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To evaluate the dose of alfaxalone needed for induction of anesthesia following sedation with medetomidine-vatinoxan plus hydromorphone (MVH), dexmedetomidine plus hydromorphone (DH), or hydromorphone (H) alone. A secondary objective included evaluating selected cardiopulmonary variables before, during, and after sedation and general anesthesia with sevoflurane in healthy dogs. Prospective, randomized, masked, crossover. Eight healthy Beagle dogs, 3–4 years old. All dogs received three intramuscular (IM) treatments: H (0.1 mg kg−1), DH (0.005 mg kg−1 + 0.1 mg kg−1, respectively), or MVH (0.01 mg kg−1 + 0.2 mg kg−1 + 0.1 mg kg−1, respectively) at least 6 days apart. General anesthesia was induced with alfaxalone 20 minutes after treatment administration and maintained for 60 minutes with 2.8% sevoflurane (expired). Sedation scores, selected cardiopulmonary variables, and recovery scores were measured before, during, and after anesthesia at selected timepoints. Mixed-effects ANOVA and ANOVA on ranks were used to evaluate differences between treatments, time, and their interaction, and Tukey–Kramer method was used for post hoc analysis (p < 0.05). Data are presented as mean ± SD or median (range). Dogs given MVH required a lower dose of alfaxalone for induction of anesthesia (0.77 ± 0.4 mg kg−1) compared to DH and H (1.16 ± 0.34 mg kg−1; p = 0.02, 1.13 ± 0.18 mg kg−1; p = 0.02), and had a higher incidence (50%; p = 0.038) and longer duration [median; 10 (0–35) minutes] of hypotension during sevoflurane anesthesia compared to H [0%; 0 (0–0) minutes; p = 0.040] but not DH (p = 0.272). Premedication with MVH provided the greatest alfaxalone-sparing effect. However, this treatment was associated with lower arterial pressures and clinically relevant hypotension. Off-label use of medetomidine-vatinoxan before sevoflurane-based anesthesia should be used with caution due to a high incidence of hypotension. [ABSTRACT FROM AUTHOR]

Semen collection in cats in the clinic setting can be difficult. However, semen analysis is vital when evaluating breeding soundness of a male. Electroejaculation (EEJ) is currently the most reliable semen collection method but requires specialized equipment and training of the operator. Chemical ejaculation followed by urethral catheterization (UC) is a technique that allows semen collection without special equipment: a catheter is placed into the urethra of a sedated tom and semen is collected passively into the catheter. Earlier studies used the sedative medetomidine at high doses for this procedure. However, medetomidine has been replaced with dexmedetomidine in some countries. This study sought to compare the results of EEJ and UC for semen collection in the domestic cat using dexmedetomidine, a potent α2-adrenoceptor agonist (α2A), as a substitute for medetomidine at the equivalent dose to that used in earlier studies. Twelve domestic cats were collected thrice at weekly intervals. All cats received intramuscular ketamine (5 mg/kg) and intramuscular dexmedetomidine (30 μg/kg) for initial cleanout via EEJ, then randomly underwent either EEJ or UC one week apart. The EEJ was performed under the same anesthetic protocol as the initial cleanout. The UC was performed using intramuscular dexmedetomidine at a dose of 60 μg/kg. Success of collection, total sperm number, sperm morphology, and motility characteristics were analyzed. Sperm was collected successfully from all 12 cats via EEJ and from 11/12 via UC. There were no significant differences in the percentage of total motile, progressively motile, or morphologically normal sperm between ejaculate types when averaged across all cats or individual cats. Although UC yielded a lower volume and higher concentration ejaculate, it consistently produced a lower total sperm number than ejaculates retrieved via EEJ (17.91 x 106 total sperm for UC versus 46.51 x 106 total sperm for EEJ). These results indicated that dexmedetomidine is a very effective sedative and performed satisfactorily in both procedures at the doses used in this study. It was also safe with no adverse effects on healthy toms. EEJ remained the most reliable in terms of assessing semen quality and retrieving semen with adequate number of sperm for breeding purposes. However, UC with dexmedetomidine at this dose demonstrated a 92 % success rate, presenting itself as a remarkably consistent alternative. • 50 mcg/kg dexmedetomidine produces a representative sperm sample in cats. • Chemical and electroejaculation yield comparable ejaculate concentration in cats. • Chemical and electroejaculation motilities and morphology are comparable in cats. • Electroejaculation yields higher volume and sperm number than chemical ejaculation. • Nucleocounter and hemocytometer concentration measurements are equivalent. [ABSTRACT FROM AUTHOR]

Craniotomy is associated with several undesirable effects including postoperative pain. This systematic review and meta-analysis aimed to evaluate evidence on the efficacy and safety of dexmedetomidine (DEX) for pain management in patients undergoing craniotomy. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The protocol was registered in Open Science Framework. We searched for existing randomized controlled studies published before June 2023 that used DEX during the perioperative period in craniotomy in PubMed, Scopus, and the Cochrane Library. A meta-analysis was conducted in RevMan. Cochrane RoB2 and GRADE were used for quality assessment. A total of 19 randomized controlled trials comprising 3153 patients were included. Pain intensity was lower in the DEX group than the control group at a mean difference [95% confidence interval] of –0.64 [–1.16, –0.13], P -value = 0.01. The DEX group overall consumed less opioids in comparison with the control group at a mean difference = –4.00 [–6.16, –1.83], P value = 0.0003. However, heterogeneity was considerable for both outcomes (I2 = 81% and I2 = 96%, respectively). There was no difference between the DEX and control groups in the time to first postanalgesic requirement, hypertension, hypotension, or cough. The results showed that the use of DEX was associated with lower pain intensity and less opioid use. Patients in the DEX group experienced fewer episodes of nausea and vomiting, agitation, and shivering but more episodes of bradycardia. There was no difference between DEX and control groups in other adverse events. [ABSTRACT FROM AUTHOR]

To determine if perioperative administration of dexmedetomidine affects postoperative fluid intake in tonsillectomy patients. A retrospective chart review was performed at University Medical Center, Texas Tech Health Science Center, Lubbock, Texas. The study identified 534 patients within the last five years who met the criteria. Common indications for the surgeries included recurrent tonsillitis, obstructive sleep apnea, and sleep disordered breathing. Patients with concurrent peritonsillar abscess drainage, microlaryngoscopy, bronchoscopy, supraglottoplasty, and other procedures that may impact fluid intake were excluded. The relationship between dexmedetomidine and fluid intake was evaluated using bivariate analysis as well as multivariable regression to account for possible confounders such as age, concurrent medication, surgery type, and method of surgery using STATA statistical software, version 17.0 (StataCorp LLC, College Station, TX). Administration of dexmedetomidine did not significantly impact the amount of fluid intake, fluid intake per kilogram per hour, or average postoperative pain levels in patients who underwent tonsillectomy or adenotonsillectomy in the bivariate analysis (p = 0.217, 0.489, 0.512 respectively) and multiple regression model (p = 0.156, 0.802, 0.795) Dexmedetomidine does not negatively influence postoperative fluid intake levels in patients and should continue to be utilized in appropriately selected patients experiencing anxiety or agitation prior to surgery. [ABSTRACT FROM AUTHOR]

Sedation is used widely on critical care and is necessary to facilitate and alleviate the stress of invasive and potentially painful organ supportive therapies. Its use, however, is associated with morbidity and mortality. Treatments therefore need to be minimized and optimized wherever possible with overtreatment being avoided. It should be patient centred, with a focus of treating pain and agitation and delirium, common symptoms in critical care. Delirium itself is associated with morbidity and mortality and as such, all healthcare professionals involved with the care of the critically ill have a duty to identify, manage and minimize this distressing complication. [ABSTRACT FROM AUTHOR]

This article is an update of anaesthesia for common paediatric ear, nose and throat (ENT) procedures. ENT pathology is the most common indication for surgery in children. An increasing proportion are performed as day cases, even in the presence of comorbidities such as obstructive sleep apnoea (OSA), so judicious selection of suitable children remains important. Considerations include severity of disease, known difficult airway, complex comorbidities, and the surgical centre. The anaesthetic management of frequently performed paediatric ENT procedures will be discussed, including recent advances in ENT surgery that have an impact on the anaesthetist. [ABSTRACT FROM AUTHOR]

To compare the analgesic and sleep quality effects of dexmedetomidine infusion versus placebo in patients undergoing cardiac surgery with ultra-fast track extubation. The randomized, double-blind clinical trial study. At a single academic center hospital. We included patients aged 25 to 65 scheduled for elective cardiac surgery under general anesthesia with cardiopulmonary bypass from October 2021 to December 2022. After immediate extubation in the operating room, the patients who were allocated at first after providing their consent to either the dexmedetomidine group (Dex) or the placebo group (Placebo) received continuous infusion of dexmedetomidine (0.2 μg/kg/h) or saline for 12 hours postoperatively. The groups' demographic and perioperative variables were not statistically significant. Total morphine consumption in milligrams at 12 and 24 hours after administered study drug, total sleep time in hours by BIS value ≤85, and sleep quality with the Richard-Campbell Sleep Questionnaire were compared. The analysis included 22 Dex and 23 Placebo patients. The consumption of morphine was not statistically different between the Dex and Placebo groups at 12 and 24 hours (p = 0.707 and p = 0.502, respectively). The Dex group had significantly longer sleep time (8.7 h [7.8, 9.5]) than the Placebo group (5.8 h [2.9, 8.5]; p = 0.007). The Dex group also exhibited better sleep quality (7.9 [6.7, 8.7] vs 6.6 [5.2, 8.0]; p = 0.038). Sedation with low-dose dexmedetomidine infusion for ultra-fast track extubation following cardiac surgery enhances sleep duration and quality. [Display omitted] [ABSTRACT FROM AUTHOR]

Epidural analgesia has emerged as a commonly used method for relieving labor pain. However, epidural-related maternal fever (ERMF) is characterized by a high occurrence rate and can have detrimental consequences for the well-being of both the mother and the fetus. This study aimed to investigate the functional role and underlying mechanism of dexmedetomidine (DEX) in ERMF. Ropivacaine (ROP)-induced human umbilical vein endothelial cells (HUVECs) were treated with DEX and/or transfected with ALKBH5 or FUNDC1 overexpression plasmid. qPCR and Western blot were adopted for mitophagy and pyroptosis marker protein detection. Autophagosomes were observed through electron microscopy, Caspase-1/PI double-positive cells were determined using flow cytometry. Inflammation-related factors were quantified using ELISA. The N6-methyladenosine (m6A) modification of FUNDC1 mRNA was examined using methylated RNA immunoprecipitation (MeRIP) and the binding between ALKBH5 and FUNDC1 mRNA was confirmed by RNA immunoprecipitation (RIP). In ROP-induced HUVECs, there was a significant upregulation in ALKBH5 and FUNDC1, resulting in a notable increase in inflammation, pyroptosis, and mitophagy. The administration of DEX demonstrated the ability to alleviate ROP-induced pyroptosis and promote protective mitophagy. Interestingly, DEX treatment significantly reduced the interaction between ALKBH5 and FUNDC1 mRNA, while simultaneously increasing the m6A level of FUNDC1 mRNA in ROP-treated cells. Moreover, the overexpression of FUNDC1 partially reversed the effects of ALKBH5 overexpression on mitophagy and pyroptosis in HUVECs. DEX can promote mitophagy and inhibit pyroptosis through the ALKBH5/FUNDC1 axis in ERMF, indicating its potential as a therapeutic strategy for clinical ERMF treatment. • Dexmedetomidine (DEX) enhances mitophagy and alleviates pyroptosis in ropivacaine-induced HUVECs. • DEX regulates ALKBH5-mediated m6A modification of FUNDC1 mRNA. • DEX inhibits pyroptosis through ALKBH5/FUNDC1-mediated mitophagy. [ABSTRACT FROM AUTHOR]

Dexmedetomidine is increasingly used for surgical patients requiring general anaesthesia. However, its effectiveness on patient-centred outcomes remains uncertain. Our main objective was to evaluate the patient-centred effectiveness of intraoperative dexmedetomidine for adult patients requiring surgery under general anaesthesia. We conducted a systematic search of MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL from inception to October 2023. Randomised controlled trials (RCTs) comparing intraoperative use of dexmedetomidine with placebo, opioid, or usual care in adult patients requiring surgery under general anaesthesia were included. Study selection, data extraction, and risk of bias assessment were performed by two reviewers independently. We synthesised data using a random-effects Bayesian regression framework to derive effect estimates and the probability of a clinically important effect. For continuous outcomes, we pooled instruments with similar constructs using standardised mean differences (SMDs) and converted SMDs and credible intervals (CrIs) to their original scale when appropriate. We assessed the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Our primary outcome was quality of recovery after surgery. To guide interpretation on the original scale, the Quality of Recovery-15 (QoR-15) instrument was used (range 0–150 points, minimally important difference [MID] of 6 points). We identified 49,069 citations, from which 44 RCTs involving 5904 participants were eligible. Intraoperative dexmedetomidine administration was associated with improvement in postoperative QoR-15 (mean difference 9, 95% CrI 4–14, n =21 RCTs, moderate certainty of evidence). We found 99% probability of any benefit and 88% probability of achieving the MID. There was a reduction in chronic pain incidence (odds ratio [OR] 0.42, 95% CrI 0.19–0.79, n =7 RCTs, low certainty of evidence). There was also increased risk of clinically significant hypotension (OR 1.98, 95% CrI 0.84–3.92, posterior probability of harm 94%, n =8 RCTs) and clinically significant bradycardia (OR 1.74, 95% CrI 0.93–3.34, posterior probability of harm 95%, n =10 RCTs), with very low certainty of evidence for both. There was limited evidence to inform other secondary patient-centred outcomes. Compared with placebo or standard of care, intraoperative dexmedetomidine likely results in meaningful improvement in the quality of recovery and chronic pain after surgery. However, it might increase clinically important bradycardia and hypotension. PROSPERO (CRD42023439896). [ABSTRACT FROM AUTHOR]

Non-intubated video-assisted thoracoscopic surgery combines a minimally invasive technique with multimodal locoregional analgesia to enhance recovery. The mainstay sedation protocol involves propofol and fentanyl. Dexmedetomidine, given its opioid-sparing effect with minimal respiratory depression, facilitates sedation in non-intubated patients. This study aimed to evaluate the efficacy of dexmedetomidine during non-intubated video-assisted thoracoscopic surgery. A total of 114 patients who underwent non-intubated video-assisted thoracoscopic surgery between June 2015 and September 2017 were retrospectively evaluated. Of these, 34 were maintained with dexmedetomidine, propofol, and fentanyl, and 80 were maintained with propofol and fentanyl. After a 1:1 propensity score-matched analysis incorporating sex, body mass index, American Society of Anesthesiologists classification, pulmonary disease and hypertension, the clinical outcomes of 34 pairs of patients were assessed. The dexmedetomidine group showed a significantly lower opioid consumption [10.3 (5.7–15.1) vs. 18.8 (10.0–31.0) mg, median (interquartile range); P = 0.001] on postoperative day 0 and a significantly shorter postoperative length of stay [3 (2–4) vs. 4 (3–5) days, median (interquartile range), P = 0.006] than the control group. During operation, the proportion of vasopressor administration was significantly higher in the dexmedetomidine group [18 (53) vs. 7 (21), patient number (%), P = 0.01]. On the other hand, the difference of the hypotension and bradycardia incidence, short-term morbidity and mortality rates between each group were nonsignificant. Adding adjuvant dexmedetomidine to propofol and fentanyl is safe and feasible for non-intubated video-assisted thoracoscopic surgery. With its opioid-sparing effect and shorter postoperative length of stay, dexmedetomidine may enhance recovery after surgery. [Display omitted] [ABSTRACT FROM AUTHOR]

Dexmedetomidine utilisation in paediatric patients is increasing. We hypothesised that intraoperative use of dexmedetomidine in children is associated with longer postanaesthesia care unit length of stay, higher healthcare costs, and side-effects. We analysed data from paediatric patients (aged 0–12 yr) between 2016 and 2021 in the Bronx, NY, USA. We matched our cohort with the Healthcare Cost and Utilization Project-Kids' Inpatient Database (HCUP-KID). Among 18 104 paediatric patients, intraoperative dexmedetomidine utilisation increased from 51.7% to 85.7% between 2016 and 2021 (P <0.001). Dexmedetomidine was dose-dependently associated with a longer postanaesthesia care unit length of stay (adjusted absolute difference [AD adj ] 19.7 min; 95% confidence interval [CI]: 18.0–21.4 min; P <0.001, median length of stay of 122 vs 98 min). The association was magnified in children aged ≤2 yr undergoing short (≤60 min) ambulatory procedures (AD adj 33.3 min; 95% CI: 26.3–40.7 min; P <0.001; P -for-interaction <0.001). Dexmedetomidine was associated with higher total hospital costs of USD 1311 (95% CI: USD 835–1800), higher odds of intraoperative mean arterial blood pressure below 55 mm Hg (adjusted odds ratio [OR adj ] 1.27; 95% CI: 1.16–1.39; P <0.001), and higher odds of heart rate below 100 beats min−1 (OR adj 1.32; 95% CI: 1.21–1.45; P <0.001), with no preventive effects on emergence delirium requiring postanaesthesia i.v. sedatives (OR adj 1.67; 95% CI: 1.04–2.68; P =0.034). Intraoperative use of dexmedetomidine is associated with unwarranted haemodynamic effects, longer postanaesthesia care unit length of stay, and higher costs, without preventive effects on emergence delirium. [ABSTRACT FROM AUTHOR]

• 14.5 % of the moderate-to-severe traumatic brain injury patients were exposed to early dexmedetomidine. • There was no significant association between early dexmedetomidine exposure and day 3 biomarkers. • Dexmedetomidine might be a safe choice for ICU sedation. Traumatic brain injury (TBI) triggers autonomic dysfunction and inflammatory response that can result in secondary brain injuries. Dexmedetomidine is an alpha-2 agonist that may modulate autonomic function and inflammation and has been increasingly used as a sedative agent for critically ill TBI patients. We aimed to investigate the association between early dexmedetomidine exposure and blood-based biomarker levels in moderate-to-severe TBI (msTBI). We conducted a retrospective cohort study using data from the Transforming Clinical Research and Knowledge in Traumatic Brain Injury Study (TRACK-TBI), which enrolled acute TBI patients prospectively across 18 United States Level 1 trauma centers between 2014–2018. Our study population focused on adults with msTBI defined by Glasgow Coma Scale score 3–12 after resuscitation, who required mechanical ventilation and sedation within the first 48 h of ICU admission. The study's exposure was early dexmedetomidine utilization (within the first 48 h of admission). Primary outcome included brain injury biomarker levels measured from circulating blood on day 3 following injury, including glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neuron-specific enolase (NSE), S100 calcium-binding protein B (S100B) and the inflammatory biomarker C-reactive protein (CRP). Secondary outcomes assessed biomarker levels on days 5 and 14. Linear mixed-effects regression modelling of the log-transformed response variable was used to analyze the association of early dexmedetomidine exposure with brain injury biomarker levels. Among the 352 TRACK-TBI subjects that met inclusion criteria, 50 (14.2 %) were exposed to early dexmedetomidine, predominantly male (78 %), white (81 %), and non-Hispanic (81 %), with mean age of 39.8 years. Motor vehicle collisions (27 %) and falls (22 %) were common causes of injury. No significant associations were found between early dexmedetomidine exposure with day 3 brain injury biomarker levels (GFAP, ratio = 1.46, 95 % confidence interval [0.90, 2.34], P = 0.12; UCH-L1; ratio = 1.17 [0.89, 1.53], P = 0.26; NSE, ratio = 1.19 [0.92, 1.53], P = 0.19; S100B, ratio = 1.01 [0.95, 1.06], P = 0.82; hs-CRP, ratio = 1.29 [0.91, 1.83], P = 0.15). The hs-CRP level at day 14 in the dexmedetomidine group was higher than that of the non-exposure group (ratio = 1.62 [1.12, 2.35], P = 0.012). There were no significant associations between early dexmedetomidine exposure and day 3 brain injury biomarkers in msTBI. Our findings suggest that early dexmedetomidine use is not correlated with either decrease or increase in brain injury biomarkers following msTBI. Further research is necessary to confirm these findings. [ABSTRACT FROM AUTHOR]

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This article reviews the highlights of pertinent literature of interest to the congenital cardiac anesthesiologist published in 2023. After a search of the US National Library of Medicine PubMed database, several topics emerged where significant contributions were made in 2023. The authors of this article considered the following topics noteworthy to be included in this review: (1) advancements in percutaneous mechanical support in children with congenital heart disease, (2) children with pulmonary hypertension undergoing surgery for congenital heart disease, (3) dexmedetomidine in pediatric cardiac surgery, and (4) recommendations for pediatric heart surgery in the United States: Implications for pediatric cardiac anesthesia. [ABSTRACT FROM AUTHOR]

Intraoperative opioid use is associated with postoperative nausea and vomiting, respiratory depression, and persistent postoperative pain, all of which contribute to increased length of stay and health care costs. Although research shows adding dexmedetomidine as an adjunct leads to reduced opioid-related postoperative complications, many anesthesia providers are not using this medication. The purpose of this quality improvement project was to increase the use of dexmedetomidine among anesthesia providers to improve outcomes among spinal and orthopedic surgery patients. Quality improvement study. The project consisted of a preimplementation retrospective chart review, a preimplementation staff survey, the implementation of an anesthesia training bundle, a postimplementation staff survey, and a postimplementation retrospective chart review. The team provided ongoing support for the use of dexmedetomidine with resource flyers, a recorded presentation, and provider support. Preimplementation surveys indicated staff readiness for change and identified the lack of availability of dexmedetomidine within the operating rooms as the barrier to use. After receiving education, staff requested dexmedetomidine to be stocked within every operating room. Utilization increased by 67% after the implementation of the anesthesia training bundle. While there was no significant change in opioid-related complications as is found in the literature, the project education and support led to anesthesia provider interest in using dexmedetomidine, resulting in a significant increase in use. Similar projects should include education for postanesthesia care nurses. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of opioid-free anesthesia (OFA) in laparoscopic gastrectomy and identify the psychological factors that could influence the efficacy of OFA. 120 patients undergoing laparoscopic gastrectomy were allocated to either the opioid-based anesthesia group (OA) (n = 60) or the OFA (n = 60) group. Remifentanil was administered to the OA group intraoperatively, whereas dexmedetomidine and lidocaine were administered to the OFA group. The interaction effect of the psychological factors on OFA was analyzed using the aligned rank transform for nonparametric factorial analyses. The opioid requirement for 24 h after surgery was lower in the OFA group than in the OA group (fentanyl equivalent dose 727 vs. 650 μg, p = 0.036). The effect of OFA was influenced by the pain catastrophizing scale (p = 0.041), temporal pain summation (p = 0.046), and pressure pain tolerance (p = 0.034). This indicates that patients with pain catastrophizing or high pain sensitivity significantly benefited from OFA, whereas patients without these characteristics did not. This study demonstrated that OFA with dexmedetomidine and lidocaine effectively reduced the postoperative 24-h opioid requirements following laparoscopic gastrectomy, which was modified by baseline pain catastrophizing and pain sensitivity. The study protocol was approved by the Institutional Review Board of Yonsei University Health System Gangnam Severance Hospital (#3–2021-0295) and registered at ClinicalTrials.gov (NCT05076903). [ABSTRACT FROM AUTHOR]

To compare the effects of constant rate infusions (CRI) of fentanyl or dexmedetomidine, combined with lidocaine and ketamine, on cardiovascular response during surgery, sevoflurane requirement and postoperative pain in dogs undergoing mastectomy. Prospective, randomized, blinded, clinical trial. A total of 29 female dogs with mammary tumors. Premedication consisted of intramuscular acepromazine and morphine. General anesthesia was induced with intravenous propofol and maintained with sevoflurane. Dogs were randomized to be administered intravenous DLK [dexmedetomidine 1 μg kg–1 loading dose (LD) and 1 μg kg–1 hour–1; lidocaine 2 mg kg–1 LD and 3 mg kg–1 hour–1; ketamine 1 mg kg–1 LD and 0.6 mg kg–1 hour–1; n = 14] or FLK (fentanyl 5 μg kg–1 LD and 9 μg kg–1 hour–1; same doses of lidocaine and ketamine; n = 15) during anesthesia. Cardiorespiratory variables and end-tidal sevoflurane (F e′ Sevo) were recorded during surgery. The number of dogs administered ephedrine to treat arterial hypotension [mean arterial pressure (MAP) < 60 mmHg] was recorded. Meloxicam was administered to both groups. Postoperative pain and rescue analgesia requirement were assessed for 24 hours using the short form of the Glasgow Composite Measure Pain Scale. Data were compared using a mixed effects model or a Mann–Whitney test. More dogs required ephedrine in FLK than in DLK (67% versus 7%). Heart rate was not significantly different between groups, whereas lower values of MAP (p ≤ 0.01) and F e′ Sevo (p = 0.018) were observed in FLK than in DLK. Rescue analgesia was administered to 2/15 dogs in FLK and 0/14 dogs in DLK. Based on the cardiovascular response during surgery, intraoperative infusions of FLK and DLK provided adequate antinociception. Infusion of DLK provided greater stability of blood pressure. Both protocols resulted in minimal need for additional analgesia within 24 hours postoperatively. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine what is considered a long oral surgery and conduct a cost-effective analysis of sedative agents used for intravenous sedation (IVS) and sedation protocols for such procedures. Pubmed and Google Scholar databases were used to identify human studies employing IVS for extractions and implant-related surgeries, between 2003 and July/2023. Sedation protocols and procedure lengths were documented. Sedative satisfaction, operator satisfaction, and sedation assessment were also recorded. Cost estimation was based on The British National Formulary (BNF). To assess bias, the Cochrane Risk of Bias tools were employed. This review identified 29 randomised control trials (RCT), six cohorts, 14 case-series, and one case-control study. The study defined long procedures with an average duration of 31.33 minutes for extractions and 79.37 minutes for implant-related surgeries. Sedative agents identified were midazolam, dexmedetomidine, propofol, and remimazolam. Cost analysis revealed midazolam as the most cost-effective option (<10 pence per procedure per patient) and propofol the most expensive option (approximately £46.39). Bias analysis indicated varying degrees of bias in the included studies. Due to diverse outcome reporting, a comparative network approach was employed and revealed benefits of using dexmedetomidine, propofol, and remimazolam over midazolam. Midazolam, dexmedetomidine, propofol, and remimazolam demonstrated safety and efficacy as sedative agents for conscious IVS in extended procedures like extractions or implant-related surgeries. While midazolam is the most cost-effective option, dexmedetomidine, propofol, and remimazolam offer subjective and clinical benefits. The relatively higher cost of propofol may impede its widespread use. Dexmedetomidine and remimazolam stand out as closely priced options, necessitating further clinical investigations for comparative efficacy assessment. [ABSTRACT FROM AUTHOR]

• Postoperative gastrointestinal dysfunction commonly occurs cesarean section. • Delayed recovery in gastrointestinal function can lead to many complications. • Intravenous dexmedetomidine could accelerate gastrointestinal function recovery. • This method can shorten the postoperative hospital stay and reduce medical costs. Gastrointestinal dysfunction after cesarean section negatively affects postoperative recovery. Dexmedetomidine has been shown to improve postoperative gastrointestinal function in patients undergoing lumbar spinal fusion surgery and laparoscopic gastrectomy, but its role in cesarean section has not been fully elucidated. The study aimed to investigate the effect of dexmedetomidine on gastrointestinal function after cesarean section. 220 pregnant women who underwent elective cesarean section were randomized into group D and group S. Group D patients received a loading dose of 0.5 μg/kg of dexmedetomidine for 10 mins followed by a maintenance dose of 0.5 μg/kg/h intravenously immediately after the umbilical cord was cut intraoperatively, whereas the other group (group S) received an equivalent quantity of normal saline as loading and maintenance dose IV by infusion pump. The primary outcome was time to first flatus after surgery (hours). Secondary outcomes included time to first feces and first bowel sounds (hours), incidence rates of postoperative gastrointestinal complications, and the length of postoperative hospital stay (days). Modified intention-to-treat analysis showed that patients in Group D had a significantly shorter time to first flatus (21 [16 to 28.25] vs. 25 [18 to 32.25] h; P = 0.014), time to first feces (45.5 [35.75 to 55.25] vs. 53 [40 to 60] h; P = 0.019), and time to first bowel sounds (P = 0.010), a lower incidence of abdominal distension (21[20.6 %] vs. 36[34.3 %], P = 0.027), shorter length of postoperative hospital stay (P = 0.010) compared to patients in Group S. Intraoperative dexmedetomidine infusion reduces the time to first flatus, the incidence of abdominal distension, and shortens the length of hospital stay, promoting gastrointestinal function after cesarean section. [ABSTRACT FROM AUTHOR]

Sleep disruption is a common occurrence during medical care and is detrimental to patient recovery. Long-term sedation in the critical care setting is a modifiable factor that affects sleep, but the impact of different sedative–hypnotics on sleep homeostasis is not clear. We conducted a systematic comparison of the effects of prolonged sedation (8 h) with i.v. and inhalational agents on sleep homeostasis. Adult Sprague–Dawley rats (n =10) received dexmedetomidine or midazolam on separate days. Another group (n =9) received propofol or sevoflurane on separate days. A third group (n =12) received coadministration of dexmedetomidine and sevoflurane. Wakefulness (wake), slow-wave sleep (SWS), and rapid eye movement (REM) sleep were quantified during the 48-h post-sedation period, during which we also assessed wake-associated neural dynamics using two electroencephalographic measures: theta-high gamma phase-amplitude coupling and high gamma weighted phase-lag index. Dexmedetomidine-, midazolam-, or propofol-induced sedation increased wake and decreased SWS and REM sleep (P <0.0001) during the 48-h post-sedation period. Sevoflurane produced no change in SWS, decreased wake for 3 h, and increased REM sleep for 6 h (P <0.02) post-sedation. Coadministration of dexmedetomidine and sevoflurane induced no change in wake (P >0.05), increased SWS for 3 h, and decreased REM sleep for 9 h (P <0.02) post-sedation. Dexmedetomidine, midazolam, and coadministration of dexmedetomidine with sevoflurane reduced wake-associated phase-amplitude coupling (P ≤0.01). All sedatives except sevoflurane decreased wake-associated high gamma weighted phase-lag index (P <0.01). In contrast to i.v. drugs, prolonged sevoflurane sedation produced minimal changes in sleep homeostasis and neural dynamics. Further studies are warranted to assess inhalational agents for long-term sedation and sleep homeostasis. [ABSTRACT FROM AUTHOR]

Efficacy of dexmedetomidine (DEX) as a cardioprotective agent in Indonesian children undergoing classic tetralogy of Fallot (TOF) repair with cardiopulmonary bypass (CPB). A prospective, parallel trial using block randomization along with double-blinded preparation of treatment agents by other parties. National Cardiovascular Center Harapan Kita, Indonesia. Sixty-six children with classic TOF scheduled for corrective surgery. No children were excluded. All patients had fulfilled the criteria for analysis. A total of 0.5 µg/kg bolus of DEX was added to the CPB priming solution, followed by 0.25 µg/kg/h maintenance during bypass. The placebo group used normal saline. Follow-ups were up to 30 days. Troponin I was lower in the DEX group at 6 hours (30.48 ± 19.33 v 42.73 ± 27.16, p = 0.039) and 24 hours after CPB (8.89 ± 5.42 v 14.04 ± 11.17, p = 0.02). Within a similar timeframe, DEX successfully lowered interleukin-6 (p = 0.03; p = 0.035, respectively). Lactate was lower in the Dex group at 1, 6, and 24 hours after CPB (p < 0.01; p = 0.048; p = 0.035; respectively). Dexmedetomidine increased cardiac output and index from 6 hours after bypass, but vice versa in systemic vascular resistance. Reduction of vasoactive inotropic score was seen during intensive care unit monitoring in the Dex group (p = 0.049). Nevertheless, DEX did not significantly affect the length of ventilation (p = 0.313), intensive care unit stay (p = 0.087), and mortality (p > 0.99). Dexmedetomidine during CPB is an effective cardioprotective agent in TOF children having surgery. Postoperative mortality was comparable across groups. [ABSTRACT FROM AUTHOR]

• Dexmedetomidine could reduce the severity and prevalence of PPD. • Continuous postoperative infusion by PCIA was more promising administration way. • DEX ≤ 2.0 μg/kg preserved anti-PPD efficacy while reducing cardiovascular response. • Dexmedetomidine showed a unique superiority in safety and auxiliary anesthesia. The efficacy of perioperative dexmedetomidine (DEX) infusion as a precaution against postpartum depression (PPD) in women undergoing cesarean section has not been substantiated systematically. A literature search for RCTs on DEX against PPD was retrieved in the following databases from inception to January 3, 2024: PubMed, Embase, Web of Science, the Cochrane Library, CNKI, Wanfang, CBM, VIP, etc. A total of 13 RCTs with 1711 participants were included. Meta-analysis was performed by RevMan5.3 and Stata16 using a random-effects model. EPDS scores were significantly decreased in the DEX group within one week or over one week postpartum compared to the control group (SMD = −1.25, 95 %CI: −1.73 to −0.77; SMD = −1.08, 95 %CI: −1.43 to −0.73). The prevalence of PPD was significantly inferior to the control at both time points (RR = 0.36, 95 %CI: 0.24 to 0.54; RR = 0.39, 95 %CI: 0.26 to 0.57). Univariate meta -regression suggested that age influenced the heterogeneity of the EPDS scores (P = 0.039), and DEX infusion dose was a potential moderator (P = 0.074). The subgroup analysis results of PPD scores at both time points were consistent, showing that: ① Mothers younger than 30 years old had better sensitivity to DEX for treating PPD. ② The anti-PPD efficacy of continuous infusion of DEX by PCIA was superior to both single infusion and combined infusion. ③ DEX showed a better anti-PPD effect when the total infusion dose was ≤ 2 μg/kg. Moreover, DEX improved analgesia and sleep quality, provided appropriate sedation, and reduced the incidence of nausea, vomiting, and chills. The current evidence confirmed the prophylaxis and superiority of DEX for PPD. More high-quality, large-scale RCTs are required for verifying the reliability and formulating administration methods. [ABSTRACT FROM AUTHOR]

To evaluate cardiovascular effects of oral tasipimidine on propofol-isoflurane anaesthesia with or without methadone and dexmedetomidine at equianaesthetic levels. Prospective, placebo-controlled, blinded, experimental trial. A group of seven adult Beagle dogs weighing (mean ± standard deviation) 12.4 ± 2.6 kg and a mean age of 20.6 ± 1 months. The dogs underwent four treatments 60 minutes before induction of anaesthesia with propofol. PP: placebo orally and placebo (NaCl 0.9%) intravenously (IV); TP: tasipimidine 30 μg kg–1 orally and placebo IV; TMP: tasipimidine 30 μg kg–1 orally and methadone 0.2 mg kg–1 IV; and TMPD: tasipimidine 30 μg kg–1 orally with methadone 0.2 mg kg–1 and dexmedetomidine 1 μg kg–1 IV followed by 1 μg kg–1 hour–1. Isoflurane in oxygen was maintained for 120 minutes at 1.2 individual minimum alveolar concentration preventing motor movement. Cardiac output (CO), tissue blood flow (tbf), tissue oxygen saturation (stO 2) and relative haemoglobin content were determined. Arterial and mixed venous blood gases, arterial and pulmonary artery pressures and heart rate (HR) were measured at baseline; 60 minutes after oral premedication; 5 minutes after IV premedication; 15, 30, 60, 90 and 120 minutes after propofol injection; and 30 minutes after switching the vaporiser off. Data were analysed by two-way anova for repeated measures; p < 0.05. Tasipimidine induced a significant 20–30% reduction in HR and CO with decreases in MAP (10–15%), tbf (40%) and stO 2 (43%). Blood pressure and oxygenation variables were mainly influenced by propofol-isoflurane-oxygen anaesthesia, preceded by short-lived alterations related to IV methadone and dexmedetomidine. Tasipimidine induced mild to moderate cardiovascular depression. It can be incorporated into a common anaesthetic protocol without detrimental effects in healthy dogs, when anaesthetics are administered to effect and cardiorespiratory function is monitored. [ABSTRACT FROM AUTHOR]

To compare the perioperative analgesic effects of an opioid-free (OFA) and an opioid-sparing (OSA) anaesthetic protocol in dogs undergoing laparoscopic ovariectomy. Prospective, randomized, blinded, clinical trial. A group of 28 client-owned dogs. Dogs were allocated to one of two groups. The OFA group was administered intramuscular (IM) dexmedetomidine 5 μg kg–1 and ketamine 1 mg kg–1, followed by two intraoperative constant rate infusions (CRIs) of dexmedetomidine (3 μg kg–1 hour–1) and lidocaine (1 mg kg–1 loading dose, 2 mg kg–1 hour–1). The OSA group was administered IM dexmedetomidine 5 μg kg–1, ketamine 1 mg kg–1 and methadone 0.2 mg kg–1, followed by two intraoperative saline CRIs. In both groups, anaesthesia was induced with intravenous (IV) propofol 2 mg kg–1 and diazepam 0.2 mg kg–1 and maintained with isoflurane. Rescue dexmedetomidine (0.5 μg kg–1) was administered IV if there was a 20% increase in cardiovascular variables compared with pre-stimulation values. Ketorolac (0.5 mg kg–1) was administered IV when the surgery ended. Postoperative analgesia was evaluated using the Short Form-Glasgow Composite Measure Pain Scale and methadone (0.2 mg kg–1) was administered IM if the pain score was ≥ 6/24. Statistical analysis included mixed analysis of variance, Chi-square test and Mann–Whitney U test. There were no significant differences in the intraoperative monitored variables between groups. The OFA group showed a significantly lower intraoperative rescue analgesia requirement (p = 0.016) and lower postoperative pain scores at 3 (p =0.001) and 6 (p < 0.001) hours. No dogs were administered rescue methadone postoperatively. Although both groups achieved acceptable postoperative pain scores with no need for further intervention, the analgesic efficacy of the OFA protocol was significantly superior to that of the OSA protocol presented and was associated with a lower intraoperative rescue analgesia requirement and early postoperative pain scores. [ABSTRACT FROM AUTHOR]

To evaluate the effect of oral tasipimidine on dog handling, ease of catheter placement and propofol and isoflurane requirements for anaesthesia. Placebo-controlled, randomized, blinded, experimental trial. A group of seven adult Beagle dogs weighing (mean ± standard deviation) 13.1 ± 2.7 kg with a mean age of 18.6 ± 1 months. The dogs underwent four treatments before induction of anaesthesia with propofol. PP: placebo orally (PO) 60 minutes before induction of anaesthesia followed by placebo (NaCl 0.9%) intravenously (IV). TP: tasipimidine 30 μg kg–1 (PO) 60 minutes before induction of anaesthesia followed by placebo (NaCl 0.9%) IV. TMP: tasipimidine 30 μg kg–1 PO 60 minutes before induction of anaesthesia followed by methadone 0.2 mg kg–1 IV. TMPD: tasipimidine 30 μg kg–1 PO 60 minutes before induction of anaesthesia followed by methadone 0.2 mg kg–1 and dexmedetomidine 1 μg kg–1 IV followed by a dexmedetomidine constant rate infusion of 1 μg kg–1 hour–1. Sedation, response to catheter placement, intubation quality, time to loss of consciousness, time to intubation, required dose of propofol and minimum alveolar isoflurane concentration preventing motor movement (MAC NM) were determined. A mixed-model analysis or the Friedman and Mann–Whitney test were used; p -value < 0.05. Response to catheter placement did not differ between treatments. Tasipimidine alone reduced the propofol dose by 30%. Addition of methadone or methadone and dexmedetomidine reduced the propofol dose by 48% and 50%, respectively. Isoflurane MAC NM was reduced by 19% in tasipimidine-medicated dogs, whereas in combination with methadone or methadone and dexmedetomidine, isoflurane MAC NM was reduced by 35%. An anxiolytic dose of tasipimidine induced mild signs of sedation in dogs and reduced propofol and isoflurane requirements to induce and maintain anaesthesia, which needs to be considered in an anaesthetic plan. [ABSTRACT FROM AUTHOR]

Dopaminergic neurons in the ventral tegmental area (VTA) are crucially involved in regulating arousal, making them a potential target for reversing general anesthesia. Electrical deep brain stimulation (DBS) of the VTA restores consciousness in animals anesthetized with drugs that primarily enhance GABA A receptors. However, it is unknown if VTA DBS restores consciousness in animals anesthetized with drugs that target other receptors. To evaluate the efficacy of VTA DBS in restoring consciousness after exposure to four anesthetics with distinct receptor targets. Sixteen adult Sprague-Dawley rats (8 female, 8 male) with bipolar electrodes implanted in the VTA were exposed to dexmedetomidine, fentanyl, ketamine, or sevoflurane to produce loss of righting, a proxy for unconsciousness. After receiving the dopamine D1 receptor antagonist, SCH-23390, or saline (vehicle), DBS was initiated at 30 μA and increased by 10 μA until reaching a maximum of 100 μA. The current that evoked behavioral arousal and restored righting was recorded for each anesthetic and compared across drug (saline/SCH-23390) condition. Electroencephalogram, heart rate and pulse oximetry were recorded continuously. VTA DBS restored righting after sevoflurane, dexmedetomidine, and fentanyl-induced unconsciousness, but not ketamine-induced unconsciousness. D1 receptor antagonism diminished the efficacy of VTA stimulation following sevoflurane and fentanyl, but not dexmedetomidine. Electrical DBS of the VTA restores consciousness in animals anesthetized with mechanistically distinct drugs, excluding ketamine. The involvement of the D1 receptor in mediating this effect is anesthetic-specific. • VTA DBS restores consciousness from mechanistically distinct anesthetics. • VTA DBS does not restore consciousness following ketamine. • Righting is delayed by D1R antagonism in sevoflurane- and fentanyl-treated rats. • D1R antagonism does not affect DBS-induced arousal and righting in dexmedetomidine-treated rats. [ABSTRACT FROM AUTHOR]

The highly selective α2-adrenoceptor agonist dexmedetomidine is a commonly used sedative drug for patients undergoing anesthesia and intensive care treatment. Several studies have indicated that dexmedetomidine may have a potential role in preventing and treating perioperative tachyarrhythmias. However, the specific effect and mechanism of action of dexmedetomidine in this context remain unclear. Dexmedetomidine is known to regulate the electrophysiologic function of the myocardium by inhibiting the function of the sinus node and atrioventricular node, as well as affecting myocardial repolarization. This paper aims to provide a theoretical basis for the prevention and treatment of perioperative arrhythmias by summarizing the effects of dexmedetomidine on myocardial electrophysiologic function and its impact on different types of arrhythmias. [ABSTRACT FROM AUTHOR]

Dexmedetomidine (Dex) is a highly selective α2 adrenoceptor agonist that reduces blood pressure and heart rate. However, its ability to provide stable hemodynamics and a clinically significant reduction in blood loss in spine surgery is still a matter of debate. This study aimed to investigate the effects of Dex on intraoperative hemodynamics and blood loss in patients undergoing spine surgery. The Web of Science, MEDLINE, EMBASE, and the Cochrane Library were searched up to February 2023 for randomized controlled trials (RCTs) including patients undergoing spine surgeries under general anaesthesia and comparing Dex and saline. A fixed- or random-effect model was used depending on heterogeneity. Results Twenty-one RCTs, including 1388 patients, were identified. Dex added the overall risk of intraoperative hypotension (odds ratio [OR]: 2.11; 95% confidence interval [ CI ]: 1.24 – 3.58; P =0.006) and bradycardia (OR: 2.48; 95% CI : 1.57 – 3.93; P =0.0001). The use of a loading dose of Dex led to significantly increased risks of intraoperative hypotension (OR: 2.00; 95% CI : 1.06 – 3.79; P =0.03) and bradycardia (OR: 2.28; 95% CI : 1.42 3.66; P =0.0007). For patients receiving total intravenous anesthesia, there was an increased risk of hypotension (OR: 2.90; 95% CI : 1.24 – 6.82; P=0.01) and bradycardia (OR: 2.66; 95% CI : 1.53 - 4.61; P =0. 0005). For patients in the inhalation anesthesia group, only an increased risk of bradycardia (OR: 4.95; 95% CI : 1.41 – 17.37; P=0.01) was observed. No significant increase in the risk of hypotension and bradycardia was found in the combined intravenous-inhalation anesthesia group. The incidence of severe hypotension (OR: 2.57; 95% CI : 1.05 – 6.32; P =0.04), but not mild hypotension, was increased. Both mild (OR: 2.55; 95% CI : 1.06 – 6.15; P =0.04) and severe (OR: 2.45; 95% CI : 1.43 – 4.20; P =0.001) bradycardia were associated with a higher risk. The overall analyses did not reveal significant reduction in intraoperative blood loss. However, a significant decrease in blood loss was observed in total inhalation anesthesia subgroup (mean difference [MD]: –82.97; 95% CI : -109.04––56.90; P < 0.001). Dex increases the risks of intraoperative hypotension and bradycardia in major spine surgery. The administration of a loading dose of Dex and the utilization of various anesthesia maintenance methods may potentially impact hemodynamic stability and intraoperative blood loss. [ABSTRACT FROM AUTHOR]

Analyze the effectiveness of dexmedetomidine compared to midazolam for the treatment of ketamine-induced emergence delirium in noncardiac surgical patients. Systematic review. Guidelines outlined in the Preferred Reporting Items For Systematic Reviews and Meta-analyses (PRISMA)22 were used for this review. PubMed, Cumulative Index To Nursing And Allied Health Literature (CINAHL), MEDLINE, The Cochrane Library, EBSCOhost, National Institute of Health clinical trials, Google Scholar, and gray literature were searched for relevant studies. Only peer-reviewed nonexperimental studies, quasi-experimental studies, and randomized control trials with or without meta-analysis were included. The evidence was assessed using the Johns Hopkins Nursing Evidence-Based Practice guidelines for quality ratings and evidence level. Five blinded randomized controlled trials, three quasi-experimental studies, and two retrospective nonexperimental studies comprised of 1,024 subjects were evaluated for this review. Dexmedetomidine was more effective at reducing ketamine-induced delirium in adult patients, although midazolam attenuated the psychomimetic effects of ketamine better in pediatric patients. Furthermore, postanesthesia care unit discharge times were similar between patients treated with dexmedetomidine and midazolam. The studies in this review were categorized as Level I, Level II, or Level III and rated Grade A, implying strong confidence in the actual effects of dexmedetomidine in all outcome measures of the review. The current evidence suggests that dexmedetomidine is an effective alternative for alleviating ketamine-induced delirium in noncardiac adult surgical patients. Multiple studies in this review noted improved hemodynamics and reduced postoperative analgesic requirements after administration of dexmedetomidine in conjunction with ketamine. [ABSTRACT FROM AUTHOR]

Remifentanil-induced hyperalgesia (RIH) represents a significant clinical challenge due to the widespread use of opioids in pain management. However, the molecular and cellular mechanisms underlying RIH remain elusive. This study aimed to unravel the role of spinal cord microglia, focusing on the Nrf2/HO-1 signaling pathway and TRPV4 channels in the development of RIH. We used both in vivo and in vitro models to investigate the activation state of spinal cord microglia, the expression of TRPV4 channels, and the modulation of the Nrf2/HO-1 pathway under remifentanil exposure. In addition, we evaluated the potential therapeutic effects of dexmedetomidine, a perioperative α2-adrenergic agonist, on RIH and its related molecular pathways. Our results revealed a prominent role of spinal cord microglia in RIH, demonstrating an apparent microglial M1 polarization and increased TRPV4 channel expression. A notable observation was the downregulation of the Nrf2/HO-1 pathway, which was associated with increased neuroinflammation and mechanical allodynia. By upregulating or overexpressing Nrf2, we confirmed its ability to inhibit TRPV4 and thereby attenuate RIH-associated mechanical allodynia, M1 polarization, and neuroinflammation. Encouragingly, dexmedetomidine demonstrated therapeutic potential by positively modulating the Nrf2-TRPV4 nexus, attenuating mechanical allodynia, and reducing microglial inflammation. Our research highlights the critical role of spinal cord microglia in RIH mediated by the Nrf2-TRPV4 axis. The ability of dexmedetomidine to modulate this axis suggests its potential as an adjunctive therapy to remifentanil in mitigating RIH. Further studies are imperative to explore the broader implications and practical applicability of our findings. [Display omitted] • TRPV4 mediates spinal dorsal horn microglia M1 polarization and remifentanil-induced hyperalgesia (RIH). • Nrf2 regulates microglia M1 polarization via suppressing TRPV4 in vitro and in vivo. • Nrf2 gates RIH via suppressing TRPV4-related microglia neuroinflammation. • Targeting Nrf2-TRPV4 axis serves as promising strategy for RIH management. • Dexmedetomidine alleviated RIH via regulating microglial Nrf2-TRPV4 axis. [ABSTRACT FROM AUTHOR]

To report the effects of alfaxalone and dexmedetomidine based sedation protocols on echocardiographic and hemodynamic variables in cats with hypertrophic cardiomyopathy (HCM) during sedation and inhalational anesthesia. Prospective, randomized, experimental study. A group of 10 client-owned cats with subclinical HCM. Cats were administered one of two sedative intramuscular combinations: protocol ABM (alfaxalone 2 mg kg–1, butorphanol 0.4 mg kg–1, midazolam 0.2 mg kg–1; n = 5) or protocol DBM (dexmedetomidine 8 μg kg–1, butorphanol 0.4 mg kg–1, midazolam 0.2 mg kg–1; n = 5). General anesthesia was induced with intravenous alfaxalone and maintained with isoflurane in oxygen. Echocardiographic variables and noninvasive arterial blood pressures were obtained before sedation, following sedation, and during inhalational anesthesia. Sedation scores and alfaxalone induction dose requirements were recorded. Descriptive statistics are reported for cardiovascular variables. During sedation, echocardiographic and hemodynamic variables remained within normal limits with protocol ABM, whereas protocol DBM was characterized by bradycardia, low cardiac index and elevated blood pressure. During isoflurane anesthesia, both protocols demonstrated similar hemodynamic performance, with heart rates of 98 ± 12 and 89 ± 11 beats min–1, cardiac index values of 68 ± 17 and 47 ± 13 mL min–1 kg–1 and Doppler blood pressures of 72 ± 15 and 79 ± 20 mmHg with protocols ABM and DBM, respectively. A reduction in myocardial velocities were also observed during atrial and ventricular contraction with both protocols during isoflurane anesthesia. An alfaxalone based protocol offered hemodynamic stability during sedation in cats with HCM; however, both dexmedetomidine and alfaxalone based protocols resulted in clinically relevant hemodynamic compromise during isoflurane anesthesia. Further studies are required to determine optimal sedative and anesthetic protocols in cats with HCM. [ABSTRACT FROM AUTHOR]

To test whether labetalol improved cardiovascular function in anaesthetized dogs injected with dexmedetomidine. Prospective, randomized, blinded, clinical trial. A group of 20 healthy client-owned dogs undergoing ovariohysterectomy. Each dog received dexmedetomidine (5 μg kg–1) and methadone (0.2 mg kg–1) intramuscularly. General anaesthesia was induced with propofol and maintained with isoflurane in oxygen. All dogs were mechanically ventilated, and epidural anaesthesia with lidocaine was performed. Standard anaesthetic monitoring, invasive blood pressure, oesophageal Doppler and near-infrared tissue perfusion/oxygenation were applied. Peak velocity (PV), mean acceleration and stroke distance (SD) from the oesophageal Doppler were recorded. Arterial elastance (Ea) was calculated. Tissue oxygenation (rStO 2) was also recorded. Prior to surgery, animals received either 0.1 mg kg–1 of labetalol intravenously (IV) over 60 seconds or the equivalent volume of saline. Data were recorded for 20 minutes. Age, weight and propofol dose were compared with a Wilcoxon rank-sum test. The effects of time, treatment and their interaction with haemodynamic and perfusion variables were analysed with mixed-effect models and Tukey's post hoc tests. Significant effects of the interaction between treatment and time were observed whereby heart rate (HR) was higher in dogs given labetalol (p = 0.01), whereas arterial blood pressure and Ea were lower (p < 0.01). Similarly, PV, SD and rStO 2 were higher in the labetalol group, and significant effects were detected for the interaction between treatment and time (p < 0.01). Labetalol at a dose of 0.1 mg kg–1 IV in dogs under general anaesthesia and administered a pre-anaesthetic medication of dexmedetomidine produced mild vasodilation (reduction of Ea), resulting in an increase in HR and left ventricular outflow. Although labetalol could be an effective option to achieve haemodynamic optimization after dexmedetomidine-induced vasoconstriction, future studies are needed to assess long-term effects. [ABSTRACT FROM AUTHOR]

Information integration and network science are important theories for quantifying consciousness. However, whether these theories propose drug- or conscious state-related changes in EEG during anaesthesia-induced unresponsiveness remains unknown. A total of 72 participants were randomised to receive i.v. infusion of propofol, dexmedetomidine, or ketamine at a constant infusion rate until loss of responsiveness. High-density EEG was recorded during the consciousness transition from the eye-closed baseline to the unresponsiveness state and then to the recovery of the responsiveness state. Permutation cross mutual information (PCMI) and PCMI-based brain networks in broadband (0.1–45 Hz) and sub-band frequencies were used to analyse drug- and state-related EEG signature changes. PCMI and brain networks exhibited state-related changes in certain brain regions and frequency bands. The within-area PCMI of the frontal, parietal, and occipital regions, and the between-area PCMI of the parietal–occipital region (median [inter-quartile ranges]), baseline vs unresponsive were as follows: 0.54 (0.46–0.58) vs 0.46 (0.40–0.50), 0.58 (0.52–0.60) vs 0.48 (0.44–0.53), 0.54 (0.49–0.59) vs 0.47 (0.42–0.52) decreased during anaesthesia for three drugs (P <0.05). Alpha PCMI in the frontal region, and gamma PCMI in the posterior area significantly decreased in the unresponsive state (P <0.05). The frontal, parietal, and occipital nodal clustering coefficients and parietal nodal efficiency decreased in the unresponsive state (P <0.05). The increased normalised path length in delta, theta, and gamma bands indicated impaired global integration (P <0.05). The three anaesthetics caused changes in information integration patterns and network functions. Thus, it is possible to build a quantifying framework for anaesthesia-induced conscious state changes on the EEG scale using PCMI and network science. [ABSTRACT FROM AUTHOR]

Dental anxiety is a widespread complication occurring in pediatric patients during dental visits and may lead to undesirable complications. Esketamine may be effective in anxiety. The objective of this study was to investigate the effect of premedication with a dexmedetomidine-esketamine combination compared with dexmedetomidine alone on dental anxiety in preschool children undergoing dental treatment under general anesthesia. This is a prospective, double-blinded, randomized controlled trial. A total of 84 patients were scheduled for elective outpatient dental caries treatment under general anesthesia. Patients were randomly premedicated with intranasal dexmedetomidine (group D) or intranasal dexmedetomidine-esketamine (group DS). The primary outcome was the level of dental anxiety assessed by the Modified Child Dental Anxiety Scale (MCDAS) at 2 h after surgery. Secondary outcomes included level of dental anxiety at 1 day and 7 days after surgery, the incidence of dental anxiety at 2 h, 1 day, and 7 days after surgery, sedation onset time, overall success of sedation, acceptance of mask induction, postoperative pain intensity, incidence of emergence agitation in PACU, adverse reactions, HR, and SpO2 before premedication (baseline) and at 10, 20, and 30 min after the end of study drug delivery. The dental anxiety in group DS was lower than that in group D at 2 h, 1 day, and 7 days postoperatively (P = 0.04, 0.004, and 0.006, respectively). The incidences of dental anxiety in group DS were lower than those in group D at 2 h (53 % vs 76 %, P = 0.03), 1 day (47 % vs 71 %, P = 0.04), and 7 days (44 % vs 71 %, P = 0.02) after surgery. Group DS had a higher success rate of sedation (P = 0.03) but showed a lower MAS score (P = 0.005) and smoother hemodynamics (P < 0.01) after drug administration than group D. Group DS showed a significantly lower incidence rate of emergence agitation (P = 0.03) and postoperative pain intensity (P = 0.006) than that in group D during the anesthesia recovery time. The occurrence of adverse reactions was similar in both groups (P > 0.05). We did not analyze and correct for the learning effect caused by repeated applications of the MCDAS and MCDAS scores on the 1 day after surgery were obtained by telephone follow-up. Compared to premedication with dexmedetomidine alone, premedication with intranasal dexmedetomidine combined with esketamine could significantly improve dental anxiety in preschool children undergoing dental treatment under general anesthesia. • Evidence regarding effects of esketamine on dental anxiety has been limited. • Intranasal dexmedetomidine combined with esketamine improves dental anxiety in children undergoing dental surgery. • Premedication with dexmedetomidine and esketamine reduces emergence agitation and postoperative pain in children. [ABSTRACT FROM AUTHOR]

This pilot study was designed to investigate the antidepressant effects of dexmedetomidine (DEX), a selective α2-adrenergic receptor agonist, in patients with treatment-resistant depression (TRD). The antidepressant effects of dexmedetomidine was compared with ECT, which is widely used in clinical practice for treatment of patients with TRD. Seventy six patients with TRD were randomly assigned to receive 10 sessions of DEX infusions or electroconvulsive therapy (ECT) treatment. The primary outcome was the changes of depression severity determined by the improvement of 24-item Hamilton Depression Rating Scale (HDRS-24). The second outcomes were the rates of therapeutic response (reduction in HDRS-24 ≥ 50 %) and remission (HDRS-24 ≤ 10 and reduction in HDRS-24 ≥ 60 %) at posttreatment and after 3 months of follow-up visits. We found that 10 sessions of DEX infusions or ECT treatments significantly improved HDRS-24 scores at posttreatment and after 3 months of follow-up visits compared with the baseline. In addition, there was no significant difference between DEX infusions and ECT treatments regarding HDRS-24 at these evaluating points. Furthermore, the depression severity dropped to mild after 2 sessions of DEX infusion. In contrast, at least 6 sessions of ECT treatment were needed to achieve a same level. Finally, the rates of therapeutic response and remission were comparable between the two groups. No serious adverse events were observed. Based on current published evidence, we conclude that DEX exhibits rapid and durable antidepressant properties similar to ECT but with fewer side effects. • Ten sessions of DEX infusions or ECT treatments significantly improved HDRS-24 scores. • DEX infusion displays a fast onset of action in antidepressant and anxiolytic effects. • The rates of therapeutic response and remission are similar between the two groups. • The TRD patients receiving 10 sessions of DEX treatment are safety and well tolerable. [ABSTRACT FROM AUTHOR]

Intraoperative opioid use has a positive relationship with postoperative nausea and vomiting (PONV), and opioid-free anaesthesia (OFA) might reduce PONV. We investigated whether OFA compared with opioid-based anaesthesia would reduce PONV during the first 2 postoperative days among patients undergoing thoracoscopic lung resection. In this randomised controlled trial, 120 adult patients were randomly assigned (1:1, stratified by sex) to receive either OFA with esketamine, dexmedetomidine, and sevoflurane, or opioid-based anaesthesia with sufentanil and sevoflurane. A surgical pleth index (SPI) of 20–50 was applied for intraoperative analgesia provision. All subjects received PONV prophylaxis (dexamethasone and ondansetron) and multimodal analgesia (flurbiprofen axetil, ropivacaine wound infiltration, and patient-controlled sufentanil). The primary outcome was the occurrence of PONV during the first 48 h after surgery. The median age was 53 yr and 66.7% were female. Compared with opioid-based anaesthesia, OFA significantly reduced the incidence of PONV (15% vs 31.7%; odds ratio [OR]=0.38, 95% confidence interval [CI], 0.16–0.91; number needed to treat, 6; P =0.031). Secondary and safety outcomes were comparable between groups, except that OFA led to a lower rate of vomiting (OR=0.23, 95% CI, 0.08–0.77) and a longer length of PACU stay (median difference=15.5 min, 95% CI, 10–20 min). The effects of OFA on PONV did not differ in the prespecified subgroups of sex, smoking status, and PONV risk scores. In the context of PONV prophylaxis and multimodal analgesia, SPI-guided opioid-free anaesthesia halved the incidence of PONV after thoracoscopic lung resection, although it was associated with a longer stay in the PACU. Chinese Clinical Trial Registry (ChiCTR2200059710). [ABSTRACT FROM AUTHOR]

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. 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). 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). 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. NCT0507270. [ABSTRACT FROM AUTHOR]

Catheter-related bladder discomfort (CRBD) is an unpleasant experience for patients during postoperative recovery. Dexmedetomidine is an effective therapy for CRBD; however, little is known about dexmedetomidine administration for treating CRBD during recovery. This study was conducted to determine the 90% effective dose (ED90) of dexmedetomidine to provide adequate treatment for CRBD during recovery. Prospective, single-blind dose-finding study. This open-label, single-group trial included severe postoperative CRBD patients aged 18 to 80 years and the American Society of Anesthesiologists' physical status class I or II in the postanesthesia care unit. All patients were assigned to receive intravenous dexmedetomidine. The dose of dexmedetomidine was determined using the modified Dixon's up-and-down method. The first patient was treated with 0.4 mcg/kg dexmedetomidine. An increment or decrement of 0.05 mcg/kg dexmedetomidine was used based on the response of the previous patient. A successful treatment was defined as the transition from severe CRBD to mild CRBD. Probit regression was applied to calculate the ED90 of dexmedetomidine. A total of 29 patients were recruited, of whom 14 patients (48.3%) underwent successful treatment. The ED90 of dexmedetomidine required for successfully treating postoperative CRBD was 0.55 mcg/kg (95% confidence interval: 0.49–1.54 mcg/kg). The ED90 of dexmedetomidine for the successful treatment of severe postoperative CRBD during recovery is 0.55 mcg/kg. [ABSTRACT FROM AUTHOR]

To screen modulators of biogenic amine (BA) neurotransmission for the ability to cause fentanyl to decrease isoflurane minimum alveolar concentration (MAC) in cats, and to test whether fentanyl plus a combination of modulators decreases isoflurane MAC more than fentanyl alone. Prospective, experimental study. A total of six adult male Domestic Short Hair cats. Each cat was anesthetized in three phases with a 1 week washout between studies. In phase 1, anesthesia was induced and maintained with isoflurane, and MAC was measured in duplicate using a tail clamp stimulus and standard bracketing technique. A 21 ng mL–1 fentanyl target-controlled infusion was then administered and MAC measured again. In phase 2, a single cat was administered a single BA modulator (buspirone, haloperidol, dexmedetomidine, pregabalin, ramelteon or trazodone) in a pilot drug screen, and isoflurane MAC was measured before and after fentanyl administration. In phase 3, isoflurane MAC was measured before and after fentanyl administration in cats co-administered trazodone and dexmedetomidine, the two BA modulator drugs associated with fentanyl MAC-sparing in the screen. Isoflurane MAC-sparing by fentanyl alone, trazodone–dexmedetomidine and trazodone–dexmedetomidine–fentanyl was evaluated using paired t tests with p < 0.05 denoting significant effects. The MAC of isoflurane was 1.87% ± 0.09 and was not significantly affected by fentanyl administration (p = 0.09). In the BA screen, cats administered trazodone or dexmedetomidine exhibited 26% and 22% fentanyl MAC-sparing, respectively. Trazodone–dexmedetomidine co-administration decreased isoflurane MAC to 1.50% ± 0.14 (p < 0.001), and the addition of fentanyl further decreased MAC to 0.95% ± 0.16 (p < 0.001). Fentanyl alone does not affect isoflurane MAC in cats, but co-administration of trazodone and dexmedetomidine causes fentanyl to significantly decrease isoflurane requirement. [ABSTRACT FROM AUTHOR]

• Using sedative and analgesic drugs during NIV can bring clinical benefits in patients with acute respiratory failure. • Dexmedetomidine was superior to other sedatives and analgesics for some clinical outcomes. • The vital signs of patients must be closely monitored when using sedative and analgesic drugs. The use of sedative and analgesic drugs during non-invasive ventilation (NIV) in patients with acute respiratory failure (ARF) is controversial. To assess the clinical effectiveness of sedative and analgesic medications used during NIV for patients with ARF to no sedation or analgesia. In addition, to investigate the characteristics of dexmedetomidine in comparison to other medications. PubMed, Embase, Web of Science, Cochrane Library and China National Knowledge Infrastructure (CNKI) were searched. Mean differences (MDs) or pooled risk ratios (RRs) were computed using random-effects models. We applied the Cochrane risk-of-bias assessment tool 2.0 to assess the methodological quality of eligible studies and the GRADE approach to evaluate the evidence certainty. Twenty-one studies were selected. Whether in Group A (using sedative and analgesic drugs vs. nonuse) or Group B (using dexmedetomidine vs. other drugs), the rates of tracheal intubation and delirium, the length of NIV, and the length of stay in the intensive care unit (ICU LOS) all decreased in both experimental groups (P < 0.05). And there were no significant differences in all-cause mortality and the incidence of hypotension between the two groups (P > 0.05), while both Group A and Group B's experimental groups had greater incidences of bradycardia. Administering sedative and analgesic medications during NIV can reduce the risk of tracheal intubation and delirium. Additionally, dexmedetomidine outperformed other sedative medications in terms of these clinical outcomes, making it the better option when closely monitoring patients' vital signs. [ABSTRACT FROM AUTHOR]

Optimal sedation management for pediatric dental treatment demands special focus as it's tubeless and shares a same oral space. The study was to evaluate dexmedetomidine compared to midazolam for intranasal premedication in pediatric dental treatment under intravenous deep sedation. A hundred children aged 3–7 years scheduled for elective dental treatment under intravenous deep sedation anesthesia were enrolled, of whom 50 children (Group D) were intranasally premedicated with 2.0 μg/kg dexmedetomidine and the remaining 50 children (Group M) received traditional 0.2 mg/kg midazolam. Acceptance rate of venipuncture was regarded as the primary endpoint. The acceptance rate of venipuncture in Group D and Group M were 76% versus 52%, respectively (P = 0.021). More children in Group M complained about bitter/sour taste than Group D (62% vs. 8%, P < 0.001). Intraoperatively, children in Group M were found to have more choking cough than Group D (30% vs. 9%, P = 0.003), and patients in Group M required more suction (18 [36%] in Group M vs. 4 [8%] in Group D, P = 0.001). There were no significant differences between the groups in the incidences of temporal hypoxemia (SpO 2 ≤ 90%), however, two children in Group M experienced hypoxemia over 10 s. Compared to the 0.2 mg/kg midazolam, children premedicated with 2.0 μg/kg intranasal dexmedetomidine showed superior venipuncture acceptance, had less intraoperative choking cough and required fewer suction. It seems to be a good alternative to midazolam as premedication for deep sedation in pediatric dental treatment. [ABSTRACT FROM AUTHOR]

Previous studies have shown that a single infusion of lipopolysaccharide (LPS) into the uterus induces mammary gland inflammation. However, repeated LPS infusions return the mammary glands to their basal state of inflammation. To confirm that this is a state of tolerance to LPS, we examined whether tolerance induced by repeated intrauterine LPS infusions limits mammary gland inflammation following subsequent intramammary LPS infusions. In the first experiment, three goats were treated with repeated intrauterine infusions of LPS dissolved in black ink for 5 consecutive days. Blood and milk samples were collected at 2, 4, 6, 12, 24, 48, 72, 96, and 120 h and smeared on glass slides to confirm the translocation of LPS from the uterus to the mammary gland. Black particles were detected in the blood and milk samples more than 2 h after the first infusion and in the connective tissue of the mammary gland after day 5. In the second experiment, goats were divided into two groups: an intrauterine infusion group (IU; n = 7) and a control group (CON; n = 6). The IU group received an intrauterine infusion of 100 μg of LPS in saline for 5 days. Subsequently, LPS was infused into the mammary glands of both groups to examine the effect of intrauterine treatment on the mammary inflammatory response after intramammary LPS infusion. Blood and milk samples were collected at 6, 12, and 24 h, and then daily until 7 d after the intramammary LPS challenge. Interestingly, a significant increase in the milk somatic cell count (SCC), IL-8, IL-1β, and TNF-α concentrations were observed in the CON group compared to the IU group. This suggests that pretreatment with repeated intrauterine infusions of LPS suppresses the inflammatory responses to subsequent intramammary LPS challenges. • Repeated intrauterine infusions of LPS suppresses the inflammatory responses against subsequent LPS intramammary challenges. • This indicates the occurrence of endotoxin tolerance in the mammary gland. • LPS infused into the uterus could translocate through the bloodstream and reach the mammary glands [ABSTRACT FROM AUTHOR]

We know that syndromic conditions and severe chronic diseases can be associated with symptoms that may interfere with sleep, significantly impacting the life quality of children and caregivers. Drugs commonly used in treating insomnia, such as melatonin, benzodiazepines, niaprazine, and antihistamines, are often either ineffective or associated with adverse effects, requiring new therapeutic perspectives. Dexmedetomidine is a selective alpha-2 agonist with hypnotic and anxiolytic effects, which, by stimulating alpha-2 adrenergic receptors in the locus coeruleus, induces sleep comparable to stages 2–3 of the non-REM phase without substantially affecting the respiratory drive during sedation. Its use has already been extensively described in pediatric intensive care or procedural sedation literature. In 2018, the Italian Medicines Agency (Agenzia Italiana Del Farmaco AIFA) authorized the off-label use of dexmedetomidine outside of intensive care in Children undergoing palliative treatment to control distressing symptoms related to pathology and refractory sleep disorders, and the literature reported cases of children who received dexmedetomidine at home. Our study aims to describe the home use of dexmedetomidine in children with insomnia or intractable dystonic states. We conducted a retrospective analysis through a questionnaire addressed to 12 Italian pediatric palliative care centers regarding the home use of dexmedetomidine in sleep disorders and intractable dystonic states. We collected a case series of 9 children treated with dexmedetomidine at home, 8 via intranasal and 1 via intravenous route. All children received the first drug administration in the hospital or hospice during a dedicated admission, under close monitoring of vital signs parameters for 72 hours (3 days, range 2–7 days). After discharge, the potential side effects of the drug were explained to the patient's families, and, once informed consent was obtained, the home administration of dexmedetomidine continued, with follow-up by the palliative care team. At home, dexmedetomidine was administered for 3000 days (minimum 1 month, maximum 36 months). The first patient was treated for 1095 days, from 2019 to 2021 (discontinued due to underlying condition-related death). All patients observed a persistent benefit from the treatment on symptoms, and none of them discontinued dexmedetomidine administration due to drug-related adverse effects or perceived lack of therapeutic efficacy. Therefore, its use at home may represent a promising therapeutic approach for intractable sleep disorders or dystonic states in pediatric palliative care children. Further studies are needed to confirm our results. [ABSTRACT FROM AUTHOR]