Life-saving NMR: Septic shock

Life saver

NMR spectroscopy could be used to save the lives of children with septic shock by revealing the tell-tale profile of metabolites associated with the severest cases of this condition.

Septic shock is a potentially life-threatening medical condition that can arise as a result of severe infection and sepsis (a state of whole body inflammatory response). The causative microbe can be present throughout the body or localized in a particular tissue or organ and still cause this response. In severe cases it can lead to multiple organ dysfunction syndrome and ultimately death. The worst cases are seen in children, the elderly and those with compromised immune systems, treatment in an intensive care unit is often required. Unfortunately, for between one in four and one in two patients the condition is fatal, it is thus crucial if lives are to be saved to develop rapid and straightforward techniques with which to detect the condition at its earliest stages.

Intensive care

Beata Mickiewicz, Hans Vogel, Hector Wong and Brent Winston of the department of Biological Sciences, at the University of Calgary, in Canada, were focused on paediatric septic shock, they were hoping to determine whether a metabolomics approach using NMR might be used as a diagnostic tool in paediatric intensive care units (PICU). As such, they obtained serum samples from sixty patients with septic shock and forty patients in a PICU with systemic inflammatory response syndrome (SIRS) with no suspected infection and another forty children with no illness. The team used proton NMR to analyse and quantify the substances present in the serum samples using what they describe as a "targeted profiling methodology".

The team explains that such profiling allows them to spot patterns in the concentrations of various metabolites that should be different between the three groups of samples, those with septic shock, those inflammation but no infection and the healthy samples. In order to enhance the differences in the appropriate spectra the team used multivariate statistical analysis. The team was able to produce good predictive models from these supervised analyses and could segregate patient populations on this basis. "Some of the metabolite concentrations identified in serum samples changed markedly indicating their influence on the separation between patient groups," the team reports. They further add that, "These metabolites represent a composite biopattern of the paediatric metabolic response to septic shock and might be considered as the basis for a biomarker panel for the diagnosis of septic shock and its mortality in PICU."

Gut reaction

Separate research earlier this year focused on another aspect of septic shock. It was understood that organ failure in shock and sepsis involves the intestine, arising when the mucosal barrier of the small intestine becomes permeable. There was speculation that bacteria in the intestine and their toxins are responsible for the subsequent organ failure but experimental therapeutic interventions against these bacteria does not apparently reduced mortality. Now, research from the University of California, San Diego [Sci Translat Med, 2013, online] hints that it is the powerful digestive enzymes in the gut that may be to blame. Geert Schmid-Schönbein and colleagues published evidence to support this hypothesis and showed that inhibition of pancreatic digestive enzymes after the onset of three different shock models in laboratory rats, reduced organ damage and increased long-term survival of the animals.