Postoperative cognitive dysfunction increases mortality and morbidity in perioperative patients and has become a major concern for patients and caregivers. Previous studies demonstrated that synaptic plasticity is closely related to cognitive function, anesthesia and surgery inhibit synaptic function. In central nervous system, autophagy is vital to synaptic plasticity, homeostasis of synapticproteins, synapse elimination, spine pruning, proper axon guidance, and when dysregulated, is associated with behavioral and memory functions disorders. The mammalian target of rapamycin (mTOR) negatively regulates the process of autophagy. This study aimed to explore whether rapamycin can ameliorate anesthesia/surgery-induced cognitive deficits by inhibiting mTOR, activating autophagy and rising synaptic plasticity-related proteins in the hippocampus. Aged C57BL/6J mice were used to establish POCD models with exploratory laparotomy under isoflurane anesthesia. The Morris Water Maze (MWM) was used to measure reference memory after anesthesia and surgery. The levels of mTOR phosphorylation (p-mTOR), Beclin-1 and LC3-II were examined on postoperative days 1, 3 and 7 by western blotting. The levels of synaptophysin (SYN) and postsynaptic density protein 95 (PSD-95) in the hippocampus were also examined by western blotting. Here we showed that anesthesia/surgery impaired reference memory and induced the activation of mTOR, decreased the expression of autophagy-related proteins such as Beclin-1 and LC3-II. A corresponding decline in the expression of neuronal/synaptic, plasticity-related proteins such as SYN and PSD-95 was also observed. Pretreating mice with rapamycin inhibited the activation of mTOR and restored autophagy function, also increased the expression of SYN and PSD-95. Furthermore, anesthesia/surgery-induced learning and memory deficits were also reversed by rapamycin pretreatment. In conclusion, anesthesia/surgery induced mTOR hyperactivation and autophagy impairments, and then reduced the levels of SYN and PSD-95 in the hippocampus. An mTOR inhibitor, rapamycin, ameliorated anesthesia/surgery-related cognitive impairments by inhibiting the mTOR activity, inducing activation of autophagy, enhancing SYN and PSD-95 expression.

BackgroundCardiac surgery patients often experience several types of tachyarrhythmias after admission to the intensive care unit (ICU), which increases mortality and morbidity. Dexmedetomidine (DEX) is a popular medicine used for sedation in the ICU, and its other pharmacological characteristics are gradually being uncovered.PurposeTo determine whether DEX has an antiarrhythmic effect after cardiac surgery.MethodsThe three primary databases MEDLINE, Embase (OVID SP) and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched, and all English-language and randomized control-designed clinical publications comparing DEX to control medicines for sedation after elective cardiac surgery were included. Two colleagues independently extracted the data and performed other quality assessments. A subgroup analysis was performed according to the different medicines used and whether cardiopulmonary bypass (CPB) was applied. All tachyarrhythmias that occurred in the atria and ventricles were analyzed.ResultsA total of 1295 patients in 9 studies met the selection criteria among 2587 studies that were screened. After quantitative synthesis, our results revealed that the DEX group was associated with a lower incidence of ventricular arrhythmia (VA, OR 0.24, 95% CI 0.09–0.64, I2 = 0%, P = 0.005) than the control group. Subgroup analysis did not reveal a significant difference between the DEX and propofol subgroups (OR 0.13, 95% CI 0.03–0.56, I2 = 0%, P = 0.007). Additionally, no difference in the incidence of atrial fibrillation (AF) was observed regardless of the different control medicines (OR 0.82, 95% CI 0.60–1.10, I2 = 25%, P = 0.19) or whether CPB was applied.ConclusionsThis meta-analysis revealed that DEX has an antiarrhythmic effect that decreases the incidence of VA compared to other drugs used for sedation following cardiac surgery. DEX may not have an effect on AF, but cautious interpretation should be exercised due to high heterogeneity.

PurposeCardiac surgery patients always present with atrial fibrillation (AF) after admission to the intensive care unit, leading to high mortality and lengthy hospitalization. Dexmedetomidine (DEX) is a popular medication used for sedation in the intensive care unit; however, whether it can reduce AF needs to be analyzed.Materials and methodsThree primary databases, Medline, Embase (Ovid SP) and the Cochrane Central Register of Controlled Trials (CENTRAL), were searched. All English language and randomized control designed clinical publications comparing DEX to control medicines for sedation after elective cardiac surgery were included. Two independent colleagues conducted the data extraction and quality assessments. The subgroup analysis was performed according to the medicine used, age, AF history, and whether previous beta-blocker premedication and cardiopulmonary bypass (CPB) were applied. The overall incidence of AF was analyzed.ResultsA total of 1,295 patients in nine studies met the selection criteria among 2,587 studies screened from the database. After quantitative synthesis, our results revealed that the DEX group was not associated with a decreased incidence of AF compared with the placebo (risk ratio [RR] 0.76, 95% CI 0.37, 1.55, P=0.44) and morphine groups (RR 0.86, 95% CI 0.56, 1.31, P=0.48). Subgroup analysis also indicated that the DEX vs propofol comparison exhibited no difference: 1) for patients of age >60 years (P=0.69) or ≤60 years (P=0.69); 2) under CPB surgery (P=0.45) or without CPB surgery (P=0.88); 3) with beta-blocker premedication (P=0.32) or without beta-blocker premedication (P=0.90); and 4) with AF history (RR 1.07, 95% CI 0.85, 1.36, P=0.57) or without AF history (P=0.30).ConclusionThis meta-analysis revealed that DEX could not reduce the incidence of AF compared to control medicines following cardiac surgery. DEX may have an increased influence on AF occurrence if patients had a history of AF. However, cautious interpretation should be made due to high clinical heterogeneity.

Objective This study was performed to determine the effect of dexmedetomidine (DEX) administration on myocardial damage in cardiac surgery with sevoflurane postconditioning. Methods We retrospectively examined all cardiac valve replacement surgeries from 1 April 2016 to 30 April 2017. Eligible patients were divided into two groups based on whether DEX was infused. DEX infusion was permitted only between intubation and the beginning of cardiopulmonary bypass (CPB). Sevoflurane was inhaled via the standard postconditioning procedure starting at aortic declamping. The cardiac troponin I (cTnI) level was measured at different time points. The postoperative outcomes and complications were also analyzed. Results One hundred patients were included in the study (DEX group, n = 53; non-DEX group, n = 47). Increased cTnI levels were significantly correlated with the New York Heart Association classification, CPB time, and DEX use. DEX use and the CPB time were potential independent factors contributing to changes in the cTnI level. The cTnI level at 6, 12, and 24 hours postoperatively was remarkably lower in the DEX than non-DEX group by 1.14, 7.83, and 5.86 ng/mL, respectively. Conclusions DEX decreased the cTnI level after CPB when sevoflurane postconditioning was used, especially at 6, 12, and 24 hours postoperatively.

Background Cardiac surgery patients are always companied with several kinds of tachyarrhythmias after admission to intensive care unit (ICU), which highly related to more mortality and morbidity. Dexmedetomidine (DEX) is the popular medicine used for sedation in ICU, whether or not have the antiarrhythmic effect need to be analyzed. Methods The three primary database, such as MEDLINE, Embase(OVID SP) and the Cochrane Central Register of Controlled Trials (CENTRAL), were searched, all of the English language and randomized-control designed clinical publications comparing DEX to control medicines for sedation after elective cardiac surgery were included. Two independent colleagues conduct data extraction or other quality assessment. Subgroup analysis was carried out by different medicine used or whether or not Cardiopulmonary Bypass (CPB) applied. All of the tachyarrhythmias happened in atria and ventricles were analyzed. Results A total of 1295 patients in 9 studies met the selection criteria among 2587 studies that screened from the database. After quantitative synthesis, our results revealed that DEX group was associated with low incidence of Ventricular Arrhythmia (VA, OR 0.24,95% CI 0.09,0.64, I2=0%, P=0.005) compared to control group, and this outcome was graded moderate quality of evidence. Subgroup analysis also indicated that DEX VS propofol subgroup had obvious difference (OR 0.13,95% CI 0.03,0.56, I2=0%, P=0.007). No difference was found with low quality of evidence in DEX VS control group for Atrial Fibrillation (AF, OR 0.82,95% CI 0.60,1.10, I2=25%, P=0.19), the subgroup analysis got the consistent results, but the subgroup analysis by CPB showed high heterogeneity (VA, I2=59%, P=0.27), eventually the stability of the results was confirmed after sensitivity analysis (I2=19%, P=0.83). No obvious publication bias was found by Funnel plot. Conclusions This meta-analysis revealed with strong evidence that DEX has antiarrhythmic effect to decrease the incidence of VT and VF comparing to other control drugs following cardiac surgery. No difference was found with low quality of evidence in DEX VS control group for Atrial Fibrillation, but cautious interpretation should be noticed to the influence on AF, especially occurred under CPB.