Sedation versus general anesthesia on all-cause mortality in patients undergoing percutaneous procedures: a systematic review and meta-analysis.

BACKGROUND: The comparison between sedation and general anesthesia (GA) in terms of all-cause mortality remains a subject of ongoing debate. The primary objective of our study was to investigate the impact of GA and sedation on all-cause mortality in order to provide clarity on this controversial topic. METHODS: A systematic review and meta-analysis were conducted, incorporating cohort studies and RCTs about postoperative all-cause mortality. Comprehensive searches were performed in the PubMed, EMBASE, and Cochrane Library databases, with the search period extending until February 28, 2023. Two independent reviewers extracted the relevant information, including the number of deaths, survivals, and risk effect values at various time points following surgery, and these data were subsequently pooled and analyzed using a random effects model. RESULTS: A total of 58 studies were included in the analysis, with a majority focusing on endovascular surgery. The findings of our analysis indicated that, overall, and in most subgroup analyses, sedation exhibited superiority over GA in terms of in-hospital and 30-day mortality. However, no significant difference was observed in subgroup analyses specific to cerebrovascular surgery. About 90-day mortality, the majority of studies centered around cerebrovascular surgery. Although the overall pooled results showed a difference between sedation and GA, no distinction was observed between the pooled ORs and the subgroup analyses based on RCTs and matched cohort studies. For one-year all-cause mortality, all included studies focused on cardiac and macrovascular surgery. No difference was found between the HRs and the results derived from RCTs and matched cohort studies. CONCLUSIONS: The results suggested a potential superiority of sedation over GA, particularly in the context of cardiac and macrovascular surgery, mitigating the risk of in-hospital and 30-day death. However, for the longer postoperative periods, this difference remains uncertain. TRIAL REGISTRATION: PROSPERO CRD42023399151; registered 24 February 2023.

Codon Pattern and Context Analysis in Genes Triggering Alzheimer's Disease and Latent Tau Protein Aggregation Post-Anesthesia Exhibited Unique Molecular Patterns Associated with Functional Aspects.

Background: Previous reports have demonstrated post-operative dementia and Alzheimer's disease (AD), and increased amyloid-ß levels and tau hyperphosphorylation have been observed in animal models post-anesthesia. Objective: After surgical interventions, loss in memory has been observed that has been found linked with genes modulated after anesthesia. Present study aimed to study molecular pattern present in genes modulated post anesthesia and involved in characters progressing towards AD. Methods: In the present study, 17 transcript variants belonging to eight genes, which have been found to modulate post-anesthesia and contribute to AD progression, were envisaged for their compositional features, molecular patterns, and codon and codon context-associated studies. Results: The sequences' composition was G/C rich, influencing dinucleotide preference, codon preference, codon usage, and codon context. The G/C nucleotides being highly occurring nucleotides, CpGdinucleotides were also preferred; however, CpG was highly disfavored at p3-1 at the codon junction. The nucleotide composition of Cytosine exhibited a unique feature, and unlike other nucleotides, it did not correlate with codon bias. Contrarily, it correlated with the sequence lengths. The sequences were leucine-rich, and multiple leucine repeats were present, exhibiting the functional role of neuroprotection from neuroinflammation post-anesthesia. Conclusions: The analysis pave the way to elucidate unique molecular patterns in genes modulated during anesthetic treatment and might help ameliorate the ill effects of anesthetics in the future.

Caloric restriction increases the resistance of aged heart to myocardial ischemia/reperfusion injury via modulating AMPK-SIRT1-PGC1a energy metabolism pathway.

A large number of data suggest that caloric restriction (CR) has a protective effect on myocardial ischemia/reperfusion injury (I/R) in the elderly. However, the mechanism is still unclear. In this study, we created the I/R model in vivo by ligating the mice left coronary artery for 45 min followed by reperfusion. C57BL/6J wild-type mice were randomly divided into a young group fed ad libitum (y-AL), aged fed ad libitum (a-AL) and aged calorie restriction group (a-CR, 70% diet restriction), and fed for 6 weeks. The area of myocardial infarction was measured by Evan's blue-TTC staining, plasma cholesterol content quantified by ELISA, fatty acids and glucose measured by Langendorff working system, as well as protein expression of AMPK/SIRT1/PGC1a signaling pathway related factors in myocardial tissue detected by immunoblotting. Our results showed that CR significantly reduced infarct size in elderly mice after I/R injury, promoted glycolysis regardless of I/R injury, and restored myocardial glucose uptake in elderly mice. Compared with a-AL group, CR significantly promoted the expression of p-AMPK, SIRT1, p-PGC1a, and SOD2, but decreased PPARγ expression in aged mice. In conclusion, our results suggest that CR protects elderly mice from I/R injury by altering myocardial substrate energy metabolism via the AMPK/SIRT1/PGC1a pathway.

Sevoflurane preconditioning protects against acute MI/R injury via enhancing AdipoR1-Cav3 interaction and alleviating endoplasmic reticulum stress.

Whether and how sevoflurane preconditioning (SevoPre) exerts protection against acute myocardial ischemia/reperfusion (MI/R) injury remains elusive. We observed significant myocardial injury, as evidenced by infarct size, cardiomyocyte apoptosis, and circulating troponin-I, at 3 h of MI/R in both wildtype and adiponectin knockout mice. The injury was significantly ameliorated by SevoPre in wildtype mice, but not in adiponectin knockout mice. In wildtype mice, we found that MI/R could increase endoplasmic reticulum stress of cardiomyocytes, and impair association of adiponectin receptor 1 and ceveolin-3, both of which processes were largely restored by SevoPre. In summary, we demonstrated that significant injury had already took place at 3 h of MI/R, which could be ameliorated by SevoPre via promoting affinity of adiponectin receptor 1 and ceveolin-3, and then attenuating endoplasmic reticulum stress of cardiomyocytes.

Small intestine proteomics coupled with serum metabolomics reveal disruption of amino acid metabolism in Chinese hamsters with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia, with metabolic disturbances resulting from defects in insulin secretion, insulin resistance (IR), or both. Chinese hamsters have potential value as non-obese animal models of spontaneous T2DM for studying the pathogenesis and molecular characteristics of diabetes. In this study, the molecular characteristics of the Chinese hamster diabetes animal model were investigated through small intestine proteomics and serum metabolomics. A total of 213 differentially abundant proteins and 14 differentially abundant metabolites were identified through liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-time of flight mass spectrometry (GC-TOF/MS) analysis, respectively. Annotation by bioinformatics analysis revealed that these differentially abundant proteins in the small intestine were commonly associated with abnormal glucose and lipid metabolism, IR, impaired insulin secretion, amino acid metabolism disorders, and inflammatory dysregulation. Moreover, differentially abundant metabolites in the serum were amino acids and were related to diabetic IR. Through the analysis of small intestine proteomics and serum metabolomics in the Chinese hamster diabetes model, we provide a preliminary understanding of the diabetic characteristics of this model from a molecular perspective. This study provides data incentivizing the popularization and application of Chinese hamsters in T2DM research. SIGNIFICANCE: Spontaneous rodent models of diabetes, such as Chinese hamsters, effectively summarizes the clinical characteristics of type 2 diabetes and has high applicative value for studying the pathophysiology of diabetes. In order to explore the potential value of the Chinese hamster diabetes animal model in the study of the T2DM molecular mechanism, we performed small intestine proteomic analysis and serum metabolomic analysis in Chinese hamsters for the first time. After an integrated analysis of proteomics and metabolomics, we have a preliminary understanding of the diabetic characteristics of this model from a molecular perspective. Further, we found that in the occurrence and development of T2DM, the metabolic abnormalities of this model are particularly prominent, especially the metabolism of amino acids. These findings not only provide basic data in support of the popularization and application of the current model in T2DM research, but also provide a new perspective for the exploration of mechanisms related to T2DM.

Propofol Affects Different Human Brain Regions Depending on Depth of Sedation(△).

OBJECTIVE: To investigate the effect of propofol on brain regions at different sedation levels and the association between changes in brain region activity and loss of consciousness using blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) and bispectral index (BIS) monitoring. METHODS: Forty-eight participants were enrolled at Peking Union Medical College Hospital from October 2011 to March 2012 and randomly assigned to a mild or a deep sedation group using computer- generated random numbers. Preliminary tests were performed a week prior to scanning to determine target effect site concentrations based on BIS and concomitant Observer's Assessment of Alertness/Sedation scores while under propofol. Within one week of the preliminary tests where propofol dose-response was established, BOLD-fMRI was conducted to examine brain activation with the subject awake, and with propofol infusion at the sedation level. RESULTS: Mild propofol sedation inhibited left inferior parietal lobe activation. Deep sedation inhibited activation of the left insula, left superior temporal gyrus, and right middle temporal gyrus. Compared with mild sedation, deep propofol sedation inhibited activation of the left thalamus, precentral gyrus, anterior cingulate, and right basal nuclei. CONCLUSION: Mild and deep propofol sedation are associated with inhibition of different brain regions, possibly explaining differences in the respective loss of consciousness processes.

Sevoflurane preconditioning improving cerebral focal ischemia-reperfusion damage in a rat model via PI3K/Akt signaling pathway.

In this study, we aimed to assess the neuroprotective effect of sevoflurane preconditioning in a cerebral focal ischemia-reperfusion rat model. Sixty Sprague Dawley rats were divided into six groups: sham operated group, cerebral focal ischemia-reperfusion (CIR) group, CIR+sevoflurane preconditioning (SP) (2%) group, CIR+sevoflurane preconditioning (2.5%) group, CIR+sevoflurane preconditioning (3%) group, and CIR+sevoflurane preconditioning (3.5%) group. All subjects were euthanized 2days post-surgery and their hippocampus tissues were removed. Tissue malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-Px) levels were measured and hippocampus tissue samples were examined histopathologically. Results showed that significant difference in antioxidant, immunity indexes, and apoptosis-related protein expression was detected in hippocampus tissue between sham-operated control and CIR groups. Sevoflurane preconditioning significantly dose-dependently reduced MDA, IL-1ß, IL-6, IL-10 and TNF-α levels and enhanced antioxidant enzyme activities in hippocampus tissue of CIR+SP groups compared to CIR group. In addition, sevoflurane preconditioning significantly dose-dependently upregulated PI3K, p-Akt and Bcl-2 levels and downregulated caspase-3 and Bax levels in hippocampus tissue of CIR+SP groups compared to CIR group. It can be concluded that sevoflurane preconditioning demonstrates a strong and ameliorative effect on cerebral I/R damage in rats. The neuroprotective mechanisms of sevoflurane preconditioning are associated with its properties of anti-apoptosis and anti-oxidation as well as regulation of PI3K and p-Akt signal activation.

Effect of Sevoflurane postconditioning on gene expression in brain tissue of the middle cerebral artery occlusion rat model.

Ischemic postconditioning has been described in both heart and brain. The first aim of this study was to evaluate the effects of Sevoflurane postconditioning (SP) on brain biochemical parameters, Bcl-2, Bax, c-Fos and Caspase-3 protein levels and Bcl-2, Bax, TNF-α and Caspase-3 mRNA expression in the middle cerebral artery occlusion model. Results showed that SP markedly decreased cerebral oxidative injury and improved immunity activity. In addition, SP significantly enhanced cerebral Bcl-2, c-Fos and decreased Bax, Caspase-3 proteins positive expression. Reverse transcription polymerase chain reaction analysis showed that SP markedly enhanced Bcl-2, and decreased Bax, TNF-α and Caspase-3 mRNA expression. Our results confirm that SP can play the protective action against cerebral ischemia reperfusion-induced brain injury by regulating cerebral antioxidant enzymes activities, Bcl-2, Bax, c-Fos and Caspase-3 protein positive expression levels and Bcl-2, Bax, TNF-α and Caspase-3 mRNA expression.

[An audit of perioperative fluid management and electrolyte monitoring in children undergoing surgery for scoliosis].

OBJECTIVE: To audite and compare the perioperative practices of intravenous fluids and electrolyte & glucose monitoring in children undergoing operations for scoliosis in 2008, 2010, prior to and after the publication of guideline in 2009. METHODS: Retrospective audit was conducted at Peking Union Medical College Hospital, a tertiary referral teaching hospital in Beijing, China. Children under 14 years old with scoliosis treated surgically in 2008 and 2010 were recruited. The following data were collected from medical files: age, gender, weight, duration of hospitalization, concurrent illness, operation, anesthesia, fluid prescribed during perioperative fasting period, electrolyte monitoring and postoperative pain control, etc. RESULTS: Among 235 American Society of Anesthesiologists (ASA) I-II cases, 75 children received dextrose 5% or saline 0.9% during the preoperative fasting period. Intraoperatively, the anesthesiologists preferred dextrose 5% or saline 0.9% in children under 6 years old (n = 15, 2008; n = 15, 2010) and Ringer's solution in those aged 6 - 14 years (n = 84, 2008; n = 94, 2010) and hypotonic fluid was not used. And 82.3% and 94.3% of them received electrolyte examinations preoperatively. The electrolyte results were unavailable postoperatively in 27/122 (in 2008) and 13/113 (in 2010) and serum electrolytes were not assessed before fluid treatment postoperatively. Electrolytes were monitored only once in 82.3% (in 2008) and 70.5% (in 2010) patients. Compared with the preoperative concentration of sodium ion, the mean decrease was approximately 2.0 mmol/L at Day 1 postoperation. Hyponatremia at Day 1 postoperation in 2010 was more common than that in 2008 (26.2% vs 23.6%; P = 0.044). But no significant difference existed between the incidence of hyperglycemia of the same day in 2008 and that in 2010 (P = 0.306). CONCLUSION: Compared with that in 2008, our recent practice of intravenous fluid prescription and electrolyte monitoring is ill-consistent with the recommendations in 2009. Implementation of optimal perioperative fluid management is warranted.

Inhibition of sevoflurane postconditioning against cerebral ischemia reperfusion-induced oxidative injury in rats.

The volatile anesthetic sevoflurane is capable of inducing preconditioning and postconditioning effects in the brain. In this study, we investigated the effects of sevoflurane postconditioning on antioxidant and immunity indexes in cerebral ischemia reperfusion (CIR) rats. Rats were randomly assigned to five separate experimental groups I-V. In the sham group (I), rats were subjected to the same surgery procedures except for occlusion of the middle cerebral artery and exposed to 1.0 MAC sevoflurane 90 min after surgery for 30 min. IR control rats (group II) were subjected to middle cerebral artery occlusion (MCAO) for 90 min and exposed to O2 for 30 min at the beginning of reperfusion. Sevoflurane 0.5, 1.0 and 1.5 groups (III, IV, V) were all subjected to MCAO for 90 min, but at the beginning of reperfusion exposed to 0.5 MAC, 1.0 MAC or 1.5 MAC sevoflurane for 30 min, respectively. Results showed that sevoflurane postconditioning can decrease serum tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), nitric oxide (NO), nitric oxide synthase (NOS) and increase serum interleukin-10 (IL-10) levels in cerebral ischemia reperfusion rats. In addition, sevoflurane postconditioning can still decrease blood lipid, malondialdehyde (MDA) levels, infarct volume and increase antioxidant enzymes activities, normal pyramidal neurons density in cerebral ischemia reperfusion rats. It can be concluded that sevoflurane postconditioning may decrease blood and brain oxidative injury and enhance immunity indexes in cerebral ischemia reperfusion rats.

[Psychedelic effects of subanesthetic doses of ketamine].

OBJECTIVE: To study the psychedelic effects in healthy volunteers when given subanesthetic dose of ketamine. METHODS: Thirteen male healthy volunteers aged 24-39 years were enrolled. All subjects received subanesthetic doses of ketamine using target control infusion. A stepwise series of target plasma concentrations (0, 100, 200, and 300 ng/ml) were maintained for 20 minutes each. Visual analogue scale (VAS) of mechanical pain by von Frey hair was evaluated, and then the volunteers completed a VAS rating of 13 symptom scales. Pictures were shown to them at the same time. Heart rate, mean blood pressure, and SpO2 were monitored throughout the infusion. RESULTS: During the process of analgesia, ketamine produced dose-related analgesic effects. With the increase of ketamine dose, some psychedelic effects became more obvious and the memory impairment became worse stepwisely. CONCLUSION: Target control infusion of subanesthetic doses of ketamine produce obvious psychedelic effects in healthy volunteers.

[Comparison of cerebral state index and bispectral index accuracies in sedation monitoring during target control infusion of midazolam].

OBJECTIVE: To compare the accuracies of cerebral state index (CSI) and bispectral index (BIS) in sedation monitoring during target control infusion of midazolam. METHODS: Twenty informed adult male volunteers were intravenously administered with midazolam through plasma target control infusion from 30ng/ml (in increments of 10ng/ml every time) until they became unresponsive to tactile stimulation (i. e., mild prodding or shaking). The BIS and CSI were continuously recorded simultaneously. Sedation was assessed using the Observers' Assessment of Alertness/Sedation (OAA/S) scale at each time when Ct equaled to Ce. The electroencephalogram (EEG) parameters were correlated with the OAA/S scores using nonparametric Spearman's correlation analysis. The prediction probabilities were calculated at the points of lost of verbal contact (LVC) and lost of responses to stimulus (LOR). BIS05, BIS50, BIS95, and CSI05, CSI50, CSI95 were also calculated for LVC and LOR. RESULTS: BIS and CSI were well correlation with OAA/S scales during both the onset and recovery phases. When the sedation level increased, BIS and CSI progressively decreased. The prediction probabilities of BIS and CSI were 84%, 74% for LVC and 79%, 68% for LOR, while the BIS05, BIS50, and BIS95 as well as CSI05, CSI50, and CSI95 were 85.5, 60.6, and 35.7 (for BISs) and 82.2, 65.2, and 30.3 (for CSIs) at the point of LVC and 79.7, 47.6, and 15.6 (for BISs) and 75.9, 43.4, and 11 (for CSIs) at the point of LOR. CONCLUSIONS: Both CSI and BIS seem to be useful parameters for assessing midazolam-induced sedation. BIS is superior in the prediction of LVC and LOR.