Effects of penehyclidine hydrochloride combined with dexmedetomidine on pulmonary function in patients undergoing heart valve surgery: a double-blind, randomized trial.

AIM: To investigate the effects of penehyclidine hydrochloride combined with dexmedetomidine on pulmonary function in patients undergoing heart valve surgery with cardiopulmonary bypass (CPB). METHODS: A total of 180 patients undergoing elective heart valve surgery with CPB were randomly divided into four groups: 45 in group P (intravenous penehyclidine hydrochloride 0.02 mg/kg 10 min before anesthesia induction and at the beginning of CPB, total 0.04 mg/kg); 43 in group D (dexmedetomidine 0.5 µg/kg/h after induction of anesthesia until the end of anesthesia); 44 in group PD ( penehyclidine hydrochloride 0.04 mg/kg combined with dexmedetomidine 0.5 µg/kg/h intravenously during anesthesia); and 43 in group C (same amount of normal saline 10 min before and after anesthesia induction, to the end of anesthesia, and at the beginning of CPB). The main outcomes were the incidence and severity of postoperative pulmonary complications (PPCs). The secondary outcomes were: (1) extubation time, length of stay in intensive care, and postoperative hospital stay, and adverse events; and (2) pulmonary function evaluation indices (oxygenation index and respiratory index) and plasma inflammatory factor concentrations (tumor necrosis factor-α, interleukin-6, C-reactive protein and procalcitonin) during the perioperative period. RESULTS: The incidence of PPCs in groups P, D and PD after CPB was lower than that in group C (P < 0.05), and the incidence in group PD was significantly lower than that in groups P and D (P < 0.05). The scores for PPCs in groups P, D and PD were lower than those in group C (P < 0.05). CONCLUSION: Combined use of penehyclidine hydrochloride and dexmedetomidine during anesthesia reduced the occurrence of postoperative pulmonary dysfunction, and improved the prognosis of patients undergoing heart valve surgery with CPB. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry on 3/11/2020 (Registration No.: ChiCTR2000039610).

Propofol-induced sleep ameliorates cognition impairment in sleep-deprived rats.

PURPOSE: Propofol has been shown to clear sleep debt in rats after sleep deprivation (SD). We examined whether or not propofol-assisted sleep can restore cognitive function in SD rats and explored the possible mechanisms. METHODS: A sleep deprivation model was established by housing 9 to 12 week-old rats to a multiplatform water tank for 96 h. Model rats were then intraperitoneally injected with different concentrations of propofol or 10% fat emulsion (vehicle control). All treatment groups were examined for spatial learning and memory ability in the Morris water maze (MWM). After euthanasia, morphological changes in the hippocampus, hippocampal neurons, and mitochondria were examined by hematoxylin-eosin staining and transmission electron microscopy. Serum and hippocampal levels of IL-1ß, TNF-α, and hippocampal concentrations of ATP and Cyt-c were measured by ELISA (enzyme-linked immunosorbent assay). Immunohistochemistry and Western blotting were performed to assess hippocampal expression of Bcl-2, Bax, and cleaved caspase-3. RESULTS: Results showed that escape latencies in MWM training trials were significantly shorter and target crossings in the memory probe trial significantly greater in propofol-treated SD model rats compared to vehicle-treated SD rats. Propofol also reduced the number of apoptotic bodies in the hippocampal CA1 region. Sleep deprivation reduced IL-1ß and ATP in hippocampus while increasing TNF-α and Cyt-c, and propofol treatment reversed all these changes. There was no significant difference in Bcl-2 expression between propofol- and vehicle-treated SD rats, but pro-apoptotic Bax and cleaved caspase-3 expression levels were significantly reduced by propofol in SD rats. CONCLUSIONS: Propofol-assisted sleep restored cognitive function in SD rats possibly by attenuating mitochondria-mediated neuronal apoptosis in the hippocampus.

Propofol protects hippocampal neurons in sleep-deprived rats by inhibiting mitophagy and autophagy.

BACKGROUND: Sleep deprivation (SD) causes a disturbance in the cognitive function of rats. While propofol has a powerful sedative and hypnotic effect and is an antioxidant, its effect on the cognitive function of rats following SD remains unknown. The purpose of this study was to explore the protective effects of propofol on excessive autophagy and mitophagy in the hippocampus of rats after SD. METHODS: Adult male rats were intraperitoneally injected with 30 mg/kg of propofol after 96 hours of SD. Then we evaluated the effect of propofol on the cognitive function of sleep deprived rats by the Morris water maze. Transmission electron microscopy, Western blotting, PCR, immunohistochemistry, autophagy enhancer and autophagy inhibitor were used to study the effect of propofol on hippocampal neurons of rat with excessive autophagy and mitophagy. RESULTS: The behavioral experimental results of the Morris water maze showed that propofol improved the learning and memory ability of sleep-deprived rats. The expression of Beclin1, PINK1, parkin, p62, and LC3 protein increased significantly after sleep deprivation. While the intervention of propofol could significantly reduce the expression of these proteins, rapamycin treatment eliminated this effect. CONCLUSIONS: Our findings showed that propofol could reduce the impairment of learning and memory in sleep-deprived rats by inhibiting excessive autophagy and mitophagy in hippocampal neurons. This strategy may provide an application basis for the clinical use of propofol in patients with chronic insomnia.

Effect of remimazolam induction on hemodynamics in patients undergoing valve replacement surgery: A randomized, double-blind, controlled trial.

BACKGROUND: The stability of hemodynamics during anesthesia induction in patients undergoing valve replacement surgery is particularly important. Remimazolam is a new type of benzodiazepine drug, with supposed advantages of rapid induction, rapid recovery, stable hemodynamics, and mild respiratory inhibition. AIM: To evaluate the effect of remimazolam anesthesia induction on hemodynamics in patients undergoing valve replacement surgery. METHODS: This randomized, double-blind, controlled trial enrolled consecutive patients undergoing mitral valve replacement (MVR)/aortic valve replacement (AVR)/double-valve replacement (DVR) surgery on cardiopulmonary bypass (CPB). The study was conducted according to the Consolidated Standards of Reporting Trials statement. Participants were randomly assigned to receive either remimazolam or propofol induction of 30 patients each. All patients, data collectors, and data analyzers were blinded to the group allocation. The primary outcomes were the fluctuations in hemodynamic parameters (the difference of maximum or minimum heart rate to baseline, ▲HR, the difference of maximum or minimum mean arterial pressure to baseline, ▲MAP), the occurrence of cardiovascular events (hypotension, severe bradycardia), and the cumulative norepinephrine doses used per patient, averaged per group during induction. The secondary outcomes were hemodynamic parameters (heart rate, HR, mean arterial pressure, MAP, bispectral index, BIS, plasma lactic acid, Lac, and blood glucose, Glu values). RESULTS: A total of 60 patients with heart valve replacement were included in the final analysis, with 30 patients in each group. The ▲MAP was significantly lower in the remimazolam group than in the propofol group during induction (p < .05). The incidences of hypotension and the cumulative norepinephrine doses used per patient, averaged per group during induction were significantly lower in the remimazolam group than in the propofol group (p < .05). CONCLUSION: Remimazolam may be safe and effective for induction and may as an alternative to propofol during anesthesia induction in patients undergoing valve replacement surgery.