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).

Safety and efficacy of a low-dose combination of midazolam, alfentanil, and propofol for deep sedation of elderly patients undergoing ERCP.

BACKGROUND: Proper sedation of patients, particularly elderly individuals, who are more susceptible to sedation-related complications, is of significant importance in endoscopic retrograde cholangiopancreatography (ERCP). This study aims to assess the safety and efficacy of a low-dose combination of midazolam, alfentanil, and propofol for deep sedation in elderly patients undergoing ERCP, compared to a group of middle-aged patients. METHODS: The medical records of 610 patients with common bile duct stones who underwent elective ERCP under deep sedation with a three-drug regimen, including midazolam, alfentanil, and propofol at Shandong Provincial Third Hospital from January 2023 to September 2023 were retrospectively reviewed in this study. Patients were categorized into three groups: middle-aged (50-64 years, n = 202), elderly (65-79 years, n = 216), and very elderly (≥ 80 years, n = 192). Intraoperative vital signs and complications were compared among these groups. RESULTS: The three groups showed no significant difference in terms of intraoperative variation of systolic blood pressure (P = 0.291), diastolic blood pressure (P = 0.737), heart rate (P = 0.107), peripheral oxygen saturation (P = 0.188), bispectral index (P = 0.158), and the occurrence of sedation-related adverse events including hypotension (P = 0.170) and hypoxemia (P = 0.423). CONCLUSION: The results suggest that a low-dose three-drug regimen consisting of midazolam, alfentanil, and propofol seems safe and effective for deep sedation of elderly and very elderly patients undergoing ERCP procedures. However, further studies are required to verify these findings and clarify the benefits and risks of this method.

Pharmacological Investigation of Hypoalbuminemia on the Prolonged and Potentiated Action of Midazolam in Rats.

Midazolam (MDZ) is clinically used for its sedative and anticonvulsant properties. However, its prolonged or potentiated effects are sometimes concerning. The main binding protein of MDZ is albumin, and reduced serum albumin levels could lead to MDZ accumulation, thereby potentiating or prolonging its effects. Previous investigations have not thoroughly examined these phenomena from a behavioral pharmacology standpoint. Consequently, this study aimed to evaluate both the prolonged and potentiated effects of MDZ, as well as the effects of serum albumin levels on the action of MDZ in low-albumin rats. Male Wistar rats were classified into control (20% protein diet), low-protein (5% protein), and non-protein groups (0% protein diet) and were fed the protein-controlled diets for 30 d to obtain low-albumin rats. The locomotor activity and muscle relaxant effects of MDZ were evaluated using the rotarod, grip strength, and open-field tests conducted 10, 60, and 120 min after MDZ administration. Serum albumin levels decreased significantly in the low-protein and non-protein diet groups compared with those in the control group. Compared with the control rats, low-albumin rats demonstrated a significantly shorter time to fall, decreased muscle strength, and a significant decrease in the distance traveled after MDZ administration in the rotarod, grip strength, and open-field tests, respectively. Decreased serum albumin levels potentiated and prolonged the effects of MDZ. Hence, serum albumin level is a critical parameter associated with MDZ administration, which should be monitored, and any side effects related to decreased albumin levels should be investigated.

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.

Zolpidem Stimulant Effect and Dependence: A Case Report on Intranasal Use.

Zolpidem is a widely used hypnotic. Dependence on zolpidem due to the induction of euphoria is a rare condition, while intranasal misuse of zolpidem is a rather new phenomenon. We present the first case of a patient who developed zolpidem dependence, which was associated with the prompt onset of euphoria exclusively following intranasal use. Mr. A was a 51-year-old polydrug abuser with antisocial personality disorder and a physical dependence on zolpidem. Over several years, he consumed 500 mg of the drug daily, usually divided into 30 mg doses, exclusively via the nasal route because unlike the oral administration of the same dose of the drug, intranasal administration induced euphoria. Euphoric effects manifested 3-5 minutes after taking the drug, and pronounced withdrawal symptoms (i.e., profuse sweating, tremors, nausea, vomiting, diarrhea, and inability to drink and eat), present 7-8 hours after the use could disappear within 3-5 minutes upon drug re-administration. The dependence was managed through a slow tapering of the zolpidem use. Clinicians should be aware that intranasal use of zolpidem could be associated with euphoric effects and the development of addiction. The potential for misuse of zolpidem via the nasal route may be of interest for future research.

[Simultaneous determination of six benzodiazepine sedatives residue in aquatic products by high performance liquid chromatography-triple quadrupole mass spectrometry].

OBJECTIVE: To establish a method for the simultaneous determination of 6 benzodiazepine sedatives residue in aquatic products by high performance liquid chromatography-triple quadrupole mass spectrometry. METHODS: The samples were extracted with acetonitrile and purified by C_(18 )solid phase extraction column. The sample solution was separated by Waters ACQUITY UPLC BEH C_(18 )column(2.1 mm×50 mm, 1.7 µm) using 0.1% formic acid and methanol as mobile phase for gradient elution, determined in multiple reaction monitoring mode and quantified by internal standard method. RESULTS: Six benzodiazepine sedatives had a good linear relationship in the range of 1.0-50.0 µg/L with r>0.9990, the limits of detection and limits of quantification were 0.3 and 1.0 µg/kg. Average recoveries for the analytes at 3 spiked levels ranged from 74.2%-108.0% with relative standard deviations of 1.1%-6.7%(n=6). CONCLUSION: The method is simple, rapid, sensitive and accurate, which is suitable for simultaneous determination of 6 benzodiazepine sedatives residue in aquatic products.

Safety profile of hypnotics or sedatives on community-dwelling older adults aged 75 or older in Japan: A retrospective propensity-matched cohort study.

OBJECTIVE: The purpose of the study is to assess if daily use of hypnotics increases mortality, aspiration pneumonia and hip fracture among relatively healthy individuals aged 75 years or older who lead independent lives in the community. METHOD AND PATIENTS: Of the adults aged 75 years or older residing in Hokkaido prefecture of Japan (n = 705,538), those who did not meet several exclusion criteria were eligible for generating propensity score-matched cohorts (n = 214,723). Exclusion criteria included co-prescribed medications acting on the central nervous system, diagnoses of malignant neoplasm, dementia, depression, etc. We compared 33,095 participants who were prescribed hypnotics for daily use (hypnotic group) with a propensity score-matched cohort without a prescription (control group). Participants were followed for more than 42 months. RESULTS: During the 42-month follow-up period, the incidence of the three outcome measures in the hypnotics group was significantly higher than that in the control group (aspiration pneumonia p < 0.001, hip fracture p = 0.007, and all-cause mortality p < 0.001). Sensitivity analyses utilizing inverse probability weighting demonstrated hazard ratios of 1.083 [1.023-1.146] for mortality, 1.117 [1.014-1.230] for aspiration pneumonia, and 1.720 [1.559-1.897] for hip fracture. Meanwhile, the attribute risk differences were 2.7, 1.5, and 1.0 per 1000 patient-years, respectively. CONCLUSIONS: Although daily use of hypnotics increased the risk of three events, their attribute risk differences were fewer than 3.0 per 1000 patient-years. The results will help provide guidance on whether it is reasonable to prescribe hypnotics to geriatric population aged 75 or older leading independent lives in the community. CLINICAL TRIAL REGISTRATION: UMIN-CTR UMIN000048398.

Utilization of antidepressants, anxiolytics, and hypnotics during the COVID-19 pandemic.

Since the onset of the COVID-19 pandemic, there have been concerns over the mental health impact of COVID-19. This is a review of the utilization of antidepressants, anxiolytics, and hypnotics since the COVID-19 pandemic was declared on March the 11th 2020. A number of reports so far have been based on large prescription databases for administrative use at the national or regional level, but mainly in high-income countries. We found studies reporting increased prescription rates of antidepressants, anxiolytics, and hypnotics during March 2020, which has been interpreted as hoarding of such medications. In the following months, most studies of antidepressant prescription rates did not display a clear pattern of change compared with prepandemic trends. In later phases of the pandemic small increases in utilization of antidepressants, with higher than predicted prescription rates, have been the most consistent finding, especially in youth. In most high-income countries, there were increasing trends in utilization of antidepressants also before 2020, which needs to be considered when estimating utilization during the pandemic, whereas for anxiolytics and hypnotics, the prepandemic patterns of prescriptions were more varying. Overall, after March 2020 we could not find any distinct changes in the utilization of anxiolytics and hypnotics during the COVID-19 pandemic. Most studies did not contain information about the prevalence of indicated psychiatric disorders in the studied populations. More studies are needed about the long-term effects of COVID-19, particularly regarding utilization of antidepressants. Research relating antidepressant utilization with the prevalence of major depression and anxiety disorders would promote a better understanding of how well antidepressant prescription rates reflect the needs of the population.

Palliative sedation - revised recommendations.

Palliative sedation is defined as the monitored use of medications intended to induce a state of decreased or absent awareness (unconsciousness) to relieve the burden of otherwise intractable suffering in a manner ethically acceptable to the patient, their family, and healthcare providers. In Switzerland, the prevalence of continuous deep sedation until death increased from 4.7% in 2001 to 17.5% of all deceased in 2013, depending on the research method used and on regional variations. Yet, these numbers may be overestimated due to a lack of understanding of the term "continuous deep sedation" by for example respondents of the questionnaire-based study. Inadequately trained and inexperienced healthcare professionals may incorrectly or inappropriately perform palliative sedation due to uncertainties regarding its definitions and practice. Therefore, the expert members of the Bigorio group and the authors of this manuscript believe that national recommendations should be published and made available to healthcare professionals to provide practical, terminological, and ethical guidance. The Bigorio group is the working group of the Swiss Palliative Care Society whose task is to publish clinical recommendations at a national level in Switzerland. These recommendations aim to provide guidance on the most critical questions and issues related to palliative sedation. The Swiss Society of Palliative Care (palliative.ch) mandated a writing board comprising four clinical experts (three physicians and one ethicist) and two national academic experts to revise the 2005 Bigorio guidelines. A first draft was created based on a narrative literature review, which was internally reviewed by five academic institutions (Lausanne, Geneva, Bern, Zürich, and Basel) and the heads of all working groups of the Swiss Society of Palliative Care before finalising the guidelines. The following themes are discussed regarding palliative sedation: (a) definitions and clinical aspects, (b) the decision-making process, (c) communication with patients and families, (d) patient monitoring, (e) pharmacological approaches, and (f) ethical and controversial issues. Palliative sedation must be practised with clinical and ethical accuracy and competence to avoid harm and ethically questionable use. Specialist palliative care teams should be consulted before initiating palliative sedation to avoid overlooking other potential treatment options for the patient's symptoms and suffering.

Apnea during moderate to deep sedation using continuous infusion of remimazolam compared to propofol and dexmedetomidine: A retrospective observational study.

Remimazolam's rapid onset and offset make it an innovative sedative for use during regional anesthesia. However, its respiratory safety profile is not well understood. We compared the continuous infusion of remimazolam with commonly used sedatives, propofol and dexmedetomidine, after regional anesthesia. In this retrospective study, the incidence of apnea (>10 seconds) was assessed in patients who underwent orthopedic surgery under regional anesthesia and received moderate to deep sedation using continuous infusion of remimazolam (group R: 0.1 mg/kg in 2 minutes followed by 0.5 mg/kg/hr). The incidence was compared with that of propofol (group P: 2-3 µg/mL target-controlled infusion) and dexmedetomidine (group D: 1 µg/kg in 10 minutes followed by 0.4-1 µg/kg/hr). Propensity score weighted multivariable logistic regression model was utilized to determine the effects of the sedative agents on the incidence of apnea. A total of 634 (191, 278, and 165 in group R, P, and D) cases were included in the final analysis. The incidence of apnea was 63.9%, 67.3%, and 48.5% in group R, P, and D, respectively. The adjusted odds ratios for apnea were 2.33 (95% CI, 1.50 to 3.61) and 2.50 (95% CI, 1.63 to 3.85) in group R and P, compared to group D. The incidence of apnea in patients receiving moderate to deep sedation using continuous infusion of remimazolam with dosage suggested in the current study was over 60%. Therefore, careful titration and respiratory monitoring is warranted.

Treatment Failure and Long-Term Prescription Risk for Guideline-Recommended Hypnotics in Japan.

Importance: Although insomnia guidelines recommend the use of several individual hypnotics, the most useful hypnotic for treating insomnia in a clinical setting remains unclear. Objective: To determine which guideline-recommended hypnotics have lower risks of monotherapy failure and which hypnotics have a higher risk of long-term prescription for insomnia treatment. Design, Setting, and Participants: This retrospective observational cohort study used data from the Japan Medical Data Center Claims Database from April 1, 2005, to March 31, 2021. Participants included adults whose first prescribed pharmaceutical treatment for insomnia was guideline-recommended hypnotic monotherapy. Data were analyzed from December 24, 2022, to September 26, 2023. Exposures: Suvorexant, ramelteon, eszopiclone, zolpidem, and triazolam monotherapy. Main Outcomes and Measures: The primary outcome was monotherapy failure, defined as a change in hypnotic or having an additional hypnotic prescribed for insomnia within 6 months of the first prescription of a guideline-recommended hypnotic monotherapy. The secondary outcome was monotherapy discontinuation, defined as no prescription of any hypnotic for 2 consecutive months within 6 months after prescribing a guideline-recommended hypnotic in patients for whom monotherapy did not fail. Monotherapy failure and discontinuation were compared using Cox proportional hazards and logistic regression models, respectively. Results: The study included 239 568 adults (median age, 45 [IQR, 34-55] years; 50.2% women) whose first prescription for insomnia was guideline-recommended hypnotic monotherapy. During the 6-month follow-up period, 24 778 patients (10.3%) experienced failure of monotherapy with a guideline-recommended hypnotic. In comparison with eszopiclone, there were more cases of monotherapy failure for ramelteon (adjusted hazard ratio [AHR], 1.23 [95% CI], 1.17-1.30; P < .001), fewer cases for zolpidem (AHR, 0.84 [95% CI, 0.81-0.87]; P < .001) and triazolam (AHR, 0.82 [95% CI, 0.78-0.87]; P < .001), and no significant difference between suvorexant and eszopiclone. Among those without monotherapy failure, monotherapy was discontinued in 84.6% of patients, with more discontinuations for ramelteon (adjusted odds ratio [AOR], 1.31 [95% CI, 1.24-1.40]; P < .001) and suvorexant (AOR, 1.20 [95% CI, 1.15-1.26]; P < .001) than for eszopiclone and no significant difference between zolpidem or triazolam and eszopiclone. Conclusions and Relevance: Due to uncontrolled confounding factors in this cohort study, no conclusions regarding the pharmacologic properties of guideline-recommended hypnotics can be drawn based on these results. Further studies accounting for confounding factors, including diagnoses of chronic vs acute insomnia disorder, insomnia and psychiatric symptom severity, and physician attitudes toward hypnotic prescription, are needed.

Optimizing patient outcomes: a comprehensive evaluation of protocolized sedation in intensive care settings: a systematic review and meta-analysis.

INTRODUCTION: Amidst the routine utilization of protocolized sedation in ventilated ICU patients, existing management guidelines exhibit a lack of unanimous recommendations for its widespread adoption. This study endeavors to comprehensively assess the effectiveness and safety of protocolized sedation in critically ill ventilated patients. OBJECTIVE: The primary objective of this study was to systematically review and conduct a meta-analysis of clinical trials comparing protocolized sedation with standard management in critically ill ventilated patients. Key outcomes under scrutiny include ICU and hospital mortality, ventilation days, duration of ICU stay, and incidents of self-extubation. The evaluation incorporates the Risk of Bias 2 (RoB2) tool to assess the quality of included studies. Data analysis utilizes a random-effects model for relative risk (RR) and mean differences. Subgroup analysis categorizes sedation protocols into algorithmic or daily interruption, addressing potential heterogeneity. Additionally, a GRADE evaluation is performed to ascertain the overall certainty of the evidence. RESULTS: From an initial pool of 1504 records, 10 studies met the inclusion criteria. Protocolized sedation demonstrated a reduced RR for mortality (RR: 0.80, 95% CI 0.68-0.93, p < 0.01, I2 = 0%) and a decrease in ventilation days (mean difference: - 1.12, 95% CI - 2.11 to - 0.14, p = 0.03, I2 = 84%). Furthermore, there was a notable reduction in ICU stay (mean difference: - 2.24, 95% CI - 3.59 to - 0.89, p < 0.01, I2 = 81%). However, incidents of self-extubation did not exhibit a significant difference (RR: 1.20, 95% CI 0.49-2.94, p = 0.69, I2 = 35%). Subgroup analyses effectively eliminated heterogeneity (I2 = 0%), and the GRADE evaluation yielded moderate results for mortality, ventilation days, and ICU duration. CONCLUSION: Protocolized sedation, whether implemented algorithmically or through daily interruption, emerges as a safe and effective approach when compared to standard management in ventilated ICU patients. The findings from this study contribute valuable insights to inform evidence-based practices in sedation management for this critical patient population.

Optimal flow of high-flow nasal cannula oxygenation to prevent desaturation during sedation for bronchoscopy: a randomized controlled study.

BACKGROUND: Although high-flow nasal cannula (HFNC) oxygenation is currently recommended to prevent desaturation during sedation for bronchoscopy, there is no consensus on an optimal flow rate. OBJECTIVE: To determine the optimal oxygen flow rate for HFNC to effectively prevent desaturation during sedation for bronchoscopy. DESIGN: Prospective, randomized, and controlled study. METHODS: Patients (n = 240) scheduled for bronchoscopy were randomized to receive HFNC with propofol sedation (fraction of inspired oxygen, 100%) at one of six flow rates of 10, 20, 30, 40, 50, and 60 L/min, designated as groups 1-6, respectively. RESULTS: The incidence of desaturation significantly decreased by increasing the oxygen flow rate (42.5%, 17.5%, 15%, 10%, 2.5%, and 0% for groups 1-6, respectively, p < 0.0001). The optimal oxygen flow rate for HFNC determined by probit regression to effectively prevent desaturation in 95% of patients was 43.20 (95% confidence interval, 36.43-55.96) L/min. The requirement for airway intervention was significantly decreased by increasing the oxygen flow rate. CONCLUSION: An HFNC flow rate of 50-60 L/min is recommended to prevent desaturation during sedation for bronchoscopy. REGISTRATION: NCT05298319 at ClinicalTrials.gov.

High-flow nasal cannula oxygenation during bronchoscopyMany patients undergo a special test to check their airways for problems. Sometimes, doctors need to take out a small part of the area that's causing trouble to find out what's wrong. But during this test, some patients can struggle to get enough oxygen, which can even be life-threatening. To help with this, there's a device called a high-flow nasal cannula (HFNC). It gives patients adjustable amounts of oxygen, like a gentle breeze into their nose. But doctors weren't sure how much oxygen was best during this test. So, we studied 240 patients using HFNC at different oxygen levels­like slow, medium, and fast flows. We found that the higher the oxygen flow, the less likely patients were to have oxygen problems. For example, at the lowest flow (10 liters per minute), about 42.5% of patients had oxygen trouble, but at the highest flow (60 liters per minute), none did. And we figured out that a flow rate around 43.2 liters per minute would prevent 95% patients from having oxygen problems. So, we recommend using a flow rate between 50 and 60 liters per minute during this test to keep patients safe from oxygen issues.

Clinical Application and Research Progress of Remimazolam for Pediatric Patients.

Remimazolam is a novel ultrashort-acting benzodiazepine that allosterically modulates γ-aminobutyric acid type A (GABAA) receptors to exert sedative effects. Remimazolam has the properties of controllable sedation, rapid onset, and a short duration of action, along with minor depression of circulation and respiration. Remimazolam has been approved for clinical use since 2020 in Japan, and it has been applied for procedural sedation, general anesthesia induction and maintenance, and sedation in ICU patients, and has been proven to be safe and effective. Currently, no consensus has been reached on the clinical application of remimazolam in pediatric patients. This review introduces the clinical research progress and limitations of remimazolam in recent years, aiming to supply scientific guidance and a theoretical reference for the application of remimazolam in pediatric anaesthesia.

Alpha 2 agonists for sedation to produce better outcomes from critical illness (A2B trial): protocol for a mixed-methods process evaluation of a randomised controlled trial.

INTRODUCTION: An association between deep sedation and adverse short-term outcomes has been demonstrated although this evidence has been inconsistent. The A2B (alpha-2 agonists for sedation in critical care) sedation trial is designed to determine whether the alpha-2 agonists clonidine and dexmedetomidine, compared with usual care, are clinically and cost-effective. The A2B intervention is a complex intervention conducted in 39 intensive care units (ICUs) in the UK. Multicentre organisational factors, variable cultures, perceptions and practices and the involvement of multiple members of the healthcare team add to the complexity of the A2B trial. From our pretrial contextual exploration it was apparent that routine practices such as type and frequency of pain, agitation and delirium assessment, as well as the common sedative agents used, varied widely across the UK. Anticipated challenges in implementing A2B focused on the impact of usual practice, perceptions of risk, ICU culture, structure and the presence of equipoise. Given this complexity, a process evaluation has been embedded in the A2B trial to uncover factors that could impact successful delivery and explore their impact on intervention delivery and interpretation of outcomes. METHODS AND ANALYSIS: This is a mixed-methods process evaluation guided by the A2B intervention logic model. It includes two phases of data collection conducted during and at the end of trial. Data will be collected using a combination of questionnaires, stakeholder interviews and routinely collected trial data. A framework approach will be used to analyse qualitative data with synthesis of data within and across the phases. The nature of the relationship between delivery of the A2B intervention and the trial primary and secondary outcomes will be explored. ETHICS AND DISSEMINATION: All elements of the A2B trial, including the process evaluation, are approved by Scotland A Research Ethics Committee (Ref. 18/SS/0085). Dissemination will be via publications, presentations and media engagement. TRIAL REGISTRATION NUMBER: NCT03653832.

Volatile versus propofol sedation after cardiac valve surgery: a single-center prospective randomized controlled trial.

BACKGROUND: Optimal intensive care of patients undergoing valve surgery is a complex balancing act between sedation for monitoring and timely postoperative awakening. It remains unclear, if these requirements can be fulfilled by volatile sedations in intensive care medicine in an efficient manner. Therefore, this study aimed to assess the time to extubation and secondary the workload required. METHODS: We conducted a prospective randomized single-center trial at a tertiary university hospital to evaluate the postoperative management of open valve surgery patients. The study was randomized with regard to the use of volatile sedation compared to propofol sedation. Sedation was discontinued 60 min after admission for critical postoperative monitoring. RESULTS: We observed a significantly earlier extubation (91 ± 39 min vs. 167 ± 77 min; p < 0.001), eye-opening (86 ± 28 min vs. 151 ± 71 min; p < 0.001) and command compliance (93 ± 38 min vs. 164 ± 75 min; p < 0.001) using volatile sedation, which in turn was associated with a significantly increased workload of a median of 9:56 min (± 4:16 min) set-up time. We did not observe any differences in complications. Cardiopulmonary bypass time did not differ between the groups 101 (IQR 81; 113) versus 112 (IQR 79; 136) minutes p = 0.36. CONCLUSIONS: Using volatile sedation is associated with few minutes additional workload in assembling and enables a significantly accelerated evaluation of vulnerable patient groups. Volatile sedation has considerable advantages and emerges as a safe sedation technique in our vulnerable study population. TRIAL REGISTRATION: Clinical trials registration (NCT04958668) was completed on 1 July 2021.

Effectiveness and safety of remimazolam combined with alfentanil in hysteroscopic examination: A prospective, randomized, single-blind trial.

BACKGROUND: Remimazolam is a novel, ultrashort-acting benzodiazepine. This study aimed to compare the efficacy and safety of remimazolam and propofol for hysteroscopic examination, to determine the optimal dose of remimazolam combined with alfentanil for painless hysteroscopy, and to calculate its median effective dose (ED50). METHODS: Step 1: A total of 208 patients undergoing hysteroscopic examination were prospectively included in this study. Patients were randomized into 4 groups: 0.2 mg/kg remimazolam (group A), 0.25 mg/kg remimazolam besylate (group B), 0.3 mg/kg remimazolam (group C), and 2 mg/kg propofol (group D), with 52 patients in each group. One minute after losing consciousness, patients received an intravenous injection of alfentanil at 5 µg/kg, followed by a continuous infusion of alfentanil at 0.5 µg/kg/min. If patients showed frowning, movement, or MOAA/S > 1, sedatives were added: 0.05 mg/kg/dose of remimazolam for groups A, B, and C, and 0.5 mg/kg/dose of propofol for group D. Step 2: Dixon's up-and-down method was used to calculate the ED50 of remimazolam combined with alfentanil during hysteroscopic examination. MAIN RESULTS: The sedation success rates of the remimazolam groups were 88.46%, 94.23%, and 98.08%, respectively, compared to 96.15% in the propofol group, with no significant difference (P = .175). MAP in groups A and B was higher than in group D (P < .05), and significantly higher in group C than in group D (P = .0016). SpO2 values in groups A, B, and C were higher than in group D at T2 to T3 (P < .001). HR in groups A, B, and C was significantly higher than in group D (P < .001). The ED50 of remimazolam combined with alfentanil in hysteroscopy was 0.244 mg/kg, 95%CI (0.195-0.22) and ED95 was 0.282 mg/kg, 95%CI (0.261-1.619). CONCLUSION: In hysteroscopy, the sedative effect of remimazolam is like that of propofol, with 0.25 mg/kg remimazolam showing better safety and efficacy, and less impact on the respiratory and circulatory systems. Additionally, under the influence of alfentanil, the ED50 of remimazolam in hysteroscopy is 0.244 mg/kg, with no severe adverse reactions observed.

Real-time ultrasound-guided sacral plexus block combined with mild sedation for hemorrhoidectomy and hemorrhoidal artery ligation in a patient with amyotrophic lateral sclerosis: a case report.

BACKGROUND: Patients with amyotrophic lateral sclerosis present perioperative challenges for clinical anesthesiologists for anesthesia-associated complications. CASE PRESENTATION: A 54-year-old Han woman with a 2-year history of amyotrophic lateral sclerosis was scheduled for hemorrhoidectomy and hemorrhoidal artery ligation. We performed real-time ultrasound-guided sacral plexus block with dexmedetomidine under standard monitoring. The anesthesia method met the surgical demands and avoided respiratory complications during the procedures. There was no neurological deterioration after the surgery and 3 months after, the patient was discharged. CONCLUSIONS: Real-time ultrasound-guided sacral plexus block combined with mild sedation may be an effective and safe technique in patients with amyotrophic lateral sclerosis undergoing hemorrhoidectomy and hemorrhoidal artery ligation.

COMPARISON OF THREE MIDAZOLAM-BASED SEDATION PROTOCOLS IN BUDGERIGARS (MELOPSITTACUS UNDULATUS) AND BLACK-CHEEKED LOVEBIRDS (AGAPORNIS NIGRIGENIS).

This randomized, crossover study evaluated three sedation protocols administered subcutaneously in nine budgerigars (Melopsittacus undulatus) and nine black-cheeked lovebirds (Agapornis nigrigenis). All protocols included midazolam (5 mg/kg), combined with butorphanol (5 mg/kg) (BM), medetomidine (20 lg/kg) (MM), or alfaxalone (13 mg/kg) (AM). Mortalities from suspected cardiorespiratory arrest were observed when AM was used in lovebirds, even after reduction of alfaxalone dosage to 3 mg/kg, and therefore this protocol was excluded from further use in this species. Induction and recovery times were recorded and their quality assessed. Sedation depth and heart and respiratory rates were measured every 5 min and radiographic positioning was attempted at 10 and 20 min. At 30 min, midazolam and medetomidine were reversed with flumazenil (0.05 mg/kg, SC), and atipamezole (0.2 mg/kg, SC), respectively. MM consistently provided deep sedation in both species, with successful radiographic positioning at every attempt. As expected, heart rate was often lower with MM than with other protocols, but no associated complications were noted. In budgerigars, BM had the lowest radiographic positioning success rate (10 min: 5/9, 20 min: 3/9), whereas in lovebirds it provided significantly deeper sedation (P < 0.001), allowing radiographic positioning in all subjects. In both species, BM provided the shortest recovery times. AM resulted in reliable radiographic positioning of all budgerigars at 10 min, but not at 20 min (5/ 9), and provided consistently poor recoveries. This study highlights how differently two psittacine species of similar size may react to the same sedation protocols. AM sedation cannot be fully reversed and produced significant undesirable effects, several of which have been previously reported with alfaxalone administration to avian species. The authors therefore caution against using alfaxalone-midazolam combinations in budgerigars and black-cheeked lovebirds. Both BM and MM provided reliable sedation in these species, and appear to be suitable alternatives to AM.