TILTomorrow today: dynamic factors predicting changes in intracranial pressure treatment intensity after traumatic brain injury
Abstract
AbstractPractices for controlling intracranial pressure (ICP) in traumatic brain injury (TBI) patients admitted to the intensive care unit (ICU) vary considerably between centres. To help understand the rational basis for such variance in care, this study aims to identify the patient-level predictors of changes in ICP management. We extracted all heterogeneous data (2008 pre-ICU and ICU variables) collected from a prospective cohort (n = 844, 51 ICUs) of ICP-monitored TBI patients in the Collaborative European NeuroTrauma Effectiveness Research in TBI study. We developed the TILTomorrow modelling strategy, which leverages recurrent neural networks to map a token-embedded time series representation of all variables (including missing values) to an ordinal, dynamic prediction of the following day’s five-category therapy intensity level (TIL(Basic)) score. With 20 repeats of fivefold cross-validation, we trained TILTomorrow on different variable sets and applied the TimeSHAP (temporal extension of SHapley Additive exPlanations) algorithm to estimate variable contributions towards predictions of next-day changes in TIL(Basic). Based on Somers’ Dxy, the full range of variables explained 68% (95% CI 65–72%) of the ordinal variation in next-day changes in TIL(Basic) on day one and up to 51% (95% CI 45–56%) thereafter, when changes in TIL(Basic) became less frequent. Up to 81% (95% CI 78–85%) of this explanation could be derived from non-treatment variables (i.e., markers of pathophysiology and injury severity), but the prior trajectory of ICU management significantly improved prediction of future de-escalations in ICP-targeted treatment. Whilst there was no significant difference in the predictive discriminability (i.e., area under receiver operating characteristic curve) between next-day escalations (0.80 [95% CI 0.77–0.84]) and de-escalations (0.79 [95% CI 0.76–0.82]) in TIL(Basic) after day two, we found specific predictor effects to be more robust with de-escalations. The most important predictors of day-to-day changes in ICP management included preceding treatments, age, space-occupying lesions, ICP, metabolic derangements, and neurological function. Serial protein biomarkers were also important and may serve a useful role in the clinical armamentarium for assessing therapeutic needs. Approximately half of the ordinal variation in day-to-day changes in TIL(Basic) after day two remained unexplained, underscoring the significant contribution of unmeasured factors or clinicians’ personal preferences in ICP treatment. At the same time, specific dynamic markers of pathophysiology associated strongly with changes in treatment intensity and, upon mechanistic investigation, may improve the timing and personalised targeting of future care.
Article Details
Authors (257)
Shubhayu Bhattacharyay
Florian D. van Leeuwen
Erta Beqiri
Cecilia A. I. Åkerlund
Lindsay Wilson
David W. Nelson
David K. Menon
Cecilia Åkerlund
Krisztina Amrein
Nada Andelic
Lasse Andreassen
Audny Anke
Anna Antoni
Gerard Audibert
Philippe Azouvi
Maria Luisa Azzolini
Ronald Bartels
Pál Barzó
Romuald Beauvais
Ronny Beer
Bo-Michael Bellander
Antonio Belli
Habib Benali
Maurizio Berardino
Luigi Beretta
Morten Blaabjerg
Peter Bragge
Alexandra Brazinova
Vibeke Brinck
Joanne Brooker
Camilla Brorsson
Andras Buki
Monika Bullinger
Manuel Cabeleira
Alessio Caccioppola
Emiliana Calappi
Maria Rosa Calvi
Department of Anesthesia and Critical Care, IRCCS San Raffaele Scientific Institute, Milan
Peter Cameron
Guillermo Carbayo Lozano
Marco Carbonara
Simona Cavallo
Giorgio Chevallard
Arturo Chieregato
Giuseppe Citerio
Hans Clusmann
Mark Coburn
Jonathan Coles
Jamie D. Cooper
Marta Correia
Amra Čović
Nicola Curry
Endre Czeiter
Marek Czosnyka
Claire Dahyot-Fizelier
Paul Dark
Division of Immunology, Immunity to Infection and Respiratory Medicine, University of Manchester, Manchester, United Kingdom
Helen Dawes
Véronique De Keyser
Vincent Degos
Francesco Della Corte
Hugo den Boogert
Bart Depreitere
Đula Đilvesi
Abhishek Dixit
Emma Donoghue
Jens Dreier
Guy-Loup Dulière
Ari Ercole
Patrick Esser
Erzsébet Ezer
Martin Fabricius
Valery L. Feigin
Kelly Foks
Shirin Frisvold
Alex Furmanov
Pablo Gagliardo
Damien Galanaud
Dashiell Gantner
Guoyi Gao
Pradeep George
Alexandre Ghuysen
Lelde Giga
Ben Glocker
Jagoš Golubovic
Pedro A. Gomez
Johannes Gratz
Benjamin Gravesteijn
Francesca Grossi
Russell L. Gruen
Deepak Gupta
Juanita A. Haagsma
Iain Haitsma
Raimund Helbok
Eirik Helseth
Lindsay Horton
Jilske Huijben
Peter J. Hutchinson
Bram Jacobs
Stefan Jankowski
Mike Jarrett
Ji-yao Jiang
Faye Johnson
Kelly Jones
Mladen Karan
Angelos G. Kolias
Erwin Kompanje
Daniel Kondziella
Evgenios Kornaropoulos
Lars-Owe Koskinen
Noémi Kovács
Ana Kowark
Alfonso Lagares
Linda Lanyon
Steven Laureys
Fiona Lecky
Didier Ledoux
Rolf Lefering
Valerie Legrand
Aurelie Lejeune
Leon Levi
Roger Lightfoot
Hester Lingsma
Andrew I. R. Maas
Ana M. Castaño-León
Marc Maegele
Marek Majdan
Alex Manara
Geoffrey Manley
Costanza Martino
Hugues Maréchal
Julia Mattern
Catherine McMahon
Béla Melegh
David Menon
Tomas Menovsky
Ana Mikolic
Benoît Misset
Visakh Muraleedharan
Lynnette Murray
Ancuta Negru
David Nelson
Virginia Newcombe
Daan Nieboer
József Nyirádi
Otesile Olubukola
Matej Oresic
Fabrizio Ortolano
Aarno Palotie
Paul M. Parizel
Jean-François Payen
Natascha Perera
Vincent Perlbarg
Paolo Persona
Wilco Peul
Anna Piippo-Karjalainen
Matti Pirinen
Dana Pisica
Horia Ples
Suzanne Polinder
Inigo Pomposo
Jussi P. Posti
Louis Puybasset
Andreea Radoi
Arminas Ragauskas
Rahul Raj
Malinka Rambadagalla
Isabel Retel Helmrich
Jonathan Rhodes
Sylvia Richardson
Sophie Richter
Samuli Ripatti
Saulius Rocka
Cecilie Roe
Olav Roise
Jonathan Rosand
Jeffrey V. Rosenfeld
Christina Rosenlund
Guy Rosenthal
Rolf Rossaint
Sandra Rossi
Daniel Rueckert
Martin Rusnák
Juan Sahuquillo
Oliver Sakowitz
Renan Sanchez-Porras
János Sándor
Nadine Schäfer
Silke Schmidt
Herbert Schoechl
Guus Schoonman
Rico Frederik Schou
Elisabeth Schwendenwein
Charlie Sewalt
Ranjit D. Singh
Toril Skandsen
Peter Smielewski
Department of Clinical Neurosciences, University of Cambridge
Abayomi Sorinola
Emmanuel Stamatakis
Simon Stanworth
Robert Stevens
William Stewart
Ewout W. Steyerberg
Nino Stocchetti
Nina Sundström
Riikka Takala
Viktória Tamás
Tomas Tamosuitis
Mark Steven Taylor
Aurore Thibaut
Braden Te Ao
Olli Tenovuo
Alice Theadom
Matt Thomas
Dick Tibboel
Marjolein Timmers
Christos Tolias
Tony Trapani
Cristina Maria Tudora
Andreas Unterberg
Peter Vajkoczy
Shirley Vallance
Egils Valeinis
Zoltán Vámos
Mathieu van der Jagt
Gregory Van der Steen
Joukje van der Naalt
Jeroen T. J. M. van Dijck
Inge A. M. van Erp
Thomas A. van Essen
Wim Van Hecke
Caroline van Heugten
Ernest van Veen
Thijs Vande Vyvere
Roel P. J. van Wijk
Alessia Vargiolu
Emmanuel Vega
Kimberley Velt
Jan Verheyden
Paul M. Vespa
Anne Vik
Rimantas Vilcinis
Victor Volovici
Nicole von Steinbüchel
Daphne Voormolen
Petar Vulekovic
Kevin K. W. Wang
Daniel Whitehouse
Eveline Wiegers
Guy Williams
Stefan Winzeck
Stefan Wolf
Zhihui Yang
Peter Ylén
Alexander Younsi
Frederick A. Zeiler
Veronika Zelinkova
Agate Ziverte
Tommaso Zoerle