Skip to main content
main-content

01.12.2018 | Research | Ausgabe 1/2018 Open Access

Critical Care 1/2018

Brain death and postmortem organ donation: report of a questionnaire from the CENTER-TBI study

Zeitschrift:
Critical Care > Ausgabe 1/2018
Autoren:
Ernest van Veen, Mathieu van der Jagt, Maryse C. Cnossen, Andrew I. R. Maas, Inez D. de Beaufort, David K. Menon, Giuseppe Citerio, Nino Stocchetti, Wim J. R. Rietdijk, Jeroen T. J. M. van Dijck, Erwin J. O. Kompanje, CENTER-TBI investigators and participants
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s13054-018-2241-4) contains supplementary material, which is available to authorized users.
Abbreviations
AAN
American Academy of Neurology
BDD
Brain death determination
CENTER-TBI
Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury
CSF
Cerebrospinal fluid
ECG
Electrocardiography
GCS
Glasgow Coma Scale
ICU
Intensive care unit
LSM
Life-sustaining measures
TBI
Traumatic brain injury
UK
United Kingdom

Background

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”) [ 1]. 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 [ 2]. In 1981, the Uniform Determination of Death Act made death determined by neurological and cardiovascular criteria equivalent [ 3]. The American Academy of Neurology (AAN) in 1995 published guidelines for brain death determination (BDD) [ 4], and updated these in 2010 [ 5]. 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 [ 6].
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.

Methods

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. [ 9].
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.
Table 1
Topics covered, related questions for each topic, and response rate per question
Topics covered in this study
Questions related to this topic
Response rate, N (%)
Practices around brain death
 Criteria for BDD
When do you declare a patient brain dead?
67 (99%)
 Brain death and withdrawal of LSM
Must the patient, who is not suitable for organ donation, be declared brain dead before withdrawing life-sustaining measures?
67 (99%)
Practices around postmortem organ donation
 Donation after circulatory death
Would you consider organ donation after circulatory arrest in a patient in whom mechanical ventilation will be withdrawn, but who is not brain dead?
66 (97%)
 Ventricular drain removal and organ donation
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?
67 (99%)
 Declaration of death and hands-off time in donors and nondonors
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?
64 (94%)
 
After withdrawal of mechanical ventilation and after circulatory arrest, after how many minutes circulatory arrest do you declare the patient dead in cases not suitable as organ donor?
66 (97%)
BDD brain death determination, CSF cerebrospinal fluid, LSM life-sustaining measures

Analyses

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.

Results

Center characteristics

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).
Table 2
Practices around brain death
 
Region
Answer
Sample total
( N = 67)
Baltic States
( N = 5)
Eastern Europe
( N = 6)
Israel
( N = 2)
Northern Europe
( N = 9)
Southern Europe
( N = 12)
United Kingdom
( N = 8)
Western Europe
( N = 25)
When do you declare a patient brain dead?
 With GCS 3, fixed dilated pupils, and no confounding factors (e.g., hypothermia, barbiturates)
0
0
0
0
0
0
0
0
 With GCS 3 and absent brain stem reflexes, and no confounding factors
0
0
0
0
0
0
0
0
 With GCS 3, absent brain stem reflexes and apnea, and no confounding factors
31
20
17
0
78
0
88
20
 With GCS 3, absent brain stem reflexes, apnea and ancillary test(s) (e.g., EEG or cerebral angiography), and absence of confounding factors
64
80
83
100
22
100
0
72
 Per national protocol a
4
0
0
0
0
0
13
8
Must the patient, who is not suitable for organ donation, be declared brain dead before withdrawing LSM?
 No, the prospect of a very poor prognosis can be enough
61
0
17
0
78
42
100
80
 No, GCS 3 and fixed dilated pupils and no confounders is enough to stop treatment
13
0
0
50
22
8
0
20
 Yes, this is mandatory by law in my country
18
80
17
50
0
50
0
0
 Yes, it is not mandatory by law, but I always do that to be sure
7
20
67
0
0
0
0
0
Data presented as percentage
EEG electroencephalography, GCS Glasgow Coma Scale, LSM life-sustaining measures
aAdditional categorical responses, while free text responses were sufficiently similar. This does not mean that the other centers do not follow their national protocol
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?

Organ donation after circulatory arrest was forbidden in 30 (45%) centers (Fig.  1 and Table  3).
Table 3
Practices around circulatory arrest organ donation and ventricular drain removal
 
Region
Answer
Sample total
( N = 66)
Baltic States
( N = 5)
Eastern Europe
( N = 6)
Israel
( N = 2)
Northern Europe
( N = 9)
Southern Europe
( N = 12)
United Kingdom
( N = 8)
Western Europe
( N = 24)
Would you consider organ donation after circulatory arrest in a patient in whom mechanical ventilation will be withdrawn, but who is not brain dead?
 No, this is forbidden in my country
45
80
67
50
67
42
0
42
 No, although it would be permitted, I would not do this
15
20
33
0
22
33
0
4
 Yes, sometimes
20
0
0
50
11
25
13
29
 Yes, always
20
0
0
0
0
0
88
25
 
Sample total
( N = 67)
Baltic States
( N = 5)
Eastern Europe
( N = 6)
Israel
( N = 2)
Northern Europe
( N = 9)
Southern Europe
( N = 12)
United Kingdom
( N = 8)
Western Europe
( N = 25)
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 then becomes a suitable candidate for organ donation?
 No, never
33
80
33
0
0
17
88
28
 Yes, sometimes
51
20
50
100
100
50
13
48
 Yes, always
16
0
17
0
0
33
0
24
Data presented as percentage
CSF cerebrospinal fluid
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).
Table 4
Practices around the hands-off time after circulatory arrest
 
Region
Answer
Sample total
( N = 64)
Baltic States
( N = 5)
Eastern Europe
( N = 6)
Israel
( N = 2)
Northern Europe
( N = 9)
Southern Europe
( N = 12)
United Kingdom
( N = 8)
Western Europe
( N = 22)
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?
 Directly after circulatory arrest determined after a “flatliner-ECG” on the monitor
16
40
0
50
11
8
0
23
 After 1-min “flatliner-ECG” indicating circulatory arrest
5
0
0
50
0
8
0
5
 After 2-min “flatliner-ECG”
2
0
0
0
0
0
0
5
 After 5-min “flatliner-ECG”
23
20
33
0
11
17
50
23
 After 10-min “flatliner-ECG”
5
20
17
0
0
0
0
5
 After loss of pulsatile arterial curve on the invasive arterial blood pressure tracing
6
20
17
0
0
0
0
9
 After 20-min “flatliner-ECG” a
11
0
0
0
0
58
0
0
 Not done in our hospital/country a
19
0
17
0
78
0
0
18
 Other, please specify b
14
0
17
0
0
8
50
14
 
Sample total
( N = 66)
Baltic States
( N = 5)
Eastern Europe
( N = 6)
Israel
( N = 2)
Northern Europe
( N = 9)
Southern Europe
( N = 12)
United Kingdom
( N = 8)
Western Europe
( N = 24)
After withdrawal of mechanical ventilation and after circulatory arrest, after how many minutes circulatory arrest do you declare the patient dead in cases not suitable as organ donor?
 Directly after circulatory arrest determined after a “flatliner-ECG” on the monitor
32
40
17
100
11
17
13
50
 After 1-min “flatliner-ECG” indicating circulatory arrest
5
0
0
0
0
0
0
13
 After 2-min “flatliner-ECG”
0
0
0
0
0
0
0
0
 After 5-min “flatliner-ECG”
23
20
17
0
22
25
38
21
 After 10-min “flatliner-ECG”
6
20
33
0
0
 
0
0
 After loss of pulsatile arterial curve on the invasive arterial blood pressure tracing
6
20
33
0
11
0
0
0
 After 20-min “flatliner-ECG” a
9
0
0
0
0
50
0
0
 Not done in our hospital/country a
8
0
0
0
33
0
0
8
 Other, please specify c
12
0
0
0
22
0
50
8
Data presented as percentage
EEG electroencephalography
aAdditional categorical responses, while free text responses were sufficiently similar
bSpecifications filled in under “other”: “two minutes after loss of pulsatile arterial curve on the invasive arterial blood pressure tracing”; “after 3 min”; “No carotid pulses and apnoea”; “absence central pulse for 5 mins confirmed by observation for further 5 mins”; “National guidance 5 mins mechanical asystole”; “apnea test positivity”; “according to the Dutch law on organ donation”; “Protokollbogen zur Feststellung des irreversiblen Hirnfunktionsausfalls”; “at the beginning of the commission observation (6 h before)”
cSpecifications filled in under “other”: “Control 10 min later”; “After clinical death diagnosis: listen to heart sound, examination of pupils”; “At decision of the physician”; “No carotid pulses and apnoea”; “absence central pulse for 5 mins confirmed by observation for further 5 mins”; “apnea test positivity”; “according to the Dutch law on organ donation”; “Protokollbogen zur Feststellung des irreversiblen Hirnfunktionsausfalls”; “at the beginning of the commission observation (6 h before)”
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.

Discussion

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 [ 10]. 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 [ 1119]. Interestingly, however, there have been calls to abandon ancillary tests for BDD [ 20]. 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. [ 11]. 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 [ 23]. 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) [ 23]. 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 [ 24]. 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.

Conclusion

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.

Acknowledgements

Cecilia Ackerlund 1, Hadie Adams 2, Vanni Agnoletti 3, Judith Allanson 4, Krisztina Amrein 5, Norberto Andaluz 6, Nada Andelic 7, Lasse Andreassen 8, Azasevac Antun 9, Audny Anke 10, Anna Antoni 11, Hilko Ardon 12, Gérard Audibert 13, Kaspars Auslands 14, Philippe Azouvi 15, Maria Luisa Azzolini 16, Camelia Baciu 17, Rafael Badenes 18, Ronald Bartels 19, Pál Barzó 20, Ursula Bauerfeind 21, Romuald Beauvais 22, Ronny Beer 23, Francisco Javier Belda 18, Bo-Michael Bellander 24, Antonio Belli 25, Rémy Bellier 26, Habib Benali 27, Thierry Benard 26, Maurizio Berardino 28, Luigi Beretta 16, Christopher Beynon 29, Federico Bilotta 18, Harald Binder 11, Erta Biqiri 17, Morten Blaabjerg 30, Hugo den Boogert 19, Pierre Bouzat 31, Peter Bragge 32, Alexandra Brazinova 33, Vibeke Brinck 34, Joanne Brooker 35, Camilla Brorsson 36, Andras Buki 37, Monika Bullinger 38, Emiliana Calappi 39, Maria Rosa Calvi 16, Peter Cameron 40, Guillermo Carbayo Lozano 41, Marco Carbonara 39, Elsa Carise 26, K. Carpenter 42, Ana M. Castaño-León 43, Francesco Causin 44, Giorgio Chevallard 17, Arturo Chieregato 17, Giuseppe Citerio 45,46, Maryse Cnossen 47, Mark Coburn 48, Jonathan Coles 49, Lizzie Coles-Kemp 50, Johnny Collett 50, Jamie D. Cooper 51, Marta Correia 52, Amra Covic 53, Nicola Curry 54, Endre Czeiter 55, Marek Czosnyka 56, Claire Dahyot-Fizelier 26, François Damas 57, Pierre Damas 58, Helen Dawes 59, Véronique De Keyser 60, Francesco Della Corte 61, Bart Depreitere 62, Godard C. W. de Ruiter 63, Dula Dilvesi 9, Shenghao Ding 64, Diederik Dippel 65, Abhishek Dixit 66, Emma Donoghue 40, Jens Dreier 67, Guy-Loup Dulière 57, George Eapen 68, Heiko Engemann 53, Ari Ercole 66, Patrick Esser 59, Erzsébet Ezer 69, Martin Fabricius 70, Valery L. Feigin 71, Junfeng Feng 64, Kelly Foks 65, Francesca Fossi 17, Gilles Francony 31, Ulderico Freo 72, Shirin Frisvold 73, Alex Furmanov 74, Pablo Gagliardo 75, Damien Galanaud 27, Dashiell Gantner 40, Guoyi Gao 76, Karin Geleijns 42, Pradeep George 1, Alexandre Ghuysen 77, Lelde Giga 78, Benoit Giraud 26, Ben Glocker 79, Jagos Golubovic 9, Pedro A. Gomez 43, Francesca Grossi 61, Russell L. Gruen 80, Deepak Gupta 81, Juanita A. Haagsma 47, Iain Haitsma 82, Jed A. Hartings 83, Raimund Helbok 23, Eirik Helseth 84, Daniel Hertle 30, Astrid Hoedemaekers 85, Stefan Hoefer 53, Lindsay Horton 86, Jilske Huijben 47, Peter J. Hutchinson 2, Asta Kristine Håberg 87, Bram Jacobs 88, Stefan Jankowski 68, Mike Jarrett 34, Bojan Jelaca 9, Ji-yao Jiang 76, Kelly Jones 89, Konstantinos Kamnitsas 79, Mladen Karan 6, Ari Katila 90, Maija Kaukonen 91, Thomas Kerforne 26, Riku Kivisaari 91, Angelos G. Kolias 2, Bálint Kolumbán 92, Erwin Kompanje 93, Ksenija Kolundzija 94, Daniel Kondziella 70, Lars-Owe Koskinen 36, Noémi Kovács 92, Alfonso Lagares 43, Linda Lanyon 1, Steven Laureys 95, Fiona Lecky 96, Christian Ledig 79, Rolf Lefering 97, Valerie Legrand 98, Jin Lei 64, Leon Levi 99, Roger Lightfoot 100, Hester Lingsma 47, Dirk Loeckx 101, Angels Lozano 18, Andrew I. R. Maas 60, Stephen MacDonald 102, Marc Maegele 103, Marek Majdan 33, Sebastian Major 104, Alex Manara 105, Geoffrey Manley 106, Didier Martin 107, Leon Francisco Martin 101, Costanza Martino 3, Armando Maruenda 18, Hugues Maréchal 57, Alessandro Masala 3, Julia Mattern 29, Charles McFadyen 66, Catherine McMahon 108, Béla Melegh 109, David Menon 66, Tomas Menovsky 60, Cristina Morganti-Kossmann 110, Davide Mulazzi 39, Visakh Muraleedharan 1, Lynnette Murray 40, Holger Mühlan 111, Nandesh Nair 60, Ancuta Negru 112, David Nelson 1, Virginia Newcombe 66, Daan Nieboer 47, Quentin Noirhomme 95, József Nyirádi 5, Mauro Oddo 113, Annemarie Oldenbeuving 114, Matej Oresic 115, Fabrizio Ortolano 39, Aarno Palotie 116,117,118, Paul M. Parizel 119, Adriana Patruno 120, Jean-François Payen 31, Natascha Perera 22, Vincent Perlbarg 27, Paolo Persona 121, Wilco Peul 63, Anna Piippo-Karjalainen 91, Sébastien Pili Floury 122, Matti Pirinen 116, Horia Ples 112, Maria Antonia Poca 123, Suzanne Polinder 47, Inigo Pomposo 41, Jussi Posti 90, Louis Puybasset 124, Andreea Radoi 123, Arminas Ragauskas 125, Rahul Raj 91, Malinka Rambadagalla 126, Ruben Real 53, Veronika Rehorčíková 33, Jonathan Rhodes 127, Samuli Ripatti 116, Saulius Rocka 125, Cecilie Roe 128, Olav Roise 129, Gerwin Roks 130, Jonathan Rosand 131, Jeffrey Rosenfeld 110, Christina Rosenlund 132, Guy Rosenthal 74, Rolf Rossaint 48, Sandra Rossi 121, Daniel Rueckert 79, Martin Rusnák 133, Marco Sacchi 17, Barbara Sahakian 66, Juan Sahuquillo 123, Oliver Sakowitz 134,135, Francesca Sala 120, Renan Sanchez-Porras 134, Janos Sandor 136, Edgar Santos 29, Luminita Sasu 61, Davide Savo 120, Nadine Schäffer 103, Inger Schipper 137, Barbara Schlößer 21, Silke Schmidt 111, Herbert Schoechl 138, Guus Schoonman 130, Rico Frederik Schou 139, Elisabeth Schwendenwein 11, Michael Schöll 29, Özcan Sir 140, Toril Skandsen 141, Lidwien Smakman 63, Dirk Smeets 101, Peter Smielewski 56, Abayomi Sorinola 142, Emmanuel Stamatakis 66, Simon Stanworth 54, Nicole Steinbüchel 143, Ana Stevanovic 48, Robert Stevens 144, William Stewart 145, Ewout W. Steyerberg 47,146, Nino Stocchetti 147, Nina Sundström 36, Anneliese Synnot 34,148, Fabio Silvio Taccone 18, Riikka Takala 90, Viktória Tamás 142, Päivi Tanskanen 91, Mark Steven Taylor 33, Braden Te Ao 71, Olli Tenovuo 90, Ralph Telgmann 53, Guido Teodorani 149, Alice Theadom 71, Matt Thomas 105, Dick Tibboel 42, Christos Tolias 150, Jean-Flory Luaba Tshibanda 151, Tony Trapani 40, Cristina Maria Tudora 112, Peter Vajkoczy 67, Shirley Vallance 43, Egils Valeinis 78, Gregory Van der Steen 60, Mathieu van der Jagt 152, Joukje van der Naalt 88, Jeroen T. J. M. van Dijck 63, Thomas A. van Essen 63, Wim Van Hecke 101, Caroline van Heugten 59, Dominique Van Praag 60, Thijs Vande Vyvere 101, Julia Van Waesberghe 48, Audrey Vanhaudenhuyse 27,95, Alessia Vargiolu 120, Emmanuel Vega 153, Kimberley Velt 47, Jan Verheyden 101, Paul M. Vespa 154, Anne Vik 155, Rimantas Vilcinis 156, Giacinta Vizzino 17, Carmen Vleggeert-Lankamp 63, Victor Volovici 82, Daphne Voormolen 47, Peter Vulekovic 9, Zoltán Vámos 69, Derick Wade 59, Kevin K. W. Wang 157, Lei Wang 64, Lars Wessels 158, Eno Wildschut 42, Guy Williams 66, Lindsay Wilson 86, Maren K. L. Winkler 104, Stefan Wolf 158, Peter Ylén 159, Alexander Younsi 29, Menashe Zaaroor 99, Yang Zhihui 160, Agate Ziverte 78, Fabrizio Zumbo 3.
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.

Funding

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 (e.j.o.kompanje@erasmusmc.nl) 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

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://​creativecommons.​org/​licenses/​by/​4.​0/​), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://​creativecommons.​org/​publicdomain/​zero/​1.​0/​) applies to the data made available in this article, unless otherwise stated.
Zusatzmaterial
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 1/2018

Critical Care 1/2018 Zur Ausgabe

Neu im Fachgebiet AINS

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update AINS und bleiben Sie gut informiert – ganz bequem per eMail.

Bildnachweise