S, Beurskens LW, Weijman G, Tibboel D, van den Akker EL, IJsselstijn H. Nationwide Evaluation of Congenital Hypothyroidism Screening during Neonatal Extracorporeal Membrane Oxygenation. Neonatology. 2017;111(2):93-99. doi: 10.1159/000448238. Epub 2016 Sep 17.
- Snoek KG, Capolupo I, Morini F, van Rosmalen J, Greenough A, van Heijst A, Reiss IK, IJsselstijn H, Tibboel D; Congenital Diaphragmatic Hernia EURO Consortium. Score for Neonatal Acute Physiology-II Predicts Outcome in Congenital Diaphragmatic Hernia Patients. Pediatr Crit Care Med. 2016 Jun;17(6):540-6.
- Snoek KG, Kraemer US, Ten Kate CA, Greenough A, van Heijst A, Capolupo I, Schaible T, van Rosmalen J, Wijnen RM, Reiss IK, Tibboel D. High-Sensitivity Troponin T and N-Terminal Pro-Brain Natriuretic Peptide in Prediction of Outcome in Congenital Diaphragmatic Hernia: Results from a Multicenter, Randomized Controlled Trial. J Pediatr. 2016 Jun;173:245-249.e4.
- Madderom MJ, Schiller RM, Gischler SJ, van Heijst AF, Tibboel D, Aarsen FK, IJsselstijn H. Growing Up After Critical Illness: Verbal, Visual-Spatial, and Working Memory Problems in Neonatal Extracorporeal Membrane Oxygenation Survivors. Crit Care Med. 2016 Jun;44(6):1182-90.
- Toussaint LC, van der Cammen-van Zijp MH, Janssen AJ, Tibboel D, van Heijst AF, IJsselstijn H. Perceived Motor Competence Differs From Actual Performance in 8-Year-Old Neonatal ECMO Survivors. Pediatrics. 2016 Mar;137(3):e20152724.
- Kleiber N, de Wildt SN, Cortina G, Clifford M, van Rosmalen J, van Dijk M, Tibboel D, Millar J. A Comparative Analysis of Preemptive Versus Targeted Sedation on Cardiovascular Stability After High-Risk Cardiac Surgery in Infants. Pediatr Crit Care Med. 2016 Apr;17(4):321-31.
- Snoek KG, Capolupo I, van Rosmalen J, Hout Lde J, Vijfhuize S, Greenough A, Wijnen RM, Tibboel D, Reiss IK; CDH EURO Consortium. Conventional Mechanical Ventilation Versus High-frequency Oscillatory Ventilation for Congenital Diaphragmatic Hernia: A Randomized Clinical Trial (The VICI-trial). Ann Surg. 2016 May;263(5):867-74.
- Akin S, Dos Reis Miranda D, Caliskan K, Soliman OI, Guven G, Struijs A, van Thiel RJ, Jewbali LS, Lima A, Gommers D, Zijlstra F, Ince C. Functional evaluation of sublingual microcirculation indicates successful weaning from VA-ECMO in cardiogenic shock. Crit Care. 2017 Oct 26;21(1):265. doi: 10.1186/s13054-017-1855-2.
- Kara A, Akin S, Dos Reis Miranda D, Struijs A, Caliskan K, van Thiel RJ, Dubois EA, de Wilde W, Zijlstra F, Gommers D, Ince C. Microcirculatory assessment of patients under VA-ECMO. Crit Care. 2016 Oct 25;20(1):344
- Drumpt AS van, Kroon HM, Grüne F, van Thiel R, Spaander MCW, Wijnhoven BPL, Dos Reis Miranda D. Surgery for a large tracheoesophageal fistula using extracorporeal membrane oxygenation. J Thorac Dis. 2017 Sep;9(9):E735-E738. doi: 10.21037/jtd.2017.08.03.
- Uil CA den, Dos Reis Miranda D, Van Mieghem NM, Jewbali LS.A Niche Indication for Intra-Aortic Balloon Pump Counterpulsation: Aortic Valve Opening in a Surgically Vented Left Ventricle on Venoarterial ECMO. JACC Cardiovasc Interv. 2017 Jul 24;10(14):e133-e134. doi: 10.1016/j.jcin.2017.04.011.
- Lorusso R, Taccone FS, Belliato M, Delnoij T, Zanatta P, Cvetkovic M, Davidson M, Belohlavek J, Matta N, Davis C, Ijsselstijn H, Mueller T, Muellenbach R, Donker D, David P, Di Nardo M, Vlasselaers D, Dos Reis Miranda D, Hoskote A; Euro-ELSO Working Group on Neurologic Monitoring and Outcome. Brain monitoring in adult and pediatric ECMO patients: the importance of early and late assessments. Minerva Anestesiol. 2017 Oct;83(10):1061-1074.
- Uil CA den, Akin S, Jewbali LS, Dos Reis Miranda D, Brugts JJ, Constantinescu AA, Kappetein AP, Caliskan K. Short-term mechanical circulatory support as a bridge to durable left ventricular assist device implantation in refractory cardiogenic shock: a systematic review and meta-analysis. Eur J Cardiothorac Surg. 2017 Jul 1;52(1):14-25.
- Uil CA den, Jewbali LS, Heeren MJ, Constantinescu AA, Van Mieghem NM, Reis Miranda DD. Isolated left ventricular failure is a predictor of poor outcome in patients receiving veno-arterial extracorporeal membrane oxygenation. Eur J Heart Fail. 2017 May;19 Suppl 2:104-109.
- Ince C, Boerma EC, Cecconi M, de Backer D, et al 2018. Second consensus on the assessment of sublingual microcirculation in criticaly ill patients. Intensive Care Med. 2018; 44:281-299.
PhD theses of the last five years
- Top APC, Microcirculation in critically ill children(Co)promotor(s): Tibboel, prof. dr. D; Ince, prof. dr. C; Dijk, dr. M vanPhD EUR (t1); 27-1-2011
- Spoel M. The air that we breathe: Respiratory morbidity in children with congenital pulmonary malformationsCo)promotor(s): Tibboel, prof. dr. D; Jongste, prof. dr JC de; Meijers-IJsselstijn, Dr. HPhD EUR (t.1); 15-6-2012
- Madderom MJ. Long-term follow-up of children treated with neonatal extracorporeal membrane oxygenation: neuropsychological outcome.(Co-)Promotor(s): Tibboel, prof. dr. D; Heijst, Dr. AFJ van; IJsselstijn, dr. HPhD EUR (t1); 5-6-2013
- Buijs EAB. Critically ill children and the microcirculation. Go with the flow?Promotors: Tibboel, prof. dr D; Ince, prof. dr. CPhD EUR (t1); 24-6-2014
- Harms FA. Towards non‐invasive monitoring of mitochondrial functionPromotor: Stolker, prof. dr. RJ. Co-promotor: Mik, dr. E. G.PhD EUR (t1); 26-11-2014
- Zwiers JM. Do not squeeze the kidneys! Acute Kidney Injury in Critically Ill Children.Promotor: Tibboel, prof. dr. DPhD EUR (t1); 17-6-2015
- Houmes RJM. Pediatric extracorporeal membrane oxygenation, Why, When and HowPromotor: Tibboel, prof. dr D, Co-promotor: Wildschut, dr. E.D.PhD EUR (t1); 25-5-2016
- Snoek KG. A dive into the wondrous world of congenital diaphragmatic hernia. Promotor: Prof. Dr. R.M.H. Wijnen, Prof. Dr. D. Tibboel. June 15, 2016
- Mous D. Pulmonary Vascular Defects in Congenital Diaphragmatic Hernia. The quest for early factors and intervention. Promotors: Prof. Dr. D. Tibboel, Prof. Dr. R.M.H. Wijnen. November 30 2017
- Leeuwen L. From the first breath of life: congenital diaphragmatic hernia, the child at risk. Promotors: Prof. Dr. D. Tibboel, Prof. Dr. R.M.H. Wijnen. December 12 2017
- Kleiber N. Analgosedatives in the pediatric intensive care. More than sleep alone? Promotors: Prof. Dr. D. Tibboel, Prof. Dr. S.N. de Wildt. December 21 2017
- Schiller R. The vulnerable brain. Neurodevelopment after neonatal critical illness. Promotors: Prof. Dr. D. Tibboel, Prof. Dr. F.C. Verhulst. May 29 2018
Non-scientific publications related to the ACE
- Brandpunt: Dilemma's op de kinder IC - 3-10-2017: https://pers.kro-ncrv.nl/programmas/brandpunt/brandpunt-dilemmas-op-de-kinder-ic