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The Artificial Intelligence Clinician learns optimal treatment strategies for sepsis in intensive care

Abstract

Sepsis is the third leading cause of death worldwide and the main cause of mortality in hospitals1,2,3, but the best treatment strategy remains uncertain. In particular, evidence suggests that current practices in the administration of intravenous fluids and vasopressors are suboptimal and likely induce harm in a proportion of patients1,4,5,6. To tackle this sequential decision-making problem, we developed a reinforcement learning agent, the Artificial Intelligence (AI) Clinician, which extracted implicit knowledge from an amount of patient data that exceeds by many-fold the life-time experience of human clinicians and learned optimal treatment by analyzing a myriad of (mostly suboptimal) treatment decisions. We demonstrate that the value of the AI Clinician’s selected treatment is on average reliably higher than human clinicians. In a large validation cohort independent of the training data, mortality was lowest in patients for whom clinicians’ actual doses matched the AI decisions. Our model provides individualized and clinically interpretable treatment decisions for sepsis that could improve patient outcomes.

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Fig. 1: Data flow of the AI Clinician.
Fig. 2: Selection of the best AI policy and model calibration.
Fig. 3: Comparison of clinician and AI policies in eRI and average dose excess received per patient of both drugs in eRI with corresponding mortality.

Data availability

MIMIC-III is openly available. Access to the eRI data is restricted to the Philips eICU Research Institute. The eICU Collaborative Research Database contains a sample of over 200,000 patient stays from the eRI database that is freely available. The databases were queried in pgAdmin 4 v 1.3, and computations were implemented in Matlab R2017a (MathWorks, Inc.). Access to the computer code used in this research is available by request to the corresponding authors. To facilitate the reproduction of our results, we provide the list of anonymous patient identifiers for both databases in Supplementary Data 1 and 2.

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Acknowledgements

We are grateful to F. Doshi-Velez and O. Gottesman for their assistance with the methodology. We are grateful for support from the National Institute of Health Research (NIHR) Comprehensive Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London. We are thankful to the Laboratory of Computational Physiology at the Massachusetts Institute of Technology and the eICU Research Institute for providing the data used in this research. M.K. and this project are funded by the Engineering and Physical Sciences Research Council and an Imperial College President’s PhD Scholarship. A.C.G. is funded by an NIHR Research Professorship award (RP-2015-06-018). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

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Contributions

M.K., A.C.G. and A.A.F. conceived the overall study. M.K. and A.A.F. designed and conducted the experiments and analyzed the data. L.A.C. and O.B. contributed to the experimental design and analyses. O.B. provided key input in extracting and processing data from the eRI. All authors contributed to the interpretation of the results and M.K. drafted the manuscript, which was reviewed, revised and approved by all authors.

Corresponding authors

Correspondence to Anthony C. Gordon or A. Aldo Faisal.

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Competing interests

The authors declare competing interests: A.C.G. reports that outside of this work he has received speaker fees from Orion Corporation Orion Pharma and Amomed Pharma. He has consulted for Ferring Pharmaceuticals, Tenax Therapeutics, Baxter Healthcare, Bristol-Myers Squibb and GSK, and received grant support from Orion Corporation Orion Pharma, Tenax Therapeutics and HCA International with funds paid to his institution. L.A.C. receives funding from Philips Healthcare. O.B. is an employee of Philips Healthcare. A.A.F. has received funding from Fresenius-KABI. M.K. does not have competing financial interests.

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Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–4 and Supplementary Tables 1–3

Reporting Summary

Supplementary Data 1

MIMIC-III patient identifiers

Supplementary Data 2

eRI patient identifiers

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Komorowski, M., Celi, L.A., Badawi, O. et al. The Artificial Intelligence Clinician learns optimal treatment strategies for sepsis in intensive care. Nat Med 24, 1716–1720 (2018). https://doi.org/10.1038/s41591-018-0213-5

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