Sepsis can be caused by a broad range of pathogens, it is an uncontrolled inflammatory response, that could deteriorate into septic shock and death. Sepsis has a high mortality rate, five times higher than stroke and ten times the myocardial infarction. Unfortunately sepsis is little known, that is why every year the 13th of September the World Sepsis Day is celebrated. The current clinical guidelines for the sepsis treatment act only on symptoms and do not aim at resolving the root causes of organ dysfunctions or to prevent secondary comorbidities, such as cognitive impairment or cardiovascular diseases.
An animal sepsis model was described in a recent study Persistent hyperammonia and altered concentrations of urea cycle metabolites in a 5-day swine experiment of sepsis published in Scientific Reports and authored by Manuela Ferrario from Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano together with an international team of researchers form Inselspital, Bern, Switzerland and from Mario Negri Institute, Milan. Sepsis condition was induced in pigs, which were monitored with standard monitoring system and resuscitated with the standard therapy commonly used in patients (vasopressors, fluids and antibiotics). Blood and cerebrospinal (CSF)samples were collected at baseline, after the insult and every day up to 3 days after the start of resuscitation. The samples were analyzed through a mass spectrometer for the quantification of metabolites.
The study confirmed the early response to inflammation and cytokine storms with alterations in lipid and glucose metabolism. There was a rise in ammonia concentration, with altered concentrations of metabolites in the urea cycle which occurs in the liver. Some alterations in metabolites concentration observed in the blood were observed also in the CSF but later. Among these, the alteration of the tyrosine and phenylalanine balance which are precursors of dopamine, epinephrine, norepinephrine, which play an important role in the brain.
The main feature of this experiment is the long observation time after sepsis that enabled to determine magnitude and time course of a large number of metabolic changes in responses to the inflammatory insult and the subsequent standardized sepsis treatment and these results could pave the way to develop new biomarkers for early identification of organ dysfunctions, such liver failure or encephalopathy, more effective than the actual laboratory measures such as bilirubin and transaminases.
