Intravenous infusion of dexmedetomidine during the surgery to prevent postoperative delirium and postoperative cognitive dysfunction undergoing non-cardiac surgery: a meta-analysis of randomized controlled trials.

BACKGROUND: Dexmedetomidine plays a pivotal role in mitigating postoperative delirium and cognitive dysfunction while enhancing the overall quality of life among surgical patients. Nevertheless, the influence of dexmedetomidine on such complications in various anaesthesia techniques remains inadequately explored. As such, in the present study, a meta-analysis was conducted to comprehensively evaluate its effects on postoperative delirium and cognitive dysfunction. METHODS: A number of databases were searched for randomised controlled trials comparing intravenous dexmedetomidine to other interventions in preventing postoperative delirium and cognitive dysfunction in non-cardiac and non-neurosurgical patients. These databases included PubMed, Embase, and Cochrane Library. Statistical analysis and graphing were performed using Review Manager, STATA, the second version of the Cochrane risk-of-bias tool for randomised controlled trials, and GRADE profiler. MAIN RESULTS: This meta-analysis comprised a total of 24 randomised controlled trials, including 20 trials assessing postoperative delirium and 6 trials assessing postoperative cognitive dysfunction. Across these 24 studies, a statistically significant positive association was observed between intravenous administration of dexmedetomidine and a reduced incidence of postoperative delirium (RR: 0.55; 95% CI 0.47 to 0.64, p < 0.00001, I2 = 2%) and postoperative cognitive dysfunction (RR: 0.60; 95% CI 0.38 to 0.96, p = 0.03, I2 = 60%). Subgroup analysis did not reveal a significant difference in the incidence of postoperative delirium between the general anaesthesia and non-general anaesthesia groups, but a significant difference was observed in the incidence of postoperative cognitive dysfunction. Nonetheless, when the data were pooled, it was evident that the utilisation of dexmedetomidine was associated with an increased incidence of hypotension (RR: 1.42; 95% CI 1.08 to 1.86, p = 0.01, I2 = 0%) and bradycardia (RR: 1.66; 95% CI 1.23 to 2.26, p = 0.001, I2 = 0%) compared with other interventions. However, there was no significantly higher occurrence of hypertension in the DEX groups (RR = 1.35, 95% CI 0.81-2.24, p = 0.25, I2 = 0%). CONCLUSION: Compared with other interventions, intravenous dexmedetomidine infusion during non-cardiac and non-neurosurgical procedures may significantly reduce the risk of postoperative delirium and cognitive dysfunction. The results of subgroup analysis reveal a consistent preventive effect on postoperative delirium in both general and non-general anaesthesia groups. Meanwhile, continuous infusion during general anaesthesia was more effective in reducing the risk of cognitive dysfunction. Despite such findings, hypotension and bradycardia were more frequent in patients who received dexmedetomidine during surgery.

The role of dexmedetomidine administered via intravenous infusion as adjunctive therapy to mitigate postoperative delirium and postoperative cognitive dysfunction in elderly patients undergoing regional anesthesia: a meta-analysis of randomized controlled trials.

STUDY OBJECTIVE: This meta-analysis aimed to assess whether continuous intravenous administration of DEX during surgery can be part of the measures to prevent the onset of postoperative delirium and postoperative cognitive dysfunction in elderly individuals following regional anesthesia. METHODS: We searched the databases of PubMed, Embase, the Cochrane Library and China National Knowledge Infrastructure (by June 1, 2023) for all available randomized controlled trials assessing whether intravenous application of dexmedetomidine can help with postoperative delirium and postoperative cognitive dysfunction in the elderly with regional anesthesia. Subsequently, we carried out statistical analysis and graphing using Review Manager software (RevMan version 5.4.1) and STATA software (Version 12.0). MAIN RESULTS: Within the scope of this meta-analysis, a total of 18 randomized controlled trials were included. Among them, 10 trials aimed to assess the incidence of postoperative delirium as the primary outcome, while the primary focus of the other 8 trials was on the incidence of postoperative cognitive dysfunction. The collective evidence from these 10 studies consistently supports a positive relationship between the intravenous administration of dexmedetomidine and a decreased risk of postoperative delirium (RR: 0.48; 95%CI: 0.37 to 0.63, p < 0.00001, I2 = 0%). The 8 literature articles and experiments evaluating postoperative cognitive dysfunction showed that continuous intravenous infusion of dexmedetomidine during the entire surgical procedure exhibited a positive preventive effect on cognitive dysfunction among the elderly population with no obvious heterogeneity (RR: 0.35; 95%CI: 0.25 to 0.49,p < 0.00001, I2 = 0%). CONCLUSION: Administering dexmedetomidine intravenously during surgery can potentially play a significant role in preventing postoperative delirium and postoperative cognitive dysfunction in patients older than 60 years with regional anesthesia according to this meta-analysis.

Postoperative blood glucose increase is associated with futile recanalization in patients with successful thrombectomy: a retrospective study.

BACKGROUND: Timely recognition of futile recanalization might enable a prompt response and an improved outcome in post-thrombectomy patients. This study aims to evaluate whether postoperative blood glucose increase (BGI) could act as an indicator of futile recanalization in patients receiving a successful thrombectomy. METHODS: This is a single-center, retrospective analysis of patients with anterior circulation large-vessel occlusion and successful thrombectomy between February 2019 and June 2022. BGI was defined as a higher level of blood glucose at the first postoperative morning than at admission. Futile recanalization was defined as patients with a modified Rankin Scale score of 3-6 at 90 days after onset. Multivariable binary logistic regression was used to assess the association of BGI with futile recanalization. RESULTS: A total of 276 patients were enrolled, amongst which 120 patients (43.5%) had BGI. Futile recanalization was more prevalent among patients with BGI compared to those without (70.0 vs. 49.4%, P = 0.001). After adjusting for potential confounders, BGI was associated with a higher likelihood of futile recanalization (adjusted OR: 2.97, 95%CI: 1.50-5.86, P = 0.002). This association was consistently observed regardless of diabetes history, occlusion site, time from symptom onset to groin puncture, or reperfusion status. CONCLUSION: Our findings support BGI serving as an indicator of futile recanalization in patients with anterior circulation large-vessel occlusion and successful thrombectomy.

Postoperative fibrinogen-to-albumin ratio acting as an indicator of futile recanalization in patients with successful thrombectomy.

BACKGROUND: Timely recognition of futile recanalization might enable a prompter response and thus improve outcomes in patients receiving successful thrombectomy. This study aims to evaluate whether postoperative fibrinogen-to-albumin ratio (FAR) could act as an indicator of futile recanalization. METHODS: This is a single-center, retrospective analysis of patients with acute anterior circulation large-vessel occlusion and successful thrombectomy between May 2019 and June 2022. FAR was defined as postoperative blood levels of fibrinogen divided by those of albumin, and dichotomized into high and low levels based on the Youden index. Futile recanalization was defined as patients achieving a successful recanalization with a modified Rankin Scale score of 3-6 at 90 days. Multivariable logistic regression was used to assess the association of FAR with futile recanalization. RESULTS: A total of 255 patients were enrolled, amongst which 87 patients (34.1%) had high postoperative FAR. Futile recanalization was more prevalent among patients with high FAR compared to those with low FAR (74.7% vs. 53.0%, p = .001). After adjusting for potential confounders, high postoperative FAR was found to independently correspond with the occurrence of futile recanalization (adjusted OR 2.40, 95%CI 1.18-4.87, p = .015). This association was consistently observed regardless of prior antithrombotic therapy, treatment of intravenous thrombolysis, occlusion site, time from symptom onset to groin puncture, and reperfusion status. CONCLUSION: Our findings support high postoperative FAR serving as an indicator of futile recanalization in patients with anterior circulation large-vessel occlusion and successful thrombectomy.

The efficacy and safety of opioid-free anesthesia combined with ultrasound-guided intermediate cervical plexus block vs. opioid-based anesthesia in thyroid surgery-a randomized controlled trial.

PURPOSE: In the context of the current comfort medicine and enhanced recovery after surgery, there is a demand for a new anesthesia method to reduce adverse reactions and accelerate recovery after surgery. This randomized controlled trial aimed to compare the efficacy and safety between opioid-free anesthesia (OFA) combined with ultrasound-guided intermediate cervical plexus block (ICPB) and opioid-based anesthesia in patients after thyroid surgery. METHODS: In this study, 75 patients scheduled for thyroid surgery under general anesthesia were randomly allocated into two groups. The primary outcome included the incidence of nausea within 24 h after surgery. The main secondary outcomes included the incidence of vomiting and the visual analog score (VAS) scores within 24 h after surgery as well as the quality of recovery 40 questionnaires (QoR-40) scores 24 h after surgery. RESULTS: In the OFA group, the incidence of postoperative nausea was 6.1%, compared to 39.4% in the control group (p = 0.001). No patient presented with postoperative vomiting in the OFA group, while 15.2% of patients suffered from postoperative vomiting in the control group (p = 0.063). The VAS scores of patients in the postanesthetic care unit (PACU) and 2 h, 4 h, and 6 h after surgery were lower in the OFA group, and the difference is statistically significant. Besides, the VAS scores of patients at rest (p = 1.000) and during swallowing (p = 1.000) 24 h after surgery were comparable. CONCLUSION: Compared with opioid-based anesthesia, the OFA combined with the ultrasound-guided ICPB can better improve patients' postoperative recovery, reduce nausea, and decrease pain scores. TRIAL REGISTRATION: Chinese Clinical Trial Regisrty, ChiCTR2200056344, https://www.chictr.org.cn.

The Neuroprotective Effect of Hemin and the Related Mechanism in Sevoflurane Exposed Neonatal Rats.

BACKGROUND: Many studies have reported that sevoflurane can increase neuronal apoptosis and result in cognitive deficits in rodents. Although neurotoxicity may be associated with mitochondrial dysfunction and oxidative stress, the exact mechanism remains unclear. In order to evaluate potential treatment therapies, we studied the effects of hemin on neurotoxicity of neonatal rat sevoflurane exposure. METHODS: Postnatal day (P) seven rats were assigned randomly to four groups; (1) group C: non-anesthesia, (2) group H: intraperitoneal hemin (50 mg kg-1) treatment on days 5 and 6, (3) group S: 3% sevoflurane exposure for 4 h, and (4) group SH: hemin treatment + sevoflurane exposure. The expression of neuroglobin in neonatal hippocampus was determined by western blot and immunohistochemistry. Neuroglobin was localized by immunofluorescence. Western blot for the expression of cleaved caspase-3 and TUNEL were used to detect neonatal hippocampal apoptosis, and cytochrome c was used to evaluate mitochondrial function. Drp-1 and Mfn-2 immunoblotting were used to assess mitochondrial dynamics. The Morris water maze test was performed to detect cognitive function in the rats on P30. RESULTS: Exposure to sevoflurane increased the expression of cleaved caspase-3, cytochrome c, and Drp1 in the neonatal hippocampus and resulted in cognitive deficiency but decreased expression of Mfn2. Hemin reduced apoptosis, improved mitochondrial dynamics and ameliorated the cognitive impairment caused by sevoflurane exposure. CONCLUSION: Hemin reduced neuronal apoptosis, improved mitochondrial dynamics and protected against cognitive deficits induced by sevoflurane in neonatal rats. This neuroprotective effect may be achieved by increasing the expression of neuroglobin.

Sevoflurane induces neurotoxicity in the developing rat hippocampus by upregulating connexin 43 via the JNK/c-Jun/AP-1 pathway.

As one of the most popular anesthetics, sevoflurane is widely used in pediatric anesthesia. Unfortunately, an increasing number of studies have demonstrated that sevoflurane has potential neurotoxic effects on the developing brain and cognition, even in adolescence. Connexin 43 (Cx43) has been documented to contribute to cognitive dysfunction. The present study hypothesized that Cx43 may participate in sevoflurane-induced neuroinjury and investigated the underlying mechanisms in young Sprague Dawley (SD) rats. Seven-day-old SD rats (P7) were exposed to 3% sevoflurane for 4 h. The levels of Cx43,mitogen-activated protein kinase (MAPK) signaling pathway components(including total and phosphorylated p38, extracellular signal-regulated kinase (ERK), and c-Jun n-terminal kinase (JNK) and activator protein 1(AP-1) transcription factors (including total and phosphorylated c-Fos, and c-Jun) were assessed by Western blot analysis. Neuronal apoptosis was detected using immunohistochemistry (IHC). The Morris water maze (MWM) was performed to evaluate cognitive function from P28 to P33. The results showed that anesthesia with 3% sevoflurane for 4 h increased Cx43 levels in the rat hippocampus from 6 h to 3 d, and compared with sevoflurane exposure in the control group rats, exposure in P7 SD rats also increased the ratios of phosphorylated JNK to JNK and, phosphorylated c-Jun to c-Jun in the hippocampus from 6 h to 3 d. All these effects could be alleviated by pretreatment with the JNK inhibitor SP600125 (10 mg/kg). Neuroapoptosis was similarly increased from 6 h to 1 d after inhaled sevoflurane exposure. Finally, the MWM indicated that sevoflurane could increase the escape latency and, decrease the number of platform crossings from P28 to P33. Overall, our findings suggested that sevoflurane increased Cx43 expression and induced to apoptosis by activating the JNK/c-Jun signaling pathway in the hippocampus of P7 rats. This finding may reveal a new strategy for preventing sevoflurane-induced neuronal dysfunction.

Dexmedetomidine Ameliorates the Neurotoxicity of Sevoflurane on the Immature Brain Through the BMP/SMAD Signaling Pathway.

Numerous studies have demonstrated that general anesthetics might damage the nervous system, thus, the effect of general anesthetics on the developing brain has attracted much attention. Dexmedetomidine (Dex) exhibits a certain neuroprotective effect, but the mechanism is obscure. In our study, pregnant rats on gestational day 20 (G20) were exposed to 3% sevoflurane for 2 h or 4 h, and the neuronal apoptosis in hippocampal CA1 region of the offspring rats was detected by quantification of TUNEL positive cells and cleaved-caspase3 (cl-caspase3). Different doses of Dex were intraperitoneally injected before sevoflurane anesthesia; then, the expression of apoptotic-related proteins including BCL-2, BAX and cl-caspase3 as well as amyloid precursor protein (APP, a marker of axonal injury), p-CRMP-2 and CRMP-2 were measured at postnatal days 0, 1and 3 (P0, P1, and P3, respectively). As an antagonist of the bone morphgenetic proteins (BMP) receptor, DMH1 was co-administered with sevoflurane plus Dex to investigate whether BMP/SMAD is associated with the neuroprotective effects of Dex. The results showed that prenatal sevoflurane anesthesia for 4 h activated apoptosis transiently, as manifested by the caspase3 activity peaked on P1 and disappeared on P3. In addition, the expressions of APP and p-CRMP-2/CRMP-2 in postnatal rat hippocampus were significantly increased, which revealed that prenatal sevoflurane anesthesia caused axonal injury of offspring. The long-term learning and memory ability of offspring rats was also impaired after prenatal sevoflurane anesthesia. These damaging effects of sevoflurane could be mitigated by Dex and DMH1 reversed the neuroprotective effect of Dex. Our results indicated that prenatal exposure to 3% sevoflurane for 4 h increased apoptosis and axonal injury, even caused long-term learning and memory dysfunction in the offspring rats. Dex dose-dependently reduced sevoflurane- anesthesia-induced the neurotoxicity by activating the BMP/SMAD signaling pathway.