Sepsis-Associated Aromatic Metabolites: Universal Markers of Bacterial Inflammation and Mortality in High-Risk Patients

Introduction. Postoperative infectious complications, especially in critically ill patients, have a high mortality risk. The early diagnosis of such complications and mortality prediction in the intensive care unit (ICU) are urgent tasks.

Objective. We aimed to identify and measure tyrosine and phenylalanine metabolites that are clinically significant for the diagnosis of infectious complications and to carry out mortality prediction in critically ill patients.

Materials and methods. A total of 298 patients were examined, including patients with acute abdominal surgical diseases (n = 58); patients after cardiac surgery (n = 79) or neurosurgery (n = 82); and other high-risk patients on the day of admission to the ICU, regardless of the main pathology (n = 79). The level of aromatic metabolites in the blood serum or cerebrospinal fluid samples of patients was determined by means of gas chromatography.

Results. In patients with acute surgical diseases of the abdominal cavity with bacterial–inflammatory complications (n=35), the median serum levels of phenyllactic (PhLA) and 4-hydroxyphenyllactic acid (p-HPhLA) were 2.5 (p<0.001) and 1.5 (p=0.048) times higher, respectively, than those of patients without an infectious process (n=23). Six hours after cardiac surgery, in patients who subsequently developed infectious complications (n=26), the median serum levels of p-HPhLA and the sum of sepsis-associated metabolites were 1.4 (p=0.010) and 1.6 (p=0.002) times higher, respectively, than those of patients who did not develop complications (n=36). In post-neurosurgical patients with signs of secondary meningitis (n=30), the median level of p-HPhLA in the cerebrospinal fluid was 2.7 times higher (p<0.001) than that of patients without signs of secondary meningitis (n=52). On admission to the ICU, non-survived patients (n=35) had at least 5-fold higher median serum levels of p-HPhLA and other sepsis-associated metabolites (p<0.001) compared with survivors (n=44).

Conclusions: The levels of sepsis-associated metabolites of tyrosine and phenylalanine can be used to predict the development of infectious complications and mortality in high-risk patients.