Abstract

BackgroundSeptic 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.MethodsPatients 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.ResultsA 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.ConclusionsSeptic 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.

Highlights

  • Septic shock is a leading cause of mortality and morbidity in the intensive care unit (ICU)

  • The results showed that greater values of heart rate (OR for each 10 beats/min increase: 4.38; 95% Confidence interval (CI) 2.85–6.73; p < 0.001), class 3 (OR: 1.93; 95% CI 1.49–2.50; p < 0.001) and class 5 were associated with increased risk of fluid overloading (Fig. 4C)

  • Relative hazard could be varying over time and our model reported the average value for a given dose

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Summary

Introduction

Septic shock is a leading cause of mortality and morbidity in the intensive care unit (ICU). The Surviving Sepsis Campaign guidelines recommend several goals (i.e., urine output, mean blood pressure and ­ScvO2) to guide resuscitation [6, 7], the specific strategy must be individualized because the responses to a given intervention can vary greatly among septic shock patients. Since sepsis and/or septic shock is a heterogeneous clinical syndrome, many clinical trials targeting sepsis population usually result in neutral findings [2, 10, 11]. In these trials, some patients may benefit from a certain intervention, but others will be harmed by the intervention, resulting in a neutral effect in the overall population. 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

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