Time interval between alfentanil and rocuronium administration necessary to prevent rocuronium-induced withdrawal movement.

BACKGROUND: We aimed to determine the time interval between alfentanil and rocuronium administration, at a 50% probability of preventing pain-induced withdrawal movement from rocuronium injection (TimeAR50). METHODS: A total of 64 patients scheduled for general anesthesia were enrolled in this study (33 men and 31 women). Anesthesia was induced with target-controlled infusion of propofol, at an effect-site target concentration of 3 µg/mL. Then, alfentanil 15 µg/kg was injected for 30 s. After 60 s, rocuronium 0.6 mg/kg was administered to the first patient. The Dixon's up-and-down method was used to determine the time interval for each subsequent patient (interval of 5 s). Mean arterial pressure (MAP) and heart rate (HR) were recorded at three time points: T0, pre-induction; T1, before rocuronium injection; and T2, 1 min after rocuronium injection. RESULTS: The TimeAR50 ± standard deviation (SD) was 5.6 ± 3.7 s and 21.9 ± 5.6 s in the male and female patients, respectively. Based on the probit regression, the TimeAR50 was 4.7 s (95% confidence interval [CI], 1.2-7.6 s) and 20.3 s (95% CI, 7.7-26.1 s) in the male and female patients, respectively. The TimeAR95 was 10.6 s (95% CI, 7.7-25.3 s) and 35.0 s (95% CI, 28.1-95.5 s) in the male and female patients, respectively, with significantly higher values in females than in males (P < 0.001). Compared with the T0, MAP and HR decreased significantly at T1 and T2 in both groups. CONCLUSION: The TimeAR50 required for preventing rocuronium-induced withdrawal movement were 4.7 s and 20.3 s in male and female patients, respectively. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trials Registry on April 7, 2021 (URL: http://www.chictr.org.cn . Registry number: ChiCTR2100045137 ) .

Isoflurane protects against injury caused by deprivation of oxygen and glucose in microglia through regulation of the Toll-like receptor 4 pathway.

Oxygen and glucose deprivation (OGD) are the most important factors related to tissue damage resulting from stroke. Microglial cells have been found to be very vulnerable to ischemia and OGD. It has been reported that isoflurane exposure can protect the mammalian brain from insults such as ischemic stroke; however, the effects of isoflurane on OGD-induced injury in microglia are as yet unknown. In this study, we investigated the effects of isoflurane on OGD-induced injury in microglia. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) revealed that OGD did indeed induce cell death in microglia. However, isoflurane preconditioning attenuated OGD-induced cell death. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay demonstrated that isoflurane treatment alleviated OGD-induced apoptosis. Toll-like receptor 4 (TLR4) plays a considerable role in the induction of innate immune and inflammatory responses. Our results indicate that isoflurane preconditioning inhibits the upregulation of TLR4 as well as the activation of its downstream molecules, such as c-Jun N-terminal kinase (JNK) and nuclear factor kappa B (NF-κB), in BV-2 microglia exposed to OGD. Importantly, we also found that isoflurane pretreatment significantly reduces the production of proinflammatory factors such as tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-ß, and nitric oxide (NO). The results indicate that TLR4 and its downstream NF-κB-dependent signaling pathway contribute to the neuroprotection of microglia exposed to OGD/reoxygenation by administration of isoflurane.