Background Postoperative pulmonary complications are common. Aging and respiratory disease provoke airway hyperresponsiveness, high-risk surgery induces diaphragmatic dysfunction, and general anesthesia contributes to atelectasis and peripheral airway injury. This study therefore tested the hypothesis that inhalation of penehyclidine, a long-acting muscarinic antagonist, reduces the incidence of pulmonary complications in high-risk patients over the initial 30 postoperative days. Methods This single-center double-blind trial enrolled 864 patients age over 50 yr who were scheduled for major upper-abdominal or noncardiac thoracic surgery lasting 2 h or more and who had an Assess Respiratory Risk in Surgical Patients in Catalonia score of 45 or higher. The patients were randomly assigned to placebo or prophylactic penehyclidine inhalation from the night before surgery through postoperative day 2 at 12-h intervals. The primary outcome was the incidence of a composite of pulmonary complications within 30 postoperative days, including respiratory infection, respiratory failure, pleural effusion, atelectasis, pneumothorax, bronchospasm, and aspiration pneumonitis. Results A total of 826 patients (mean age, 64 yr; 63% male) were included in the intention-to-treat analysis. A composite of pulmonary complications was less common in patients assigned to penehyclidine (18.9% [79 of 417]) than those receiving the placebo (26.4% [108 of 409]; relative risk, 0.72; 95% CI, 0.56 to 0.93; P = 0.010; number needed to treat, 13). Bronchospasm was less common in penehyclidine than placebo patients: 1.4% (6 of 417) versus 4.4% (18 of 409; relative risk, 0.327; 95% CI, 0.131 to 0.82; P = 0.011). None of the other individual pulmonary complications differed significantly. Peak airway pressures greater than 40 cm H2O were also less common in patients given penehyclidine: 1.9% (8 of 432) versus 4.9% (21 of 432; relative risk, 0.381; 95% CI, 0.171 to 0.85; P = 0.014). The incidence of other adverse events, including dry mouth and delirium, that were potentially related to penehyclidine inhalation did not differ between the groups. Conclusions In high-risk patients having major upper-abdominal or noncardiac thoracic surgery, prophylactic penehyclidine inhalation reduced the incidence of pulmonary complications without provoking complications. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New
Parkinson's disease (PD) is a chronic, progressive neurodegenerative disorder characterized by motor impairments and loss of dopaminergic neurons in the substantia nigra. FLZ (formulated as: N-2-(4-hydroxy-phenyl)-ethyl]-2-(2, 5-dimethoxy-phenyl)-3-(3-methoxy-4-hydroxy-phenyl)-acrylamide) is a novel synthetic derivative of squamosamide from a Chinese herb and has been proven to protect dopaminergic neurons in subacute PD models. However, whether FLZ has a neuroprotective effect on chronic PD model is still unknown. The present study was designed to verify the neuroprotection of FLZ on chronic PD mouse model induced by MPTP combined with probenecid (MPTP/p). The results showed that treatment of mice with FLZ for 9 weeks significantly improved motor behavior and dopaminergic neuronal function of mice injected with MPTP/p. The beneficial effects of FLZ attributed to the elevation of dopaminergic neuron number, dopamine level, and tyrosine hydroxylase (TH) activity, as well as decrease of α-synuclein (α-Syn) expression, α-Syn phosphorylation, nitration, and aggregation. Moreover, FLZ decreased the interaction between α-Syn and TH, which eventually improved dopaminergic neuronal function. Mechanistic study demonstrated that FLZ increased Akt and mTOR phosphorylation, suggesting that FLZ activated Akt/mTOR signaling pathway and this might be involved in the neuroprotection of FLZ. The present results provided more elaborate in vivo evidences to support the neuroprotective effect of FLZ on dopaminergic neurons of chronic PD mouse model and the potential of FLZ to be developed as new drug to treat PD.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.