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1.
Chest ; 163(1): e19-e22, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36628680

RESUMO

CASE PRESENTATION: A 67-year-old woman with hypertension, type 2 diabetes mellitus, and hypothyroidism presented for an elective blepharoplasty. She underwent monitored anesthesia care with propofol and dexmedetomidine. No inhaled gases or neuromuscular blockade were administered during the procedure.


Assuntos
Dexmedetomidina , Diabetes Mellitus Tipo 2 , Hipertensão , Hipotensão , Bloqueio Neuromuscular , Propofol , Feminino , Humanos , Idoso , Diabetes Mellitus Tipo 2/complicações , Hipotensão/diagnóstico , Hipotensão/etiologia , Hipertensão/diagnóstico , Hipertensão/etiologia
2.
Int J Mol Sci ; 24(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36614208

RESUMO

Methotrexate (MTX) is a widely used neurotoxic drug with broad antineoplastic and immunosuppressant spectra. However, the exact molecular mechanisms by which MTX inhibits hippocampal neurogenesis are yet unclear. Dexmedetomidine (Dex), an α2-adrenergic receptor agonist, has recently shown neuroprotective effects; however, its full mechanism is unexplored. This study investigated the potential of Dex to mitigate MTX-induced neurotoxicity and memory impairment in rats and the possible role of the miR-15a/ROCK-1/ERK1/2/CREB/BDNF pathway. Notably, no former studies have linked this pathway to MTX-induced neurotoxicity. Male Sprague Dawley rats were placed into four groups. Group 1 received saline i.p. daily and i.v. on days 8 and 15. Group 2 received Dex at 10 µg/kg/day i.p. for 30 days. Group 3 received MTX at 75 mg/kg i.v. on days 8 and 15, followed by four i.p. doses of leucovorin at 6 mg/kg after 18 h and 3 mg/kg after 26, 42, and 50 h. Group 4 received MTX and leucovorin as in group 3 and Dex daily dosages as in group 2. Bioinformatic analysis identified the association of miR-15a with ROCK-1/ERK1/2/CREB/BDNF and neurogenesis. MTX lowered hippocampal doublecortin and Ki-67, two markers of neurogenesis. This was associated with the downregulation of miR-15a, upregulation of its target ROCK-1, and reduction in the downstream ERK1/2/CREB/BDNF pathway, along with disturbed hippocampal redox state. Novel object recognition and Morris water maze tests demonstrated the MTX-induced memory deficiencies. Dex co-treatment reversed the MTX-induced behavioral, biochemical, and histological alterations in the rats. These neuroprotective actions could be partly mediated through modulating the miR-15a/ROCK-1/ERK1/2/CREB/BDNF pathway, which enhances hippocampal neurogenesis.


Assuntos
Dexmedetomidina , MicroRNAs , Ratos , Masculino , Animais , Metotrexato/toxicidade , Metotrexato/metabolismo , Ratos Sprague-Dawley , Dexmedetomidina/farmacologia , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Sistema de Sinalização das MAP Quinases , Leucovorina/farmacologia , Hipocampo/metabolismo , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/metabolismo , Neurogênese , MicroRNAs/metabolismo
3.
Clin J Pain ; 39(2): 85-90, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36650604

RESUMO

OBJECTIVES: The optimal dosage of dexmedetomidine (DEX) for postoperative analgesia of quadratus lumborum block (QLB) after laparoscopic myomectomy is not clear. Our study evaluated the analgesic and adverse effects of different doses of locally administered DEX. MATERIALS AND METHODS: Patients underwent laparoscopic myomectomy were enrolled in this randomized controlled trial. Transmuscular bilateral QLB was conducted postoperatively using local anesthetic plus different doses of DEX, as an adjuvant, per side. Numeric rating scales (NRS) of pain score and heart rate (HR) were assessed after performing QLB. Additional analgesics through patient-controlled analgesia pump, recovery time to first flatus, hospital stay, and other outcomes were also compared. RESULTS: A total of 150 participants were randomly divided into 3 groups (DEX1 group: 0.1 µg/kg; DEX2 group: 0.3 µg/kg; DEX3 group: 0.5 µg/kg), 50 for each group. Compared with the DEX1 group, NRS pain scores were lower in groups DEX2 and DEX3 ( P <0.017) 20 minutes after QLB and the significance lasted for 24 hours. Patients in groups DEX2 and DEX3 needed fewer additional analgesics than the group DEX1 ( P <0.017). HR in groups DEX2 and DEX3 was lower than the group DEX1 10 minutes and 20 minutes after QLB, respectively ( P <0.017). Sixty minutes after QLB, HR in the DEX3 group was still lower than the other groups. More patients in the DEX3 group were found bradycardia. Satisfaction score of postoperative analgesia was higher in groups DEX2 and DEX3 than the DEX1 group ( P <0.017). DISCUSSION: The results suggest that solution of DEX 0.3 µg/kg in ropivacaine 0.25% for QLB is recommended to relieve postoperative pain after laparoscopic myomectomy effectively and safely.


Assuntos
Dexmedetomidina , Laparoscopia , Miomectomia Uterina , Feminino , Humanos , Dexmedetomidina/uso terapêutico , Miomectomia Uterina/efeitos adversos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Anestésicos Locais/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Analgésicos/uso terapêutico , Analgesia Controlada pelo Paciente , Analgésicos Opioides , Ultrassonografia de Intervenção/métodos
4.
Trials ; 24(1): 62, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36703176

RESUMO

AIMS: This trial aims to assess whether dexmedetomidine can reduce the incidence of postoperative cognitive dysfunction in elderly orthopaedic patients and explore the specific mechanism. BACKGROUND: Postoperative cognitive dysfunction is a common complication after orthopaedic surgery that results in poor prognosis and increases the length of hospital stays and costs. Dexmedetomidine has been confirmed as a drug that can improve postoperative cognitive dysfunction in some studies. However, to date, the specific mechanism by which dexmedetomidine improves postoperative cognitive dysfunction is still elusive. METHODS/DESIGN: A single-centre, prospective, double-blinded, randomized controlled trial will be conducted at Hebei General Hospital. Ninety-six elderly patients who undergo total hip or knee replacement will be studied in this trial and randomly divided into two groups. Patients in the experimental group will receive a loading dose of 0.5 µg/kg dexmedetomidine for 10 min and then a maintenance dose of 0.5 µg/kg/h dexmedetomidine until 30 min before the end of the operation, and patients in the control group will be infused with an equal volume of normal saline. The incidence of postoperative cognitive dysfunction will be the primary outcome. Changes in the balance of T helper 17 cell and regulatory T cell; the levels of matrix metalloproteinase 9, S-100ß, IL-17A, and IL-10; perioperative complications; hospitalization duration; and intraoperative blood loss will be the secondary outcomes. DISCUSSION: The consequences of this trial will show that dexmedetomidine can improve postoperative cognitive dysfunction in elderly orthopaedic patients, which may be related to the balance of T helper 17/regulatory T cells. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200055802 . Registered on 20 January 2022.


Assuntos
Disfunção Cognitiva , Dexmedetomidina , Procedimentos Ortopédicos , Complicações Cognitivas Pós-Operatórias , Idoso , Humanos , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/prevenção & controle , Dexmedetomidina/uso terapêutico , Método Duplo-Cego , Procedimentos Ortopédicos/efeitos adversos , Complicações Cognitivas Pós-Operatórias/diagnóstico , Complicações Cognitivas Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 37(1): 106-114, 2023 Jan 15.
Artigo em Chinês | MEDLINE | ID: mdl-36708123

RESUMO

Objective: To summarize the research progress of the analgesic effect of adductor canal block (ACB) applied to knee arthroplasty, in order to find the ACB mode that can obtain better effectiveness. Methods: The research progress of the analgesic effect of ACB after knee arthroplasty was reviewed by widely consulting the related literature on ACB at home and abroad in recent years. Results: In recent years, multimodal analgesia has become the mainstay of postoperative pain management after knee arthroplasty. Among these, ACB replaces the once "gold standard" femoral nerve block (FNB) by offering comparable and effective analgesia with better preservation of quadriceps function. It is generally safe and efficient to use 0.2% ropivacaine ACB with initial loading doses of 15-30 mL and continual loading doses of less than 8 mL/hour to give analgesia comparable to FNB with minimal impact on lower extremity muscular strength. However, the risk of patient falls must still be taken into consideration by medical staff. Adjuvants like dexmedetomidine and dexamethasone used in ACB can increase the analgesic duration and postoperative analgesic impact. As a perineural adjunct for ACB, 1 µg/kg dexmedetomidine may strike a balance between safety and analgesic efficacy. Conclusion: ACB is a safe and effective analgesia method after knee arthroplasty. The adductor canal anatomy, the optimum blocking strategy and blocking site of ACB are all hotly debated and still require additional study due to the significant variety of the nerve structures in adductor canal.


Assuntos
Artroplastia do Joelho , Dexmedetomidina , Bloqueio Nervoso , Humanos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Nervo Femoral , Artroplastia do Joelho/métodos , Dexmedetomidina/farmacologia , Bloqueio Nervoso/métodos , Analgésicos Opioides/farmacologia
6.
BMJ Open ; 13(1): e063976, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36690404

RESUMO

INTRODUCTION: Postoperative delirium (POD) is a common surgical complication. The incidence is 19% in neurological procedures, and advanced age is a risk factor for neurological procedures. Many studies have shown that dexmedetomidine (DEX) reduced the incidence of delirium after non-cardiac surgery in elderly patients. However, there are few studies focus on the effect of DEX on POD in elderly patients undergoing neurosurgery. METHODS AND ANALYSIS: This is a randomised, double-blinded, paralleled-group and controlled trial. Patients older than 65 years and scheduled for elective craniotomy will be randomly assigned to the DEX group and the control group. After endotracheal intubation, patients in the DEX group will be administered with continuous DEX infusion at rate of 0.4 µg/kg/hour until the surgical haemostasis. In the control group, patients will receive the identical volume of normal saline in the same setting. The primary outcome is the incidence of POD during the first 5 days. Delirium will be evaluated through a combination of three methods, including the Richmond Agitation Sedation Scale (RASS), the confusion assessment method for ICU (CAM-ICU) and the 3 min diagnostic interview for CAM (3D-CAM). The RASS, CAM-ICU and 3D-CAM will be evaluated two times per day (08:00-10:00 and 18:00-20:00 hours) during the first postoperative 5 days. Secondary outcomes include pain severity score, quality of recovery, quality of sleep, cognitive function, psychological health state, intraoperative data, physiological status, length of stay in ICU and hospital, hospitalisation costs, non-delirium complications, and 30-day all-cause mortality. ETHICS AND DISSEMINATION: The protocol (V.4.0) has been approved by the medical ethics committee of Beijing Tiantan Hospital, Capital Medical University (KY2021-194-03). The findings of the study will be disseminated in a peer-reviewed journal and at a scientific conference. TRIAL REGISTRATION NUMBER: NCT05168280.


Assuntos
Dexmedetomidina , Delírio do Despertar , Humanos , Idoso , Dexmedetomidina/uso terapêutico , Delírio do Despertar/induzido quimicamente , Método Duplo-Cego , Unidades de Terapia Intensiva , Craniotomia , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
PLoS One ; 18(1): e0278846, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36649357

RESUMO

This meta-analysis aimed to analyze and compare the efficacy and safety of remifentanil and dexmedetomidine applied respectively for controlled hypotension under general anesthesia. We searched the Cochrane Library, PubMed, EMBASE, Web of Science, CNKI, SinoMed, Wanfang, and VIP databases, as well as dissertations and conference papers, to obtain randomized controlled trials comparing remifentanil and dexmedetomidine applied respectively for controlled hypotension before August 23, 2021. The primary outcomes included hemodynamic profiles, surgical field score, and blood loss. Extubation time, sedation and pain score at the PACU, and perioperative adverse events were the secondary outcomes. Nine randomized controlled trials with 543 patients (272 in the dexmedetomidine group and 271 in the remifentanil group) were eventually included. This meta-analysis indicated no significant difference between dexmedetomidine and remifentanil in terms of surgical field score, blood loss, minimum values of mean arterial pressure (MD 0.24 with 95% CI [-1.65, 2.13], P = 0.80, I2 = 66%) and heart rate (MD 0.42 [-1.33, 2.17], P = 0.64, I2 = 40%), sedation scores at the PACU (MD -0.09 [-0.69, 0.50], P = 0.76, I2 = 92%), and incidence of bradycardia (OR 2.24 [0.70, 7.15], P = 0.17, I2 = 0%). Compared with remifentanil, dexmedetomidine as the controlled hypotensive agent showed a lower visual analogue score at the PACU (MD -1.01 [-1.25, -0.77], P<0.00001, I2 = 0%) and incidence of shivering (OR 0.22 [0.08, 0.60], P = 0.003, I2 = 0%), nausea, and vomiting (OR 0.34 [0.13, 0.89], P = 0.03, I2 = 0%). However, extubation time was shorter in the remifentanil group (MD 3.34 [0.75, 5.93], P = 0.01, I2 = 90%). In conclusion, dexmedetomidine and remifentanil are both effective in providing satisfactory controlled hypotension and surgical conditions. Dexmedetomidine is better in easing postoperative pain at the PACU and reducing the occurrence of shivering, nausea, and vomiting. Meanwhile, remifentanil is a fast-track anesthesia with a shorter extubation time. Given the limitations of this meta-analysis, further studies are needed for a more definitive comparison of the efficacy and safety of dexmedetomidine and remifentanil.


Assuntos
Dexmedetomidina , Hipotensão Controlada , Humanos , Remifentanil , Dexmedetomidina/efeitos adversos , Anestesia Geral/efeitos adversos , Náusea , Vômito
8.
Trials ; 24(1): 2, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36597163

RESUMO

BACKGROUND: Oral chloral hydrate is widely used in pediatric sedation. Intranasal dexmedetomidine has been increasingly used for pediatric sedation; however, its improvement is warranted. The combination of dexmedetomidine with ketamine can improve onset and hemodynamic stability while maintaining sedative efficacy. This study aims to determine the efficacy and safety of intranasal combination of dexmedetomidine and ketamine compared to oral chloral hydrate. METHODS: This is a prospective, parallel-arm, single-blinded, two-center, superiority randomized controlled trial with 1:1 allocation, designed to compare the effects of intranasal combination of dexmedetomidine and ketamine with those of oral chloral hydrate. We shall enroll 136 patients aged < 7 years old in this study. Prior to the procedure, we shall randomize each patient into the control group (oral chloral hydrate 50 mg/kg) or study group (intranasal dexmedetomidine 2 µg/kg and ketamine 3 mg/kg). The primary outcome will be the rate of achieving an adequate sedation level (6-point Pediatric Sedation State Scale 1, 2, or 3) within 15 min. In addition, we shall measure the sedation time, sedation failure rate, completion of procedure, adverse events, patient acceptance, and physician satisfaction. DISCUSSION: This study will provide evidence of the efficacy and safety of the intranasal combination of dexmedetomidine and ketamine in comparison with oral chloral hydrate. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04820205. Registered on 19th March 2021.


Assuntos
Dexmedetomidina , Ketamina , Criança , Humanos , Administração Intranasal , Administração Oral , Hidrato de Cloral/administração & dosagem , Dexmedetomidina/administração & dosagem , Hipnóticos e Sedativos/administração & dosagem , Ketamina/administração & dosagem , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto , Combinação de Medicamentos
9.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(1): 155-160, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-36647659

RESUMO

Objective: To study the postoperative analgesic effect of ropivacaine combined with dexmedetomidine for serratus anterior plane block (SAPB) under ultrasound visualization plus patient-controlled intravenous analgesia (PCIA) in patients undergoing thoracoscopic radical resection of lung cancer. Methods: A total of 129 patients undergoing elective thoracoscopic surgery were enrolled. The patients were randomly assigned to three groups ( n=43 in each group), a normal saline group (control group), a ropivacaine mesylate group (Group R) and a ropivacaine mesylate combined with dexmetomidine hydrochloride group (Group RD). After operation, ultrasound-guided SAPB was performed and patients in the three groups received the injection of 0 mL of 0.9% normal saline, 25 mL of 0.5% ropivacaine, and 25 mL of 0.5% ropivacaine+1 µg/kg dextrometomidine hydrochloride mixture, respectively. In addition, PCIA was used for all the patients. The button on the PCIA pump was pressed when the postoperative pain visual analogue score (VAS)≥4 on coughing, and rescue analgesic of sufentanil was given intravenously at 2.5 µg/bolus. The primary outcome was the VAS scores at rest and on coughing at 10 min (T 1), 6 h (T 2), 12 h (T 3), 24 h (T 4), and 48 h (T 5) after extubation. The secondary outcomes included hemodynamics, the quality of sleep for the first 3 nights after operation, number of times the button on the PCIA pump was pressed, intraoperative and postoperative opioid dosage, time of first postoperative rescue analgesic, duraion of intubation, length of stay at the hospital, adverse reactions, etc. Results: Compared with those of the control group, the VAS scores of the Group R and Group RD were significantly lower at 10 min, 6 h, and 12 h after extubation ( P<0.05). In comparison with Group R, the number of patients requiring rescue analgesia, the time of first postoperative rescue analgesic, the number of times the button on the PCIA pump was pressed, and the total dose of rescue sufentanil were all significantly lower ( P<0.05) in the Group RD. Patients in the Group RD had better sleep quality in the second and third nights after operation and lower incidence of nausea and vomiting ( P<0.05). Conclusion: 0.5% ropivacaine and 1 µg/kg dexmedetomidine SAPB combined with PCIA can significantly reduce postoperative pain and improve postoperative recovery quality in patients undergoing thoracoscopic radical resection of lung cancer.


Assuntos
Dexmedetomidina , Neoplasias Pulmonares , Humanos , Ropivacaina/uso terapêutico , Dexmedetomidina/uso terapêutico , Sufentanil/uso terapêutico , Solução Salina , Analgesia Controlada pelo Paciente/efeitos adversos , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Analgésicos/uso terapêutico , Neoplasias Pulmonares/cirurgia
10.
Mol Med Rep ; 27(1)2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36321783

RESUMO

Allergic asthma is a chronic inflammatory disease in which oxidative stress serves a pivotal role. In clinical practice, dexmedetomidine (DEX), an α­2­adrenergic receptor agonist, is used as a sedative. DEX exhibits antioxidative and organ­protective properties. In a murine model of asthma, DEX has a therapeutic effect via the toll like receptor 4/NF­ÐºB signaling pathway; however, whether DEX can exert an antioxidative effect on asthma has yet to be elucidated. In the present study, a T helper (Th)2­dominant murine asthma model was established. DEX treatment significantly reduced eosinophilic airway inflammation, mucus overproduction and airway hyperresponsiveness, as well as the concentrations of Th2 cytokines. The lung tissues of mice with asthma were characterized by redox imbalance (increased oxidative stress and impaired antioxidant capacity). DEX treatment alleviated this imbalance by decreasing the levels of malondialdehyde and reactive oxygen species, and increasing the levels of glutathione. Furthermore, the nuclear factor erythroid 2­related factor 2 (Nrf2) signaling pathway was inhibited in the lung tissues of asthmatic mice; these effects were noted in its downstream genes, heme oxygenase 1 and glutathione peroxidase 4. In mice with asthma, DEX treatment induced the expression of these antioxidant genes and the activation of Nrf2, whereas ML385 (an inhibitor of Nrf2) partially abrogated the antioxidative and therapeutic effects of DEX. To the best of our knowledge, the present study is the first to demonstrate the protective effect of DEX on Th2­dominant asthma through the activation of the Nrf2 signaling pathway. The results suggested that the antioxidative properties of DEX could be beneficial in clinical application of DEX for the relief of asthmatic symptoms.


Assuntos
Asma , Dexmedetomidina , Animais , Camundongos , Antioxidantes/farmacologia , Asma/metabolismo , Dexmedetomidina/farmacologia , Inflamação/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Transdução de Sinais
11.
Med Gas Res ; 13(3): 112-117, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36571375

RESUMO

Electroconvulsive therapy (ECT) is one of the therapeutic opportunities for patients with psychological disorders when they may decline to take medication. We sought to systematically compare the anesthetic efficacy of ketamine, propofol, and dexmedetomidine for electroconvulsive therapy in treatment-resistant major depressive disorder patients. This double-blind trial enrolled treatment-resistant major depressive disorder patients (n = 85) who had been hospitalized for ECT in the Amir Kabir Hospital's psychiatric ward (Arak, Iran). The ketamine, propofol, and dexmedetomidine groups received a dose of 0.2 µg/kg ketamine, 1.5 mg/kg propofol, and 0.8 mg/kg dexmedetomidine, respectively. In all intervention groups, 10 mL of interventional drugs was injected intravenously for 10 minutes, and in the placebo group, 10 mL of normal saline was given over the same period. The dexmedetomidine group's blood pressure was revealed comparatively lower at all times. Dexmedetomidine-treated patients showed their marked satisfaction, while those treated with propofol had shorter recovery time, shorter seizure duration, and shorter time to achieve an Aldrete score of 9-10 and increased relaxation, and next dexmedetomidine produced deeper relaxation. Propofol could shorten recovery time and seizure duration, and enhance relaxation, while dexmedetomidine was associated with higher patient satisfaction. Considering that any anesthetic which does not shorten seizure duration may serve efficiently for ECT and that ketamine-treated patients had more prolonged seizure duration, the preferred drug can hence be considered from various angles, thereby offering anesthetic agents with highly favorable efficacy in treatment-resistant major depressive disorder patients needing ECT. The drug choice thus depends on physical conditions, underlying diseases, and psychiatrist consultation.


Assuntos
Anestesia , Transtorno Depressivo Maior , Dexmedetomidina , Eletroconvulsoterapia , Ketamina , Propofol , Humanos , Propofol/efeitos adversos , Ketamina/farmacologia , Ketamina/uso terapêutico , Eletroconvulsoterapia/efeitos adversos , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/psicologia , Dexmedetomidina/farmacologia , Dexmedetomidina/uso terapêutico , Anestésicos Intravenosos/efeitos adversos , Resultado do Tratamento , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico
12.
Res Vet Sci ; 154: 124-131, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36584520

RESUMO

The aim of this randomized, prospective clinical study was to evaluate the efficacy of dexmedetomidine combined with bupivacaine on sciatic and femoral nerve blocks in dogs. Thirty dogs were selected for elective unilateral tibial plateau levelling osteotomy, and each subject was assigned randomly to receive perineural bupivacaine 0.5% (0.1 mL/kg) and intramuscular dexmedetomidine (0.5 µg/kg) in the BDs group, perineural bupivacaine 0.5% (0.1 mL/kg) plus dexmedetomidine (0.5 µg/kg) in the BDloc group, and perineural bupivacaine 0.5% (0.1 mL/kg) plus intramuscular administration of saline solution the in Bupi group. Nerve blocks were guided by electrolocation. The main intraoperative parameters were registered 10 min before the start of surgery (BASE) and during the skin incision (SKIN), the osteotomy (BONE) and the suture (SUTURE). At 2, 4, 6, 8, 10, 15, 20 and 24 h after blocks, the Glasgow Composite Pain scale (GPCs) was used to identify the degree of pain during the postoperative period. Patients with scores ≥5/20 received rescue analgesia and were excluded. Furthermore, heart rate, mean arterial pressure, footstep capacity, reaction to wound touch and femoral and sciatic skin sensitivity were registered. Parametric data were compared at each time point of the study with the one-way ANOVA for repeated measures and Fisher's test for yes/no variables analysis (p < 0.05). No subject required intraoperative rescue analgesia. In BDloc group, the GCPs score was <5/20 for all dogs at all times of the study, and 70% of dogs did not need systemic analgesia. In the Bupi and BDs groups, 100% of subjects achieved a score ≥ 5/20 between 8 and 10 h after the blocks, and 100% of subjects showed femoral and sciatic skin sensitivity and required rescue analgesia within 10 h. Our results showed that the addition of dexmedetomidine as an adjuvant to bupivacaine in SF blocks may prolong the sensory block and ensure sufficient analgesia for up to 24 h in dogs undergoing TPLO surgery.


Assuntos
Dexmedetomidina , Doenças do Cão , Cães , Animais , Bupivacaína/farmacologia , Bupivacaína/uso terapêutico , Dexmedetomidina/farmacologia , Dexmedetomidina/uso terapêutico , Estudos Prospectivos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/veterinária , Nervo Isquiático/cirurgia , Osteotomia/veterinária , Osteotomia/métodos , Anestésicos Locais/farmacologia , Anestésicos Locais/uso terapêutico , Doenças do Cão/cirurgia
13.
Anesthesiology ; 138(2): 164-171, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36534899

RESUMO

BACKGROUND: Delirium is a critical postoperative complication in older patients. Based on the hypothesis that intraoperative dexmedetomidine sedation would lower postoperative delirium than propofol sedation would, the authors compared the incidence of postoperative delirium in older adults, using the mentioned sedatives. METHODS: This double-blinded, randomized controlled study included 748 patients, aged 65 yr or older, who were scheduled for elective lower extremity orthopedic surgery, between June 2017 and October 2021. Patients were randomized equally into two groups in a 1:1 ratio according to the intraoperative sedative used (dexmedetomidine vs. propofol). The postoperative delirium incidence was considered the primary outcome measure; it was determined using the confusion assessment method, on the first three postoperative days. The mean arterial pressure and heart rate were evaluated as secondary outcomes. RESULTS: The authors enrolled 732 patients in the intention-to-treat analyses. The delirium incidence was lower in the dexmedetomidine group than in the propofol group (11 [3.0%] vs. 24 [6.6%]; odds ratio, 0.42; 95% CI, 0.201 to 0.86; P = 0.036). During sedation, the mean arterial pressure (median [interquartile range] mmHg) was higher in the dexmedetomidine group (77 [71 to 84]) than in the propofol group (74 [69 to 79]; P < 0.001); however, it significantly fell lower (74 [68 to 80]) than that of the propofol group (80 [74 to 87]) in the postanesthesia care unit (P < 0.001). Lower heart rates (beats/min) were recorded with the use of dexmedetomidine than with propofol, both during sedation (60 [55 to 66] vs. 63 [58 to 70]) and in the postanesthesia care unit (64 [58 to 72] vs. 68 [62-77]; P < 0.001). CONCLUSIONS: Dexmedetomidine showed a lower incidence of postoperative delirium than propofol in healthy older adults undergoing lower extremity orthopedic surgery.


Assuntos
Raquianestesia , Delírio , Dexmedetomidina , Delírio do Despertar , Propofol , Humanos , Idoso , Propofol/efeitos adversos , Dexmedetomidina/efeitos adversos , Delírio do Despertar/induzido quimicamente , Raquianestesia/efeitos adversos , Delírio/induzido quimicamente , Delírio/epidemiologia , Hipnóticos e Sedativos/efeitos adversos , Extremidade Inferior/cirurgia
15.
Eur J Pharm Biopharm ; 183: 47-60, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36565969

RESUMO

The purpose of this study was to prepare a dexmedetomidine (Dex) 72 h long-acting patch by the combined use of ion-pair strategy and chemical enhancers (CEs), and to investigate molecular mechanisms of drug-loading enhancement and controlled release. The formulation of patch was optimized by single-factor investigation and Box-Behnken design. The pharmacokinetics, analgesic pharmacodynamics and irritation of the formulation were evaluated, respectively. Moreover, the effects of ion-pairs and CEs on the patch were characterized by DSC, rheology study, FTIR, and molecular docking, and the effects on the skin were evaluated by Attenuated Total Reflection Fourier Transform Infrared Spectroscopy (ATR-FTIR), Raman study, and molecular dynamics, respectively. The optimized formulation was 17.00 % (w/w) Dex-NA (Naphthoic acid), 7.20 % Polyglyceryl-3 dioleate (POCC), 25-AAOH as pressure sensitive adhesives (PSA) and 66.50 µm in thickness. Compared with the control group (Cmax = 62.02 ± 16.55 ng/mL, MRT0-t = 26.74 ± 1.27 h), the pharmacokinetics behavior of the optimization group was more stable and durable (Cmax = 31.22 ± 13.26 ng/mL, MRT0-t = 33.62 ± 1.62 h). Besides, it also showed good analgesic effect and no obvious irritation. The results indicated that Dex-NA both increased the drug-PSA interactions and inhibited the penetration of the drug into the skin. POCC increased the molecular mobility of the PSA and disrupted skin lipids thereby improving the drug penetration rate. In summary, the Dex long-acting patch was developed, which provided a reference for the combined application of ion-pair strategy and CEs in other long-acting transdermal delivery.


Assuntos
Dexmedetomidina , Absorção Cutânea , Dexmedetomidina/farmacologia , Dexmedetomidina/metabolismo , Simulação de Acoplamento Molecular , Preparações de Ação Retardada/farmacologia , Adesivo Transdérmico , Pele/metabolismo , Administração Cutânea , Adesivos/química , Espectroscopia de Infravermelho com Transformada de Fourier
16.
Br J Anaesth ; 130(2): 142-153, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36494207

RESUMO

BACKGROUND: Dexmedetomidine is a widely used anaesthetic adjuvant for cancer resection surgeries. However, recent reports suggest that it may promote tumour growth or metastasis, so it is essential to clarify its tumour-related effects. METHODS: Seven syngeneic murine tumour models were used to assess the impact of dexmedetomidine on primary tumour growth, spontaneous tumour metastasis, and surgical resection-associated metastasis. Cancer cell proliferation and apoptosis experiments, terminal deoxynucleotidyl transferase dUTP nick-end labelling assays, immune cell analysis, specific T-cell depletion experiments, and gene transcription analysis were conducted to identify the underlying mechanisms. RESULTS: Dexmedetomidine did not affect growth of EO771 or 4T1 breast tumours, LAP0297 or LLC lung tumours, MCA205 fibrosarcoma, or their spontaneous lung metastases. It did not promote lung metastasis after breast cancer resection. Dexmedetomidine significantly suppressed MCA38 and CT26 colorectal tumour growth (P<0.01) and promoted apoptosis in MCA38 tumour tissues (P<0.05) without affecting proliferation and apoptosis of MCA38 tumour cells in vitro, suggesting indirect anti-tumour effects. Dexmedetomidine increased the proportions of intratumour CD4+ T (P<0.01), CD8+ T (P<0.001), and natural killer cells (P<0.01), and it upregulated transcription of the cytotoxicity-related genes Infg, Tnfa, and Cxcl9 (P<0.05) in MCA38 tumours. Either CD8+ or CD4+ T-cell depletion reversed the anti-tumour effects of dexmedetomidine on MCA38 tumours (P<0.05). CONCLUSIONS: Dexmedetomidine conferred colorectal tumour-type specific suppression by modulation of tumour CD4+ and CD8+ T cells without tumour-enhancing effects.


Assuntos
Neoplasias da Mama , Neoplasias Colorretais , Dexmedetomidina , Neoplasias Pulmonares , Humanos , Camundongos , Animais , Feminino , Dexmedetomidina/farmacologia , Dexmedetomidina/uso terapêutico , Modelos Animais de Doenças , Linfócitos T CD8-Positivos/patologia , Neoplasias Pulmonares/patologia
17.
Br J Anaesth ; 130(2): e307-e316, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36517290

RESUMO

BACKGROUND: Delirium is common, especially after neurosurgery. Dexmedetomidine might reduce delirium by improving postoperative analgesia and sleep quality. We tested the primary hypothesis that dexmedetomidine administration during intracerebral tumour resection reduces the incidence of postoperative delirium. METHODS: This randomised, double-blind, placebo-controlled trial was conducted in two tertiary-care hospitals in Beijing. We randomised 260 qualifying patients to either dexmedetomidine (n=130) or placebo (n=130). Subjects assigned to dexmedetomidine were given a loading dose of 0.6 µg kg-1 followed by continuous infusion at 0.4 µg kg-1 h-1 until dural closure; subjects in the placebo group were given comparable volumes of normal saline. The primary outcome was the incidence of delirium, which was assessed with the Confusion Assessment Method twice daily during the initial 5 postoperative days. RESULTS: The average (standard deviation) age of participating patients was 45 (12) yr, duration of surgery was 4.2 (1.5) h, and patients assigned to dexmedetomidine were given an average of 126 (45) µg of dexmedetomidine. There was less delirium during the initial 5 postoperative days in patients assigned to dexmedetomidine (22%, 28 of 130 patients) than in those given placebo (46%, 60 of 130 patients) with a risk ratio of 0.51 (95% confidence interval: 0.36-0.74, P<0.001). Postoperative pain scores with movement, and recovery and sleep quality were improved by dexmedetomidine (P<0.001). The incidence of safety outcomes was similar in each group. CONCLUSIONS: Prophylactic intraoperative dexmedetomidine infusion reduced by half the incidence of delirium during the initial 5 postoperative days in patients recovering from elective brain tumour resection. CLINICAL TRIAL REGISTRATION: NCT04674241.


Assuntos
Neoplasias Encefálicas , Delírio , Dexmedetomidina , Delírio do Despertar , Humanos , Dexmedetomidina/uso terapêutico , Delírio/etiologia , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/tratamento farmacológico , Neoplasias Encefálicas/cirurgia , Método Duplo-Cego
18.
Aging Clin Exp Res ; 34(3): 611-618, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34550563

RESUMO

OBJECTIVE: To clarify the effect of an intraoperative low-dose dexmedetomidine infusion on emergence agitation following general anaesthesia in elderly patients. METHODS: Eighty elderly patients (> 64-years-old) following elective general anaesthesia for radical cancer surgeries were randomly allocated into two groups (n = 40 each): the dexmedetomidine group (Group D) and the normal saline group (Group C). Anaesthesia was maintained with continuous intravenous infusion of dexmedetomidine at - 0.2 µg kg-1 h-1 in Group D, and an equal volume of normal saline (0.5 ml kg-1 h-1) was given in Group C. All patients were observed for 30 min in the post-anaesthesia care unit (PACU), AFPS and NRS were recorded every 2 min, and the total doses of nalbuphine and fentanyl were calculated in the PACU. MAP and HR were recorded at the time of 10 min (T1), 20 min (T2), 30 min (T3) after dexmedetomidine or saline pumping, and before extubation (T4), immediately after extubation (T5), and 5 min after extubation (T6). We also documented some durations, including anaesthesia duration (D1), surgery duration (D2), duration from the end of surgery to extubation (D3), and emergence agitation duration (D4). RESULTS: The MAP in Group C was significantly higher than that in Group D (P < 0.05), and there were no significant changes between the two groups in HR and MAP within each time point and D1, D2, D3, and D4. The incidence of agitation, NRS score and total dose of nalbuphine and fentanyl were all lower in Group D than in Group C (P < 0.05). CONCLUSION: An intraoperative low-dose dexmedetomidine continuous infusion can reduce emergence agitation following general anaesthesia in elderly patients (> 64-years-old), remain stable in terms of haemodynamics, and not lead to delays in anaesthesia recovery time and extubation time.


Assuntos
Dexmedetomidina , Delírio do Despertar , Idoso , Período de Recuperação da Anestesia , Anestesia Geral/efeitos adversos , Método Duplo-Cego , Delírio do Despertar/prevenção & controle , Fentanila/efeitos adversos , Humanos , Hipnóticos e Sedativos/efeitos adversos
19.
Oxid Med Cell Longev ; 2022: 5126042, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36531207

RESUMO

Ischemic stroke is the most common type of cerebrovascular disease with high mortality and poor prognosis, and cerebral ischemia-reperfusion (CI/R) injury is the main murderer. Here, we attempted to explore the effects and mechanism of Xuesaitong (XST) combined with dexmedetomidine (Dex) on CI/R injury in rats. First, a rat model of CI/R injury was constructed via the middle cerebral artery occlusion (MCAO) method and treated with XST and Dex alone or in combination. Then, on the 5th and 10th days of treatment, the neurological impairment was assessed using the modified neurological severity scores (mNSS), the 8-arm radial maze test (8ARMT), novel object recognition test (NORT), and fear conditioning test (FCT). H&E staining was performed to observe the pathological changes of the hippocampus. ELISA and related kits were used to assess the monoamine neurotransmitters and antioxidant enzyme activities in the hippocampus. The ATP, mitochondrial membrane potential levels, and qRT-PCR of genes related to mitochondrial function were determined to assess mitochondrial functions in the hippocampus and western blot to determine Keap1/Nrf2 signaling pathway and mitophagy-related protein expression. The results showed that XST combined with Dex significantly reduced mNSS, improved spatial memory and learning deficits, and enhanced fear memory and cognitive memory ability in CI/R rats, which was superior to single-drug treatment. Moreover, XST combined with Dex treatment improved hippocampal histopathological damage; significantly increased the levels of monoamine neurotransmitters, neurotrophic factors, ATP, and mitochondrial membrane potential; and upregulated the activities of antioxidant enzymes and the expression of mitophagy-related proteins in the hippocampus of CI/R rats. XST combined with Dex treatment also activated the Keap1/Nrf2 signaling and upregulated the protein expression of downstream antioxidant enzymes HO-1 and NQ. Altogether, this study showed that a combination of XST and Dex could activate the Keap1/Nrf2 signaling and mitophagy to protect rats from CI/R-related neurological impairment.


Assuntos
Isquemia Encefálica , Dexmedetomidina , Traumatismo por Reperfusão , Ratos , Animais , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Dexmedetomidina/farmacologia , Dexmedetomidina/uso terapêutico , Antioxidantes/farmacologia , Mitofagia , Traumatismo por Reperfusão/patologia , Transdução de Sinais , Infarto da Artéria Cerebral Média/metabolismo , Hipocampo/metabolismo , Trifosfato de Adenosina/farmacologia , Isquemia Encefálica/tratamento farmacológico
20.
BMC Anesthesiol ; 22(1): 398, 2022 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-36544098

RESUMO

OBJECTIVE: The aim of this prospective randomized double-blind study is to evaluate whether oral dexmedetomidine (DEX) premedication could increase sedation in order to reduce preoperative anxiety and inhibit stress response during general anesthesia tracheal intubation. MATERIALS: A total of 100 ASA I and II adult patients undergoing elective neurosurgery were randomly divided into the control group (C group, n = 50) and the oral DEX premedication (DEX group, n = 50). Patients were administrated 4 µg/kg dexmedetomidine orally pre-anesthesia 120 min. Hemodynamic variables were monitored and recorded from premedication to 10 min after tracheal intubation. The primary outcome, the sedation level of all participants, was evaluated by Richmond Agitation Sedation Scale (RASS), and Numerical Rating Scale was to measure their intensity of thirst and satisfaction of patients' family members. During general anesthesia induction, the total dosage of induction anesthetics and complications relative to anesthesia induction were recorded. After tracheal intubation, blood sample was drain from radial atrial line to measure levels of adrenocorticotropic hormone (ACTH) and cortisol. RESULTS: RASS scores at 60 min after premedication and on arrival in the operating room were significantly reduced in the DEX group (P < 0.001). Oral DEX premedication not only increased the intensity of thirst but also the satisfaction of their family members (P < 0.001). The cortisol level after tracheal intubation was deduced by oral DEX premedication (P < 0.05). Oral DEX premedication reduced heart rate (HR) and mean arterial pressure (MAP) on arrival in the operating room, and HR when tracheal intubation (P < 0.05). During the whole process of anesthesia induction, although the lowest MAP in two groups were not significantly different, the lowest HR was significantly lower in the DEX group (P < 0.05). Oral DEX premedication might reduce HR from premedication to 10 min after tracheal intubation. However MAP was reduced just from premedication to on arrival in the operating room. Total induction dosages of propofol, midazolam, sulfentanil and rocuronium were similar in two groups (P > 0.05), as well as the complications relative to anesthesia induction and cases of rescue dopamine therapy were similar (P > 0.05). CONCLUSION: Oral DEX 4 µg/kg premedication was an efficient intervention to increase preoperative sedation and reduce stress reaction induced by general anesthesia tracheal intubation, but also it was with the stable hemodynamic during the process of general anesthesia tracheal intubation, and improved the satisfaction of patients' family members. In this study, the sparing-anesthetic effect of 4 µg/kg DEX oral premedication was not significant, and this would be needed to study in future. TRIAL REGISTRATION: This trail was registered at Chinese Clinical Trial Registry ( https://www.chictr.org.cn , Jie Gao) on 15/04/2021, registration number was ChiCTR2100045458.


Assuntos
Anestésicos , Dexmedetomidina , Humanos , Adulto , Hipnóticos e Sedativos/farmacologia , Método Duplo-Cego , Estudos Prospectivos , Hidrocortisona , Anestesia Geral , Intubação Intratraqueal
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