Development and External Validation of a Machine Learning Model for the Early Prediction of Doses of Harmful Intracranial Pressure in Patients with Severe Traumatic Brain Injury

Journal of Neurotrauma, vol. 40, pp. 514–522

Abstract

Treatment and prevention of elevated intracranial pressure (ICP) is crucial in patients with severe traumatic brain injury (TBI). Elevated ICP is associated with secondary brain injury, and both intensity and duration of an episode of intracranial hypertension, often referred to as "ICP dose," are associated with worse outcomes. Prediction of such harmful episodes of ICP dose could allow for a more proactive and preventive management of TBI, with potential implications on patients' outcomes. The goal of this study was to develop and validate a machine-learning (ML) model to predict potentially harmful ICP doses in patients with severe TBI. The prediction target was defined based on previous studies and included a broad range of doses of elevated ICP that have been associated with poor long-term neurological outcomes. The ML models were used, with minute-by-minute ICP and mean arterial blood pressure signals as inputs. Harmful ICP episodes were predicted with a 30 min forewarning. Models were developed in a multi-center dataset of 290 adult patients with severe TBI and externally validated on 264 patients from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) dataset. The external validation of the prediction model on the CENTER-TBI dataset demonstrated good discrimination and calibration (area under the curve: 0.94, accuracy: 0.89, precision: 0.87, sensitivity: 0.78, specificity: 0.94, calibration-in-the-large: 0.03, calibration slope: 0.93). The proposed prediction model provides accurate and timely predictions of harmful doses of ICP on the development and external validation dataset. A future interventional study is needed to assess whether early intervention on the basis of ICP dose predictions will result in improved outcomes.

Authors 50

1. Giorgia Carra

   Universitair Ziekenhuis Leuven · KU Leuven

   Affiliation as printed

   Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, and UZ Leuven and KU Leuven, Leuven, Belgium

2. Fabián Güiza

   Universitair Ziekenhuis Leuven · KU Leuven

   Affiliation as printed

   Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, and UZ Leuven and KU Leuven, Leuven, Belgium

3. Ian Piper
   Affiliation as printed

   Intensive Care Monitoring Research and Paediatric Critical Care, Edinburgh Royal Hospital for Children and Young People, Edinburgh, United Kingdom

4. Giuseppe Citerio

   University of Milano-Bicocca

   Affiliation as printed

   University of Milan-Bicocca, School of Medicine and Surgery and Department of Emergency and Intensive Care, Monza, Italy

5. Andrew I.R. Maas

   University of Antwerp · Antwerp University Hospital

   Affiliation as printed

   Department of Neurosurgery, Antwerp University Hospital and University of Antwerp, Edegem, Belgium

6. Bart P. Depreitere

   Universitair Ziekenhuis Leuven · KU Leuven

   Affiliation as printed

   Department of Neurosurgery, UZ Leuven and KU Leuven, Leuven, Belgium

7. Geert Meyfroidt corresponding

   Universitair Ziekenhuis Leuven · KU Leuven

   Affiliation as printed

   Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, and UZ Leuven and KU Leuven, Leuven, Belgium

8. Audny Anke

   University Hospital of North Norway · Universitair Ziekenhuis Leuven · KU Leuven

   Affiliation as printed

   Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, UZ Leuven and KU Leuven, Herestraat 49, 3000 Leuven, Belgium

   Department of Physical Medicine and Rehabilitation, University hospital Northern Norway

9. Ronny Beer

   Innsbruck Medical University · Universität Innsbruck

   Affiliation as printed

   Department of Neurology, Neurological Intensive Care Unit, Medical University of Innsbruck, Innsbruck, Austria

   Intensive Care Monitoring research and Paediatric Critical Care. Edinburgh Royal Hospital for Children and Young People 50 Little France Crescent, Edinburgh bio Quarter Edinburgh, EH16 4TJ

10. Bo‐Michael Bellander

    Karolinska University Hospital · University of Milano-Bicocca

    Affiliation as printed

    Department of Neurosurgery & Anesthesia & intensive care medicine, Karolinska University Hospital, Stockholm, Sweden

    University of Milan-Bicocca, School of Medicine and Surgery and Department of Emergency and Intensive Care, Monza, Italy

11. Erta Beqiri

    University of Antwerp · Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda · Antwerp University Hospital

    Affiliation as printed

    Department of Neurosurgery, Antwerp University Hospital and University of Antwerp, Wilrijkstraat 10, 2650 Edegem, Belgium

    NeuroIntensive Care, Niguarda Hospital, Milan, Italy

12. András Büki

    Universitair Ziekenhuis Leuven · University of Pecs · KU Leuven

    Affiliation as printed

    Department of Neurosurgery, Medical School, University of Pécs, Hungary and Neurotrauma Research Group,

    Department of Neurosurgery, UZ Leuven and KU Leuven, Herestraat 49, 3000 Leuven, Belgium

    János Szentágothai Research Centre, University of Pécs, Hungary

13. Manuel Teixeira Cabeleira

    University of Cambridge · Addenbrooke's Hospital

    Affiliation as printed

    Brain Physics Lab, Division of Neurosurgery, Dept of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK

14. Marco Carbonara

    Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

    Affiliation as printed

    Neuro ICU, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy

15. Arturo Chieregato

    University of Antwerp · Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda · Antwerp University Hospital

    Affiliation as printed

    Department of Neurosurgery, Antwerp University Hospital and University of Antwerp, Wilrijkstraat 10, 2650 Edegem, Belgium

    NeuroIntensive Care, Niguarda Hospital, Milan, Italy

16. Milano Bicocca
17. Hans Clusmann Aachen Department of Neurosurgery, Medical Faculty

    RWTH Aachen University

    Affiliation as printed

    Department of Neurosurgery, Medical Faculty RWTH Aachen University, Aachen, Germany

18. Endre Czeiter

    University of Pecs

    Affiliation as printed

    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

19. Marek Czosnyka

    University of Cambridge · Addenbrooke's Hospital

    Affiliation as printed

    Brain Physics Lab, Division of Neurosurgery, Dept of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK

20. Ari Ercole

    University of Cambridge · Addenbrooke's Hospital

    Affiliation as printed

    Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK

21. Shirin Frisvold

    University Hospital of North Norway

    Affiliation as printed

    Department of Anesthesiology and Intensive care, University Hospital Northern Norway, Tromso, Norway

22. Raimund Helbok

    Innsbruck Medical University · Universität Innsbruck

    Affiliation as printed

    Department of Neurology, Neurological Intensive Care Unit, Medical University of Innsbruck, Innsbruck, Austria

    Intensive Care Monitoring research and Paediatric Critical Care. Edinburgh Royal Hospital for Children and Young People 50 Little France Crescent, Edinburgh bio Quarter Edinburgh, EH16 4TJ

23. Stefan Jankowski

    Universitair Ziekenhuis Leuven · Sheffield Teaching Hospitals NHS Foundation Trust

    Affiliation as printed

    Intensive Care Medicine, University Hospitals Leuven, Leuven, Belgium

    Neurointensive Care, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

    CENTER-TBI High-Resolution ICU (HR ICU) Sub-Study Participants and Investigators*

24. Daniel Kondziella

    Rigshospitalet · Capital Region of Denmark

    Affiliation as printed

    Departments of Neurology, Clinical Neurophysiology and Neuroanesthesiology, Region Hovedstaden Rigshospitalet, Copenhagen, Denmark

25. Lars‐Owe Koskinen

    Umeå University

    Affiliation as printed

    Department of Clinical Neuroscience, Neurosurgery, Umeå University, Umeå, Sweden

26. Ana Kowark Aachen Department of Anaesthesiology

    Universitätsklinikum Aachen

    Affiliation as printed

    Department of Anaesthesiology, University Hospital of Aachen, Aachen, Germany

27. David Krishna Menon

    University of Cambridge · Addenbrooke's Hospital

    Affiliation as printed

    Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK

28. Kirsten Moeller

    Rigshospitalet

    Affiliation as printed

    Department Neuroanesthesiology, Region Hovedstaden Rigshospitalet, Copenhagen, Denmark

29. David Nelson

    Karolinska University Hospital · University of Milano-Bicocca

    Affiliation as printed

    Department of Neurosurgery & Anesthesia & intensive care medicine, Karolinska University Hospital, Stockholm, Sweden

    University of Milan-Bicocca, School of Medicine and Surgery and Department of Emergency and Intensive Care, Monza, Italy

30. Anna Piippo-Karjalainen

    Helsinki University Hospital

    Affiliation as printed

    Helsinki University Central Hospital, Helsinki, Finland

31. Andreea Rădoi

    Vall d'Hebron Hospital Universitari

    Affiliation as printed

    Department of Neurosurgery, Vall d'Hebron University Hospital, Barcelona, Spain

32. Arminas Ragauskas

    Universitair Ziekenhuis Leuven · Sheffield Teaching Hospitals NHS Foundation Trust

    Affiliation as printed

    Intensive Care Medicine, University Hospitals Leuven, Leuven, Belgium

    Neurointensive Care, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

    CENTER-TBI High-Resolution ICU (HR ICU) Sub-Study Participants and Investigators*

33. Rahul Raj

    Helsinki University Hospital

    Affiliation as printed

    Helsinki University Central Hospital, Helsinki, Finland

34. Jonathan R. Rhodes

    NHS Lothian

    Affiliation as printed

    Department of Anaesthesia, Critical Care & Pain Medicine NHS Lothian & University of Edinburg, Edinburgh, UK

35. Saulius Ročka

    Kaunas University of Technology · Vilnius University

    Affiliation as printed

    Department of Neurosurgery, Kaunas University of technology and Vilnius University, Vilnius, Lithuania

36. Rolf Rossaint Aachen Department of Anaesthesiology

    Universitätsklinikum Aachen

    Affiliation as printed

    Department of Anaesthesiology, University Hospital of Aachen, Aachen, Germany

37. Juan Sahuquillo

    Vall d'Hebron Hospital Universitari

    Affiliation as printed

    Department of Neurosurgery, Vall d'Hebron University Hospital, Barcelona, Spain

38. Oliver Werner Sakowitz

    University Hospital Heidelberg · Klinikum Ludwigsburg

    Affiliation as printed

    Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany

    Klinik für Neurochirurgie, Klinikum Ludwigsburg, Ludwigsburg, Germany

39. Peter S. Smielewski

    University of Cambridge · Addenbrooke's Hospital

    Affiliation as printed

    Brain Physics Lab, Division of Neurosurgery, Dept of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK

40. Nino Stocchetti

    University of Milan · Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

    Affiliation as printed

    Department of Pathophysiology and Transplantation, Milan University, and Neuroscience ICU,

    Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milano, Italy

41. Nina Sundström

    Lithuanian University of Health Sciences · University of Turku · Turku University Hospital · Humboldt-Universität zu Berlin · University of Manitoba · Charité - Universitätsmedizin Berlin · Umeå University

    Affiliation as printed

    Department of Neurosurgery, Charité -Universitätsmedizin Berlin, corporate member of Freie

    Department of Neurosurgery, Kaunas University of Health Sciences, Kaunas, Lithuania

    Department of Radiation Sciences, Biomedical Engineering, Umea University, Umea, Sweden

    Neuro-intensive Care Unit, Kaunas University of Health Sciences, Kaunas, Lithuania

    Neurologie, Neurochirurgie und Psychiatrie, Charité -Universitätsmedizin Berlin, Berlin, Germany

    Perioperative Services, Intensive Care Medicine, and Pain Management , Turku University Central Hospital and University of Turku, Turku, Finland

    Rehabilitation and Brain Trauma, Turku University Central Hospital and University of Turku, Turku, Finland

    Section of Neurosurgery, Department of Surgery, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada

    Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany

42. Riikka TakalaTurku

    Universitair Ziekenhuis Leuven · Sheffield Teaching Hospitals NHS Foundation Trust

    Affiliation as printed

    Intensive Care Medicine, University Hospitals Leuven, Leuven, Belgium

    Neurointensive Care, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

    CENTER-TBI High-Resolution ICU (HR ICU) Sub-Study Participants and Investigators*

43. Tomas Tamošuitis

    Universitair Ziekenhuis Leuven · Sheffield Teaching Hospitals NHS Foundation Trust

    Affiliation as printed

    Intensive Care Medicine, University Hospitals Leuven, Leuven, Belgium

    Neurointensive Care, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

    CENTER-TBI High-Resolution ICU (HR ICU) Sub-Study Participants and Investigators*

44. Olli S. Tenovuo

    Universitair Ziekenhuis Leuven · Sheffield Teaching Hospitals NHS Foundation Trust

    Affiliation as printed

    Intensive Care Medicine, University Hospitals Leuven, Leuven, Belgium

    Neurointensive Care, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

    CENTER-TBI High-Resolution ICU (HR ICU) Sub-Study Participants and Investigators*

45. Andreas Wilhelm Unterberg

    University Hospital Heidelberg

    Affiliation as printed

    Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany

46. Peter Vajkoczy

    Universitair Ziekenhuis Leuven · Sheffield Teaching Hospitals NHS Foundation Trust

    Affiliation as printed

    Intensive Care Medicine, University Hospitals Leuven, Leuven, Belgium

    Neurointensive Care, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

    CENTER-TBI High-Resolution ICU (HR ICU) Sub-Study Participants and Investigators*

47. Alessia Vargiolu

    Azienda Ospedaliera San Gerardo

    Affiliation as printed

    NeuroIntensive Care Unit, Department of Anesthesia & Intensive Care, ASST di Monza, Monza, Italy

48. Rimantas Vilcinis

    Universitair Ziekenhuis Leuven · Sheffield Teaching Hospitals NHS Foundation Trust

    Affiliation as printed

    Intensive Care Medicine, University Hospitals Leuven, Leuven, Belgium

    Neurointensive Care, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

    CENTER-TBI High-Resolution ICU (HR ICU) Sub-Study Participants and Investigators*

49. Alexander Younsi

    Universitair Ziekenhuis Leuven · Sheffield Teaching Hospitals NHS Foundation Trust

    Affiliation as printed

    Intensive Care Medicine, University Hospitals Leuven, Leuven, Belgium

    Neurointensive Care, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

    CENTER-TBI High-Resolution ICU (HR ICU) Sub-Study Participants and Investigators*

50. Frederick Adam Zeiler

    University of Cambridge · Addenbrooke's Hospital

    Affiliation as printed

    Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK