Primary versus early secondary referral to a specialized neurotrauma center in patients with moderate/severe traumatic brain injury: a CENTER TBI study
Authors: Sewalt Charlie Aletta , Gravesteijn Benjamin Yaël , Menon David , Lingsma Hester Floor , Maas Andrew I. R. , Stocchetti Nino , Venema Esmee , Lecky Fiona E. ,   CENTER TBI Participants and Investigators, Åkerlund Cecilia , Amrein Krisztina , Andelic Nada , Andreassen Lasse , Anke Audny , Antoni Anna , Audibert Gérard , Azouvi Philippe , Azzolini Maria Luisa , Bartels Ronald , Barzó Pál , Beauvais Romuald , Beer Ronny , Bellander Bo-Michael , Belli Antonio , Benali Habib , Berardino Maurizio , Beretta Luigi , Blaabjerg Morten , Bragge Peter , Brazinova Alexandra , Brinck Vibeke , Brooker Joanne , Brorsson Camilla , Buki Andras , Bullinger Monika , Cabeleira Manuel , Caccioppola Alessio , Calappi Emiliana , Calvi Maria Rosa , Cameron Peter , Lozano Guillermo Carbayo , Carbonara Marco , Chevallard Giorgio , Chieregato Arturo , Citerio Giuseppe , Cnossen Maryse , Coburn Mark , Coles Jonathan , Cooper D. Jamie , Correia Marta , Čović Amra , Curry Nicola , Czeiter Endre , Czosnyka Marek , Dahyot-Fizelier Claire , Dawes Helen , De Keyser Véronique , Degos Vincent , Corte Francesco Della , Boogert Hugo den , Depreitere Bart , Đilvesi Đula , Dixit Abhishek , Donoghue Emma , Dreier Jens , Dulière Guy-Loup , Ercole Ari , Esser Patrick , Ezer Erzsébet , Fabricius Martin , Feigin Valery L. , Foks Kelly , Frisvold Shirin , Furmanov Alex , Gagliardo Pablo , Galanaud Damien , Gantner Dashiell , Gao Guoyi , George Pradeep , Ghuysen Alexandre , Giga Lelde , Glocker Ben , Golubovic Jagoš , Gomez Pedro A. , Gratz Johannes , Gravesteijn Benjamin , Grossi Francesca , Gruen Russell L. , Gupta Deepak , Haagsma Juanita A. , Haitsma Iain , Helbok Raimund , Helseth Eirik , Horton Lindsay , Huijben Jilske , Hutchinson Peter J. , Jacobs Bram , Jankowski Stefan , Jarrett Mike , Jiang Ji-yao , Jones Kelly , Karan Mladen , Kolias Angelos G. , Kompanje Erwin , Kondziella Daniel , Koraropoulos Evgenios , Koskinen Lars-Owe , Kovács Noémi , Lagares Alfonso , Lanyon Linda , Laureys Steven , Lecky Fiona , Lefering Rolf , Legrand Valerie , Lejeune Aurelie , Levi Leon , Lightfoot Roger , Lingsma Hester , Maas Andrew I. R. , Castaño-León Ana M. , Maegele Marc , Majdan Marek , Manara Alex , Manley Geoffrey , Martino Costanza , Maréchal Hugues , Mattern Julia , McMahon Catherine , Melegh Béla , Menon David , Menovsky Tomas , Mulazzi Davide , Muraleedharan Visakh , Murray Lynnette , Nair Nandesh , Negru Ancuta , Nelson David , Newcombe Virginia , Nieboer Daan , Noirhomme Quentin , Nyirádi József , Olubukola Otesile , Oresic Matej , Ortolano Fabrizio , Palotie Aarno , Parizel Paul M. , Payen Jean-François , Perera Natascha , Perlbarg Vincent , Persona Paolo , Peul Wilco , Piippo-Karjalainen Anna , Pirinen Matti , Ples Horia , Polinder Suzanne , Pomposo Inigo , Posti Jussi P. , Puybasset Louis , Radoi Andreea , Ragauskas Arminas , Raj Rahul , Rambadagalla Malinka , Real Ruben , Rhodes Jonathan , Richardson Sylvia , Richter Sophie , Ripatti Samuli , Rocka Saulius , Roe Cecilie , Roise Olav , Rosand Jonathan , Rosenfeld Jeffrey V. , Rosenlund Christina , Rosenthal Guy , Rossaint Rolf , Rossi Sandra , Rueckert Daniel , Rusnák Martin , Sahuquillo Juan , Sakowitz Oliver , Sanchez-Porras Renan , Sandor Janos , Schäfer Nadine , Schmidt Silke , Schoechl Herbert , Schoonman Guus , Schou Rico Frederik , Schwendenwein Elisabeth , Sewalt Charlie , Skandsen Toril , Smielewski Peter , Sorinola Abayomi , Stamatakis Emmanuel , Stanworth Simon , Kowark Ana , Stevens Robert , Stewart William , Steyerberg Ewout W. , Stocchetti Nino , Sundström Nina , Synnot Anneliese , Takala Riikka , Tamás Viktória , Tamosuitis Tomas , Taylor Mark Steven , Ao Braden Te , Tenovuo Olli , Theadom Alice , Thomas Matt , Tibboel Dick , Timmers Marjolein , Tolias Christos , Trapani Tony , Tudora Cristina Maria , Vajkoczy Peter , Vallance Shirley , Valeinis Egils , Vámos Zoltán , Van der Steen Gregory , van der Naalt Joukje , van Dijck Jeroen T. J. M. , van Essen Thomas A. , Van Hecke Wim , van Heugten Caroline , Van Praag Dominique , Vyvere Thijs Vande , Vanhaudenhuyse Audrey , van Wijk Roel P. J. , Vargiolu Alessia , Vega Emmanuel , Velt Kimberley , Verheyden Jan , Vespa Paul M. , Vik Anne , Vilcinis Rimantas , Volovici Victor , von Steinbüchel Nicole , Voormolen Daphne , Vulekovic Petar , Wang Kevin K. W. , Wiegers Eveline , Williams Guy , Wilson Lindsay , Winzeck Stefan , Wolf Stefan , Yang Zhihui , Ylén Peter , Younsi Alexander , Zeiler Frederik A. , Zelinkova Veronika , Ziverte Agate , Zoerle Tommaso 
Published: August 2021

Abstract
Background
Prehospital care for patients with traumatic brain injury (TBI) varies with some emergency medical systems recommending direct transport of patients with moderate to severe TBI to hospitals with specialist neurotrauma care (SNCs). The aim of this study is to assess variation in levels of early secondary referral within European SNCs and to compare the outcomes of directly admitted and secondarily transferred patients.

Methods
Patients with moderate and severe TBI (Glasgow Coma Scale < 13) from the prospective European CENTER-TBI study were included in this study. All participating hospitals were specialist neuroscience centers. First, adjusted between-country differences were analysed using random effects logistic regression where early secondary referral was the dependent variable, and a random intercept for country was included. Second, the adjusted effect of early secondary referral on survival to hospital discharge and functional outcome [6 months Glasgow Outcome Scale Extended (GOSE)] was estimated using logistic and ordinal mixed effects models, respectively.

Results
A total of 1347 moderate/severe TBI patients from 53 SNCs in 18 European countries were included. Of these 1347 patients, 195 (14.5%) were admitted after early secondary referral. Secondarily referred moderate/severe TBI patients presented more often with a CT abnormality: mass lesion (52% vs. 34%), midline shift (54% vs. 36%) and acute subdural hematoma (77% vs. 65%). After adjusting for case-mix, there was a large European variation in early secondary referral, with a median OR of 1.69 between countries. Early secondary referral was not associated with functional outcome (adjusted OR 1.07, 95% CI 0.78–1.69), nor with survival at discharge (1.05, 0.58–1.90).

Conclusions
Across Europe, substantial practice variation exists in the proportion of secondarily referred TBI patients at SNCs that is not explained by case mix. Within SNCs early secondary referral does not seem to impact functional outcome and survival after stabilisation in a non-specialised hospital. Future research should identify which patients with TBI truly benefit from direct transportation.