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Published in: BMC Medical Informatics and Decision Making 1/2021

Open Access 01-12-2021 | COVID-19 | Research

Reinforcement learning assisted oxygen therapy for COVID-19 patients under intensive care

Authors: Hua Zheng, Jiahao Zhu, Wei Xie, Judy Zhong

Published in: BMC Medical Informatics and Decision Making | Issue 1/2021

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Abstract

Background

Patients with severe Coronavirus disease 19 (COVID-19) typically require supplemental oxygen as an essential treatment. We developed a machine learning algorithm, based on deep Reinforcement Learning (RL), for continuous management of oxygen flow rate for critically ill patients under intensive care, which can identify the optimal personalized oxygen flow rate with strong potentials to reduce mortality rate relative to the current clinical practice.

Methods

We modeled the oxygen flow trajectory of COVID-19 patients and their health outcomes as a Markov decision process. Based on individual patient characteristics and health status, an optimal oxygen control policy is learned by using deep deterministic policy gradient (DDPG) and real-time recommends the oxygen flow rate to reduce the mortality rate. We assessed the performance of proposed methods through cross validation by using a retrospective cohort of 1372 critically ill patients with COVID-19 from New York University Langone Health ambulatory care with electronic health records from April 2020 to January 2021.

Results

The mean mortality rate under the RL algorithm is lower than the standard of care by 2.57% (95% CI: 2.08–3.06) reduction (P < 0.001) from 7.94% under the standard of care to 5.37% under our proposed algorithm. The averaged recommended oxygen flow rate is 1.28 L/min (95% CI: 1.14–1.42) lower than the rate delivered to patients. Thus, the RL algorithm could potentially lead to better intensive care treatment that can reduce the mortality rate, while saving the oxygen scarce resources. It can reduce the oxygen shortage issue and improve public health during the COVID-19 pandemic.

Conclusions

A personalized reinforcement learning oxygen flow control algorithm for COVID-19 patients under intensive care showed a substantial reduction in 7-day mortality rate as compared to the standard of care. In the overall cross validation cohort independent of the training data, mortality was lowest in patients for whom intensivists’ actual flow rate matched the RL decisions.
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Literature
1.
go back to reference Tzotzos SJ, Fischer B, Fischer H, Zeitlinger M. Incidence of ARDS and outcomes in hospitalized patients with COVID-19: a global literature survey. Crit Care. 2020;24(1):1–4.CrossRef Tzotzos SJ, Fischer B, Fischer H, Zeitlinger M. Incidence of ARDS and outcomes in hospitalized patients with COVID-19: a global literature survey. Crit Care. 2020;24(1):1–4.CrossRef
2.
go back to reference Whittle JS, Pavlov I, Sacchetti AD, Atwood C, Rosenberg MS. Respiratory support for adult patients with COVID-19. J Am Coll Emerg Physicians Open. 2020;1(2):95–101.CrossRef Whittle JS, Pavlov I, Sacchetti AD, Atwood C, Rosenberg MS. Respiratory support for adult patients with COVID-19. J Am Coll Emerg Physicians Open. 2020;1(2):95–101.CrossRef
3.
go back to reference Jamshidi MB, Lalbakhsh A, Talla J, Peroutka Z, Hadjilooei F, Lalbakhsh P, Jamshidi M, Spada L, Mirmozafari M, Dehghani M, et al. Artificial intelligence and COVID-19: deep learning approaches for diagnosis and treatment. IEEE Access. 2020;8:109581–95.CrossRef Jamshidi MB, Lalbakhsh A, Talla J, Peroutka Z, Hadjilooei F, Lalbakhsh P, Jamshidi M, Spada L, Mirmozafari M, Dehghani M, et al. Artificial intelligence and COVID-19: deep learning approaches for diagnosis and treatment. IEEE Access. 2020;8:109581–95.CrossRef
4.
go back to reference Jamshidi MB, Lalbakhsh A, Talla J, Peroutka Z, Roshani S, Matousek V, Roshani S, Mirmozafari M, Malek Z, La-Spada L. Deep Learning Techniques and COVID-19 Drug Discovery: Fundamentals, State-of-the-Art and Future Directions. Emerg Technol Dur Era COVID-19 Pandemic. 2021;348:9–31.CrossRef Jamshidi MB, Lalbakhsh A, Talla J, Peroutka Z, Roshani S, Matousek V, Roshani S, Mirmozafari M, Malek Z, La-Spada L. Deep Learning Techniques and COVID-19 Drug Discovery: Fundamentals, State-of-the-Art and Future Directions. Emerg Technol Dur Era COVID-19 Pandemic. 2021;348:9–31.CrossRef
5.
go back to reference Marini JJ, Gattinoni L. Management of COVID-19 respiratory distress. JAMA. 2020;323(22):2329–30.CrossRef Marini JJ, Gattinoni L. Management of COVID-19 respiratory distress. JAMA. 2020;323(22):2329–30.CrossRef
6.
go back to reference Attaway AH, Scheraga RG, Bhimraj A, Biehl M, Hatipoğlu U. Severe covid-19 pneumonia: pathogenesis and clinical management. BMJ. 2021;372:n436.CrossRef Attaway AH, Scheraga RG, Bhimraj A, Biehl M, Hatipoğlu U. Severe covid-19 pneumonia: pathogenesis and clinical management. BMJ. 2021;372:n436.CrossRef
7.
go back to reference Zhang B, Zhou X, Qiu Y, Song Y, Feng F, Feng J, Song Q, Jia Q, Wang J. Clinical characteristics of 82 cases of death from COVID-19. PLoS ONE. 2020;15(7):e0235458.CrossRef Zhang B, Zhou X, Qiu Y, Song Y, Feng F, Feng J, Song Q, Jia Q, Wang J. Clinical characteristics of 82 cases of death from COVID-19. PLoS ONE. 2020;15(7):e0235458.CrossRef
8.
go back to reference Lillicrap TP, Hunt JJ, Pritzel A, Heess N, Erez T, Tassa Y, Silver D, Wierstra D: Continuous control with deep reinforcement learning. arXiv:1509.02971; 2015. Lillicrap TP, Hunt JJ, Pritzel A, Heess N, Erez T, Tassa Y, Silver D, Wierstra D: Continuous control with deep reinforcement learning. arXiv:​1509.​02971; 2015.
9.
go back to reference Zheng H, Ryzhov IO, Xie W, Zhong J: Personalized multimorbidity management for patients with type 2 diabetes using reinforcement learning of electronic health records. Drugs 2021; 1–12. Zheng H, Ryzhov IO, Xie W, Zhong J: Personalized multimorbidity management for patients with type 2 diabetes using reinforcement learning of electronic health records. Drugs 2021; 1–12.
10.
go back to reference Ernst D, Stan G, Goncalves J, Wehenkel L: Clinical data based optimal STI strategies for HIV: a reinforcement learning approach. In: Proceedings of the 45th IEEE Conference on Decision and Control: 13–15 Dec. 2006; 2006. P. 667–72. Ernst D, Stan G, Goncalves J, Wehenkel L: Clinical data based optimal STI strategies for HIV: a reinforcement learning approach. In: Proceedings of the 45th IEEE Conference on Decision and Control: 13–15 Dec. 2006; 2006. P. 667–72.
11.
go back to reference Zhao Y, Zeng D, Socinski MA, Kosorok MR. Reinforcement learning strategies for clinical trials in nonsmall cell lung cancer. Biometrics. 2011;67(4):1422–33.CrossRef Zhao Y, Zeng D, Socinski MA, Kosorok MR. Reinforcement learning strategies for clinical trials in nonsmall cell lung cancer. Biometrics. 2011;67(4):1422–33.CrossRef
12.
go back to reference Escandell-Montero P, Chermisi M, Martínez-Martínez JM, Gómez-Sanchis J, Barbieri C, Soria-Olivas E, Mari F, Vila-Francés J, Stopper A, Gatti E, et al. Optimization of anemia treatment in hemodialysis patients via reinforcement learning. Artif Intell Med. 2014;62(1):47–60.CrossRef Escandell-Montero P, Chermisi M, Martínez-Martínez JM, Gómez-Sanchis J, Barbieri C, Soria-Olivas E, Mari F, Vila-Francés J, Stopper A, Gatti E, et al. Optimization of anemia treatment in hemodialysis patients via reinforcement learning. Artif Intell Med. 2014;62(1):47–60.CrossRef
13.
go back to reference Liu S, See KC, Ngiam KY, Celi LA, Sun X, Feng M. Reinforcement learning for clinical decision support in critical care: comprehensive review. J Med Internet Res. 2020;22(7):e18477.CrossRef Liu S, See KC, Ngiam KY, Celi LA, Sun X, Feng M. Reinforcement learning for clinical decision support in critical care: comprehensive review. J Med Internet Res. 2020;22(7):e18477.CrossRef
14.
go back to reference Komorowski M, Celi LA, Badawi O, Gordon AC, Faisal AA. The artificial intelligence clinician learns optimal treatment strategies for sepsis in intensive care. Nat Med. 2018;24(11):1716–20.CrossRef Komorowski M, Celi LA, Badawi O, Gordon AC, Faisal AA. The artificial intelligence clinician learns optimal treatment strategies for sepsis in intensive care. Nat Med. 2018;24(11):1716–20.CrossRef
15.
go back to reference Prasad N, Cheng L-F, Chivers C, Draugelis M, Engelhardt BE: A reinforcement learning approach to weaning of mechanical ventilation in intensive care units. 2017. Prasad N, Cheng L-F, Chivers C, Draugelis M, Engelhardt BE: A reinforcement learning approach to weaning of mechanical ventilation in intensive care units. 2017.
16.
go back to reference Sutton RS, Barto AG. Reinforcement Learning: An Introduction. 2nd ed. The MIT Press; 2018. Sutton RS, Barto AG. Reinforcement Learning: An Introduction. 2nd ed. The MIT Press; 2018.
17.
go back to reference Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: a meta-analysis. Clin Chim Acta. 2020;506:145–8.CrossRef Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: a meta-analysis. Clin Chim Acta. 2020;506:145–8.CrossRef
18.
go back to reference Moradi EV, Teimouri A, Rezaee R, Morovatdar N, Foroughian M, Layegh P, Kakhki BR, Koupaei SRA, Ghorani V. Increased age, neutrophil-to-lymphocyte ratio (NLR) and white blood cells count are associated with higher COVID-19 mortality. Am J Emerg Med. 2021;40:11–4.CrossRef Moradi EV, Teimouri A, Rezaee R, Morovatdar N, Foroughian M, Layegh P, Kakhki BR, Koupaei SRA, Ghorani V. Increased age, neutrophil-to-lymphocyte ratio (NLR) and white blood cells count are associated with higher COVID-19 mortality. Am J Emerg Med. 2021;40:11–4.CrossRef
19.
go back to reference Zhou X, Chen D, Wang L, Zhao Y, Wei L, Chen Z, Yang B. Low serum calcium: a new, important indicator of COVID-19 patients from mild/moderate to severe/critical. Biosci Rep. 2020;40(12):BSR20202690.CrossRef Zhou X, Chen D, Wang L, Zhao Y, Wei L, Chen Z, Yang B. Low serum calcium: a new, important indicator of COVID-19 patients from mild/moderate to severe/critical. Biosci Rep. 2020;40(12):BSR20202690.CrossRef
20.
go back to reference Wang C, Deng R, Gou L, Fu Z, Zhang X, Shao F, Wang G, Fu W, Xiao J, Ding X. Preliminary study to identify severe from moderate cases of COVID-19 using combined hematology parameters. Ann Transl Med. 2020;8(9):593.CrossRef Wang C, Deng R, Gou L, Fu Z, Zhang X, Shao F, Wang G, Fu W, Xiao J, Ding X. Preliminary study to identify severe from moderate cases of COVID-19 using combined hematology parameters. Ann Transl Med. 2020;8(9):593.CrossRef
21.
go back to reference Cheng Y, Luo R, Wang K, Zhang M, Wang Z, Dong L, Li J, Yao Y, Ge S, Xu G. Kidney impairment is associated with in-hospital death of COVID-19 patients. MedRxiv. 2020. Cheng Y, Luo R, Wang K, Zhang M, Wang Z, Dong L, Li J, Yao Y, Ge S, Xu G. Kidney impairment is associated with in-hospital death of COVID-19 patients. MedRxiv. 2020.
22.
go back to reference Zhu L, She Z-G, Cheng X, Qin J-J, Zhang X-J, Cai J, Lei F, Wang H, Xie J, Wang W. Association of blood glucose control and outcomes in patients with COVID-19 and pre-existing type 2 diabetes. Cell Metab. 2020;31(6):1068-1077.e1063.CrossRef Zhu L, She Z-G, Cheng X, Qin J-J, Zhang X-J, Cai J, Lei F, Wang H, Xie J, Wang W. Association of blood glucose control and outcomes in patients with COVID-19 and pre-existing type 2 diabetes. Cell Metab. 2020;31(6):1068-1077.e1063.CrossRef
23.
go back to reference Chen D, Li X, Song Q, Hu C, Su F, Dai J, Ye Y, Huang J, Zhang X. Assessment of hypokalemia and clinical characteristics in patients with coronavirus disease 2019 in Wenzhou, China. JAMA Netw Open. 2020;3(6):e2011122–e2011122.CrossRef Chen D, Li X, Song Q, Hu C, Su F, Dai J, Ye Y, Huang J, Zhang X. Assessment of hypokalemia and clinical characteristics in patients with coronavirus disease 2019 in Wenzhou, China. JAMA Netw Open. 2020;3(6):e2011122–e2011122.CrossRef
24.
go back to reference Rice TW, Wheeler AP, Bernard GR, Hayden DL, Schoenfeld DA, Ware LB, Network A. Health NIo: comparison of the SpO2/FIO2 ratio and the PaO2/FIO2 ratio in patients with acute lung injury or ARDS. Chest. 2007;132(2):410–7.CrossRef Rice TW, Wheeler AP, Bernard GR, Hayden DL, Schoenfeld DA, Ware LB, Network A. Health NIo: comparison of the SpO2/FIO2 ratio and the PaO2/FIO2 ratio in patients with acute lung injury or ARDS. Chest. 2007;132(2):410–7.CrossRef
25.
go back to reference Chen W, Janz DR, Shaver CM, Bernard GR, Bastarache JA, Ware LB. Clinical characteristics and outcomes are similar in ARDS diagnosed by oxygen saturation/Fio2 ratio compared with Pao2/Fio2 ratio. Chest. 2015;148(6):1477–83.CrossRef Chen W, Janz DR, Shaver CM, Bernard GR, Bastarache JA, Ware LB. Clinical characteristics and outcomes are similar in ARDS diagnosed by oxygen saturation/Fio2 ratio compared with Pao2/Fio2 ratio. Chest. 2015;148(6):1477–83.CrossRef
26.
go back to reference Cummings MJ, Baldwin MR, Abrams D, Jacobson SD, Meyer BJ, Balough EM, Aaron JG, Claassen J, Rabbani LE, Hastie J. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. The Lancet. 2020;395(10239):1763–70.CrossRef Cummings MJ, Baldwin MR, Abrams D, Jacobson SD, Meyer BJ, Balough EM, Aaron JG, Claassen J, Rabbani LE, Hastie J. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. The Lancet. 2020;395(10239):1763–70.CrossRef
27.
go back to reference Bradburn MJ, Clark TG, Love SB, Altman DG. Survival analysis part II: multivariate data analysis–an introduction to concepts and methods. Br J Cancer. 2003;89(3):431–6.CrossRef Bradburn MJ, Clark TG, Love SB, Altman DG. Survival analysis part II: multivariate data analysis–an introduction to concepts and methods. Br J Cancer. 2003;89(3):431–6.CrossRef
28.
go back to reference Ho C-H, Chen C-L, Yu C-C, Yang Y-H, Chen C-Y. High-flow nasal cannula ventilation therapy for obstructive sleep apnea in ischemic stroke patients requiring nasogastric tube feeding: a preliminary study. Sci Rep. 2020;10(1):1–8.CrossRef Ho C-H, Chen C-L, Yu C-C, Yang Y-H, Chen C-Y. High-flow nasal cannula ventilation therapy for obstructive sleep apnea in ischemic stroke patients requiring nasogastric tube feeding: a preliminary study. Sci Rep. 2020;10(1):1–8.CrossRef
29.
go back to reference Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the chinese center for disease control and prevention. JAMA. 2020;323(13):1239–42.CrossRef Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the chinese center for disease control and prevention. JAMA. 2020;323(13):1239–42.CrossRef
30.
go back to reference Nicholson TW, Talbot NP, Nickol A, Chadwick AJ, Lawton O. Respiratory failure and non-invasive respiratory support during the covid-19 pandemic: an update for re-deployed hospital doctors and primary care physicians. BMJ. 2020;369:m2446.CrossRef Nicholson TW, Talbot NP, Nickol A, Chadwick AJ, Lawton O. Respiratory failure and non-invasive respiratory support during the covid-19 pandemic: an update for re-deployed hospital doctors and primary care physicians. BMJ. 2020;369:m2446.CrossRef
31.
go back to reference Qin C, Zhou L, Hu Z, Yang S, Zhang S, Chen M, Yu H, Tian DS, Wang W. Clinical characteristics and outcomes of COVID-19 patients with a history of stroke in Wuhan, China. Stroke. 2020;51(7):2219–23.CrossRef Qin C, Zhou L, Hu Z, Yang S, Zhang S, Chen M, Yu H, Tian DS, Wang W. Clinical characteristics and outcomes of COVID-19 patients with a history of stroke in Wuhan, China. Stroke. 2020;51(7):2219–23.CrossRef
32.
go back to reference Elamari S, Motaib I, Zbiri S, Elaidaoui K, Chadli A, Elkettani C. Characteristics and outcomes of diabetic patients infected by the SARS-CoV-2. Pan Afr Med J. 2020;37:32.CrossRef Elamari S, Motaib I, Zbiri S, Elaidaoui K, Chadli A, Elkettani C. Characteristics and outcomes of diabetic patients infected by the SARS-CoV-2. Pan Afr Med J. 2020;37:32.CrossRef
Metadata
Title
Reinforcement learning assisted oxygen therapy for COVID-19 patients under intensive care
Authors
Hua Zheng
Jiahao Zhu
Wei Xie
Judy Zhong
Publication date
01-12-2021
Publisher
BioMed Central
Keyword
COVID-19
Published in
BMC Medical Informatics and Decision Making / Issue 1/2021
Electronic ISSN: 1472-6947
DOI
https://doi.org/10.1186/s12911-021-01712-6

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