Abstract Background and Purpose: Anesthetic inhalation induction could be one of the most stressful experiences for children. While, either oral midazolam or nasal dexmedetomidine as premedication remains less than ideal. This study was to assess the efficacy and safety when those two premeds were applied together in children undergoing minor surgeries. Experimental Approach: One hundred and thirty-eight children aged 2-6 years old were randomly allocated into three equal groups based on the premedication routes: Group M with oral midazolam 0.5 mg.kg-1, Group D with intranasal dexmedetomidine 2 μg.kg-1 and Group MD with intranasal dexmedetomidine 1 μg.kg-1 plus oral midazolam 0.5 mg.kg-1, respectively. The primary outcome was the satisfactory compliance rate during inhalation induction with sevoflurane using induction compliance checklist. The secondary outcomes were the preoperative m-YPAS scores when the children arrived in the holding area, sedation level, behavior scores, parental separation anxiety scores, mask acceptance scale (MAS), the incidence of emergence agitation, recovery time and other adverse events. Key Results: Subjects in Group MD showed higher satisfactory compliance rate (n=38, P=0.0049) and satisfactory MAS (n=38, P=0.0049) on anesthesia inhalation induction. Compared to the Group M and D, Subjects in Group MD had significantly shorter onset time to achieve the satisfactory sedation level (P<0.001) and higher sedation score at 20 and 30min after drug administration (P<0.001). Conclusion and Implications: We conclude that combined intranasal dexmedetomidine 1μg.kg-1 and oral midazolam 0.5 mg.kg-1 significantly improved the compliance during inhalation induction with sevoflurane, and had quicker onset to reach satisfactory sedation level in children.

Background and Purpose: Surgery remains the first-line treatment of ovarian cancer. However, perioperative risk factors including the choice of anaesthetics may influence its recurrence after surgery. In the current study, it was hypothesised that inhalational anaesthetic sevoflurane and intravenous anaesthetic propofol might affect cancer cellular metabolism and signalling, which might interfere the malignancy of ovarian cancer cells. Experimental Approach: Cultured ovarian cancer cells were exposed to 2.5% sevoflurane or administered with 4 μg/mL propofol for 2 hours followed by 24 hours recovery. Their cell viability, proliferation, migration and invasion were assessed using cell counting kit-8, Ki-67 staining, wound healing and Transwell assay. Cellular signalling biomarkers were measured using immunofluorescent staining and/or Western blot. Cultured media were collected for 1H-NMR spectroscopy-based metabolomics analysis. Key Results: The cell viability, proliferation, migration, and invasion of ovarian cancer cells were enhanced by sevoflurane but suppressed by propofol. Sevoflurane increased the GLUT1, MPC1, GLUD1, p-Erk1/2, and HIF-1α expressions but decreased the PEDF expression. In contrast to the sevoflurane treatment, the “mirror changes” of these cellular markers were observed with propofol. Sevoflurane increased levels of isopropanol but decreased glucose and glutamine levels in the media, but the opposite changes of those metabolites were found after propofol treatment. Conclusion and Implications: These data indicated that unlike propofol, sevoflurane enhanced ovarian cancer cell metabolism and activated PEDF/Erk/HIF-1α cellular signalling pathway, suggesting that sevoflurane might have pro-tumour property but propofol might afford an anti-tumour property. The translational value of this work warrants further study.