A1 Refereed original research article in a scientific journal
TILTomorrow today: dynamic factors predicting changes in intracranial pressure treatment intensity after traumatic brain injury
Authors: Bhattacharyay, Shubhayu; van Leeuwen, Florian D.; Beqiri, Erta; Åkerlund, Cecilia A. I.; Wilson, Lindsay; Steyerberg, Ewout W.; Nelson, David W.; Maas, Andrew I. R.; Menon, David K.; Ercole, Ari; the CENTER-TBI investigators and participants
Publisher: Springer Science and Business Media LLC
Publication year: 2025
Journal: Scientific Reports
Article number: 95
Volume: 15
Issue: 1
eISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-024-83862-x
Publication's open availability at the time of reporting: Open Access
Publication channel's open availability : Open Access publication channel
Web address : https://doi.org/10.1038/s41598-024-83862-x
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/515515719
Self-archived copy's licence: CC BY
Self-archived copy's version: Publisher`s PDF
Practices 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. © The Author(s) 2024.
Author keywordsData mining; Intensive care unit; Intracranial pressure; Machine learning; Therapy intensity level; Traumatic brain injury
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Funding information in the publication:
This research was supported by the National Institute for Health Research (NIHR) Brain Injury MedTech Co-operative. CENTER-TBI was supported by the European Union 7th Framework programme (EC grant 602150). Additional funding was obtained from the Hannelore Kohl Stiftung (Germany), from OneMind (USA), from Integra LifeSciences Corporation (USA), and from NeuroTrauma Sciences (USA). CENTER-TBI also acknowledges interactions and support from the International Initiative for TBI Research (InTBIR) investigators. S.B. is funded by a Gates Cambridge Scholarship and a Paul & Daisy Soros Fellowship. E.B. is funded by the Medical Research Council (MR N013433-1) and by a Gates Cambridge Scholarship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We are grateful to the patients and families of our study for making our efforts to improve TBI care possible. S.B. would like to thank Kathleen Mitchell-Fox (Princeton University) for offering comments on the manuscript.