[go: up one dir, main page]
More Web Proxy on the site http://driver.im/ Skip to main content
Log in

Sensitivity analysis–based sepsis prognosis using artificial intelligence

  • Original Article
  • Published:
Research on Biomedical Engineering Aims and scope Submit manuscript

Abstract

Sepsis is a life-threatening condition which may arise from an extreme response of the body to an infection. While worldwide figures are unknown, it is estimated that sepsis causes millions of yearly fatalities. In this context, it is important to develop tools for decision support and training of healthcare professionals. This paper proposes that artificial intelligence tools be used for prognosis of septic patients. The model used is a neural network trained and validated with cross-validation. The information used includes data regarding patient history and treatment. More importantly, this paper also presents a principled approach of using sensitivity analysis for the identification of discriminatory variables when these are of mixed types such as binary, categorical, and integer. While initial results, validated on over 5000 patients, already show both specificity and sensitivity above 80% and good model robustness against errors in most inputs, even better performance is attained through the utilization of sensitivity analysis to select the variables used as inputs. This work presents a promising tool for input selection in contexts of limited data availability, and successfully applies this technique to obtain a high-performance model for prognosis of septic patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
£29.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (United Kingdom)

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Explore related subjects

Discover the latest articles, news and stories from top researchers in related subjects.

References

  • Abadi, M, Agarwal A, Barham P, Brevdo E, Chen Z, Citro C, Corrado GS, Davis A, Dean J, Devin M, Ghemawat S, Goodfellow I, Harp A, Irving G, Isard M, Jia Y, Jozefowicz R, Kaiser L, Kudlur M, Levenberg J, Mané D., Monga R, Moore S, Murray D, Olah C, Schuster M, Shlens J, Steiner B, Sutskever I, Talwar K, Tucker P, Vanhoucke V, Vasudevan V, Viégas F., Vinyals O, Warden P, Wattenberg M, Wicke M, Yu Y, Zheng X. 2015. TensorFlow: Large-scale machine learning on heterogeneous systems Software available from tensorflow.org.

  • Bouch, DC, Thompson JP. Severity scoring systems in the critically ill. Continuing Education in Anaesthesia, Critical Care & Pain 2008;8:181–85.

    Article  Google Scholar 

  • Chicco, D, Jurman G. 2020. The advantages of the Matthews Correlation Coefficient (MCC) over F1 score and accuracy in binary classification evaluation BMC Genomics 21.

  • Dietterich, TG. Approximate statistical test for comparing supervised classification learning algorithms. Neural Comput 1998;10:1895–23.

    Article  Google Scholar 

  • Fawcett, T. An introduction to ROC analysis. Pattern Recogn Lett 2006;27:861–74.

    Article  Google Scholar 

  • Flanagan, JR, Pittet D, Li N, Thievent B, Suter P, Wenzel R. Predicting survival of patients with sepsis by use of regression and neural network models. Clinical Performance and Quality Health Care 1996;4:96–103.

    Google Scholar 

  • Fleischmann, C, Scherag A, Adhikari NK, Hartog CS, Tsaganos T, Schlattmann P, Angus DC, Reinhart K. Assessment of global incidence and mortality of hospital-treated sepsis. Current estimates and limitations. Am J Respir Crit Care Med 2016;193:259–72.

    Article  Google Scholar 

  • Gevrey, M, Dimopoulos I, Lek S. Review and comparison of methods to study the contribution of variables in artificial neural network models,. Ecol Model 2003;160:249–64.

    Article  Google Scholar 

  • Innocenti, F, Tozzi C, Donnini C, De Villa E, Conti A, Zanobetti M, Pini R. SOFA score in septic patients: incremental prognostic value over age, comorbidities, and parameters of sepsis severity. Intern Emerg Med 2018;13:405–12.

    Article  Google Scholar 

  • Jaimes, F, Farbiarz J, Alvarez D, Martínez C. Comparison between logistic regression and neural networks to predict death in patients with suspected sepsis in the emergency room. Critical Care 2005;9: R150.

    Article  Google Scholar 

  • Kam, HJ, Kim HY. Learning representations for the early detection of sepsis with deep neural networks. Comput Biol Med 2017;89:248–55.

    Article  Google Scholar 

  • Kibe, S, Adams K, Barlow G. Diagnostic and prognostic biomarkers of sepsis in critical care,. J Antimicrob Chemother 2011;66:ii33–40.

    Article  Google Scholar 

  • Kingma, D, Ba J. 2014. Adam: A method for stochastic optimization International Conference on Learning Representations.

  • Liu, X, Shen Y, Li Z, Fei A, Wang H, Ge Q, Pan S. Prognostic significance of APACHE II score and plasma supar in Chinese patients with sepsis: a prospective observational study. BMC Anesthesiol 2015; 16:46.

    Article  Google Scholar 

  • Machado, FR, Cavalcanti AB, Bozza FA, Ferreira EM, Carrara FSA, Sousa JL, Caixeta N, Salomao R, Angus DC, Azevedo LCP, et al. The epidemiology of sepsis in Brazilian intensive care units (the Sepsis PREvalence Assessment Database, SPREAD): an observational study. The Lancet Infectious Diseases 2017;17:1180–89.

    Article  Google Scholar 

  • Martin, GS. Sepsis, severe sepsis and septic shock: changes in incidence, pathogens and outcomes,. Expert Rev Anti-Infect Ther 2012;10:701–06.

    Article  Google Scholar 

  • McLymont, N, Glover GW. 2016. Scoring systems for the characterization of sepsis and associated outcomes Annals of Translational Medicine 4.

  • Morris, MD. Factorial sampling plans for preliminary computational experiments. Technometrics 1991;33:161–74.

    Article  Google Scholar 

  • Nachimuthu, SK, Haug PJ. Early detection of sepsis in the emergency department using dynamic Bayesian networks. AMIA Annual Symposium Proceedingsinfo American Medical Informatics Association 653; 2012.

  • Nguyen, HB, Van Ginkel C, Batech M, Banta J, Corbett SW. Comparison of predisposition, insult/infection, response, and organ dysfunction, acute physiology and chronic health evaluation ii, and mortality in emergency department sepsis in patients meeting criteria for early goal-directed therapy and the severe sepsis resuscitation bundle. Am J Crit Care 2012;27:362–69.

    Article  Google Scholar 

  • Okuyama, IF. 2015. Neural Networks For Sepsis Prediction 005/2015 Instituto Tecnológico de Aeronáutica, São José dos Campos, Brazil.

  • Pedregosa, F, Varoquaux G, Gramfort A, Michel V, Thirion B, Grisel O, Blondel M, Prettenhofer P, Weiss R, Dubourg V, Vanderplas J, Passos A, Cournapeau D, Brucher M, Perrot M., Édouard Duchesnay. Scikit-learn: Machine learning in Python. J Mach Learn Res 2011; 12:2825–30.

    MathSciNet  MATH  Google Scholar 

  • Pentoś, K. The methods of extracting the contribution of variables in artificial neural network models–comparison of inherent instability. Comput Electron Agric 2016;127:141–146.

    Article  Google Scholar 

  • Polikar, R, Upda L, Upda S, Honavar V. Learn++: An incremental learning algorithm for supervised neural networks. IEEE Transactions on Systems, Man, and Cybernetics, Part C: Applications and Reviews 2001;31:497–508.

    Article  Google Scholar 

  • Rathour, S, Kumar S, Hadda V, Bhalla A, Sharma N, Varma S. PIRO concept: staging of sepsis. J Postgrad Med 2015;61:235.

    Article  Google Scholar 

  • Refaeilzadeh, P, Tang L, Liu H. Cross-validation,. Encyclopedia of Database Systems Springer pp. 532–538; 2009.

  • Ruiz, GO, Castell CD. Epidemiology of severe infections in Latin American intensive care units. Revista Brasileira de Terapia Intensiva 2016;28:261–63.

    Article  Google Scholar 

  • Sadaka, F, EthmaneAbouElMaali C, Cytron MA, Fowler K, Javaux VM, O’Brien J. Predicting mortality of patients with sepsis: A comparison of APACHE II and APACHE III scoring systems,. Journal of Clinical Medicine Research 2017;9:907.

    Article  Google Scholar 

  • Schuh, CJ. Sepsis and septic shock analysis using neural networks. Fuzzy Information Processing Society, NAFIPS’07 Annual Meeting of the North American IEEE, pp. 650–654; 2007.

  • Singer, M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche J-D, Coopersmith CM, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). Jama 2016;315:801–10.

    Article  Google Scholar 

  • Taylor, RA, Pare JR, Venkatesh AK, Mowafi H, Melnick ER, Fleischman W, MHall K. Prediction of in-hospital mortality in emergency department patients with sepsis: A local big data–driven, machine learning approach,. Acad Emerg Med 2016;23:269–78.

    Article  Google Scholar 

  • Tu, JV. Advantages and disadvantages of using artificial neural networks versus logistic regression for predicting medical outcomes. J Clin Epidemiol 1996;49:1225–31.

    Article  Google Scholar 

  • Zurada, JM, Malinowski A, Cloete I. Sensitivity analysis for minimization of input data dimension for feedforward neural network. Circuits and Systems, ISCAS’94., 1994 IEEE International Symposium on 6 IEEE pp. 447–450; 1994.

  • de Alencar Saraiva, JL, Júnior M, Júnior O, Kadirkamanathan V, Silva E, Kienitz K. Sepsis patient outcome prediction using machine learning. Costa-Felix R., Machado J., Alvarenga A. (eds) XXVI Brazilian Congress on Biomedical Engineering. IFMBE Proceedings, vol 70/1. Springer, pp. 795–799; 2019.

Download references

Acknowledgments

Support from FAPESP (Brazil), as well as from from CNPq (Brazil), is gratefully acknowledged. We also thank Marcus Victor Henrique Júnior and Igor Franzoni Okuyama for support and valuable discussions in early stages of this research.

Funding

This study was funded by Fapesp (grants number 2017/11272-2 and 2017/25497-6) and by CNPq (306900/2018-1).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to José Lucas de Alencar Saraiva.

Ethics declarations

Conflict of interest

Author José Lucas de Alencar Saraiva declares that he has no conflict of interest. Author Otávio Monteiro Becker Júnior declares that he has no conflict of interest. Author Eliezer Silva declares that he has no conflict of interest. Author Visakan Kadirkamanathan declares that he has no conflict of interest. Author Karl Heinz Kienitz declares that he has no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Appendix

Appendix

This appendix presents the mean effects of the inputs which were ranked with the highest relevance, the mean effect having been defined in “Sensitivity analysis”.

Ranking

Input

Mean

  

Effect

1

Length of hospital stay

19%

2

Length of ICU stay

13%

3

Days of mechanical ventilation

4.6%

 

on ICU

 

4

Age

3.5%

5

Country

3.2%

6

AIDS

1.7%

7

Patient moved intermediate

1.7%

8

Other disabled condition

1.6%

9

Other immunosuppression

1.5%

 

condition

 

10

Utilization of albumin

1.2%

11

Days of vasopressor on ICU

1.0%

12

Apache Score

0.9%

13

Serious trauma

0.9%

14

Sedation days on ICU

0.9%

15

Mechanical ventilation days

0.9%

16

Utilization of antibiotics

0.8%

17

Location prior ICU

0.8%

18

Enteral treatment

0.8%

19

Days of vasopressor

0.8%

20

Radiotherapy

0.7%

21

Xigris (drotrecogin alfa) utilization

0.7%

22

Severe sepsis diagnosis

0.7%

 

in internation

 

23

Tachpynea

0.6%

24

Renal replacement utilization

0.6%

25

Mechanical ventilation utilization

0.6%

26

Renal failure

0.6%

27

Sedation days

0.6%

28

Other typical presentation condition

0.5%

29

Days of PRNTRL medication

0.5%

 

on ICU

 

30

Respiratory failure

0.5%

31

Fluid resuscitation

0.5%

32

Days of renal replacement

0.5%

33

Strong severe sepsis suspicion

0.5%

34

Hepatic failure

0.5%

35

Days of unfractionated mechanical

0.5%

 

heart valve

 

36

Vasopressor utilization

0.5%

37

Platelet transfusion

0.4%

38

Days of albumin on ICU

0.4%

39

Site of infection

0.4%

40

Chronic steroids

0.4%

41

Gamma globulin treatment

0.4%

42

Days of Xigris on ICU

0.4%

43

Days of enteral treatment on ICU

0.4%

44

Days of low-dose steroids

0.4%

45

Clinical status

0.4%

46

Neurological failure

0.4%

47

Tachycardia

0.3%

48

Fluid resuscitation days on ICU

0.3%

49

Renal replacement days

0.3%

50

Low-dose steroids utilization

0.3%

51

Renal replacement days on ICU

0.3%

52

Cardiovascular failure

0.2%

t53

Utilization of low molecular

0.2%

 

weight heparin

 

54

Chemotherapy

0.2%

55

Days of platelet transfusion on ICU

0.2%

56

Utilization of unfractionated heparin

0.2%

57

Liver disease

0.2%

58

High dose steroids utilization

0.2%

59

Beginning of sepsis

0.2%

60

Utilization of sedatives

0.2%

61

Days of enteral treatment

0.2%

62

Active cancer

0.2%

63

Type of ICU

0.2%

64

Chronic lung disease

0.2%

65

Heart disease

0.1%

66

Days of unfractionated heparin on ICU

0.1%

67

Severe sepsis primary diagnosis

0.1%

68

Days of fluid resuscitation on ICU

0.1%

69

Surgical drainage

0.1%

70

Utilization of PRNTRL medication

0.1%

71

Days of high dose steroids

0.1%

72

SIRS immune dysregulation

0.1%

73

Days of nitric oxide

0.1%

74

Days of low-dose steroids on ICU

0.1%

75

Utilization of antithrombin

0.1%

76

Days of Xigris (drotrecogin alfa)

0.1%

 

on ICU

 

77

Days of nitric oxide on ICU

0.1%

78

Chronic renal insufficiency

0.1%

79

Hematological failure

0.1%

80

Other surgical procedure

0.1%

81

Days of high-dose steroids on ICU

0.0%

82

Type of infection

0.0%

83

Removal of obstruction

0.0%

84

Days of antithrombin treatment

0.0%

85

Days of antithrombin treatment on ICU

0.0%

86

Gender

0.0%

87

Proven severe sepsis

0.0%

88

Days of gamma globulin treatment

0.0%

89

Utilization of nitric oxide

0.0%

90

HIV

0.0%

91

Leukocytosis

0.0%

92

Usage of unfractionated mechanical

− 0.1%

 

heart valve

 

93

Days of low molecular weight heparin

− 0.1%

 

on ICU

 

94

Days of unfractionated heparin

− 0.1%

95

Metabolic failure

− 0.1%

96

Days of albumin

− 0.1%

97

Days of unfractionated mechanical heart

− 0.1%

 

valve on ICU

 

98

Days of PRNTRL medication

− 0.1%

99

Diabetes

− 0.1%

100

Days of gamma globulin on ICU

− 0.1%

101

Days of low molecular weight heparin

− 0.2%

102

Origin of infection

− 0.2%

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

de Alencar Saraiva, J.L., Becker, O.M., Silva, E. et al. Sensitivity analysis–based sepsis prognosis using artificial intelligence. Res. Biomed. Eng. 36, 449–461 (2020). https://doi.org/10.1007/s42600-020-00083-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s42600-020-00083-7

Keywords

Navigation