title: Predictive value of lactate in unselected critically ill patients: an analysis using fractional polynomials.
abstract: OBJECTIVE
  Hyperlactatemia has long been associated with poor clinical outcome in varieties of intensive care unit (ICU) patients. However, the impact of temporal changes in lactate has not been well established and there are some shortcomings in model building in previous studies. The present study aims to investigate the association of initial lactate and normalization time with hazard by using fractional polynomial Cox proportional hazard model.
  
  
  METHODS
  A large clinical database named Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC-II) was employed for analysis. Demographics, comorbidities, laboratory findings were extracted and were compared between survivors and non-survivors by using univariable analysis. Cox proportional hazard model was built by purposeful selection of covariate with initial lactate (L0) and normalization time (T) remaining in the model. Best fit model was selected by using deviance difference test and comparisons between fractional polynomial regression models of different degrees were performed by using closed test procedure.
  
  
  RESULTS
  A total of 6,291 ICU patients were identified to be eligible for the present study, including 1,675 non-survivors and 4,616 survivors (mortality rate: 26.6%). Patients with lactate normalization had significantly reduced hazard rate as compared to those without normalization (log-rank test: P<0.05). The best powers of L0 in the model were -2 and -1 with the deviance of 19,944.51, and the best powers of T were 0.5 and 3 with the deviance of 7,965.63. The adjusted hazard ratio for the terms L0(-2) and L0(-1) were 1.13 (95% CI: 1.09-1.18) and 0.43 (95% CI: 0.34-0.54); and the adjusted hazard ratio for the terms T(0.5) and T(3) were 7.42 (95% CI: 2.85-19.36) and 3.06×10(-6) (95% CI: 3.01×10(-11)-0.31).
  
  
  CONCLUSIONS
  Initial lactate on ICU admission is associated with death hazard and the relationship follows a fractional polynomial pattern with the power of -2 and -1. Delayed normalization of lactate is predictive of high risk of death when it is measured within 150 hours after ICU admission.
authors.affiliation: Department of Critical Care Medicine, Jinhua Municipal Central Hospital, Jinhua Hospital of Zhejiang University, Jinhua 321000, China.
authors.forename: Zhongheng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Critical Care Medicine, Jinhua Municipal Central Hospital, Jinhua Hospital of Zhejiang University, Jinhua 321000, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Critical Care Medicine, Jinhua Municipal Central Hospital, Jinhua Hospital of Zhejiang University, Jinhua 321000, China.
authors.forename: Hongying
authors.initials: H
authors.lastname: Ni
authors.affiliation: Department of Critical Care Medicine, Jinhua Municipal Central Hospital, Jinhua Hospital of Zhejiang University, Jinhua 321000, China.
authors.forename: Haozhe
authors.initials: H
authors.lastname: Fan
keywords: Fractional polynomial; critically ill; intensive care unit (ICU); lactate normalization; mortality
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