Central α2-adrenergic mechanisms regulate human sympathetic neuronal discharge strategies.

The present study investigated the impact of central α2-adrenergic mechanisms on sympathetic action potential (AP) discharge, recruitment and latency strategies. We used the microneurographic technique to record muscle sympathetic nerve activity and a continuous wavelet transform to investigate postganglionic sympathetic AP firing during a baseline condition and an infusion of a α2-adrenergic receptor agonist, dexmedetomidine (10 min loading infusion of 0.225 µg kg-1; maintenance infusion of 0.1-0.5 µg kg h-1) in eight healthy individuals (28 ± 7 years, five females). Dexmedetomidine reduced mean pressure (92 ± 7 to 80 ± 8 mmHg, P < 0.001) but did not alter heart rate (61 ± 13 to 60 ± 14 bpm; P = 0.748). Dexmedetomidine reduced sympathetic AP discharge (126 ± 73 to 27 ± 24 AP 100 beats-1, P = 0.003) most strongly for medium-sized APs (normalized cluster 2: 21 ± 10 to 5 ± 5 AP 100 beats-1; P < 0.001). Dexmedetomidine progressively de-recruited sympathetic APs beginning with the largest AP clusters (12 ± 3 to 7 ± 2 clusters, P = 0.002). Despite de-recruiting large AP clusters with shorter latencies, dexmedetomidine reduced AP latency across remaining clusters (1.18 ± 0.12 to 1.13 ± 0.13 s, P = 0.002). A subset of six participants performed a Valsalva manoeuvre (20 s, 40 mmHg) during baseline and the dexmedetomidine infusion. Compared to baseline, AP discharge (Δ 361 ± 292 to Δ 113 ± 155 AP 100 beats-1, P = 0.011) and AP cluster recruitment elicited by the Valsalva manoeuvre were lower during dexmedetomidine (Δ 2 ± 1 to Δ 0 ± 2 AP clusters, P = 0.041). The reduction in sympathetic AP latency elicited by the Valsalva manoeuvre was not affected by dexmedetomidine (Δ -0.09 ± 0.07 to Δ -0.07 ± 0.14 s, P = 0.606). Dexmedetomidine reduced baroreflex gain, most strongly for medium-sized APs (normalized cluster 2: -6.0 ± 5 to -1.6 ± 2 % mmHg-1; P = 0.008). These data suggest that α2-adrenergic mechanisms within the central nervous system modulate sympathetic postganglionic neuronal discharge, recruitment and latency strategies in humans. KEY POINTS: Sympathetic postganglionic neuronal subpopulations innervating the human circulation exhibit complex patterns of discharge, recruitment and latency. However, the central neural mechanisms governing sympathetic postganglionic discharge remain unclear. This microneurographic study investigated the impact of a dexmedetomidine infusion (α2-adrenergic receptor agonist) on muscle sympathetic postganglionic action potential (AP) discharge, recruitment and latency patterns. Dexmedetomidine infusion inhibited the recruitment of large and fast conducting sympathetic APs and attenuated the discharge of medium sized sympathetic APs that fired during resting conditions and the Valsalva manoeuvre. Dexmedetomidine infusion elicited shorter sympathetic AP latencies during resting conditions but did not affect the reductions in latency that occurred during the Valsalva manoeuvre. These data suggest that α2-adrenergic mechanisms within the central nervous system modulate sympathetic postganglionic neuronal discharge, recruitment and latency strategies in humans.

TREK-1 channel as a therapeutic target for dexmedetomidine-mediated neuroprotection in cerebral ischemia.

Our objective is to explore the protective effect of Dexmedetomidine on brain apoptosis and its mechanism through TREK-1 pathway. Forty male Sprague-Dawley rats were allocated into four groups: Sham, Cerebral Ischemia/Reperfusion Injury (CIRI), 50 µg/kg Dex, and 100 µg/kg Dex. A rat model of middle cerebral artery occlusion (MCAO) was employed to simulate cerebral embolism. Primary cortical neurons were exposed to Dex for 48 h, with some receiving additional treatment with 100 µM yohimbine hydrochloride (YOH) or TREK-1 small interfering RNA (siRNA). Neuronal damage was assessed using hematoxylin and eosin (HE) staining. Cell viability and apoptosis were measured by Cell Counting Kit-8 (CCK8) and flow cytometry, respectively. Protein and gene expression levels of Bcl-2, Bax, and TREK-1 were determined by Western blot and real-time polymerase chain reaction (PCR). Histopathological changes revealed that Dex treatment at both 50 µg/kg and 100 µg/kg significantly mitigated neuronal damage compared to the CIRI group. YOH treatment and Trek1 siRNA significantly reduced cell viability (p < 0.05). The mRNA expression and protein levels of TREK-1 and Bax were remarkably increased, while mRNA expression and protein levels of Bcl-2 was seriously decreased after CIRI modeling. In contrast, Dex treatment at both concentrations led to decreased TREK-1 and Bax expression and increased Bcl-2 expression in primary cortical neurons. Addition of 100 µM YOH and Trek1 siRNA reversed the effects of Dex on apoptosis-related genes (p < 0.05). Dex exerts neuroprotective effects through the TREK-1 pathway in vivo and in vitro.

Dexmedetomidine alleviates hippocampal neuronal loss and cognitive decline in rats undergoing open surgery under sevoflurane anaesthesia by suppressing CCAAT/enhancer-binding protein beta.

Dexmedetomidine (Dex) may exert neuroprotective effects by attenuating inflammatory responses. However, whether Dex specifically improves postoperative cognitive dysfunction (POCD) by inhibiting microglial inflammation through what pathway remains unclear. In this study, the POCD model was constructed by performing open surgery after 3 h of continuous inhalation of 3% sevoflurane to rats, which were intraperitoneally injected with 25 µg/kg Dex .5 h before anaesthesia. The results displayed that Dex intervention decreased rat escape latency, maintained swimming speed and increased the number of times rats crossed the platform and the time spent in the target quadrant. Furthermore, the rat neuronal injury was restored, alleviated POCD modelling-induced rat hippocampal microglial activation and inhibited microglial M1 type polarization. Besides, we administered Dex injection and/or CCAAT/enhancer-binding protein beta (CEBPB) knockdown on the basis of sevoflurane exposure and open surgery and found that CEBPB was knocked down, resulting in the inability of Dex to function, which confirmed CEBPB as a target for Dex treatment. To sum up, Dex improved POCD by considering CEBPB as a drug target to activate the c-Jun N-terminal kinase (JNK)/p-38 signaling pathway, inhibiting microglial M1 polarization-mediated inflammation in the central nervous system.

Dexmedetomidine inhibited arrhythmia susceptibility to adrenergic stress in RyR2R2474S mice through regulating the coupling of membrane potential and intracellular calcium.

BACKGROUND: Dexmedetomidine (DEX), a highly selective α2-adrenoceptor agonist, can decrease the incidence of arrhythmias, such as catecholaminergic polymorphic ventricular tachycardia (CPVT). However, the underlying mechanisms by which DEX affects cardiac electrophysiological function remain unclear. METHODS: Ryanodine receptor (RyR2) heterozygous R2474S mice were used as a model for CPVT. WT and RyR2R2474S/+ mice were treated with isoproterenol (ISO) and DEX, and electrocardiograms were continuously monitored during both in vivo and ex vivo experiments. Dual-dye optical mapping was used to explore the anti-arrhythmic mechanism of DEX. RESULTS: DEX significantly reduced the occurrence and duration of ISO-induced of VT/VF in RyR2R2474S/+ mice in vivo and ex vivo. DEX remarkably prolonged action potential duration (APD80) and calcium transient duration (CaTD80) in both RyR2R2474S/+ and WT hearts, whereas it reduced APD heterogeneity and CaT alternans in RyR2R2474S/+ hearts. DEX inhibited ectopy and reentry formation, and stabilized voltage-calcium latency. CONCLUSION: DEX exhibited an antiarrhythmic effect through stabilizing membrane voltage and intracellular Ca2+. DEX can be used as a beneficial perioperative anesthetic for patients with CPVT or other tachy-arrhythmias.

Effects of dexmedetomidine on depression-like behaviour in chronic restraint stress mice: Involvement of specific brain regions.

It is crucial to develop novel antidepressants. Dexmedetomidine (DEX) can exert antidepressant effects, but its underlying mechanism remains unclear. We used chronic restraint stress (CRS) to induce depression-like behaviour in mice and administered low-dose DEX (2 µg/kg per day) during CRS modelling or one injection of high-dose DEX (20 µg/kg) after CRS. The results of the behavioural tests revealed that both methods ameliorated CRS-induced depression. The brain slices of the mice were subjected to immunohistochemical staining for c-fos and phosphorylated ERK (pERK). Results showed that the continuous low-dose DEX-treated group, but not the single high-dose DEX-treated group expressed less c-fos in the nucleus locus coeruleus (LC) with a mean optical density (MOD) of 0.06. Other brain regions, including the dentate gyrus (DG), pyriform cortex (Pir), anterior part of paraventricular thalamic nucleus (PVA), arcuate nucleus (Arc), and core or shell of accumbens nucleus (Acbc or Acbs), presented differences in c-fos expression. In contrast, the low-dose DEX-treated group exhibited three-fold greater pERK expression in the LC of the CRS mice, with a MOD of 0.15. Pir, cingulate cortex (Cg) and, anterior and posterior part of paraventricular thalamic nucleus (PVA and PVP) exhibited pERK expression differences due to distinct reagent treatments. These changes indicate that the responses of brain regions to different DEX administration methods and doses vary. This study confirmed the ability of DEX to ameliorate CRS-induced depression and identified candidate target brain regions, thus providing new information for the antidepressant mechanism of DEX.

Perioperative acute kidney injury: The renoprotective effect and mechanism of dexmedetomidine.

Dexmedetomidine (DEX) is a highly selective and potent α2-adrenoceptor (α2-AR) agonist that is widely used as a clinical anesthetic to induce anxiolytic, sedative, and analgesic effects. In recent years, a growing body of evidence has demonstrated that DEX protects against acute kidney injury (AKI) caused by sepsis, drugs, surgery, and ischemia-reperfusion (I/R) in organs or tissues, indicating its potential role in the prevention and treatment of AKI. In this review, we summarized the evidence of the renoprotective effects of DEX on different models of AKI and explored the mechanism. We found that the renoprotective effects of DEX mainly involved antisympathetic effects, reducing inflammatory reactions and oxidative stress, reducing apoptosis, increasing autophagy, reducing ferroptosis, protecting renal tubular epithelial cells (RTECs), and inhibiting renal fibrosis. Thus, the use of DEX is a promising strategy for the management and treatment of perioperative AKI. The aim of this review is to further clarify the renoprotective mechanism of DEX to provide a theoretical basis for its use in basic research in various AKI models, clinical management, and the treatment of perioperative AKI.

Dexmedetomidine mitigates lidocaine-induced spinal cord injury by repressing ferritinophagy-mediated ferroptosis by increasing CISD2 expression in rat models.

Dexmedetomidine (DEX) has been confirmed to exert neuroprotective effects in various nerve injury models by regulating ferroptosis, including spinal cord injury (SCI). Although it has been established that CDGSH iron sulfur domain 2 (CISD2) can regulate ferroptosis, whether DEX can regulate ferroptosis by CISD2 in SCI remains unclear. Lidocaine was used to induce PC12 cells and stimulate rats to establish SCI models in vitro and in vivo. MTT assays were performed to analyze cell viability. Ferroptosis was assessed by determining the levels of cellular reactive axygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and Fe2+. Ferritinophagy was analyzed by LysoTracker staining, FerroOrange staining, and immunofluorescence. Western blotting was carried out to quantify the levels of several proteins. Fluorescence microscopy was also used to observe cell autophagy. The morphology of mitochondria within the tissue was observed under transmission electron microscopy (TEM). DEX treatment weakened lidocaine-induced elevation of ROS, Fe2+, and MDA and reduced GSH in PC12 cells, indicating that DEX treatment weakened lidocaine-induced ferroptosis in PC12 cells. Similarly, lidocaine promoted autophagy, Fe2+, and microtubule-associated protein 1 light chain 3 (LC3) in PC12 cells and suppressed ferritin and p62 protein levels, indicating that DEX could weaken lidocaine-induced ferritinophagy in PC12 cells. DEX treatment improved the BBB score, reduced tissue damage, increased the number of neurons, and alleviated mitochondrial damage by inhibiting ferroptosis and ferritinophagy in lidocaine-induced SCI rat models. The decreased CISD2, ferritin heavy chain 1 (FTH1), solute carrier family 7-member 11-glutathione (SLC7A11), and glutathione peroxidase 4 (GPX4) protein levels and the elevated nuclear receptor coactivator 4 (NCOA4) protein levels in rat models in the lidocaine group were weakened by DEX treatment. Moreover, CISD2 inhibition reversed the inhibitory effects of DEX treatment on lidocaine-induced ferroptosis and ferritinophagy in PC12 cells significantly. Taken together, DEX treatment could impair lidocaine-induced SCI by inhibiting ferroptosis and ferritinophagy by upregulating CISD2 in rat models.

Resolving neuroinflammatory and social deficits in ASD model mice: Dexmedetomidine downregulates NF-κB/IL-6 pathway via α2AR.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that severely affects individuals' daily life and social development. Unfortunately, there are currently no effective treatments for ASD. Dexmedetomidine (DEX) is a selective agonist of α2 adrenergic receptor (α2AR) and is widely used as a first-line medication for sedation and hypnosis in clinical practice. In recent years, there have been reports suggesting its potential positive effects on improving emotional and cognitive functions. However, whether dexmedetomidine has therapeutic effects on the core symptoms of ASD, namely social deficits and repetitive behaviors, remains to be investigated. In the present study, we employed various behavioral tests to assess the phenotypes of animals, including the three-chamber, self-grooming, marble burying, open field, and elevated plus maze. Additionally, electrophysiological recordings, western blotting, qPCR were mainly used to investigate and validate the potential mechanisms underlying the role of dexmedetomidine. We found that intraperitoneal injection of dexmedetomidine in ASD model mice-BTBR T+ Itpr3tf/J (BTBR) mice could adaptively improve their social deficits. Further, we observed a significant reduction in c-Fos positive signals and interleukin-6 (IL-6) expression level in the prelimbic cortex (PrL) of the BTBR mice treated with dexmedetomidine. Enhancing or inhibiting the action of IL-6 directly affects the social behavior of BTBR mice. Mechanistically, we have found that NF-κB p65 is a key pathway regulating IL-6 expression in the PrL region. In addition, we have confirmed that the α2AR acts as a receptor switch mediating the beneficial effects of dexmedetomidine in improving social deficits. This study provides the first evidence of the beneficial effects of dexmedetomidine on core symptoms of ASD and offers a theoretical basis and potential therapeutic approach for the clinical treatment of ASD.

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.

The bioenergetics of traumatic brain injury and its long-term impact for brain plasticity and function.

Mitochondria provide the energy to keep cells alive and functioning and they have the capacity to influence highly complex molecular events. Mitochondria are essential to maintain cellular energy homeostasis that determines the course of neurological disorders, including traumatic brain injury (TBI). Various aspects of mitochondria metabolism such as autophagy can have long-term consequences for brain function and plasticity. In turn, mitochondria bioenergetics can impinge on molecular events associated with epigenetic modifications of DNA, which can extend cellular memory for a long time. Mitochondrial dysfunction leads to pathological manifestations such as oxidative stress, inflammation, and calcium imbalance that threaten brain plasticity and function. Hence, targeting mitochondrial function may have great potential to lessen the outcomes of TBI.

Comparative analysis of dexmedetomidine, midazolam, and propofol impact on epilepsy-related mortality in the ICU: insights from the MIMIC-IV database.

BACKGROUND: Dexmedetomidine (Dex), midazolam, and propofol are three distinct sedatives characterized by varying pharmacological properties. Previous literature has indicated the positive impact of each of these sedatives on ICU patients. However, there is a scarcity of clinical evidence comparing the efficacy of Dex, midazolam, and propofol in reducing mortality among people with epilepsy (PWE). This study aimed to assess the impact of Dex, midazolam, and propofol on the survival of PWE. METHODS: The data were retrospectively retrieved from the Medical Information Mart for Intensive Care (MIMIC)-IV database (version 2.0). PWE were categorized into Dex, midazolam, and propofol groups based on the intravenously administered sedatives. PWE without standard drug therapy were included in the control group. Comparative analyses were performed on the data among the groups. RESULTS: The Dex group exhibited a significantly lower proportion of in-hospital deaths and a markedly higher in-hospital survival time compared to the midazolam and propofol groups (p < 0.01) after propensity score matching. Kaplan-Meier curves demonstrated a significant improvement in survival rates for the Dex group compared to the control group (p = 0.025). Analysis of Variance (ANOVA) revealed no significant differences in survival rates among the Dex, midazolam, and propofol groups (F = 1.949, p = 0.143). The nomogram indicated that compared to midazolam and propofol groups, Dex was more effective in improving the survival rate of PWE. CONCLUSION: Dex might improve the survival rate of PWE in the ICU compared to no standard drug intervention. However, Dex did not exhibit superiority in improving survival rates compared to midazolam and propofol.

Dexmedetomidine Sublingual Film: A New Treatment to Reduce Agitation in Schizophrenia and Bipolar Disorders.

OBJECTIVE: The objective of this study was to review the available literature for dexmedetomidine sublingual film use in the treatment of acute agitation associated with schizophrenia and bipolar disorders. DATA SOURCES: A literature search of PubMed (January 2017-March 2023) and EMBASE (January 2017-March 2023) was performed using the terms: Igalmi, dexmedetomidine, schizophrenia, bipolar disorder, and agitation. Additional information sources include ClinicalTrials.gov, scientific posters, and articles identified through review of references from clinical trials publications. STUDY SELECTION AND DATA EXTRACTION: Relevant English-language articles conducted in humans were considered, with a preference for phase 3 clinical trials. Trial analyses and articles discussing pharmacology, pharmacokinetics, efficacy, and safety were also evaluated. DATA SYNTHESIS: Dexmedetomidine sublingual film was evaluated for use in schizophrenia in the SERENITY 1 pivotal trial and for bipolar disorders in the SERENITY 2 pivotal trial. Both studies found treatment of mild to moderate agitation with dexmedetomidine sublingual film 180 and 120 µg to be superior to placebo in reducing the severity of agitation. Treatment effect was seen as early as 20 minutes. Somnolence was the most common adverse effect in both studies. Cardiovascular adverse effects were mild and transient in most cases. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Dexmedetomidine sublingual film is a new and novel treatment for agitation and gives clinicians an alternative to antipsychotic and benzodiazepine use. It has advantageous properties including its noninvasive route of administration, fast absorption, and rapid onset of effect. Cost may limit its use. CONCLUSION: Dexmedetomidine sublingual film provides an alternative approach to treatment of acute agitation in adults with schizophrenia and bipolar disorders based on both mechanism of action and route of administration.

Impact of Dexmedetomidine Dosing and Timing on Acute Kidney Injury and Renal Outcomes After Cardiac Surgery: A Meta-Analytic Approach.

BACKGROUND: Acute kidney injury (AKI) is a common and serious complication following cardiac surgery. Dexmedetomidine, a highly selective α2-adrenergic agonist, has shown potential renoprotective effects, but previous studies have yielded conflicting results. OBJECTIVE: This meta-analysis aimed to evaluate the efficacy and safety of dexmedetomidine in preventing AKI and reducing postoperative serum creatinine levels in adult patients undergoing cardiac surgery. METHODS: We comprehensively searched 5 databases for randomized controlled trials comparing dexmedetomidine with control groups in adult cardiac surgery patients. The main outcomes were the incidence of AKI and change in postoperative serum creatinine levels. Meta-analyses were conducted using RevMan 5.4 models, and subgroup analyses were performed based on dexmedetomidine dosing and timing of administration. Continuous outcomes were combined and analyzed using either mean difference (M.D.), while dichotomous outcomes were analyzed using risk ratio (RR) with 95% confidence intervals (CI). RESULTS: Our study included a total of 14 trials involving 2744 patients. Dexmedetomidine administration significantly reduced the incidence of AKI compared to control groups (RR = 0.54, 95% CI: 0.41-0.70, P < 0.00001). Postoperative serum creatinine levels were also lower with dexmedetomidine (MD = -0.14 mg/dL, 95% CI: -0.28 to -0.001, P =0.04). Subgroup analyses revealed that higher initial doses (>0.5 µg/kg) and administration during intraoperative and postoperative periods were associated with more pronounced renoprotective effects. Dexmedetomidine did not significantly affect mortality but reduced the duration of the length of hospital stay and mechanical ventilation. CONCLUSIONS AND RELEVANCE: This meta-analysis demonstrates that dexmedetomidine administration, particularly at higher doses and during both intraoperative and postoperative periods, reduces the risk of AKI in adults undergoing cardiac surgery. These findings support the use of dexmedetomidine as a preventive strategy to enhance renal outcomes in this population.

Pharmacological Prevention of Postoperative Delirium in Adults: A Review of Recent Literature.

PURPOSE OF REVIEW: Postoperative delirium (POD) is a common complication that has important implications for surgical patients, often leading to both short- and long-term cognitive deficits, worse outcomes, and increased healthcare costs. Given these implications, there may be a benefit in reducing the incidence of POD. Pharmacologic interventions may have the potential to reduce the risk of a patient developing POD. RECENT FINDINGS: Recently studied therapies include dexmedetomidine, propofol, haloperidol, ketamine, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, acetaminophen, melatonin/ramelteon, corticosteroids, midazolam, physostigmine, and neostigmine. In addition, the implementation of regional anesthesia and reduction of overall anesthetic depth have been examined. Of these therapies, dexmedetomidine has been studied the most and has the most supporting evidence for prevention of POD, but current studies lack clarity on optimal dosing and timing of dexmedetomidine administration. Acetaminophen, corticosteroids, and melatonin/ramelteon are other plausible medications that have potential for reducing POD incidence, but they all require further investigation. Reduction of anesthetic depth and regional anesthetics are options for anesthetic management that show promise but still lack enough supporting evidence in recent literature to receive a strong recommendation. Future research should focus on identifying optimal strategies for the implementation of the pharmacological options listed, including doses and timing of administration. Attention should be given to dexmedetomidine given its promise demonstrated by recent literature.

Prevention of post-operative delirium using an overnight infusion of dexmedetomidine in patients undergoing cardiac surgery: a pragmatic, randomized, double-blind, placebo-controlled trial.

BACKGROUND: After cardiac surgery, post-operative delirium (PoD) is acknowledged to have a significant negative impact on patient outcome. To date, there is no valuable and specific treatment for PoD. Critically ill patients often suffer from poor sleep condition. There is an association between delirium and sleep quality after cardiac surgery. This study aimed to establish whether promoting sleep using an overnight infusion of dexmedetomidine reduces the incidence of delirium after cardiac surgery. METHODS: Randomized, pragmatic, multicentre, double-blind, placebo controlled trial from January 2019 to July 2021. All adult patients aged 65 years or older requiring elective cardiac surgery were randomly assigned 1:1 either to the dexmedetomidine group or the placebo group on the day of surgery. Dexmedetomidine or matched placebo infusion was started the night after surgery from 8 pm to 8 am and administered every night while the patient remained in ICU, or for a maximum of 7 days. Primary outcome was the occurrence of postoperative delirium (PoD) within the 7 days after surgery. RESULTS: A total of 348 patients provided informed consent, of whom 333 were randomized: 331 patients underwent surgery and were analysed (165 assigned to dexmedetomidine and 166 assigned to placebo). The incidence of PoD was not significantly different between the two groups (12.6% vs. 12.4%, p = 0.97). Patients treated with dexmedetomidine had significantly more hypotensive events (7.3% vs 0.6%; p < 0.01). At 3 months, functional outcomes (Short-form 36, Cognitive failure questionnaire, PCL-5) were comparable between the two groups. CONCLUSION: In patients recovering from an elective cardiac surgery, an overnight infusion of dexmedetomidine did not decrease postoperative delirium. Trial registration This trial was registered on ClinicalTrials.gov (number: NCT03477344; date: 26th March 2018).

Insight into Cardioprotective Effects and Mechanisms of Dexmedetomidine.

PURPOSE: Cardiovascular disease remains the leading cause of death worldwide. Dexmedetomidine is a highly selective α2 adrenergic receptor agonist with sedative, analgesic, anxiolytic, and sympatholytic properties, and several studies have shown its possible protective effects in cardiac injury. The aim of this review is to further elucidate the underlying cardioprotective mechanisms of dexmedetomidine, thus suggesting its potential in the clinical management of cardiac injury. RESULTS AND CONCLUSION: Our review summarizes the findings related to the involvement of dexmedetomidine in cardiac injury and discusses the results in the light of different mechanisms. We found that numerous mechanisms may contribute to the cardioprotective effects of dexmedetomidine, including the regulation of programmed cell death, autophagy and fibrosis, alleviation of inflammatory response, endothelial dysfunction and microcirculatory derangements, improvement of mitochondrial dysregulation, hemodynamics, and arrhythmias. Dexmedetomidine may play a promising and beneficial role in the treatment of cardiovascular disease.

Expanding eligibility for intracranial electroencephalography using Dexmedetomidine Hydrochloride in children with behavioral dyscontrol.

INTRODUCTION: Invasive intracranial electroencephalography (IEEG) is advantageous for identifying epileptogenic foci in pediatric patients with medically intractable epilepsy. Patients with behavioral challenges due to autism, intellectual disabilities, and hyperactivity have greater difficulty tolerating prolonged IEEG recording and risk injuring themselves or others. There is a need for therapies that increase the safety of IEEG but do not interfere with IEEG recording or prolong hospitalization. Dexmedetomidine Hydrochloride's (DH) use has been reported to improve safety in patients with behavioral challenges during routine surface EEG recording but has not been characterized during IEEG. Here we evaluated DH administration in pediatric patients undergoing IEEG to assess its safety and impact on the IEEG recordings. METHODS: A retrospective review identified all pediatric patients undergoing IEEG between January 2016 and September 2022. Patient demographics, DH administration, DH dose, hospital duration, and IEEG seizure data were analyzed. The number of seizures recorded for each patient was divided by the days each patient was monitored with IEEG. The total number of seizures, as well as seizures per day, were compared between DH and non-DH patients via summary statistics, multivariable linear regression, and univariate analysis. Other data were compared across groups with univariate statistics. RESULTS: Eighty-four pediatric patients met the inclusion criteria. Eighteen (21.4 %) received DH treatment during their IEEG recording. There were no statistical differences between the DH and non-DH groups' demographic data, length of hospital stays, or seizure burden. Non-DH patients had a median age of 12.0 years (interquartile range: 7.25-15.00), while DH-receiving patients had a median age of 8.0 years old (interquartile range: 3.00-13.50) (p = 0.07). The non-DH cohort was 57.6 % male, and the DH cohort was 50.0 % male (p = 0.76). The median length of IEEG recordings was 5.0 days (interquartile range: 4.00-6.25) for DH patients versus 6.0 days (interquartile range: 4.00-8.00) for non-DH patients (p = 0.25). Median total seizures recorded in the non-DH group was 8.0 (interquartile range: 5.00-13.25) versus 15.0 in the DH group (interquartile range: 5.00-22.25) (p = 0.33). Median total seizures per day of IEEG monitoring were comparable across groups: 1.50 (interquartile range: 0.65-3.17) for non-DH patients compared to 2.83 (interquartile range: 0.89-4.35) (p = 0.25) for those who received DH. Lastly, non-DH patients were hospitalized for a median of 8.0 days (interquartile range: 6.00-11.25), while DH patients had a median length of stay of 7.00 days (interquartile range: 5.00-8.25) (p = 0.27). No adverse events were reported because of DH administration. CONCLUSIONS: Administration of DH was not associated with adverse events. Additionally, the frequency of seizures captured on the IEEG, as well as the duration of hospitalization, were not significantly different between patients receiving and not receiving DH during IEEG. Incorporating DH into the management of patients with behavioral dyscontrol and intractable epilepsy may expand the use of IEEG to patients who previously could not tolerate it, improve safety, and preserve epileptic activity during the recording period.

Effects of an intraoperative intravenous Bolus Dose of Dexmedetomidine on postoperative catheter-related bladder discomfort in male patients undergoing transurethral resection of bladder tumors: a randomized, double-blind, controlled trial.

PURPOSE: To investigate whether the effect of intravenous bolus doses of dexmedetomidine on postoperative catheter-related bladder discomfort (CRBD) was dose-dependent in male patients undergoing transurethral resection of bladder tumors (TURBT). METHODS: The study protocol was registered at the Chinese Clinical Trial Registry (ChiCTR 2,000,034,657, date of registration: July 14, 2020). Adult male patients were randomized to one of four groups: placebo (Group C); dexmedetomidine 0.2 µg/kg (Group D 0.2); dexmedetomidine 0.5 µg/kg (Group D 0.5); or dexmedetomidine 1 µg/kg (Group D 1). The primary outcome was the incidence of moderate-to-severe CRBD at 0, 1, 6, 24, and 48 h postoperatively. RESULTS: The incidence of moderate-to-severe CRBD was significantly lower in Group D 0.5 and Group D 1 than in Group C at 0 h (13% vs. 40%, P = 0.006; 8% vs. 40%, P = 0.001), 1 h (15% vs. 53%, P < 0.001; 13% vs. 53%, P < 0.001), and 6 h (10% vs. 32%, P = 0.025; 8% vs. 32%, P = 0.009) postoperatively. Compared with baseline, both the MAP and HR were significantly lower in Group D 1 at 1 min ([94 ± 15] vs. [104 ± 13] mm Hg, P = 0.003; [64 ± 13] vs. [73 ± 13] bpm, P = 0.001) and 30 min ([93 ± 10] vs. [104 ± 13] mm Hg, P < 0.001; [58 ± 9] vs. [73 ± 13] bpm, P < 0.001) postextubation. CONCLUSION: The effect of intravenous bolus doses of dexmedetomidine on postoperative CRBD was dose-independent, whereas intravenous administration of 0.5 µg/kg dexmedetomidine reduced the early postoperative incidence of CRBD with minimal side effects. TRIAL REGISTRATION: Clinical trial number and registry URL: ChiCTR 2,000,034,657, http://www.chictr.org.cn , date of registration: July 14, 2020.

Electroencephalographic signatures of consciousness: uncovering the fake news.

Amongst electroencephalographic markers of anaesthetic-induced unresponsiveness, those that estimate loss of frontoparietal functional connectivity detect loss of sensory perceptual connection with the outside world, rather than full phenomenological unconsciousness. This transition to unconsciousness is manifest as further incremental changes in indices of electroencephalographic complexity.

Opioid-free versus opioid-sparing anaesthesia in ambulatory total hip arthroplasty: a randomised controlled trial.

BACKGROUND: Enhanced recovery after surgery pathways are essential for ambulatory surgery. They usually recommend lower intraoperative opioid use to avoid opioid-related adverse effects. This has led to opioid-sparing anaesthesia (OSA) techniques, with the extreme approach of opioid-free anaesthesia (OFA) mostly with dexmedetomidine. As evidence is lacking in day-case primary total hip arthroplasty, this study was performed to assess the potential benefits in postoperative analgesia of OFA over OSA. METHODS: In this single-centre, prospective, triple blind study, we randomly allocated 80 patients undergoing day-case primary THA under general anaesthesia. Patients received a total intravenous anaesthesia with a laryngeal mask and multimodal analgesic regimen with non-opioid analgesics. The OSA group received low dose of sufentanil, and the OFA group received dexmedetomidine The primary outcome was the opioid consumption in the first 24 h in oral morphine equivalents (OME). RESULTS: There was no difference in median cumulative OME consumption at 24 h between the OSA and OFA groups (12 [0-25] mg vs 16 [0-30] mg, respectively; P=0.7). Pain scores were similar and low in both groups with comparable walking recovery time. Adverse events were sparse and equivalent in both groups except for dizziness, which was more frequent in the OSA group (P<0.05). CONCLUSIONS: In day-case total hip arthoplasty under general anaesthesia, opioid-free anaesthesia and opioid-sparing anaesthesia both provide early recovery and effective postoperative pain relief. When compared with opioid-sparing anaesthesia, opioid-free anaesthesia does not decrease opioid consumption in the first 24 h. These findings do not suggest any significant benefit from complete intraoperative avoidance of opioids. CLINICAL TRIAL REGISTRATION: NCT0507270.