Comparison of sedation with dexmedetomidine administered subcutaneously at 2 different locations on the head in dogs.

Objective: This study aimed to compare the sedative effects of dexmedetomidine administered to dogs subcutaneously (SC) at the Governing Vessel 20 (GV20) acupuncture point and at another point on the head. Animals and procedure: Ten client-owned dogs were included. Dogs were sedated 2 times, 14 d apart, with 200 µg/m2 of dexmedetomidine, SC, at GV20 and at a point at the base of the ear (SC-head). The sedation was assessed with a sedation scale and a Dynamic and Interactive Visual Analogue Scale (DIVAS). The ease of performing radiographic studies, physiological parameters, and adverse events were recorded. Statistical linear mixed-effect models (ANOVA) were applied. Statistical significance was set at P < 0.05. Results: The time to sedation and sedation scores were similar for both groups. The level of sedation achieved was adequate to perform orthopedic radiographs for 9/10 (90%) cases in the GV20 group and 8/10 (80%) cases in the SC-head group. Heart and respiratory rates decreased significantly over time in both groups (P < 0.001). Adverse events were infrequent and self-limiting. Conclusion: Our study provides evidence that SC administration of dexmedetomidine on the head, at the GV20 point or at the base of the ear, is easy and provides a sufficient level of sedation to obtain orthopedic radiographs in dogs.

Comparaison de la sédation avec de la dexmédétomidine administrée par voie sous-cutanée à deux sites différents sur la tête de chiens. Objectif: Cette étude a pour but de comparer les effets sédatifs de la dexmédétomidine administrée par voie sous-cutanée (SC) au point d'acupuncture VG20 et à un autre point sur la tête, non lié à la relaxation/sédation, chez le chien. Animaux et procédure: Dix chiens de clients ont été inclus dans cette étude clinique, prospective, croisée, randomisée et à l'aveugle. Les chiens ont été sédatés deux fois, à 14 jours d'intervalle, avec une injection de 200 µg/m2 de dexmédétomidine sous-cutanée au point d'acupuncture VG20 et à un autre point sur la tête, à la base de l'oreille (SC-tête). La durée et la qualité de la sédation ont été évaluées avec une échelle de sédation et une échelle analogue visuelle dynamique et interactive (DIVAS). La facilité de réaliser des études radiographiques, les paramètres physiologiques et les effets secondaires ont été enregistrés. Des modèles statistiques linéaires à effet mixte (ANOVA) ont été réalisés. Les résultats étaient considérés comme significatifs quand P < 0,05. Résultats: Le temps nécessaire pour atteindre un niveau de sédation adéquat et les scores de sédation étaient comparables entre les deux groupes. Le niveau de sédation était adéquat pour réaliser des radiographies orthopédiques chez 9/10 (90 %) des cas dans le groupe VG20 et 8/10 (80 %) des cas dans le groupe SC-tête. Les fréquences cardiaque et respiratoire diminuaient significativement dans le temps pour les 2 groupes (P < 0,001). Les effets indésirables étaient peu fréquents et auto-limitants. Conclusion: Notre étude suggère que l'administration sous-cutanée de dexmédétomidine sur la tête, que ce soit au point VG20 ou à la base de l'oreille, est facile et permet d'obtenir un niveau de sédation suffisant pour réaliser des radiographies orthopédiques chez des chiens sains.(Traduit par les auteurs).

Mechanism of dexmedetomidine protection against cisplatin induced acute kidney injury in rats.

OBJECTIVE: This study explored the molecular mechanisms by which dexmedetomidine (Dex) alleviates cisplatin (CP)-induced acute kidney injury (AKI) in rats. METHODS: CP-induced AKI models were established, and Dex was intraperitoneally injected at different concentrations into rats in the model groups. Subsequently, rats were assigned to the control, CP, CP + Dex 10 µg/kg, and CP + Dex 25 µg/kg groups. After weighing the kidneys of the rats, the kidney arterial resistive index was calculated, and CP-induced AKI was evaluated. In addition, four serum biochemical indices were measured: histopathological damage in rat kidneys was detected; levels of inflammatory factors, interleukin (IL)-1ß, IL-18, IL-6, and tumor necrosis factor alpha, in kidney tissue homogenate of rats were assessed through enzyme-linked immunosorbent assay (ELISA); and levels of NLRP-3, caspase-1, cleaved caspase-1, gasdermin D (GSDMD), and GSDMD-N in kidney tissues of rats were determined via western blotting. RESULTS: Dex treatment reduced nephromegaly and serum clinical marker upregulation caused by CP-induced AKI. In addition, hematoxylin and eosin staining revealed that Dex treatment relieved CP-induced kidney tissue injury in AKI rats. ELISA analyses demonstrated that Dex treatment reduced the upregulated levels of proinflammatory cytokines in the kidney tissue of AKI rats induced by CP, thereby alleviating kidney tissue injury. Western blotting indicated that Dex alleviated CP-induced AKI by inhibiting pyroptosis mediated by NLRP-3 and caspase-1. CONCLUSION: Dex protected rats from CP-induced AKI, and the mechanism may be related to NLRP-3/Caspase-1-mediated pyroptosis.

The Safety and Efficacy of Remimazolam Compared to Dexmedetomidine for Awake Tracheal Intubation by Flexible Bronchoscopy: A Randomized, Double-Blind, Controlled Trial.

Background: Remimazolam is a novel ultra-short-acting benzodiazepine sedative that has the potential to be an alternative for procedural sedation due to its rapid sedation and recovery, no accumulation effect, stable hemodynamics, minimal respiratory depression, anterograde amnesia effect, and specific antagonist. Here, we aimed to compare the safety and efficacy of remimazolam with dexmedetomidine for awake tracheal intubation by flexible bronchoscopy (ATI-FB). Methods: Ninety patients scheduled for ATI-FB were randomly divided into three groups, each consisting of 30 cases: dexmedetomidine 0.6 µg/kg + sufentanil (group DS), remimazolam 0.073 mg/kg + sufentanil (group R1S), or remimazolam 0.093 mg/kg + sufentanil (group R2S). The primary outcome was the success rate of sedation. Secondary outcomes were MOAA/S scores, hemodynamic and respiratory parameters, intubation conditions, intubation time, tracheal intubation amnesia, and adverse events. Results: The success rates of sedation in groups R2S and DS were higher than that in group R1S (93.3%, 86.7%, respectively, vs 58.6%; P = 0.002), and intubation conditions were better than those in group R1S (P < 0.05). Group R2S had shorter intubation times than groups R1S and DS (P = 0.003), and a higher incidence of tracheal intubation amnesia than group DS (P = 0.006). No patient in the three groups developed hypoxemia or hypotension, and there were no significant differences in oligopnea, PetCO2, or bradycardia (P > 0.05). Conclusion: In conclusion, both DS and R2S had higher success rates of sedation, better intubation conditions, and minor respiratory depression, but R2S, with its shorter intubation time, higher incidence of anterograde amnesia, and ability to be antagonized by specific antagonists, may be a good alternative sedation regimen for patients undergoing ATI-FB.

Effect of Postoperative Prolonged sedation with Dexmedetomidine after successful reperfusion with Endovascular Thrombectomy on long-term prognosis in patients with acute ischemic stroke (PPDET): study protocol for a randomized controlled trial.

BACKGROUND: Endovascular thrombectomy (EVT) is a standard treatment for acute ischemic stroke (AIS) with large vessel occlusion. Hypertension and increased blood pressure variability within the first 24 h after successful reperfusion are related to a higher risk of symptomatic intracerebral hemorrhage and higher mortality. AIS patients might suffer from ischemia-reperfusion injury following reperfusion, especially within 24 h. Dexmedetomidine (DEX), a sedative commonly used in EVT, can stabilize hemodynamics by inhibiting the sympathetic nervous system and alleviate ischemia-reperfusion injury through anti-inflammatory and antioxidative properties. Postoperative prolonged sedation for 24 h with DEX might be a potential pharmacological approach to improve long-term prognosis after EVT. METHODS: This single-center, open-label, prospective, randomized controlled trial will include 368 patients. The ethics committee has approved the protocol. After successful reperfusion (modified thrombolysis in cerebral infarction scores 2b-3, indicating reperfusion of at least 50% of the affected vascular territory), participants are randomly assigned to the intervention or control group. In the intervention group, participants will receive 0.1~1.0 µg/kg/h DEX for 24 h. In the control group, participants will receive an equal dose of saline for 24 h. The primary outcome is the functional outcome at 90 days, measured with the categorical scale of the modified Rankin Scale, ranging from 0 (no symptoms) to 6 (death). The secondary outcome includes (1) the changes in stroke severity between admission and 24 h and 7 days after EVT, measured by the National Institute of Health Stroke Scale (ranging from 0 to 42, with higher scores indicating greater severity); (2) the changes in ischemic penumbra volume/infarct volume between admission and 7 days after EVT, measured by neuroimaging scan; (3) the length of ICU/hospital stay; and (4) adverse events and the all-cause mortality rate at 90 days. DISCUSSION: This randomized clinical trial is expected to verify the hypothesis that postoperative prolonged sedation with DEX after successful reperfusion may promote the long-term prognosis of patients with AIS and may reduce the related socio-economic burden. TRIAL REGISTRATION: ClinicalTrials.gov NCT04916197. Prospectively registered on 7 June 2021.

[Pediatric procedural sedation: a new protocol implemented]. / Implémentation d'un nouveau protocole pour la sédation procédurale pédiatrique.

Pediatric procedural sedation is a difficult exercise aiming to find the balance between optimal quality of a medical imaging or act, and maximal reduction of risks for the patient. Harmlessness of chloral hydrate has been recently questioned, thus promoting the use of the dexmedetomidine for these kinds of procedures. In this context we decided to develop a new protocol at the CHUV. We tested different combinations of molecules until we found the best association and dosage. We present here the analysis of our patient cohort, attesting the efficiency, reliability, and safety of combined dexmedetomidine and midazolam given intranasal for pediatric MRI.

La sédation procédurale pédiatrique représente un défi pour garantir la qualité optimale d'un examen ou d'un acte médical tout en assurant la sécurité maximale du patient. Comme l'innocuité de l'hydrate de chloral semble être remise en question, la communauté médicale se dirige de plus en plus vers l'usage intranasal de la dexmédétomidine pour les sédations. Dans ce contexte, nous avons élaboré un nouveau protocole au CHUV, après avoir testé différentes combinaisons médicamenteuses dans le cadre d'examen d'imagerie (IRM). Sur la base de nos résultats, il semble que l'efficacité, la fiabilité et la sécurité de la combinaison de dexmédétomidine et de midazolam par voie intranasale soient très satisfaisantes.

Effect of Dexmedetomidine on Intraoperative Hemodynamics and Blood Loss in Patients Undergoing Spine Surgery: A Systematic Review and Meta-Analysis.

Objective 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.Methods 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).Conclusions 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.

Safety and efficacy of dexmedetomidine vs. midazolam in complex gastrointestinal endoscopy: A systematic review and meta-analysis.

OBJECTIVE: This study aims to perform a meta-analysis to evaluate the safety and efficacy of dexmedetomidine versus midazolam for complex digestive endoscopy procedures, with the goal of offering comprehensive clinical evidence. METHODS: Following predefined inclusion criteria, five databases were systematically searched, with a focus on identifying randomized controlled trials (RCTs) that compared the administration of dexmedetomidine and midazolam during complex digestive endoscopy procedures. The statistical software Stata 15.1 was employed for meticulous data analysis. RESULTS: Sixteen RCTs were encompassed, involving a total of 1218 patients. In comparison to the midazolam group, dexmedetomidine administration was associated with a reduced risk of respiratory depression (RR=0.25, 95 %CI: 0.11-0.56) and hypoxemia (RR=0.22, 95 %CI: 0.12-0.39). Additionally, the dexmedetomidine group exhibited lower incidence rates of choking (RR=0.27, 95 %CI: 0.16-0.47), physical movement (RR=0.16, 95 %CI: 0.09-0.27), and postoperative nausea and vomiting (RR=0.56,95 %CI: 0.34-0.92). Patients and endoscopists in the dexmedetomidine group reported higher levels of satisfaction (patient satisfaction: SMD=0.73, 95 %CI: 0.26-1.21; endoscopist satisfaction: SMD=0.84, 95 %CI: 0.24-1.44). The incidence of hypotension and anesthesia recovery time did not significantly differ between the two groups (hypotension: RR=1.73,95 %CI:0.94-3.20; anesthesia recovery time: SMD=0.02, 95 %Cl: 0.44-0.49). It is noteworthy that the administration of dexmedetomidine was associated with a significant increase in the incidence of bradycardia in patients. CONCLUSION: Compared to midazolam, dexmedetomidine exhibits a favorable safety profile for use in complex gastrointestinal endoscopy by significantly reducing the risk of respiratory depression and hypoxemia. Despite this, dexmedetomidine is associated with a higher incidence of bradycardia. These findings underscore the need for further research through larger, multi-center studies to thoroughly investigate dexmedetomidine's safety and efficacy.

Retrospective Analysis of Perioperative Dexmedetomidine Use in Retina Surgeries: Impact on Postanesthesia Care.

BACKGROUND AND OBJECTIVE: Dexmedetomidine (Precedex®) has been linked to depressive hemodynamic effects and increased length of stay in the post-anesthesia care unit (PACU) when used in ambulatory phacoemulsification procedures. We aimed to determine the prevalence and impact of dexmedetomidine use during ambulatory vitreoretinal procedures. PATIENTS AND METHODS: This retrospective cohort study involved 9,666 adult vitrectomies. Cases were divided into groups by anesthesia type: general anesthesia (GA) and monitored anesthesia care (MAC). For each group, various factors were compared between those who did and did not receive dexmedetomidine. Chi-squared and t tests were used for comparisons. RESULTS: Changes in mean arterial pressure in the MAC group were -1.69 ± 0.23 mmHg for no dexmedetomidine patients and -6.31 ± 0.39 mmHg for dexmedetomidine patients (P < 0.01). In the GA group, mean arterial pressure was -6.1 ± 0.35 mmHg for no dexmedetomidine patients and -11.18 ± 0.88 mmHg for dexmedetomidine patients (P < 0.01). PACU Phase II time in the MAC group was 36.93 ± 0.37 minutes and 40.67 ± 0.86 minutes for no dexmedetomidine and dexmedetomidine patients, respectively (P < 0.01). In the GA group, PACU Phase II time was 58.63 ± 0.95 minutes and 65.19 ± 2.38 minutes for no dexmedetomidine and dexmedetomidine patients, respectively (P < 0.01). CONCLUSIONS: Dexmedetomidine use in vitrectomies was associated with significant PACU delays. These delays may stem from adverse hemodynamic effects. [Ophthalmic Surg Lasers Imaging Retina 2024;55:86-91.].

Safety and effcacy of remimazolam tosilate for sedation during combined spinal-epidural anesthesia for orthopedic procedures: a randomized controlled trial.

OBJECTIVE: The objective of this study was to assess the efficacy and safety of Remimazolam in the context of combined spinal-epidural anesthesia for sedation during orthopedic surgery. METHODS: This randomized controlled trial enrolled patients scheduled for orthopedic surgery under combined spinal-epidural anesthesia (N = 80), who were randomly allocated to receive either dexmedetomidine (Group-D) or remimazolam (Group-R). The target sedation range aimed for a Ramsay score of 2-5 or a BIS value of 60-80 to evaluate the effectiveness and safety of remimazolam during sedation. RESULTS: The time taken to achieve the desired level of sedation was significantly shorter in the remimazolam group compared to the dexmedetomidine group (3.69 ± 0.75 vs. 9.59 ± 1.03; P < 0.0001). Patients in the remimazolam group exhibited quicker recovery, fewer intraoperative adverse events, more consistent vital signs, and greater satisfaction at various time points throughout the surgery. CONCLUSION: This preliminary study demonstrates that remimazolam tosilate serves as a safe and effective sedative for orthopedic surgery performed under combined spinal-epidural anesthesia, in comparison with dexmedetomidine.

Comparison of the effect of dexmedetomidine intrathecal injection and intravenous infusion on subarachnoid blockade during knee arthroscopy procedures: a randomized controlled trial.

BACKGROUND: Comparison of whether intrathecal dexmedetomidine prolongs spinal anesthesia-associated sensorimotor blockade more than intravenous infusion during knee arthroscopy procedures performed under subarachnoid blockade. METHODS: Ninety patients aged 18-75 years, ASA class I-II, who underwent knee arthroscopy between October 2022 and April 2023 were randomized into intrathecal、intravenous and control groups.Subjects received three modes of administration: an intrathecal group (2 ml of 1% ropivacaine + 1 ml of 5 µg dexmedetomidine, along with intravenous saline infusion), an intravenous group (intrathecal 2 ml of 1% ropivacaine + 1 ml of 0.9% saline, with dexmedetomidine pumped intravenously at a dose of 0.5 µg/kg/h), and a control group (intrathecal 2 ml of 1% ropivacaine + 1 ml of 0.9% saline, along with intravenous saline infusion). Total analgesic duration, duration of sensory and motor blockade, Ramsay sedation score, Visual Analogue Score (VAS) at different postoperative time points, and occurrence of adverse effects were recorded. RESULTS: The total analgesia duration was significantly longer in the intrathecal group than in the intravenous and control groups (352.13 ± 51.70 min VS 273.47 ± 62.57 min VS 241.41 ± 59.22 min, P < 0.001).The onset of sensory block was shorter in the intrathecal group than in the intravenous and control groups (4 [3-4]min VS 5 [4-5]min VS 5 [4-5]min; P < 0.001);the onset of motor block was shorter in the intrathecal group than in the intravenous group and the control group (5 [4-5]min VS 5 [5-6]min VS 6[5.5-7]min; P < 0.001).Sedation scores were higher in the intravenous group than in the intrathecal and control groups (P < 0.001). At 5 h postoperatively, the VAS score in the intrathecal group was lower than that in the intravenous and control groups (P < 0.001). At 24 h postoperatively, the VAS score in the intrathecal group was lower than that in the control group (P < 0.001). In addition, the incidence of bradycardia was significantly higher in the intravenous group than in the intrathecal and control groups (30%, 6.5%, and 3.4%, respectively; P = 0.018, P = 0.007). CONCLUSIONS: Intrathecal administration of dexmedetomidine did prolong the total analgesia duration, as well as accelerate the onset of sensory-motor blockade compared with intravenous infusion, and did not result in any hemodynamic instability or other adverse events at the doses studied. TRIAL REGISTRATION: This single-center, prospective, RCT has completed the registration of the Chinese Clinical Trial Center at 26/09/2023 with the registration number ChiCTR2300076170.

Effects of dexmedetomidine combined with etomidate on postoperative cognitive function in older patients undergoing total intravenous anaesthesia: a randomized, double-blind, controlled trial.

BACKGROUND: Etomidate has been advocated for anesthesia in older and critically ill patients because of its hemodynamic stability. Clinical studies have shown that dexmedetomidine has neuroprotective and anti-inflammatory properties and improves postoperative cognitive dysfunction in older patients. The present study was to evaluate the effects of the combination of etomidate and dexmedetomidine with different anaesthesia time on postoperative cognitive function in older patients. METHODS: A total of 132 older patients undergoing ureteroscopic holmium laser lithotripsy were randomly divided into EN group and ED group equally. Patients whose surgery time was less than or equal to 1 h in each group were allocated to short-time surgery group (EN1 group and ED1 group), and whose surgery time was more than 1h were allocated to long-term surgery group (EN2 group and ED2 group). The primary outcome was the score of the Mini-Mental State Examination. The secondary outcomes were State-Trait Anxiety Inventory scores, Riker sedation agitation scores, Zung Self-Rating Depression Scale scores, the memory span for Arabic numerals, the plasma concentrations of S-100 calcium-binding protein B and neuron specific enolase, the time to spontaneous respiration, recovery, and extubation. RESULTS: The MMSE scores at t2-3 were higher in ED1 and ED2 groups than in EN1 and EN2 groups (p<0.05). Compared with ED1 and ED2 groups, the ZSDS scores, the S-AI scores and the T-AI scores at t1-2 were higher in EN1 and EN2 groups (p<0.05), respectively. The recalled Arabic numbers at t1-3 were higher in ED2 group than in EN2 group (p<0.05). The plasma concentration of S-100ß at t1-2 in EN1 group and t1-3 in EN2 group were higher than that in ED1 and ED2 groups (p<0.05), respectively. Compared with ED1 and ED2 groups, the plasma concentrations of NSE were higher at t1-3 in EN1 group and t1-4 in EN2 group (p<0.05), respectively. CONCLUSION: The administration of dexmedetomidine could improve postoperative cognitive dysfunction, emergence agitation, depression and anxiety, attenuate the plasma concentrations of S-100ß and NSE in older patients undergoing total intravenous anaesthesia with etomidate. TRIAL REGISTRATION: Registration number: ChiCTR1800015421, Date: 29/03/2018.

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

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

Comparison of dexmedetomidine and opioids as local anesthetic adjuvants in patient controlled epidural analgesia: a meta-analysis.

BACKGROUND: Data on the efficacy and incidence of adverse effects associated with dexmedetomidine (DEX) as a local anesthetic adjuvant for patient-controlled epidural analgesia (PCEA) are inconclusive. This meta-analysis assessed the efficacy and risks of DEX for PCEA using opioids as a reference. METHODS: Two researchers independently searched PubMed, Embase, Cochrane Library, and China Biology Medicine for randomized controlled trials comparing DEX and opioids as local anesthetic adjuvants in PCEA. RESULTS: In total, 636 patients from seven studies were included in this meta-analysis. Postoperative patients who received DEX had lower visual analog scale (VAS) scores than those who received opioids at 4-8 h (mean difference [MD]: 0.61, 95% CI [0.45, 0.76], P < 0.001, I2 = 0%), 12 h (MD: 0.85, 95% CI [0.61, 1.09], P < 0.001, I2 = 0%), 24 h (MD: 0.59, 95% CI [0.06, 1.12], P = 0.030, I2 = 82%), and 48 h (MD: 0.54, 95% CI [0.05, 1.02], P = 0.030, I2 = 91%). Additionally, patients who received DEX had a lower incidence of itching (odds ratio [OR]: 2.86, 95% CI [1.18, 6.95], P = 0.020, I2 = 0%) and nausea and vomiting (OR: 6.83, 95% CI [3.63, 12.84], P < 0.001, I2 = 24%). In labor analgesia, no significant differences in neonatal (pH and PaO2 of cord blood, fetal heart rate) or maternal outcomes (duration of labor stage, mode of delivery) were found between the DEX and opioid groups. CONCLUSIONS: Compared with opioids, using DEX as a local anesthetic adjuvant in PCEA improved postoperative analgesia and reduced the incidence of itching and nausea and vomiting without increasing the incidence of adverse events.

Comparison of remimazolam and dexmedetomidine for intraoperative sedation in patients undergoing lower extremity surgery under spinal anesthesia: a randomized clinical trial.

BACKGROUND: Dexmedetomidine sedation has advantages, such as low incidence of respiratory depression and prolonged block duration, but also significant disadvantages, such as slow onset, high rate of sedation failure, and a long context-sensitive half-life. Remimazolam provides rapid sedation and recovery, high sedation efficacy and has minimal hemodynamic effects. We hypothesized that patients who received remimazolam would require less rescue midazolam than dexmedetomidine. METHODS: Patients (n=103) scheduled for surgery under spinal anesthesia were randomized to receive dexmedetomidine (DEX group) or remimazolam (RMZ group) targeting a Modified Observer's Assessment of Alertness/Sedation score of 3 or 4. Rescue midazolam was administered if the patient failed to be sedated after the initial loading dose or despite infusion rate adjustment. RESULTS: Rescue midazolam administration was significantly higher in the DEX group (0% vs 39.2%; p<0.001). Patients in the RMZ group reached the target sedation level more rapidly. The incidences of bradycardia (0% vs 25.5%; p<0.001) and hypertension (0% vs 21.6%; p<0.001) were higher in the DEX group. Respiratory depression occurred at a higher rate in the RMZ group (21.2% vs 2.0%; p=0.002), but no patients required manual ventilation. Patients in the RMZ group recovered faster, had a shorter PACU stay and higher satisfaction scores. Hypotensive episodes in the PACU were more frequent in the DEX group (1.9% vs 29.4%; p<0.001). CONCLUSIONS: Remimazolam showed excellent sedation efficacy, minimal hemodynamic effects, and fewer adverse events in the PACU than dexmedetomidine. However, it is important to note that respiratory depression was more frequent with the use of remimazolam. TRIAL REGISTRATION NUMBER: NCT05447507.

Dexmedetomidine improves pulmonary outcomes in thoracic surgery under one-lung ventilation: A meta-analysis.

INTRODUCTION: Dexmedetomidine improves intrapulmonary shunt in thoracic surgery and minimizes inflammatory response during one-lung ventilation (OLV). However, it is unclear whether such benefits translate into less postoperative pulmonary complications (PPCs). Our objective was to determine the impact of dexmedetomidine on the incidence of PPCs after thoracic surgery. METHODS: Major databases were used to identify randomized trials that compared dexmedetomidine versus placebo during thoracic surgery in terms of PPCs. Our primary outcome was atelectasis within 7 days after surgery. Other specific PPCs included hypoxemia, pneumonia, and acute respiratory distress syndrome (ARDS). Secondary outcome included intraoperative respiratory mechanics (respiratory compliance [Cdyn]) and postoperative lung function (forced expiratory volume [FEV1]). Random effects models were used to estimate odds ratios (OR). RESULTS: Twelve randomized trials, including 365 patients in the dexmedetomidine group and 359 in the placebo group, were analyzed in this meta-analysis. Patients in the dexmedetomidine group were less likely to develop postoperative atelectasis (2.3% vs 6.8%, OR 0.42, 95%CI 0.18-0.95, P = 0.04; low certainty) and hypoxemia (3.4% vs 11.7%, OR 0.26, 95%CI 0.10-0.68, P = 0.01; moderate certainty) compared to the placebo group. The incidence of postoperative pneumonia (3.2% vs 5.8%, OR 0.57, 95%CI 0.25-1.26, P = 0.17; moderate certainty) or ARDS (0.9% vs 3.5%, OR 0.39, 95%CI 0.07-2.08, P = 0.27; moderate certainty) was comparable between groups. Both intraoperative Cdyn and postoperative FEV1 were higher among patients that received dexmedetomidine with a mean difference of 4.42 mL/cmH2O (95%CI 3.13-5.72) and 0.27 L (95%CI 0.12-0.41), respectively. CONCLUSION: Dexmedetomidine administration during thoracic surgery may potentially reduce the risk of postoperative atelectasis and hypoxemia. However, current evidence is insufficient to demonstrate an effect on pneumonia or ARDS.

Efficacy and safety of dexmedetomidine for analgesia and sedation in neonates: a systematic review.

Opioids and benzodiazepines have historically been employed for pain relief; however, they are associated with detrimental long-term neurodevelopmental consequences. Dexmedetomidine, a highly selective alpha-2-adrenoreceptor agonist, has piqued interest as a viable alternative for neonates, owing to its potential analgesic and neuroprotective attributes. We conducted a systematic review to assess the efficacy and safety of dexmedetomidine utilization in neonates. We conducted a comprehensive search of Ovid, MEDLINE, EMBASE, PubMed, Cochrane, and CINAHL, spanning from January 2010 to September 2022. Our review encompassed six studies involving 252 neonates. Overall, dexmedetomidine may be effective in achieving sedation and analgesia. Furthermore, it may reduce the need for adjunctive sedation or analgesia, shorten the time to extubation, decrease the duration of mechanical ventilation, and accelerate the attainment of full enteral feeds. Notably, no significant adverse effects associated with dexmedetomidine were reported. Nevertheless, additional well-designed studies to establish both the efficacy and safety of dexmedetomidine in neonatal care are needed.

The effect of age on outpatient pediatric procedural sedation with intranasal dexmedetomidine and oral midazolam.

Procedural sedation for diagnostic examination is a common practice in children. The study aims to analyze the sedative effect and safety of intranasal dexmedetomidine combined with oral midazolam in outpatient pediatric procedural sedation across different age groups and to assess the incidence of sedation failure. From February 2021 to September 2021, children who underwent procedural sedation were retrospectively enrolled. The children were divided into 4 groups based on age: the infant group (0 to 1 year old), toddler group (1 to 3 years old), preschool group (3 to 6 years old), and school-age group (6 to 12 years old). Two-mcg/kg intranasal dexmedetomidine and 0.5-mg/kg oral midazolam were used for sedation. The sedation success rate after rescue, sedation success rate, onset time of sedation, and the sedation time were recorded. The incidence of adverse events and the risk factors for sedation failure were also analyzed. A total of 4758 patients were identified. After exclusion, 3149 patients were ultimately enrolled. The combination of 2-mcg/kg intranasal dexmedetomidine and 0.5-mg/kg oral midazolam resulted in a total success rate of 99.7% and a sedation success rate of 91.4%. The sedation success rate varied among the four groups: 90.2% in the infant group, 93.1% in the toddler group, 92.7% in the preschool group, and 78.4% in the school-age group. The sedation success rate was significantly lower in the school-age group compared to the other three groups (P < 0.001). The onset time of sedation was shorter in infant (22 min, IQR: 18-28 min, P < 0.001) and longer in the school-age group (30 min, IQR: 25-35 min, P < 0.05). Additionally, the infants had a longer sedation time (110 min, IQR: 90-135 min, P < 0.001) and a higher rate of delayed recovery (27.5%, all P < 0.001). The incidence of adverse events was low (4.70%), which bradycardia (2.03%) being the most common. Age (0-1 year and > 6 years), weight, ASA class II, and history of failed sedation were identified as risk factors of sedation failure.   Conclusion: Intranasal administration of 2-mcg/kg dexmedetomidine combined with oral administration of 0.5-mg/kg midazolam was found to be efficient and safety for pediatric procedural sedation. Different age groups of children exhibited distinct sedation characteristics, and age was identified as a risk factor affecting the efficacy of sedation. What is Known: • Procedural sedation for diagnostic examination is a common practice in children. • The combination of dexmedetomidine with midazolam can improve sedative effects. What is New: • The success rate of sedation using a combination of 2-mcg/kg intranasal dexmedetomidine and 0.5-mg/kg oral midazolam was significantly lower in school-age children as compared to infants, toddlers, and preschoolers. • The onset time of sedation increased with age, and the sedation time was found to be longer in infant patients.

Intensive Care Unit Analgosedation After Cardiac Surgery in Children with Williams Syndrome : a Matched Case-Control Study.

OBJECTIVE: Cardiovascular abnormalities are common in patients with Williams syndrome and frequently require surgical intervention necessitating analgesia and sedation in a population with a unique neuropsychiatric profile, potentially increasing the risk of adverse cardiac events during the perioperative period. Despite this risk, the overall postoperative analgosedative requirements in patients with WS in the cardiac intensive care unit have not yet been investigated. Our primary aim was to examine the analgosedative requirement in patients with WS after cardiac surgery compared to a control group. Our secondary aim was to compare the frequency of major ACE and mortality between the two groups. DESIGN: Matched case-control study. SETTING: Pediatric CICU at a Tertiary Children's Hospital. PATIENTS: Patients with WS and age-matched controls who underwent cardiac surgery and were admitted to the CICU after cardiac surgery between July 2014 and January 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Postoperative outcomes and total doses of analgosedative medications were collected in the first six days after surgery for the study groups. Median age was 29.8 (12.4-70.8) months for WS and 23.5 (11.2-42.3) months for controls. Across all study intervals (48 h and first 6 postoperative days), there were no differences between groups in total doses of morphine equivalents (5.0 mg/kg vs 5.6 mg/kg, p = 0.7 and 8.2 mg/kg vs 10.0 mg/kg, p = 0.7), midazolam equivalents (1.8 mg/kg vs 1.5 mg/kg, p = 0.4 and 3.4 mg/kg vs 3.8 mg/kg, p = 0.4), or dexmedetomidine (20.5 mcg/kg vs 24.4 mcg/kg, p = 0.5 and 42.3 mcg/kg vs 39.1 mcg/kg, p = 0.3). There was no difference in frequency of major ACE or mortality. CONCLUSIONS: Patients with WS received similar analgosedative medication doses compared with controls. There was no significant difference in the frequency of major ACE (including cardiac arrest, extracorporeal membrane oxygenation, and surgical re-intervention) or mortality between the two groups, though these findings must be interpreted with caution. Further investigation is necessary to elucidate the adequacy of pain/sedation control, factors that might affect analgosedative needs in this unique population, and the impact on clinical outcomes.

Comparison of Two Dexmedetomidine Administration Strategies on the Incidence of Postoperative Respiratory Complications: A Retrospective, Inverse Probability of Treatment Weighted Study.

Randomized controlled trials have shown a higher risk of postoperative hypoxemia and delayed extubation with opioid-free anesthesia (OFA), compared with opioid anesthesia. The practice of OFA is not standardized. The objective of this study is to investigate the association between the dexmedetomidine administration protocol used and the occurrence of postoperative respiratory complications. This work is a retrospective, propensity score-adjusted study (inverse probability of treatment weighting) conducted between January 2019 and September 2021 in a French tertiary care university hospital, including 180 adult patients undergoing major digestive surgery. Comparison of 2 anesthesia protocols: with a continuous intravenous maintenance dose of dexmedetomidine following a bolus (group B+M, n = 105) or with a bolus dose alone (group B, n = 75). The main outcome measure was a composite respiratory end point within 24 hours of surgery. There was no significant difference in the incidence of overall respiratory complications, as assessed by the primary end point. Nevertheless, there were more patients with postoperative hypercapnia in group B+M than in group B (16% vs 2.5%, P = .004). Patients in group B+M were extubated later than patients in group B (group B+M, median 40 minutes, IQR 20-74 minutes; group B, median 20 minutes, IQR 10-50 minutes; P = .004). Our study showed negative results for the primary end point. However, data on the increased risk of postoperative hypercapnia in patients receiving a maintenance dose of dexmedetomidine are new. Other prospective randomized studies with greater power are necessary to confirm these data and to make OFA safer, by reducing the prescribed doses of dexmedetomidine.

The Influence of Dexmedetomidine as an Adjuvant in Intrathecal Labor Analgesia: A Multicenter Study on Efficacy and Maternal Satisfaction.

In this study, we examined the impact of dexmedetomidine (DEX) on the effectiveness of epidural analgesia and labor outcomes. We administered different doses of DEX combined with 0.1% ropivacaine for epidural analgesia to evaluate the clinical effects and safety. To assess the effects of different concentrations of DEX in parturient women receiving epidural analgesia, we conducted a randomized double-blind trial. We selected 400 parturient women and randomly assigned them to 4 groups, with 100 parturient women in each group: S0.1 (0.1 µg/mL DEX), S0.2 (0.2 µg/mL DEX), S0.3 (0.3 µg/mL DEX), and a control group (0.3 µg/mL sufentanil). Post-analgesia, we recorded the Bromage score, duration of labor, method of delivery, bleeding, neonatal Apgar score, adverse reactions, and maternal satisfaction. The number of patients with a Bromage score of ≥2 and the incidence of bradycardia were higher in the S0.3 group compared with the other 3 groups (P < .05), whereas the high satisfaction rate was lower in the S0.3 group (P < .05). Moreover, we found that the number of times that additional patient-controlled analgesia was administered was higher in the S0.1 group compared with the remaining 3 groups (P < .05). The control group exhibited a higher incidence of pruritus than the other 3 groups (P < .05). In conclusion, when administering spinal anesthesia for the relief of labor pain, epidural analgesia with 0.1% ropivacaine combined with 0.2 µg/mL DEX provides relatively ideal analgesic effects, higher maternal satisfaction, and reduces the incidence of pruritus, compared with the combination of 0.1% ropivacaine and 0.3 µg/mL sufentanil.