Critical Care (Jul 2021)

Individualized resuscitation strategy for septic shock formalized by finite mixture modeling and dynamic treatment regimen

  • Penglin Ma,
  • Jingtao Liu,
  • Feng Shen,
  • Xuelian Liao,
  • Ming Xiu,
  • Heling Zhao,
  • Mingyan Zhao,
  • Jing Xie,
  • Peng Wang,
  • Man Huang,
  • Tong Li,
  • Meili Duan,
  • Kejian Qian,
  • Yue Peng,
  • Feihu Zhou,
  • Xin Xin,
  • Xianyao Wan,
  • ZongYu Wang,
  • Shusheng Li,
  • Jianwei Han,
  • Zhenliang Li,
  • Guolei Ding,
  • Qun Deng,
  • Jicheng Zhang,
  • Yue Zhu,
  • Wenjing Ma,
  • Jingwen Wang,
  • Yan Kang,
  • Zhongheng Zhang

DOI
https://doi.org/10.1186/s13054-021-03682-7
Journal volume & issue
Vol. 25, no. 1
pp. 1 – 16

Abstract

Read online

Abstract Background Septic shock comprises a heterogeneous population, and individualized resuscitation strategy is of vital importance. The study aimed to identify subclasses of septic shock with non-supervised learning algorithms, so as to tailor resuscitation strategy for each class. Methods Patients with septic shock in 25 tertiary care teaching hospitals in China from January 2016 to December 2017 were enrolled in the study. Clinical and laboratory variables were collected on days 0, 1, 2, 3 and 7 after ICU admission. Subclasses of septic shock were identified by both finite mixture modeling and K-means clustering. Individualized fluid volume and norepinephrine dose were estimated using dynamic treatment regime (DTR) model to optimize the final mortality outcome. DTR models were validated in the eICU Collaborative Research Database (eICU-CRD) dataset. Results A total of 1437 patients with a mortality rate of 29% were included for analysis. The finite mixture modeling and K-means clustering robustly identified five classes of septic shock. Class 1 (baseline class) accounted for the majority of patients over all days; class 2 (critical class) had the highest severity of illness; class 3 (renal dysfunction) was characterized by renal dysfunction; class 4 (respiratory failure class) was characterized by respiratory failure; and class 5 (mild class) was characterized by the lowest mortality rate (21%). The optimal fluid infusion followed the resuscitation/de-resuscitation phases with initial large volume infusion and late restricted volume infusion. While class 1 transitioned to de-resuscitation phase on day 3, class 3 transitioned on day 1. Classes 1 and 3 might benefit from early use of norepinephrine, and class 2 can benefit from delayed use of norepinephrine while waiting for adequate fluid infusion. Conclusions Septic shock comprises a heterogeneous population that can be robustly classified into five phenotypes. These classes can be easily identified with routine clinical variables and can help to tailor resuscitation strategy in the context of precise medicine.

Keywords