Zona incerta mediates early life isoflurane-induced fear memory deficits.

The potential long-term effects of anesthesia on cognitive development, especially in neonates and infants, have raised concerns. However, our understanding of its underlying mechanisms and effective treatments is still limited. In this study, we found that early exposure to isoflurane (ISO) impaired fear memory retrieval, which was reversed by dexmedetomidine (DEX) pre-treatment. Measurement of c-fos expression revealed that ISO exposure significantly increased neuronal activation in the zona incerta (ZI). Fiber photometry recording showed that ZI neurons from ISO mice displayed enhanced calcium activity during retrieval of fear memory compared to the control group, while DEX treatment reduced this enhanced calcium activity. Chemogenetic inhibition of ZI neurons effectively rescued the impairments caused by ISO exposure. These findings suggest that the ZI may play a pivotal role in mediating the cognitive effects of anesthetics, offering a potential therapeutic target for preventing anesthesia-related cognitive impairments.

Successful Second Awake Craniotomy Reoperation With Dexmedetomidine After an Initial Abandonment Case Due to Restlessness.

Awake craniotomy (AC) is sometimes aborted due to poor arousal and restlessness. Dexmedetomidine (DEX), an α2-adrenoreceptor agonist, has sedative, analgesic, and anesthetic-sparing effects, with a low risk of respiratory depression, making it effective for intraoperative pain and agitation during the awake phase. We report a case in which AC was successfully performed in combination with low-dose continuous administration of DEX during reoperation in a patient who experienced poor arousal and restlessness during their first surgery, leading to the abandonment of AC. The patient is a 48-year-old male who is scheduled for AC reoperation. Two years ago, the first AC was scheduled and performed under anesthesia with propofol and remifentanil. However, AC was abandoned due to poor intraoperative arousal and restlessness. At reoperation, general anesthesia was induced with propofol and continuous administration of remifentanil (0.1 µg/kg/min); following anesthesia induction (continuous infusion of propofol, remifentanil, and a bolus infusion of fentanyl), DEX was also administered (0.2 µg/kg/hour). We performed a scalp nerve block. Before the awake phase, the propofol dose was decreased as was DEX to 0.1 µg/kg/hour, and propofol and remifentanil were discontinued. The patient gradually awoke without any agitation and restlessness 24 min after stopping propofol and remifentanil and could perform language tasks without any complications. In this case, AC was successfully performed in combination with continuous low-dose administration of DEX at the time of reoperation in a patient who experienced poor arousal and restlessness during their first operation and had to discontinue AC.

Awake reduction of hangman's fracture: An era of dexmedetomidine.

Hangman's fracture is a kind of unstable cervical spine injury which should be treated promptly to avoid life threatening consequences. Advanced neurological monitoring is essential during surgical intrervention. Resource limited setting, where advanced monitors like SSEP and MEP are not available makes it challenging to assess proper reduction of cervical spine without neurological compromise. Dexmedetomidine proved to be very useful drug to assess the neurological status intra operatively by awake sedation.

Dexmedetomidine Inhibits Hippocampal Neuronal Damage Caused by Persistent Isoflurane-Induced Hypotension in Rat Model of Chronic Cerebral Hypoperfusion.

Purpose The purpose of this study was to investigate the effect of dexmedetomidine (DEX) on hypotension-induced neuronal damage in a chronic cerebral hypoperfusion (CCH) model of rats, an established model of cerebral white matter lesions (WML) in humans, which is prevalent in the elderly and closely related to cognitive decline. Methods The CCH model rats were randomly assigned to one of four groups: normotension + no DEX (NN) group (n = 6), normotension + DEX (ND) group (n = 6), hypotension + no DEX (HN) group (n = 6), or hypotension + DEX (HD) group (n = 6). Under isoflurane anesthesia, mean arterial blood pressure was maintained at or above 80 mmHg (normotension) or below 60 mmHg (hypotension) for a duration of two hours. The DEX groups received 50 µg of DEX intraperitoneally. Two weeks later, the Y-maze test and, after preparing brain slices, immunohistochemical staining were performed using antibodies against neuronal nuclei (NeuN), microtubule-associated protein 2 (MAP2), glial fibrillary acidic protein (GFAP), and Ionized calcium-binding adapter molecule 1 (Iba1). Results Behavioral observations showed no significant differences among the groups. Significant reductions of both NeuN-positive cells and the MAP2-positive area were found in the hippocampal CA1 in the HN group compared with NN and ND groups, but not in the HD group. GFAP and Iba-1-positive areas were significantly increased in the HN group, but not in the HD group. Conclusion DEX significantly ameliorated hypotension-induced neuronal damage and both astroglial and microglial activation in the CA1 region of CCH rats.

Effects of perioperative dexmedetomidine on delayed graft function following renal transplant: a systematic review and meta-analysis.

BACKGROUND: Dexmedetomidine, a highly selective alpha-2 adrenoceptor agonist with sedative and analgesic effects, has been suggested in recent studies to possess renoprotective properties. Dexmedetomidine may reduce the incidence of delayed graft function and contribute to effective pain control post-renal transplantation. The primary objective of this systematic review was to assess whether dexmedetomidine decreases the occurrence of delayed graft function in renal transplant patients. METHODS: Databases including MEDLINE, EMBASE, and CENTRAL were comprehensively searched from their inception until March 2023. The inclusion criteria covered all Randomized Clinical Trials (RCTs) and observational studies comparing dexmedetomidine to control in adult patients undergoing renal transplant surgery. Exclusions comprised case series and case reports. RESULTS: Ten RCTs involving a total of 1,358 patients met the eligibility criteria for data synthesis. Compared to the control group, the dexmedetomidine group demonstrated a significantly lower incidence of delayed graft function (OR = 0.71, 95% CI 0.52-0.97, p = 0.03, GRADE: Very low, I2 = 0%). Dexmedetomidine also significantly prolonged time to initiation of rescue analgesia (MD = 6.73, 95% CI 2.32-11.14, p = 0.003, GRADE: Very low, I2 = 93%) and reduced overall morphine consumption after renal transplant (MD = -5.43, 95% CI -7.95 to -2.91, p < 0.0001, GRADE: Very low, I2 = 0%). The dexmedetomidine group exhibited a significant decrease in heart rate (MD = -8.15, 95% CI -11.45 to -4.86, p < 0.00001, GRADE: Very low, I2 = 84%) and mean arterial pressure compared to the control group (MD = -6.66, 95% CI -11.27 to -2.04, p = 0.005, GRADE: Very low, I2 = 87%). CONCLUSIONS: This meta-analysis suggests that dexmedetomidine may potentially reduce the incidence of delayed graft function and offers a superior analgesia profile as compared to control in adults undergoing renal transplants. However, the high degree of heterogeneity and inadequate sample size underscore the need for future adequately powered trials to confirm these findings.

[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.

Combination of dexamethasone and dexmedetomidine as adjuvants of transversus abdominis plane block for postoperative analgesia in gastric cancer patients: A double-blinded randomized controlled trial.

STUDY OBJECTIVE: We conducted this double-blinded randomized controlled trial to examine whether the combination of dexamethasone and dexmedetomidine as adjuvants of transversus abdominis plane (TAP) block could improve analgesia efficacy and duration for gastric cancer patients. DESIGN: Randomized controlled trial. SETTING: The preoperative area, operating room, postanesthesia recovery room and bed ward. PATIENTS: A total of 312 adult patients (104 per group) with gastric cancer were included. INTERVENTIONS: Patients received bilateral subcostal TAP block with three different anesthetics (60 ml 0.25% ropivacaine added with 10 mg dexamethasone and 1 µg·kg-1 dexmedetomidine [A] or 10 mg dexamethasone [B] or 1 µg·kg-1 dexmedetomidine [C]). MEASUREMENTS: The primary outcome was the incidence of moderate-to-severe pain 24 h on movement. Secondary outcomes included incidence of moderate-to-severe pain, pain score, opioids use, recovery quality and adverse events. MAIN RESULTS: The incidence of moderate-to-severe pain on movement 24 h postoperatively of group A was significantly lower than group B (45.19% vs 63.46%; RR 0.71; 95% CI, 0.55 to 0.92) and group C (45.19% vs 73.08%, RR 0.62; 95% CI, 0.49 to 0.79). The median moving pain scores decreased significantly at 24 h (3.00 [3.00,5.00] vs 4.00 [3.00,6.00] vs 4.00 [3.00,5.00]; P < 0.001). There were significant differences in the opioids consumption within the first 24 h (27.5 [17.0,37.2] vs 30.0 [20.0,42.0] vs 32.0 [25.0,44.0] mg; P = 0.01) and the duration to first rescue analgesia (65.5 ± 26.7 vs 45.9 ± 34.5 vs 49.2 ± 27.2 h; P = 0.04). CONCLUSIONS: The combination with dexamethasone and dexmedetomidine as adjuvants for TAP block reduced the incidence of moderate-to-severe pain and pain score both on movement and at rest at 24 h with prolonged duration to first rescue analgesia after gastric cancer surgery. TRIAL REGISTRATION NUMBER: ChiCTR2000037981.

Alleviation effects of dexmedetomidine on myocardial ischemia/reperfusion injury through fatty acid metabolism pathway via Elovl6.

Dexmedetomidine (Dex) is widely used in the sedation in intensive care units and as an anesthetic adjunct. Considering the anti-inflammatory and antioxidant properties of Dex, we applied in vivo rat model as well as in vitro cardiomyocyte models (embryonic rat cardiomyocytes H9c2 cells and neonatal rat cardiomyocytes, NRCMs) to evaluate the effects of Dex against myocardial ischemia reperfusion (I/R) injury. Transcriptomic sequencing for gene expression in heart tissues from control rats and Dex-treated rats identified that genes related to fatty acid metabolism were significantly regulated by Dex. Among these genes, the elongation of long-chain fatty acids (ELOVL) family member 6 (Elovl6) was most increased upon Dex-treatment. By comparing the effects of Dex on both wild type and Elovl6-knockdown H9c2 cells and NRCMs under oxygen-glucose deprivation/reoxygenation (OGD/R) challenge, we found that Elovl6 knockdown attenuated the protection efficiency of Dex, which was supported by the cytotoxicity endpoints (cell viability and lactate dehydrogenase release) and apoptosis as well as key gene expressions. These results indicate that Dex exhibited the protective function against myocardial I/R injury via fatty acid metabolism pathways and Elovl6 plays a key role in the process, which was further confirmed using palmitate exposure in both cells, as well as in an in vivo rat model. Overall, this study systematically evaluates the protective effects of Dex on the myocardial I/R injury and provides better understanding on the fatty acid metabolism underlying the beneficial effects of Dex.

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.

Effects of different doses of dexmedetomidine combined with sufentanil in intravenous controlled analgesia after Salter osteotomy in children.

Background: This study aimed to investigate the effect of different doses of dexmedetomidine combined with sufentanil on postoperative analgesia in developmental hip dislocation in children after Salter osteotomy. Methods: The clinical data of 98 children with developmental hip dislocation, who underwent Salter osteotomy in our center between January 2020 and February 2023, were selected. The children were randomly divided into four groups based on the application of patient-controlled intravenous analgesia (sufentanil + granisetron ± dexmedetomidine). All children received 1 µg/kg/day of sufentanil and 3 mg of granisetron. Group A did not receive dexmedetomidine, and Groups B, C, and D received 0.5, 0.75, and 1.0 µg/kg/day of dexmedetomidine, respectively. The pain indicators and immune factor levels of children in each group were compared. Results: The heart rate (HR) and respiratory rate (RR) 2 h after operation in Groups C and D were significantly lower than those in Groups A and B (P < 0.05). The pain scores decreased over time after treatment in all groups. When compared at the same time point, children in Group D had the lowest pain scores, which were significantly lower than the other three groups (P < 0.05). The total consumption of sufentanil in Groups C and D was significantly lower than that in Group A (P < 0.05). On the first day after surgery, the children in Group D had lower levels of serum adrenocorticotropic hormone, interleukin-6, and corticosterone than those in Group A (P < 0.05). Conclusion: Administration of 1.0 µg/kg/day of dexmedetomidine combined with sufentanil in intravenous controlled analgesia after Salter osteotomy for developmental hip dislocation in children has a better analgesic effect, less consumption of sufentanil, and low incidence of opioid adverse reactions.

Dexmedetomidine in paediatric anaesthesia: a call for action?

Dexmedetomidine is increasingly used in paediatric anaesthesia practice. In this issue of the British Journal of Anaesthesia, a retrospective hospital registry study in anaesthetised children showed that intraoperative use of dexmedetomidine was dose-dependently associated with a longer postanaesthesia care unit length of stay. Dexmedetomidine administration was also associated with higher total hospital costs and higher odds of unwarranted haemodynamic effects, while the onset of emergence delirium was not reduced. Although these results could curb enthusiasm for paediatric use of dexmedetomidine, they might also trigger discussion about our approach in the postoperative period to children having received dexmedetomidine intraoperatively.

Effects of dexmedetomidine and ketorolac applied for patient­controlled analgesia on the balance of Th1/Th2 and level of VEGF in patients undergoing laparoscopic surgery for cervical cancer: A randomized controlled trial.

The aim of the present study was to explore the effects of dexmedetomidine (DEX) combined with ketorolac on postoperative patient-controlled analgesia (PCA), the balance of Th1/Th2 and the level of vascular endothelial growth factor (VEGF) in patients with cervical cancer following laparoscopic radical surgery. A total of 70 women with cervical cancer undergoing laparoscopic radical hysterectomy were enrolled in the study to randomly receive postoperative dexmedetomidine combined with ketorolac analgesia (DK group) and postoperative sufentanil analgesia (SUF group). The primary outcomes were the serum levels of interleukin-4 (IL-4), interferon-γ (IFN-γ) and VEGF, and the IFN-γ/IL-4 ratio 30 min before induction (T0), and 24 and 48 h after surgery. Secondary outcomes included numerical rating scale scores at 0 h (T0), 4 h (T1), 12 h (T2), 24 h (T3) and 48 h (T4) postoperatively, cumulative times of rescue analgesia, as well as the incidence of postoperative side effects within 48 h from surgery. Patients in the DK group reported similar analgesic effects as patients in the SUF group at T2, T3 and T4, and the incidence of postoperative nausea and vomiting was significantly lower in the DK group. In the DK group, the serum concentration of IFN-γ and IFN-γ/IL-4 ratio at 24 and 48 h after surgery were higher compared with those in the SUF group. Conversely, the serum concentrations of IL-4 at 24 h after surgery and VEGF at 24 and 48 h after surgery were significantly lower. The results indicated that the combination of DEX and ketorolac for PCA significantly improved postoperative pain and decreased the serum level of VEGF, which are associated with tumor angiogenesis. In addition, it maintained the homeostasis of postoperative immune dysfunction of patients with cervical cancer by shifting the balance between type 1 T helper cells and type 2 T helper cell (Th1/Th2 balance) to Th1 (registration no. ChiCTR1900027979; December 7, 2019).

Programmed death of cardiomyocytes in cardiovascular disease and new therapeutic approaches.

Cardiovascular diseases (CVDs) have a complex pathogenesis and pose a major threat to human health. Cardiomyocytes have a low regenerative capacity, and their death is a key factor in the morbidity and mortality of many CVDs. Cardiomyocyte death can be regulated by specific signaling pathways known as programmed cell death (PCD), including apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis, etc. Abnormalities in PCD can lead to the development of a variety of cardiovascular diseases, and there are also molecular-level interconnections between different PCD pathways under the same cardiovascular disease model. Currently, the link between programmed cell death in cardiomyocytes and cardiovascular disease is not fully understood. This review describes the molecular mechanisms of programmed death and the impact of cardiomyocyte death on cardiovascular disease development. Emphasis is placed on a summary of drugs and potential therapeutic approaches that can be used to treat cardiovascular disease by targeting and blocking programmed cell death in cardiomyocytes.

Association between Dexmedetomidine Use and Mortality in Patients with COVID-19 Receiving Invasive Mechanical Ventilation: A U.S. National COVID Cohort Collaborative (N3C) Study.

(1) Background/Objectives: Dexmedetomidine is a sedative for patients receiving invasive mechanical ventilation (IMV) that previous single-site studies have found to be associated with improved survival in patients with COVID-19. The reported clinical benefits include dampened inflammatory response, reduced respiratory depression, reduced agitation and delirium, improved preservation of responsiveness and arousability, and improved hypoxic pulmonary vasoconstriction and ventilation-perfusion ratio. Whether improved mortality is evident in large, multi-site COVID-19 data is understudied. (2) Methods: The association between dexmedetomidine use and mortality in patients with COVID-19 receiving IMV was assessed. This retrospective multi-center cohort study utilized patient data in the United States from health systems participating in the National COVID Cohort Collaborative (N3C) from 1 January 2020 to 3 November 2022. The primary outcome was 28-day mortality rate from the initiation of IMV. Propensity score matching adjusted for differences between the group with and without dexmedetomidine use. Adjusted hazard ratios (aHRs) for 28-day mortality were calculated using multivariable Cox proportional hazards models with dexmedetomidine use as a time-varying covariate. (3) Results: Among the 16,357,749 patients screened, 3806 patients across 17 health systems met the study criteria. Mortality was lower with dexmedetomidine use (aHR, 0.81; 95% CI, 0.73-0.90; p < 0.001). On subgroup analysis, mortality was lower with earlier dexmedetomidine use-initiated within the median of 3.5 days from the start of IMV-(aHR, 0.67; 95% CI, 0.60-0.76; p < 0.001) as well as use prior to standard, widespread use of dexamethasone for patients on respiratory support (prior to 30 July 2020) (aHR, 0.54; 95% CI, 0.42-0.69; p < 0.001). In a secondary model that was restricted to 576 patients across six health system sites with available PaO2/FiO2 data, mortality was not lower with dexmedetomidine use (aHR 0.95, 95% CI, 0.72-1.25; p = 0.73); however, on subgroup analysis, mortality was lower with dexmedetomidine use initiated earlier than the median dexmedetomidine start time after IMV (aHR, 0.72; 95% CI, 0.53-0.98; p = 0.04) and use prior to 30 July 2020 (aHR, 0.22; 95% CI, 0.06-0.78; p = 0.02). (4) Conclusions: Dexmedetomidine use was associated with reduced mortality in patients with COVID-19 receiving IMV, particularly when initiated earlier, rather than later, during the course of IMV as well as use prior to the standard, widespread usage of dexamethasone during respiratory support. These particular findings might suggest that the associated mortality benefit with dexmedetomidine use is tied to immunomodulation. However, further research including a large randomized controlled trial is warranted to evaluate the potential mortality benefit of DEX use in COVID-19 and evaluate the physiologic changes influenced by DEX that may enhance survival.

Dexmedetomidine ameliorates x-ray-induced myocardial injury via alleviating cardiomyocyte apoptosis and autophagy.

BACKGROUND: Radiotherapy is a primary local treatment for tumors, yet it may lead to complications such as radiation-induced heart disease (RIHD). Currently, there is no standardized approach for preventing RIHD. Dexmedetomidine (Dex) is reported to have cardio-protection effects, while its role in radiation-induced myocardial injury is unknown. In the current study, we aimed to evaluate the radioprotective effect of dexmedetomidine in X-ray radiation-treated mice. METHODS: 18 male mice were randomized into 3 groups: control, 16 Gy, and 16 Gy + Dex. The 16 Gy group received a single dose of 16 Gy X-ray radiation. The 16 Gy + Dex group was pretreated with dexmedetomidine (30 µg/kg, intraperitoneal injection) 30 min before X-ray radiation. The control group was treated with saline and did not receive X-ray radiation. Myocardial tissues were collected 16 weeks after X-ray radiation. Hematoxylin-eosin staining was performed for histopathological examination. Terminal deoxynucleotidyl transferase dUTP nick-end labeling staining was performed to assess the state of apoptotic cells. Immunohistochemistry staining was performed to examine the expression of CD34 molecule and von Willebrand factor. Besides, western blot assay was employed for the detection of apoptosis-related proteins (BCL2 apoptosis regulator and BCL2-associated X) as well as autophagy-related proteins (microtubule-associated protein 1 light chain 3, beclin 1, and sequestosome 1). RESULTS: The findings demonstrated that 16 Gy X-ray radiation resulted in significant changes in myocardial tissues, increased myocardial apoptosis, and activated autophagy. Pretreatment with dexmedetomidine significantly protects mice against 16 Gy X-ray radiation-induced myocardial injury by inhibiting apoptosis and autophagy. CONCLUSION: In summary, our study confirmed the radioprotective effect of dexmedetomidine in mitigating cardiomyocyte apoptosis and autophagy induced by 16 Gy X-ray radiation.

Methadone in combination with magnesium, ketamine, lidocaine, and dexmedetomidine improves postoperative outcomes after coronary artery bypass grafting: an observational multicentre study.

BACKGROUND: An optimal pharmacological strategy for fast-track cardiac anesthesia (FTCA) is unclear. This study evaluated the effectiveness and safety of an FTCA program using methadone and non-opioid adjuvant infusions (magnesium, ketamine, lidocaine, and dexmedetomidine) in patients undergoing coronary artery bypass grafting. METHODS: This retrospective, multicenter observational study was conducted across private and public teaching sectors. We studied patients managed by a fast-track protocol or via usual care according to clinician preference. The primary outcome was the total mechanical ventilation time in hours adjusted for hospital, body mass index, category of surgical urgency, cardiopulmonary bypass time and EuroSCORE II. Secondary outcomes included successful extubation within four postoperative hours, postoperative pain scores, postoperative opioid requirements, and the development of postoperative complications. RESULTS: We included 87 patients in the fast-track group and 88 patients in the usual care group. Fast-track patients had a 35% reduction in total ventilation hours compared with usual care patients (p = 0.007). Thirty-five (40.2%) fast-track patients were extubated within four hours compared to 10 (11.4%) usual-care patients (odds ratio: 5.2 [95% CI: 2.39-11.08; p < 0.001]). Over 24 h, fast-track patients had less severe pain (p < 0.001) and required less intravenous morphine equivalent (22.00 mg [15.75:32.50] vs. 38.75 mg [20.50:81.75]; p < 0.001). There were no significant differences observed in postoperative complications or length of hospital stay between the groups. CONCLUSION: Implementing an FTCA protocol using methadone, dexmedetomidine, magnesium, ketamine, lignocaine, and remifentanil together with protocolized weaning from a mechanical ventilation protocol is associated with significantly reduced time to tracheal extubation, improved postoperative analgesia, and reduced opioid use without any adverse safety events. A prospective randomized trial is warranted to further investigate the combined effects of these medications in reducing complications and length of stay in FTCA. TRIALS REGISTRATION: The study protocol was registered in the Australian New Zealand Clinical Trials Registry ( https://www.anzctr.org.au/ACTRN12623000060640.aspx , retrospectively registered on 17/01/2023).

Dexmedetomidine-ketamine combination versus fentanyl-midazolam for patient sedation during flexible bronchoscopy: a prospective, single-blind, randomized controlled trial.

BACKGROUND: Sedation during flexible bronchoscopy (FB) should maintain an adequate respiratory drive, ensure maximum comfort for the patient, and warrant that the objectives of the procedure are achieved. Nevertheless, the optimal sedation method for FB has yet to be established. This study aimed to compare the standard recommended combination of midazolam-fentanyl (MF) with that of dexmedetomidine-ketamine (DK) for patient sedation during FB. METHODS: Patients subjected to FB were randomly assigned to a DK (n = 25) and an MF group (n = 25). The primary outcome was the rate of critical desaturation events (arterial oxygen saturation < 80% with nasal oxygen supply 2 L/min). Secondary outcomes included sedation depth, hemodynamic complications, adverse events, and patient and bronchoscopist satisfaction. RESULTS: The incidence rates of critical desaturation events were similar between the two groups (DK: 12% vs. MF: 28%, p = 0.289). DK achieved deeper maximum sedation levels (higher Ramsay - lower Riker scale; p < 0.001) and was associated with longer recovery times (p < 0.001). Both groups had comparable rates of hemodynamic and other complications. Patient satisfaction was similar between the two groups, but bronchoscopist satisfaction was higher with the DK combination (p = 0.033). CONCLUSION: DK demonstrated a good safety profile in patients subjected to FB and achieved more profound sedation and better bronchoscopist satisfaction than the standard MF combination without increasing the rate of adverse events.

Dexmedetomidine as a Short-Use Analgesia for the Immature Nervous System.

Pain management in neonates continues to be a challenge. Diverse therapies are available that cause loss of pain sensitivity. However, because of side effects, the search for better options remains open. Dexmedetomidine is a promising drug; it has shown high efficacy with a good safety profile in sedation and analgesia in the immature nervous system. Though dexmedetomidine is already in use for pain control in neonates (including premature neonates) and infants as an adjunct to other anesthetics, the question remains whether it affects the neuronal activity patterning that is critical for development of the immature nervous system. In this study, using the neonatal rat as a model, the pharmacodynamic effects of dexmedetomidine on the nervous and cardiorespiratory systems were studied. Our results showed that dexmedetomidine has pronounced analgesic effects in the neonatal rat pups, and also weakly modified both the immature network patterns of cortical and hippocampal activity and the physiology of sleep cycles. Though the respiration and heart rates were slightly reduced after dexmedetomidine administration, it might be considered as the preferential independent short-term therapy for pain management in the immature and developing brain.

Intraoperative Dexmedetomidine for Prevention of Postoperative Cognitive Dysfunction and Delirium in Elderly Patients with Lobectomy: A Propensity Score-Matched, Retrospective Study.

Purpose: This study aims to investigate whether dexmedetomidine could prevent postoperative cognitive dysfunction and delirium in patients with lobectomy. Patients and Methods: Patients with lung cancer who underwent thoracoscopic lobectomy under general anesthesia were enrolled in this study and divided into dexmedetomidine group or control group. Propensity-score match (PSM) was used to reduce the bias and imbalance of confounding variables. After PSM, 87 patients in each group were included. Primary outcomes were postoperative cognitive function and delirium. Secondary outcomes include plasma TNF-α, IL-6, and S100 ß protein concentrations. Adverse events were also collected. Results: There were no significant differences in the demographic characteristics and hemodynamic parameters between the two groups. Compared with the control group, the MoCA scores were significantly higher (P<0.01), while the incidence of delirium (P<0.01) and the plasma TNF-α (P<0.01), IL-6 (P<0.01), and S100 ß protein (P<0.01) concentrations were significantly lower in the dexmedetomidine group at 7 days post-operatively. The incidences of adverse events were similar between the two groups. Conclusion: Dexmedetomidine could prevent postoperative cognitive dysfunction and delirium in patients with lobectomy by decreasing neuroinflammation.

Protective effect of dexmedetomidine against delayed bone healing caused by morphine via PI3K/Akt mediated Nrf2 antioxidant defense system.

Background: As a class of analgesics, opioids are frequently used to treat both acute and chronic moderate to severe pain. Patients frequently receive opioid painkillers after orthopedic accidents or surgeries. Evidence suggests that opioid drug users have a 55.1% higher risk of fracture and poor bone repair than non-users of opioid drugs. The key pathogenic alterations in the incidence and progression of poor bone repair are over apoptosis and aging of osteoblasts due to the stress caused by oxidation. Dexmedetomidine (Dex) has been proven to protect against a variety of degenerative illnesses by reducing oxidative stress. However, nothing is known about how it affects bone repair. Methods: PI3K/Akt/Nrf2 pathway was detected by immunofluorescence and Western blot. SOD, CAT, JC-1, dihydroethidium and mitosox were used in the Oxidative Stress. Micro-CT, H&E and Masson's staining, immunohistochemically were performed to evaluate the therapeutic effects of DEX on calvarial defects in the morphine-induced rat model. Results: We found that morphine-induced an imbalance in the metabolism and catabolism of primary rat Osteoblasts. However, these conditions could be inhibited by DEX treatment. In the meantime, DEX induced the expression of Nrf2-regulated antioxidant enzymes such as NQO1, HO-1, GCLm, GCLc, and TrxR1. DEX-mediated Nrf2 activation is linked to the PI3K/Akt signaling system. Furthermore, it has been established that intravenous DEX enhanced the growth of bone healing in a model of a surgically produced rat cranial lesion. Conclusion: This is the first description of the unique DEX mechanism acting as a Nrf2 activator against morphine-mediated oxidative harm, raising the possibility that the substance may be used to prevent bone defects.