Circadian rhythms are biological rhythms with a period of around 24 hours. In this study, we compared the metabolome of the liver of medaka during the day and night. To comprehensively analyze the circadian variations in the levels of metabolites in the liver, livers were isolated from Zeitgeber time (ZT)4 and ZT16, and the variations in metabolite levels were evaluated. Inosinemonophosphate (IMP) and uridinemonophosphate (UMP) were found to be increased at night, indicating that nucleotide synthesis is most active during the night. Furthermore, the levels of metabolites of the tricarboxylic acid cycle were also reduced at night. In addition, the levels of many amino acids were reduced during the night, suggesting that the amino acids had been degraded. Moreover, the citrulline/ornithine ratio, which is related to arginine consumption, was lower during the day than at night. This pattern suggests that the urea cycle is activated during the day, whereas large amounts of nitric oxide and citrulline may be produced from arginine via nitric oxide synthase during the night. The results of this metabolomic analysis may be useful in future fundamental research to provide insight into chronobiology as well as applied research on drug evaluations using medaka as a model species.

Remimazolam was first approved in 2020 as a general anesthetic for adults and still does not have pediatric labeling. Our study will be the first pilot program that administers remimazolam as an adjunct to a general endotracheal anesthetic in children. Between August 2020 and December 2022, electronic medical records were collected for all children who received remimazolam during anesthesia. The remimazolam dosing regimen was extrapolated from the adult package insert, with intravenous induction doses of 12 mg/kg/h administered until the desired effect was achieved. Subsequent infusions were given at a rate of 1–2 mg/kg/h, accompanied by intermittent boluses of 0.2 mg/kg, with all dosing adjustments made according to the anesthesiologist’s clinical discretion. A total of 418 children (mean 4.6 yrs, 68.7% ASA 1 and 2) underwent surgeries which averaged 81.2 min. A total of 75.2% of patients had greater than a 20% change (increase or decrease) in MAP (lowest or highest) from baseline, and 203 (49.3%) patients had greater than a 30% change (increase or decrease) in MAP (lowest or highest) from baseline. A total of 5% received ephedrine to treat unanticipated hemodynamic variability. Discharge criteria were met within an average of 13.8 min after arrival at the post-anesthesia care unit. Remimazolam may offer the benefits of rapid recovery following general endotracheal anesthesia. The risk of hemodynamic variability which necessitates and responds to ephedrine should be anticipated.