2.Dexmedetomidine improves alcohol withdrawal symptom via activating α2 adrenergic receptor in rat hippocampus.
Ting ZENG ; Hong-Yan ZHANG ; Xin ZHAO ; Yan LIU ; Yan-Zhong GUAN
Acta Physiologica Sinica 2022;74(4):541-547
The purpose of this study was to investigate the effects of α2 adrenergic receptor agonist dexmedetomidine on withdrawal symptoms in alcohol-dependent rats and the underlying mechanism, so as to provide a scientific basis for the treatment of alcohol withdrawal syndrome (AWS). Adult Sprague-Dawley (SD) male rats were orally administered with 6% aqueous alcohol continuously for 28 d to establish alcohol drinking model, and then stopped drinking to induce AWS. Enzyme-linked immunosorbent assay (ELISA) was used to determine the content of norepinephrine (NE) in the locus coeruleus and hippocampus of rats. Dexmedetomidine (5, 10, and 20 μg/kg) was intraperitoneally injected respectively when the rats showed significant AWS. In some rats, α2 adrenergic receptor antagonist yohimbine was injected into hippocampus in advance. The results showed that, compared with the control group, the 6 h withdrawal group exhibited significantly increased AWS score and amount of repeat drinking. The NE contents in hippocampus and locus coeruleus of the last drinking and the 6 h withdrawal groups were significantly increased compared with those of the control group. Dexmedetomidine intervention significantly decreased AWS score and hippocampus NE content in the 6 h withdrawal group, while yohimbine could reverse these effects of dexmedetomidine. These results suggest that dexmedetomidine might improve the withdrawal symptoms in alcohol-dependent rats via activating α2 adrenergic receptor.
Adrenergic alpha-2 Receptor Agonists/therapeutic use*
;
Alcoholism/drug therapy*
;
Animals
;
Dexmedetomidine/therapeutic use*
;
Hippocampus/metabolism*
;
Male
;
Norepinephrine
;
Rats
;
Rats, Sprague-Dawley
;
Receptors, Adrenergic, alpha-2/metabolism*
;
Substance Withdrawal Syndrome/drug therapy*
;
Yohimbine/pharmacology*
3.Cardiac Protection Mechanism and Clinical Application of Dexmedetomidine.
Yi-Cheng YANG ; Bei-Er CHEN ; Kai-Yan YE ; Wan-Ying HE ; Zhi-Qiang XIAO ; Chang-Ming XIONG
Acta Academiae Medicinae Sinicae 2022;44(1):130-135
Dexmedetomidine is an α2 adrenoceptor agonist and has cardioprotective effect,the mechanism of which is being studied.Increasing studies have proved the clinical value of dexmedetomidine in reducing postoperative complications and improving the prognosis of patients.Therefore,this review summarizes the cardiac protection mechanism of dexmedetomidine based on the existing studies and expounds the application of dexmedetomidine in the perioperative period of cardiovascular surgery.
Dexmedetomidine/therapeutic use*
;
Heart
;
Humans
4.Prevention of dexmedetomidine on postoperative delirium and early postoperative cognitive dysfunction in elderly patients undergoing hepatic lobectomy.
Yixun TANG ; Yongsheng WANG ; Gaoyin KONG ; Yuan ZHAO ; Lai WEI ; Jitong LIU
Journal of Central South University(Medical Sciences) 2022;47(2):219-225
OBJECTIVES:
Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are common operative neurocognitive disorders, which places a heavy burden on patients, families and society. Therefore, it is very important to search for preventive drugs. Previous studies have demonstrated that perioperative use of dexmedetomidine resulted in a decrease the incidence of POD and POCD. But the specific effect of dexmedetomidine on elderly patients undergoing hepatic lobectomy and its potential mechanism are not clear. This study aims to evaluate the efficacy of intraoperative use of dexmedetomidine on preventing POD and POCD in elderly patients undergoing hepatic lobectomy and the influence on the balance between proinflammation and anti-inflammation.
METHODS:
This trial was designed as a single-center, prospective, randomized, controlled study. One hundred and twenty hospitalized patients from January 2019 to December 2020, aged 60-80 years old with American Society of Anesthesiologists (ASA) II-III and scheduled for hepatic lobectomy, were randomly allocated into 3 groups (n=40) using a random number table: A C group, a Dex1 group, and a Dex2 group. After anesthesia induction, saline in the C group, dexmedetomidine [0.3 μg/(kg·h)] in the Dex1 group, and dexmedetomidine [0.6 μg/(kg·h)] in the Dex2 group were infused until the end of operation. The incidences of hypotension and bradycardia were compared among the 3 groups. Confusion Assessment Method (CAM) for assessing POD and Mini Mental State Examination (MMSE) for evaluating POCD were recorded and venous blood samples were obtained for the determination of neuron specific enolase (NSE), TNF-α, IL-1β, and IL-10 at the different time below: the time before anesthesia (T0), and the first day (T1), the third day (T2), the fifth day (T3), and the seventh day (T4) after operation.
RESULTS:
Compared with the C group, the incidences of bradycardia in the Dex1 group or the Dex2 group increased (both P<0.05) and there was no difference in hypotension in the Dex1 group or the Dex2 group (both P>0.05). The incidences of POD in the C group, the Dex1 group, and the Dex2 group were 22.5%, 5.0%, and 7.5%, respectively. The incidences of POD in the Dex1 group or the Dex2 group declined significantly as compared to the C group (both P<0.05). However, there is no difference in the incidence of POD between the Dex1 group and the Dex2 group (P>0.05). The incidences of POCD in the C group, the Dex1 group, and the Dex2 group were 30.0%, 12.5%, and 10.0%, respectively. The incidences of POCD in the Dex1 group and the Dex2 group declined significantly as compared to the C group (both P<0.05). And no obvious difference was seen in the incidence of POCD in the Dex1 group and the Dex2 group (P>0.05). Compared with the C group, the level of TNF-α and IL-1β decreased and the level of IL-10 increased at each time points (from T1 to T4) in the Dex1 group and the Dex2 group (all P<0.05). Compared with the Dex1 group, the level of IL-1β at T2 and IL-10 from T1 to T3 elevated in the Dex2 group (all P<0.05). Compared with the T0, the concentrations of NSE in C group at each time points (from T1 to T4) and in the Dex1 group and the Dex2 group from T1 to T3 increased (all P<0.05). Compared with the C group, the level of NSE decreased from T1 to T4 in the Dex1 group and the Dex2 group (all P<0.05).
CONCLUSIONS
Intraoperative dexmedetomidine infusion can reduce the incidence of POCD and POD in elderly patients undergoing hepatic lobectomy, and the protective mechanism appears to involve the down-regulation of TNF-α and IL-1β and upregulation of IL-10 expression, which lead to rebalance between proinflammation and anti-inflammation.
Aged
;
Aged, 80 and over
;
Bradycardia
;
Cognitive Dysfunction/prevention & control*
;
Delirium/prevention & control*
;
Dexmedetomidine/therapeutic use*
;
Humans
;
Hypotension/drug therapy*
;
Interleukin-10
;
Middle Aged
;
Postoperative Cognitive Complications/prevention & control*
;
Postoperative Complications/epidemiology*
;
Prospective Studies
;
Tumor Necrosis Factor-alpha
5.Dexmedetomidine combined with protective lung ventilation strategy provides lung protection in patients undergoing radical resection of esophageal cancer with one-lung ventilation.
Zheng GONG ; Xiaomao LONG ; Huijun WEI ; Ying TANG ; Jun LI ; Li MA ; Jun YU
Journal of Zhejiang University. Medical sciences 2020;40(7):1013-1017
OBJECTIVE:
To investigate the effect of dexmedetomidine combined with pulmonary protective ventilation against lung injury in patients undergoing surgeries for esophageal cancer with one-lung ventilation (OLV).
METHODS:
Forty patients with undergoing surgery for esophageal cancer with OLV were randomly divided into pulmonary protective ventilation strategy group (F group) and dexmedetomidine combined with protective ventilation strategy group (DF group; =20). In F group, lung protective ventilation strategy during anesthesia was adopte, and in DF group, the patients received intravenous infusion of dexmedetomidine hydrochloride (0.3 μg · kg ·h) during the surgery starting at 10 min before anesthesia induction in addition to protective ventilation strategy. Brachial artery blood was sampled before ventilation (T), at 30 and 90 min after the start of OLV (T and T, respectively) and at the end of the surgery (T) for analysis of superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), arterial oxygenation pressure (PaO), oxygenation index (OI) and lung compliance (CL).
RESULTS:
At the time points of T, T and T, SOD level was significantly higher and IL-6 level was significantly lower in the DF group than in F group ( < 0.05). The patients in DF group showed significantly higher PaO, OI and CL index than those in F group at all the 3 time points.
CONCLUSIONS
Dexmedetomidine combined with pulmonary protective ventilation strategy can reduce perioperative lung injury in patients undergoing surgery for esophageal cancer with OLV by suppressing inflammation and oxidative stress to improve lung function and reduce adverse effects of the surgery.
Analgesics, Non-Narcotic
;
pharmacology
;
therapeutic use
;
Dexmedetomidine
;
pharmacology
;
therapeutic use
;
Esophageal Neoplasms
;
drug therapy
;
surgery
;
Humans
;
Lung
;
drug effects
;
surgery
;
One-Lung Ventilation
;
Oxidative Stress
;
drug effects
;
Treatment Outcome
6.Dose-response Relationship of Dexmedetomidine Combined with Sufentail for Postoperative Intravenous Analgesia in Video-assisted Thoracoscopic Surgery.
Xiao Lu TAN ; Ya Yu CHEN ; Bo HU ; Qiao Mei ZHOU ; Wei Dong SHAO ; Bo XU ; Hai Ping XIAO ; Xing An ZHANG
Acta Academiae Medicinae Sinicae 2019;41(3):373-378
Objective To investigate the 50% effective dose(ED)and 95% effective dose(ED)of dexmedetomidine(DEX)combined with 0.032 μg/(kg·h)sufentanil as well as its analgesic effect for patient-controlled intravenous analgesia(PCIA)after video-assisted thoracoscopic surgery(VATS).Methods Totally 25 patients undergoing elective VATS were enrolled. DEX and 0.032 μg/(kg·h)sufentanil were used for postoperative PCIA. The loading dose of DEX was 0.048 μg/(kg·h),and the dose difference between two adjacent patients was 0.008 μg/(kg·h). The DEX dose of a current patient was determined by whether the previous patient was satisfied with postoperative analgesic effect. If the previous patient was satisfied with postoperative analgesic effect,the DEX dose of the current patient was decreased by 0.008 μg/(kg·h);and if the previous analgestic effect was not satisfactory,DEX dose of the current patient was increased by 0.008 μg/(kg·h). The study endpoint was dexmedetomidine dose was<0.008 μg/(kg· h) within 7 upper and lower cycles in 7 consecutive cases. Finally,the probability unit regression was used to estimate the ED and ED of DEX and their 95% .Results When DEX combined with 0.032 μg/(kg·h) sufentanil was used for postoperative PCIA in young patients undergoing VATS,the ED and EDof DEX were 0.0346 μg/(kg· h)[95%:0.0283-0.0408 μg/(kg·h)] and 0.0459 μg/(kg·h)[95%:0.0400-0.0880 μg/(kg·h)],respectively. No adverse reaction such as vomiting,respiratory depression,or bradycardia occurred. The average Visual Analogue Scale(VAS)scores at rest(=-5.128,=0.000)and cough(Z=-6.642,=0.000)and the Ramsay sedation score(Z=-2.335,=0.020)within 6 hours after surgery were higher than those after 6 hour.Conclusion DEX combined with 0.032 μg/(kg·h) sufentanil are effective for postoperative PCIA in patients undergoing VATS when the ED and ED are 0.0346 μg/(kg·h)and 0.0459 μg/(kg·h),respectively.
Analgesia, Patient-Controlled
;
Analgesics, Non-Narcotic
;
administration & dosage
;
therapeutic use
;
Dexmedetomidine
;
administration & dosage
;
therapeutic use
;
Dose-Response Relationship, Drug
;
Drug Therapy, Combination
;
Humans
;
Pain, Postoperative
;
drug therapy
;
Sufentanil
;
administration & dosage
;
therapeutic use
;
Thoracic Surgery, Video-Assisted
7.Effect of dexmedetomidine on supraclavicular brachial plexus block: a randomized double blind prospective study.
Yan LI ; Hui WANG ; Ying DENG ; Yao YAO ; Min LI
Journal of Peking University(Health Sciences) 2018;50(5):845-849
OBJECTIVE:
To evaluate the effect of dexmedetomidine combined with ropivacaine on brachial plexus block in patients scheduled for elective shoulder arthroscopy.
METHODS:
Ninety patients with American Society of Anesthesiologists (ASA) I or II, scheduled for elective shoulder arthroscopy, were randomly divided into three groups. In group R (n=30), the patients were given 10 mL of 0.375% ropivacaine in branchial plexus block (interscalene approach guided by ultrasound), in group D1 (n=30), the patients were given 10 mL of 0.375% ropivacaine (interscalene approach guided by ultrasound) + dexmedetomidine 0.2 μg/(kg×h) (intravenous pump infusion), and in group D2 (n=30), the patients were given 10 mL of 0.375% ropivacaine (interscalene approach guided by ultrasound) + dexedetomidine 0.7 μg/(kg×h) (intravenous pump infusion). To evaluate the effect of brachial plexus block before general anesthesia. Group D1 and group D2 were given dexmedetomidine intravenously for 1.0 μg/kg during 10 min, then the drug was pumped by 0.2 μg/(kg×h) and 0.7 μg/(kg×h) respectively until 30 min before the operation finished. Changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and before anesthesia (T0), 10 min (T1), 30 min (T2) after giving dexmedetomidine, discontinue medication (T3), after operation (T4), and extubation (T5) were investigated. Motor and sensory block onset times, block durations, and duration of analgesia were recorded. The scores of pain after operation and the adverse effects of shiver, hypopiesia, drowsiness, and blood loss were recorded during operation.
RESULTS:
Compared with group R, the duration of analgesia and duration of sensory block in group D1 and group D2 were significant longer (P<0.01), there was no significant difference between groups D1 and D2 (P>0.05). Compared with group R, at each time point of T1-T5, the heart rate and systolic blood pressure in group D1 and group D2 were significantly decreased (P<0.01). Compared with D1 group, the incidence of hypotension and bradycardia in group D2 were significantly different (P<0.05).
CONCLUSION
Intravenous dexmedetomidine could prolong the duration of analgesia time and sensory block within the brachial plexus block, inhibiting the stress response during arthroscopic shoulder surgery. Compared with high-dose, low-dose can provide safer and better clinical effect and reduce the adverse effects of dexmedetomidine.
Analgesics, Non-Narcotic
;
Anesthetics, Local/therapeutic use*
;
Arthroscopy
;
Brachial Plexus
;
Brachial Plexus Block
;
Dexmedetomidine/therapeutic use*
;
Double-Blind Method
;
Humans
;
Hypnotics and Sedatives/pharmacology*
;
Prospective Studies
;
Ropivacaine/therapeutic use*
;
Shoulder Joint/surgery*
8.A National Multicenter Survey on Management of Pain, Agitation, and Delirium in Intensive Care Units in China.
Jing WANG ; Zhi-Yong PENG ; Wen-Hai ZHOU ; Bo HU ; Xin RAO ; Jian-Guo LI
Chinese Medical Journal 2017;130(10):1182-1188
BACKGROUNDThe management of pain, agitation, and delirium (PAD) in Intensive Care Unit (ICU) is beneficial for patients and makes it widely applied in clinical practice. Previous studies showed that the clinical practice of PAD in ICU was improving; yet relatively little information is available in China. This study aimed to investigate the practice of PAD in ICUs in China.
METHODSA multicenter, nationwide survey was conducted using a clinician-directed questionnaire from September 19 to December 18, 2016. The questionnaire focused on the assessment and management of PAD by the clinicians in ICUs. The practice of PAD was compared among the four regions of China (North, Southeast, Northwest, and Southwest). The data were expressed as percentage and frequency. The Chi-square test, Fisher's exact test, and line-row Chi-square test were used.
RESULTSOf the 1011 valid questionnaire forms, the response rate was 80.37%. The clinicians came from 704 hospitals across 158 cities of China. The rate of PAD assessment was 75.77%, 90.21%, and 66.77%, respectively. The rates of PAD scores were 45.8%, 68.94%, and 34.03%, respectively. The visual analog scale, Richmond agitation-sedation scale, and confusion assessment method for the ICU were the first choices of scales for PAD assessment. Fentanyl, midazolam, and dexmedetomidine were the first choices of agents for analgesic, sedation, and delirium treatment. While choosing analgesics and sedatives, the clinicians put the pharmacological characteristics of drugs in the first place (66.07% and 76.36%). Daily interruption for sedation was carried out by 67.26% clinicians. Most of the clinicians (87.24%) used analgesics while using sedatives. Of the 738 (73%) clinicians titrating the sedatives on the basis of the proposed target sedation level, 268 (26.61%) clinicians just depended on their clinical experience. Totally, 519 (51.34%) clinicians never used other nondrug strategies for PAD. The working time of clinicians was an important factor in the management of analgesia and sedation rather than their titles and educational background. The ratios of pain score and sedation score in the Southwest China were the highest and the North China were the lowest. The ratios of delirium assessment and score were the same in the four regions of China. Moreover, the first choices of scales for PAD in the four regions were the same. However, the top three choices of agents in PAD treatment in the four regions were not the same.
CONCLUSIONSThe practice of PAD in China follows the international guidelines; however, the pain assessment should be improved. The PAD practice is a little different across the four regions of China; however, the trend is consistent.
TRIAL REGISTRATIONThe study is registered at http://www.clinicaltrials.gov (No. ChiCTR-OOC-16009014, www.chictr. org.cn/index.aspx.).
Delirium ; drug therapy ; Dexmedetomidine ; therapeutic use ; Fentanyl ; therapeutic use ; Haloperidol ; therapeutic use ; Humans ; Hypnotics and Sedatives ; therapeutic use ; Intensive Care Units ; statistics & numerical data ; Midazolam ; therapeutic use ; Pain ; drug therapy ; Pain Management ; methods ; Pain Measurement ; methods ; Surveys and Questionnaires
9.Analgesic and Sedative Effect of Acupuncture Combined with Medicine on Patients Undergiong Cardiac Surgery.
Hui-jie YU ; Xiao-qin XU ; Song-ao XU ; Xu JUN ; Wei-zhong CAO
Chinese Journal of Integrated Traditional and Western Medicine 2016;36(3):289-293
OBJECTIVETo observe analgesic and sedative effect of acupuncture combined with medicine (ACM) on patients undergiong cardiac surgery.
METHODSA total of 50 patients with cardiac surgery from January 2012 to October 2014 were randomly assigned to the conventional analgesia group (group A) and the ACM analgesia group (group B), 25 in each group. Patients in group A were subjected to analgesia and sedation by injecting dexmedetomidine, while patients in group B were subjected to analgesia and sedation by electro-acupuncture [EA, Shenting (GV24); Yintang (EX-HN3)] combined with injection of dexmedetomidine. Morphine hydrochloride injection was performed when analgesia and sedation effect was ineffective in the two groups. The indicators of patients at different time points in the two groups were observed, such as static and dynamic VAS scores, SAS scores, mean arterial pressure (MAP), heart rate (HR), oxygen saturation (SpO2). The injection dosage of dexmedetomidine and morphine hydrochloride, analgesia satisfaction rate, sedation satisfaction rate, the incidences of adverse reactions during treatment such as bradycardia and low blood pressure, mechanical ventilation time, ICU time, and hospitalization expense were observed and recorded in the two groups.
RESULTSThere was no statistical difference in static and dynamic VAS scores, SAS score, MAP, HR and SpO2 between the two groups at different time points (P > 0.05). The injection dosage of dexmedetomidine and morphine hydrochloride was significantly reduced in group B than in group A (P < 0.05). The analgesia satisfaction rate of patients in group B was much higher than that in group A (P < 0.05). The incidence of bradycardia also obviously decreased more in group B than in group A (P < 0.05). There was no statistical difference in patients' sedation satisfaction rate, incidences of low blood pressure, delirium, vomiting; mechanical ventilation time, ICU time, or hospitalization expense between the two groups (P > 0.05).
CONCLUSIONThe analgesia method of ACM could reduce the dosage of traditional analgesic drugs and the occurrence of partial adverse reactions.
Acupuncture Analgesia ; Analgesia ; methods ; Analgesics ; therapeutic use ; Cardiac Surgical Procedures ; Dexmedetomidine ; therapeutic use ; Electroacupuncture ; Heart Rate ; Humans ; Hypnotics and Sedatives ; therapeutic use ; Morphine ; therapeutic use ; Pain ; prevention & control ; Pain Management ; methods ; Respiration, Artificial
10.Effect of Dexmedetomidine Combined Electrical Stimulation on Coanitive Function of Patients Receiving Extracerebral Intervention.
Jun YUAN ; Yu WU ; Ji-yong LI ; Xi CHEN ; Li ZHANG ; Yu-feng LIU ; Sheng-xiong TONG ; Fang-fang DENG
Chinese Journal of Integrated Traditional and Western Medicine 2016;36(3):285-288
OBJECTIVETo explore the effect of dexmedetomidine combined electrical stimulation on cognitive function of neurosurgical diseases patients treated by extracerebral intervention.
METHODSTotally 122 patients with neurosurgical diseases who underwent selective intervention were randomly assigned to the observation group and the control group, 61 cases in each group. Patients in the control group recieved anesthesia by dexmedetomidine. Those in the observation group received electrical stimulation at Baihui (DU20), Yintang ( EX-HN3), and Neiguan (PC6) before dexmedetomidine anesthesia. The cognitive function of patients at preoperative day 1 and postoperative day 1 was respectively evaluated by Mini-Mental State Examinations (MMSE). Serum NSE, S-100β, IL-1β, IL-6, and TNF-α levels were detected in the two groups before intervention and immediately after intervention using ELISA.
RESULTSMMSE scores of two groups were significantly reduced at post-intervention day 1, as compared with one day before intervention. MMSE score of the observation group at post-intervention day 1 was (23.15 ± 1.87) points, significantly higher than that of the control group [ (19.34 ± 1.64) points , (P < 0.05)]. The postoperative cognitive dysfunction (POCD) incidence rate of the observation group was 16.4% (10/61), significantly lower than that of the control group [39.3% (24/61); P < 0.05]. Compared with before intervention, NSE and S-100β protein levels, IL-1β, IL-6 and α-TNF levels of the two groups increased (P < 0.05). Post-intervention NSE and S-100β protein levels, IL-1β, IL-6 and α-TNF levels were significantly lower in the observation group than in the control group (P < 0.05).
CONCLUSIONDexmedetomidine combied electrical stimulation could effectively prevent the occurrence of postoperative cognition, and reduce levels of NSA, S-100β, IL-1β, IL-6 and TNF-α.
Acupuncture Points ; Anesthesia ; methods ; Cognition ; Cognition Disorders ; prevention & control ; Dexmedetomidine ; therapeutic use ; Electric Stimulation Therapy ; Humans ; Interleukin-1beta ; blood ; Interleukin-6 ; blood ; Neuropsychological Tests ; Neurosurgical Procedures ; Phosphopyruvate Hydratase ; blood ; Postoperative Complications ; Postoperative Period ; S100 Calcium Binding Protein beta Subunit ; blood ; Tumor Necrosis Factor-alpha ; blood

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