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Dexmedetomidine as an adjunct to peripheral nerve blocks in pediatric patients

World Journal of Pediatrics 2022年第4期18卷 251-262页

作者： Jing Yang Yu Cui Rong Cao Qing-Hua Huang Qian-Qian Zhang Department of Anesthesiology The Affiliated HospitalSchool of MedicineUESTC Chengdu Women’s&Children’s Central HospitalNo.1617Riyue AvenueQingyang DistrictChengdu 610091China

Background Combining local anesthetics with Dexmedetomidine(DEX)for nerve blocks has been tested and confirmed as an alternative technique to strengthen analgesia in adults,but the evidence supported this proposal in pediatrics was not convincing enough.Thus,we intend to conduct a meta-analysis to make an appraisal of the effects of DEX as a local anesthetic adjuvant on peripheral nerve blocks in children.Methods The analysis has been registered on https://www.***.york.***.uk/prospero/with the registration number CRD42021254029 on June 10th,2021.PubMed,Ovid MEDLINE,Embase and Cochrane central register were searched for the randomized controlled trials(RCTs)that are relevant to child/pain/DEX or block up to April 30,2021.Results Eight RCTs were included for data analysis.The pooled results showed a significantly reduced number of patients who required postoperative analgesics within DEX groups[odds ratio=0.1,95%confidence interval(CI)0.03-0.32,P<0.001].And DEX significantly prolonged the duration of analgesia of local anesthetics in the meantime[standardized mean difference(SMD)=4.93,95%CI 3.02-6.83,P<0.001].Nevertheless,adding DEX as an adjunct to local anesthetics would significantly decrease heart rate(SMD=-0.95,95%CI-1.45 to-0.45,P<0.001)and increase sedation score(SMD=1.6,95%CI 0.53-2.66,P=0.003)simultaneously.Conclusions Adding DEX as an adjunct to peripheral nerve blocks can prolong analgesia until postoperative 8 hours in pediatric patients.However,the benefits should be weighed against the increasing risk of bradycardia and sedation in critical children.

关键词： Block Child Dexmedetomidine Pain

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Perioperative Dexmedetomidine administration does not reduce the risk of acute kidney injury after non-cardiac surgery:a meta-analysis

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Chinese Medical Journal 2022年第23期135卷 2798-2804页

作者： Bin Hu Tian Tian Xintao Li Weichao Liu Yinggui Chen Tianyu Jiang Peishan Chen Fushan Xue Department of Anesthesiology Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China

Background:Post-operative acute kidney injury(AKI)is one of the most common and serious complications after major surgery and is significantly associated with increased risks of morbidity and mortality.This meta-analysis was conducted to evaluate the effects of perioperative Dexmedetomidine(Dex)administration on the occurrence of AKI and the outcomes of recovery after non-cardiac surgery.Methods:The PubMed,Embase,Web of Science,and Cochrane Library databases were systematically searched for studies comparing the effects of Dexvs.placebo on kidney function after non-cardiac surgery,and a pooled fixed-effect meta-analysis of the included studies was performed.The primary outcome was the occurence of post-operative AKI.The secondary outcomes included the occurence of intra-operative hypotension and bradycardia,intensive care unit(ICU)admission,duration of ICU stay,and hospital length of stay(LOS).Results:Six studies,including four randomized controlled trials(RCTs)and two observational studies,with a total of 2586 patients were selected.Compared with placebo,Dex administration could not reduce the odds of post-operative AKI(odds ratio[OR],0.44;95%confidence interval(CI),0.18-1.06;P=0.07;I^(2)=0.00%,P=0.72)in RCTs,but it showed a significant renoprotective effect(OR,0.67;95%CI,0.48-0.95;P=0.02;I^(2)=0.00%,P=0.36)in observational studies.Besides,Dex administration significantly increased the odds of intra-operative bradycardia and shortened the duration of ICU stay.However,there was no significant difference in the odds of intra-operative hypotension,ICU admission,and hospital LOS.Conclusions:This meta-analysis suggests that perioperative Dex administration does not reduce the risk of AKI after non-cardiac surgery.However,the quality of evidence for this result is low due to imprecision and inconsistent types of non-cardiac operations.Thus,large and high-quality RCTs are needed to verify the real effects of perioperative Dex administration on the occurrence of AKI and the outcomes of recovery after non-cardiac surgery

关键词： Dexmedetomidine Non-cardiac surgery Acute kidney injury Meta-analysis

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Comparative observation of the effectiveness and safety of remimazolam besylate versus Dexmedetomidine in gastrointestinal surgery in obese patients

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WORLD JOURNAL OF GASTROINTESTINAL SURGERY 2024年第5期16卷 1320-1327页

作者： Deng, Yu-Fu Jiang, Xue-Run Feng, Zeng-Guang Xiangtan Cent Hosp Dept Anesthesiol 120 Heping Rd Xiangtan 411100 Hunan Peoples R China

BACKGROUND Surgery for obese patients carries a higher risk of anesthesia complications compared with surgery for nonobese patients. Thus, a safe and effective anesthesia strategy is necessary to improve the medical experience of such patients and ensure their safety. AIM To compared the effectiveness and safety of remimazolam besylate versus Dexmedetomidine (DEX) in gastrointestinal surgery in obese patients. METHODS The study cohort included 60 obese patients undergoing gastrointestinal surgery between July 2021 and April 2023, comprising 30 patients who received DEX intervention (control group) and 30 patients who received remimazolam besylate intervention (research group). Heart rate (HR), respiratory rate (RR), mean arterial pressure (MAP), blood oxygen saturation (SpO(2)), safety (nausea and vomiting, bradycardia, hypotension, and apnea), anesthesia and examination indices [induction time, anesthesia recovery time, and postanesthesia care unit (PACU) discharge time], sedation effect (Ramsay Sedation Scale), and postoperative pain visual analog scale were comparatively analyzed before anesthesia (T0), during anesthesia (T1), and after anesthesia (T2). RESULTS At T1, the research group showed significantly smaller changes in HR, RR, MAP, and SpO(2) than the control group, with a significantly lower adverse reaction rate and shorter induction, anesthesia recovery, and PACU discharge times. Additionally, the intra- and postoperative Ramsay Sedation Scale scores were statistically higher in the research group than in the control group. CONCLUSION Remimazolam besylate was significantly more effective than DEX in gastrointestinal surgery in obese patients and had a higher safety profile and value in clinical promotion.

关键词： Remimazolam besylate Dexmedetomidine Obesity Gastrointestinal surgery Effectiveness Safety SEDATION EFFICACY

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Brain protective effect of Dexmedetomidine vs propofol for sedation during prolonged mechanical ventilation in non-brain injured patients

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World Journal of Psychiatry 2024年第3期14卷 370-379页

作者： Hong-Xun Yuan Li-Na Zhang Gang Li Li Qiao Intensive Care Unit Peking University International HospitalBeijing 102206China Central Operating Room The Affiliated Beijing Chaoyang Hospital of Capital Medical UniversityBeijing 100020China

BACKGROUND Dexmedetomidine and propofol are two sedatives used for long-term sedation.It remains unclear whether Dexmedetomidine provides superior cerebral protection for patients undergoing long-term mechanical ventilation.AIM To compare the neuroprotective effects of Dexmedetomidine and propofol for sedation during prolonged mechanical ventilation in patients without brain injury.METHODS Patients who underwent mechanical ventilation for>72 h were randomly assigned to receive sedation with Dexmedetomidine or propofol.The Richmond Agitation and Sedation Scale(RASS)was used to evaluate sedation effects,with a target range of-3 to 0.The primary outcomes were serum levels of S100-βand neuron-specific enolase(NSE)every 24 h.The secondary outcomes were remifentanil dosage,the proportion of patients requiring rescue sedation,and the time and frequency of RASS scores within the target range.RESULTS A total of 52 and 63 patients were allocated to the Dexmedetomidine group and propofol group,respectively.Baseline data were comparable between groups.No significant differences were identified between groups within the median duration of study drug infusion[52.0(IQR:36.0-73.5)h vs 53.0(IQR:37.0-72.0)h,P=0.958],the median dose of remifentanil[4.5(IQR:4.0-5.0)μg/kg/h vs 4.6(IQR:4.0-5.0)μg/kg/h,P=0.395],the median percentage of time in the target RASS range without rescue sedation[85.6%(IQR:65.8%-96.6%)vs 86.7%(IQR:72.3%-95.3),P=0.592],and the median frequency within the target RASS range without rescue sedation[72.2%(60.8%-91.7%)vs 73.3%(60.0%-100.0%),P=0.880].The proportion of patients in the Dexmedetomidine group who required rescue sedation was higher than in the propofol group with statistical significance(69.2%vs 50.8%,P=0.045).Serum S100-βand NSE levels in the propofol group were higher than in the Dexmedetomidine group with statistical significance during the first six and five days of mechanical ventilation,respectively(all PDexmedetomidine demonstrated stronger protective effects on the brain compare

关键词： Dexmedetomidine Propofol Sedation Prolonged mechanical ventilation Brain protective

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Effect of Dexmedetomidine on Maintaining Perioperative Hemodynamic Stability in Elderly Patients:A Systematic Review and Meta-analysis

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Chinese Medical Sciences Journal 2023年第1期38卷 1-10页

作者： Li-Juan Tian Yun-Tai Yao Su Yuan Zheng Dai Department of Anesthesiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100037China Department of Anesthesiology Yunnan Fuwai Cardiovascular HospitalKunming 650102China

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 1.0μg/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.

关键词： Dexmedetomidine elderly patient hemodynamics perioperative period

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Dexmedetomidine Promotes Angiogenesis and Vasculogenic Mimicry in Human Hepatocellular Carcinoma through α^(2)-AR/HIF-1α/VEGFA Pathway

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Biomedical and Environmental Sciences 2022年第10期35卷 931-942页

作者： FANG Tao LIN Li YE Zhi Jian FANG Lian SHI Shuai YU Ke Da MIAO Hui Hui LI Tian Zuo Department of Anesthesiology Beijing Shijitan HospitalCapital Medical UniversityBeijing 100038China Department of Anesthesiology The Affiliated Jinhua Hospital of Wenzhou Medical UniversityJinhua 321000ZhejiangChina IVF centre The Affiliated Jinhua Hospital of Wenzhou Medical UniversityJinhua 321000ZhejiangChina

Objective Dexmedetomidine(DEX),the most specificα^(2)-adrenergic receptor agonist widely used for its sedative and analgesic properties,has been reported to upregulate HIF-1αexpression to protect hypoxic and ischemic tissues.However,it is largely unclear whether DEX can also upregulate Hypoxiainducible factor-1 alpha(HIF-1α)expression and its downstream vascular endothelial growth factor-A(VEGFA)in cancer tissues with oxygen-deficient tumor microenvironment.Methods We used SMMC-7721 cells,MHCC97-H cells,and a mouse model of orthotopic hepatic carcinoma to explore the effect of DEX on angiogenesis and vasculogenic mimicry(VM)and its mechanism.Under normoxic(20%O^(2))and hypoxic(1%O^(2))conditions,DEX was used to intervene cells,and yohimbine was used to rescue them.Results The results showed that DEX promoted angiogenesis and VM in human liver cancer cells within a certain dose range,and the addition of yohimbine inhibited this effect.DEX could activate HIF-1α/VEGFA pathway,which was further verified by silencing HIF-1α.Consistently,in vivo results also showed that DEX can up-regulate HIF-1α/VEGFA expression,and enhance the number of VM channels and microvessel density(MVD).Conclusion We believe that HIF-1α/VEGFA might be an important signaling pathway by which DEX promotes angiogenesis and VM formation in human hepatocellular carcinoma,whereasα^(2)-adrenergic receptor mediation might be the critical mechanisms.

关键词： Hepatocellular carcinoma Dexmedetomidine Yohimbine α^(2)-adrenergic receptor HIF-1a VEGFA Vascular mimicry Angiogenesis

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Dexmedetomidine Attenuates High Glucose-induced HK-2 Epithelial-mesenchymal Transition by Inhibiting AKT and ERK

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Biomedical and Environmental Sciences 2020年第5期33卷 323-330页

作者： PAN Qi Zheng LI Kai YANG Zhuo Dong GAO Ming SHI Jia Hong REN Shu Ping ZHAO Guo Qing Department of Anesthesiology China-Japan Union HospitalJilin UniversityChangchun 130033JilinChina Department of Occupational and Environmental Health School of Public HealthJilin UniversityChangchun 130021JilinChina Department of Ultrasound China-Japan Union HospitalJilin UniversityChangchun 130033JilinChina

Objective To explore the protective effects of Dexmedetomidine(Dex)against high glucose-induced epithelial-mesenchymal transition in HK-2 cells and relevant mechanisms.Methods HK-2 cells were exposed to either glucose or glucose+Dex for 6 h.The production of ROS,morphology of HK-2 cells,and cell cycle were detected.Moreover,the expression of AKT,p-AKT,ERK,pERK,PI3 K,E-Cadherin,Claudin-1,andα-SMA were determined and compared between HK-2 cells exposed to glucose and those exposed to both glucose and Dex with or without PI3 K/AKT pathway inhibitor LY294002 and ERK pathway inhibitor U0126.Results Compared with HK-2 cells exposed to high level of glucose,the HK-2 cells exposed to both high level of glucose and Dex showed:(1)lower level of ROS production;(2)cell morphology was complete;(3)more cells in G1 phase;(4)lower expression of p-AKT,p-ERK andα-SMA,higher expression of ECadherin and Claudin-1.PI3 K/AKT inhibitor LY294002 and ERK inhibitor U0126 decreased the expression of p-AKT,p-ERK andα-SMA,and increased the expression of E-Cadherin and Claudin-1.Conclusion Dex can attenuate high glucose-induced HK-2 epithelial-mesenchymal transition by inhibiting AKT and ERK.

关键词： Dexmedetomidine Epithelial-mesenchymal transition High glucose Oxidative stress HK-2 cells

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Tiletamine/zolazepam and Dexmedetomidine with tramadol provide effective general anesthesia in rats

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Animal Models and Experimental Medicine 2021年第1期4卷 40-46页

作者： Vudhiporn Limprasutr Patrick Sharp Katechan Jampachaisri Cholawat Pacharinsak Sumit Durongphongtorn Department of Pharmacology and Physiology Faculty of Pharmaceutical SciencesChulalongkorn UniversityBangkokThailand Research Clusters:Preclinical Toxicity and Efficacy Assessment of Medicines and Chemicals Chulalongkorn UniversityBangkokThailand Animal Resources Centre MurdochWAAustralia Department of Mathematics Faculty of SciencesNaresuan UniversityPhitsanulokThailand Department of Comparative Medicine School of MedicineStanford UniversityStanfordCAUSA Department of Veterinary Surgery Faculty of Veterinary ScienceChulalongkorn UniversityBangkokThailand

Background:Tiletamine/zolazepam is a dissociative anesthetic combination commonly used in small animals but information is limited in rats.The alpha-2 agonist,Dexmedetomidine,has gained popularity in laboratory animal anesthesia.Tramadol is a weak opioid mu agonist.The aim of this study was to assess whether the tiletamine/zolazepam/Dexmedetomidine(ZD)combination effectively provides a surgical anesthesia plane comparable to tiletamine/zolazepam/Dexmedetomidine with tramadol(ZDT)in a minor procedure in rats.Methods:Rats were induced with ZD or ZDT.After the loss of paw withdrawal,a small incision was made on the rats’left thighs as a surgical stimulus.Rats were maintained under a surgical anesthesia plane by assessing the loss of the paw withdrawal reflex for 45 minutes,then atipamezole was administered.Monitored anesthesia parameters included:(a)physiological parameters-pulse rate(PR),respiratory rate(RR),tissue oxygen saturation(%SpO 2),and body temperature;(b)duration parameters-induction time,onset and duration of surgical anesthesia plane,onset of recovery,and recovery time.Results:PR was significantly lower at 10 minutes in ZD and 5 minutes in ZDT groups.No difference was observed for RR,%SpO 2,and body temperature.Likewise,there were no differences for duration parameters:induction time was less than 3 minutes;onset and duration of surgical anesthesia plane were approximately 5 and 45 minutes,respectively;onset of recovery(time to move)was 51 minutes;and recovery time was 52 minutes,respectively.Conclusion:These data suggest the ZD combination provides a surgical anesthesia plane comparable to ZDT in a rat incisional pain model.

关键词： anesthesia Dexmedetomidine rats tiletamine tramadol

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Dexmedetomidine attenuates inflammation and pancreatic injury in a rat model of experimental severe acute pancreatitis via cholinergic anti-inflammatory pathway

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Chinese Medical Journal 2020年第9期133卷 1073-1079页

作者： Dong-Ya Huang Qiang Li Chen-Yuan Shi Chao-Qun Hou Yi Miao Hong-Bing Shen Department of Pancreas Center The First Affiliated Hospital with Nanjing Medical UniversityNanjingJiangsu 210029China Department of Epidemiology and Biostatistics School of Public HealthNanjing Medical UniversityNanjingJiangsu 211116China

Background:Excessive inflammatory responses play a critical role in the development of severe acute pancreatitis(SAP),and controlling such inflammation is vital for managing this often fatal disease.Dexmedetomidine has been reported to possess protective properties in inflammatory diseases.Therefore,this study aimed to investigate whether Dexmedetomidine pre-treatment exerts an anti-inflammatory effect in rats with SAP induced by sodium taurocholate,and if so,to determine the potential mechanism.Methods:SAP was induced with sodium taurocholate.Rats received an intraperitoneal injection of Dexmedetomidine 30 min before sodium taurocholate administration.α-bungarotoxin,a selective alpha-7 nicotinic acetylcholine receptor(α7nAchR)antagonist,was injected intra-peritoneally 30 min before Dexmedetomidine administration.The role of the vagus nerve was evaluated by performing unilateral cervical vagotomy before the administration of Dexmedetomidine.Efferent discharge of the vagal nerve was recorded by the BL-420F Data Acquisition&Analysis System.Six hours after onset,serum pro-inflammatory cytokine(tumor necrosis factorα[TNF-α]and interleukin 6[IL-6])levels and amylase levels were determined using an enzyme-linked immunosorbent assay and an automated biochemical analyzer,respectively.Histopathological changes in the pancreas were observed after hematoxylin and eosin staining and scored according to Schmidt criteria.Results:Pre-treatment with Dexmedetomidine significantly decreased serum levels of TNF-α,IL-6,and amylase,strongly alleviating pathological pancreatic injury in the rat model of SAP(TNF-α:174.2±30.2 vs.256.1±42.4 pg/ml;IL-6:293.3±46.8 vs.421.7±48.3 pg/ml;amylase:2102.3±165.3 vs.3186.4±245.2 U/L).However,the anti-inflammatory and pancreatic protective effects were abolished after vagotomy or pre-administration ofα-bungarotoxin.Dexmedetomidine also significantly increased the discharge frequency and amplitude of the cervical vagus nerve in the SAP rat model(discharge frequency:456.8±50.3 vs.332.4±25.1 Hz;dischar

关键词： Dexmedetomidine Severe acute pancreatitis Cholinergic anti-inflammatory pathway Inflammation Vagus nerve α7nAChR

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Brain interstitial fluid drainage and extracellular space affected by inhalational isoflurane: in comparison with intravenous sedative Dexmedetomidine and pentobarbital sodium

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Science China(Life Sciences) 2020年第9期63卷 1363-1379页

作者： Guomei Zhao Hongbin Han Jun Yang Min Sun Dehua Cui Yuanyuan Li Yajuan Gao Jing Zou Department of Radiology Peking University Third HospitalBeijing 100191China Beijing Key Laboratory of Magnetic Resonance Imaging Technology Beijing 100191China Institute of Medical Technology Peking UniversityBeijing 100191China Department of Neurosurgery Peking University Third HospitalBeijing 100191China Department of Cardiology Peking University Shougang HospitalBeijing 100144China

Brain interstitial fluid drainage and extracellular space are closely related to waste clearance from the brain. Different anesthetics may cause different changes of brain interstitial fluid drainage and extracellular space but these still remain unknown. Herein,effects of the inhalational isoflurane, intravenous sedative Dexmedetomidine and pentobarbital sodium on deep brain matters’ interstitial fluid drainage and extracellular space and underlying mechanisms were investigated. When compared to intravenous anesthetic Dexmedetomidine or pentobarbital sodium, inhalational isoflurane induced a restricted diffusion of extracellular space, a decreased extracellular space volume fraction, and an increased norepinephrine level in the caudate nucleus or thalamus with the slowdown of brain interstitial fluid drainage. A local administration of norepinephrine receptor antagonists, propranolol,atipamezole and prazosin into extracellular space increased diffusion of extracellular space and interstitial fluid drainage whilst norepinephrine decreased diffusion of extracellular space and interstitial fluid drainage. These findings suggested that restricted diffusion in brain extracellular space can cause slowdown of interstitial fluid drainage, which may contribute to the neurotoxicity following the waste accumulation in extracellular space under inhaled anesthesia per se.

关键词： interstitial fluid deep brain extracellular space isoflurane Dexmedetomidine pentobarbital sodium norepinephrine

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