Dream of the Endless: Updates in Agents for Procedural Sedation.

Procedural sedation and analgesia is an essential activity in the emergency department for managing pain and anxiety during a variety of medical procedures. Various pharmacotherapy options, including opioid analgesics, antiemetics, anticholinergics, sedatives, and ketamine have been utilized, all with their unique efficacy and safety profiles. This review highlights the challenges associated with using certain agents and discusses emerging trends such as the use of newer synthetic opioids and the expanding use of dexmedetomidine. Overall, the selection of the optimal agents for procedural sedation and analgesia should be guided based on the unique characteristics of each agent tailored to the needs of the specific procedure, along with consideration for individual patient characteristics.

Brown adipose tissue-derived FGF21 mediates the cardioprotection of dexmedetomidine in myocardial ischemia/reperfusion injury.

Brown adipose tissue (BAT) plays a critical role in regulating cardiovascular homeostasis through the secretion of adipokines, such as fibroblast growth factor 21 (FGF21). Dexmedetomidine (DEX) is a selective α2-adrenergic receptor agonist with a protection against myocardial ischemia/reperfusion injury (MI/RI). It remains largely unknown whether or not BAT-derived FGF21 is involved in DEX-induced cardioprotection in the context of MI/RI. Herein, we demonstrated that DEX alleviated MI/RI and improved heart function through promoting the release of FGF21 from interscapular BAT (iBAT). Surgical iBAT depletion or supplementation with a FGF21 neutralizing antibody attenuated the beneficial effects of DEX. AMPK/PGC1α signaling-induced fibroblast growth factor 21 (FGF21) release in brown adipocytes is required for DEX-mediated cardioprotection since blockade of the AMPK/PGC1α axis weakened the salutary effects of DEX. Co-culture experiments showed that DEX-induced FGF21 from brown adipocytes increased the resistance of cardiomyocytes to hypoxia/reoxygenation (H/R) injury via modulating the Keap1/Nrf2 pathway. Our results provided robust evidence that the BAT-cardiomyocyte interaction is required for DEX cardioprotection, and revealed an endocrine role of BAT in DEX-mediating protection of hearts against MIRI.

Opioid-free anesthesia with esketamine-dexmedetomidine versus opioid-based anesthesia with propofol-remifentanil in shoulder arthroscopy: a randomized controlled trial.

BACKGROUND: OFA (Opioid-free anesthesia) has the potential to reduce the occurrence of opioid-related adverse events and enhance postoperative recovery. Our research aimed to investigate whether OFA, combining esketamine and dexmedetomidine, could serve as an alternative protocol to traditional OBA (opioid-based anesthesia) in shoulder arthroscopy, particularly in terms of reducing PONV (postoperative nausea and vomiting). METHODS: A total of 60 patients treated with shoulder arthroscopy from September 2021 to September 2022 were recruited. Patients were randomly assigned to the OBA group (n = 30) and OFA group (n = 30), receiving propofol-remifentanil TIVA (total intravenous anesthesia) and esketamine-dexmedetomidine intravenous anesthesia, respectively. Both groups received ultrasound-guided ISBPB(interscalene brachial plexus block)for postoperative analgesia. RESULTS: The incidence of PONV on the first postoperative day in the ward (13.3% vs. 40%, P < 0.05) was significantly lower in the OFA group than in the OBA group. Moreover, the severity of PONV was less severe in the OFA group than in the OBA group in PACU (post-anesthesia care unit) (0 [0, 0] vs. 0 [0, 3], P<0.05 ) and in the ward 24 h postoperatively ( 0 [0, 0] vs. 0 [0, 2.25], P<0.05). Additionally, the OFA group experienced a significantly shorter length of stay in the PACU compared to the OBA group (39.4 ± 6.76 min vs. 48.7 ± 7.90 min, P < 0.001). CONCLUSIONS: Compared to the OBA with propofol-remifentanil, the OFA with esketamine- dexmedetomidine proved to be feasible for shoulder arthroscopy, resulting in a reduced incidence of PONV and a shorter duration of stay in the PACU. TRIAL REGISTRATION: The Chinese Clinical Trial Registry (No: ChiCTR2100047355), 12/06/2021.

Comparing the Sedative Effects of Intranasal Dexmedetomidine, Midazolam, and Ketamine in Outpatient Pediatric Surgeries: A Randomized Clinical Trial.

Background: The management of preoperative anxiety in pediatric patients, as well as its implications, has remained challenging for anesthesiologists. In this study, we compared the safety and efficacy of intranasal dexmedetomidine, midazolam, and ketamine as surgical premedication in children. Methods: This double-blinded randomized clinical trial was conducted at two tertiary hospitals in January 2014, on 90 children aged between 2-7 years old. The participants' American Society of Anesthesiologists (ASA) physical status was I or II, and they were scheduled for elective unilateral inguinal herniorrhaphy. Using the block randomization method, the patients were randomly assigned to three groups, each receiving intranasal dexmedetomidine (2 µg/Kg), midazolam (0.2 mg/Kg), and ketamine (8 mg/Kg) 60 min before induction of anesthesia. Anxiety and sedation state were evaluated before drug administration, and then every 10 min for the next 50 min. Parental separation anxiety, mask acceptance, postoperative agitation, pain, nausea, and vomiting were also recorded and compared between these groups. All the statistical analyses were performed using SPSS software (version 21.0). P<0.05 was considered statistically significant. Results: Ketamine indicated the strongest sedative effect 10, 20, and 30 min after administration of premedication (P<0.001, P=0.03, P=0.01, respectively). However, dexmedetomidine was more effective than other drugs after 40 and 50 min (P<0.001). Other variables indicated no statistically significant difference. Conclusion: In case of emergencies, intranasal ketamine, with the shortest time of action, could be administered. Intranasal dexmedetomidine, which was revealed to be the most potent drug in this study, could be administrated 40-50 min before elective pediatric surgeries.Trial registration number: IRCT2013081614372N1.

Perioperative dexmedetomidine-induced delirium in a patient with schizophrenia: a case report.

BACKGROUND: Dexmedetomidine is a selective α2 receptor agonist with sedative, analgesic, anxiolytic, and anti-sympathetic effects. Dexmedetomidine is widely used for various surgical procedures performed under general anaesthesia and sedation in the intensive care unit. Dexmedetomidine was known to relieve or improve the symptoms of delirium. Schizophrenia is a common psychiatric disease, and the number of surgical patients with schizophrenia is increasing gradually. Dexmedetomidine-induced delirium in patients with schizophrenia is a particular case. CASE PRESENTATION: This patient was a 75-year-old woman (height: 156 cm; weight: 60 kg) with a 5-year history of schizophrenia. Her schizophrenia was well controlled with medications. She was scheduled for open reduction and internal fixation for a patellar fracture. Spinal anaesthesia was administered for surgery, and dexmedetomidine was administered intravenously to maintain sedation. The patient became delirious half an hour after the surgery began. The intravenous infusion of dexmedetomidine was discontinued immediately, intravenous propofol was subsequently administered, and the patient stopped experiencing dysphoria and fell asleep. After surgery, the patient stopped using propofol and recovered smoothly. She was transferred back to the general ward and was discharged from the hospital without any abnormal conditions on the 9th day after surgery. CONCLUSIONS: To the best of our knowledge, this is the first report of a patient with schizophrenia who developed delirium during the infusion of a normal dose of dexmedetomidine without an intravenous injection of any other sedative. The exact mechanism causing dexmedetomidine-induced delirium remains unclear, and this adverse reaction is rare and easy to ignore. Clinicians and pharmacists should be vigilant in identifying this condition.

Exploring the Potential Role of Dexmedetomidine in Reducing Postoperative Cognitive Dysfunction in Elderly Hip Fracture Patients.

BACKGROUND: Hip fractures are prevalent in the elderly; however, Postoperative Cognitive Dysfunction (POCD) is a possible complication of hip fracture surgery in elderly patients. This study examines the influence and the underlying mechanism of dexmedetomidine on POCD in elderly patients following hip fracture surgery. METHODS: The retrospective study involved elderly patients with hip fracture who were treated at the Fifth Affiliated Hospital of Xinjiang Medical University from October 2021 to August 2022. During the surgery procedures, dexmedetomidine was administrated and the peripheral blood samples were collected from the patients. Inflammatory factors were measured using Enzyme-linked immunosorbent assay (ELISA), while pyroptosis-related proteins were detected through quantitative reverse transcription PCR (RT-qPCR) and western blot. Additionally, the levels of CD4+T and CD8+T cells were assessed using flow cytometry. An aged rats hip fracture model was established to further investigate the impact of dexmedetomidine on postoperative mobility, cognition function, pyroptosis and immune cells in rats. RESULTS: Postoperative cognitive function in patients did not show significant alteration when compared with pre-operation levels (p > 0.05). There were notable reduction in the levels of interleukin-18 (IL-18), Caspase-3, Gasdermin-D (GSDMD) and NLR Family Pyrin Domain Containing 3 (NLRP3) (p < 0.001), accompanied by an increase in the proportion of CD4+T cells and an decrease in CD8+T cells after operation (p < 0.01). In aged rats, postoperative exploratory activities increased compared to their preoperative state. Compared with preoperative levels, the levels of interleukin-1ß (IL-1ß), IL-18, Caspase-3, GSDMD, and NLRP3 were significantly decreased (p < 0.001), the proportion of CD4+T cells was increased, and the proportion of CD8+T cells was decreased postoperatively (p < 0.01). CONCLUSIONS: Although there was no significant alteration in postoperative cognitive function in patients, dexmedetomidine may still play a role in mitigating POCD potentially due to its effects on reducing immune inflammation and pyroptosis markers. Further research is needed to fully understand the underlying mechanisms and its clinical implications.

Ropivacaine combined with dexmedetomidine in ultrasound-guided axillary brachial plexus block in children, a randomized controlled trial.

OBJECTIVE: In this study, we evaluated the efficacy and safety of 1 µg/kg dexmedetomidine as an adjuvant treatment to ropivacaine in children undergoing upper limb surgeries under ultrasound-guided axillary brachial plexus blocks and general anesthesia. METHODS: We enrolled 90 children (aged 1-8 years; ASA I-II) undergoing closed reduction and internal fixation for upper extremity fractures at the Xiamen Children's Hospital and randomly assigned them to one of two groups: L (injection with 0.25% ropivacaine) or D (injection with 0.25% ropivacaine containing 1 µg/kg dexmedetomidine) using the random number table method. The main outcome indicators recorded were the facial expression, leg activity, position, crying, and Face, Legs, Activity, Cry, and Consolability (FLACC) scale scores of children after surgery and the duration of block and analgesia maintenance. The secondary outcome indicators were vital sign data at the time of ultrasound probe placement (T1), at the time of block completion (T2), prior to the beginning of surgery (T3), 5 min after the beginning of surgery (T4), and at the end of surgery (T5), as well as the time of postoperative recovery, the number of cases of remedial analgesia, and complications. RESULTS: There was no statistical difference between the two groups in terms of general data, block completion time, postoperative recovery time, and complications (P > 0.05). Compared to the L group, the D group had significantly lower FLACC scores at 6 h after surgery, as well as significantly lower systolic blood pressure, diastolic blood pressure, and heart rate values at T4 and T5, and significantly longer duration of postoperative analgesia maintenance (all P < 0.05). CONCLUSION: Dexmedetomidine (1 µg/kg) as a local anesthetic adjuvant to ropivacaine can alleviate pain at 6 h postoperatively, prolong analgesia maintenance, and reduce intraoperative blood pressure and heart rate in pediatric patients undergoing closed reduction and internal fixation for upper extremity fractures, with no obvious complications or delayed recovery. CLINICAL REGISTRY NUMBER: Registration website: www.chictr.org.cn, Registration number: ChiCTR2200065163, Registration date: October, 30, 2022.

Mapping Theme Trends and Research Frontiers in Dexmedetomidine Over Past Decade: A Bibliometric Analysis.

Background: Dexmedetomidine, an α2-adrenergic receptor (α2-AR) agonist, is extensively used in clinical and animal studies owing to its sedative, analgesic, and anxiolytic effects. The diverse range of research domains associated with dexmedetomidine poses challenges in defining pivotal research directions. Therefore, this study aimed to conduct a qualitative and quantitative bibliometric study in the field of dexmedetomidine over the past decade to establish current research trends and emerging frontiers. Methods: Relevant publications in the field of dexmedetomidine between 2014 and 2023 were extracted from the Web of Science Core Collection database. The bibliometric analysis, incorporating statistical and visual analyses, was conducted using CiteSpace (6.1.R6) and R (4.3.1). Results: The present study encompassed a total of 5,482 publications, exhibiting a consistent upward trend over the past decade. The United States and its institutions had the highest centrality. Ji, Fuhai, and Ebert, Thomas J. were identified as the most productive author and the most cited author, respectively. As anticipated, the most cited journal was Anesthesiology. Moreover, cluster analysis of cited references and co-occurrence of keywords revealed that recent studies were primarily focused on sedation, delirium, and opioid-free anesthesia. Finally, a timeline view of keywords clusters and keywords burst demonstrated that primary research frontiers were stress response, neuroinflammation, delirium, opioid-free anesthesia, peripheral nerve block, and complications. Conclusion: Current research trends and directions are focused on sedation, delirium, and opioid-free anesthesia, as evidenced by our results. The frontier of future research is anticipated to encompass basic investigations into dexmedetomidine, including stress response and neuroinflammation, as well as clinical studies focusing on delirium, opioid-free anesthesia, peripheral nerve block, and associated complications.

Effects of dexmedetomidine, fentanyl and magnesium sulfate added to ropivacaine on sensory and motor blocks in lower abdominal surgery: a randomized clinical trial.

This study aimed to compare the effects of intrathecal dexmedetomidine, fentanyl and magnesium sulfate added to ropivacaine on the onset and duration of sensory and motor blocks in lower abdominal surgery. This double-blind randomized clinical trial included 90 patients scheduled for lower abdominal surgery at Vali-Asr Hospital in Arak, Iran. The enrolled patients were randomly divided into three equal groups and then underwent spinal anesthesia. The first group received 10 µg of dexmedetomidine, the second group received 50 µg of fentanyl, and the third group received 200 mg of 20% magnesium sulfate intrathecally in addition to 15 mg of 0.5% ropivacaine. In the dexmedetomidine group, the mean arterial blood pressure was lower than the other two groups (P = 0.001). Moreover, the time to onset of sensory block (P = 0.001) and the mean duration of sensory block (P = 0.001) were shorter and longer, respectively, in the dexmedetomidine group than in the other two groups. In the dexmedetomidine group, the mean time to onset of motor block (P = 0.001) and the mean duration of motor block (P = 0.001) were lower and higher than in the other two groups, respectively. There was no significant difference in visual analog scale score, heart rate, administered opioid, and drug side effects among the three groups. Dexmedetomidine caused early sensory and motor blocks while prolonging the duration of sensory and motor blocks compared with the other two groups. In addition, dexmedetomidine reduced mean arterial blood pressure in patients. Based on the findings of this study, it is recommended that dexmedetomidine can be used in order to enhance the quality of sensory and motor block in patients.

[Comparison of the effects of child-centered playful companionship and pharmacological sedation in alleviating preoperative anxiety in preschool children].

Objective: To investigate the effectiveness of child-centered playful companionship and sedative medication in alleviating preoperative anxiety in preschool children. Methods: A retrospective analysis was conducted on 3 825 preschool children (3-6 years) who underwent elective surgery at Shanghai Children's Medical Center from April 2021 to March 2022. The children were divided into three groups based on the preoperative anxiolytic intervention: child-centered playful companionship group (n=2 198), pharmacological sedation group (n=1 281), and no intervention group (n=346). The pharmacological sedation group received intranasal dexmedetomidine at 2 µg/kg or oral midazolam syrup at 0.5 mg/kg. The child-centered playful companionship group received care from certified preoperative sedation nurses using a child-centered playful nursing model. The no intervention group did not receive any anti-anxiety measures due to various subjective and objective reasons. Preoperative separation anxiety scores (PSAS), sedation medication usage, and Ramsay sedation scores were recorded for all children. The primary outcome was the success rate of separation based on PSAS scores across different anxiolytic intervention groups, while the secondary outcome was the Ramsay sedation score. Results: The child-centered playful companionship group included 1 462 boys and 736 girls, with a median age [M (Q1, Q3)]of 59 (49, 69) months. The pharmacological sedation group included 824 boys and 457 girls, with a median age of 52 (42, 61) months; and the no intervention group included 212 boys and 134 girls, with a median age of 57 (48, 69) months. The success rate of separation in the child-centered playful companionship group was 95.6% (2 102/2 198), and in the pharmacological sedation group was 93.8% (1 202/1 281), both significantly higher than the 43.6% (151/346) of the no intervention group (all P<0.05). Among the 1 281 children in the pharmacological sedation group, 785 received oral midazolam and 496 received intranasal dexmedetomidine. Compared to the intranasal dexmedetomidine group, the oral midazolam group was younger, had a lower body weight and a higher proportion of American Society of Anesthesiologists (ASA) class Ⅲ (all P<0.05). The success rate of separation was 93.4% (733/785) in the oral midazolam group and 94.6% (469/496) in the intranasal dexmedetomidine group, with no statistically significant difference (P=0.392). The Ramsay sedation score was 2 (2, 2) in the intranasal dexmedetomidine group, better than the 2 (2, 2) of the oral midazolam group (P=0.024). Conclusion: Both child-centered playful companionship and pharmacological sedation effectively alleviate preoperative anxiety in preschool children.

Comparative evaluation of intranasal dexmedetomidine, intranasal midazolam, and nitrous oxide for conscious sedation of anxious children undergoing dental treatment: A randomized cross-over trial.

BACKGROUND: Pharmacological methods, specifically sedatives, have gained popularity in managing the behavior of children during dental appointments. AIM: The aim of this study was to compare 1 m/kg intranasal dexmedetomidine, 0.3 mg/kg intranasal midazolam, and nitrous oxide in evaluating the level of sedation, behavior of the child, onset of sedation, physiologic signs, and adverse effects. MATERIALS AND METHODS: In this cross-over trial, 15 children aged 6-8 years were randomized to receive intranasal atomized dexmedetomidine, intranasal atomized midazolam, and inhalation nitrous oxide at three separate visits. After administering the sedative agent, a single pulpectomy was performed during each appointment, and the outcomes were recorded. The washout period between each visit was 1 week. RESULTS: All three sedative agents were equally effective in controlling overall behavior. Dexmedetomidine showed lower sedation level scores (agitated; score 9) than the other groups. There was a statistically significant difference in the onset of sedation, with dexmedetomidine having the longest onset of 36.2 ± 9.47 min. Coughing and sneezing were predominantly observed after administration of intranasal midazolam. Oxygen saturation levels were statistically lower in the intranasal midazolam group during local anesthesia administration and post-treatment. CONCLUSION: 0.3 mg/kg intranasal midazolam is as effective as nitrous oxide sedation for controlling behavior and providing adequate sedation in pediatric dental patients. However, 1 m/kg dexmedetomidine did not provide the same level of sedation and had a significantly longer onset. 0.3 mg/kg intranasal midazolam is an effective alternative to nitrous oxide sedation in anxious children.

[Effects of Dexmedetomidine on the Recovery Quality of Donors Undergoing Pure Laparoscopic Donor Hepatectomy]. / å³ç¾Žæ‰˜å’ªå®šå¯¹è ¹è ”é•œä¾›è‚èŽ·å–æœ¯ä¾›è€ è‹é†’æœŸæ¢å¤è´¨é‡çš„å½±å“.

Objective: To investigate the effects of intraoperative intravenous administration of dexmedetomidine (DEX) on the recovery quality of donors undergoing pure laparoscopic donor hepatectomy. Methods: A total of 56 liver donors who were going to undergo scheduled pure laparoscopic donor hepatectomy were enrolled and randomly assigned to two groups, a DEX group ( n=28) and a control group ( n=28). Donors in the DEX group received DEX infusion at a dose of 1 µg/kg over 15 minutes through a continuous pump, which was followed by DEX at 0.4 µg/(kg·h) until the disconnection of the portal branch. Donors in the control group were given an equal volume of 0.9% normal saline at the same infusion rate and over the same period of time as those of the dex infusion in the DEX group. The primary outcome was the incidence of emergence agitation (EA). The Aono's Four-point Scale (AFPS) score was used to assess EA. The secondary observation indicators included intraoperative anesthesia and surgery conditions, spontaneous respiration recovery time, recovery time, extubation time, scores for the Ramsay Sedation Scale, the incidence of chills, numeric rating scale (NRS) score for pain, and blood pressure and heart rate after extubation. Results: The incidence of EA was 10.7% and 39.3% in the DEX group and the control group, respectively, and the incidence of EA was significantly lower in the DEX group than that in the control group ( P=0.014). The APFS scores after extubation in the DEX group were lower than those in the control group (1 [1, 1] vs. 2 [1, 3], P=0.005). Compared to the control group, the dosages of intraoperative propofol and remifentanil were significantly reduced in the DEX group ( P<0.05). During the recovery period, the number of donors requiring additional boluses of analgesia, the blood pressure, and the heart rate were all lower in the DEX group than those in the control group ( P<0.05). No significant differences between the two groups were observed in the spontaneous respiration recovery time, recovery time, extubation time, the incidence of chills, NRS score, scores for the Ramsay Sedation Scale, and the length-of-stay in postanesthesia care unit (PACU) ( P>0.05). Conclusion: DEX can reduce the incidence of EA after pure laparoscopic donor hepatectomy and improve the quality of recovery without prolonging postoperative recovery time or extubation time.

Effect of esketamine combined with dexmedetomidine on delirium in sedation for mechanically ventilated ICU patients: protocol for a nested substudy within a randomized controlled trial.

BACKGROUND: Use of sedatives and analgesics is associated with the occurrence of delirium in critically ill patients receiving mechanical ventilation. Dexmedetomidine reduces the occurrence of delirium but may cause hypotension, bradycardia, and insufficient sedation. This substudy aims to determine whether the combination of esketamine with dexmedetomidine can reduce the side effects and risk of delirium than dexmedetomidine alone in mechanically ventilated patients. METHODS: This single-center, randomized, active-controlled, superiority trial will be conducted at The First Affiliated Hospital of Nanjing Medical University. A total of 134 mechanically ventilated patients will be recruited and randomized to receive either dexmedetomidine alone or esketamine combined with dexmedetomidine, until extubation or for a maximum of 14 days. The primary outcome is the occurrence of delirium, while the second outcomes include the number of delirium-free days; subtype, severity, and duration of delirium; time to first onset of delirium; total dose of vasopressors and antipsychotics; duration of mechanical ventilation; ICU and hospital length of stay (LOS); accidental extubation, re-intubation, re-admission; and mortality in the ICU at 14 and 28 days. DISCUSSION: There is an urgent need for a new combination regimen of dexmedetomidine due to its evident side effects. The combination of esketamine and dexmedetomidine has been applied throughout the perioperative period. However, there is still a lack of evidence on the effects of this regimen on delirium in mechanically ventilated ICU patients. This substudy will evaluate the effects of the combination of esketamine and dexmedetomidine in reducing the risk of delirium for mechanically ventilated patients in ICU, thus providing evidence of this combination to improve the short-term prognosis. The study protocol has obtained approval from the Medical Ethics Committee (ID: 2022-SR-450). TRIAL REGISTRATION: ClinicalTrials.gov: NCT05466708, registered on 20 July 2022.

Comparing different postoperative sedation strategies for patients in the intensive care unit after cardiac surgery: A systematic review of randomized controlled trials and network meta-analysis.

BACKGROUND: Various postoperative sedation protocols with different anaesthetics lead to profound effects on the outcomes for post-cardiac surgery patients. However, a comprehensive analysis of optimal postoperative sedation strategies for patients in the intensive care unit (ICU) after cardiac surgery is lacking. METHODS: We systematically searched for randomized controlled trials (RCTs) in databases including PubMed and Embase. The primary outcome measured the duration of mechanical ventilation (MV) in the ICU, and the secondary outcome encompassed the length of stay (LOS) in the ICU and hospital and the monitoring adverse events. RESULTS: The literature included 18 RCTs (1652 patients) with 13 sedation regimens. Dexmedetomidine plus ketamine and sevoflurane were associated with a significantly reduced duration of MV when compared with propofol. Our results also suggested that dexmedetomidine plus ketamine may associated with a shorter LOS in ICU, and sevoflurane associated with a shorter LOS in the hospital, respectively. CONCLUSIONS: The combination of dexmedetomidine and ketamine seems to be a better option for adult patients needing sedation after cardiac surgery, and the incidence of side effects is lower with dexmedetomidine. These findings have potential implications for medication management in the perioperative pharmacotherapy of cardiac surgery patients.

Study on the preventive effect of dexmedetomidine on anesthetic associated sleep disturbance in young to middle-aged female patients undergoing hysteroscopy: a study protocol for a crossover randomized controlled trial.

BACKGROUND: Postoperative sleep disturbance has a potentially detrimental effect on postoperative recovery. Perioperative patients are affected by several factors. General anesthesia induces a non-physiological state that does not resemble natural sleep. Exposure to propofol/sevoflurane can lead to desynchronization of the circadian rhythm, which may result in postoperative sleep disturbance characterized by mid-cycle advancement of sleep and daytime sleepiness. Dexmedetomidine is a highly selective α2-adrenoceptor agonist with a unique sedative effect that facilitates the transition from sleep to wakefulness. Basic research has shown that dexmedetomidine induces deep sedation, similar to physical sleep, and helps maintain forebrain connectivity, which is likely to reduce delirium after surgery. The aim of this study is to evaluate the influence of exposure to the mono-anesthetic propofol on the development of postoperative sleep disturbance in young and middle-aged female patients undergoing hysteroscopy and whether prophylactic administration of dexmedetomidine influences reducing postoperative sleep disturbance. METHODS: This prospective randomized controlled trial (RCT) will include 150 patients undergoing hysteroscopy at the First Affiliated Hospital of Xiamen University. Participants will be randomly assigned to three groups in a 1:1:1 ratio. The dexmedetomidine group will have two subgroups and will receive a nasal spray of 0.2 µg/kg or 0.5 µg/kg 25 min before surgery, while the control group will receive a saline nasal spray. Three groups will undergo hysteroscopy with propofol-based TIVA according to the same scheme. Sleep quality will be measured using a wearable device and double-blind sleep assessments will be performed before surgery and 1, 3, and 7 days after surgery. SPSS 2.0 is used for statistical analysis. A χ2 test is used to compare groups, and t-test is used to determine statistical the significance of continuous variables. DISCUSSION: The purpose of this study is to investigate the incidence of propofol-associated sleep disorders and to test a combination of dexmedetomidine anesthesia regimen for the prevention of postoperative sleep disorders. This study will help to improve patients' postoperative satisfaction and provide a new strategy for comfortable perioperative medical treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT06281561. Registered on February 24, 2024.

Dexmedetomidine as a total intravenous anesthetic in pediatric patients undergoing cleft lip and palate surgery: a case series.

BACKGROUND: Surgery for pediatric cleft lip and palate repair often utilizes high-dose opioids and inhaled anesthesia, thereby causing postoperative complications such as desaturation and/or severe agitation after anesthesia. These complications are detrimental to the child and medical personnel and cause tremendous psychologic stress to parents. Our aim is to decrease these complications through dexmedetomidine, an alpha-2 receptor agonist with anxiolytic, sympatholytic, and analgetic properties. Devoid of respiratory depressant effect, it allows patients to maintain effective ventilation and reduce agitation, postoperatively. Its unique anesthetic property may shed light on providing safe anesthesia and gentle emergence to this young, vulnerable population. CASE PRESENTATION: A total of 21 patients of Sundanese ethnicity, aged 3 months to 8 years (9 males and 12 females), underwent cleft lip or cleft palate surgery using total intravenous dexmedetomidine. Anesthesia was induced using sevoflurane, fentanyl, and propofol, and airway was secured. Intravenous dexmedetomidine 1.5 µg/kg was administered within 10 minutes, and a maintenance dose of 1.5 µg/kg/hour was continued as the sole anesthetic maintenance agent thereafter. Hemodynamics and anesthetic depth using Patient State Index (SEDLine™ monitor, Masimo Corporation, Irvine, CA, USA) were monitored carefully throughout the surgical procedure. Dexmedetomidine did not cause any hemodynamic derangements or postoperative complications in any of our patients. We found agitation in 9.5% (2/21) of patients. CONCLUSION: Dexmedetomidine can be used as a total intravenous anesthetic agent to maintain anesthesia and provide gentle emergence to infants and young children undergoing cleft lip and palate repair.

Dexmedetomidine's protective mechanism against hyperoxic injury in neonatal rats.

Bronchopulmonary dysplasia (BPD) is a common serious complication of premature babies. No effective means control it. Hyperoxia damage is one of the important mechanisms of BPD. The reaserach confirmed pyroptosis existed in BPD. Dexmedetomidine is a new, high-specific α2 receptor agonist. Previous research foundation found that dexmedetomidine has a protective effect on BPD. To investigate how dexmedetomidine improves hyperoxic lung injury in neonatal mice by regulating pyroptosis. Neonatal rats were randomly divided into four groups: normal control group, hyperoxic injury group, air plus dexmedetomidine group, and hyperoxia plus dexmedetomidine group. After seven days the lungs of rats in each group were extracted, and the wet-to-dry weight ratio of the lung was measured. The lung injury in rats was observed using hematoxylin-eosin staining. Additionally, the expression and localization of nucleotide-binding oligomerization domain-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), and gasdermin D (GSDMD) proteins were examined in the lungs of rats using immunofluorescence staining. The mRNA levels of NLRP3, ASC, caspase-1, and interleukin 18 (IL-18) in the lungs of rats were determined using real-time PCR. Moreover, the protein levels of NLRP3, ASC, caspase-1/cleaved caspase-1, interleukin 1beta (IL-1ß), IL-18, and tunor necrosis factor alpha (TNF-α) were detected in lungs of rats using Western blot. The extent of mitochondrial damage in lung tissues of each group was observed by transmission electron microscopy. The lung tissue injury of the neonatal rats was significantly improved in the hyperoxia plus dexmedetomidine group compared to the hyperoxic injury group. Furthermore, the expressions of pyroptosis-related proteins such as NLRP3, ASC, cleaved-caspase-1, and GSDMD were significantly decreased, along with the expressions of inflammatory factors in lung tissues. By inhibiting the NLRP3/caspase-1/GSDMD pyroptosis pathway, dexmedetomidine reduces the activation and release of inflammatory factors and provides a protective effect against hyperoxic lung injury in neonatal mice.

Intraoperative Dexmedetomidine Use for Enhanced Recovery after Surgery (ERAS) in Cardiac Surgery-Single Center Retrospective Observational Cohort Study.

Background and Objectives: Dexmedetomidine, an alpha-2 agonist, is used as an adjunct to anesthesia in enhanced recovery after surgery (ERAS) programs. One of its advantages is the opioid-sparing effect which can facilitate early extubation and recovery. When the ERAS cardiac society was set in 2017, our facility was already using the ERAS program, in which the "fast-track Anesthesia" was facilitated by the intraoperative infusion of dexmedetomidine. Our objective is to share our experience and investigate the potential impact of intraoperative dexmedetomidine use as a part of the ERAS program on patient outcomes in elective cardiac surgery. Materials and Methods: An observational retrospective cohort study was conducted at a university hospital in Switzerland. The patients who underwent elective cardiac surgery with cardiopulmonary bypass between 1 June 2017 and 31 August 2018 were included in this analysis (n = 327). Regardless of the surgery type, all the patients received a standardized fast-track anesthesia protocol inclusive of dexmedetomidine infusion, reduced opioid dose, and parasternal nerve block. The primary outcome was the postoperative time when the criteria for extubation were met. Three groups were identified: group 0-(extubated in the operating room), group < 6 (extubated in less than 6 h), and group > 6 (extubated in >6 h). The secondary outcomes were adverse events, length of stay in ICU and in hospital, and total hospitalization costs. Results: Dexmedetomidine was well-tolerated, with no significant adverse events reported. Early extubation was performed in 187 patients (57%). Group 3 had a significantly longer length of stay in the ICU (median: 70 h vs. 25 h) and in hospital (17 vs. 12 days), and consequently higher total hospitalization costs (CHF 62,551 vs. 38,433) compared to the net data from the other two groups (p < 0.0001). Conclusions: Our findings suggest that dexmedetomidine can be safely used as part of the opioid-sparing anesthesia protocol in patients undergoing elective cardiac surgery with cardiopulmonary bypass with the potential to facilitate early extubation, shorter ICU and hospital stays, and reduced hospitalization costs.

Dexmedetomidine administration as a possible cognitive enhancer through increasing the level of brain-derived neurotrophic factors in surgical patients: a systematic review and meta-analysis.

OBJECTIVE: This meta-analysis aimed to investigate the effect of dexmedetomidine on brain-derived neurotrophic factor (BDNF) levels in individuals undergoing various medical procedures. We systematically searched electronic databases and manually identified relevant articles to assess the impact of dexmedetomidine on BDNF levels in surgical patients. METHODS: A comprehensive literature search was conducted in PubMed, Scopus, Embase, and Web of Science databases with no language restrictions. Studies that examined the effects of dexmedetomidine administration on BDNF levels in surgical patients were included. RESULTS: The overall analysis revealed a statistically significant increase in BDNF levels in individuals receiving dexmedetomidine compared to controls (Standardized Mean Difference SMD = 1.65, 95% CI: 1.02 to 2.28; I2: 89%). Subgroup analyses based on the anesthesia method (p < 0.01), and the type of surgery (p < 0.01) showed significant between-group differences (Fig. 3). The results of the sensitivity analyses indicated that individual studies did not significantly affect the overall results. CONCLUSION: This meta-analysis indicates that dexmedetomidine administration is associated with a significant increase in BDNF levels in individuals undergoing surgical procedures. These findings highlight the potential role of dexmedetomidine in modulating BDNF levels, which may have implications for optimizing perioperative neuroprotective strategies and improving patient outcomes.

Dexmedetomidine facilitates autophagic flux to promote liver regeneration by suppressing GSK3ß activity in mouse partial hepatectomy.

INTRODUCTION: Dexmedetomidine (DEX), a highly selective α2-adrenergic receptor agonist, is widely used for sedation and anesthesia in patients undergoing hepatectomy. However, the effect of DEX on autophagic flux and liver regeneration remains unclear. OBJECTIVES: This study aimed to determine the role of DEX in hepatocyte autophagic flux and liver regeneration after PHx. METHODS: In mice, DEX was intraperitoneally injected 5 min before and 6 h after PHx. In vitro, DEX was co-incubated with culture medium for 24 h. Autophagic flux was detected by LC3-II and SQSTM1 expression levels in primary mouse hepatocytes and the proportion of red puncta in AML-12 cells transfected with FUGW-PK-hLC3 plasmid. Liver regeneration was assessed by cyclinD1 expression, Edu incorporation, H&E staining, ki67 immunostaining and liver/body ratios. Bafilomycin A1, si-GSK3ß and Flag-tagged GSK3ß, α2-ADR antagonist, GSK3ß inhibitor, AKT inhibitor were used to identify the role of GSK3ß in DEX-mediated autophagic flux and hepatocyte proliferation. RESULTS: Pre- and post-operative DEX treatment promoted liver regeneration after PHx, showing 12 h earlier than in DEX-untreated mice, accompanied by facilitated autophagic flux, which was completely abolished by bafilomycin A1 or α2-ADR antagonist. The suppression of GSK3ß activity by SB216763 and si-GSK3ß enhanced the effect of DEX on autophagic flux and liver regeneration, which was abolished by AKT inhibitor. CONCLUSION: Pre- and post-operative administration of DEX facilitates autophagic flux, leading to enhanced liver regeneration after partial hepatectomy through suppression of GSK3ß activity in an α2-ADR-dependent manner.