Metabolic signatures of sepsis: clinical phenotypes and mapping patient’s journey in the icu
File(s)
Author(s)
Hussain, Humma
Type
Thesis
Abstract
Sepsis is a complex syndrome which originates from a dysregulated host response to an infection causing organ dysfunction. It affects 48.9 million people annually, with 11 million deaths on yearly basis. Sepsis associated mortality in the intensive care units (ICUs) is still one of the major health concerns. The heterogeneity of this life-threatening condition makes it challenging to understand and manage. Finding better ways to monitor patients with sepsis over the course of their ICU will allow better prognostication, assessment of treatment response may aid understanding of sepsis pathology.
In this study, metabolic phenotyping, a technique with a great potential for identifying changes in metabolism was employed. Serum samples collected from patients with septic shock enrolled into two clinical trials were profiled using analytical platforms, nuclear magnetic resonance spectroscopy (NMR) and ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS). Both untargeted data and targeted panels of small molecules, lipids and lipoproteins were obtained using NMR and UHPLC-MS to investigate how the metabolic profiles of patients with septic shock differ based on outcome, organ failure and treatment at enrolment and over the course of the ICU stay. Various bioinformatic techniques including univariate, multivariate, and linear mixed effect modelling were used.
Overall, the study revealed that there are baseline differences in the small molecule and lipid profiles of survivors and non-survivors. However, the metabolic trajectories for survivors and non-survivors were similar as the metabolic concentration changes over time occur in the same direction in the two clinical groups. Patients with more severe organ failure had the highest levels of metabolites whilst the treatment analysis revealed no significant metabolite changes between treatment arms in the clinical trial population. In summary, this study further contributes to the sepsis field by providing an understanding of the dynamic nature of metabolism in patients with septic shock.
In this study, metabolic phenotyping, a technique with a great potential for identifying changes in metabolism was employed. Serum samples collected from patients with septic shock enrolled into two clinical trials were profiled using analytical platforms, nuclear magnetic resonance spectroscopy (NMR) and ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS). Both untargeted data and targeted panels of small molecules, lipids and lipoproteins were obtained using NMR and UHPLC-MS to investigate how the metabolic profiles of patients with septic shock differ based on outcome, organ failure and treatment at enrolment and over the course of the ICU stay. Various bioinformatic techniques including univariate, multivariate, and linear mixed effect modelling were used.
Overall, the study revealed that there are baseline differences in the small molecule and lipid profiles of survivors and non-survivors. However, the metabolic trajectories for survivors and non-survivors were similar as the metabolic concentration changes over time occur in the same direction in the two clinical groups. Patients with more severe organ failure had the highest levels of metabolites whilst the treatment analysis revealed no significant metabolite changes between treatment arms in the clinical trial population. In summary, this study further contributes to the sepsis field by providing an understanding of the dynamic nature of metabolism in patients with septic shock.
Version
Open Access
Date Issued
2023-03-31
Date Awarded
01/01/2024
License URL
Advisor
Antcliffe, David
Jiménez, Beatriz
Sponsor
National Institute for Health Research (Great Britain)
Publisher Department
Department of Surgery & Cancer
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)