Abstract
Background: Intensive Care Resources are heavily utilized during the COVID-19 pandemic. However, risk stratification and prediction of SARS-CoV-2 patient clinical outcomes upon ICU admission remain inadequate. This study aimed to develop a machine learning model, based on retrospective & prospective clinical data, to stratify patient risk and predict ICU survival and outcomes. Methods: A Germany-wide electronic registry was established to pseudonymously collect admission, therapeutic and discharge information of SARS-CoV-2 ICU patients retrospectively and prospectively. Machine learning approaches were evaluated for the accuracy and interpretability of predictions. The Explainable Boosting Machine approach was selected as the most suitable method. Individual, non-linear shape functions for predictive parameters and parameter interactions are reported. Results: 1039 patients were included in the Explainable Boosting Machine model, 596 patients retrospectively collected, and 443 patients prospectively collected. The model for prediction of general ICU outcome was shown to be more reliable to predict “survival”. Age, inflammatory and thrombotic activity, and severity of ARDS at ICU admission were shown to be predictive of ICU survival. Patients’ age, pulmonary dysfunction and transfer from an external institution were predictors for ECMO therapy. The interaction of patient age with D-dimer levels on admission and creatinine levels with SOFA score without GCS were predictors for renal replacement therapy. Conclusions: Using Explainable Boosting Machine analysis, we confirmed and weighed previously reported and identified novel predictors for outcome in critically ill COVID-19 patients. Using this strategy, predictive modeling of COVID-19 ICU patient outcomes can be performed overcoming the limitations of linear regression models. Trial registration “ClinicalTrials” (clinicaltrials.gov) under NCT04455451.
| Originalsprache | Englisch |
|---|---|
| Aufsatznummer | 295 |
| Zeitschrift | Critical Care |
| Jahrgang | 25 |
| Ausgabenummer | 1 |
| ISSN | 1364-8535 |
| DOIs | |
| Publikationsstatus | Veröffentlicht - 12.2021 |
Fördermittel
Open Access funding enabled and organized by Projekt DEAL. This work was funded by a grant from the Deutsche Forschungsgemeinschaft DFG RO 3671/8-1 to P.R. O.K. received funding from the Bundesministerium für Bildung und Forschung (BMBF) (DIFUTURE, 01ZZ1804D). Funding of the participating centers: Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe University, Frankfurt, Germany: This work was funded by the grant Horizon 2020 Framework Programme, Call: H2020-SC1-PHE-CORONAVIRUS-2020–2-CNECT; Project: 101015930 — ENVISION to K.Z. Harry Magunia: HM received a speaker’s honorarium from CSL Behring (Germany) outside the submitted work. Simone Lederer: SL has no competing interests to report. Raphael Verbuecheln: RV has no competing interests to report. Bryant Joseph Gilot: BJG has no competing interests to report. Michael Koeppen: MK has no competing interests to report. Helene A Haeberle: HH has no competing interests to report. Valbona Mirakaj: VM has no competing interests to report. Pascal Hoffmann: PH has no competing interests to report. Gernot Marx: GM reports personal fees from Philips Health Care, personal fees from B. Braun, during the conduct of the study; and GM is co-founder of Clinomics GmbH, Germany. Johannes Bickenbach: JB reports personal fees from Biotest AG, Germany, during the conduct of the study. Boris Nohe: BN has no competing interests to report. Michael Lay: ML has no competing interests to report. Claudia Spies: CS reports no conflicts of interests within the submitted manuscript, she reports grants from outside the submitted manuscript from Drägerwerk AG & Co. KGaA, grants from Deutsche Forschungsgemeinschaft / German Research Society, grants from Deutsches Zentrum für Luft- und Raumfahrt e. V. (DLR) /German Aerospace Center, grants from Einstein Stiftung Berlin/ Einstein Foundation Berlin, grants from Gemeinsamer Bundesausschuss / Federal Joint Committee (G-BA), grants from Inneruniversitäre Forschungsförderung / Inner University Grants, grants from Projektträger im DLR / Project Management Agency, grants from Stifterverband/Non-Profit Society Promoting Science and Education, grants from WHOCC, grants from Baxter Deutschland GmbH, grants from Cytosorbents Europe GmbH, grants from Edwards Lifesciences Germany GmbH, grants from Fresenius Medical Care, grants from Grünenthal GmbH, grants from Masimo Europe Ltd., grants from Pfizer Pharma PFE GmbH, personal fees from Georg Thieme Verlag, grants from Dr. F. Köhler Chemie GmbH, grants from Sintetica GmbH, grants from Stifterverband für die deutsche Wissenschaft e.V. / Philips, grants from Stiftung Charité, grants from AGUETTANT Deutschland GmbH, grants from AbbVie Deutschland GmbH & Co. KG, grants from Amomed Pharma GmbH, grants from InTouch Health, grants from Copra System GmbH, grants from Correvio GmbH, grants from Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V., grants from Deutsche Gesellschaft für Anästhesiologie & Intensivmedizin (DGAI, grants from Stifterverband für die deutsche Wissenschaft e.V. / Metronic, grants from Philips ElectronicsNederland BV, grants from BMG, grants from BMBF, grants from BMBF, grants from Deutsche Forschungsgemeinschaft / German Research Society, outside the submitted work; In addition, Dr. Spies has a patent 10 2014 215 211.9 licensed, a patent 10 2018 114 364.8 licensed, a patent 10 2018 110 275.5 licensed, a patent 50 2015 010 534.8 licensed, a patent 50 2015 010 347.7 licensed, and a patent 10 2014 215 212.7 licensed. Andreas Edel: AE has no competing interests to report. Fridtjof Schiefenhövel: FS has no competing interests to report. Tim Rahmel: TR has no competing interests to report. Christian Putensen: CP has no competing interests to report. Timur Sellmann: TS has no competing interests to report. Thea Koch: TK has no competing interests to report. Timo Brandenburger: TBra has no competing interests to report. Detlef Kindgen-Milles: DKM has co competing interests to report. Thorsten Brenner: TBre reports grants from Deutsche Forschungsgemeinschaft (DFG), Dietmar Hopp Stiftung and Stiftung Universitätsmedizin Essen, personal fees from CSL Behring GmbH, Schöchl medical education GmbH, Boehringer Ingelheim Pharma GmbH, Biotest AG, Baxter Deutschland GmbH, Astellas Pharma GmbH, B. Braun Melsungen AG and MSD Sharp & Dohme GmbH outside the submitted work. Marc Berger: MB has no competing interests to report. Kai Zacharowski: KZ has no competing interests to report. Elisabeth Adam: EA has no competing interests to report. Matthias Posch: MP has no competing interests to report. Onnen Moerer: OM has no competing interests to report. Christian S. Scheer: CS has no competing interests to report. Daniel Sedding: DS has no competing interests to report. Markus A. Weigand: MW has no competing interests to report. Falk Fichtner: FF has no competing interests to report. Carla Nau: CN has no competing interests to report. Florian Prätsch: FP has no competing interests to report. Thomas Wiesmann: TW reports personal fees from Pajunk, Germany, personal fees from Vygon, Germany, outside the submitted work. Christian Koch: CK has no competing interests to report. Gerhard Schneider: GS has no competing interests to report. Tobias Lahmer: TL has no competing interests to report. Andreas Straub: AS reports personal fees from CSL Behring GmbH (Munich, Germany), personal fees from Schöchl Medical Education GmbH (Mattsee, Austria), personal fees from Aspen Germany GmbH (Munich, Germany), outside the submitted work. Andreas Meiser: AM reports personal fees from Sedana Medical, Danderyd, Sweden, outside the submitted work. Manfred Weiss: MW has no competing interests to report. Bettina Jungwirth: BJ has no competing interests to report. Frank Wappler: FW has no competing interests to report. Patrick Meybohm: PM has no competing interests to report. Johannes Herrmann: JH has no competing interests to report. Nisar Malek: NM has no competing interests to report. Oliver Kohlbacher: OK has no competing interests to report. Stephanie Biergans: SB has no competing interests to report. Peter Rosenberger: PR has no competing interests to report. The authors and collaborators thank the employees of the participating intensive care units for their immeasurable efforts in the care of COVID-19 patients. The authors thank Nico Pfeifer, Medical Informatics, University of T?bingen, Germany, for the numerous fruitful discussions and valuable input on the application of ML methods. The authors thank Sascha Rehm and Christian Erhardt (meDIC, University Hospital of T?bingen, Germany) for server and REDCap administration and support.
Coronavirus-Bezug
- Forschung zu SARS-CoV-2 / COVID-19