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BACKGROUND: The main goal of the pediatric dentist is to address and reduce children's fear and anxiety during the dental treatment, especially when conventional behavior-guiding strategies fail. In such cases, the use of pharmacological agents becomes an essential factor to consider. OBJECTIVE: The objective of the study was to compare the efficacy, safety, and acceptability of intranasal ketamine (INK) with the combination of intranasal midazolam and dexmedetomidine (INMzD) in pediatric dental patients for the procedural sedation. PATIENTS AND METHODS: Forty-seven children aged 3-9 years who required dental procedures such as extractions, pulpectomy, and restorations were randomly distributed into two groups using the envelope drawing method. Group INK received 7 mg/kg INK, whereas Group INMzD received a combination of midazolam spray (0.3 mg/kg) and atomized dexmedetomidine (3 µg/kg). RESULTS: INK showed faster onset, faster recovery, and shorter discharge time than INMzD. Both groups had acceptable physiological parameters and no postoperative complications. INK was more accepted by the patients than INMzD. CONCLUSIONS: In terms of efficacy, safety, and acceptability, INK outperformed the combination of INMzD for the procedural sedation.

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BACKGROUND: To compare the efficacy and safety of ciprofol, propofol, propofol and etomidate mixture or ciprofol and etomidate mixture in patients undergoing painless gastroscopic anesthesia, and to explore the optimal plan to relieve the patient's discomfort. METHODS: A total of 120 patients scheduled for painless gastroscopy were randomly assigned to 4 groups: propofol (Group P), ciprofol (Group C), propofol-etomidate mixture (Group P-E), and ciprofol-etomidate mixture (Group C-E). The success rate of gastroscopy examination, patient satisfaction, incidence of injection pain, hemodynamic parameters, induction time, procedure time, the consumption of drugs, awakening time, and incidence of adverse events were evaluated. RESULTS: All patients in the study successfully completed the gastroscopy. The satisfaction of patients in Group C-E was significantly higher than that in Group P (P < .05), but there was no statistical significance in the patient satisfaction among the other groups. Compared with Group P, the incidence of injection pain in Groups C and C-E significantly decreased (P < .05). There were no significant differences in the SBP, diastolic blood pressure, HR, and SpO2 among the 4 groups (P > .05). The awakening time of Group C was significantly longer than that of Groups P and P-E (P < .05), but there was no statistically significant difference in the awakening time of other groups. CONCLUSION: Ciprofol demonstrated efficacy in inducing sedation or anesthesia during painless gastroscopy that was similar to propofol, while exhibiting a comparable safety profile. Moreover, the combination of propofol and etomidate, as well as the combination of ciprofol and etomidate, were both shown to be equally safe and effective for this clinical application. These findings suggest that ciprofol can be considered as a safe and effective alternative for painless gastroscopy, and the ciprofol-etomidate mixture may be a better choice.

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Pediatric procedural sedation (PPS), formerly known as conscious sedation, is often used outside the operating room for various procedures. Twenty years ago, nearly all cases of PPS were performed by pediatric intensivists, dentists, emergency medicine physicians, and anesthesiologists, due to the urgent nature of procedures in their settings. However, with the emergence of pediatric hospital medicine as a board-certified subspecialty, many children's hospitals have created dedicated PPS teams. These teams, composed of highly trained physicians and ancillary staff, are well-suited for procedures, quality measures, and multidisciplinary care. The wider availability of sedation outside the operating room allows other pediatric subspecialties, such as surgery and oncology, to use PPS in ensuring safe and timely interventions for their patients. This article will cover PPS as an alternative to anesthesia for otherwise healthy children and aim to answer frequent questions that arise regarding medications, risks, and candidacy for PPS. [Pediatr Ann. 2024;53(9):e324-e329.].

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BACKGROUND: The clinical evidence for the effects of different doses of intranasal dexmedetomidine on emergence delirium/ emergence agitation (ED/EA) in children is lacking. METHODS: We searched the PubMed, EMBASE and Cochrane Library from the establishment of the databases until December 30, 2023. All randomized controlled trials that evaluated the effect of different dosage of intranasl dexamedetomidine in children younger than 18 years on postoperative ED/ EA were included. Data analysis was conducted using R 4.3.0. RESULTS: A total of 15 randomized controlled trials involving 1566 children were included. Compared to 0.5 µg/kg (RR = 4.81, 95%CI = 1.66-13.94), and normal saline (RR = 8.23, 95%CI = 4.63-14.65), intranasal dexmedetomidine at doses of 2 µg/kg significantly reduced the incidence of ED/ EA in children. 2 µg/kg was the most effective dosage in reducing the incidence of ED/ EA (Probability of rank = 0.75), the incidence of severe ED/ EA (Probability of rank = 0.45), and ED/ EA score (Probability of rank = 0.65). Moreover, intranasal dexmedetomidine at doses of 2 µg/kg significantly reduced the PACU pain compared to 0.5 µg/kg (RR = 0.42, 95%CI = -0.22-1.06), 1 µg/kg (RR = 0.18, 95%CI = -0.26-0.63), 1.5 µg/kg (RR = 1.00, 95%CI = -0.54-0.75), and normal saline (RR = 8.23, 95%CI = 4.63-14.65), with a probability of rank = 0.45. CONCLUSION: 2µg/kg intranasal dexmedetomidine is the optimum dose for reducing the occurrence of ED/ EA and postoperative pain. However, further research is required to verify our findings.

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BACKGROUND: Off-label intranasal administration of injectable dexmedetomidine has been widely applied in the pediatric sedation setting. However, the development of an improved drug delivery system that is easy to use is needed. We developed a novel dexmedetomidine nasal spray that can be administered directly without dilution or configuration for pediatric pre-anesthetic sedation. This nasal spray has a fixed dose and is stable during storage. To the best of our knowledge, this is the first licensed nasal spray preparation of dexmedetomidine worldwide. OBJECTIVE: To evaluate the pre-anesthetic sedation efficacy and safety of the novel dexmedetomidine nasal spray in children. METHODS: The study was conducted at 11 sites in China between 24 November 2021 and 20 May 2022 and was registered in ClinicalTrials.gov (NCT05111431, first registration date: 20/10/2021). Subjects (n = 159) between 2 and 6 years old who were to undergo elective surgery were randomized to the dexmedetomidine group (n = 107) or the placebo group (n = 52) in a 2:1 ratio. The dosage was 30 µg or 50 µg based on the stratified body weight. The primary outcome measure was the proportion of subjects who achieved the desired child-parent separation and Ramsay scale ≥ 3 within 45 min of administration. Safety was monitored via the assessments of adverse events, blood pressure, heart rate, respiratory rate and blood oxygen saturation. RESULTS: The proportion of subjects achieving desired parental separation and Ramsay scale ≥ 3 within 45 min was significantly higher in the dexmedetomidine group (94.4%) vs the placebo group (32.0%) (P < 0.0001). As compared with placebo, dexmedetomidine treatment led to more subjects achieving Ramsay scale ≥ 3 or UMSS ≥ 2, and shorter time to reach desired parental separation, Ramsay scale ≥ 3 and UMSS ≥ 2 (all P < 0.0001). Adverse events were reported in 90.7% and 84.0% of subjects in the dexmedetomidine and placebo groups, respectively, and all the events were mild or moderate in severity. CONCLUSIONS: This novel dexmedetomidine nasal spray presented effective pre-anesthetic sedation in children with a tolerable safety profile.

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THE AIM OF THE PRESENT STUDY: The aim of the present study was to do a comparison of the recovery profiles and airway-related adverse events of pediatric magnetic resonance imaging (MRI) sedation patients who received propofol alone to those who received midazolam alone. METHODS: This retrospective cohort study was approved by the Mutah University Ethical Approval Committee (No. 2378). A search of the patients' medical records was performed between September 2021 and April 2022 to identify children aged 4 months-11 years who received propofol or midazolam for MRI sedation. The patients were subdivided into two groups: Those who had propofol alone (propofol group) and those who received midazolam (midazolam group) for pediatric MRI sedation. In propofol group, a 1-2 mg/kg of propofol bolus was given to have a deep sedation (Ramsay Sedation Scale score of 5). Patients in midazolam group received 0.05 mg/kg of midazolam. During the maintenance state of sedation, the patient received 150 µg/kg/min of propofol, and the infusion rate was adjusted in 25 µg/kg/min increments up or down at the discretion of the anesthesiologists to maintain a state of deep sedation. The major targets of this study were recovery profiles (time to awake and time to discharge) and airway-related intervention ratios in pediatric MRI sedation patients. Patient demographics, MRI sedation, and recovery data, including propofol induction dose, airway intervention, and sedation-related adverse events from the pediatric sedation recovery unit were also collected. RESULTS: The mean (standard deviation [SD]) propofol induction dose was higher compared to midazolam group (2.4 [0.7] mg vs. 1.3 [0.5] mg; mean difference, 1.1 mg; P < 0.001). The mean (SD) infusion rate was higher in propofol group compared to midazolam group (161.3 [37.6] µg/min/kg vs. 116.2 [25.6] µg/min/kg; mean difference 45.1 µg/min/kg; P < 0.001). The mean (SD) propofol total dose was higher in propofol group compared to midazolam group (236.3 [102.4] mg vs. 180.7 [80.9] mg; mean difference, 155.4 mg; P < 0.001). The mean (SD) time to awake was longer in midazolam group compared to propofol group (21.2 [5.6] min vs. 23.0 [7.1] min; mean difference, 1.8 min; P < 0.001). The mean (SD) time to discharge was longer in midazolam group compared to propofol group (34.5 [6.9] min vs. 38.6 [9.4] min; mean difference, 4.1 min; 95% confidence interval, 3.0-5.1; P < 0.001). CONCLUSION: The administration of midazolam during pediatric MRI sedation can decrease the frequency of airway complications without prolonging the clinically significant recovery profile.

Résumé Objectif de l'étude:L'objectif de la présente étude était de comparer les profils de récupération et les événements indésirables liés aux voies respiratoires chez les patients pédiatriques sous sédation pour une imagerie par résonance magnétique (IRM) ayant reçu du propofol seul à ceux ayant reçu du midazolam seul.Méthodes:Cette étude de cohorte rétrospective a été approuvée par le Comité d'éthique de l'Université de Mutah (No. 2378). Une recherche dans les dossiers médicaux des patients a été réalisée entre septembre 2021 et avril 2022 pour identifier les enfants âgés de 4 mois à 11 ans ayant reçu du propofol ou du midazolam pour une sédation en IRM. Les patients ont été subdivisés en deux groupes : ceux ayant reçu uniquement du propofol (groupe propofol) et ceux ayant reçu du midazolam (groupe midazolam) pour la sédation pédiatrique en IRM. Dans le groupe propofol, un bolus de 1 à 2 mg/kg de propofol a été administré pour atteindre une sédation profonde (score de 5 sur l'échelle de sédation de Ramsay). Les patients du groupe midazolam ont reçu 0,05 mg/kg de midazolam. Pendant la phase de maintien de la sédation, les patients ont reçu 150 µg/kg/min de propofol, et la vitesse de perfusion a été ajustée par paliers de 25 µg/ kg/min, à la discrétion des anesthésistes, pour maintenir un état de sédation profonde. Les principaux objectifs de cette étude étaient les profils de récupération (temps de réveil et temps de sortie) et les taux d'interventions liées aux voies respiratoires chez les patients pédiatriques sous sédation pour IRM. Les données démographiques des patients, les détails de la sédation en IRM et les données de récupération, y compris la dose d'induction de propofol, les interventions liées aux voies respiratoires, et les événements indésirables liés à la sédation dans l'unité de récupération pédiatrique ont également été collectés.Résultats:La dose moyenne (écart-type [ET]) d'induction de propofol était plus élevée par rapport au groupe midazolam (2,4 [0,7] mg contre 1,3 [0,5] mg; différence moyenne, 1,1 mg; P<0,001). Le taux de perfusion moyen (ET) était plus élevé dans le groupe propofol par rapport au groupe midazolam (161,3 [37,6] µg/min/kg contre 116,2 [25,6] µg/min/kg; différence moyenne, 45,1 µg/min/kg; P<0,001). La dose totale moyenne (ET) de propofol était plus élevée dans le groupe propofol par rapport au groupe midazolam (236,3 [102,4] mg contre 180,7 [80,9] mg; différence moyenne, 155,4 mg; P<0,001). Le temps moyen (ET) pour se réveiller était plus long dans le groupe midazolam par rapport au groupe propofol (21,2 [5,6] min contre 23,0 [7,1] min; différence moyenne, 1,8 min; P<0,001). Le temps moyen (ET) de sortie était plus long dans le groupe midazolam par rapport au groupe propofol (34,5 [6,9] min contre 38,6 [9,4] min; différence moyenne, 4,1 min; intervalle de confiance à 95 %, 3,0­5,1; P<0,001).Conclusion:L'administration de midazolam lors de la sédation pédiatrique pour IRM peut diminuer la fréquence des complications des voies respiratoires sans prolonger de manière significative le profil de récupération clinique.

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An intravenous (IV) administration of midazolam may result in seizure-like activity or movement. This report describes 5 neonates who developed seizure-like movements after IV midazolam injection. The patients presented between 2019 and 2022 and were admitted to a neonatal intensive care unit located within an academic centre in Muscat, Oman. The abnormal movements occurred shortly after IV bolus administration of midazolam. None of the patients experienced seizure-like movements after receiving midazolam infusions. The seizure-like movements were aborted either spontaneously or by antiseizure medications. In addition, seizure recurrence was not observed in any of the infants during the later stages of their treatment. Since this adverse effect might be related to the speed of the bolus administration, IV midazolam must be given as a slow bolus over 2-3 minutes followed by a slow flush of normal saline. To prevent midazolam's potential adverse effect on newborns, neonatal caregivers must be aware of it.

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BACKGROUND: Sedation at the end of life is used to relieve distressing symptoms including agitation and delirium. Standard care may include infused benzodiazepines or antipsychotics. These agents often result in deep sedation with loss of interaction with loved ones, which may be distressing. OBJECTIVE: The DREAMS (Dexmedetomidine for the Reduction of End-of-life Agitation and for optiMised Sedation) trial aimed to compare the sedative and antidelirium effects of the alpha-2 agonist dexmedetomidine, a novel palliative care sedative, compared with midazolam, a benzodiazepine when administered by subcutaneous infusion at the end of life, with doses of both agents targeting lighter, or potentially interactive sedation. METHODS: Participants were recruited from adult inpatients admitted for end-of-life care under a palliative care team in regional New South Wales, Australia. Inclusion criteria included patients older than 18 years, with a preference for lighter sedation at the end of life. Exclusion criteria included severe cardiac dysfunction (contraindication to dexmedetomidine). Participants consented and were placed on a treatment-pending list. Upon experiencing terminal deterioration, patients were randomized to either arm 1 (dexmedetomidine) or arm 2 (midazolam) as their treatment arm. These treatments were administered by continuous subcutaneous infusion. The level of consciousness and agitation of the patients were measured by the Richmond Agitation-Sedation Scale-Palliative version and the Memorial Delirium Assessment Score. Richmond Agitation-Sedation Scale-Palliative version assessments were performed by both nursing and medical staff, while Memorial Delirium Assessment Score assessments were carried out by medical staff only. Families and patients were asked to complete, as able, a patient comfort assessment form, to gauge perceptions of distress. Data were collected and matched with the breakthrough medication doses administered, along with qualitative comments in the medical record. In addition, the study tracked symptoms and patient functional status that were recorded as part of the Palliative Care Outcomes Collaborative, a national tracking project for monitoring symptom outcomes in palliative care. RESULTS: The DREAMS trial was funded in May 2020, approved by the ethics committee in November 2020, and started recruiting participants in May 2021. Data collection commenced in May 2021 and is anticipated to continue until December 2024. Publication of results is anticipated from 2024 to 2026. CONCLUSIONS: The evidence base for sedative dosing in palliative care for distress and agitation is not robust, with standard care based primarily on clinical experience and not robust scientific evidence. This study is important because it will compare a standard and a novel sedative used in end-of-life treatment. By assessing the potential efficacy and benefits of both, it seeks to optimize the quality of dying by providing targeted sedation that can improve the communication between dying patients and their loved ones. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Register ACTRN12621000052831; https://uat.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380889. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55129.

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The soy isoflavone daidzin (DZN) has been considered a hopeful bioactive compound having diverse biological activities, including anxiolytic, memory-enhancing, and antiepileptic effects, in experimental animals. However, its sedative and hypnotic effects are yet to be discovered. This study aimed to evaluate its sedative/hypnotic effect on Swiss mice. Additionally, in silico studies were also performed to see the possible molecular mechanisms behind the tested neurological effect. For this, male Swiss albino mice were treated with DZN (5, 10, or 20 mg/kg) intraperitoneally (i.p.) with or without the standard GABAergic medication diazepam (DZP) and/or flumazenil (FLU) and checked for the onset and duration of sleeping time using thiopental sodium-induced as well as DZP-induced sleeping tests. A molecular docking study was also performed to check its interaction capacity with the α1 and ß2 subunits of the GABAA receptor. Findings suggest that DZN dose-dependently and significantly reduced the latency while increasing the duration of sleep in animals. In combination therapy, DZN shows synergistic effects with the DZP-2 and DZP-2 + FLU-0.01 groups, resulting in significantly (p < 0.05) reduced latency and increased sleep duration. Further, molecular docking studies demonstrate that DZN has a strong binding affinity of - 7.2 kcal/mol, which is closer to the standard ligand DZP (- 8.3 kcal/mol) against the GABAA (6X3X) receptor. Molecular dynamic simulations indicated stability and similar binding locations for DZP and DZN with 6X3X. In conclusion, DZN shows sedative effects on Swiss mice, possibly through the GABAA receptor interaction pathway.

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OBJECTIVE: To compare the efficacy of dexmedetomidine versus ketofol for moderate sedation in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). STUDY DESIGN: Randomised controlled trial. Place and Duration of the Study: Department of Anaesthesia, SICU and Pain Management, Sindh Institute of Urology and Transplantation, Karachi, Paksitan, from December 2021 to June 2022. METHODOLOGY: Sixty-two patients aged 20-60 years of any gender scheduled for elective ERCP were included. Patients were randomly divided into Dexmedetomidine group (2ml ampule of 100ug/ml diluted in 18ml of normal saline) and Ketofol group (2ml ketamine and 10ml of propofol 1% diluted in 8ml of normal saline) for sedation. The mean difference in time to achieve Ramsay Sedation Scale (RSS) score of 4 and Modified Aldrete's Score (MAS) of 9 were noted as outcomes in each group. In addition, complications during the procedure and recovery were also noted. RESULTS: The mean age was 39.15 ± 9.82 years. There were 33 (53.2%) males and 29 (46.8%) females. The mean time to achieve RSS 4 was significantly lower in patients who were treated with Dexmedetomidine as compared to Ketofol, i.e., 11.84 ± 1.77 minutes vs. 13.10 ± 1.64 minutes respectively (p-value 0.005, 95% CI -2.12 to -0.39). Similarly, the mean time to achieve MAS score 9 was significantly lower in patients who were treated with Dexmedetomidine as compared to Ketofol, i.e., 11.19 ± 1.72 minutes vs. 12.23 ± 1.84 minutes, respectively (p-value 0.026, 95% CI -1.94 to -0.13). CONCLUSION: Dexmedetomidine proved to be more effective than Ketofol for sedation in ERCP, achieving faster sedation and quicker recovery. KEY WORDS: Dexmedetomidine, Ketofol, Sedation, Endoscopic Retrograde Cholangiopancreatography.

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Dual orexin receptor antagonists (DORAs) are approved for the treatment of sleep onset and/or sleep maintenance insomnia. In the present disclosure, we report the discovery of a new class of DORAs designed to treat sleep disorders requiring a fast onset and a short duration of action (<4 h). We used early human pharmacokinetic-pharmacodynamic (PK-PD) predictions and in vivo experiments to identify DORAs eliciting this specific hypnotic profile. A high-throughput screening campaign revealed hits based on a rarely precedented tricyclic pyrazolidine scaffold. After unsuccessful structure-activity-relationship (SAR) studies on this hit series, a scaffold hopping exercise, aimed at reducing the molecular complexity of the tricyclic scaffold, resulted in the discovery of the 2-acyl-1-biarylmethylpyrazolidine series. SAR studies on this achiral series gave rise to the lead compound DORA 42. In vitro and in vivo parameters of DORA 42, and its PK-PD simulation for human use are detailed.

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PURPOSE: Shock, cardiovascular problems, and respiratory failure constitute the main causes of death in patients cared in medical emergency rooms. Patients commonly require orotracheal intubation (OTI), a fact that has been intensified by diseases that generate important and fatal hemodynamic and respiratory problems in the affected patient. METHODS: Although etomidate (ETO) is a highly used anesthetic for OTI, its use remains controversial in several scenarios. Some studies refer to an increase in mortality with its use in critically patients, while others do not refer to a difference. Therefore, we evaluated the mortality of patients submitted to OTI in the public hospital of a public federal university, with the use of ETO and other sedative-hypnotic drugs used in the induction of the performance of OTI, with the in-hospital mortality of patients cared in hospital. RESULTS: The results demonstrate that the use of ETO as a hypnotic for OTI in the emergency room is not associated with a significant difference in morbidity or early mortality, within 30 days of hospitalization, compared with other hypnotics. CONCLUSIONS: There was no difference in mortality between patients intubated in the emergency department who used ETO and those who used non-ETO hypnotic within 72 hours and 30 days.

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Background: Insomnia is a common sleep disorder, associated with multiple health concerns. Current medications for insomnia are associated with higher safety risks if clinical practice guidelines or monograph recommendations are not followed. This study aims to understand real-world prescribing practices among patients with insomnia in Canada, including medication utilization, potentially inappropriate medication use, cost incurred, and lines of treatment.Methods: This retrospective observational study utilized longitudinal drug claims data from 2018 to 2020 from the Canadian IQVIA National Private Drug Plan and Ontario Drug Benefit databases. Patients with any claims for medications approved for insomnia in Canada were identified. Four types of inappropriate medication usage were defined: (1) elevated daily dose; (2) extended duration of use for benzodiazepines (BZD) and/or Z-drugs; (3) combination use; and (4) opioid overlap with BZD and/or Z-drugs.Results: In 2019, 597,222 patients with insomnia were identified; 64% were female, with an average age of 55 years. Inappropriate medication use was noted in 52.5% of adult patients (aged 18-65 years) and 69.5% of senior patients (aged >65 years). Extended duration was the most common inappropriate medication usage category. The annual cost of medications for insomnia was $54.8 million, and $30.3 million (55.2%) met inappropriate medication use criteria.Conclusion: High prevalence of inappropriate medications usage in insomnia raises serious safety concerns for patients suffering from insomnia, particularly seniors, while also placing a substantial burden on the Canadian public and private health systems. This highlights an unmet need for better education regarding current guidelines and more effective and safer treatment options.

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BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure that has become an important tool in the diagnosis and staging of mediastinal lymph node lesions in lung cancer. Adequate sedation is an important part of the procedure as it provides patient comfort and potentially increases diagnostic yield. The sedation modality varies among centers and includes moderate sedation/conscious sedation, deep sedation, and general anesthesia. The object of this study will be the evaluation of patient's comfort and level of satisfaction with the involved health care providers (bronchoscopist and anesthesiologist) of remifentanil administration in target-controlled infusion (TCI) for conscious sedation in patients undergoing EBUS­TBNA, with a prospective randomized study design versus the of standard sedation protocol with midazolam and/or fentanest and/or propofol. METHODS: This study was carried out at the "Campus Biomedico di Roma" University Hospital between September 2021 and November 2021, with a total number of 30 patients enrolled who met the eligibility criteria, randomly divided into 2 groups: group 1 "REMIFENTANIL TCI" (experimental group) where the patients performed the EBUS-TBNA procedure under conscious sedation with infusion of remifentanil TCI with a target between 3 ng/mL and 6 ng/mL and group 2 "STANDARD" (control group) with patients undergoing conscious sedation with the association of midazolam and/or fentanest and/or propofol in refracted boluses based on clinical needs. Complications, safety, and level of satisfaction of the operator, the anesthesiologist, and the patient were evaluated. RESULTS: The results show that sedation with remifentanil in TCI can improve the comfort level of patients, reducing the risks associated with the procedure (lower frequency of oversedations and hypotension), allowing for greater intraprocedural safety. Furthermore, the level of satisfaction of the anesthesiologist and that of the operator appears to be significantly higher in the Remifentanil group. CONCLUSION: The execution of a mild to moderate sedation with Remifentanil in TCI in patients undergoing EBUS is safe, tolerated, and allows to obtain greater intraprocedural comfort. Further studies and larger and more representative samples are obviously needed to confirm and strengthen the validity of a remifentanil TCI-based sedation in endoscopic diagnostics.

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Combinations of a low dose of opioid, such as thiafentanil, and a high dose of medetomidine, are increasingly being used for immobilization of African ungulates. Both drugs can have undesirable cardiorespiratory effects. In this study we assessed whether vatinoxan, a peripherally acting alpha2-adrenergic receptor antagonist, can be used to alleviate some of these effects without affecting the immobilization quality. Eight healthy, female, boma-confined blesbok (Damaliscus pygargus phillipsi), weighing a mean (SDtion) of 56.8 (4.4) kg, were immobilized twice in a randomized cross-over study with a 2-wk washout period using (1) 0.5 mg thiafentanil + 1.5 mg medetomidine (TM), (2) TM + vatinoxan: 0.5 mg thiafentanil + 1.5 mg medetomidine + 15 mg vatinoxan per milligram medetomidine (total of 22.5 mg, administered intramuscularly at 10 min post recumbency). Heart rate, respiratory rate, rectal temperature, oxygen saturation (SpO2), arterial blood pressure, and sedation scores from 1 to 5 (1 = limited effect; 5 = excessively deep) were measured every 5 min. Arterial blood gases (PaO2 and PaCO2) were measured at 10, 15, 25, and 35 min postrecumbency and the alveolar--arterial oxygen gradient (P[A-a]O2) was calculated. Induction times and immobilization quality did not differ between groups. The heart rate was significantly higher and the mean arterial pressure significantly lower in blesbok after receiving vatinoxan. All animals were hypoxemic and there were no significant differences in the respiratory rates, PaO2, PaCO2, SpO2, or P(A-a)O2 gradients at any time point. Although vatinoxan did not improve respiratory variables and blood oxygenation in these animals, the change in cardiovascular variables may suggest that it improves tissue perfusion, a positive outcome that requires further investigation.

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Twenty lesser chevrotains (Tragulus sp.), 10 males and 10 females, were anesthetized with a combination of butorphanol-midazolam-medetomidine (BMidM), to assess the efficacy of this protocol for short procedures in this genus. The animals received BMidM (0.32, 0.06, 0.15 mg/kg, respectively) intramuscularly via hand injection. Physiological variables were recorded once the animals reached a working depth of anesthesia that lasted 30 min (range 12-60 min). At the end of the procedure, medetomidine and butorphanol were antagonized with atipamezole (0.75 mg/kg) and naltrexone (0.3 mg/kg) intramuscularly, respectively. Induction and recovery were 9.4 ± 4.0 min and 10.2 ± 4.1 min, respectively. Supplementation with isoflurane via face mask was required in five animals to reach light anesthesia. Times to reach the various stages of anesthesia were compared between sexes. There was no difference between males and females reaching the different stages of anesthesia, except for the time required to reach the ambulatory stage, in which females took a significantly longer time (11.8 min vs 7.8 min for the males) to stand after the injection of the antagonists (P = 0.02). Heart rate, respiratory rate, rectal temperature, and peripheral hemoglobin oxygen saturation were similar between sexes and stable throughout the procedure. At the dosage tested BMidM was a reliable and safe protocol for short, minimally invasive procedures in lesser chevrotains with a fast induction and smooth recovery without complications.

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Administration of butorphanol, azaperone, and medetomidine (BAM) for immobilization of black howler monkeys (Alouatta pigra) has not been previously reported. In this observational study, 0.02 ml/kg of compounded BAM (butorphanol 27.3 mg/ml, azaperone 9.1 mg/ml, medetomidine 10.9 mg/ml) was administered IM in 10 captive black howler monkeys. Time to immobilization was recorded, an arterial blood gas performed, and at 5-min intervals, HR, RR, oscillometric arterial blood pressure, SPO2, and rectal temperature were measured. Naltrexone and atipamezole were administered IM at procedure completion and recovery times were recorded. If invasive procedures such as surgery were necessary and additional drugs needed, further data from that individual was removed from data analysis. Final BAM dosages were 0.55 ± 0.12 mg/kg butorphanol, 0.19 ± 0.04 mg/kg azaperone, and 0.22 ± 0.05 mg/kg medetomidine. Nine of 10 monkeys achieved sedation allowing for physical exam, venipuncture, and tuberculin skin testing within 4 ± 2 min. No monkeys reached a plane of immobilization allowing for intubation. Physiologic variables were acceptable for this species. Hypoxemia (SPO2 < 95%) was observed in three monkeys via pulse oximetry, and normoxemia was observed on arterial blood gas. Recovery was smooth and rapid. Therefore, BAM is a viable option for noninvasive procedures or as a premedication prior to induction of anesthesia in black howler monkeys.

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Topicality: Providing assistance to patients with polytrauma, in a state of alcohol intoxication, complicated by alcoholic delirium, is a serious problem when providing anesthesia care and, in particular, choosing drugs for sedation. Considering the severity of mechanical damage, complications associated with alcohol intoxication and serious biochemical disorders of the body, namely carbohydrate, lipid metabolism, electrolyte changes, on which the activity of all systems depends, it is necessary to study the influence on the course of these processes, depending on the choice of their medicinal corrections. PURPOSE: The purpose of the work is to choose a sedation method to improve the results of treatment of patients with polytrauma and alcohol withdrawal, based on the study of changes in carbohydrate metabolism indicator. MATERIALS AND METHODS: The paper analyzes the results of a study of 80 patients with polytrauma and chronic alcohol intoxication with a state of alcohol withdrawal, complicated by alcoholic delirium, who received intensive therapy in the 12-bed department of anesthesiology and intensive therapy for patients with combined trauma of the KNP «Kharkiv City Clinical Hospital of Emergency Medical Care¼ named after Prof. O. I. Meschaninov¼ KhMR. All patients were diagnosed with polytrauma (thoracic and/or abdominal trauma: rib fractures, hemo-, pneumothorax, hematomas of the liver or spleen, fracture of the bones of the waist, and/or upper and/or lower limbs, fracture of the pelvis). In the course of the research, to achieve the goal, the main indicators of carbohydrate metabolism were determined, which were evaluated by the content of key metabolites: glucose, pyruvic acid, lactate. The study was conducted on the 1st, 3rd and 7th day of hospitalization of the patients. RESULTS AND DISCUSSION: In all traumatized patients with alcohol withdrawal syndrome and alcoholic delirium with the use of dexmedetomidine for sedation (group 1) and in patients who were used as sedatives, diazepam and haloperidol (group 2), changes in these parameters were observed in the blood, compared to healthy people of the control group. As for the glucose content in the blood of the patients of the 1st group, on the first day, persistent hyperglycemia was observed in them 1.7 times higher than this indicator in healthy people. Next, patients' blood glucose levels were determined on the 3rd and 7th day after hospitalization. Glucose content on the 3rd day decreased by 9.4% compared to the level determined on the first day. On the 7th day, the content of glucose in the blood decreased to normal values, which is 26.5% lower compared to the content of glucose in the blood on the first day. In the 2nd group of patients, where diazepam and haloperidol were used on the first day, hyperglycemia was also observed - 1.9 times higher than this indicator in the control group of healthy individuals. On the third day, the level of glucose in the blood decreased by 6%. And on the 7th day, it decreased by 20.5%. Thus, hyperglycemia was observed in the blood of victims with alcohol withdrawal syndrome, complicated by delirium during hospitalization, on the 3rd day of hospitalization (first and second groups) and on the 7th day in patients of the second group, which indicates violation of carbohydrate metabolism and the development of hypoxia, with impaired liver and pancreas function. In accordance with the aim and objectives of the study, the blood content of the main metabolites of glucose metabolism - pyruvate and lactate - was also studied upon admission to the hospital and one week after treatment, which made it possible to comprehensively assess possible carbohydrate metabolism disorders and characterize the features of the body's energy supply in the combination of polytrauma and withdrawal alcohol, complicated by alcoholic delirium. According to the results of the research, there is an increase in the content of lactate and pyruvate in patients with polytrauma against the background of chronic alcoholism compared to healthy people. When analyzing the content of lactate in the blood of patients with polytrauma and alcohol withdrawal syndrome, complicated by alcoholic delirium upon admission to the intensive care unit, a significant increase of this indicator was observed by 97.1% and 113.0%, respectively, in patients of the first and second groups. One week after the intensive therapy, the patients of the 1st group had a significant decrease in the lactate content in the blood - by 13% (Р<0.0001) compared to the content of this indicator at the time of admission to the hospital. In the blood of the patients of the 2nd group, on the 7th day, the lactate content remained unchanged, and by 106.3% it exceeded this biochemical indicator in the blood of the control group. Hyperpyruvatemia was also observed - when entering the hospital in patients of the 2nd group, the content was 55.4% higher compared to healthy people, remained elevated after a week of treatment - by 30.1%, and did not return to normal values. In the patients of the first group, upon admission to the hospital, the pyruvate content in the blood was 53.0% higher compared to the control group, and on the 7th day it significantly decreased by 18.9%, but did not reach the values of the control group (remained at 24, 1% higher compared to the control). The cause of hyperpyruvatemia and hyperlactatemia in patients may also be a violation of their enzymatic transformation into decay products. Lactate is the final product of anaerobic oxidation of glucose, it is formed due to the transformation of pyruvate, under the conditions of action of the lactate dehydrogenase enzyme in conditions of hypoxia. An important indicator of the state of carbohydrate metabolism, namely the balance of anaerobic and aerobic processes in the body, is the lactate / pyruvate ratio, which in the control group was 14.33 [13.82; 14.49]. In the patients of the first group, an increase in this ratio was observed - and it was 18.46 [18.3; 20.59] and 19.81 [18.96; 21,17] upon admission to the intensive care unit and one week after treatment, respectively. Practically the same value of this ratio was observed in patients of the second group - 19.65 [18.97; 22.3] and 22.73 [21.32 23.91], respectively, according to the time of intensive therapy. The latest figures indicate the restructuring of the energy supply of body tissues during the stay of patients in the intensive care unit. CONCLUSIONS: Thus, in patients with polytrauma and alcohol withdrawal syndrome, complicated by alcoholic delirium, there is an intensification of the processes of anaerobic glycolysis, which is evidenced by an increase in the content of pyruvate, lactate, the lactate/pyruvate ratio, and is accompanied by a hypoxic state. When comparing the terms of stay in the intensive care unit, it was determined that the use of dexmedetomidine for the treatment of alcoholic delirium compared to benzodiazepines allows reducing the time of intensive care by 34 hours. Thus, in group 2, the duration of intensive therapy for alcoholic delirium was 89 [82-96.2] hours, while in group 1 it was reduced to 55 [52.2-59.8] (p=0.020427). In addition, it was found that the consumption of drugs by patients was different. During the first day, it was 20 [20-30] mg in group 1, and 40 [40-50] mg in group 2. The groups also differed significantly in terms of the total dose of the drug during intensive therapy, so in patients of group 1, the total consumption was 30 [30-40] mg, in group 2 - 80 [80-90] mg (p=0.033011).

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BACKGROUND: Emergence delirium (ED) is a common occurrence in pediatric postanesthesia events, leading to negative outcomes. Dexmedetomidine (DEX), as an anesthesia adjuvant, has shown promise in preventing ED in adult surgeries, and it has been increasingly used in pediatric surgical settings. However, its effectiveness in other postanesthesia events, such as MRI examinations and ambulatory surgery centers, remains unclear. This meta-analysis aims to assess the safety and efficacy of DEX in preventing ED in various pediatric postanesthesia events beyond surgery. METHODS: Prospective randomized controlled trials were searched in Pubmed, Web of Science, and EBSCO until October 13, 2023. Comparisons were made between DEX and other sedatives or analgesics in different postanesthesia events (including surgery operations, the examination of MRI, day surgery, and invasive action). Subgroup analyses were conducted based on drug delivery methods, medication timing, DEX dosages, use of analgesics, event types, and recovery time. RESULTS: A total of 33 trials involving 3395 patients were included. DEX significantly reduced the incidence of ED (odds ratios [OR] = 0.23, 95% confidence interval [CI]: 0.19-0.27, I2 = 37%, P < .00001). Intranasal delivery of DEX was the most effective (OR 0.18, 95% CI: 0.10-0.32, P < .00001, I2 = 0%). DEX also showed benefits in day surgery and mask insertion events (OR 0.30, 95% CI: 0.14-0.26, P = .001, I2 = 0%). CONCLUSION: DEX demonstrates superior efficacy in preventing ED in pediatric postanesthesia events compared to other sedatives and analgesics. Its use is recommended in various settings for its safety and effectiveness in managing ED.

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