In metabolomics a “snapshot” of the current metabolic state of an organism, a metabolic profile, is obtained from biofluid samples. Despite emerging metabolomics studies in the field of clinical anaesthesia and intensive care, the effects of routinely used anaesthetics/sedatives on the circulating human metabolome have remained largely unexplored. Recently, metabolic profiling upon hospital admission in out-of-hospital cardiac arrest (OHCA) enabled stratification of patient risk groups with respect to mortality. Identification of previously unrecognized metabolic routes associated with patient outcome after OHCA might contribute to the discovery of novel biomarkers.

This study examined two separate study populations. First, a randomised controlled phase IV clinical drug trial in which 160 healthy male subjects received equipotent doses (EC50 for verbal command) of dexmedetomidine, propofol, S-ketamine, sevoflurane, or placebo. Nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography tandem mass spectrometry targeted metabolic profiling was conducted at baseline, at the end of anaesthetic/sedative administration (at 60 min), and at 70 min after anaesthetic/sedative cessation. Second, a randomised 2-group phase II clinical drug trial of 110 OHCA patients receiving targeted temperature management at 33 °C alone or in combination with inhaled xenon. The NMR metabolic profile was analysed upon hospital admission and at 24 and 72 h.

In healthy male subject statistically significant changes vs. placebo were observed in 21.5%, 35.4%, 3.6% and 1.5% of the analysed 195 metabolites in dexmedetomidine, propofol, S-ketamine and sevoflurane groups, respectively. Dexmedetomidine caused e.g. a wide-ranging decrease in bile acids and oxylipins, S-ketamine decreased branched chain amino acids (BCAA), and propofol altered the lipid profile while 9,10- and 12,13-dihydroxyoctadecenoic acid were markedly increased. In contrast, sevoflurane demonstrated relative inertness. In OHCA patients at 24 h, increased levels of lactate and decreased amounts of BCAAs leucine and valine associated with 6-month mortality. At 72 h, increases in the levels of lactate and alanine, and a decreased small HDL cholesteryl ester content (S-HDL-CE) associated with mortality.

In conclusion, exposure to routinely used anaesthetics/sedatives triggered unique alterations in the metabolic profiles. Furthermore, in OHCA patients at 24 and 72 h the concentrations of lactate, alanine, leucine, valine, and S-HDL-CE associated with 6-month mortality. Xenon did not alter the NMR metabolic profile.