The primary intravenous anesthetics employed in clinical practice encompass dexmedetomidine (Dex), propofol, ketamine, etomidate, midazolam, and remimazolam. Apart from their established sedative, analgesic, and anxiolytic properties, an increasing body of research has uncovered neuroprotective effects of intravenous anesthetics in various animal and cellular models, as well as in clinical studies. However, there also exists conflicting evidence pointing to the potential neurotoxic effects of these intravenous anesthetics. The role of intravenous anesthetics for neuro on both sides of protection or toxicity has been rarely summarized. Considering the mentioned above, this work aims to offer a comprehensive understanding of the underlying mechanisms involved both in the central nerve system (CNS) and the peripheral nerve system (PNS) and provide valuable insights into the potential safety and risk associated with the clinical use of intravenous anesthetics.
Animals ; Humans ; Anesthetics, Intravenous/adverse effects* ; Neuroprotective Agents/pharmacology* ; Propofol ; Neurotoxicity Syndromes/prevention & control* ; Central Nervous System/drug effects* ; Dexmedetomidine

Objective Dexmedetomidine is a highly selective alpha-2 adrenergic receptor agonist with sedative and analgesic properties but without respiratory depression effect and has been widely used in perioperative anesthesia. Here we performed a systematic review and meta-analysis to evaluate the effect of dexmedetomidine on maintaining perioperative hemodynamic stability in elderly patients.Methods PubMed, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang Data were searched for randomized-controlled trials (RCTs) on the application of dexmedetomidine in maintaining perioperative hemodynamic stability in elderly patients from their inception to September, 2021. The standardized mean differences (SMD) with 95% confidence interval (CI) were employed to analyze the data. The random-effect model was used for the potential clinical inconsistency.Results A total of 12 RCTs with 833 elderly patients (dexmedetomidine group, 546 patients; control group, 287 patients) were included. There was no significant increase in perioperative heart rate (HR), mean arterial pressure (MAP), and diastolic blood pressure (DBP) in the dexmedetomidine group before and during the operation. In addition, the variations of hemodynamic indexes including HR, MAP, SBP (systolic blood pressure), and DBP were significantly lower in the dexmedetomidine group compared with the control group (HR: SMD = -0.87, 95% CI: -1.13 to -0.62; MAP: SMD = -1.12, 95% CI: -1.60 to -0.63; SBP: SMD = -1.27, 95% CI: -2.26 to -0.27; DBP: SMD = -0.96, 95% CI: -1.33 to -0.59). Subgroup analysis found that with the prolongation of 1.0 μg/kg dexmedetomidine infusion, the patient's heart rate declined in a time-dependent way.Conclusion Dexmedetomidine provides more stable hemodynamics during perioperative period in elderly patients. However, further well-conducted trials are required to assess the effective and safer doses of dexmedetomidine in elderly patients.
Humans ; Aged ; Dexmedetomidine/adverse effects* ; Hemodynamics ; Hypnotics and Sedatives/pharmacology* ; Blood Pressure ; Heart Rate

OBJECTIVE: To investigate the effect of dexmedetomidine (DEX) on renal function after laparoscopic radical nephrectomy. METHODS: We reviewed the clinical data of 282 patients with renal cell carcinoma (RCC), who underwent laparoscopic radical nephrectomy (LRN) in the Department of Urology, Third Medical Center of PLA General Hospital from November, 2020 and June, 2022.According to whether DEX was used during the operation, the patients were divided into DEX group and control group, and after propensity score matching, 99 patients were finally enrolled in each group.The incidence of acute kidney injuries were compared between the two groups.Serum creatinine (sCr) data within 3 months to 1 year after the operation were available in 51 patients, including 26 in DEX group and 25 in the control group, and the incidence of chronic kidney disease (CKD) was compared between the two groups. RESULTS: After propensity score matching and adjustment for significant covariates, there were no significant differences in postoperative levels of sCr, cystatin C (CysC), β2-microglobulin (β2-MG), hemoglobin (Hb), or C-reactive protein (CRP), extubation time, incidence of AKI, or length of hospital stay between the two groups (P>0.05).The intraoperative urine volume was significantly higher in DEX group than in the control group (P < 0.05).A significant correlation between AKI and CKD was noted in the patients (P < 0.05).The incidence of CKD did not differ significantly between the two groups (P>0.05). CONCLUSION DEX can not reduce the incidence of AKI or CKD after LRN.
Humans ; Dexmedetomidine ; Incidence ; Propensity Score ; Renal Insufficiency, Chronic/epidemiology* ; Kidney Neoplasms/surgery* ; Nephrectomy/adverse effects* ; Laparoscopy/adverse effects* ; Acute Kidney Injury/prevention & control* ; Retrospective Studies

OBJECTIVES: To study the safety and efficacy of dexmedetomidine hydrochloride combined with midazolam in fiberoptic bronchoscopy in children. METHODS: A total of 118 children who planned to undergo fiberoptic bronchoscopy from September 2018 to February 2021 were enrolled. They were divided into a control group ( RESULTS: Compared with the control group, the observation group had significantly decreased MAP at T CONCLUSIONS Dexmedetomidine hydrochloride combined with midazolam is a safe and effective way to administer general anesthesia for fiberoptic bronchoscopy in children, which can ensure stable vital signs during examination, reduce intraoperative adverse reactions and postoperative agitation, shorten examination time, and increase amnesic effect.
Bronchi ; Bronchoscopy ; Child ; Dexmedetomidine/adverse effects* ; Humans ; Hypnotics and Sedatives/adverse effects* ; Midazolam ; Prospective Studies

PURPOSE: To investigate whether dexmedetomidine (Dex) can reduce the production of inflammatory factor IL-1β by inhibiting the activation of NLRP3 inflammasome in hippocampal microglia, thereby alleviating the inflammatory response of the central nervous system induced by surgical injury. METHODS: Exploratory laparotomy was used in experimental models in this study. Totally 48 Sprague Dawley male rats were randomly divided into 4 groups (n = 12 for each), respectively sham control (group A), laparotomy only (group B); and Dex treatment with different doses of 5 μg/kg (group D1) or 10 μg/kg (group D2). Rats in groups D1 and D2 were intraperitoneally injected with corresponding doses of Dex every 6 h. The rats were sacrificed 12 h after operation; the hippocampus tissues were isolated, and frozen sections were made. The microglia activation was estimated by immunohistochemistry. The protein expression of NLRP3, caspase-1, ASC and IL-1β were detected by immunoblotting. All data were presented as mean ± standard deviation, and independent sample t test was used to analyze the statistical difference between groups. RESULTS: The activated microglia in the hippocampus of the rats significantly increased after laparotomy (group B vs. sham control, p < 0.01). After Dex treatment, the number was decreased in a dose-dependent way (group D1 vs. D2, p < 0.05), however the activated microglia in both groups were still higher than that of sham controls (both p < 0.05). Further Western blot analysis showed that the protein expression levels of NLRP3, caspase-1, ASC and downstream cytokine IL-1β in the hippocampus from the laparotomy group were significantly higher than those of the sham control group (all p < 0.01). The elevated expression of these proteins was relieved after Dex treatment, also in a dose-dependent way (D2 vs. D1 group, p < 0.05). CONCLUSION Dex can inhibit the activation of microglia and NLRP3 inflammasome in the hippocampus of rats after operation, and the synthesis and secretion of IL-1β are also reduced in a dose-dependent manner by using Dex. Hence, Dex can alleviate inflammation activation on the central nervous system induced by surgical injury.
Animals ; Dexmedetomidine ; administration & dosage ; pharmacology ; Dose-Response Relationship, Drug ; Hippocampus ; metabolism ; Immunohistochemistry ; Inflammasomes ; metabolism ; Inflammation Mediators ; metabolism ; Injections, Intraperitoneal ; Interleukin-1beta ; metabolism ; Laparotomy ; adverse effects ; Male ; Microglia ; metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein ; metabolism ; Rats, Sprague-Dawley ; Time Factors

Transurethral resection has been the gold standard in the operative management of benign prostatic hyperplasia and bladder tumor; however, it is associated with several complications that may cause patient discomfort. We evaluated the usefulness of continuous infusion of dexmedetomidine on emergence agitation, hemodynamic status, and recovery profiles in patients undergoing elective surgery by a randomized clinical trial. Sixty patients aged 30 to 80 yr who were scheduled for elective transurethral resection under general anesthesia were included in this study. Participants were randomly assigned to two groups (control group, group C; dexmedetomidine group, group D). A total of 60 male patients were enrolled in this study and randomly assigned to group C (n=30) or group D (n=30). The quality of emergence in group D was marked by a significantly lower incidence of emergence agitation than in group C (P=0.015). Patients in group D therefore felt less discomfort induced by the indwelling Foley catheter than those in group C (P=0.022). No statistically significant differences were found between the two groups with respect to side effects including bradycardia (P=0.085), hypotension (P=0.640), and postoperative nausea and vomiting (P=0.389). Our study showed that intraoperative dexmedetomidine infusion effectively reduced the incidence and intensity of emergence agitation and catheter-induced bladder discomfort without delaying recovery time and discharge time, thus providing smooth emergence during the recovery period in patients undergoing transurethral resection (Clinical Trial Registry No. KT0001683).
Adult ; Aged ; Aged, 80 and over ; Blood Pressure ; Bradycardia/etiology ; Dexmedetomidine/adverse effects/*therapeutic use ; Hemodynamics ; Humans ; Hypnotics and Sedatives/adverse effects/*therapeutic use ; Hypotension/etiology ; Male ; Middle Aged ; Nausea/etiology ; Prostatic Hyperplasia/*surgery ; Psychomotor Agitation/*drug therapy ; *Transurethral Resection of Prostate ; Vomiting/etiology

PURPOSE: During emergence from anesthesia for a craniotomy, maintenance of hemodynamic stability and prompt evaluation of neurological status is mandatory. The aim of this prospective, randomized, double-blind study was to compare the effects of dexmedetomidine and remifentanil on airway reflex and hemodynamic change in patients undergoing craniotomy. MATERIALS AND METHODS: Seventy-four patients undergoing clipping of unruptured cerebral aneurysm were recruited. In the dexmedetomidine group, patients were administered dexmedetomidine (0.5 µg/kg) for 5 minutes, while the patients of the remifentanil group were administered remifentanil with an effect site concentration of 1.5 ng/mL until endotracheal extubation. The incidence and severity of cough and hemodynamic variables were measured during the recovery period. Hemodynamic variables, respiration rate, and sedation scale were measured after extubation and in the post-anesthetic care unit (PACU). RESULTS: The incidence of grade 2 and 3 cough at the point of extubation was 62.5% in the dexmedetomidine group and 53.1% in the remifentanil group (p=0.39). Mean arterial pressure (p=0.01) at admission to the PACU and heart rate (p=0.04 and 0.01, respectively) at admission and at 10 minutes in the PACU were significantly lower in the dexmedetomidine group. Respiration rate was significantly lower in the remifentanil group at 2 minutes (p<0.01) and 5 minutes (p<0.01) after extubation. CONCLUSION: We concluded that a single bolus of dexmedetomidine (0.5 µg/kg) and remifentanil infusion have equal effectiveness in attenuating coughing and hemodynamic changes in patients undergoing cerebral aneurysm clipping; however, dexmedetomidine leads to better preservation of respiration.
Adult ; Aged ; Airway Extubation ; *Anesthesia Recovery Period ; Cough/drug therapy ; *Craniotomy/adverse effects ; Dexmedetomidine/*pharmacology/therapeutic use ; Double-Blind Method ; Female ; Hemodynamics/*drug effects ; Humans ; Male ; Middle Aged ; Piperidines/*pharmacology/therapeutic use ; Prospective Studies ; Reflex/*drug effects ; Respiratory System/blood supply/*drug effects/physiopathology ; Young Adult

PURPOSETo evaluate midazolam sequential with dexmedetomidine for agitated patients undergoing weaning to implement light sedation in ICU.

METHODSThis randomized, prospective study was conducted in Tianjin Third Central Hospital, China. Using a sealed-envelope method, the patients were randomly divided into 2 groups (40 patients per group). Each patient of group A received an initial loading dose of midazolam at 0.3-3mg/kg·h 24 h before extubation, followed by an infusion of dexmedetomidine at a rate of 0.2-1 μg/kg·h until extubation. Each patient of group B received midazolam at a dose of 0.3-3 mg/kg·h until extubation. The dose of sedation was regulated according to RASS sedative scores maintaining in the range of -2-1. All patients were continuously monitored for 60 min after extubation. During the course, heart rate (HR), mean artery pressure (MAP), extubation time, adverse reactions, ICU stay, and hospital stay were observed and recorded continuously at the following time points: 24 h before extubation (T1), 12 h before extubation (T2), extubation (T3), 30 min after extubation (T4), 60 min after extubation (T5).

RESULTSBoth groups reached the goal of sedation needed for ICU patients. Dexmedetomidine was associated with a significant increase in extubation quality compared with midazolam, reflected in the prevalence of delirium after extubation (20% (8/40) vs 45% (18/40)), respectively (p= 0.017). There were no clinically significant decreases in HR and MAP after infusing dexmedetomidine or midazolam. In the group A, HR was not significantly increased after extubation; however, in the group B, HR was significantly increased compared with the preextubation values (p < 0.05). HR was significantly higher in the group B compared with the group A at 30 and 60 min after extubation (both, p <0.05). Compared with preextubation values, MAP was significantly increased at extubation in the group B (p < 0.05) and MAP was significantly higher at T3, T4, T5 in the group B than group A (p < 0.05). There was a significant difference in extubation time ((3.0 ± 1.5) d vs (4.3 ± 2.2) d, p < 0.05), ICU stay ((5.4 ± 2.1) d vs (8.0 ± 1.4) d, p < 0.05), hospital stay ((10.1 ± 3.0) d vs (15.3 ± 2.6) d, p <0.05) between group A and B.

CONCLUSIONMidazolam sequential with dexmedetomidine can reach the goal of sedation for ICU agitated patients, meanwhile it can maintain the respiratory and circulation parameters and reduce adverse reactions.

Adult ; Aged ; Critical Care ; methods ; Delirium ; drug therapy ; etiology ; Dexmedetomidine ; administration & dosage ; Female ; Humans ; Hypnotics and Sedatives ; administration & dosage ; Intensive Care Units ; Length of Stay ; Male ; Midazolam ; administration & dosage ; Middle Aged ; Prognosis ; Prospective Studies ; Respiration, Artificial ; adverse effects ; methods ; Risk Assessment ; Statistics, Nonparametric ; Treatment Outcome ; Ventilator Weaning ; adverse effects ; psychology

OBJECTIVETo investigate the protective effects of dexmedetomidine (Dex) against glutamate-induced cytotoxicity in PC12 cells and its mechanism.

METHODSPC12 cells were treated with varying concentrations of dexmedetomidine 1 h before exposure to a high concentration of glutamate. The cell viability was measured by MTT assay, and LDH release, MDA content and SOD activity were measured. The level of ROS was tested by DCFH-DA staining and flow cytometry. The level of intracellular Cawas detected by Fluo-8 staining and flow cytometry, and the mitochondrial membrane potential (MMP) was determined with JC-1 staining and flow cytometry.

RESULTSWithin the concentration range of 0.01 to 100 µmol/L, Dex dose-dependently protected PC12 cells against glutamate-induced cytotoxicity. Treatment with 100 µmol/L Dex significantly increased the cell viability to (86.6∓2.2)% of that of the control cells (P<0.01) and decreased LDH release to 1.4∓0.1 folds of the control level (P<0.01). In PC12 cells exposed to glutamate, Dex pretreatment significantly reduced MDA content (P<0.01), enhanced SOD activity (P<0.01), inhibited ROS overproduction (P<0.01), reduced intracellular Calevel (P<0.01) and maintained a stable MMP (P<0.01).

CONCLUSIONDexmedetomidine can protect PC12 cells against glutamate-induced injury possibly in relation with its anti-oxidative activity, inhibitory effect on intracellular calcium overload and protective effect of the mitochondria.

Animals ; Apoptosis ; Calcium ; metabolism ; Cell Survival ; drug effects ; Dexmedetomidine ; pharmacology ; Glutamic Acid ; adverse effects ; Membrane Potential, Mitochondrial ; Mitochondria ; drug effects ; metabolism ; PC12 Cells ; Rats ; Reactive Oxygen Species ; metabolism

PURPOSE: Intranasal dexmedetomidine is an effective sedative for premedication and is regularly used to reduce preoperative tension and anxiety in children. This study aimed to assess the effect of intranasally adjunctive dexmedetomidine on perioperative sedative and analgesic requirements in adults. MATERIALS AND METHODS: Patients were randomly divided into four groups to receive preoperative administration of saline, intranasal dexmedetomidine 1 µg/kg and 2 µg/kg, and intravenous dexmedetomidine 1 µg/kg, respectively. Propofol and remifentanil were target-controlled infused to maintain intraoperative bispectral index at 45-55 and blood pressure at baseline value±20%. Sufentanil was administered to maintain postoperative visual analogue scale ≤3. Perioperative anesthetics requirements were compared using nonparametric tests. RESULTS: Intranasal dexmedetomidine significantly attenuated propofol requirements for anesthesia induction and maintenance in a dose-dependent manner. Patients given intranasal dexmedetomidine 2 µg/kg required less remifentanil for anesthesia maintenance. The first postoperative request for sufentanil analgesia was delayed in patients given intranasal dexmedetomidine 2 µg/kg. The anesthetics-sparing effect of intranasal dexmedetomidine was significantly weaker than intravenous dexmedetomidine at the same dose of 1 µg/kg. The incidences of adverse events, including hemodynamic instability and delayed recovery, were comparable with and without intranasal dexmedetomidine. CONCLUSION: Intranasal administration of dexmedetomidine can reduce perioperative anesthetic requirements, and a dose of dexmedetomidine 2 µg/kg produces a better effect in adults. The anesthetics-sparing effect of intranasal dexmedetomidine 1 µg/kg is less than that with the same intravenous dose of dexmedetomidine.
*Administration, Intranasal ; Adult ; *Anesthesia, General ; Child ; Dexmedetomidine/*administration & dosage/adverse effects/*pharmacology ; Double-Blind Method ; Female ; Humans ; Hypnotics and Sedatives/*administration & dosage/adverse effects/*pharmacology ; Male ; Middle Aged ; Pain Measurement ; *Perioperative Care ; Premedication