Dexmedetomidine infusion for emergence coughing prevention in patients undergoing an endovascular interventional procedure: A randomized dose-finding trial.

OBJECTIVE: Dexmedetomidine has been introduced in emergence coughing, agitation, and shivering prevention. This study aimed to investigate the optimal dose of dexmedetomidine for emergence cough prophylaxis. METHODS: In this randomized, double-blinded, and prospective trial, 356 patients scheduled for an endovascular interventional procedure were randomly assigned to 0.3 (D 0.3), 0.4 (D 0.4), 0.5 (D 0.5), and 0.6 (D 0.6) µg·kg-1·h-1 dexmedetomidine rate, or saline control (C), from anesthesia induction until the end of surgery. The primary outcomes measured were cough grade and frequency. Additionally, groups were compared according to mean arterial pressure (MAP), heart rate, agitation, shivering, postoperative nausea and vomiting (PONV), extubation time, sedation scores, and postoperative first night sleep quality (secondary outcomes). RESULTS: A total of 351 patients were included in the analysis. The respective incidences of D 0.3, D 0.4, and D 0.5 versus C group were: 78.6%, 68.6%, 53.4% and 42.9% vs 89.7% for cough (p = 0.002, p < 0.001, and p < 0.001 between group D 0.4, D 0.5 and D 0.6 vs C, respectively); 30%, 27.1%, 20.5%, 15.7% vs 44.1% for agitation (p = 0.04, p = 0.003, and p < 0.001 between group D 0.4, D 0.5 and D 0.6 vs C, respectively); 8.6%, 7.1%, 6.8%, 5.7% vs 22.1% for shivering (p = 0.027, p = 0.013, p = 0.01, and p = 0.01 between D 0.3, D 0.4, D 0.5 and D 0.6 vs C, respectively); and 52.9%, 57.1%, 42.5%, 44.3% vs 61.8% for poor sleep quality (p = 0.02 and p = 0.04 between group D 0.5 and D 0.6 vs C, respectively). D 0.4, D 0.5 and D 0.6 showed lower MAP during extubation, compared with the C group. Also, D 0.5 and D 0.6 presented a slight delay in extubation (3.1 and 3.3 min longer than C; p = 0.002 and p < 0.001, respectively). Meanwhile, the frequency of atropine, vasopressor administration, PONV and dizziness were similar to the control. CONCLUSIONS: Both 0.5 and 0.6 µg·kg-1·h-1 dexmedetomidine infusion rates effectively mitigated emergence coughing with prolonged extubation time, besides sleep disturbance. D 0.4, D 0.5, and D 0.6 reduced agitation and sustained hemodynamic stability. Finally, the four doses applied were effective in shivering attenuation.

Penehyclidine hydrochloride inhibits TLR4 signaling and inflammation, and attenuates blunt chest trauma and hemorrhagic shock-induced acute lung injury in rats.

Blunt chest trauma with hemorrhagic shock (THS) frequently induces pulmonary inflammation that leads to acute lung injury (ALI). Penehyclidine hydrochloride (PHC) possesses anti­inflammatory properties that may attenuate the systemic inflammatory response. The present study aimed to evaluate the molecular mechanism of PHC in modifying THS­induced ALI in rats. Rats underwent either THS or a sham procedure. At 6 h subsequent to blunt chest trauma, arterial blood was drawn for blood gas and pro­inflammatory factors analyses, and lung tissue samples were collected to examine pulmonary histopathological alterations, the wet/dry weight ratio, myeloperoxidase activity, and the protein expression levels of Toll-like receptor 4 (TLR4), phosphorylated (p­)p38 mitogen­activated protein kinase (MAPK), nuclear factor (NF)­κB and activator protein­1 (AP­1). THS caused significant reductions in heart rate and mean arterial blood pressure, and was associated with significant increases in tumor necrosis factor­α, interleukin (IL)­6, IL­1ß, p­p38MAPK, NF­κB and AP­1 activation, in addition to TLR4 expression, in the lung. PHC effectively attenuated THS­induced ALI, and inhibited TLR4 expression, reduced the activation of p­p38MAPK, NF­κB and AP­1, and downregulated the expression of pro­inflammatory mediators. In conclusion, the results of the present study demonstrated that PHC may exert an anti­inflammatory effect and attenuate THS­induced ALI by inhibiting the TLR4 signaling pathway. These preclinical findings may offer a novel therapeutic strategy to restrict TLR4 overactivation in ALI.

Impact of 4HPR on the expression of E-Cad in human bladder transitional epithelial cancer cells T24.

Previous researches showed that the expression level of E-Cad in most infiltrating cancer cells was reduced or negative. This study explored whether 4HPR restrained the infiltration of bladder cancer cells through regulating the expression of E-Cad. The infiltrating bladder cancer cells T24 were cultured, and then treated by a proper dosage of drug. Their viability was a determined by MTT method. Western blotting and RT-PCR were adopted to detect the changes of E-Cad gene expression at both protein and mRNA levels. Moreover, immunofluorescent staining and confocal fluorescence microscopy were employed for the observation of the expression of E-Cad. The result showed that, at both mRNA and protein levels, the expression level of E-Cad in T24 cells treated by 4HPR was significantly higher than that of control group, while the ß-Cat expression was also relocated from the cell nucleus to cytoplasm. Our findings suggested that the regulatory function of 4HPR on infiltration of bladder cancer cells T24 is at least partly achieved by regulating the expression of E-Cad.