Comparison of S-ketamine and midazolam for intravenous preoperative sedative and anxiolytic effects in preschool children: study protocol for a randomized controlled clinical trial.

BACKGROUND: Preoperative anxiety management is gaining particular attention in paediatric anaesthesia. Pharmacological and non-pharmacological resorts can be implemented to address this special issue. Despite the various approaches currently used for preoperative sedation in children, the different sedative and anti-anxiety effects between the newly marketed anaesthetic, S-ketamine, and the traditional sedative, midazolam, are still unclear. METHODS: This is a patient- and assessor-blinded randomized controlled clinical trial. Participants (n = 110) will receive S-ketamine (0.5 mg/kg) or midazolam (0.08 mg/kg) intravenously administrated at a ratio of 1:1 in the anaesthesia holding area. The primary outcome of this study is the sedative effect evaluated via the change in the modified Yale preoperative anxiety scale. It will be performed at two timepoints: in the pre-anaesthetic holding area before premedication (baseline, marked as T0) and about 5 min after premedication in the operating room without the existence of their guardians (marked as T1). Our secondary objectives include the parent separation anxiety score, postoperative agitation, caregivers' and anaesthesia care providers' satisfaction, and mask compliance. DISCUSSION: This randomized controlled trial is the first study to compare the anti-anxiety effect of intravenous S-ketamine and midazolam. We will provide a new approach for the clinical management of preoperative anxiety in preschool children posted for elective surgery. TRIAL REGISTRATION: ChiCTR2300069998. Registered on 30 March 2023.

Antioxidant and anti-inflammatory activities of N-acetyldopamine dimers from Periostracum Cicadae.

A known N-acetyldopamine dimer, (2R,3S)-2-(3',4'-dihydroxyphenyl)-3-acetylamino-7-(N-acetyl-2''-aminoethyl)-1,4-benzodioxane (1) and a new N-acetyldopamine dimer, (2R,3S)-2-(3',4'-dihydroxyphenyl)-3-acetylamino-7-(N-acetyl-2''-aminoethylene)-1,4-benzodioxane (2) were isolated from the methanolic extracts of Periostracum Cicadae. Compounds 1 and 2 inhibited the Cu2+ -mediated, 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH)-mediated, and 3-morpholinosydnonimine (SIN)-1-mediated LDL oxidation in the thiobarbituric acid-reactive substances (TBARS) assay. The antioxidant activities of 1 and 2 were tested with respect to other parameters, such as lag time of conjugated diene formation, relative electrophoretic mobility (REM), and apoB-100 fragmentation on copper-mediated LDL-oxidation. Compounds 1 and 2 also showed 1,1-diphenyl-2-picrylhydrasyl (DPPH) radical scavenging activity. Compound 2 was more efficient than compound 1 at inhibiting the reactive oxygen species (ROS) generation, nitric oxide (NO) production, and nuclear factor-kappaB (NF-kappaB) activity as well as the expression of pro-inflammatory molecules such as inducible nitric oxide synthase (iNOS), interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and cyclooxygenase (COX)-2 in LPS-induced RAW264.7 cells.