Respiratory complications of propofol,sevoflurane,and dexmedetomidine anesthesia for fiberoptic bronchoscopy in children aged 1 month to 3 years:a randomized trial

Objective To evaluate the effect of propofol,sevoflurane,and dexmedetomidine on respiratory complications inchildren undergoing fiberoptic bronchoscopy(FOB).Methods This double-blind randomized clinical trial was conductedamong 120 children aged 1 month to 3 years undergoing FOB.The patients were randomized into 3 groups(n=40)foranesthesia induction with sevoflurane inhalation,1 mg/kg propofol,or 1μg/kg dexmedetomidine before bronchoscopy,andthe changes in hemodynamic parameters,sedation level,and respiratory complications during and after the procedure wereassessed.Results The patients'heart rate during bronchoscopy was significantly lower and the mean arterial blood pressuresignificantly higher in dexmedetomidine group than in sevoflurane and propofol groups(P<0.05).Cough duringbronchoscopy did not occur in any of the cases in propofol group,while the highest frequency of cough was recorded indexmedetomidine group.The incidence of laryngospasm in the propofol group(12.5%)was significantly lower than those insevoflurane and dexmedetomidine groups(30%and 32.5%,respectively)(P<0.05).Conclusion Sevoflurane and propofol aresafe and suitable for anesthesia induction in children below 3 years of age undergoing diagnostic FOB and can achieve bettersedative effect and lower the incidences of cough and respiratory complications as compared with dexmedetomidine.

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

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.

Dexmedetomidine ameliorates diabetic intestinal injury by promoting the polarization of M2 macrophages through the MMP23B pathway

BACKGROUND Diabetes is often associated with gastrointestinal dysfunctions,which can lead to hypoglycemia.Dexmedetomidine(DEX)is a commonly used sedative in perioperative diabetic patients and may affect gastrointestinal function.AIM To investigate whether sedative doses of DEX alleviate diabetes-caused intestinal dysfunction.METHODS Sedation/anesthesia scores and vital signs of streptozotocin(STZ)-induced diabetic mice under DEX sedation were observed.Diabetic mice were divided into saline and DEX groups.After injecting sedatives intraperitoneally,tight junctions(TJs)and apoptotic levels were evaluated 24 hours later to assess the intestinal barrier function.The role of DEX was validated using Villin-MMP23B flox/flox mice with intestinal epithelial deletion.In vitro,high glucose and hyperosmolarity were used to culture Caco-2 monolayer cells with STZ intervention.Immunofluorescence techniques were used to monitor the barrier and mitochondrial functions.RESULTS MMP23B protein levels in the intestinal tissue of STZ-induced diabetic mice were significantly higher than those in the intestinal tissue of control mice,with the DEX group displaying decreased MMP23B levels.Diabetes-mediated TJ disruption,increased intestinal mucosal permeability,and systemic inflammation in wild-type mice might be reversed by DEX.In Caco-2 cells,MMP23B was associated with increased reactive oxygen species accumulation,mitochondrial membrane potential depolarization,and TJ disruption.CONCLUSION DEX reduces MMP23B,which may potentially contribute to STZ-induced intestinal barrier dysfunction,affecting TJ modification through mitochondrial dysfunction.

Effects of ulinastatin combined with dexmedetomidine on cognitive dysfunction and emergence agitation in elderly patients who underwent total hip arthroplasty

BACKGROUND With the continuous growth of the modern elderly population,the risk of fracture increases.Hip fracture is a common type of fracture in older people.Total hip arthroplasty(THA)has significant advantages in relieving chronic pain and promoting the recovery of hip joint function.AIM To investigate the effect of ulinastatin combined with dexmedetomidine(Dex)on the incidences of postoperative cognitive dysfunction(POCD)and emergence agitation in elderly patients who underwent THA.METHODS A total of 397 patients who underwent THA from February 2019 to August 2022.We conducted a three-year retrospective cohort study in Shaanxi Provincial People’s Hospital.Comprehensive demographic data were obtained from the electronic medical record system.We collected preoperative,intraoperative,and postoperative data.One hundred twenty-nine patients who were administered Dex during the operation were included in the Dex group.One hundred fifty patients who were intravenously injected with ulinastatin 15 min before anesthesia induction were included in the ulinastatin group.One hundred eighteen patients who were administered ulinastatin combined with Dex during the operation were included in the Dex+ulinastatin group.The patients’perioperative conditions,hemodynamic indexes,postoperative Mini-Mental State Examination(MMSE)scores,Ramsay score,incidence of POCD,and serum inflammatory cytokines were evaluated.RESULTS There was a significant difference in the 24 h visual analogue scale score among the three groups,and the score in the Dex+ulinastatin group was the lowest(P<0.05).Compared with the Dex and ulinastatin group,the MMSE scores of the Dex+ulinastatin group were significantly increased at 1 and 7 d after the operation(all P<0.05).Compared with those in the Dex and ulinastatin groups,incidence of POCD,levels of serum inflammatory cytokines in the Dex+ulinastatin group were significantly decreased at 1 and 7 d after the operation(all P<0.05).The observer’s assessment of the alertness/sedation score and Ramsay score of the Dex+ulinastatin group were significantly different from those of the Dex and ulinastatin groups on the first day after the operation(all P<0.05).CONCLUSION Ulinastatin combined with Dex can prevent the occurrence of POCD and emergence agitation in elderly patients undergoing THA.

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

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 P<0.05).CONCLUSION Dexmedetomidine demonstrated stronger protective effects on the brain compared to propofol for long-term mechanical ventilation in patients without brain injury.

Impact of dexmedetomidine-assisted anesthesia in elderly patients undergoing radical resection of colon cancer

BACKGROUND Radical resection of colon cancer under general anesthesia is one of the main treatment methods for this malignancy.However,due to the physiological charac-teristics of elderly patients,the safety of perioperative anesthesia needs special attention.As anα2-adrenergic receptor agonist,dexmedetomidine(Dex)has attracted much attention from anesthesiologists due to its stabilizing effect on heart rate and blood pressure,inhibitory effect on inflammation,and sedative and analgesic effects.Its application in general anesthesia may have a positive impact on the quality of anesthesia and postoperative recovery in elderly patients undergoing radical resection of colon cancer.METHODS A total of 165 colon cancer patients who underwent radical surgery for colon cancer under general anesthesia at Qingdao University Affiliated Haici Hospital,Qingdao,China were recruited and divided into two groups:A and B.In group A,Dex was administered 30 min before surgery,while group B received an equivalent amount of normal saline.The hemodynamic changes,pulmonary compliance,airway pressure,inflammatory factors,confusion assessment method scores,Ramsay Sedation-Agitation Scale scores,and cellular immune function indicators were compared between the two groups.RESULTS Group A showed less intraoperative hemodynamic fluctuations,better pulmonary compliance,and lower airway resistance compared with group B.Twelve hours after the surgery,the serum levels of TLR-2,TLR-4,IL-6,and TNF-αin group A were significantly lower than those of group B(P<0.05).After extubation,the Ramsay Sedation-Agitation Scale score of group A patients was significantly higher than that of group B patients,indicating a higher level of sedation.The incidence of delirium was significantly lower in group A than in group B(P<0.05).CONCLUSION The use of Dex as an adjunct to general anesthesia for radical surgery in elderly patients with colon cancer results in better effectiveness of anesthesia.

Application value of dexmedetomidine in anesthesia for elderly patients undergoing radical colon cancer surgery

BACKGROUND Colon cancer presents a substantial risk to the well-being of elderly people worldwide.With advancements in medical technology,surgical treatment has become the primary approach for managing colon cancer patients.However,due to age-related physiological changes,especially a decline in cognitive function,older patients are more susceptible to the effects of surgery and anesthesia,increasing the relative risk of postoperative cognitive dysfunction(POCD).There-fore,in the surgical treatment of elderly patients with colon cancer,it is of pa-ramount importance to select an appropriate anesthetic approach to reduce the occurrence of POCD,protect brain function,and improve surgical success rates.METHODS One hundred and seventeen patients with colon cancer who underwent elective surgery under general anesthesia were selected and divided into two groups:A and B.Group A received Dex before anesthesia induction,and B group received an equivalent amount of normal saline.Changes in the mini-mental state exami-nation,regional cerebral oxygen saturation(rSO2),bispectral index,glucose uptake rate(GluER),lactate production rate(LacPR),serum S100βand neuron-specific enolase(NSE),POCD,and adverse anesthesia reactions were compared between the two groups.RESULTS Surgical duration,duration of anesthesia,and intraoperative blood loss were comparable between the two groups(P>0.05).The overall dosage of anesthetic drugs used in group A,including propofol and remifentanil,was significantly lower than that used in group B(P<0.05).Group A exhibited higher rSO2 values at the time of endotracheal intubation,30 min after the start of surgery,and immediately after extubation,higher GluER values and lower LacPR values at the time of endotra-cheal intubation,30 min after the start of surgery,immediately after extubation,and 5 min after extubation(P<0.05).Group A exhibited lower levels of serum S100βand NSE 24 h postoperatively and a lower incidence of cognitive dysfunction on the 1st and 5th postoperative days(P<0.05).CONCLUSION The use of Dex in elderly patients undergoing radical colon cancer surgery helps maintain rSO2 Levels and reduce cerebral metabolic levels and the incidence of anesthesia-and surgery-induced cognitive dysfunction.

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

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.

Influences of dexmedetomidine on stress responses and postoperative cognitive and coagulation functions in patients undergoing radical gastrectomy under general anesthesia

BACKGROUND Radical gastrectomy(RG)is commonly used in the treatment of patients with gastric cancer(GC),but this procedure may lead to stress responses,postoperative cognitive dysfunction,and blood coagulation abnormalities in patients.AIM To investigate the influences of dexmedetomidine(DEX)on stress responses and postoperative cognitive and coagulation functions in patients undergoing RG under general anesthesia(GA).METHODS One hundred and two patients undergoing RG for GC under GA from February 2020 to February 2022 were retrospectively reviewed.Of these,50 patients had received conventional anesthesia intervention[control group(CG)]and 52 patients had received DEX in addition to routine anesthesia intervention[observation group(OG)].Inflammatory factor(IFs;tumor necrosis factor-α,TNF-α;interleukin-6,IL-6),stress responses(cortisol,Cor;adrenocorticotropic hormone,ACTH),cognitive function(CF;Mini-Mental State Examination,MMSE),neurological function(neuron-specific enolase,NSE;S100 calciumbinding protein B,S100B),and coagulation function(prothrombin time,PT;thromboxane B2,TXB2;fibrinogen,FIB)were compared between the two groups before surgery(T0),as well as at 6 h(T1)and 24 h(T2)after surgery.RESULTS Compared with T0,TNF-α,IL-6,Cor,ACTH,NSE,S100B,PT,TXB2,and FIB showed a significant increase in both groups at T1 and T2,but with even lower levels in OG vs CG.Both groups showed a significant reduction in the MMSE score at T1 and T2 compared with T0,but the MMSE score was notably higher in OG compared with CG.CONCLUSION In addition to a potent inhibitory effect on postoperative IFs and stress responses in GC patients undergoing RG under GA,DEX may also alleviate the coagulation dysfunction and improve the postoperative CF of these patients.

Clinical Observation of Hemodynamic and Cerebral Protective Effects of Different Doses of Dexmedetomidine in Patients with Traumatic Brain Injury

Background: Patients with craniocerebral trauma may suffer ischemic brain injury and neurological dysfunction due to immune inflammation and neuroendocrine reactions. Dexmedetomidine (Dex) is one of the commonly used anesthetic drugs in clinic. Studies have shown Dex has the function of protecting brain nerves and inhibiting inflammation. However, there are few studies on the effects of different doses of dexmedetomidine on patients undergoing surgery. The purpose of this study is to observe the effects of different doses of Dex on hemodynamics and brain protection in patients undergoing brain trauma surgery. Materials and Methods: Eighty patients with craniocerebral trauma surgery were randomly divided into study group (group A, n = 40) and control group (group B, n = 40) by random number table method. Dex pump volume was 0.5 μg/kg/h in group A and 1.0 μg/kg/h in group B. Heart rate (HR) and mean arterial pressure (MAP) were recorded before anesthesia induction (T0), immediately after endotracheal intubation (T1) and at the end of operation (T2). The serum levels of central nervous system specific protein (S-100β) and neuron specific enolase (NSE) were measured and compared between the two groups at T0 and T2. Results: HR and MAP in group A were significantly higher than those in group B at T2, and the difference was statistically significant (P P β and NSE in both groups at T2 were lower than those at T0, and the concentrations of S-100β and NSE in group A were significantly lower than those in group B at T2 (P Conclusions: 0.5 μg/kg dose of Dex is stable in hemodynamics and has a better protective effect on brain function in patients with traumatic brain injury.

Dexmedetomidine-induced anesthesia in elderly patients undergoing hip replacement surgery

BACKGROUND A femoral neck fracture is a common and frequently reported issue in orthopedics, with a greater rate of incidence among the elderly. Due to their advanced age and the presence of some primary diseases, both anesthesia and surgery are increasingly difficult in elderly patients with a femoral neck fractures. In fact,general anesthesia can easily induce complications such as cognitive dysfunction,which is not conducive to postoperative recovery.AIM To analyze the efficacy of dexmedetomidine in inducing anesthesia for elderly patients undergoing hip replacement surgery.METHODS A total of 98 elderly patients undergoing hip replacement in our hospital from June 2020 to June 2021 were randomly divided into control group(49 cases) and observation group(49 cases). The control group was given general anesthesia, and the observation group was combined with dexmedetomidine for anesthesia on the basis of the control group. Both groups were observed until the patients were discharged. The vital signs, serum inflammatory factors and renal function indexes of the two groups were compared before, during and 6 h after operation.The postoperative recovery and adverse events of the two groups were statistically analyzed.RESULTS Compared with the mean arterial pressure of the two groups, the intraoperative and postoperative 6 h was higher than that before the operation, the intraoperative was lower than the postoperative 6 h(P < 0.05);the blood oxygen saturation of the two groups was higher than that before operation and 6 h after operation, and the observation group was higher than the control group 6 h after operation(P < 0.05). The heart rate of the two groups was lower during and 6 h after operation than that before operation, and higher at 6 h after operation than that during operation(P < 0.05).The levels of serum C-reactive protein, tumor necrosis factor-α, interleukin-1β and kidney injury molecule-1 in the two groups were higher during operation and 6 h after operation than those before operation(P < 0.05). The level of serum urea nitrogen in the two groups was higher than that before operation, and that in the observation group was lower than that in the control group(P < 0.05). During hospitalization, the first time of getting out of bed, recovery time of grade Ⅱ muscle strength, recovery time of grade Ⅲ muscle strength and hospitalization time in the observation group were shorter than those in the control group(P < 0.05).CONCLUSION Dexmedetomidine can effectively improve the vital signs of elderly patients undergoing hip replacement surgery, reduce the body’s inflammatory response and renal function damage, and promote postoperative recovery. Meanwhile, dexmedetomidine showcased a good safety profile and a good anesthetic outcome.

Hemodynamic instability following intravenous dexmedetomidine infusion for sedation under brachial plexus block: Two case reports

BACKGROUND Dexmedetomidine(DMED)is frequently used as a sedative in several medical fields.The benefits of DMED include enhanced quality of regional anesthesia,prolonged analgesia,and postoperative opioid-sparing when administered intravenously or perineurally in combination with regional anesthesia.Severe hemodynamic complications,such as profound bradycardia and hypotension,can occur after DMED administration in critically ill patients or overdosage;however,there are few reports of complications with DMED administration following brachial plexus block(BPB).CASE SUMMARY We present two cases of hemodynamic instability that occurred following the initial loading of DMED under supraclavicular BPB.A healthy 29-year-old man without any medical history showed profound bradycardia after receiving a loading dose of DMED 0.9μg/kg for 9 min.DMED administration was promptly stopped,and after receiving a second dose of atropine,the heart rate recovered.A 62-year-old woman with a history of cardiomyopathy became hypotensive abruptly,requiring the administration of inotrope and vasopressors after receiving a reduced loading dose of 0.5μg/kg for 10 min.Half of the recommended loading dose of DMED was administered due to the underlying heart dysfunction.Decrea-sed blood pressure was maintained despite the intravenous administration of ephedrine.With continuous infusion of dopamine and norepinephrine,the vital signs were maintained within normal ranges.Inotropic and vasopressor support was required for over 6 h after the initial loading dose of DMED.CONCLUSION DMED administration following BPB could trigger hemodynamic instability in patients with decreased cardiac function as well as in healthy individuals.

Dexmedetomidine mediates the mechanism of action of ferroptosis in mice with Alzheimer’s disease by regulating the mTOR-TFR1 pathway

BACKGROUND Alzheimer’s disease(AD)is the most common neurodegenerative disorder,and there are currently no effective drugs to delay progression of the disease.Ferroptosis may play a vital part in AD,and is therefore receiving increasing attention by researchers.AIM To investigate the effects of dexmedetomidine(Dex)on ferroptosis in AD mouse hippocampus.METHODS Hippocampal neurons(HNs)HT22 were induced by amyloidβ-protein(Aβ)and both in vitro and in vivo AD mouse models were prepared via injections.The cellcounting kit-8 assay and immunofluorescence technique were adopted to determine cell proliferation activity and intracellular Fe2+levels,and the TBA method and microplate method were employed for malondialdehyde and glutathione measurements,respectively.Hippocampal tissue damage was determined using hematoxylin and eosin and Nissl staining.Mouse learning and memory ability in each group was assessed by the Morris water maze test,and the expression levels of mammalian target of rapamycin(mTOR)signal molecules and ferroptosis-related proteins transferrin receptor 1(TFR1),SLC7A11 and glutathione peroxidase 4 were examined by western blotting.RESULTS Dex enhanced lipid peroxidation and iron influx in mouse HNs in both in vitro and in vivo experiments,while inhibition of the mTOR axis blocked this process.These findings demonstrate that Dex can inhibit ferroptosis-induced damage in mouse HNs by activating mTOR-TFR1 signaling to regulate ferroptosis-associated proteins,thus alleviating cognitive dysfunction in AD mice.CONCLUSION Dex can activate the mTOR-TFR1 axis to inhibit ferroptosis in mouse HNs,thereby improving the learning and memory ability of mice.

Clonidine use during dexmedetomidine weaning:A systematic review

BACKGROUND Dexmedetomidine is a centrally acting alpha-2A adrenergic agonist that is commonly used as a sedative and anxiolytic in the intensive care unit(ICU),with prolonged use increasing risk of withdrawal symptoms upon sudden discontinuation.As clonidine is an enterally available alpha-2A adrenergic agonist,it may be a suitable agent to taper off dexmedetomidine and reduce withdrawal syndromes.The appropriate dosing and conversion strategies for using enteral clonidine in this context are not known.The objective of this systematic review is to summarize the evidence of enteral clonidine application during dexmedetomidine weaning for prevention of withdrawal symptoms.AIM To systematically review the practice,dosing schema,and outcomes of enteral clonidine use during dexmedetomidine weaning in critically ill adults.METHODS This was a systematic review of enteral clonidine used during dexmedetomidine weaning in critically ill adults(≥18 years).Randomized controlled trials,prospective cohorts,and retrospective cohorts evaluating the use of clonidine to wean patients from dexmedetomidine in the critically ill were included.The primary outcomes of interest were dosing and titration schema of enteral clonidine and dexmedetomidine and risk factors for dexmedetomidine withdrawal.Other secondary outcomes included prevalence of adverse events associated with enteral clonidine use,re-initiation of dexmedetomidine,duration of mechanical ventilation,and ICU length of stay.RESULTS A total of 3427 studies were screened for inclusion with three meeting inclusion criteria with a total of 88 patients.All three studies were observational,two being prospective and one retrospective.In all included studies,the choice to start enteral clonidine to wean off dexmedetomidine was made at the discretion of the physician.Weaning time ranged from 13 to 167 h on average.Enteral clonidine was started in the prospective studies in a similar protocolized method,with 0.3 mg every 6 h.After starting clonidine,patients remained on dexmedetomidine for a median of 1-28 h.Following the termination of dexmedetomidine,two trials tapered enteral clonidine by increasing the interval every 24 h from 6 h to 8h,12h,and 24 h,followed by clonidine discontinuation.For indicators of enteral clonidine withdrawal,the previously tolerable dosage was reinstated for several days before resuming the taper on the same protocol.The adverse events associated with enteral clonidine use were higher than patients on dexmedetomidine taper alone with increased agitation.The re-initiation of dexmedetomidine was not documented in any study.Only 17(37%)patients were mechanically ventilated with median duration of 3.5 d for 13 patients in one of the 2 studies.ICU lengths of stay were similar.CONCLUSION Enteral clonidine is a strategy to wean critically ill patients from dexmedetomidine.There is an association of increased withdrawal symptoms and agitation with the use of a clonidine taper.

Comparison of the efficacy and safety of sedation between dexmedetomidine-remifentanil and propofol-remifentanil during endoscopic submucosal dissection

AIM: To compare the efficacy and safety of sedation protocols for endoscopic submucosal dissection(ESD) between dexmedetomidine-remifentanil and propofolremifentanil.METHODS: Fifty-nine patients scheduled for ESD were randomly allocated into a dexmedetomidineremifentanil(DR) group or a propofol-remifentanil(PR) group. To control patient anxiety, dexmedetomidine or propofol was infused to maintain a score of 4-5 on the Modified Observer's Assessment of Alertness/Sedation scale. Remifentanil was infused continuously at a rate of 6 μg/kg per hour in both groups. The ease of advancing the scope into the throat, gastric motility grading, and satisfaction of the endoscopist and patient were assessed. Hemodynamic variables and hypoxemic events were compared to evaluate patient safety.RESULTS: Demographic data were comparable between the groups. The hemodynamic variables and pulse oximetry values were stable during the procedure in both groups despite a lower heart rate in the DR group. No oxygen desaturation events occurred in either group. Although advancing the scope into the throat was easier in the PR group("very easy" 24.1% vs 56.7%, P = 0.010), gastric motility was moresuppressed in the DR group("no + mild" 96.6% vs 73.3%, P = 0.013). The endoscopists felt that the procedure was more favorable in the DR group("very good + good" 100% vs 86.7%, P = 0.042), whereas patient satisfaction scores were comparable between the groups. En bloc resection was performed 100% of the time in both groups, and the complete resection rate was 94.4% in the DR group and 100% in the PR group(P = 0.477). CONCLUSION: The efficacy and safety of dexmedetomidine and remifentanil were comparable to propofol and remifentanil during ESD. However, the endoscopists favored dexmedetomidine perhaps due to lower gastric motility.

Dexmedetomidine Alleviates Pulmonary Edema by Upregulating AQP1 and AQP5 Expression in Rats with Acute Lung Injury Induced by Lipopolysaccharide

This study aims to elucidate the mechanisms by which dexmedetomidine alleviates pulmonary edema in rats with acute lung injury induced by lipopolysaccharide （LPS）. Male Wistar rats were randomly divided into five groups： normal saline control （NS） group, receiving intravenous 0.9% normal saline （5 mL/kg）; LPS group, receiving intravenous LPS （10 mg/kg）; small-dose dexmedetomidine （S） group, treated with a small dose of dexmedetomidine （0.5 μg·kg^-1·h^-1）; medium-dose dexmedetomidine （M） group, treated with a medium dose of dexmedetomidine （2.5 μg·kg^-1·h^-1）; high-dose dexmedetomidine （H） group, treated with a high dose of dexmedetomidine （5μg·kg^-1·h^-1）. The rats were sacrificed 6 h after intravenous injection of LPS or NS, and the hmgs were removed for evaluating histological characteristics and determining the lung wet/dry weight ratio （W/D）. The levels of tumor necrosis factor-alpha （TNF-α） and interleukin-1β （IL-1β） in the lung tissues were assessed by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression levels of aquaporin-1 （AQP1） and aquaporin-5 （AQP5） were detected by RT-PCR, immunohistochemistry, and Western blot- ting. The lung tissues from the LPS groups were significantly damaged, which were less pronounced in the H group but not in the small-dose dexmedetomidine group or medium-dose dexmedetomidine group. The W/D and the concentrations of TNF-α and IL-1β in the pulmonary tissues were increased in the LPS group as compared with those in NS group, which were reduced in the H group but not in S group or M group （P〈0.01）. The expression of AQP1 and AQP5 was lower in the LPS group than in the NS group, and significantly increased in the H group but not in the S group or M group （P〈0.01）. Our findings suggest that dexmedetomidine may alleviate pulmonary edema by increasing the expression of AQP-1 and AQP-5.

Dose-related effects of dexmedetomidine on immunomodulation and mortality to septic shock in rats

BACKGROUND: Dexmedetomidine has already been used in septic patients as a new sedative agent, few studies have examined its effects on immunomodulation. Therefore, the authors have designed a controlled experimental study to characterize the immunomodulation effects of dexmedetomidine in the cecal ligation and puncture(CLP) model in rats. METHODS: After CLP, 48 Wistar rats were randomly allocated into four groups:(1) CLP group;(2) small-dose treatment group(2.5 g·kg^(-1)·h^(-1));(3) medium-dose treatment group(5.0 g·kg^(-1)·h^(-1)); and(4) large-dose treatment group(10.0 g·kg^(-1)·h^(-1)). HLA-DR and plasma cytokine(IL-4, IL-6, IL-10 and TNF-α) levels were measured, and the mean arterial blood pressure(MAP), heart rate(HR), arterial blood gases, lactate concentrations and mortality were also documented. RESULTS: The HLA-DR level, inflammatory mediator levels, MAP and HR had no obvious changes among Dexmedetomidine treatment groups(DEX groups). Compared with the CLP group, the DEX groups exhibited decreased HLA-DR levels(P_(group)=0.0202) and increased IL-6 production, which was increased at 3 h(P= 0.0113) and was then attenuated at 5 h; additionally, the DEX groups exhibited decreased HR(P<0.001) while maintaining MAP(P_(group)=0.1238), and remarkably improving lactate(P<0.0001). All of these factors led to a significant decrease in the mortality, with observed rates of 91.7%, 66.7%, 25% and 18% for the CLP, DEX2.5, DEX5.0, DEX10.0 groups, respectively.CONCLUSION: Dexmedetomidine treatment in the setting of a CLP sepsis rat model has partially induced immunomodulation that was initiated within 5 h, causing a decreased HR while maintaining MAP, remarkably improving metabolic acidosis and improving mortality dosedependently.

Neuroprotective effect of bispectral index-guided fast-track anesthesia using sevoflurane combined with dexmedetomidine for intracranial aneurysm embolization

Dexmedetomidine has sedative, anxiolytic, analgesic, anti-sympathetic, and anti-shivering effects. Dexmedetomidine might be effective in combination with sevoflurane for anesthesia, but prospective randomized controlled clinical trials with which to verify this hypothesis are lacking. In total, 120 patients who underwent embolization of an intracranial aneurysm were recruited from Anhui Provincial Hospital and Renmin Hospital of Wuhan University of China and randomly allocated to two groups. After intraoperative administration of 2% to 3% sevoflurane inhalation, one group of patients received pump-controlled intravenous injection of 1.0 ~tg/kg dexmedetomidine for 15 minutes followed by maintenance with 0.3 ~tg/kg/h until the end of surgery; the other group of patients only underwent pump-controlled infusion of saline. Bispectral index monitoring revealed that dexmedetomidine-assisted anesthesia can shorten the recovery time of spon- taneous breathing, time to eye opening, and time to laryngeal mask removal. Before anesthetic induction and immediately after laryngeal mask airway removal, the glucose and lactate levels were low, the S100~ and neuron-specific enolase levels were low, the perioperative blood pressure and heart rate were stable, and postoperative delirium was minimal. These findings indicate that dexmedetomidine can effectively assist sevoflurane for anesthesia during surgical embolization of intracranial aneurysms, shorten the time to consciousness and extubation, reduce the stress response and energy metabolism, stabilize hemodynamic parameters, and reduce adverse reactions, thereby reducing the damage to the central nervous system. This trial was registered at the Chinese Clinical Trial Registry （http：//www.chictr.org. cn/） （registration number： ChiCTR-IPR- 16008113）.

Dexmedetomidine attenuates traumatic brain injury: action pathway and mechanisms

Traumatic brain injury induces potent inflammatory responses that can exacerbate secondary blood-brain barrier（BBB） disruption, neuronal injury, and neurological dysfunction. Dexmedetomidine is a novel α2-adrenergic receptor agonist that exert protective effects in various central nervous system diseases. The present study was designed to investigate the neuroprotective action of dexmedetomidine in a mouse traumatic brain injury model, and to explore the possible mechanisms. Adult male C57 BL/6 J mice were subjected to controlled cortical impact. After injury, animals received 3 days of consecutive dexmedetomidine therapy（25 μg/kg per day）. The modified neurological severity score was used to assess neurological deficits. The rotarod test was used to evaluate accurate motor coordination and balance. Immunofluorescence was used to determine expression of ionized calcium binding adapter molecule-1, myeloperoxidase, and zonula occluden-1 at the injury site. An enzyme linked immunosorbent assay was used to measure the concentration of interleukin-1β（IL-1β）, tumor necrosis factor α, and IL-6. The dry-wet weight method was used to measure brain water content. The Evans blue dye extravasation assay was used to measure BBB disruption. Western blot assay was used to measure protein expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3（NLRP3）, caspase-1 p20, IL-1β, nuclear factor kappa B（NF-κB） p65, occluding, and zonula occluden-1. Flow cytometry was used to measure cellular apoptosis. Results showed that dexmedetomidine treatment attenuated early neurological dysfunction and brain edema. Further, dexmedetomidine attenuated post-traumatic inflammation, up-regulated tight junction protein expression, and reduced secondary BBB damage and apoptosis. These protective effects were accompanied by down-regulation of the NF-κB and NLRP3 inflammasome pathways. These findings suggest that dexmedetomidine exhibits neuroprotective effects against acute（3 days） post-traumatic inflammatory responses, potentially via suppression of NF-κB and NLRP3 inflammasome activation.

Neurotoxicity of intrathecal injections of dexmedetomidine into the rat spinal dorsal horn

To investigate the neurotoxicity of intrathecal injections of dexmedetomidine,Sprague-Dawley rats were intrathecally injected with dexmedetomidine at doses of 0.75,1.50 and 3.00μg/kg into the spinal dorsal horn.We found that c-Fos expression in the rat spinal dorsal horn peaked at 7 hours following the 3.00μg/kg dexmedetomidine injection,while the levels of c-Fos expression following 0.75 and 1.50μg/kg dexmedetomidine were similar to those in the spinal dorsal horn of normal rats. At 48 hours following administration,the level of c-Fos expression was similar to normal levels.In addition,the intrathecal injections of dexmedetomidine increased paw withdrawal mechanical thresholds and prolonged thermal tail flick latencies.These results indicate that dexmedetomidine has pronounced antinociceptive effects.However,dexmedetomidine appears to have neurotoxic effects in the spinal cord because it increased c-Fos expression in the spinal dorsal horn within 7 hours following administration.