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Forewarning of hypotensive events using a Bayesian artificial neural network in neurocritical care

  • Rob Donald
  • Tim Howells
  • Ian Piper
  • P. Enblad
  • P. Nilsson
  • I. Chambers
  • B. Gregson
  • G. Citerio
  • K. Kiening
  • J. Neumann
  • A. Ragauskas
  • J. Sahuquillo
  • R. Sinnott
  • A. Stell
  • the BrainIT Group
Original Research

Abstract

Traumatically brain injured (TBI) patients are at risk from secondary insults. Arterial hypotension, critically low blood pressure, is one of the most dangerous secondary insults and is related to poor outcome in patients. The overall aim of this study was to get proof of the concept that advanced statistical techniques (machine learning) are methods that are able to provide early warning of impending hypotensive events before they occur during neuro-critical care. A Bayesian artificial neural network (BANN) model predicting episodes of hypotension was developed using data from 104 patients selected from the BrainIT multi-center database. Arterial hypotension events were recorded and defined using the Edinburgh University Secondary Insult Grades (EUSIG) physiological adverse event scoring system. The BANN was trained on a random selection of 50% of the available patients (n = 52) and validated on the remaining cohort. A multi-center prospective pilot study (Phase 1, n = 30) was then conducted with the system running live in the clinical environment, followed by a second validation pilot study (Phase 2, n = 49). From these prospectively collected data, a final evaluation study was done on 69 of these patients with 10 patients excluded from the Phase 2 study because of insufficient or invalid data. Each data collection phase was a prospective non-interventional observational study conducted in a live clinical setting to test the data collection systems and the model performance. No prediction information was available to the clinical teams during a patient’s stay in the ICU. The final cohort (n = 69), using a decision threshold of 0.4, and including false positive checks, gave a sensitivity of 39.3% (95% CI 32.9–46.1) and a specificity of 91.5% (95% CI 89.0–93.7). Using a decision threshold of 0.3, and false positive correction, gave a sensitivity of 46.6% (95% CI 40.1–53.2) and specificity of 85.6% (95% CI 82.3–88.8). With a decision threshold of 0.3, > 15 min warning of patient instability can be achieved. We have shown, using advanced machine learning techniques running in a live neuro-critical care environment, that it would be possible to give neurointensive teams early warning of potential hypotensive events before they emerge, allowing closer monitoring and earlier clinical assessment in an attempt to prevent the onset of hypotension. The multi-centre clinical infrastructure developed to support the clinical studies provides a solid base for further collaborative research on data quality, false positive correction and the display of early warning data in a clinical setting.

Keywords

Traumatic brain injury Neuro-intensive care Bayesian prediction Clinical study results 

Notes

Acknowledgements

Funding: European 2020 IST Programme - IST-2007-217049; Investigators and participating centers: Barcelona, Spain: Prof. Sahuquillo; Cambridge, UK: Prof. Pickard; Edinburgh, UK: Prof. Whittle; Glasgow, UK: Mr. Dunn; Gothenburg, Sweden: Dr. Rydenhag; Heidelberg, Germany: Dr. Kiening; Iasi, Romania: Dr. Iencean; Kaunas, Lithuania: Prof. Pavalkis; Leipzig, Germany: Prof. Meixensberger; Leuven, Belgium: Prof. Goffin; Mannheim, Germany: Prof. Vajkoczy; Milano, Italy: Prof. Stocchetti; Monza, Italy: Dr. Citerio; Newcastle upon Tyne, UK: Dr. Chambers; Novara, Italy: Prof. Della Corte; Southampton, UK: Dr. Hell; Uppsala, Sweden: Prof. Enblad; Torino, Italy: Dr. Mascia; Vilnius, Lithuania: Prof. Jarzemaskas; Zu¨rich, Switzerland: Prof. Stocker.

BrainIT Steering Group members: IR Chambers, Newcastle upon Tyne; G Citerio, Monza; P Enblad, Uppsala; BA Gregson, Newcastle upon Tyne; T Howells, Uppsala; K Kiening, Heidelberg; J Mattern, Heidelberg; P Nilsson, Uppsala; I Piper, Glasgow; A Ragauskas, Kaunas; J Sahuquillo, Barcelona; YH Yau, Edinburgh.

BrainIT Group – Data Contributors: Professor Per Enblad, Department of Clinical Neurosciences, Section of Neurosurgery, Uppsala University Hospital, S-75185 Uppsala, Sweden. Phone: +46 18 611 0000 Fax: +46 18 558617 Email: Per.enblad@neurokir.uu.se;Dr Karl Kiening, Department of Neurosurgery, Im Neuenheimer Feld 672, 69120 Heidelberg, Germany Phone: +49 30 4505 60724, Fax: +49 30 4505 6072, Email Karl.Kiening@med.uni-heidelberg.de; Dr Giuseppe Citerio, Dipartimento di Anestesia e Rianimazione, Azienda Ospedaliera, Ospedale San Gerardo, Via Donizetti 106, 20052 Monza (Milano), Italy. Phone: +39 029 233 3293, Fax: +39 029 233 3293, Email: g.citerio@hsgerardo.org; Professor Juan Sahuquillo, Department of Neurosurgery, Neurotraumatology Research Unit, Institut Catala de la Salut, Paseo Vall d’Hebron, 119-129, 08035 Barcelona, Spain. Phone: +34 93 489 3512, Fax: +34 93 489 3513, Email: sahuquillo@wanadoo.es; Professor Arminas Ragauskas, Telematics Science Laboratory, Kaunas University of Technology, Studentu 50-449, LT3031 Kaunas, Lithuania. Phone: +370 7 736897, Fax: +370 7 736 6869, Email: telematics@tef.ktu.lt; Dr Iain Chambers, Regional Medical Physics Department, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne, NE4 6BE, UK. Phone: +44 191 273 8811, Fax: +44 191 226 0970, Email: Iain.Chambers@nuth.northy.nhs.uk; Professor Ian Whittle, Department of Clinical Neurosciences, Western General Infirmary, Crewe Road, Edinburgh, UK. Phone: +44 131 537 2103, Fax: +44 131 537 2561, Email: irw@skul.dcn.ed.ac.uk; Professor David Wyper, Department of Clinical Physics, Institute of Neurological Sciences, Southern General Hospital, 1345 Govan Road, Glasgow G51 4TF, UK. Phone: +44 (0) 141 201 2105, Fax: +44 (0) 141 201 4127, Email: Gpca12@udcf.gla.ac.uk; Dr Michael Kiefer, Department of Neurosurgery, Universitatsklinik des Saarlandes, Kirrbergerstrasse, Gebaude 90, D-66421 Homburg-Saar, Germany. Phone: +49 7841 184469, Fax: +49 6841 164480, Email: kiefer@web.de; Professor Peter Vajkoczy, Department of Neurosurgery, University Hospital Mannheim, Theodor-Kutzer-Ufer 1-3, D68167 Mannheim, Germany. Phone: +49 621 3832360, Fax: +49 621 3832004, Email: Peter.vajkoczy@nch.ma.uni-heidelberg.de; Dr Dirk de Jong, Department of Neurosurgery, University Hospital Rotterdam, Box 2040, Dr Molewaterplein 40, 3015GD Rotterdam, The Netherlands. Phone: +31 10 4087825, Fax: +31 10 4089452, Email: dejong@neuro.fgg.eur.nl; Professor Flemming Gjerris, University Clinic of Neurosurgery, Rigshospitalet, Blegdamsvej 9, DK 2100 Copenhagen, Denmark. Phone: +45 35 452390, Fax: +45 35 456575, Email: fgjerris@rh.dk; Professor Nino Stocchetti, Servizio di Anestesia e Rianimazione, Terapia Intensiva Neuroscienze, Via Francesco Sforza 35, 20122 Milano, Italy. Phone: +39 02 550 35517, Fax: +39 02 599 02239, Email: stocchet@polic.cilea.it; Dr Luciana Mascia, Department of Anaesthesia and Intensive Care Medicine, Ospedale Molinette, Corso Bramante 88, 10126 Torino, Italy. Email: Luciana.mascia@unito.it; Professor Dr Reto Stocker, Division of Surgical Intensive Care, Universitasspital Zurich, B-HOF109, Ramistrasse 100, 8091 Zurich, Switzerland. Phone: +41 1 255 2376, Fax: +41 1 255 3172, Email: Reto.stocker@chi.usz.ch; Professor Jan Goffin, Department of Neurosurgery, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium. Phone: +32 16 344290, Fax: +32 16 344285, Email: Jan.goffin@uz.kuleuven.ac.be; Dr Bertil Rydenhag, Institute of Clinical Neuroscience, Department of Neurosurgery, Sahlgrenska University Hospital, Bla Straket 7, van 5, SE 413-45 Gothenburg, Sweden. Phone: +45 31 3421578, Fax: +45 31 416719, Email: Bertil.rydenhag@neuro.gu.se; Professor John Pickard, Academic Neurosurgical Unit, Addenbrookes Hospital, Level 4, A Block, Box 167, Hills Road, Cambridge CB2 2QQ, UK. Phone: +44 01223 336946, Fax: +44 01223 3216926, Email: jdpsecretary@medschl.cam.ac.uk; Dr Sue Hill, Department of Anaesthetics, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. Phone: +44 02380 796401, Fax: +44 02380 794843, Email: sahneuro@aol.com; Professor Garth Cruickshank, University Department of Neurosurgery, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, UK. Phone: +44 0121 697 8225, Fax: +44 0121 697 8248, Email: g.s.cruickshank@bham.ac.uk; Dr Stefan Iencean, Department of Neurosurgery, SF Treime Hospital, 2 Ateneului Street, 6600 Iasi, Romania. Email: mirceasteffan@yahoo.com; Mr Lawrence Watkins, Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK. Phone: +44 0207 837 3611, Email: l.watkins@ion.ucl.ac.uk.

Compliance with ethical standards

Conflict of interest

We declare that we have no conflicts of interest.

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Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • Rob Donald
    • 1
  • Tim Howells
    • 2
  • Ian Piper
    • 3
  • P. Enblad
    • 4
  • P. Nilsson
    • 4
  • I. Chambers
    • 5
  • B. Gregson
    • 6
  • G. Citerio
    • 7
  • K. Kiening
    • 8
  • J. Neumann
    • 8
  • A. Ragauskas
    • 9
  • J. Sahuquillo
    • 10
  • R. Sinnott
    • 11
  • A. Stell
    • 12
  • the BrainIT Group
  1. 1.Stats Research LtdDingwallScotland, UK
  2. 2.Department of NeurosurgeryUppsala University HospitalUppsalaSweden
  3. 3.Institute of Neurological SciencesQueen Elizabeth University Hospital, Clinical PhysicsGlasgowScotland, UK
  4. 4.Section of NeurosurgeryUppsala UniversityUppsalaSweden
  5. 5.Department of Medical PhysicsJames Cook University HospitalMiddlesbroughUK
  6. 6.Neurosurgical Trials GroupNewcastle UniversityNewcastle upon TyneUK
  7. 7.Hospital San Gerardo, NeurorianimazioneMonzaItaly
  8. 8.Department of NeurosurgeryRuprecht-Karls-Universitat HospitalHeidelbergGermany
  9. 9.Kaunas University of TechnologyKaunasLithuania
  10. 10.Department of NeurosurgeryVall d’Hebron University HospitalBarcelonaSpain
  11. 11.Department of Information SystemsUniversity of MelbourneParkvilleAustralia
  12. 12.Department of Clinical PhysicsUniversity of GlasgowGlasgowScotland, UK

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