A prospective, open-label, randomized clinical trial to evaluate the efficacy and safety of remimazolam in patients undergoing EBUS-TBNA: REST trial design.

BACKGROUND: Remimazolam is safe and effective for moderate sedation during flexible bronchoscopy, but its safety and efficacy during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) remains undetermined. The REST trial (NCT06275594) will be a prospective randomized study of remimazolam in patients undergoing EBUS-TBNA with conscious sedation. The primary aim is to evaluate whether remimazolam is safe and effective for moderate sedation during EBUS-TBNA compared to real-world midazolam and on-label midazolam. METHODS: The REST trial will recruit 330 patients from four university hospitals with mediastinal lesions suspected of being lung cancer who are eligible for EBUS-TBNA under moderate sedation. The participants will be randomized into groups using remimazolam, real-world midazolam, and on-label midazolam (US prescribing information dosage) to perform EBUS-TBNA for procedural sedation. The primary endpoint will be procedural success using composite measures. DISCUSSION: The REST trial will prospectively evaluate the efficacy and safety of remimazolam during EBUS-TBNA under moderate sedation. It will provide information for optimizing sedation modalities and contribute to practical benefits in patients undergoing EBUS-TBNA. TRIAL REGISTRATION: ClinicalTrials.gov (NCT06275594). Prospectively registered on 15 February 2024.

Inhaled methoxyflurane - an explorable alternative to nitrous oxide?

Nitrous oxide is a widely used and well-established form of inhalation sedation in dentistry. Its properties have a wide margin of safety and allow for anxious, paediatric and adult patients to receive dental treatment with minimal impact upon discharge. Nitrous oxide has drawbacks, however, including its environmental impact and need for specialist equipment. Methoxyflurane is another drug which could prove to be an alternative to nitrous oxide. Methoxyflurane's use has proved popular within emergency medicine in Australia and New Zealand for its potent analgesic effects and recognition of its anxiolytic effect. As a result, its use in invasive outpatient procedures has now become popular. Unfortunately, there is very limited evidence of its use within dentistry as a form of inhalation sedation and analgesic. A wider evidence base should be established, as methoxyflurane could prove to be an effective and environmentally friendly alternative to nitrous oxide.

Intranasal dexmedetomidine for sedation in ABR testing in children: No pain, big gain!

OBJECTIVES: Obtaining perfect immobility or sleep in children undergoing ABR auditory brainstem response) testing can be challenging. We examined the effectiveness and safety of intranasal dexmedetomidine for sedation of children undergoing ABR testing. MATERIAL AND METHODS: We included prospectively all patients aged from 1 to 15 years for whom sedation for ABR testing was required, between July 2018 and November 2021. We administered an initial dose of 2.5 µg/kg intranasal dexmedetomidine with a repeat dose of 1 µg/kg if needed 30 min later. Collected data included success rate of sedation, sedation onset and recovery times and incidence of side effects. RESULTS: ABR testing was undertaken successfully in 57 of the 59 patients, giving a total success rate of 96,6 %. (95 % confidence interval 88.5 %-99.1 %). The median time to onset of sleep was 32 ± 18.3 min. The median duration of sedation recovery time was 48 ± 24.7 min. We recorded the adverse effects. Thirty-one patients experienced bradycardia and 28 patients experienced hypotension, all of which resolved without intervention. CONCLUSION: Intranasal dexmedetomidine is an effective, safe, simple of use and noninvasive method for sedation in children. It could have a major role in auditory brainstem response testing, specially in the case of non-cooperative children. REGISTRATION NUMBER OF THE TRIAL: NCT03530371.

A prospective, randomized, single-blinded study comparing the efficacy and safety of dexmedetomidine and propofol for sedation during endoscopic retrograde cholangiopancreatography.

BACKGROUND: Balanced propofol sedation is extensively used in endoscopic retrograde cholangiopancreatography (ERCP), but sedation-related adverse events (SRAEs) are common. In various clinical settings, the combination of dexmedetomidine with opioids and benzodiazepines has provided effective sedation with increased safety. The aim of this investigation was to compare the efficacy and safety of dexmedetomidine and propofol for sedation during ERCP. METHODS: Forty-one patients were randomly divided into two groups: the dexmedetomidine (DEX) group and the propofol (PRO) group. Patients in the DEX group received an additional bolus of 0.6 µg kg-1 dexmedetomidine followed by a dexmedetomidine infusion at 1.2 µg kg-1 h-1, whereas the PRO group received 1-2 mg kg-1 of propofol bolus followed by a propofol infusion at 2-3 mg kg-1 h-1. During ERCP, the primary outcome was the incidence of hypoxemia (SpO2 < 90% for > 10 s). Other intraoperative adverse events were also recorded as secondary outcomes, including respiratory depression (respiratory rate of < 10 bpm min-1), hypotension (MAP < 65 mmHg), and bradycardia (HR < 45 beats min-1). RESULTS: The incidence of hypoxemia was significantly reduced in the DEX group compared to the PRO group (0% versus 28.6%, respectively; P = 0.032). Patients in the PRO group exhibited respiratory depression more frequently than patients in the DEX group (35% versus 81%, respectively; P = 0.003). There were no significant differences in terms of hypotension and bradycardia episodes between groups. During the procedures, the satisfaction scores of endoscopists and patients, as well as the pain and procedure memory scores of patients were comparable between groups. CONCLUSION: In comparison with propofol, dexmedetomidine provided adequate sedation safety with no adverse effects on sedation efficacy during ERCP. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200061468, 25/06/2022.

Nontraditional approaches to sedation for anterior segment surgery: a narrative review.

PURPOSE OF REVIEW: Surgical and anesthetic technological advancement have made both cataract and noncataract anterior segment surgery significantly less invasive and time-intensive, facilitating the transition of some of these procedures from the operating room under monitored anesthesia care (MAC) to the office-based setting without MAC. This transition has been aided by the popularization of nonintravenous approaches to achieving patient sedation for these procedures. In this review, we discuss the literature surrounding traditional and nontraditional methods of achieving patient sedation for anterior segment surgery. RECENT FINDINGS: Our survey of the literature suggests that nonintravenous (IV) approaches to sedation for these procedures may be just as safe, effective, and satisfactory to patients as traditional IV approaches. SUMMARY: As anterior segment surgery becomes less invasive and less time-intensive, providers considering transitioning their cataract and anterior segment surgery out of the operating room and into the office-based setting without MAC anesthesia should consider the non-IV sedation options outlined in this review to achieve adequate patient sedation and comfort.

Effects of propofol, ketamine-propofol mixture in pediatric dental patients undergoing intravenous sedation: a clinical study.

This study aimed to evaluate the clinical effects, complications (peri- and postoperative), depth of sedation, recovery times, and changes in anxiety levels in paediatric dental patients receiving intravenous sedation with propofol and ketamine-propofol mixtures. This prospective clinical study included 69 healthy children (ASA 1) aged 3-7 years. The patients were assigned randomly to propofol group (n = 23), which received propofol; 1:3 ketofol group (n = 23), which received 1:3 ketofol; or 1:4 ketofol group (n = 23), which received 1:4 ketofol. The bispectral index (BIS) and Ramsay Sedation Scale (RSS) score were recorded at intervals of 5 min to measure the depth of sedation, and vital signs were evaluated. Peri- and postoperative complications and recovery times were recorded. Anxiety levels were also evaluated using the Facial Image Scale (FIS) and changes in saliva cortisol levels (SCLs) before and after the intravenous sedation procedure. The Kruskal‒Wallis test and Wilcoxon signed-rank test were used to determine pre- and posttreatment parameters. Dunn's test for post hoc analysis was used to determine the differences among groups. Children's pre- and posttreatment anxiety levels did not differ significantly according to FIS scores, and increases in SCLs were detected in 1:3 ketofol and 1:4 ketofol groups after dental treatment was completed. Compared with those in the other groups, the BIS values of the patients in 1:4 ketofol indicated a slightly lower depth of sedation. The recovery time of the patients in 1:3 ketofol was longer than that of patients in propofol and 1:4 ketofol. The incidence of postoperative complications (agitation, hypersalivation, nausea/vomiting, and diplopia) did not differ among the groups. Ketamine-propofol combinations provided effective sedation similar to that of propofol infusion without any serious complications during dental treatment performed under intravenous sedation. The ketofol infusion increased the anxiety level of paediatric dental patients to a greater extent than the propofol infusion.

Procedural sedation by advanced practice providers in the emergency medical service in the Netherlands: a retrospective study.

BACKGROUND: Procedural sedation and analgesia (PSA) is a technique of administering sedatives to induce a state that allows the patient to tolerate painful procedures while maintaining cardiorespiratory function, a condition that is frequently desired prehospital. Non-physician prehospital clinicians often have a limited scope of practice when it comes to providing analgesia and sedation; sometimes resulting in a crew request for back-up from physician-staffed prehospital services.". This is also the case if sedation is desirable. Advanced practice providers (APPs), who are legally authorized and trained to carry out this procedure, may be a solution when the physician-staffed service is not available or will not be available in time. METHODS: The aim of this study is to gain insight in the circumstances in which an APP, working at the Dutch ambulance service "RAV Brabant MWN" from January 2019 to December 2022, uses propofol for PSA or to provide sedation. With this a retrospective observational document study we describe the characteristics of patients and ambulance runs and evaluates the interventions in terms of safety. RESULTS: During the study period, the APPs administered propofol 157 times for 135 PSA and in 22 cases for providing sedation. The most common indication was musculoskeletal trauma such as fracture care or the reduction of joint dislocation. In 91% of the situations where propofol was used, the predetermined goal e.g. alignment of fractured extremity, repositioning of luxated joint or providing sedation the goal was achieved. There were 12 cases in which one or more adverse events were documented and all were successfully resolved by the APP. There were no cases of laryngospam, airway obstruction, nor anaphylaxis. None of the adverse events led to unexpected hospitalization or death. CONCLUSION: During the study period, the APPs performed 135 PSAs and provided 22 sedations. The success rate of predetermined goals was higher than that stated in the literature. Although there were a number of side effects, their incidences were lower than those reported in the literature, and these were resolved by the APP during the episode of care. Applying a PSA by an APP at the EMS "RAV Brabant MWN" appears to be safe with a high success rate.

Value of integrated pulmonary index monitoring for the detection of adverse respiratory events in patients undergoing sedation for gastrointestinal system endoscopy.

Objectives: To determine if the integrated pulmonary index detects changes in ventilation status early in patients undergoing gastrointestinal endoscopy under sedation, and to determine the risk factors affecting hypoxia. METHODS: The retrospective study was conducted at the endoscopy unit of a tertiary university hospital in Turkey and comprised data between October 2018 and December 2019 related to patients of either gender aged >18 years who were assessed as American Society of Anaesthesiologists grade I-III and underwent elective lower and upper gastrointestinal endoscopy. Monitoring was done with capnography in addition to standard procedures. Data was analysed using SPSS 23. RESULTS: Of the 154 patients, 94(%) were females and 60(%) were males. The overall mean age was 50.88±11.8 years (range: 20-70 years). Mean time under anaesthesia was 23.58±4.91 minutes and mean endoscopy time was 21.73±5.06 minutes. During the procedure, hypoxia was observed in 42(27.3%) patients, severe hypoxia in 23(14.9%) and apnoea in 70(45.5%). Mean time between apnoea and hypoxia was 12.59±7.99 seconds, between apnoea and serious hypoxia 21.07±17.64 seconds, between integrated pulmonary index score 1 and hypoxia 12.91±8.17 sec, between integrated pulmonary index score 1 and serious hypoxia 21.59±14.13 seconds, between integrated pulmonary index score <7 and hypoxia 19.63±8.89 seconds, between integrated pulmonary index score <7 and serious hypoxia 28.39±12.66 seconds, between end-tidal carbon dioxide and hypoxia 12.95±8.33 seconds, and between end-tidal carbon dioxide and serious hypoxia 21.29±7.55 seconds. With integrated pulmonary index score 1, sensitivity value for predicting hypoxia and severe hypoxia was 88.1% and 95.7%, respectively, and specificity was 67% and 60.3%, respectively. With integrated pulmonary index score <7, the corresponding values were 100%, 100%, 42% and 64.1%, respectively. CONCLUSIONS: Capnographic monitoring, especially the follow-up integrated pulmonary index score, was found to be valuable and reliable in terms of finding both time and accuracy of the risk factor in the diagnosis of respiratory events.

The efficacy and safety of ciprofol and propofol in patients undergoing colonoscopy: A double-blind, randomized, controlled trial.

STUDY OBJECTIVE: Propofol is a commonly utilized anesthetic for painless colonoscopy, but its usage is occasionally limited due to its potential side effects, including cardiopulmonary suppression and injection pain. To address this limitation, the novel compound ciprofol has been proposed as a possible alternative for propofol. This study sought to determine whether there are any differences in the safety and efficacy of propofol and ciprofol for painless colonoscopy. DESIGN: Randomized clinical trial. SETTING: Single-centre, class A tertiary hospital, November 2021 to November 2022. PATIENTS: Adult, American Society of Anesthesiologists Physical Status I to II and body mass index of 18 to 30 kg m-2 patients scheduled to undergo colonoscopy. INTERVENTIONS: Consecutive patients were randomly allocated in a 1:1 ratio to receive sedation for colonoscopy with ciprofol (group C) or propofol (group P). MEASUREMENTS: The primary outcome was the success rate of colonoscopy. The secondary outcomes were onset time of sedation, operation time, recovery time and discharge time, patients and endoscopists satisfaction, side effects (e.g. injection pain, myoclonus, drowsiness, dizziness, procedure recall, nausea and vomiting) and incidence rate of cardiopulmonary adverse events. MAIN RESULTS: No significant difference was found in the success rate of colonoscopy between the two groups (ciprofol 96.3% vs. propofol 97.6%; mean difference - 1.2%, 95% CI: -6.5% to 4.0%, P = 0.650). However, group C showed prolonged sedation (63.4 vs. 54.8 s, P < 0.001) and fully alert times (9 vs 8 min, P = 0.013), as well as reduced incidences of injection pain (0 vs. 40.2%, P < 0.001), respiratory depression (2.4% vs. 13.4%, P = 0.021) and hypotension (65.9% vs. 80.5%, P = 0.034). Patients satisfaction was also higher in Group C (10 vs 9, P < 0.001). CONCLUSIONS: Ciprofol can be used independently for colonoscopy. When comparing the sedation efficacy of ciprofol and propofol, a 0.4 mg kg-1 dose of ciprofol proved to be equal to a 2.0 mg kg-1 dose of propofol, with fewer side effects and greater patient satisfaction during the procedure.

The Effect of Temperament on Outcomes of Opioid and Non-Opioid Pediatric Dental Sedation.

Purpose: To assess oral sedation success using midazolam and hydroxyzine with and without meperidine, and to assess the relationship between child temperament and sedation outcomes. Methods: This study recruited children between the ages of 36 and 95 months who were randomly assigned to receive dental treatment with an oral sedation regimen of midazolam (0.5 mg/kg) and hydroxyzine (1.0 mg/kg) with or without meperidine (1.5 mg/kg). Data were collected from the treatment log and electronic health records. Parents completed the Child Behavior Questionnaire Short Form (CBQ-SF) to assess temperament. Results: The study included 37 participants. The overall treatment success rate was 54 percent. There were no significant differences in sedation outcome with age, sex, insurance status, sedation regimen, isolation method or duration of procedure. Children with high pre-operative Frankl behavioral ratings were more likely to have a successful sedation outcome (P <0.01). Children who displayed high soothability experienced higher rates of success (P =0.04), which was more pronounced in the non-opioid group (P <0.01). Conclusion: The study showed low rates of success for a relatively small sample size. There was no difference in sedation success between the opioid group and non-opioid group. However, pre-procedure behavior and temperament characteristic of sooth- ability may warrant more exploration as predictors of sedation success.

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.