Determining the risk of dying from sepsis

Disease and treatment 2. may 2024 2 min Postdoctoral Fellow and Research Specialist Sarah McGarrity Written by Kristian Sjøgren

Researchers have discovered that specific blood metabolites can predict who will die from sepsis. A researcher says that this enhances knowledge on how people can survive sepsis.

About 50 million people develop sepsis each year and 11 million people die from it worldwide.

Although sepsis is very common and doctors are quite familiar with it, the risk of dying is still frighteningly high.

One problem is that doctors have difficulty in differentiating between people with the highest and lowest risk of dying from sepsis.

A new study shows that metabolic markers in the blood can identify high-risk patients hospitalised with sepsis.

The study also enhances knowledge on what happens in the blood of people with sepsis and how drug interventions may help.

“Improved understanding of sepsis helps to enhance our ability to identify high-risk patients and to increase survival. Sepsis dysregulates blood pressure, the immune system and other body functions. We have examined how the interaction between various metabolites and the endothelial cells – the cells on the inside of blood vessels – affects the risk of dying from sepsis,” explains a researcher involved in the study, Sarah McGarrity, Postdoctoral Fellow and Research Specialist, Biomedical Center, University of Iceland, Reykjavik, Iceland and CAG Center for Endotheliomics, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.

The research has been published in the European Journal of Medical Research.

Investigated blood proteins and metabolites

The endothelial cells play a well-known major role in sepsis because they regulate blood pressure and blood clotting.

Sarah McGarrity and colleagues investigated how the concentration of two proteins related to the endothelial cells, platelet endothelial cell adhesion molecule and soluble thrombomodulin, interact with 60 blood metabolites. Both proteins reflect the extent of damage to vascular endothelial cells.

The researchers analysed the proteins and metabolites in the blood of 50 people hospitalised with sepsis in the intensive care unit at Copenhagen University Hospital – North Zealand in Hillerød, Denmark.

The researchers linked the results of this analysis to 30-day survival.

“We then used least absolute shrinkage machine and selection operator penalised regression machine learning to identify the factors most likely to predict 30-day survival for people hospitalised with sepsis,” says Sarah McGarrity.

Proteins and metabolites identify people with a high risk of severe sepsis

The results show that several metabolic biomarkers in the blood indicate a high risk of dying within 30 days of being hospitalised with sepsis.

The levels of histidine and sphingosine-1-phosphate are good predictors of who would die within 30 days and who would survive. Carnitines and amino acids are also predictors of sepsis survival.

The analysis also revealed that histidine and sphingosine-1-phosphate were both linked with increased endothelial damage and that this was linked to increased concentrations of platelet endothelial cell adhesion molecule and soluble thrombomodulin among people with both higher levels of histidine and sphingosine-1-phosphate and a higher risk of dying from sepsis.

“Our study confirmed what other studies have previously found, but until now no one had investigated both metabolites and the link to endothelial cells simultaneously and directly in blood samples from people with sepsis,” explains Sarah McGarrity.

Identifying high risk

According to Sarah McGarrity, the results have two perspectives.

More research is needed to understand why the levels of histidine, sphingosine-1-phosphate and carnitine are associated with the risk of dying from sepsis.

This part of the research aimed to understand the mechanisms behind sepsis to find an effective treatment.

The second part focused on the diagnostic potential.

Sarah McGarrity would like researchers to investigate whether analysing blood samples for these metabolites can identify high-risk patients who should be more closely monitored when hospitalised.

“We want to both identify people at higher risk and determine who is likely to survive. In this respect, we need a large study to verify that we are using the relevant biomarkers,” says Sarah McGarrity, who concludes that other researchers should investigate this part, since her research focuses more on cell experiments to understand the microvascular endothelial response as one mechanism behind sepsis.

LASSO regression shows histidine and sphingosine 1 phosphate are linked to both sepsis mortality and endothelial damage” has been published in the European Journal of Medical Research. The research was supported by the Icelandic Centre for Research and the Novo Nordisk Foundation.

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