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Published in: BMC Medical Informatics and Decision Making 1/2020

01-12-2020 | Septicemia | Research article

Validation of a machine learning algorithm for early severe sepsis prediction: a retrospective study predicting severe sepsis up to 48 h in advance using a diverse dataset from 461 US hospitals

Authors: Hoyt Burdick, Eduardo Pino, Denise Gabel-Comeau, Carol Gu, Jonathan Roberts, Sidney Le, Joseph Slote, Nicholas Saber, Emily Pellegrini, Abigail Green-Saxena, Jana Hoffman, Ritankar Das

Published in: BMC Medical Informatics and Decision Making | Issue 1/2020

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Abstract

Background

Severe sepsis and septic shock are among the leading causes of death in the United States and sepsis remains one of the most expensive conditions to diagnose and treat. Accurate early diagnosis and treatment can reduce the risk of adverse patient outcomes, but the efficacy of traditional rule-based screening methods is limited. The purpose of this study was to develop and validate a machine learning algorithm (MLA) for severe sepsis prediction up to 48 h before onset using a diverse patient dataset.

Methods

Retrospective analysis was performed on datasets composed of de-identified electronic health records collected between 2001 and 2017, including 510,497 inpatient and emergency encounters from 461 health centers collected between 2001 and 2015, and 20,647 inpatient and emergency encounters collected in 2017 from a community hospital. MLA performance was compared to commonly used disease severity scoring systems and was evaluated at 0, 4, 6, 12, 24, and 48 h prior to severe sepsis onset.

Results

270,438 patients were included in analysis. At time of onset, the MLA demonstrated an AUROC of 0.931 (95% CI 0.914, 0.948) and a diagnostic odds ratio (DOR) of 53.105 on a testing dataset, exceeding MEWS (0.725, P < .001; DOR 4.358), SOFA (0.716; P < .001; DOR 3.720), and SIRS (0.655; P < .001; DOR 3.290). For prediction 48 h prior to onset, the MLA achieved an AUROC of 0.827 (95% CI 0.806, 0.848) on a testing dataset. On an external validation dataset, the MLA achieved an AUROC of 0.948 (95% CI 0.942, 0.954) at the time of onset, and 0.752 at 48 h prior to onset.

Conclusions

The MLA accurately predicts severe sepsis onset up to 48 h in advance using only readily available vital signs extracted from the existing patient electronic health records. Relevant implications for clinical practice include improved patient outcomes from early severe sepsis detection and treatment.
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Literature
3.
go back to reference Torio CM, Celeste M, and Andrews RM. National inpatient hospital costs: the most expensive conditions by payer, 2011. (2013). Torio CM, Celeste M, and Andrews RM. National inpatient hospital costs: the most expensive conditions by payer, 2011. (2013).
4.
go back to reference Damiani E, Donati A, Serafini G, et al. Effect of performance improvement on compliance with sepsis bundles and mortality: a systematic review and meta-analysis of observational studies. PLoS ONE. 2015;10(5):1–24. Damiani E, Donati A, Serafini G, et al. Effect of performance improvement on compliance with sepsis bundles and mortality: a systematic review and meta-analysis of observational studies. PLoS ONE. 2015;10(5):1–24.
5.
go back to reference Moore L, Moore F. Early diagnosis and evidence-based care of surgical sepsis. J Intensive Care Med. 2013;28(2):107–17. CrossRefPubMed Moore L, Moore F. Early diagnosis and evidence-based care of surgical sepsis. J Intensive Care Med. 2013;28(2):107–17. CrossRefPubMed
6.
go back to reference Kenzaka T, Okayama M, Kuroki S, et al. Importance of vital signs to the early diagnosis and severity of sepsis: association between vital signs and sequential organ failure assessment score in patients with sepsis. Intern Med. 2012;51(8):871–6. CrossRefPubMed Kenzaka T, Okayama M, Kuroki S, et al. Importance of vital signs to the early diagnosis and severity of sepsis: association between vital signs and sequential organ failure assessment score in patients with sepsis. Intern Med. 2012;51(8):871–6. CrossRefPubMed
7.
go back to reference Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29(7):1303–10. CrossRefPubMed Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29(7):1303–10. CrossRefPubMed
8.
go back to reference Moore JX, Akinyemiju T, Bartolucci A, Wang HE, Waterbor J, Griffin R. A prospective study of cancer survivors and risk of sepsis within the REGARDS cohort. Cancer Epidemiol. 2018;55:30–8. CrossRefPubMedPubMedCentral Moore JX, Akinyemiju T, Bartolucci A, Wang HE, Waterbor J, Griffin R. A prospective study of cancer survivors and risk of sepsis within the REGARDS cohort. Cancer Epidemiol. 2018;55:30–8. CrossRefPubMedPubMedCentral
9.
go back to reference Çıldır E, Bulut M, Akalın H, Kocabaş E, Ocakoğlu G, Aydın ŞA. Evaluation of the modified MEDS, MEWS score and Charlson comorbidity index in patients with community acquired sepsis in the emergency department. Intern Emerg Med. 2013;8(3):255–60. CrossRefPubMed Çıldır E, Bulut M, Akalın H, Kocabaş E, Ocakoğlu G, Aydın ŞA. Evaluation of the modified MEDS, MEWS score and Charlson comorbidity index in patients with community acquired sepsis in the emergency department. Intern Emerg Med. 2013;8(3):255–60. CrossRefPubMed
10.
go back to reference Rothman M, Levy M, Dellinger RP, Jones SL, Fogerty RL, Voelker KG, Gross B, Marchetti A, Beals J. Sepsis as 2 problems: identifying sepsis at admission and predicting onset in the hospital using an electronic medical record-based acuity score. J Crit Care. 2017;38:237–44. CrossRefPubMed Rothman M, Levy M, Dellinger RP, Jones SL, Fogerty RL, Voelker KG, Gross B, Marchetti A, Beals J. Sepsis as 2 problems: identifying sepsis at admission and predicting onset in the hospital using an electronic medical record-based acuity score. J Crit Care. 2017;38:237–44. CrossRefPubMed
11.
go back to reference Levy MM, Fink MP, Marshall JC, et al. 2001 sccm/esicm/accp/ats/sis international sepsis definitions conference. Crit Care Med. 2003;31(4):1250–6. CrossRefPubMed Levy MM, Fink MP, Marshall JC, et al. 2001 sccm/esicm/accp/ats/sis international sepsis definitions conference. Crit Care Med. 2003;31(4):1250–6. CrossRefPubMed
12.
go back to reference Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 2016;315(8):801–10. CrossRefPubMedPubMedCentral Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 2016;315(8):801–10. CrossRefPubMedPubMedCentral
13.
go back to reference Hankar-Hari M, Phillips GS, Levy ML, et al. Developing a new definition and assessing new clinical criteria for septic shock: for the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):775–87. CrossRef Hankar-Hari M, Phillips GS, Levy ML, et al. Developing a new definition and assessing new clinical criteria for septic shock: for the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):775–87. CrossRef
14.
go back to reference Vincent JL, Moreno R, Takala J, Willatts S, De MA, Bruining H, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22(7):707–10. CrossRefPubMed Vincent JL, Moreno R, Takala J, Willatts S, De MA, Bruining H, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22(7):707–10. CrossRefPubMed
15.
go back to reference Subbe C, Slater A, Menon D, Gemmell L. Validation of physiological scoring systems in the accident and emergency department. Emerg Med J. 2006;23(11):841–5 (PMID:17057134). CrossRefPubMedPubMedCentral Subbe C, Slater A, Menon D, Gemmell L. Validation of physiological scoring systems in the accident and emergency department. Emerg Med J. 2006;23(11):841–5 (PMID:17057134). CrossRefPubMedPubMedCentral
16.
go back to reference Usman OA, Usman AA, Ward MA. Comparison of SIRS, qSOFA, and NEWS for the early identification of sepsis in the Emergency Department. Am J Emerg Med. 2018;37:1490–7. CrossRefPubMed Usman OA, Usman AA, Ward MA. Comparison of SIRS, qSOFA, and NEWS for the early identification of sepsis in the Emergency Department. Am J Emerg Med. 2018;37:1490–7. CrossRefPubMed
17.
go back to reference Johnson AW, Aboab J, Rafa JD, Pollard TJ, Deliberato RO, Celi LA, Stone DJ. A comparative analysis of sepsis identification methods in an electronic database. SCCM. 2018;46(4):494–9. Johnson AW, Aboab J, Rafa JD, Pollard TJ, Deliberato RO, Celi LA, Stone DJ. A comparative analysis of sepsis identification methods in an electronic database. SCCM. 2018;46(4):494–9.
18.
go back to reference Bhattacharjee P, Edelson DP, Churpek MM. Identifying patients with sepsis on the hospital wards. Chest. 2017;151(4):898–907. CrossRefPubMed Bhattacharjee P, Edelson DP, Churpek MM. Identifying patients with sepsis on the hospital wards. Chest. 2017;151(4):898–907. CrossRefPubMed
19.
go back to reference van der Woude SW, van Doormaal FF, Hutten BA, Nellen FJ, Holleman F. Classifying patients in the emergency department using SIRS, qSOFA, or MEWS. Neth J Med. 2018;76(4):158–66. PubMed van der Woude SW, van Doormaal FF, Hutten BA, Nellen FJ, Holleman F. Classifying patients in the emergency department using SIRS, qSOFA, or MEWS. Neth J Med. 2018;76(4):158–66. PubMed
21.
go back to reference Narayanan N, Gross AK, Pintens M, Fee C, MacDougall C. Effect of an electronic medical record alert for severe sepsis among. Am J Emerg Med. 2016;34(2):185–8. CrossRefPubMed Narayanan N, Gross AK, Pintens M, Fee C, MacDougall C. Effect of an electronic medical record alert for severe sepsis among. Am J Emerg Med. 2016;34(2):185–8. CrossRefPubMed
22.
go back to reference Amland RC, Hahn-Cover KE. Clinical decision support for early recognition of sepsis. Am J Med Qual. 2016;31(2):103–10. CrossRefPubMed Amland RC, Hahn-Cover KE. Clinical decision support for early recognition of sepsis. Am J Med Qual. 2016;31(2):103–10. CrossRefPubMed
24.
go back to reference Horng S, Sontag DA, Halpern Y, Jernite Y, Shapiro NI, Nathanson LA. Creating an automated trigger for sepsis clinical decision support at emergency department triage using machine learning. PLoS ONE. 2017;12(4):e0174708. CrossRefPubMedPubMedCentral Horng S, Sontag DA, Halpern Y, Jernite Y, Shapiro NI, Nathanson LA. Creating an automated trigger for sepsis clinical decision support at emergency department triage using machine learning. PLoS ONE. 2017;12(4):e0174708. CrossRefPubMedPubMedCentral
25.
go back to reference Nachimuthu SK, Haug PJ. Early detection of sepsis in the emergency department using Dynamic Bayesian Networks. AMIA Annu Symp Proc. 2012;2012:653–62. PubMedPubMedCentral Nachimuthu SK, Haug PJ. Early detection of sepsis in the emergency department using Dynamic Bayesian Networks. AMIA Annu Symp Proc. 2012;2012:653–62. PubMedPubMedCentral
26.
go back to reference Henry KE, Hager DN, Pronovost PJ, Saria S. A targeted real-time early warning score (TREWScore) for septic shock. Sci Transl Med. 2015;7(299):299ra122-299ra122. CrossRef Henry KE, Hager DN, Pronovost PJ, Saria S. A targeted real-time early warning score (TREWScore) for septic shock. Sci Transl Med. 2015;7(299):299ra122-299ra122. CrossRef
27.
go back to reference Nemati S, Holder A, Razmi F, Stanley MD, Clifford GD, Buchman TG. An interpretable machine learning model for accurate prediction of sepsis in the ICU. Crit Care Med. 2018;46(4):547–53. CrossRefPubMedPubMedCentral Nemati S, Holder A, Razmi F, Stanley MD, Clifford GD, Buchman TG. An interpretable machine learning model for accurate prediction of sepsis in the ICU. Crit Care Med. 2018;46(4):547–53. CrossRefPubMedPubMedCentral
28.
go back to reference Stanculescu I, Williams CKI, Freer Y. Autoregressive hidden Markov models for the early detection of neonatal sepsis. IEEE J Biomed Health Inform. 2014;18(5):1560–70. CrossRefPubMed Stanculescu I, Williams CKI, Freer Y. Autoregressive hidden Markov models for the early detection of neonatal sepsis. IEEE J Biomed Health Inform. 2014;18(5):1560–70. CrossRefPubMed
29.
go back to reference Stanculescu I, Williams CK, Freer Y, eds. A hierarchical switching linear dynamical system applied to the detection of sepsis in neonatal condition monitoring. UAI; 2014. Stanculescu I, Williams CK, Freer Y, eds. A hierarchical switching linear dynamical system applied to the detection of sepsis in neonatal condition monitoring. UAI; 2014.
31.
go back to reference Lauritsen SM, Kalør ME, Kongsgaard EL, Lauritsen KM, Jørgensen MJ, Lange J, Thiesson B. Early detection of sepsis utilizing deep learning on electronic health record event sequences. Artif Intell Med. 2020;19:101820. CrossRef Lauritsen SM, Kalør ME, Kongsgaard EL, Lauritsen KM, Jørgensen MJ, Lange J, Thiesson B. Early detection of sepsis utilizing deep learning on electronic health record event sequences. Artif Intell Med. 2020;19:101820. CrossRef
32.
go back to reference Shashikumar SP, Josef C, Sharma A, Nemati S. DeepAISE—an end-to-end development and deployment of a recurrent neural survival model for early prediction of sepsis; 2019. arXiv:1908.04759. Shashikumar SP, Josef C, Sharma A, Nemati S. DeepAISE—an end-to-end development and deployment of a recurrent neural survival model for early prediction of sepsis; 2019. arXiv:​1908.​04759.
34.
go back to reference Bates DW, Auerbach A, Schulam P, Wright A, Saria S. Reporting and implementing interventions involving machine learning and artificial intelligence. Ann Intern Med. 2020;172(11_Supplement):S137–44. CrossRefPubMed Bates DW, Auerbach A, Schulam P, Wright A, Saria S. Reporting and implementing interventions involving machine learning and artificial intelligence. Ann Intern Med. 2020;172(11_Supplement):S137–44. CrossRefPubMed
36.
go back to reference Islam MM, Nasrin T, Walther BA, Wu CC, Yang HC, Li YC. Prediction of sepsis patients using machine learning approach: a meta-analysis. Comput Methods Programs Biomed. 2019;1(170):1–9. CrossRef Islam MM, Nasrin T, Walther BA, Wu CC, Yang HC, Li YC. Prediction of sepsis patients using machine learning approach: a meta-analysis. Comput Methods Programs Biomed. 2019;1(170):1–9. CrossRef
38.
go back to reference Shimabukuro DW, Barton CW, Feldman MD, et al. Effect of a machine learning-based severe sepsis prediction algorithm on patient survival and hospital length of stay: a randomised clinical trial. BMJ Open Respir Res. 2017;4(1):e000234. CrossRefPubMedPubMedCentral Shimabukuro DW, Barton CW, Feldman MD, et al. Effect of a machine learning-based severe sepsis prediction algorithm on patient survival and hospital length of stay: a randomised clinical trial. BMJ Open Respir Res. 2017;4(1):e000234. CrossRefPubMedPubMedCentral
40.
go back to reference Burdick H, Pino E, Gabel-Comeau D, et al. Evaluating a sepsis prediction machine learning algorithm using minimal electronic health record data in the emergency department and intensive care unit. bioRxiv. 2017. https://doi.org/10.1101/224014. Burdick H, Pino E, Gabel-Comeau D, et al. Evaluating a sepsis prediction machine learning algorithm using minimal electronic health record data in the emergency department and intensive care unit. bioRxiv. 2017. https://​doi.​org/​10.​1101/​224014.
41.
go back to reference Calvert JS, Price DA, Chettipally UK, et al. A computational approach to early sepsis detection. Comput Biol Med. 2016a;74:69–73 (PMID: 27208704). CrossRefPubMed Calvert JS, Price DA, Chettipally UK, et al. A computational approach to early sepsis detection. Comput Biol Med. 2016a;74:69–73 (PMID: 27208704). CrossRefPubMed
42.
go back to reference Desautels T, Calvert J, Hoffman J, et al. Prediction of sepsis in the intensive care unit with minimal electronic health record data: a machine learning approach. JMIR Med Inform. 2016;4(3):28 (PMID: 27694098). CrossRef Desautels T, Calvert J, Hoffman J, et al. Prediction of sepsis in the intensive care unit with minimal electronic health record data: a machine learning approach. JMIR Med Inform. 2016;4(3):28 (PMID: 27694098). CrossRef
43.
go back to reference Calvert JS, Price DA, Chettipally UK, et al. High-performance detection and early prediction of septic shock for alcohol-use disorder patients. Ann Med Surg. 2016b;8:50–5. CrossRef Calvert JS, Price DA, Chettipally UK, et al. High-performance detection and early prediction of septic shock for alcohol-use disorder patients. Ann Med Surg. 2016b;8:50–5. CrossRef
44.
go back to reference Shao J, Zhong B. Last observation carry-forward and last observation analysis. Stat Med. 2003;22(15):2429–41 (PMID: 12872300). CrossRefPubMed Shao J, Zhong B. Last observation carry-forward and last observation analysis. Stat Med. 2003;22(15):2429–41 (PMID: 12872300). CrossRefPubMed
45.
go back to reference Ali MW, Talukder E. Analysis of longitudinal binary data with missing data due to dropouts. J Biopharm Stat. 2005;15(6):993–1007 (PMID: 16279357). CrossRefPubMed Ali MW, Talukder E. Analysis of longitudinal binary data with missing data due to dropouts. J Biopharm Stat. 2005;15(6):993–1007 (PMID: 16279357). CrossRefPubMed
46.
go back to reference Mohamadlou H, Lynn-Palevsky A, Barton C, Chettipally U, Shieh L, Calvert J, Saber NR, Das R. Prediction of acute kidney injury with a machine learning algorithm using electronic health record data. Can J Kidney Health Dis. 2018;8(5):2054358118776326 (PMID: 30094049). Mohamadlou H, Lynn-Palevsky A, Barton C, Chettipally U, Shieh L, Calvert J, Saber NR, Das R. Prediction of acute kidney injury with a machine learning algorithm using electronic health record data. Can J Kidney Health Dis. 2018;8(5):2054358118776326 (PMID: 30094049).
47.
go back to reference Rhee C, Dantes R, Epstein L, et al. Incidence and trends of sepsis in US hospitals using clinical vs claims data, 2009–2014. JAMA. 2017;318(13):1241–9. CrossRefPubMedPubMedCentral Rhee C, Dantes R, Epstein L, et al. Incidence and trends of sepsis in US hospitals using clinical vs claims data, 2009–2014. JAMA. 2017;318(13):1241–9. CrossRefPubMedPubMedCentral
48.
go back to reference Chen T, Guestrin C. XGBoost: A scalable tree boosting system. In: Paper presented at the 22nd ACM SIGKDD international conference on knowledge discovery and data mining; 2016. Chen T, Guestrin C. XGBoost: A scalable tree boosting system. In: Paper presented at the 22nd ACM SIGKDD international conference on knowledge discovery and data mining; 2016.
50.
go back to reference Sorrentino R. Large standard deviations and logarithmic-normality. Landes Biosci J. 2010;4(4):327–32. Sorrentino R. Large standard deviations and logarithmic-normality. Landes Biosci J. 2010;4(4):327–32.
51.
go back to reference Monitor CM, Fatigue A. An integrative review. Biomed Instrum Technol. 2012;46:268–77. CrossRef Monitor CM, Fatigue A. An integrative review. Biomed Instrum Technol. 2012;46:268–77. CrossRef
52.
go back to reference Iskander KN, Osuchowski MF, Stearns-Kurosawa DJ, et al. Sepsis: multiple abnormalities, heterogeneous responses, and evolving understanding. Physiol Rev. 2013;93(3):1247–88. CrossRefPubMedPubMedCentral Iskander KN, Osuchowski MF, Stearns-Kurosawa DJ, et al. Sepsis: multiple abnormalities, heterogeneous responses, and evolving understanding. Physiol Rev. 2013;93(3):1247–88. CrossRefPubMedPubMedCentral
55.
go back to reference Sudduth CL, Overton EC, Lyu PF, et al. Filtering authentic sepsis arising in the ICU using administrative codes coupled to a SIRS screening protocol. J Crit Care. 2017;1(39):220–4. CrossRef Sudduth CL, Overton EC, Lyu PF, et al. Filtering authentic sepsis arising in the ICU using administrative codes coupled to a SIRS screening protocol. J Crit Care. 2017;1(39):220–4. CrossRef
56.
go back to reference Iwashyna TJ, Odden A, Rohde J, et al. Identifying patients with severe sepsis using administrative claims: patient-level validation of the angus implementation of the international consensus conference definition of severe sepsis. Med Care. 2014;52:e39. CrossRefPubMedPubMedCentral Iwashyna TJ, Odden A, Rohde J, et al. Identifying patients with severe sepsis using administrative claims: patient-level validation of the angus implementation of the international consensus conference definition of severe sepsis. Med Care. 2014;52:e39. CrossRefPubMedPubMedCentral
57.
go back to reference Brause R, Hamker F, Paetz J, et al. Septic shock diagnosis by neural networks and rule based systems. In: Schmitt M, Teodorescu HN, Jain A, et al., editors. Computational intelligence techniques in medical diagnosis and prognosis. New York: Springer; 2002. p. 323–56. Brause R, Hamker F, Paetz J, et al. Septic shock diagnosis by neural networks and rule based systems. In: Schmitt M, Teodorescu HN, Jain A, et al., editors. Computational intelligence techniques in medical diagnosis and prognosis. New York: Springer; 2002. p. 323–56.
58.
go back to reference Shashikumar SP, Li Q, Clifford GD, et al. Multiscale network representation of physiological time series for early prediction of sepsis. Physiol Meas. 2017;38(12):2235. CrossRefPubMedPubMedCentral Shashikumar SP, Li Q, Clifford GD, et al. Multiscale network representation of physiological time series for early prediction of sepsis. Physiol Meas. 2017;38(12):2235. CrossRefPubMedPubMedCentral
Metadata
Title
Validation of a machine learning algorithm for early severe sepsis prediction: a retrospective study predicting severe sepsis up to 48 h in advance using a diverse dataset from 461 US hospitals
Authors
Hoyt Burdick
Eduardo Pino
Denise Gabel-Comeau
Carol Gu
Jonathan Roberts
Sidney Le
Joseph Slote
Nicholas Saber
Emily Pellegrini
Abigail Green-Saxena
Jana Hoffman
Ritankar Das
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Medical Informatics and Decision Making / Issue 1/2020
Electronic ISSN: 1472-6947
DOI
https://doi.org/10.1186/s12911-020-01284-x

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