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.

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.

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.

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.

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.

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.

Effects of dexmedetomidine on intestinal stress response and cellular immune function in patients with gynecologic malignancies undergoing laparoscopic surgery / 肿瘤研究与临床

Objective:To explore the effects of dexmedetomidine (DEX) on intestinal stress response and cellular immune function in patients with gynecologic malignancies undergoing laparoscopic surgery.Methods:A total of 60 patients with gynecologic malignancies who scheduled to undergo laparoscopic surgery under general anesthesia in the Second Hospital of Shanxi Medical University from March 2021 to March 2022 were selected. All patients were divided into the DEX group and the control group according to the random number table method, with 30 cases in each group. The DEX group included 12 cases of cervical cancer, 10 cases of endometrial cancer and 8 cases of ovarian cancer; the control group included 14 cases of cervical cancer, 9 cases of endometrial cancer and 7 cases of ovarian cancer. The DEX group: intravenous anesthesia was induced with a dose of DEX 0.5 μg/kg (infusion was completed within 10 min), general anesthesia was maintained with DEX 0.2 μg·kg -1·h -1 pumped intravenously, and the drug was stopped 30 min before surgery. The control group: equal amount of 0.9% sodium chloride solution was pumped intravenously. The venous blood was drawn at the time points of 10 min before general anesthesia (T 0), at the end of operation (T 1) and 1 d after the operation (T 2) to detect the stress response indicators such as cortisol (COR), epinephrine (E), norepinephrine (NE) levels, and immune indicators such as CD4 +, CD8 + proportions and CD4 +/CD8 + at T 0, T 1,and T 2. In addition, the pneumoperitoneum time, general anesthesia time, operation time and intestinal function recovery time were recorded. Results:At T 0, there were no statistically significant differences in the levels of COR, E and NE between the DEX group and the control group (all P > 0.05). At T 1, the levels of COR, E and NE were (146±12) μg/L, (158±14) ng/L, (265±12) ng/L, respectively in the control group, and (136±18) μg/L, (149±15) ng/L, (158±12) ng/L, respectively in the DEX group; the levels of COR, E and NE in the DEX group were lower than those in the control group ( t values were -2.51, -2.37, -2.08, all P < 0.05). At T 2, the levels of COR, E and NE were (124±12) μg/L, (131±16) ng/L, (234±8) ng/L, respectively in the control group, and (116±15) μg/L, (123±12) ng/L, (228±10) ng/L, respectively in the DEX group; the levels of COR, E and NE in the DEX group were also lower than those in the control group ( t values were -2.35, -2.23, -2.17, all P < 0.05). At T 0, there were no statistically significant differences in the proportions of CD4 +, CD8 + and CD4 +/CD8 + between the DEX group and the control group (all P > 0.05). At T 1, the proportions of CD4 +, CD8 + and CD4 +/CD8 + were (23±3)%, (20±3)%, 1.12±0.16, respectively in the control group, and (27±4)%, (23±4)%,1.22±0.19, respectively in the DEX group; the proportions of CD4 +, CD8 + and CD4 +/CD8 + in the DEX group were higher than those in the control group ( t values were -3.43, -2.29, 2.13, all P < 0.05). At T 2, the proportions of CD4 +, CD8 + and CD4 +/CD8 + were (26±3)%, (23±4)%, 1.17±0.16, respectively in the control group, and (31±5)%, (25±4)%, 1.26±0.19, respectively in the DEX group; the proportions of CD4 +, CD8 + and CD4 +/CD8 + in the DEX group were higher than those in the control group ( t values were -4.32, -2.02, 2.02, all P < 0.05). In addition, the time of first exhaust in the DEX group was shorter than that in the control group ( P<0.05). Conclusions:DEX can reduce the intestinal stress response of gynecologic malignancies patients undergoing laparoscopic surgery, thereby improving the immunosuppression of patients. It is also of great significance to protect intestinal mucosal barrier and recover the intestinal function, and DEX has a high safety.

Effects of different doses of dexmedetomidine on inflammatory factors and immune function during laparoscopic surgery in patients with gynecological malignant tumors / 肿瘤研究与临床

Objective:To explore the effects of different doses of dexmedetomidine (DEX) on inflammatory factors and immune function in patients with gynecological malignant tumors who underwent laparoscopic surgery.Methods:A total of 60 patients with gynecological malignant tumors who underwent laparoscopic surgery from January 2021 to December 2021 in the Second Hospital of Shanxi Medical University were selected as the research objects. All patients were divided into the control group, low-dose DEX group (group D1) and high-dose DEX group (group D2) by using random number table method, 20 cases in each group. Patients in D1 and D2 groups were intravenously pumped DEX 0.5 μg/kg and 1.0 μg/kg 10 minutes before induction of anesthesia, and then maintained with DEX 0.5 μg·kg -1·h -1 and 1.0 μg·kg -1·h -1 until 30 minutes before the end of operation; and patients in the control group were given the same amount of Nacl solution. The 10 ml peripheral venous blood were collected at 10 minutes before induction of anesthesia (T 1), 1 h after pneumoperitoneum relief (T 2) and 24 h after pneumoperitoneum relief (T 3). The changes of interleukin-6 (IL-6), interleukin-10 (IL-10), the proportion of CD4 +, the proportion of CD8 + and CD4 +/CD8 + ratio of the three groups were compared, and the cases of bradycardia and hypotension in perioperative period and the time of first exhaust after operation were recorded. Results:At T 1,T 2 and T 3, the expression level of IL-6 in the control group was (7.95±0.26) pg/ml, (8.30±0.24) pg/ml and (8.35±0.28) pg/ml, respectively, and the difference was statistically significant ( F = 14.14, P < 0.001); the expression level of IL-10 in the control group was (38.9±2.6) pg/ml, (44.5±6.6) pg/ml and (46.3±4.6) pg/ml, respectively, and the difference was statistically significant ( F = 12.45, P < 0.001); the proportion of CD4 + in the control group was (38.5±2.1)%, (29.5±4.6)% and (29.6±3.5)%, respectively, and the difference was statistically significant ( F = 40.82, P < 0.001); the ratio of CD8 + in the control group was (30.1±3.7)%, (35.1±6.3)% and (40.3±8.2)%, respectively, and the difference was statistically significant ( F = 13.02, P < 0.001); the CD4 +/CD8 + ratio in the control group was 1.29±0.14, 0.84±0.09 and 0.75±0.14, respectively, and the difference was statistically significant ( F = 99.94, P < 0.001). The expression level of IL-6 in group D1 and group D2 was (8.10±0.32) pg/ml and (8.01±0.30) pg/ml at T 2, and (8.12±0.35) pg/ml and (8.05±0.34) pg/ml at T 3,which were lower than those in the control group, and the differences were statistically significant (all P < 0.05). The expression level of IL-10 in group D2 was (40.6±3.5) pg/ml at T 2, which was lower than that in the control group, and the difference was statistically significant ( P < 0.05). At T 3, the expression level of IL-10 in group D1 and group D2 was (43.7±3.5) pg/ml and (42.4±3.9) pg/ml, which were lower than those in the control group, and the differences were statistically significant (all P < 0.05). At T 2, the proportion of CD4 + in group D2 was (34.5±4.3)%, which was higher than that in the control group, and the difference was statistically significant ( P < 0.05). At T 3, the proportion of CD4 + in group D1 and group D2 was (32.1±4.2)% and (33.7±2.8)%, which were higher than those in the control group, and the differences were statistically significant (all P < 0.05). At T 2, the proportion of CD8 + in group D2 was (30.7±5.5)%, which was lower than that in the control group, and the difference was statistically significant ( P < 0.05). At T 3, the proportion of CD8 + in group D1 and group D2 was (35.4±5.8)% and (32.5±5.1)%, which were lower than those in the control group, and the differences were statistically significant (all P < 0.05). The CD4 +/CD8 + ratio in group D1 and D2 was 0.99±0.17 and 1.14±0.16 at T 2, 0.93±0.19 and 1.05±0.16 at T 3, which were higher than those in the control group, and the differences were statistically significant (all P < 0.05). Meanwhile, 1 case of hypotension occurred in the the control group and group D1, respectively; 3 cases of bradycardia and 2 cases of hypotension occurred in the group D2. The time of exhaust in the control group was later than that in group D1 and D2, and the difference was statistically significant ( P < 0.05). Conclusions:DEX can inhibit the inflammatory reaction during laparoscopic surgery in patients with gynecological malignant tumors, reduce immune damage. The anti-inflammatory action and immune protection of high-dose of DEX is more significant compared with low-dose of DEX, while high dose of DEX is more likely to cause hemodynamic fluctuations in perioperative period.

Role of activation of VGLUT2 neurons in vagal nodose ganglion in dexmedetomidine-caused bradycardia in mice / 中华麻醉学杂志

Objective:To evaluate the role of activation of vesicular glutamate transporter 2 (VGLUT2) neurons in vagal nodose ganglion in dexmedetomidine-caused bradycardia in mice.Methods:Ninety-six SPF healthy male VGLUT2-cre mice, aged 10 weeks, weighing 20-25 g, were divided into 6 groups ( n=16 each) by the random number table method: normal saline control group (NS group), dexmedetomidine group (Dex group), viral control + chemogenetic control + dexmedetomidine group (eGFP-NS+ Dex group), viral transfection + chemogenetic control + dexmedetomidine group (hM4Di-NS+ Dex group), viral control + chemogenetic inhibition + dexmedetomidine group (eGFP-CNO+ Dex group) and viral transfection + chemogenetic inhibition + dexmedetomidine group (hM4Di-CNO+ Dex group). Dexmedetomidine 100 μg/kg was intraperitoneally injected in Dex group. The equal volume of normal saline was intraperitoneally injected in NS group. AAV2/9-hSyn-DIO-hM4Di-eGFP was injected in the right nodose ganglion in hM4Di-NS+ Dex group and hM4Di-CNO+ Dex group, and AAV2/9-hSyn-DIO-eGFP was injected in the right nodose ganglion in eGFP-NS+ Dex group and eGFP-CNO+ Dex group, allowing the virus expression for 21 days. On the 22nd day after virus injection, clozapine-n-oxide (CNO) 5 mg/kg was intraperitoneally injected in hM4Di-CNO+ Dex group and eGFP-CNO+ Dex group, the equal volume of normal saline was intraperitoneally injected in hM4Di-NS+ Dex group and eGFP-NS+ Dex group, 1 h later the efficacy of CNO reached the peak, and then dexmedetomidine 100 μg/kg was intraperitoneally injected. The respiratory rate, heart rate, SpO 2 and discharge frequency of the right vagal nodose ganglion were synchronously measured by multi-channel electrophysiology in vivo. The expression of phosphorylated extracellular signal-regulated kinase (pERK) and VGLUT2 and co-expression of pERK and VGLUT2 in the right vagal nodose ganglion were detected by immunofluorescence assay. Results:Compared with NS group, the percentage of heart rate variation and neuron firing frequency after administration were significantly increased, and pERK expression was up-regulated in the other five groups ( P<0.05). Compared with Dex group, the percentage of heart rate variation and neuron firing frequency after administration were significantly decreased, and pERK expression was down-regulated in hM4Di-CNO+ Dex group, and no significant change was found in the parameters mentioned above in hM4Di-NS+ Dex group, eGFP-NS+ Dex group and eGFP-CNO+ Dex group ( P>0.05). Compared with hM4Di-CNO+ Dex group, the percentage of heart rate variation and neuron firing frequency after administration were significantly increased, and pERK expression was up-regulated in eGFP-CNO+ Dex group ( P<0.05). There was no significant difference in the percentage of respiratory variation and SpO 2 among the six groups ( P>0.05). The expression of VGLUT2-positive neurons was abundant in nodose ganglia, and the co-expression rate of pERK and VGLUT2 was nearly 90%. The co-expression rate of pERK and VGLUT2 decreased to about 30% after inhibition of VGLUT2 neurons in ganglion. Conclusions:The mechanism by which dexmedetomidine causes bradycardia is associated with activation of VGLUT2 neurons in vagal nodose ganglia in mice.

Effect of dexmedetomidine on perioperative neurocognitive disorders in elderly frail patients undergoing hip joint surgery / 中华麻醉学杂志

Objective:To evaluate the effect of dexmedetomidine on perioperative neurocognitive disorders in elderly frail patients undergoing hip joint surgery.Methods:Sixty elderly patients of either sex, aged≥ 60 yr, weighing 40-100 kg, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ, with the Frail Scale score 3-5 points, scheduled for elective hip surgery under spinal-epidural anesthesia, were divided into 2 groups ( n=30 each) using the random number table method: control group (group C) and dexmedetomidine group (group D). Dexmedetomidine was intravenously infused at a dose of 0.5 μg/kg at 10 min before anesthesia followed by a continuous infusion of 0.2 μg·kg -1·h -1 until 10 min before the end of surgery in group D. The equal volume of 0.9% sodium chloride solution was given at the corresponding time point in group C. Blood samples from the median cubital vein were collected before surgery (T 1) and at 1 and 3 days after surgery (T 2, 3) for determination of concentrations of serum S100β and neuron-specific enolase by enzyme-related immunosorbent assay. Postoperative delirium was assessed within 3 days after surgery using the Confusion Assessment Method. Cognitive function was evaluated by Mini-Mental State Examination at T 1 and 30 days after surgery. Results:Compared with the baseline at T 1, the concentrations of serum S100β and NSE were significantly increased at T 2 and T 3 in two groups ( P<0.05). Compared with group C, the concentrations of serum S100β and neuron-specific enolase and incidence of postoperative delirium and postoperative cognitive dysfunction were significantly decreased at T 2 and T 3 in group D( P<0.05). Conclusions:Dexmedetomidine can effectively decrease the occurrence of perioperative neurocognitive disorders in elderly frail patients undergoing hip joint surgery.

Efficacy of dexmedetomidine on painless gastroenteroscopy in patients recovered from COVID-19 / 中华麻醉学杂志

Objective:To evaluate the efficacy of dexmedetomidine on painless gastroenteroscopy in the patients recovered from COVID-19.Methods:Eighty patients of either sex, aged 18-64 yr, with body mass index <30 kg/m 2, undergoing elective painless gastroenteroscopy, of American Society of Anesthesiologists physical statusⅠor Ⅱ, within 2nd to 7th weeks after diagnosis of COVID-19, who had a negative nucleic acid test or antigen test at present and presented with no respiratory symptoms in our hospital from January to February 2023, were selected and divided into 2 groups ( n=40 each) using a random number table method: dexmedetomidine group (group D) and control group (group C). Sufentanil 0.1 μg/kg was intravenously injected in two groups. Dexmedetomidine 0.2 μg/kg was intravenously injected in group D, and the equal volume of normal saline was given instead in group C. Propofol 1.5-2.0 mg/kg was intravenously injected after 2-3 min observation, and propofol 5-7 mg·kg -1·h -1 was intravenously infused to maintain sedation during operation. The development of bucking and hypoxemia during operation, total consumption of propofol, emergence time, time of hospital discharge, development of bradycardia and hypotension during operation, and scores for patients′ and endoscopic physicians′ satisfaction with anesthesia were recorded. Results:Compared with group C, the incidence of bucking and hypoxemia was significantly decreased, scores for endoscopic physicians′ satisfaction with anesthesia were increased ( P<0.05), and no significant change was found in the other parameters in group D ( P>0.05). Conclusions:Low-dose dexmedetomidine can reduce the risk of bucking and hypoxemia during operation and raise the quality of anesthesia in the patients recovered from COVID-19 undergoing painless gastroenteroscopy.

Effect of dexmedetomidine on TXNIP/ASK1 signaling pathway in a mouse model of intestinal ischemia-reperfusion / 中华麻醉学杂志

Objective:To evaluate the effect of dexmedetomidine on the thioredoxin-interacting protein (TXNIP)/apoptosis signal-regulated kinase 1 (ASK1) signaling pathway in a mouse model of intestinal ischemia-reperfusion (I/R).Methods:Thirty-two SPF healthy adult male C57BL/6J mice, aged 8-10 weeks, weighing 18-22 g, were divided into 4 groups ( n=8 each) using a random number table method: sham operation group (Sham group), intestinal I/R group (I/R group), TXNIP inhibitor resveratrol group (Res group) and dexmedetomidine group (Dex group). The mouse model of intestinal I/R injury was developed by clamping the superior mesenteric artery for 45 min followed by 120-min reperfusion in anesthetized animals. Resveratrol 30 mg/kg was intraperitoneally injected before developing the model in Res group, and dexmedetomidine 25 μg/kg was intraperitoneally injected at 30 min before ischemia in Dex group. Blood samples were collected by cardiac puncture at the end of 120-min reperfusion, then the mice were sacrificed, and the small intestine tissues were removed for microscopic examination and for determination of the serum diamine oxidase (DAO) concentration (by enzyme-linked immunosorbent assay) and expression of TXNIP, ASK1 and cleaved-caspase-3 in small intestinal tissues (by Western blot). The apoptosis rate of intestinal epithelial cells was calculated. The intestinal damage was assessed and scored according to Chiu. Results:Compared with group Sham, the Chiu′s score, serum DAO concentrations and apoptosis rate of intestinal epithelial cells were significantly increased, and the expression of TXNIP, ASK-1 and cleaved-caspase-3 was up-regulated in group I/R ( P<0.05). Compared with group I/R, the Chiu′s score, serum DAO concentration and apoptosis rate of intestinal epithelial cells were significantly decreased, and the expression of TXNIP, ASK-1 and cleaved-caspase-3 was down-regulated in group Res ( P<0.05). Compared with I/R group, the Chiu′s score, serum DAO concentration and apoptosis rate of intestinal epithelial cells were significantly decreased, and the expression of TXNIP, ASK-1 and cleaved-caspase-3 was down-regulated in Dex group ( P<0.05). Conclusions:The mechanism by which dexmedetomidine alleviates intestinal I/R injury may be related to inhibition of the TXNIP/ASK1 signaling pathway and reduction of cell apoptosis in mice.

Effect of age factors on pharmacodynamics of intranasal dexmedetomidine for sedation in pediatric patients undergoing transthoracic echocardiography / 中华麻醉学杂志

Objective:To evaluate the effect of age factors on the pharmacodynamics of intranasal dexmedetomidine for sedation in the pediatric patients undergoing transthoracic echocardiography(TTE).Methods:American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ pediatric patients, aged 1-24 months, undergoing TTE from August 2019 to May 2022, were selected. This trial was performed in two parts. Part Ⅰ Pediatric patients were divided into 4 age groups: 1-6 month group, 7-12 month group, 13-18 month group and 19-24 month group. The initial dose of dexmedetomidine was 2.0 μg/kg in 0.1 μg/kg increment/decrement. The dose of dexmedetomidine was determined by using modified Dixon′s up-and-down method. The ED 50 and 95% confidence interval of intranasally administered dexmedetomidine for sedation were calculated by the Dexon-Massey method. Part Ⅱ One hundred patients were divided into 4 age groups ( n= 25 each): 1-6 month group, 7-12 month group, 13-18 month group and 19-24 month group. The 4 groups were further divided into 5 subgroups ( n=5 each) according to the dose of dexmedetomidine: 2.1 μg/kg subgroup, 2.2 μg/kg subgroup, 2.3 μg/kg subgroup, 2.4 μg/kg subgroup, and 2.5 μg/kg subgroup. Part Ⅰ and part Ⅱ trials were combined, and the ED 95 and 95% confidence interval of intranasally administered dexmedetomidine for sedation were calculated using the probit method. Results:A total of 220 pediatric patients were enrolled. There was no significant difference in ED 50 and ED 95 of dexmedetomidine intranasally administered for sedation among groups ( P>0.05). Conclusions:The pharmacodynamics of intranasal dexmedetomidine for sedation shows no significant difference in age in the pediatric patients aged 1-24 months undergoing TTE.

Lung-protective effect of pressure-controlled volume-guaranteed ventilation combined with dexmedetomidine in pediatric patients undergoing laparoscopic surgery / 中华麻醉学杂志

Objective:To evaluate the protective effect of pressure-controlled volume-guaranteed ventilation (PC-VG) combined with dexmedetomidine on the lung of pediatric patients undergoing laparoscopic surgery.Methods:Forty-eight pediatric patients of either sex, aged 2-6 yr, weighing 8-21 kg, scheduled for elective laparoscopic pyeloplasty, were divided into 3 groups ( n=16 each) using a random number table method: volume-controlled ventilation (VCV) group (V group), PC-VG group (P group), and PC-VG combined with dexmedetomidine group (PD group). In PD group, dexmedetomidine was intravenously infused for 15 min at a loading dose of 0.5 μg/kg starting from the time point before anesthesia induction followed by a continuous infusion of 0.2-0.5 μg·kg -1·h -1 until the end of operation. VCV mode was used in group V, and PC-VG mode was used in P and PD groups, ventilator settings were adjusted to the mode with a tidal volume 6-8 ml/kg, respiratory rate 15-25 breaths/min, inspiratory/expiratory ratio 1∶2, oxygen flow rate 2 L/min, fraction of inspired oxygen 60%, and P ETCO 2 was maintained at 35-40 mmHg during mechanical ventilation in three groups. At 5 min before pneumoperitoneum (T 0), 10, 60 and 120 min of pneumoperitoneum (T 1-3) and 10 min after release of pneumoperitoneum pressure (T 4), peak airway pressure (Ppeak), mean airway pressure (Pmean), compliance of lung (C L) and airway resistance (Raw) were recorded, alveolar-arterial oxygen partial pressure difference (PA-aO 2), oxygenation index (OI), and respiratory index (RI) were recorded. The occurrence of pulmonary complications was recorded within 7 days after operation. Results:Compared with V group, the Ppeak and Raw were significantly decreased and C L was increased at T 1-4, and PA-aO 2 and RI were decreased and OI was increased at T 3, 4 in P group and PD group ( P<0.05). Compared with P group, no significant change was found in the parameters of respiratory mechanics mentioned above at each time point ( P>0.05), and PA-aO 2 and RI were decreased and OI was increased at T 3, 4 in PD group ( P<0.05). There was no significant difference in the incidence of postoperative pulmonary complications among the three groups ( P>0.05). Conclusions:PC-VG combined with dexmedetomidine has a certain lung-protective effect in pediatric patients undergoing laparoscopic surgery.