Meta-analysis of efficacy and safety of sedative therapy with midazolam and dexmedetomidine/propofol in critically ill patients undergoing mechanical ventilation / 中国药房

OBJECTIVE To systematically evaluate the efficacy and safety of midazolam and dexmedetomidine/propofol for the sedation of critically ill patients undergoing mechanical ventilation， and to provide evidence-based reference for clinical treatment. METHODS Retrieved from PubMed， Embase， Web of Science， Cochrane Library， Clinical trials. gov， China Journal Full Text Database， Chinese Science and Technology Journal Database， Wanfang database and China Biomedical Literature Database， the data on the efficacy and safety of midazolam and dexmetomidine/propofol for the sedation of critically ill patients undergoing mechanical ventilation were collected from the establishment of the database to March 31， 2023. After extracting data from clinical studies that met the inclusion criteria， the meta-analysis was conducted by using the RevMan 5.3 statistical software. RESULTS A total of 31 literature were included， with a total of 2 765 patients. Results of meta-analysis showed that the mechanical ventilation time [MD＝14.13， 95%CI （13.75， 14.52）， P＜0.000 01] and the length of hospitalization in the intensive care unit [MD＝0.92， 95%CI （0.54， 1.30）， P＜0.000 01] of patients in the midazolam group was longer than dexmedetomidine/ propofol group. The incidence of bradycardia in midazolam group was lower dexmedetomidine/propofol group [OR＝0.60， 95%CI （0.41， 0.90）， P＝0.01]， but there was no statistically significant difference in the incidence of hypotension between the two groups [OR＝0.69， 95%CI （0.47， 1.01）， P＝0.06]. The incidence of delirium [OR＝3.88， 95%CI （2.74， 5.49）， P＜0.000 01]， ventilator- associated pneumonia [OR＝2.32， 95%CI （1.19， 4.51）， P＝0.01]， and respiratory depression [OR＝5.70， 95%CI （3.09， 10.52）， P＜0.000 01] in midazolam group were higher than dexmedetomidine/propofol group. CONCLUSIONS Compared with dexmedetomidine/propofol， midazolam increases patients’ mechanical ventilation time and the length of hospitalization in the intensive care unit in terms of efficacy， and increases the risk of delirium and pulmonary complications in terms of safety， but has a smaller cardiovascular impact.

Dexmedetomidine versus sufentanil as adjuvants to bupivacaine for brachial plexus block during upper extremity surgery: a randomized clinical trial

Abstract Background: Brachial plexus block (BPB) has been accepted as a reliable alternative for general anesthesia in upper limb surgeries. Adding adjuvant drugs like dexmedetomidine and sufentanil has been shown to have clinical and pharmacologic advantages. In this randomized parallel clinical trial, we aim to compare the effects of these two adjuvants for bupivacaine in BPB. Methods: In this double-blinded study, by using computer-assisted block randomization, 40 patients ranged from 20 to 65 years old and scheduled for elective upper limb surgeries were assigned to two equal study groups (n = 20), receiving 1 mL of 5 μg.mL-1 sufentanil (group S) or 1 mL of 100 μg.mL-1 dexmedetomidine (group D) in adjunction to 30 mL of 0.5% bupivacaine for supraclavicular BPB under the guidance of ultrasonography. Characteristics of local anesthesia and postoperative analgesia were evaluated (n = 40). Results: The duration of blocks significantly improved in group S (sensory: estimated median difference (EMD) [95%CI] = 100.0 [70.0~130.0], p < 0.001; motor: EMD [95%CI] = 120.0 [100.0~130.0], p < 0.001). Group S also had significantly longer postoperative analgesia and lower opioid consumption within 24 hours after the surgery (EMD [95%CI] = 4.0 [3.0~7.0], p < 0.001; EMD [95%CI] = -5.0 [-5.0~-5.0], p < 0.001; respectively). None of the patients showed adverse effects concerning vital signs, nausea, or vomiting. Conclusion: Our study showed that during ultrasound-guided supraclavicular BPB, sufentanil is a fairly better choice than dexmedetomidine as an adjuvant for bupivacaine and can provide preferable sensory and motor blocks. No significant side effects were seen in either of the study groups.

Ultrasound Guided Fascia Iliaca Compartment Block Using Either Bupivacaine Or Bupivacaine With Dexmedetomidine For Postoperative Analgesia In Patients With Femur Fractures.

Background: Femur fractures are extremely painful due to the lowest pain threshold of the periosteum among the deep somatic structures. Perioperative Fascia Iliaca Compartment Block (FICB), when administered using a local anesthetic agent, bupivacaine, can reduce morbidity by providing satisfactory pain relief. Dexmedetomidine, an alpha-2 agonist, is known to prolong the local anesthetic effects without causing any significant side effects. We compared analgesic duration of ultrasound guided FICB with bupivacaine alone and bupivacaine with dexmedetomidine for postoperative analgesia. A prospective, randomized, double blinded study was conducted on 50 patientsMaterials And Method: aged 18 to 65 years undergoing femur fracture surgeries. Patients were divided into 2 groups of 25 each. Both groups received USG guided FICB. Group A received 28 ml 0.25% bupivacaine and 2 ml normal saline (NS). Group B received 28 ml 0.25% bupivacaine and 30 mcg dexmedetomidine in NS. Pain scores were assessed every 5 minutes until 15 minutes post FICB, during positioning for subarachnoid block and every 2 hours until 24 hours post-operatively. Total duration of analgesia, cumulative analgesia requested in 24 hours, Ramsay sedation and patient satisfaction scores were recorded. Results: The mean duration of analgesia in Group A was 419.4 ± 115.35 minutes (95%CI: 374.2 – 464.6) and in Group B was 656.6 ± 137.99 minutes (95%CI: 602.5 –710.7), p <0.001. Mean VAS score during positioning for SAB in Group A was 1.60 ± 0.50 and in Group B was 0.96 ± 0.68. USG guided FICB with dexmedetomidine is superior inConclusion: providing prolonged post-operative analgesia in comparison to bupivacaine alone

Single-bolus dexmedetomidine in prevention of emergence delirium in pediatric ophthalmic surgeries: A randomized controlled trial

Purpose: Emergency delirium (ED), a common postoperative neurologic complication, causes behavioral disturbances leading to self?traumas and also has long?term adverse effects in children. Our aim was to investigate the efficacy of a single?bolus dose of dexmedetomidine in reducing the incidence of ED. Additionally, pain relief, number of patients who needed rescue analgesia, hemodynamic parameters, and adverse events were assessed. Methods: One hundred and one patients were randomly allocated into two groups: 50 patients received 15 mL of dexmedetomidine 0.4 ?g/kg (group D) and 51 patients received volume?matched normal saline (group C). Hemodynamic parameters such as heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were monitored regularly throughout the procedure. ED was assessed with Pediatric Anesthesia Emergence Delirium Scale (PAEDS), and pain was measured using the modified Objective Pain Score (MOPS). Results: The incidences of ED and pain were higher in group C than group D (P < 0.0001 and P < 0.0001, respectively). Group D showed significant decrease in MOPS and PAEDS values at 5, 10, 15, and 20 min (P < 0.05), HR at 5 min (P < 0.0243), and SBP at 15 min (P < 0.0127). There was no significant difference in DBP between the two groups at any time point. The mean blood pressure (MBP) at 10 min was significantly less in group D than group C (P < 0.001). Conclusion: Dexmedetomidine 0.4 ?g/kg as a single bolus over 10 min immediately after intubation is effective for the prevention of ED and significantly reduces the need of rescue analgesia without compromising the hemodynamic parameters in children undergoing ophthalmic surgery.

The antioxidant effect of preischemic dexmedetomidine in a rat model: increased expression of Nrf2/HO-1 via the PKC pathway

Abstract Background The precise underlying mechanism of antioxidant effects of dexmedetomidine-induced neuroprotection against cerebral ischemia has not yet been fully elucidated. Activation of Nuclear factor erythroid 2-related factor (Nrf2) and Heme Oxygenase-1 (HO-1) represents a major antioxidant-defense mechanism. Therefore, we determined whether dexmedetomidine increases Nrf2/HO-1 expression after global transient cerebral ischemia and assessed the involvement of Protein Kinase C (PKC) in the dexmedetomidine-related antioxidant mechanism. Methods Thirty-eight rats were randomly assigned to five groups: sham (n = 6), ischemic (n = 8), chelerythrine (a PKC inhibitor; 5 mg.kg-1 IV administered 30 min before cerebral ischemia) (n = 8), dexmedetomidine (100 µg.kg-1 IP administered 30 min before cerebral ischemia (n = 8), and dexmedetomidine + chelerythrine (n = 8). Global transient cerebral ischemia (10 min) was applied in all groups, except the sham group; histopathologic changes and levels of nuclear Nrf2 and cytoplasmic HO-1 were examined 24 hours after ischemia insult. Results We found fewer necrotic and apoptotic cells in the dexmedetomidine group relative to the ischemic group (p< 0.01) and significantly higher Nrf2 and HO-1 levels in the dexmedetomidine group than in the ischemic group (p< 0.01). Additionally, chelerythrine co-administration with dexmedetomidine attenuated the dexmedetomidine-induced increases in Nrf2 and HO-1 levels (p< 0.05 and p< 0.01, respectively) and diminished its beneficial neuroprotective effects. Conclusion Preischemic dexmedetomidine administration elicited neuroprotection against global transient cerebral ischemia in rats by increasing Nrf2/HO-1 expression partly via PKC signaling, suggesting that this is the antioxidant mechanism underlying dexmedetomidine-mediated neuroprotection.

The impact of emergence delirium on hospital length of stay for children who underwent tonsillectomy/adenotonsillectomy: an observational retrospective study

Abstract Background Emergence Delirium (ED) is a combination of disturbance of perception and psychomotor agitation that is common in pediatric patients after general anesthesia, especially at preschool age. Since the effect of ED on the length of stay has been studied in adults but infrequently in children, the aim of this study was to investigate the relationship between ED and length of stay in this population. Methods A single center, retrospective, observational study was carried out in children who underwent tonsillectomy or adenotonsillectomy. The Pediatric Anesthesia Emergence Delirium (PAED) scale was used to assess ED. In addition to the time to hospital discharge (time frame 24 hours), drugs used, comorbidities, early postoperative complications, and pain were investigated if potentially associated with the complication. Results Four hundred sixteen children aged from 1.5 to 10 years (183 female, 233 male) were included. ED occurred in 25.5% of patients (n = 106). Patients were divided into the ED group and the No-ED group. The discharge time was similar in both groups. No significant differences were observed in the frequency of postoperative complications. The use of fentanyl or dexmedetomidine did not affect ED occurrence. The frequency of pain was greater in the ED group, both in the recovery room and in the ward (p= 0.01). Conclusions The occurrence of ED in children after tonsillectomy/adenotonsillectomy did not extend the length of stay.

A randomized comparative study of preoperative fentanyl and dexmedetomidine nebulization on the hemodynamic response to endotracheal intubation

Background: Intense sympathetic activity is linked to laryngoscopy and endotracheal intubation, which could lead to intraoperative problems. We undertook this study to compare the effects of preoperative nebulized Fentanyl and Dexmedetomidine on hemodynamic response to laryngoscopy and endotracheal intubation, taking advantage of their high bioavailability and better absorption through nasal mucosa. Aim and Objectives: The objectives of the study were (i) to compare the effect of preoperative nebulization on the hemodynamic response to laryngoscopy and intubation; and (ii) to assess intraoperative requirement of anesthetic agents. Materials and Methods: This prospective, randomized, and comparative study was conducted among 100 American Society of Anesthesiologists (ASA) I, II patients (of either gender) undergoing elective surgeries and requiring tracheal intubation, were randomized in two groups. Group A was given Fentanyl Nebulization (2 ?g/kg in 4 ml of 0.9% saline) and Group B was given Dexmedetomidine nebulization (1 ?g/kg in 4 ml of 0.9% saline) 10 min before anesthesia induction. Hemodynamic parameters were noted before and immediately after induction, 1 min, 5 min and 10 min after intubation. The main goal was to assess how Fentanyl and dexmedetomidine nebulization affect the laryngoscopy and intubation-induced stress response. The secondary outcome was to assess the intraoperative requirement of anesthetic agents, observe adverse effects of study drug and sedation score. Results: Dexmedetomidine nebulization was found to be more effective in blunting rise in heart rate post laryngoscopy compared to Fentanyl Nebulization (P < 0.0001) as well as in MAP after 10 min of intubation (P < 0.0001). Requirement of propofol was seen to be significantly reduced in Group B compared to Group A (P < 0.05). Sedation scores were significantly higher in Group B (P < 0.05). No evidence of side effects was observed in any group. Conclusion: Nebulisation of dexmedetomidine was found to be more effective in attenuation of stress response of laryngoscopy and intubation compared to nebulisation of fentanyl, with stable intraoperative hemodynamic and no significant side effects.

Dexmedetomidina vía nasal en colecistectomía laparoscópica / Dexmedetomidine intranasally in laparoscopic cholecystectomy

Resumen: Introducción: la dexmedetomidina es un adyuvante en el manejo anestésico perioperatorio y si se administra por vía nasal las dosis requeridas tienen mínimos efectos secundarios. Material y métodos: ensayo clínico aleatorizado doble ciego en pacientes sometidos a colecistectomía laparoscópica con anestesia general, comparando la dexmedetomidina intranasal (1 μg/kg de peso ideal) contra placebo, se comparó el efecto analgésico postoperatorio por medio de la escala visual análoga del dolor (EVA) y el consumo de opioides transanestésico. El análisis estadístico se realizó con t de Student y exacta de Fisher. Resultados: se incluyeron 54 pacientes aleatorizados en dos grupos: dexmedetomidina y control. El 81.5% de los sujetos fueron mujeres, no se encontró diferencia entre los grupos en las variables demográficas. La media de la calificación EVA a los 60 minutos para el grupo dexmedetomidina fue (2.89 ± 1.9), estadísticamente inferior comparada contra el grupo control (5.78 ± 2.3) (p ˂ 0.0001). El consumo de opioides para dexmedetomidina fue (0.424 ± 0.074 μg/h) estadísticamente menor al control (0.697 ± 0.136 μg/h) (p ˂ 0.0001) con un tamaño del efecto de Cohen de 250%. Conclusiones: disminución significativa en EVA y en el consumo de opioides con el uso de dexmedetomidina intranasal en colecistectomía laparoscópica.

Abstract: Introduction: dexmedetomidine is and useful adjuvant agent in the perioperative anesthetic management associated to nasal administration with minimum adverse effects. Material and methods: a randomized, controlled, double blind, clinical trial was carried out in elective patients undergoing laparoscopic cholecystectomy with general anesthesia. Aim of this study was to compare the postoperative analgesic effect through visual analogue scale (VAS) and the perioperative opioid consumption. Dexmedetomidine was administrated intranasally (1 μg/kg dose) versus placebo. Statistical analysis was realized through student t and Fisher Test. Results: 54 patients were randomized in two groups: dexmedetomidine vs control. Not significant differences were found between both groups in demographic variables but 81.5% were women. Mean of VAS score at 60 minutes was significantly inferior (2.89 ± 1.9) versus control group (5.78 ± 2.3) (p ˂ 0.0001). Mean of opioids consumption in dexmedetomidine group (0.424 ± 0.074 μg/h) was significant minor of control group (0.697 ± 0.136 μg/h) (p ˂ 0.0001). Size effect through Cohen test was 250%. Conclusion: statistically decrease in VAS and in opioid consumption was observed using dexmedetomidine nasally in laparoscopic cholecystectomy.

The effect of dexmedetomidine on expression of neuronal nitric oxide synthase in spinal dorsal cord in a rat model with chronic neuropathic pain / O efeito da dexmedetomidina na expressão do óxido nítrico sintase neuronal na medula espinhal dorsal em um modelo rato com dor neuropática crônica

Abstract Background Neuropathic pain typically refers to the pain caused by somatosensory system injury or diseases, which is usually characterized by ambulatory pain, allodynia, and hyperalgesia. Nitric oxide produced by neuronal nitric oxide synthase (nNOS) in the spinal dorsal cord might serve a predominant role in regulating the algesia of neuropathic pain. The high efficacy and safety, as well as the plausible ability in providing comfort, entitle dexmedetomidine (DEX) to an effective anesthetic adjuvant. The aim of this study was to investigate the effect of DEX on the expression of nNOS in spinal dorsal cord in a rat model with chronic neuropathic pain. Methods Male Sprague Dawley (SD) rats were randomly assigned into three groups: sham operation group (sham), (of the sciatic nerve) operation (CCI) group, and dexmedetomidine (DEX) group. Chronic neuropathic pain models in the CCI and DEX groups were established by sciatic nerve ligation. The thermal withdrawal latency (TWL) was measured on day 1 before operation and on day 1, 3, 7 and 14 after operation. Six animals were sacrificed after TWL measurement on day 7, and 14 days after operation, in each group, the L4-6 segment of the spinal cords was extracted for determination of nNOS expression by immunohistochemistry. Results Compared with the sham group, the TWL threshold was significantly decreased and the expression of nNOS was up-regulated after operation in the CCI and DEX groups. Compared with the CCI grou[, the TWL threshold was significantly increased and the expression of nNOS was significantly down-regulated on day 7 and 14 days after operation in the DEX group. Conclusion Down-regulated nNOS in the spinal dorsal cord is involved in the attenuation of neuropathic pain by DEX.

Resumo Antecedentes A dor neuropática refere-se tipicamente à dor causada por lesões ou doenças do sistema somatossensorial. De modo geral, é caracterizada por dor à ambulação, alodinia e hiperalgesia. O óxido nítrico produzido pela enzima óxido nítrico sintase neuronal (nNOS) na medula espinhal dorsal pode ter um papel predominante na regulação da dor neuropática. A alta eficácia e segurança, bem como a plausível capacidade de proporcionar conforto, faz com que a dexmedetomidina (DEX) seja um adjuvante anestésico eficaz. O objetivo deste estudo foi investigar o efeito da DEX na expressão de nNOS na medula espinhal dorsal em um modelo de ratos com dor neuropática crônica. Métodos Ratos Sprague Dawley (SD) machos foram distribuídos aleatoriamente em três grupos: grupo de cirurgia simulada (sham), grupo de cirurgia (do nervo ciático; CCI) e grupo dexmedetomidina (DEX). Os modelos de dor neuropática crônica nos grupos CCI e DEX foram estabelecidos por ligadura do nervo ciático. A latência de retirada térmica (TWL) foi medida no dia 1 antes da cirurgia e nos dias 1, 3, 7 e 14 após o procedimento. Seis animais de cada grupo foram eutanasiados após a medida de TWL nos dias 7 e 14 após a cirurgia e o segmento L4-6 da medula espinhal foi extraído para determinação da expressão de nNOS por imuno-histoquímica. Resultados Em comparação ao grupo sham, o limiar de TWL diminuiu significativamente e a expressão de nNOS foi regulada de maneira positiva após a cirurgia nos grupos CCI e DEX. Comparado ao grupo CCI, o limiar de TWL aumentou de forma significativa e a expressão de nNOS caiu significativamente diminuída nos dia 7 e 14 após a cirurgia no grupo DEX. Conclusão A regulação negativa de nNOS na medula espinhal dorsal está envolvida na atenuação da dor neuropática pela DEX.

Efficacy of dexmedetomidine as adjuvant to ropivacaine in paravertebral block for post-operative analgesia in breast cancer surgery

Background: Paravertebral block can be given for pain management after modified radical mastectomy (MRM). Although many additives to ropivacaine in PVB have been tried for post-operative analgesia, none has been found ideal. Aims and Objectives: We have compared the duration of analgesia in PVB using adjuvant like dexmedetomidine with ropivacaine after MRM. Materials and Methods: Sixty female patients posted for MRM and axillary dissection were split into two groups. Group R administered ultrasound-guided PVB with 20 ml ropivacaine 0.5% and Group RD administered 20 ml of 0.5% ropivacaine with dexmedetomidine 1 mcg/kg. After confirming PVB, surgery was done under general anesthesia in all patients. Time for 1st analgesia requirement was the main objective of our trial. Other objectives were to record visual analog scale scores and total analgesic need. Results: Post-operative analgesia duration was increased in the group RD (7.11 ± 1.42 h) in contrary to Group R (3.68 ± 1.85 h). Total paracetamol consumption post-operative 24 h was decreased in Group RD (1.63 ±0.89 g) in contrary to Group R (2.74 ± 0.76 g). Conclusion: Dexmedetomidine in PVB provides prolonged pain relief after MRM.

Effect of dexmedetomidine on tourniquet-induced skeletal muscle injury

SUMMARY OBJECTIVE: The aim of this study was to investigate whether dexmedetomidine could reduce tourniquet-induced skeletal muscle injury. METHODS: C57BL6 male mice were randomly assigned to sham, ischemia/reperfusion, and dexmedetomidine groups. Mice in the ischemia/reperfusion and dexmedetomidine groups received normal saline solution and dexmedetomidine intraperitoneally, respectively. The sham group underwent the same procedure as the ischemia/reperfusion group, with the exception of tourniquet application. Subsequently, the ultrastructure of the gastrocnemius muscle was observed, and its contractile force was examined. In addition, Toll-like receptor 4 and nuclear factor-κB expression within muscles was detected by Western blot. RESULTS: Dexmedetomidine alleviated myocyte damage and increased the contractility of skeletal muscles. Moreover, dexmedetomidine significantly inhibited the expression of Toll-like receptor 4/nuclear factor-κB in the gastrocnemius muscle. CONCLUSION: Taken together, these results demonstrate that dexmedetomidine administration attenuated tourniquet-induced structural and functional impairment of the skeletal muscle, partly through inactivation of the Toll-like receptor 4/nuclear factor-κB pathway.

Comparison of intranasal midazolam-fentanyl with dexmedetomidine–fentanyl as pre-medication in the paediatric age group

Background & objectives: Intranasal midazolam-fentanyl is commonly used as pre-medication in paediatric patients, but there is a risk of respiratory depression with this combination. Dexmedetomidine is a drug that preserves respiratory function. The objective of this study was to compare the efficacy of intranasal midazolam-fentanyl and dexmedetomidine-fentanyl in paediatric patients undergoing elective surgeries. Methods: Hundred children in the age group of 3-8 yr of American Society of Anaesthesiologists physical status grade 1 were randomized into two groups- group A received intranasal midazolam (0.2 mg/kg)-fentanyl (2 ?g/kg) and group B received intranasal dexmedetomidine (1 ?g/kg)-fentanyl (2 ?g/kg) 20 min before induction of general anaesthesia. Heart rate and SpO2 were monitored. Sedation score, parental separation and response to intravenous cannulation were seen after 20 min. Children were monitored for 2 h for post-operative analgesia by Oucher’s Facial Pain Scale. Results: Sedation scores were satisfactory in both groups, although children in group A were more sedated than in group B. Parental separation and response to intravenous cannulation were comparable in both the groups. The two groups were also haemodynamically comparable intraoperatively. Post-operative heart rate was also comparable at all-time intervals in both the groups except for heart rate at 100 and 120 min which were more in group A. Group A experienced more post-operative pain as assessed by Oucher’s Facial Pain Scale as compared to group B. Children receiving intranasal dexmedetomidine- fentanyl had better post-operative analgesia as compared to those who received intranasal midazolam-fentanyl. Interpretation & conclusions: Both intranasal midazolam with fentanyl and intranasal dexmedetomidine with fentanyl provided satisfactory sedation. Both groups were comparable in separation reaction and response to intravenous cannulation with better post-operative analgesia in children receiving intranasal dexmedetomidine-fentanyl.

O Pré-Condicionamento com Dexmedetomidina Atenua a Lesão de Isquemia/Reperfusão Miocárdica em Ratos, Suprimindo a Mitofagia Via Ativação do Receptor Α2-Adrenérgico / Dexmedetomidine Preconditioning Attenuates Myocardial Ischemia/Reperfusion Injury in Rats by Suppressing Mitophagy Via Activating Α2-Adrenergic Receptor

Resumo Fundamento A dexmedetomidina (DEX), um agonista específico do receptor α2-adrenérgico, é protetora contra lesão de isquemia/reperfusão miocárdica (I/R). No entanto, a associação entre a cardioproteção induzida pelo pré-condicionamento DEX e a supressão da mitofagia permanece pouco clara. Objetivo Portanto, nosso objetivo foi investigar se o pré-condicionamento com DEX alivia a I/R, suprimindo a mitofagia via ativação do receptor α2-adrenérgico. Método Sessenta corações de ratos isolados foram tratados com ou sem DEX antes de induzir isquemia e reperfusão; um antagonista do receptor α2-adrenérgico, a ioimbina (YOH), também foi administrado antes da isquemia, isoladamente ou com DEX. A frequência cardíaca (FC), pressão diastólica do ventrículo esquerdo (PDVE), pressão diastólica final do ventrículo esquerdo (PDFVE), taxa máxima e mínima de desenvolvimento da pressão ventricular esquerda (±dp/dtmax) e tamanho do infarto do miocárdio foram medidos. A ultraestrutura mitocondrial e as autofagossomas foram avaliadas por microscopia eletrônica de transmissão. O potencial de membrana mitocondrial e os níveis de espécies reativas de oxigênio (ROS) foram medidos usando os ensaios JC-1 e diacetato de diclorodi hidrofluoresceína, respectivamente. Os níveis de expressão das proteínas associadas à mitofagia Beclin1, relação LC3II/I, p62, PINK1 e Parkin foram detectados por western blotting. Resultados Em comparação com o grupo controle, no grupo isquemia/reperfusão, a FC, PDVE e ±dp/dtmax foram notavelmente diminuídas (p<0,05), enquanto os tamanhos da PDFVE e do infarto aumentaram significativamente (p<0,05). O pré-condicionamento com DEX melhorou significativamente a disfunção cardíaca, reduziu o tamanho do infarto do miocárdio, manteve a integridade estrutural mitocondrial, aumentou o potencial de membrana mitocondrial, inibiu a formação de autofagossomas e diminuiu a produção de ROS e a relação Beclin1, relação LC3II/I, expressão PINK1, Parkin e p62(p<0,05). Quando DEX e YOH foram combinados, o YOH cancelou o efeito da DEX, enquanto o uso de YOH sozinha não teve efeito. Conclusão Portanto, o pré-condicionamento DEX foi cardioprotetor contra I/R em ratos, suprimindo a mitofagia por meio da ativação do receptor α2-adrenérgico.

Abstract Background Dexmedetomidine (DEX), a specific α2-adrenergic receptor agonist, is protective against myocardial ischemia/reperfusion injury (MIRI). However, the association between DEX preconditioning-induced cardioprotection and mitophagy suppression remains unclear. Objective Hence, we aimed to investigate whether DEX preconditioning alleviates MIRI by suppressing mitophagy via α2-adrenergic receptor activation. Method Sixty isolated rat hearts were treated with or without DEX before inducing ischemia and reperfusion; an α2-adrenergic receptor antagonist, yohimbine (YOH), was also administered before ischemia, alone or with DEX. The heart rate (HR), left ventricular diastolic pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), maximal and minimal rate of left ventricular pressure development (±dp/dtmax), and myocardial infarction size were measured. The mitochondrial ultrastructure and autophagosomes were assessed using transmission electron microscopy. Mitochondrial membrane potential and reactive oxygen species (ROS) levels were measured using JC-1 and dichloride hydrofluorescein diacetate assays, respectively. The expression levels of the mitophagy-associated proteins Beclin1, LC3II/I ratio, p62, PINK1, and Parkin were detected by western blotting. Results Compared with the control group, in the ischemia/reperfusion group, the HR, LVDP, and ±dp/dtmax were remarkably decreased (p< 0.05), whereas LVEDP and infarct sizes were significantly increased (p< 0.05). DEX preconditioning significantly improved cardiac dysfunction reduced myocardial infarction size, maintained mitochondrial structural integrity, increased mitochondrial membrane potential, inhibited autophagosomes formation, and decreased ROS production and Beclin1, LC3II/I ratio, PINK1, Parkin, and p62 expression(p< 0.05). When DEX and YOH were combined, YOH canceled the effect of DEX, whereas the use of YOH alone had no effect. Conclusion Therefore, DEX preconditioning was cardioprotective against MIRI in rats by suppressing mitophagy via α2-adrenergic receptor activation.

Effects of dexmedetomidine in non-operating room anesthesia in adults: a systematic review with meta-analysis

Abstract Background: Dexmedetomidine (DEX) is an α2-adrenergic receptor agonist used for its sedative, analgesic, and anxiolytic effects. Non-Operating Room Anesthesia (NORA) is a modality of anesthesia that can be done under general anesthesia or procedural sedation or/and analgesia. In this particular setting, a level-2 sedation, such as the one provided by DEX, is beneficial. We aimed to study the effects and safety of DEX in the different NORA settings in the adult population. Methods: A systematic review with meta-analysis of randomized controlled trials was conducted. Interventions using DEX only or DEX associated with other sedative agents, in adults (18 years old or more), were included. Procedures outside the NORA setting and/or without a control group without DEX were excluded. MEDLINE, ClinicalTrials.gov, Scopus, LILACS, and SciELO were searched. The primary outcome was time until full recovery. Secondary outcomes included hemodynamic and respiratory complications and other adverse events, among others. Results: A total of 97 studies were included with a total of 6,706 participants. The meta-analysis demonstrated that DEX had a higher time until full recovery (95% CI = [0.34, 3.13] minutes, a higher incidence of hypotension (OR = 1.95 [1.25, 3.05], p = 0.003, I2 = 39%) and bradycardia (OR = 3.60 [2.29, 5.67], p < 0.00001, I2 = 0%), and a lower incidence of desaturation (OR = 0.40 [0.25, 0.66], p = 0.0003, I2 = 60%). Conclusion: DEX in NORA procedures in adults was associated with a lower incidence of amnesia and respiratory effects but had a long time to recovery and more hemodynamic complications..

Dexmedetomidine versus clonidine as an adjuvant to local anaesthetic in brachial plexus blocks: a metaanalysis of randomised controlled trials

Abstract Objective: This meta-analysis aimed to compare the efficacy and safety of dexmedetomidine and Clonidine as an adjuvant to local anesthetics in BPBs. Methods: Two investigators independently searched databases to identify all RCTs comparing the efficacy and/or safety of dexmedetomidine and Clonidine as an adjuvant to local anesthetics in BPBs. All outcomes were pooled using the inverse variance method with a random-effect model. An I2 test was used to assess heterogeneity. The source of heterogeneity was explored through meta-regression. The quality of the evidence was assessed using the GRADE approach. Results: Out of 123 full texts assessed, 24 studies (1448 patients) were included in the analysis. As compared to Clonidine, dexmedetomidine groups showed significantly longer sensory block duration (MD = 173.31; 95% CI 138.02-208.59; I2 = 99%; GRADE approach evidence: high); motor block duration (MD = 158.35; 95% CI 131.55-185.16; I2 = 98%; GRADE approach evidence: high), duration of analgesia (MD = 203.92; 95% CI 169.25-238.58; I2 = 99%; GRADE approach evidence-high), and provided higher grade quality of block (RR = 1.97; 95% CI 1.60-2.41 ; I2 = 0%; GRADE approach evidence: moderate). The block positioning technique (regression coefficient: 51.45, p = 0.005) was observed as a significant predictor of the heterogeneity in the case of sensory block duration. No significant difference was observed for the risk of hypotension (RR = 2.59; 95% CI 0.63-10.66; I2 = %). Conclusion: Moderate to high-quality evidence suggests dexmedetomidine is a more efficacious adjuvant to local anesthetic in BPBs than Clonidine.

Effect of combined sedation using multiple drugs on inflammatory cytokines in patients with acute respiratory distress syndrome

Abstract he innate immune response plays an important role in the pathophysiology of acute respiratory distress syndrome (ARDS); however, no drug has been proven to be beneficial in the management of ARDS. Therefore, the aim of this study was to investigate the effects of using combined sedatives on systemic inflammatory responses in patients with ARDS. A total of 90 patients with ARDS and an intubation time of > 120 h were randomly divided into the propofol group (group P), midazolam group (group M), and combined sedation group (group U). Patients in groups P and M were sedated with propofol and midazolam, respectively, whereas patients in group U were sedated with a combination of propofol, midazolam, and dexmedetomidine. The dosage of sedatives and vasoactive drugs, duration of mechanical ventilation, and incidence of sedative adverse reactions were documented. The dosage of sedatives and vasoactive drugs, as well as the incidence of sedative adverse reactions in group U, was significantly lower than those in groups P and M. Similarly, the duration of mechanical ventilation in group U was significantly shorter than that in groups P and M. Hence, inducing sedation through a combination of multiple drugs can significantly reduce their adverse effects, improve their sedative effect, inhibit systemic inflammatory responses, and improve oxygenation in patients with ARDS

DEX, Delirium and Dilemma

ABSTRACT Dexmedetomidine has been subjected to an extensive evaluation for its' role in the prevention of postoperative delirium following cardiac surgery. In striking contrast to the preexisting meta-analysis supporting postoperative delirium-reduction with dexmedetomidine, few recently concluded multicentric large scale randomized controlled trials suggest otherwise. This article aims to present a nuanced perspective of the evolving controversy by attempting to decode the apparent incongruences in the literature accumulating off-late, which is particularly pertinent amidst an ever-escalating heterogeneity in the current research ecosystem.

Dexmedetomidine improving complete Freund's adjuvant-induced anxiety-like and depression-like behaviour by promoting the expression of brain-derived neurotrophic factor-tyrosin kinase receptor B in mice hippocampus / 解剖学报

Objective To study the effect of dexmedetomidine (DEX), an α2- adrenoceptor agonist, on the pain-related anxiety-like and depression-like behaviour induced by complete Freund' s adjuvant (CFA) injection and its possible regulatory mechanism. Methods Thirty-six ICR female mice were randomly divided into normal saline (NS) group, CFA group and DEX + CFA group, n = 12 for each group. Chronic inflammatory pain model was established by subcutaneous injection of 10 μl CFA into the right hind limb of mice. DEX + CFA group mice were injected intraperitoneally with 0.025 mg/kg DEX 30 minutes before nociceptive behavior test, and once a day for 7 days. Von-frey fiber was used to evaluate the threshold of mechanical pain in mice, n = 12 for each group. The anxiety-like behavior of mice were detected by open field test, n = 12 for each group. Sucrose preference, tail suspension test and forced swimming test were used to detected the depression-like behavior of mice, n = 12 for each group. The expression of adrenergic receptor β2 (ADRB2), Brain-derived neurotrophic factor (BDNF), tyrosine kinase B receptor (TrkB), and glutamate receptors 1 (GluR1) and GluR2 were detected by Western blotting, n = 8 for each group. Immunohistochemical staining was used to detect the expression of recombinant doublecortin(DCX), which is a marker of newborn neurons in the hippocampus, n = 4 for each group. Results Compared with the NS group, the mechanical threshold of mice on the 1st, 3rd and 7th day after CFA injection decreased significantly (P 0.05). Compared with the NS group, the time spent in the inner ares (P<0.01), number of entering the central grid area (P<0.01) and distance travelled in the inner area (P<0.01) of CFA group mice reduced significantly, while the time (P<0.01), numbers (P < 0.05) and distance (P < 0.05) of DEX + CFA group mice entering the central grid area enhanced significantly. The result of depression-like behavior tests showed that the sucrose preference percentage (P < 0.05) reduced significantly in CFA group when compared with NS group, and the immobility time increased significantly in tail suspension test (P<0.01) and forced swimming test (P< 0.001) in CFA mice when compared with NS group, while DEX intervention could significantly increase the sucrose preference scores (P<0.05) and decreased the immobility time in tail suspension test (P<0.05) and forced swimming test (P<0.05). The result of Western blotting showed that compared with the NS group, the levels of ADRB2 (P<0.0010), BDNF (P < 0.001), TrkB (P < 0.01), GluR1 (P < 0.001) and GluR2 (P < 0.001) in the hippocampus of CFA group were significantly decreased, while DEX intervention could significantly increase the expression of ADRB2 (P<0.05), BDNF (P < 0.001), TrkB (P < 0.001), GluR1 (P < 0.001) and GluR2 (P < 0.001). Immunohistochemical result showed that compared with the NS group, the average absorbance (AA) of DCX decreased significantly in hippocampus of CFA group (P<0.05), but increased significantly in DEX+CFA group (P < 0.05). Conclusion Dexmedetomidine may promote hippocampal neurogenesis through upregulated the expression of BDNF-TrkB, thus improving CFA-induced anxiety-like and depression-like behaviors in mice.

Detection and Analysis of Blood Dexmedetomidine in Drug-Facilitated Cases / 法医学杂志

OBJECTIVES@#To establish a simple and rapid qualitative and quantitative detection method of dexmedetomidine in blood.@*METHODS@#Blood was separated on the Allure PFP Propyl liquid chromatography column with isocratic elution after it was precipitated by acetonitrile and filtered. Qualitative and quantitative analysis of dexmedetomidine was performed using positive ion scan mode and multi-reaction monitoring mode.@*RESULTS@#The limit of detection of dexmedetomidine in blood was 0.2 ng/mL and the limit of quantification was 0.5 ng/mL. The linearity of the method was good in the range of 0.5-1 000 ng/mL, and the correlation coefficient was greater than 0.99. The accuracy of the method was 90.34%-112.67% and the extraction recovery was 50.05%-91.08%, with no significant matrix effect.@*CONCLUSIONS@#This method is simple, selective and suitable for the qualitative and quantitative analysis of dexmedetomidine in blood, which can provide a reference for drug-facilitated cases involving dexmedetomidine.