- Open Access
Brain death and postmortem organ donation: report of a questionnaire from the CENTER-TBI study
Critical Carevolume 22, Article number: 306 (2018)
We aimed to investigate the extent of the agreement on practices around brain death and postmortem organ donation.
Investigators from 67 Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study centers completed several questionnaires (response rate: 99%).
Regarding practices around brain death, we found agreement on the clinical evaluation (prerequisites and neurological assessment) for brain death determination (BDD) in 100% of the centers. However, ancillary tests were required for BDD in 64% of the centers. BDD for nondonor patients was deemed mandatory in 18% of the centers before withdrawing life-sustaining measures (LSM). Also, practices around postmortem organ donation varied. Organ donation after circulatory arrest was forbidden in 45% of the centers. When withdrawal of LSM was contemplated, in 67% of centers the patients with a ventricular drain in situ had this removed, either sometimes or all of the time.
This study showed both agreement and some regional differences regarding practices around brain death and postmortem organ donation. We hope our results help quantify and understand potential differences, and provide impetus for current dialogs toward further harmonization of practices around brain death and postmortem organ donation.
Before the 1950s, death was only determined using cardiovascular criteria. Due to advances in critical care medicine, especially mechanical ventilation, a new clinical state was observed in 1958 (i.e., “coma dépassé”) . Although the systemic circulation was intact, the brain showed no objective evidence of function. This observation gave rise to the question of what “coma dépassé” meant. The successful transplantation of kidneys from a “coma dépassé” patient (1965) subsequently led to the first accepted standard for the confirmation of brain death in 1968 . In 1981, the Uniform Determination of Death Act made death determined by neurological and cardiovascular criteria equivalent . The American Academy of Neurology (AAN) in 1995 published guidelines for brain death determination (BDD) , and updated these in 2010 . In 2008, the Academy of Medical Royal Colleges in the United Kingdom (UK) provided broader guidance on the determination of death in a range of circumstances, including BDD .
Brain death and postmortem organ donation are closely linked. Also, an important, and not well investigated, issue regarding circulatory arrest organ donation is the hands-off time after circulatory arrest. Practices around all of these mentioned topics are delicate. Thus, inconsistencies between centers can be confusing for the general public, and could expose clinicians to accusations of unethical practice. Consensus regarding practices around brain death and postmortem organ donation could prevent these inconsistencies. To facilitate this consensus, the first step is to document potential differences.
The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI, www.center-tbi.eu) study addressed this issue. The CENTER-TBI study used questionnaires to create “provider profiles” of participating neurotrauma centers. One of these questionnaires intended to address specific practices around brain death and postmortem organ donation that currently provoke international discussion. Using this questionnaire, we aimed to quantify and understand potential differences, and provide impetus for current dialogs toward further harmonization of practices around brain death and postmortem organ donation. Regarding brain death, we investigated: criteria used for BDD; and the necessity of BDD before withdrawing life-sustaining measures (LSM). As for postmortem organ donation, we investigated: removal of the ventricular drain while continuing other LSM; the possibility for circulatory arrest organ donation; and the hands-off time after circulatory arrest.
CENTER-TBI and study sample
The CENTER-TBI study includes a prospective observational study on traumatic brain injury (TBI) [7, 8]. The investigators connected to this study collect data on patient characteristics, management, and outcomes in important centers from 20 countries across Europe and Israel. Investigators from all participating centers in the CENTER-TBI study were asked to complete several questionnaires. Centers were located in Austria (N = 2), Belgium (N = 4), Bosnia and Herzegovina (N = 2), Denmark (N = 2), Finland (N = 2), France (N = 7), Germany (N = 4), Hungary (N = 2), Israel (N = 2), Italy (N = 8), Latvia (N = 3), Lithuania (N = 2), the Netherlands (N = 7), Norway (N = 3), Romania (N = 1), Serbia (N = 1), Spain (N = 4), Sweden (N = 2), Switzerland (N = 1), and the UK (N = 8).
Questionnaire development and administration
More detailed information about the development, administration, and content of the questionnaires is available from an earlier publication by Cnossen et al. .
The topics covered in the current study are summarized in Table 1. A complete overview of the questionnaires for this study can be found in Additional file 1: Questionnaire 1 (questions 1, 4, 8, and 9), 7 (questions 2 and 4), and 8 (questions 9 and 11–15). In the questionnaires, we explicitly asked for the “general policy” according to the investigators. We defined this as the local standards used in more than 75% of patients, recognizing that there might be exceptions. Most questions made use of categorical answer categories. For some questions, the investigators had the option to fill in an answer that could be different from one of the options provided. These answers were marked as “other” and consisted of free text responses. Where these free text responses from different investigators were sufficiently similar, we sought to combine them to provide additional categorical responses. We did this to facilitate summary descriptive statistics.
We used descriptive statistics to describe our outcomes. We calculated frequencies and percentages for all variables related to the number of responses for that question. Centers at which the investigator did not respond to every question remained in our study, in order to keep groups for descriptive statistics as large as possible. The response rates per question are presented in Table 1. We grouped countries into seven regions: Baltic States (Latvia and Lithuania), Eastern Europe (Bosnia and Herzegovina, Hungary, Romania, and Serbia), Israel, Northern Europe (Denmark, Finland, Norway, and Sweden), Southern Europe (Italy and Spain), the United Kingdom, and Western Europe (Austria, Belgium, France, Germany, the Netherlands, and Switzerland). We examined potential differences between and within regions.
Of the 68 centers, investigators from 67 centers participated in the questionnaires (response rate: 99%) and were included in the analysis. The participating centers were mainly academic centers (N = 61, 91%), designated as a level I or II trauma center (N = 49, 73%). The average number of beds in the participating centers was 1187, of which on average 39 were intensive care unit (ICU) beds. The average number of annual treatments per ICU in 2013 was 1408, of which on average 130 were TBI patients.
Practices around brain death
When do you declare a patient brain dead?
We found agreement on the clinical evaluation (prerequisites and neurological assessment) for BDD in 100% of the centers. The clinical evaluation for BDD included: a Glasgow Coma Scale (GCS) of three, absence of brain stem reflexes, no respiratory efforts in response to an apnea test, and absence of confounding factors to evaluate consciousness (e.g., hypothermia). However, ancillary tests were required for BDD in 43 (64%) centers (Table 2).
In three regions (43%; Israel, Southern Europe, and the UK), the same criteria for BDD were used in every center of the same region. In centers from Northern Europe and the UK, ancillary tests were rarely used for BDD (N = 2, 22% and N = 0, 0%, respectively).
Must the patient, who is not suitable for organ donation, be declared brain dead before withdrawing LSM?
The declaration of brain death in nondonor patients was mandatory before withdrawing LSM in 12 (18%) centers. In 41 (61%) centers, a poor prognosis as assessed by the treating physician(s) was considered sufficient. In 9 (13%) centers, a GCS score of three, fixed dilated pupils, and absence of confounders could motivate withdrawing LSM (Table 2).
In all centers in the Baltic States (N = 5), nondonor patients were declared brain dead before withdrawing LSM. In several centers in Eastern Europe and Southern Europe (N = 1, 17% and N = 6, 50%, respectively), it was mandatory to declare a patient brain dead before withdrawing LSM in nondonor patients, whereas in other centers from the same region this was not mandatory.
Practices around postmortem organ donation
Would you consider organ donation after circulatory arrest in a patient in whom mechanical ventilation will be withdrawn, but who is not brain dead?
In all centers in the UK (N = 8), postmortem organ donation after circulatory arrest was approved. In centers in the Baltic States, Eastern Europe, and Northern Europe, organ donation after circulatory arrestwas often forbidden (N = 4, 80%; N = 4, 67% and N = 6, 67% respectively).
If the decision is made to withdraw life-sustaining measures, in a patient with high intracranial pressure, but who is not brain dead, would you remove the ventricular drain (for CSF drainage), but continue other life-sustaining measures in the hope that the patient will become brain dead and thereby becomes a suitable candidate for organ donation?
In 45 (67%) centers, the ventricular drain was sometimes or always removed. In 11 of these 45 centers (16% of the Sample total), the ventricular drain was always removed while continuing other LSM. In 22 (33%) centers, the ventricular drain was never removed while continuing other LSM (Fig. 2 and Table 3).
In 4 (80%) centers in the Baltic States and in 7 (88%) centers in the UK, the ventricular drain was never removed. In all centers from Israel (N = 2) and Northern Europe (N = 9), the ventricular drain was “sometimes” removed.
After withdrawal of mechanical ventilation and after circulatory arrest, when exactly do you declare the patient dead in case of a circulatory death organ donor, and in cases not suitable as an organ donor?
In the case of a circulatory death organ donor, it was most common (N = 15, 23%) to declare the patient dead after 5-min “flatliner-ECG”. In cases not suitable as an organ donor, it was most common (N = 21, 32%) to declare the patient dead directly after detection of a “flatliner-ECG” on the monitor (Table 4).
In all centers in Israel, nondonor patients were declared dead directly after detection of a “flatliner-ECG” on the monitor. No other region had the same answer in every center concerning the declaration of death in donor and nondonor patients.
We aimed to investigate specific practices that currently provoke international discussion in the area of brain death and postmortem organ donation. We aimed to quantify and understand potential differences, and provide impetus for current dialogs toward further harmonization of practices around brain death and postmortem organ donation.
Taking all results together, we found agreement on the clinical evaluation (prerequisites and neurological assessment) for brain death determination (BDD) across regions. In addition to this clinical evaluation, ancillary tests were required for BDD in 64% of the centers. BDD was deemed mandatory before withdrawal of life-sustaining measures (LSM) even outside the context of organ donation in 18% of the centers. As for practices around postmortem organ donation across regions, in 67% of the centers a ventricular drain was sometimes or always removed while other LSM were continued. Last, in 45% of the centers organ donation after circulatory arrest was forbidden.
We found important agreement and some differences regarding practices around brain death. Due to the broad categorical answer possibilities provided, the application of these findings is limited. First, agreement existed in all centers on the clinical evaluation for BDD, namely a Glasgow Coma Scale (GCS) of three, absence of brain stem reflexes, no respiratory efforts in response to an apnea test, and absence of confounding factors to evaluate consciousness. This is promising, in the light of recent calls to reach a worldwide consensus on how to determine brain death . However, in addition to this clinical evaluation, ancillary tests were reported to be required for BDD in two thirds of centers. These differences in the use of ancillary tests are in line with previous literature [11,12,13,14,15,16,17,18,19]. Interestingly, however, there have been calls to abandon ancillary tests for BDD . In the majority of centers from Northern Europe and the United Kingdom (UK), ancillary tests were not mandatory for BDD. This is in line with the study by Wahlster et al. . These discrepancies may suggest differences in ethical principles and regulatory practice between centers. In some centers it was mandatory to declare nondonor patients brain dead before withdrawing life-sustaining measures (LSM). Withdrawal of LSM and the declaration of brain death are two different processes. The obligation of BDD before limiting treatment is debatable, since many non-brain dead patients may have a hopeless prognosis rendering further treatment futile.
We also found differences regarding practices around postmortem organ donation. First, we found differences concerning the removal of the ventricular drain. Our questionnaire did not assess in-depth the reasons why some centers opted to discontinue drainage and remove the ventricular drain as compared to maintaining the device in place, and how such continued intervention was incorporated into the care plan. Second, we found differences with regard to the possibility for organ donation after circulatory arrest. These results are in line with previous literature [21, 22]. The ventricular drain (mentioned earlier in this paragraph) seemed to be removed more often in centers where donation after circulatory arrest was not possible. If this turns out to be general practice, this might indicate the need for reevaluation of organ donation after circulatory arrest in order to prevent future burdensome care. For international figures on donation and transplantation, we refer the reader to the Newsletter Transplant 2017 produced by the Council of Europe of the European Committee . There are no specific figures available for the centers involved in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Although the CENTER-TBI study includes important neurotrauma centers, we do not know to what extent these centers are responsible for the investigated figures of the Council of Europe. For the countries involved in our study, the number of donations after brain death in 2016 varied between 1.3 per million inhabitants (Bosnia and Herzegovina) and 33.1 per million inhabitants (Spain) . Third, we found differences in hands-off times needed after circulatory arrest in order to declare a patient dead. This could indicate a lack of clear evidence on the exact time needed to be sure the brain has irreversibly lost its function.
Some of the differences appear region specific, but for other aspects we found variation between centers within a single region. Differences were even noted between regions participating in Eurotransplant, an organization that aims to optimally distribute organs by transplanting across national borders, when no matching recipient is available on the waiting list in the donor’s country. Eurotransplant covers part of Europe, and includes eight countries: Austria, Belgium, Croatia, Germany, Hungary, the Netherlands, Luxembourg, and Slovenia. The differences found pertained to all topics covered in this study.
Present-day medicine is said to be affected by the cultural climate of the society in which it exists . This may indicate that differences in culture could explain some of the observed variation. Other results, such as possibilities for organ donation after circulatory arrest, suggest that variations have a more legal or regulatory basis. Observed within-region differences which suggest a more legal or regulatory basis raise questions regarding the level of enforcement of pertinent laws, and may indicate a lack of knowledge, regulatory implementation, or ambiguous legislation.
This study has several limitations that should be considered when interpreting the results. First, the participating neurotrauma centers represent a select group. The data obtained may therefore not be representative for all neurotrauma centers within the geographical areas studied. Second, our sample size made it difficult to apply more advanced statistics, such as a chi-square test, cluster analysis, and multidimensional scaling. Third, the results are based on the perceptions of practices reported by specific investigators rather than on clinical data. The CENTER-TBI study will further clarify actual practices around brain death and postmortem organ donation by analyzing clinical data. Fourth, investigators may have interpreted some questions incorrectly because a questionnaire does not always permit the nuances appropriate for clinical practice. In clinical practice, potential alternative options are both more numerous and complex than can be captured by a questionnaire. Last, investigators may have presented (even unwittingly) a more favorable image or presented individual preferences instead of the general policy in a center that we asked for.
Future research should focus on extending this study to a larger group of neurotrauma centers across the world in order to examine (in more advanced statistics) whether our results also apply to other centers. Furthermore, it would be interesting to study the origin of the differences found (e.g., cultural differences and differences pertaining to legislation). The complexity of some of the drivers of reported practice makes the case for mixed methods approaches to this problem, with a potentially substantive role for qualitative research methods. These strategies are important in order to inform preferred approaches to improve harmonization in neurotrauma centers across Europe and Israel.
Most importantly, current dialogs should be continued, and we hope that our findings may provide a basis toward further harmonization of practices around brain death and postmortem organ donation.
This study showed both agreement and some regional differences regarding practices around brain death and postmortem organ donation. We hope our results help quantify and understand potential differences, and provide impetus for current dialogs toward further harmonization of practices around brain death and postmortem organ donation.
American Academy of Neurology
Brain death determination
Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury
Glasgow Coma Scale
Intensive care unit
Traumatic brain injury
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Cecilia Ackerlund1, Hadie Adams2, Vanni Agnoletti3, Judith Allanson4, Krisztina Amrein5, Norberto Andaluz6, Nada Andelic7, Lasse Andreassen8, Azasevac Antun9, Audny Anke10, Anna Antoni11, Hilko Ardon12, Gérard Audibert13, Kaspars Auslands14, Philippe Azouvi15, Maria Luisa Azzolini16, Camelia Baciu17, Rafael Badenes18, Ronald Bartels19, Pál Barzó20, Ursula Bauerfeind21, Romuald Beauvais22, Ronny Beer23, Francisco Javier Belda18, Bo-Michael Bellander24, Antonio Belli25, Rémy Bellier26, Habib Benali27, Thierry Benard26, Maurizio Berardino28, Luigi Beretta16, Christopher Beynon29, Federico Bilotta18, Harald Binder11, Erta Biqiri17, Morten Blaabjerg30, Hugo den Boogert19, Pierre Bouzat31, Peter Bragge32, Alexandra Brazinova33, Vibeke Brinck34, Joanne Brooker35, Camilla Brorsson36, Andras Buki37, Monika Bullinger38, Emiliana Calappi39, Maria Rosa Calvi16, Peter Cameron40, Guillermo Carbayo Lozano41, Marco Carbonara39, Elsa Carise26, K. Carpenter42, Ana M. Castaño-León43, Francesco Causin44, Giorgio Chevallard17, Arturo Chieregato17, Giuseppe Citerio45,46, Maryse Cnossen47, Mark Coburn48, Jonathan Coles49, Lizzie Coles-Kemp50, Johnny Collett50, Jamie D. Cooper51, Marta Correia52, Amra Covic53, Nicola Curry54, Endre Czeiter55, Marek Czosnyka56, Claire Dahyot-Fizelier26, François Damas57, Pierre Damas58, Helen Dawes59, Véronique De Keyser60, Francesco Della Corte61, Bart Depreitere62, Godard C. W. de Ruiter63, Dula Dilvesi9, Shenghao Ding64, Diederik Dippel65, Abhishek Dixit66, Emma Donoghue40, Jens Dreier67, Guy-Loup Dulière57, George Eapen68, Heiko Engemann53, Ari Ercole66, Patrick Esser59, Erzsébet Ezer69, Martin Fabricius70, Valery L. Feigin71, Junfeng Feng64, Kelly Foks65, Francesca Fossi17, Gilles Francony31, Ulderico Freo72, Shirin Frisvold73, Alex Furmanov74, Pablo Gagliardo75, Damien Galanaud27, Dashiell Gantner40, Guoyi Gao76, Karin Geleijns42, Pradeep George1, Alexandre Ghuysen77, Lelde Giga78, Benoit Giraud26, Ben Glocker79, Jagos Golubovic9, Pedro A. Gomez43, Francesca Grossi61, Russell L. Gruen80, Deepak Gupta81, Juanita A. Haagsma47, Iain Haitsma82, Jed A. Hartings83, Raimund Helbok23, Eirik Helseth84, Daniel Hertle30, Astrid Hoedemaekers85, Stefan Hoefer53, Lindsay Horton86, Jilske Huijben47, Peter J. Hutchinson2, Asta Kristine Håberg87, Bram Jacobs88, Stefan Jankowski68, Mike Jarrett34, Bojan Jelaca9, Ji-yao Jiang76, Kelly Jones89, Konstantinos Kamnitsas79, Mladen Karan6, Ari Katila90, Maija Kaukonen91, Thomas Kerforne26, Riku Kivisaari91, Angelos G. Kolias2, Bálint Kolumbán92, Erwin Kompanje93, Ksenija Kolundzija94, Daniel Kondziella70, Lars-Owe Koskinen36, Noémi Kovács92, Alfonso Lagares43, Linda Lanyon1, Steven Laureys95, Fiona Lecky96, Christian Ledig79, Rolf Lefering97, Valerie Legrand98, Jin Lei64, Leon Levi99, Roger Lightfoot100, Hester Lingsma47, Dirk Loeckx101, Angels Lozano18, Andrew I. R. Maas60, Stephen MacDonald102, Marc Maegele103, Marek Majdan33, Sebastian Major104, Alex Manara105, Geoffrey Manley106, Didier Martin107, Leon Francisco Martin101, Costanza Martino3, Armando Maruenda18, Hugues Maréchal57, Alessandro Masala3, Julia Mattern29, Charles McFadyen66, Catherine McMahon108, Béla Melegh109, David Menon66, Tomas Menovsky60, Cristina Morganti-Kossmann110, Davide Mulazzi39, Visakh Muraleedharan1, Lynnette Murray40, Holger Mühlan111, Nandesh Nair60, Ancuta Negru112, David Nelson1, Virginia Newcombe66, Daan Nieboer47, Quentin Noirhomme95, József Nyirádi5, Mauro Oddo113, Annemarie Oldenbeuving114, Matej Oresic115, Fabrizio Ortolano39, Aarno Palotie116,117,118, Paul M. Parizel119, Adriana Patruno120, Jean-François Payen31, Natascha Perera22, Vincent Perlbarg27, Paolo Persona121, Wilco Peul63, Anna Piippo-Karjalainen91, Sébastien Pili Floury122, Matti Pirinen116, Horia Ples112, Maria Antonia Poca123, Suzanne Polinder47, Inigo Pomposo41, Jussi Posti90, Louis Puybasset124, Andreea Radoi123, Arminas Ragauskas125, Rahul Raj91, Malinka Rambadagalla126, Ruben Real53, Veronika Rehorčíková33, Jonathan Rhodes127, Samuli Ripatti116, Saulius Rocka125, Cecilie Roe128, Olav Roise129, Gerwin Roks130, Jonathan Rosand131, Jeffrey Rosenfeld110, Christina Rosenlund132, Guy Rosenthal74, Rolf Rossaint48, Sandra Rossi121, Daniel Rueckert79, Martin Rusnák133, Marco Sacchi17, Barbara Sahakian66, Juan Sahuquillo123, Oliver Sakowitz134,135, Francesca Sala120, Renan Sanchez-Porras134, Janos Sandor136, Edgar Santos29, Luminita Sasu61, Davide Savo120, Nadine Schäffer103, Inger Schipper137, Barbara Schlößer21, Silke Schmidt111, Herbert Schoechl138, Guus Schoonman130, Rico Frederik Schou139, Elisabeth Schwendenwein11, Michael Schöll29, Özcan Sir140, Toril Skandsen141, Lidwien Smakman63, Dirk Smeets101, Peter Smielewski56, Abayomi Sorinola142, Emmanuel Stamatakis66, Simon Stanworth54, Nicole Steinbüchel143, Ana Stevanovic48, Robert Stevens144, William Stewart145, Ewout W. Steyerberg47,146, Nino Stocchetti147, Nina Sundström36, Anneliese Synnot34,148, Fabio Silvio Taccone18, Riikka Takala90, Viktória Tamás142, Päivi Tanskanen91, Mark Steven Taylor33, Braden Te Ao71, Olli Tenovuo90, Ralph Telgmann53, Guido Teodorani149, Alice Theadom71, Matt Thomas105, Dick Tibboel42, Christos Tolias150, Jean-Flory Luaba Tshibanda151, Tony Trapani40, Cristina Maria Tudora112, Peter Vajkoczy67, Shirley Vallance43, Egils Valeinis78, Gregory Van der Steen60, Mathieu van der Jagt152, Joukje van der Naalt88, Jeroen T. J. M. van Dijck63, Thomas A. van Essen63, Wim Van Hecke101, Caroline van Heugten59, Dominique Van Praag60, Thijs Vande Vyvere101, Julia Van Waesberghe48, Audrey Vanhaudenhuyse27,95, Alessia Vargiolu120, Emmanuel Vega153, Kimberley Velt47, Jan Verheyden101, Paul M. Vespa154, Anne Vik155, Rimantas Vilcinis156, Giacinta Vizzino17, Carmen Vleggeert-Lankamp63, Victor Volovici82, Daphne Voormolen47, Peter Vulekovic9, Zoltán Vámos69, Derick Wade59, Kevin K. W. Wang157, Lei Wang64, Lars Wessels158, Eno Wildschut42, Guy Williams66, Lindsay Wilson86, Maren K. L. Winkler104, Stefan Wolf158, Peter Ylén159, Alexander Younsi29, Menashe Zaaroor99, Yang Zhihui160, Agate Ziverte78, Fabrizio Zumbo3.
1 Karolinska Institutet, INCF International Neuroinformatics Coordinating Facility, Stockholm, Sweden.
2 Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke’s Hospital & University of Cambridge, Cambridge, UK.
3 Department of Anesthesia & Intensive Care, M. Bufalini Hospital, Cesena, Italy.
4 Department of Clinical Neurosciences, Addenbrooke’s Hospital & University of Cambridge, Cambridge, UK.
5 János Szentágothai Research Centre, University of Pécs, Pécs, Hungary.
6 University of Cincinnati, Cincinnati, OH, USA.
7 Division of Surgery and Clinical Neuroscience, Department of Physical Medicine and Rehabilitation, Oslo University Hospital and University of Oslo, Oslo, Norway.
8 Department of Neurosurgery, University Hospital Northern Norway, Tromsø, Norway.
9 Department of Neurosurgery, Clinical Centre of Vojvodina, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.
10 Department of Physical Medicine and Rehabilitation, University Hospital Northern Norway.
11 Trauma Surgery, Medical University Vienna, Vienna, Austria.
12 Department of Neurosurgery, Elisabeth-TweeSteden Ziekenhuis, Tilburg, the Netherlands.
13 Department of Anesthesiology & Intensive Care, University Hospital Nancy, Nancy, France.
14 Riga Eastern Clinical University Hospital, Riga, Latvia.
15 Raymond Poincaré Hospital, Assistance Publique—Hopitaux de Paris, Paris, France.
16 Department of Anesthesiology & Intensive Care, S Raffaele University Hospital, Milan, Italy.
17 NeuroIntensive Care, Niguarda Hospital, Milan, Italy.
18 Department Anesthesiology and Surgical-Trauma Intensive Care, Hospital Clinic Universitari de Valencia, Spain.
19 Department of Neurosurgery, Radboud University Medical Center, Nijmegen, the Netherlands.
20 Department of Neurosurgery, University of Szeged, Szeged, Hungary.
21 Institute for Transfusion Medicine (ITM), Witten/Herdecke University, Cologne, Germany.
22 International Projects Management, ARTTIC, München, Germany.
23 Department of Neurology, Neurological Intensive Care Unit, Medical University of Innsbruck, Innsbruck, Austria.
24 Department of Neurosurgery & Anesthesia & Intensive Care Medicine, Karolinska University Hospital, Stockholm, Sweden.
25 NIHR Surgical Reconstruction and Microbiology Research Centre, Birmingham, UK.
26 Intensive Care Unit, CHU Poitiers, Poitiers, France.
27 Anesthesie-Réanimation, Assistance Publique—Hopitaux de Paris, Paris, France.
28 Department of Anesthesia & ICU, AOU Città della Salute e della Scienza di Torino—Orthopedic and Trauma Center, Torino, Italy.
29 Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany.
30 Department of Neurology, Odense University Hospital, Odense, Denmark.
31 Department of Anesthesiology & Intensive Care, University Hospital of Grenoble, Grenoble, France.
32 BehaviourWorks Australia, Monash Sustainability Institute, Monash University, VIC, Australia.
33 Department of Public Health, Faculty of Health Sciences and Social Work, Trnava University, Trnava, Slovakia.
34 Quesgen Systems Inc., Burlingame, CA, USA.
35 Australian & New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
36 Department of Neurosurgery, Umea University Hospital, Umea, Sweden.
37 Department of Neurosurgery, University of Pecs and MTA-PTE Clinical Neuroscience MR Research Group and Janos Szentagothai Research Centre, University of Pecs, Hungarian Brain Research Program, Pecs, Hungary.
38 Department of Medical Psychology, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
39 Neuro ICU, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.
40 ANZIC Research Centre, Monash University, Department of Epidemiology and Preventive Medicine, Melbourne, Vitoria, Australia.
41 Department of Neurosurgery, Hospital of Cruces, Bilbao, Spain.
42 Intensive Care and Department of Pediatric Surgery, Erasmus University Medical Center, Sophia Children’s Hospital, Rotterdam, the Netherlands.
43 Department of Neurosurgery, Hospital Universitario 12 de Octubre, Madrid, Spain.
44 Department of Neuroscience, Azienda Ospedaliera Università di Padova, Padova, Italy.
45 NeuroIntensive Care, ASST di Monza, Monza, Italy.
46 School of Medicine and Surgery, Università Milano Bicocca, Milan, Italy.
47 Department of Public Health, Erasmus University Medical Center, Rotterdam, the Netherlands.
48 Department of Anaesthesiology, University Hospital of Aachen, Aachen, Germany.
49 Department of Anesthesia & Neurointensive Care, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK.
50 Movement Science Group, Oxford Institute of Nursing, Midwifery and Allied Health Research, Oxford Brookes University, Oxford, UK.
51 School of Public Health & PM, Monash University and The Alfred Hospital, Melbourne, VIC, Australia.
52 Radiology/MRI Department, MRC Cognition and Brain Sciences Unit, Cambridge, UK.
53 Institute of Medical Psychology and Medical Sociology, Universitätsmedizin Göttingen, Göttingen, Germany.
54 Oxford University Hospitals NHS Trust, Oxford, UK.
55 Department of Neurosurgery, University of Pecs and MTA-PTE Clinical Neuroscience MR Research Group and Janos Szentagothai Research Centre, University of Pecs, Hungarian Brain Research Program (Grant No. KTIA 13 NAP-A-II/8), Pecs, Hungary.
56 Brain Physics Lab, Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK.
57 Intensive Care Unit, CHR Citadelle, Liège, Belgium.
58 Intensive Care Unit, CHU, Liège, Belgium.
59 Movement Science Group, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, UK.
60 Department of Neurosurgery, Antwerp University Hospital and University of Antwerp, Edegem, Belgium.
61 Department of Anesthesia & Intensive Care, Maggiore Della Carità Hospital, Novara, Italy.
62 Department of Neurosurgery, University Hospitals Leuven, Leuven, Belgium.
63 Department of Neurosurgery, Leiden University Medical Center, Leiden, the Netherlands and Departmentt of Neurosurgery, Medical Center Haaglanden, The Hague, the Netherlands.
64 Department of Neurosurgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
65 Department of Neurology, Erasmus University Medical Center, Rotterdam, the Netherlands.
66 Division of Anaesthesia, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK.
67 Neurologie, Neurochirurgie und Psychiatrie, Charité-Universitätsmedizin Berlin, Berlin, Germany.
68 Neurointensive Care, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
69 Department of Anaesthesiology and Intensive Therapy, University of Pécs, Pécs, Hungary.
70 Departments of Neurology, Clinical Neurophysiology and Neuroanesthesiology, Region Hovedstaden Rigshospitalet, Copenhagen, Denmark.
71 National Institute for Stroke and Applied Neurosciences, Faculty of Health and Environmental Studies, Auckland University of Technology, Auckland, New Zealand.
72 Department of Medicine, Azienda Ospedaliera Università di Padova, Padova, Italy.
73 Department of Anesthesiology and Intensive Care, University Hospital Northern Norway, Tromsø, Norway.
74 Department of Neurosurgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
75 Fundación Instituto Valenciano de Neurorrehabilitación (FIVAN), Valencia, Spain.
76 Department of Neurosurgery, Shanghai Renji Hospital, Shanghai Jiaotong University/School of Medicine, Shanghai, China.
77 Emergency Department, CHU, Liège, Belgium.
78 Pauls Stradins Clinical University Hospital, Riga, Latvia.
79 Department of Computing, Imperial College London, London, UK.
80 Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; and Central Clinical School, Monash University, Melbourne, Victoria, Australia.
81 Department of Neurosurgery, Neurosciences Centre & JPN Apex Trauma Centre, All India Institute of Medical Sciences, New Delhi, India.
82 Department of Neurosurgery, Erasmus University Medical Center, Rotterdam, the Netherlands.
83 Department of Neurosurgery, University of Cincinnati, Cincinnati, OH, USA.
84 Department of Neurosurgery, Oslo University Hospital, Oslo, Norway.
85 Department of Intensive Care Medicine, Radboud University Medical Centern, Nijmegen, the Netherlands.
86 Division of Psychology, University of Stirling, Stirling, UK.
87 Department of Medical Imaging, St. Olavs Hospital and Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.
88 Department of Neurology, University Medical Center Groningen, Groningen, the Netherlands.
89 National Institute for Stroke & Applied Neurosciences of the AUT University, Auckland, New Zealand.
90 Rehabilitation and Brain Trauma, Turku University Central Hospital and University of Turku, Turku, Finland.
91 Helsinki University Central Hospital, Helsinki, Finland.
92 Hungarian Brain Research Program—Grant No. KTIA 13 NAP-A-II/8, University of Pécs, Pécs, Hungary.
93 Department of Intensive Care and Department of Ethics and Philosophy of Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
94 Department of Psychiatry, Clinical centre of Vojvodina, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.
95 Cyclotron Research Center, University of Liège, Liège, Belgium.
96 Emergency Medicine Research in Sheffield, Health Services Research Section, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK.
97 Institute of Research in Operative Medicine (IFOM), Witten/Herdecke University, Cologne, Germany.
98 VP Global Project Management CNS, ICON, Paris, France.
99 Department of Neurosurgery, Rambam Medical Center, Haifa, Israel.
100 Department of Anesthesiology & Intensive Care, University Hospitals Southampton NHS Trust, Southampton, UK.
101 icoMetrix NV, Leuven, Belgium.
102 Cambridge University Hospitals, Cambridge, UK.
103 Cologne-Merheim Medical Center (CMMC), Department of Traumatology, Orthopedic Surgery and Sportmedicine, Witten/Herdecke University, Cologne, Germany.
104 Centrum für Schlaganfallforschung, Charité-Universitätsmedizin Berlin, Berlin, Germany.
105 Intensive Care Unit, Southmead Hospital, Bristol, Bristol, UK.
106 Department of Neurological Surgery, University of California, San Francisco, CA, USA.
107 Department of Neurosurgery, CHU, Liège, Belgium.
108 Department of Neurosurgery, The Walton Centre NHS Foundation Trust, Liverpool, UK.
109 Department of Medical Genetics, University of Pécs, Pécs, Hungary.
110 National Trauma Research Institute, The Alfred Hospital, Monash University, Melbourne, VIC, Australia.
111 Department Health and Prevention, University Greifswald, Greifswald, Germany.
112 Department of Neurosurgery, Emergency County Hospital Timisoara, Timisoara, Romania.
113 Centre Hospitalier Universitaire Vaudois, Lausanne, Zwitserland.
114 Department of Intensive Care, Elisabeth-TweeSteden Ziekenhuis, Tilburg, the Netherlands.
115 Department of Systems Medicine, Steno Diabetes Center, Gentofte, Denmark.
116 Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
117 Analytic and Translational Genetics Unit, Department of Medicine; Psychiatric & Neurodevelopmental Genetics Unit, Department of Psychiatry; Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
118 Program in Medical and Population Genetics; The Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
119 Department of Radiology, Antwerp University Hospital and University of Antwerp, Edegem, Belgium.
120 NeuroIntensive Care Unit, Department of Anesthesia & Intensive Care, ASST di Monza, Monza, Italy.
121 Department of Anesthesia & Intensive Care, Azienda Ospedaliera Università di Padova, Padova, Italy.
122 Intensive Care Unit, CHRU de Besançon, Besançon, France.
123 Department of Neurosurgery, Vall d’Hebron University Hospital, Barcelona, Spain.
124 Department of Anesthesiology and Critical Care, Pitié-Salpêtrière Teaching Hospital, Assistance Publique, Hôpitaux de Paris and University Pierre et Marie Curie, Paris, France.
125 Department of Neurosurgery, Kaunas University of technology and Vilnius University, Vilnius, Lithuania.
126 Rezekne Hospital, Rezekne, Latvia
127 Department of Anaesthesia, Critical Care & Pain Medicine NHS Lothian & University of Edinburg, Edinburgh, UK.
128 Department of Physical Medicine and Rehabilitation, Oslo University Hospital/University of Oslo, Oslo, Norway.
129 Division of Surgery and Clinical Neuroscience, Oslo University Hospital, Oslo, Norway.
130 Department of Neurology, Elisabeth-TweeSteden Ziekenhuis, Tilburg, the Netherlands.
131 Broad Institute, Cambridge, MA; Harvard Medical School, Boston, MA; and Massachusetts General Hospital, Boston, MA, USA.
132 Department of Neurosurgery, Odense University Hospital, Odense, Denmark.
133 International Neurotrauma Research Organisation, Vienna, Austria.
134 Klinik für Neurochirurgie, Klinikum Ludwigsburg, Ludwigsburg, Germany.
135 University Hospital Heidelberg, Heidelberg, Germany.
136 Division of Biostatistics and Epidemiology, Department of Preventive Medicine, University of Debrecen, Debrecen, Hungary.
137 Department of Traumasurgery, Leiden University Medical Center, Leiden, the Netherlands.
138 Department of Anaesthesiology and Intensive Care, AUVA Trauma Hospital, Salzburg, Austria.
139 Department of Neuroanesthesia and Neurointensive Care, Odense University Hospital, Odense, Denmark.
140 Department of Emergency Care Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
141 Department of Physical Medicine and Rehabilitation, St. Olavs Hospital and Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.
142 Department of Neurosurgery, University of Pécs, Pécs, Hungary.
143 Universitätsmedizin Göttingen, Göttingen, Germany.
144 Division of Neuroscience Critical Care, John Hopkins University School of Medicine, Baltimore, MD, USA.
145 Department of Neuropathology, Queen Elizabeth University Hospital and University of Glasgow, Glasgow, UK.
146 Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands.
147 Department of Pathophysiology and Transplantation, Milan University, and Neuroscience ICU, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.
148 Cochrane Consumers and Communication Review Group, Centre for Health Communication and Participation, School of Psychology and Public Health, La Trobe University, Melbourne, Australia.
149 Department of Rehabilitation, M. Bufalini Hospital, Cesena, Italy.
150 Department of Neurosurgery, Kings College London, London, UK.
151 Radiology/MRI Department, CHU, Liège, Belgium.
152 Department of Intensive Care, Erasmus University Medical Center, Rotterdam, the Netherlands.
153 Department of Anesthesiology-Intensive Care, Lille University Hospital, Lille, France.
154 Director of Neurocritical Care, University of California, Los Angeles, CA, USA.
155 Department of Neurosurgery, St. Olavs Hospital and Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.
156 Department of Neurosurgery, Kaunas University of Health Sciences, Kaunas, Lithuania.
157 Department of Psychiatry, University of Florida, Gainesville, FL, USA.
158 Interdisciplinary Neuro Intensive Care Unit, Charité-Universitätsmedizin Berlin, Berlin, Germany.
159 VTT Technical Research Centre, Tampere, Finland.
160 University of Florida, Gainesville, FL, USA.
Data used in preparation of this manuscript were obtained in the context of the CENTER-TBI study, a large collaborative project, supported by the Framework 7 program of the European Union (602150). The funder had no role in the design of the study, the collection, analysis, and interpretation of data, or in writing the manuscript.
DKM was supported by a Senior Investigator Award from the National Institute for Health Research (UK). The funder had no role in the design of the study, the collection, analysis, and interpretation of data, or in writing the manuscript.
Availability of data and materials
There are legal constraints that prohibit us from making the data publicly available. Since there are only a limited number of centers per country included in this study (for two countries only one center), data will be identifiable. Readers may contact Dr Erwin J. O. Kompanje (firstname.lastname@example.org) for reasonable requests for the data.
Ethics approval and consent to participate
Not applicable since no patients participated, and the centers have given consent by completing the questionnaire.
Consent for publication
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Provider profiling questionnaires used for this study (Questionnaires 1, 7, and 8). (PDF 596 kb)