Racial Inequality in Receipt of Medications for Opioid Use Disorder.

BACKGROUND: Since 2010, Black persons in the United States have had a greater increase in opioid overdose-related mortality than other groups, but national-level evidence characterizing racial and ethnic disparities in the use of medications for opioid use disorder (OUD) is limited. METHODS: We used Medicare claims data from the 2016-2019 period for a random 40% sample of fee-for-service beneficiaries who were Black, Hispanic, or White; were eligible for Medicare owing to disability; and had an index event related to OUD (nonfatal overdose treated in an emergency department or inpatient setting, hospitalization with injection drug use-related infection, or inpatient or residential rehabilitation or detoxification care). We measured the receipt of medications to treat OUD (buprenorphine, naltrexone, and naloxone), the receipt of high-risk medications (opioid analgesics and benzodiazepines), and health care utilization, all in the 180 days after the index event. We estimated differences in outcomes according to race and ethnic group with adjustment for beneficiary age, sex, index event, count of chronic coexisting conditions, and state of residence. RESULTS: We identified 25,904 OUD-related index events among 23,370 beneficiaries, with 3937 events (15.2%) occurring among Black patients, 2105 (8.1%) among Hispanic patients, and 19,862 (76.7%) among White patients. In the 180 days after the index event, patients received buprenorphine after 12.7% of events among Black patients, after 18.7% of those among Hispanic patients, and after 23.3% of those among White patients; patients received naloxone after 14.4%, 20.7%, and 22.9%, respectively; and patients received benzodiazepines after 23.4%, 29.6%, and 37.1%, respectively. Racial differences in the receipt of medications to treat OUD did not change appreciably from 2016 to 2019 (buprenorphine receipt: after 9.1% of index events among Black patients vs. 21.6% of those among White patients in 2016, and after 14.1% vs. 25.5% in 2019). In all study groups, patients had multiple ambulatory visits in the 180 days after the index event (mean number of visits, 6.6 after events among Black patients, 6.7 after events among Hispanic patients, and 7.6 after events among White patients). CONCLUSIONS: Racial and ethnic differences in the receipt of medications to treat OUD after an index event related to this disorder among patients with disability were substantial and did not change over time. The high incidence of ambulatory visits in all groups showed that disparities persisted despite frequent health care contact. (Funded by the National Institute on Drug Abuse and the National Institute on Aging.).

Benzodiazepine use in relation to long-term dementia risk and imaging markers of neurodegeneration: a population-based study.

BACKGROUND: Benzodiazepine use is common, particularly in older adults. Benzodiazepines have well-established acute adverse effects on cognition, but long-term effects on neurodegeneration and dementia risk remain uncertain. METHODS: We included 5443 cognitively healthy (MMSE ≥ 26) participants from the population-based Rotterdam Study (57.4% women, mean age 70.6 years). Benzodiazepine use from 1991 until baseline (2005-2008) was derived from pharmacy dispensing records, from which we determined drug type and cumulative dose. Benzodiazepine use was defined as prescription of anxiolytics (ATC-code: N05BA) or sedative-hypnotics (ATC-code: N05CD) between inception of pharmacy records and study baseline. Cumulative dose was calculated as the sum of the defined daily doses for all prescriptions. We determined the association with dementia risk until 2020 using Cox regression. Among 4836 participants with repeated brain MRI, we further determined the association of benzodiazepine use with changes in neuroimaging markers using linear mixed models. RESULTS: Of all 5443 participants, 2697 (49.5%) had used benzodiazepines at any time in the 15 years preceding baseline, of whom 1263 (46.8%) used anxiolytics, 530 (19.7%) sedative-hypnotics, and 904 (33.5%) used both; 345 (12.8%) participants were still using at baseline assessment. During a mean follow-up of 11.2 years, 726 participants (13.3%) developed dementia. Overall, use of benzodiazepines was not associated with dementia risk compared to never use (HR [95% CI]: 1.06 [0.90-1.25]), irrespective of cumulative dose. Risk estimates were somewhat higher for any use of anxiolytics than for sedative-hypnotics (HR 1.17 [0.96-1.41] vs 0.92 [0.70-1.21]), with strongest associations for high cumulative dose of anxiolytics (HR [95% CI] 1.33 [1.04-1.71]). In imaging analyses, current use of benzodiazepine was associated cross-sectionally with lower brain volumes of the hippocampus, amygdala, and thalamus and longitudinally with accelerated volume loss of the hippocampus and to a lesser extent amygdala. However, imaging findings did not differ by type of benzodiazepines or cumulative dose. CONCLUSIONS: In this population-based sample of cognitively healthy adults, overall use of benzodiazepines was not associated with increased dementia risk, but potential class-dependent adverse effects and associations with subclinical markers of neurodegeneration may warrant further investigation.

Analgesia and Sedation Use During Noninvasive Ventilation for Acute Respiratory Failure.

OBJECTIVES: To describe U.S. practice regarding administration of sedation and analgesia to patients on noninvasive ventilation (NIV) for acute respiratory failure (ARF) and to determine the association of this practice with odds of intubation or death. DESIGN: A retrospective multicenter cohort study. SETTING: A total of 1017 hospitals contributed data between January 2010 and September 2020 to the Premier Healthcare Database, a nationally representative healthcare database in the United States. PATIENTS: Adult (≥ 18 yr) patients admitted to U.S. hospitals requiring NIV for ARF. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 433,357 patients on NIV of whom (26.7% [95% CI] 26.3%-27.0%) received sedation or analgesia. A total of 50,589 patients (11.7%) received opioids only, 40,646 (9.4%) received benzodiazepines only, 20,146 (4.6%) received opioids and benzodiazepines, 1.573 (0.4%) received dexmedetomidine only, and 2,639 (0.6%) received dexmedetomidine in addition to opioid and/or benzodiazepine. Of 433,357 patients receiving NIV, 50,413 (11.6%; 95% CI, 11.5-11.7%) patients underwent invasive mechanical ventilation on hospital days 2-5 or died on hospital days 2-30. Intubation was used in 32,301 patients (7.4%; 95% CI, 7.3-7.6%). Further, death occurred in 24,140 (5.6%; 95% CI, 5.5-5.7%). In multivariable analysis adjusting for relevant covariates, receipt of any medication studied was associated with increased odds of intubation or death. In inverse probability weighting, receipt of any study medication was also associated with increased odds of intubation or death (average treatment effect odds ratio 1.38; 95% CI, 1.35-1.40). CONCLUSIONS: The use of sedation and analgesia during NIV is common. Medication exposure was associated with increased odds of intubation or death. Further investigation is needed to confirm this finding and determine whether any subpopulations are especially harmed by this practice.

Safety and efficacy of remimazolam versus propofol during EUS: a multicenter randomized controlled study.

BACKGROUND AND AIMS: Propofol, a widely used sedative in GI endoscopic procedures, is associated with cardiorespiratory suppression. Remimazolam is a novel ultrashort-acting benzodiazepine sedative with rapid onset and minimal cardiorespiratory depression. This study compared the safety and efficacy of remimazolam and propofol during EUS procedures. METHODS: A multicenter randomized controlled study was conducted between October 2022 and March 2023 in patients who underwent EUS procedures. Patients were randomly assigned to receive either remimazolam or propofol as a sedative agent. The primary endpoint was cardiorespiratory adverse events (AEs) during the procedure, including desaturation, respiratory depression, hypotension, and tachycardia. Secondary endpoints were the time to achieve sedation, recovery time, quality of sedation, pain at the injection site, and satisfaction of both endoscopists and patients. RESULTS: Four hundred patients enrolled in the study: 200 received remimazolam (10.8 ± 7.7 mg) and 200 received propofol (88.0 ± 49.1 mg). For cardiorespiratory AEs, the remimazolam group experienced fewer occurrences than the propofol group (8.5% vs 16%, P = .022). A nonsignificant trend was found toward less oxygen desaturation (1.0% vs 3.5%, P = .09), respiratory depression (.5% vs 1.5%, P = .62), hypotension (2.5% vs 5.5%, P = .12), and tachycardia (4.5% vs 5.5%, P = .68) with remimazolam than with propofol. Remimazolam showed a shorter induction time than propofol while maintaining comparable awakening and recovery times. Injection site pain was significantly lower in the remimazolam group than in the propofol group. The remimazolam group demonstrated a significantly higher quality of sedation and satisfaction scores than the propofol group, as evaluated by both endoscopists and patients. CONCLUSIONS: Remimazolam was superior to propofol in terms of safety and efficacy during EUS examinations. (Clinical trial registration number: KCT 0007643.).

Integration of Certified Child Life Specialists to Decrease in Periprocedural Benzodiazepine Use: A Pilot Study.

INTRODUCTION: Periprocedural anxiety is common in pediatric patients and is characterized by tension, anxiety, irritability, and autonomic activation. Periprocedural anxiety increases during certain events including admission to the preoperative area, separation from caregivers, induction of anesthesia, and IV placement. A study of children aged 2-12 showed that perioperative anxiety in children may be influenced by high parental anxiety and low sociability of the child. While these are nonmodifiable variables in the perioperative setting, there are numerous ways to ameliorate both parental and patient anxiety including the use of certified child life specialists (CCLSs) to aid in child comfort. In this study, our objective was to evaluate the integration of CCLS in our perioperative setting on the rate of benzodiazepine use. METHODS: We used a prospectively maintained database to identify patients undergoing outpatient elective surgical and radiologic procedures from July 2022 to September 2023 and January 2023 to September 2023 respectively. CCLSs were used to work with appropriately aged children in order to decrease the use of benzodiazepines and reduce possible adverse events associated with their use. RESULTS: A total of 2175 pediatric patients were seen by CCLS in same day surgery from July 2022 to September 2023. During this period, midazolam use decreased by an average of 11.4% (range 6.2%-19.3%). An even greater effect was seen in the radiologic group with 73% reduction. No adverse events were reported during this period. CONCLUSIONS: CCLSs working with age-appropriate patients in the periprocedural setting is a useful adjunct in easing anxiety in pediatric patients, reducing the need for periprocedural benzodiazepine administration and the risk of exposure to unintended side effects.

Remimazolam versus propofol for sedation in gastrointestinal endoscopic procedures: a systematic review and meta-analysis.

BACKGROUND: Propofol has a favourable efficacy profile in gastrointestinal endoscopic procedures, however adverse events remain frequent. Emerging evidence supports remimazolam use in gastrointestinal endoscopy. This systematic review and meta-analysis compares remimazolam and propofol, both combined with a short-acting opioid, for sedation of adults in gastrointestinal endoscopy. METHODS: We searched MEDLINE, Embase, and Cochrane databases for randomised controlled trials comparing efficacy-, safety-, and satisfaction-related outcomes between remimazolam and propofol, both combined with short-acting opioids, for sedation of adults undergoing gastrointestinal endoscopy. We performed sensitivity analyses, subgroup assessments by type of short-acting opioid used and age range, and meta-regression analysis using mean patient age as a covariate. We used R statistical software for statistical analyses. RESULTS: We included 15 trials (4516 subjects). Remimazolam was associated with a significantly lower sedation success rate (risk ratio [RR] 0.991; 95% confidence interval [CI] 0.984-0.998; high-quality evidence) and a slightly longer induction time (mean difference [MD] 9 s; 95% CI 4-13; moderate-quality evidence), whereas there was no significant difference between the sedatives in other time-related outcomes. Remimazolam was associated with significantly lower rates of respiratory depression (RR 0.41; 95% CI 0.30-0.56; high-quality evidence), hypotension (RR 0.43; 95% CI 0.35-0.51; moderate-quality evidence), hypotension requiring treatment (RR 0.25; 95% CI 0.12-0.52; high-quality evidence), and bradycardia (RR 0.42; 95% CI 0.30-0.58; high-quality evidence). There was no difference in patient (MD 0.41; 95% CI -0.07 to 0.89; moderate-quality evidence) and endoscopist satisfaction (MD -0.31; 95% CI -0.65 to 0.04; high-quality evidence) between both drugs. CONCLUSIONS: Remimazolam has clinically similar efficacy and greater safety when compared with propofol for sedation in gastrointestinal endoscopies.

Hypotension after general anaesthesia induction using remimazolam or propofol in geriatric patients undergoing sevoflurane anaesthesia with remifentanil: a single-centre, double-blind, randomised controlled trial.

BACKGROUND: The occurrence of hypotension after induction of general anaesthesia is common in geriatric patients, and should be prevented to minimise perioperative complications. Compared with propofol, remimazolam potentially has a lower incidence of hypotension. This study aimed to compare the incidence of hypotension after general anaesthesia induction with remimazolam or propofol in geriatric patients. METHODS: This single-centre, double-blind, randomised trial enrolled 90 patients aged ≥80 yr who received general anaesthesia for scheduled surgery. Patients were randomised to receive remimazolam (12 mg kg-1 h-1) or propofol (0.025 mg kg-1 s-1) for anaesthesia induction, with remifentanil and sevoflurane. The presence or absence of hypertension on the ward served as the stratification factor. The incidence of hypotension after the induction of general anaesthesia, defined as a noninvasive mean arterial pressure of <65 mm Hg measured every minute from initiation of drug administration to 3 min after tracheal intubation, was the primary outcome. Subgroup analysis was performed for the primary outcome using preoperative ward hypertension, clinical frailty scale, Charlson Comorbidity Index, and age. RESULTS: Three subjects were excluded before drug administration, and 87 subjects were included in the analysis. The incidence of hypotension was 72.1% (31/43) and 72.7% (32/44) with remimazolam or propofol, respectively. No statistically significant differences (adjusted odds ratio, 0.96; 95% confidence interval, 0.37-2.46; P=0.93) were observed between groups. Subgroup analysis revealed no significant differences between groups. CONCLUSIONS: Compared with propofol, remimazolam did not reduce the incidence of hypotension after general anaesthesia induction in patients aged ≥80 yr. CLINICAL TRIAL REGISTRATION: UMIN000042587.

Comparison emergence of sedation, using dexmedetomidine and remimazolam, in spinal anaesthesia - double blinded randomized controlled trial.

Background: Continuous intravenous infusion of remimazolam may be suitable for sedation in patients undergoing regional anaesthesia. However, there have been no studies comparing remimazolam and dexmedetomidine for this purpose. This study compared emergence from sedation between dexmedetomidine and remimazolam following continuous intravenous infusion in patients undergoing spinal anaesthesia. Methods: This double-blinded, randomised controlled trial assessed the sedative effects of dexmedetomidine and remimazolam. Following spinal anaesthesia, patients were sedated using continuous intravenous infusion of either dexmedetomidine (D group) or remimazolam (R group).The D group received dexmedetomidine administered at 6 mL/kg/h (6 µg/kg/h) for 10 minutes, followed by 1 mL/kg/h (1 µg/kg/h). The R group received remimazolam administered at 6 mL/kg/h (6 mg/kg/h) for 10 minutes, followed by 1 mL/kg/h (1 mg/kg/h). Sedation levels were evaluated using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale. The time to reach MOAA/S ≤ 3 from the start of drug infusion and the time to reach MOAA/S = 5 from the end of infusion were recorded. Hemodynamic parameters and respiratory rate were also monitored. Results: The R group reached MOAA/S ≤ 3 significantly faster than the D group during induction of sedation (4 ± 1 minutes and 11 ± 3 minutes, respectively, p < 0.001). The R group also reached MOAA/S = 5 significantly faster than the D group during emergence from sedation (11 ± 3 minutes and 16 ± 5 minutes, respectively, p < 0.001). Both groups maintained stable hemodynamic parameters and respiratory rate without any significant differences, although the mean heart rate was significantly lower in the D group than in the R group after the start of infusion. Conclusion: Remimazolam demonstrated significantly faster induction of and emergence from sedation compared to dexmedetomidine, with no significant differences in haemodynamics or respiratory depression.

Remimazolam for sedation and anesthesia in children: Protocol for a scoping review.

BACKGROUND: Remimazolam, a novel intravenous benzodiazepine recently approved by both the European Medicines Agency and the Food and Drug Agency, holds significant promise in clinical practice. Its pharmacodynamic profile closely mirrors that of midazolam, while its pharmacokinetics properties bear resemblance to remifentanil. Research in adult populations continues to accumulate, but the pediatric studies' pace is not significant. This scoping review aims to methodically scrutinize published studies, clinical trials, observational research, case reports, and pertinent literature to offer a comprehensive insight into the existing understanding of remimazolam in pediatric sedation and anesthesia. The synthesis of gathered evidence will discern lacunae in the literature, direct forthcoming investigations, and enlighten clinical practices. METHODS: The review will adhere to the guidelines outlined by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) for Scoping Review. A meticulous search strategy will be executed across prominent peer-reviewed databases, with concerted efforts to identify relevant gray literature. All primary investigations involving the administration of remimazolam in pediatric populations will be encompassed within the scope of this review. RESULTS: The encompassed studies will be elucidated through a narrative synopsis, complemented by descriptive statistical analyses of quantitative data where deemed applicable. CONCLUSION: The planned scoping review aims to delineate the existing evidence regarding the utilization of remimazolam in pediatric anesthesia and sedation. It will discern areas of knowledge deficiency, provide guidance for future inquiries, and enhance clinical practices within the field.

Remimazolam for sedation and anesthesia in children: A scoping review.

BACKGROUND: Remimazolam, a novel intravenous benzodiazepine recently approved by both the European Medicines Agency and the Food and Drug Agency, shows considerable promise in clinical practice. Its pharmacodynamic profile closely resembles that of midazolam, while its pharmacokinetic properties are similar to those of remifentanil. While research in adult populations continues to accumulate, the pace of pediatric studies is not as significant. This scoping review aims to systematically examine published studies, clinical trials, observational research, case reports, and relevant literature to provide a comprehensive understanding of remimazolam in pediatric sedation and anesthesia. By synthesizing the gathered evidence, we aim to identify gaps in the literature, guide future research endeavors, and inform clinical practices. METHODS: The review follows the guidelines outlined by the Preferred Reporting Items for Systematic Review and Meta-Analysis for Scoping Review. A thorough search strategy was implemented across prominent peer-reviewed databases, with focused efforts to identify relevant grey literature. All primary studies involving the use of remimazolam in pediatric populations were included in this review. RESULTS: Eighteen studies were included in this analysis, comprising 2 randomized controlled trials, 4 prospective cohort trials, 12 case reports, and 692 children in total. CONCLUSION: This scoping review highlights the increasing interest in using remimazolam as a sedative or anesthetic for children. Although initial evidence indicates its effectiveness and safety, more research is necessary to fill knowledge gaps, establish standard protocols, and optimize its use in pediatric anesthesia and sedation. Addressing these challenges will enable clinicians to improve the quality of care and outcomes for pediatric patients undergoing sedation and anesthesia.

Fewer emergency department alarms is associated with reduced use of medications for acute agitation.

BACKGROUND AND OBJECTIVES: Patient monitoring systems provide critical information but often produce loud, frequent alarms that worsen patient agitation and stress. This may increase the use of physical and chemical restraints with implications for patient morbidity and autonomy. This study analyzes how augmenting alarm thresholds affects the proportion of alarm-free time and the frequency of medications administered to treat acute agitation. METHODS: Our emergency department's patient monitoring system was modified on June 28, 2022 to increase the tachycardia alarm threshold from 130 to 150 and to remove alarm sounds for several arrhythmias, including bigeminy and premature ventricular beats. A pre-post study was performed lasting 55 days before and 55 days after this intervention. The primary outcome was change in number of daily patient alarms. The secondary outcomes were alarm-free time per day and median number of antipsychotic and benzodiazepine medications administered per day. The safety outcome was the median number of patients transferred daily to the resuscitation area. We used quantile regression to compare outcomes between the pre- and post-intervention period and linear regression to correlate alarm-free time with the number of sedating medications administered. RESULTS: Between the pre- and post-intervention period, the median number of alarms per day decreased from 1332 to 845 (-37%). This was primarily driven by reduced low-priority arrhythmia alarms from 262 to 21 (-92%), while the median daily census was unchanged (33 vs 32). Median hours per day free from alarms increased from 1.0 to 2.4 (difference 1.4, 95% CI 0.8-2.1). The median number of sedating medications administered per day decreased from 14 to 10 (difference - 4, 95% CI -1 to -7) while the number of escalations in level of care to our resuscitation care area did not change significantly. Multivariable linear regression showed a 60-min increase of alarm-free time per day was associated with 0.8 (95% CI 0.1-1.4) fewer administrations of sedating medication while an additional patient on the behavioral health census was associated with 0.5 (95% CI 0.0-1.1) more administrations of sedating medication. CONCLUSION: A reasonable change in alarm parameter settings may increase the time patients and healthcare workers spend in the emergency department without alarm noise, which in this study was associated with fewer doses of sedating medications administered.

Incompatibility of the short-acting benzodiazepine remimazolam with common perioperative medication.

BACKGROUND: Remimazolam is a relatively new benzodiazepine with growing use in procedural sedation and general anaesthesia. Initiated by case reports, the physical incompatibility of remimazolam with ringer's acetated and ringer's lactated solution has been reported. More recently, remifentanil, fentanyl, rocuronium, vecuronium, dexmedetomidine, and midazolam, have been investigated and suggested safe for coadministration with remimazolam. Apart from case reports, incompatibility for other frequently used drugs remains unknown. METHODS: Sixty-five drugs and intravenous fluids were tested for possible precipitation with remimazolam in a simulated y-site administration. Equal volumes of the test drug were injected into the remimazolam solution, examined and photo documented at 1, 15, 30 and 60 min after mixture. Examination was taken by two independent investigators. pH was measured before, and 60 min after mixing the drugs. RESULTS: Seventeen (26.15%) drugs or fluids showed precipitation, 47 (72.31%) did not show any sign of interaction. Propofol could not be assessed, because of the turbidity of the substance itself. Precipitation occurred immediately and remained stable in all timestamps. The incompatible drug-remimazolam-mixtures had a median pH of 7.15 (6.67, 8.01), the non-precipitating mixtures a median pH of 4.75 (3.8, 5.6). The pH-values of both groups were significantly different (Mann-Whitney-U-test; p < .00001). There is an increasing risk for precipitation with more basic baseline pH-levels of the tested drug. No interaction was seen in baseline pH below 5. CONCLUSIONS: Remimazolam (Byfavo®) is incompatible with ampicillin/ sulbactam, calcium gluconate, clindamycin, dexamethasone, dimenhydrinate, an 148mval/l electrolyte - glucose 1% solution (E148G1®), furosemide, a 4% gelatine volume expander (gelafundin®), heparin sodium, insulin, meropenem, sodium bicarbonate 8.4%, prednisolone, the crystalloid infusions jonosteril® and sterofundin®, thiopental and tranexamic acid. The results strongly affirm remimazolam's safety requirements: A separate line for remimazolam and an approved compatible baseline infusion is mandatory and an alternative way to administer bolus medication is required.

Effect of converting from propofol to remimazolam with flumazenil reversal on recovery from anesthesia in outpatients with mental disabilities: a randomized controlled trial.

BACKGROUND: General anesthesia is often necessary for dental treatment of outpatients with mental disabilities. Rapid recovery and effective management of postoperative nausea and vomiting (PONV) are critical for outpatients. This study aimed to investigate the effect of transitioning from propofol to remimazolam with flumazenil reversal administered toward the end of surgery during propofol-based total intravenous anesthesia (TIVA) on recovery. METHODS: Adults with mental disabilities scheduled to undergo dental treatment were randomly assigned to receive either propofol-based TIVA (Group P) or propofol-remimazolam-based TIVA with flumazenil reversal (Group PR). Propofol was replaced with remimazolam 1 h before the end of surgery in Group PR; moreover, 0.5 mg of flumazenil was administered after the neuromuscular blockade reversal agent. The primary outcome was the duration of stay in the post-anesthesia care unit (PACU). The secondary outcomes included time to eye-opening, time to extubation, occurrence of PONV, and quality of recovery. RESULTS: Fifty-four patients were included in this study. The duration of stay in the PACU in Group PR was significantly shorter than that in Group P (mean difference, 8.7 min; confidence interval [95% CI], 3.3-14.2; P = 0.002). Group PR exhibited a shorter time to eye opening (mean difference, 5.4 min; 95% CI, 3.3-8.1; P < 0.001) and time to extubation (mean difference, 5.5 min; 95% CI, 3.6-7.9; P < 0.001) than Group P. Neither group required the administration of rescue analgesics, and the incidence of PONV was not reported. CONCLUSIONS: Transitioning from propofol to remimazolam 1 h before the end of surgery followed by flumazenil reversal reduced the duration of stay in the PACU and the time to eye opening and extubation without affecting the incidence of PONV and quality of recovery. TRIAL REGISTRATION NUMBER: Clinical Research Information Service (KCT0007794), Clinical trial first registration date: 12/10/2022.

Effective remimazolam loading dose for adequate sedation in regional anesthesia.

PURPOSE: Remimazolam is a novel ultrashort-acting sedative considered appropriate for continuous infusion during surgical procedures. Nevertheless, information regarding its loading dose for sedation during surgery is limited. We aimed to determine the 90% effective dose (ED90) of the remimazolam loading dose for sedation in patients undergoing limb surgery under regional anesthesia. METHODS: We included 50 patients aged 19-80 yr undergoing limb surgery under regional anesthesia. After regional anesthesia, remimazolam besylate was administered at the assigned dose. For ten minutes after the initiation of loading, the level of sedation was evaluated using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale. The primary outcome was the ED90 based on whether patients reached a MOAA/S score of ≤ 3 points (loss of response to verbal command) within ten minutes. The secondary outcomes were the ED50 and the estimated effect site and plasma concentration at the time of achieving successful sedation. RESULTS: In total, 49 patients were included in the final analysis, and adequate sedation with the assigned loading dose was successful in 42 patients. The log-logistic function showed that the ED90 and ED50 were 0.617 mg·kg-1·hr-1 (95% confidence interval [CI], 0.511 to 0.722; 98% CI, 0.492 to 0.741) and 0.438 mg·kg-1·hr-1 (95% CI, 0.335 to 0.541; 98% CI, 0.315 to 0.560), respectively. CONCLUSION: The ED90 of the remimazolam loading dose to achieve adequate sedation in patients undergoing limb surgery under regional anesthesia was 0.617 mg·kg-1·hr-1 (95% CI, 0.511 to 0.722; 98% CI, 0.492 to 0.741). STUDY REGISTRATION: ClinicalTrials.gov (NCT05340335); first posted 22 April 2022.

RéSUMé: OBJECTIF: Le remimazolam est un nouveau sédatif à action ultracourte considéré comme approprié pour la perfusion continue pendant les interventions chirurgicales. Néanmoins, les informations concernant sa dose de charge pour la sédation pendant la chirurgie sont limitées. Notre objectif était de déterminer la dose efficace à 90 % (DE90) de la dose de charge de remimazolam pour la sédation chez la patientèle bénéficiant d'une chirurgie d'un membre sous anesthésie régionale. MéTHODE: Cinquante personnes âgées de 19 à 80 ans bénéficiant d'une chirurgie des membres sous anesthésie régionale ont été incluses. Après l'anesthésie régionale, du bésylate de remimazolam a été administré à la dose assignée. Pendant dix minutes après le début de la charge, le niveau de sédation a été évalué à l'aide de l'échelle modifiée d'évaluation de la vigilance/sédation par l'observateur (MOAA/S). Le critère d'évaluation principal était la DE90 selon que les patient·es ont atteint un score MOAA/S de ≤ 3 points (perte de réponse à la commande verbale) dans les dix minutes. Les critères d'évaluation secondaires étaient la DE50 et l'estimation du site d'effet et de la concentration plasmatique au moment de l'obtention d'une sédation réussie. RéSULTATS: Au total, 49 personnes ont été incluses dans l'analyse finale, et une sédation adéquate avec la dose de charge assignée a été couronnée de succès chez 42 d'entre elles. La fonction log-logistique a montré que les DE90 et DE50 étaient de 0,617 mg·kg−1·h−1 (intervalle de confiance [IC] à 95 %, 0,511 à 0,722; IC 98 %, 0,492 à 0,741) et 0,438 mg·kg−1·h−1 (IC 95 %, 0,335 à 0,541; IC 98 %, 0,315 à 0,560), respectivement. CONCLUSION: La DE90 de la dose de charge de remimazolam pour obtenir une sédation adéquate chez les personnes bénéficiant d'une chirurgie des membres sous anesthésie régionale était de 0,617 mg·kg−1·h−1 (IC 95 %, 0,511 à 0,722; IC 98 %, 0,492 à 0,741). ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT05340335); première publication le 22 avril 2022.

Comparison of remimazolam tosilate and propofol during induction and maintenance of general anesthesia in patients undergoing laparoscopic cholecystectomy: a prospective, single center, randomized controlled trial.

BACKGROUND: Remimazolam tosilate (RT) is a new, ultrashort-acting benzodiazepine. Here, we investigated the efficacy and safety of RT for general anesthesia in patients undergoing Laparoscopic Cholecystectomy (LC). METHODS: In this study, 122 patients undergoing laparoscopic cholecystectomy were randomly allocated to receive either remimazolam tosilate (Group RT) or propofol group (Group P). RT was administered as a slow bolus of 0.3 mg kg- 1 for induction, followed by 1.0-2.0 mg kg- 1 h- 1 for maintenance of general anesthesia. Propofol was started at 2 mg kg- 1 and followed by 4-10 mg kg- 1 h- 1 until the end of surgery. The primary outcome was the time to bispectral index (BIS) ≤ 60. The secondary outcome included the time to loss of consciousness (LoC), and the time to extubation. Adverse events were also assessed. RESULTS: A total of 112 patients were recruited for study participation. Among them, the time to BIS ≤ 60 in Group RT was longer than that in Group P (Group RT: 89.3 ± 10.7 s; Group P: 85.9 ± 9.7 s, P > 0.05). While the time to LoC comparing remimazolam and propofol showed no statistical significance (Group RT: 74.4 ± 10.3 s; Group P: 74.7 ± 9.3 s, P > 0.05). The time to extubation in Group RT was significantly longer than that in Group P (Group RT: 16.0 ± 2.6 min; Group P: 8.8 ± 4.3 min, P < 0.001). Remimazolam tosilate had more stable hemodynamics and a lower incidence of hypotension during general anesthesia. CONCLUSIONS: Remimazolam tosilate can be safely and effectively used for general anesthesia in patients undergoing Laparoscopic Cholecystectomy. It maintains stable hemodynamics during induction and maintenance of general anesthesia compared with propofol. Further studies are needed to validate the findings. TRIAL REGISTRATION: Chictr.org.cn ChiCTR2300071256 (date of registration: 09/05/2023).

The 90% effective dose (ED90) of remimazolam for inhibiting responses to the insertion of a duodenoscope during ERCP.

BACKGROUND: Compared to midazolam, remimazolam has a faster onset and offset of hypnotic effect, as well as cardiorespiratory stability, this study aims to determine the 90% effective dose (ED90) of remimazolam to inhibit responses to insertion of a duodenoscope during endoscopic retrograde cholangiopancreatography (ERCP). METHODS: A dose-response study was carried out undergoing ERCP who received remimazolam-alfentanil anesthesia using 10 µg/kg of alfentanil between September 2021 and November 2021. The initial dose of remimazolam was 0.2 mg/kg. The dose was then decided based on the responses of earlier patients by exploiting the sequential ascend and descend according to a 9: 1 biased coin design. Upon failure, the dose of remimazolam was increased by 0.025 mg/kg in the next patient. When the insertion was successful, the succeeding patient was randomized to an identical dose or a dose that was lower by 0.025 mg/kg.The ED90 of remimazolam for inhibiting responses to the insertion of a duodenoscope during ERCP was calculated. Adverse events and complications of remimazolam were recorded. RESULTS: A total of 55 elderly patients (age > 65) were included in the study. 45 successfully anesthetized patients, and 10 unsuccessfully. The ED90 of remimazolam was 0.300 mg/kg (95% CI = 0.287-0.320). ED95 was 0.315 (95% CI = 0.312-0.323) and ED99 was 0.323 (95% CI = 0.323-0.325). Among the patients, 9 patients developed hypotension, 2 patients developed bradycardia and 1 patient developed tachycardia, and hypoxia occurred in 2 patients. CONCLUSIONS: A loading dose of 0.300 mg / kg of remimazolam for elderly patients undergoing ERCP can safely, effectively, and quickly induce patients to fall asleep and inhibit responses to the insertion of a duodenoscope. TRIAL REGISTRATION: The study protocol was registered at the website ClinicalTrials.gov on 22/09/2021(NCT05053763).

The effects of remimazolam combined with sufentanil on respiration, circulation and sedation level in patients undergoing colonoscopy.

BACKGROUND: The main sedative which is propofol in painless gastroenteroscopy, has a high risk of reducing blood pressure and respiratory depression. Remimazolam (a short-acting benzodiazepine) is expected to be widely used in painless gastroenteroscopy due to its rapid onset, rapid metabolism and light respiratory and circulation inhibition. METHODS: A randomized, single-blind, parallel, controlled study, 123 outpatients who were undergoing painless colonoscopy and ramdomly divided into group A, B and C, in Hangzhou First People's Hospital, July-December 2021. All patients were intravenously injected with 5 µg sufentanil for analgesic preconditioning. The group A was induced by 0.2 mg/kg remimazolam besylate. The group B was induced by 0.25 mg/kg remimazolam besylate. And the group C was inducted by 2.0 mg /kg propofol. If the patients had limb movement or MOAA/S score > 3 and so on, remimazolam besylate was added at 2.5 mg/ time in group A and B, and propofol emulsion injection was added at 0.5 mg/kg/ time in group C. During the operation, according to the actual situation, remimazolam was per added 2.5 mg in the experimental group, and propofol was 0.5 mg/kg in the control group. Heart rate (HR), non-invasive blood pressure (BP), respiratory rate (RR), pulse oxygen saturation (SpO2), and improved vigilance/sedation score (MOAA/S) of patients was recorded from entering endoscopy room to get out of the anesthesia recovery room, also including perioperative adverse events, other medications or treatments, the time of patients waking up and leaving the hospital. RESULTS: The successful rate of induction in three groups was 100%. There was no significant difference in the sedation completion rate among the three groups (Group A:90.2%, Group B: 92.7%, Group C: 92.7%, P = 1.000). The rate of adverse events after administration: group A(27.0%) and B(36.8%) both lower than group C(71.0%),P < 0.001;There was no significant difference between group A and group B, P > 0.744;The average time from the last drug administration to meet the discharge criteria of the subjects in three groups was as follows: The average time of group A(16.2 min) and Group B(16.5 min) both shorter than group C(19.6 min), P = 0.001; There was no significant difference between group A and group B, P = 0.742. CONCLUSIONS: This study revealed that remimazolam is a safe and effective medication for colonoscopy sedation, the security of remimazolam is better than propofol, and the sedative effect with the initial dose of 0.25 mg/kg of remimazolam is optimal. TRIAL REGISTRATION: China Clinical Trial Center with registration number: 2100052615,02/11/2021.

Comparison of hypotension incidence between remimazolam and propofol in patients with hypertension undergoing neurosurgery: prospective, randomized, single-blind trial.

BACKGROUND: Remimazolam, a newer benzodiazepine that targets the GABAA receptor, is thought to allow more stable blood pressure management during anesthesia induction. In contrast, propofol is associated with vasodilatory effects and an increased risk of hypotension, particularly in patients with comorbidities. This study aimed to identify medications that can maintain stable vital signs throughout the induction phase. METHODS: We conducted a single-center, two-group, randomized controlled trial to investigate and compare the incidence of hypotension between remimazolam- and propofol-based total intravenous anesthesia (TIVA). We selected patients aged between 19 and 75 years scheduled for neurosurgery under general anesthesia, who were classified as American Society of Anesthesiologists Physical Status I-III and had a history of hypertension. RESULTS: We included 94 patients in the final analysis. The incidence of hypotension was higher in the propofol group (91.3%) than in the remimazolam group (85.4%; P = 0.057). There was no significant difference in the incidence of hypotension among the various antihypertensive medications despite the majority of patients being on multiple medications. In comparison with the propofol group, the remimazolam group demonstrated a higher heart rate immediately after intubation. CONCLUSIONS: Our study indicated that the hypotension incidence of remimazolam-based TIVA was comparable to that of propofol-based TIVA throughout the induction phase of EEG-guided anesthesia. Both remimazolam and propofol may be equally suitable for general anesthesia in patients undergoing neurosurgery. TRIAL REGISTRATION: Clinicaltrials.gov (NCT05164146).

Comparison of the effects of remimazolam tosylate and propofol on immune function and hemodynamics in patients undergoing laparoscopic partial hepatectomy: a randomized controlled trial.

BACKGROUND: Laparoscopic partial hepatectomy inevitably decrease patient immune function. Propofol has been shown to have immunomodulatory effects but is associated with hemodynamic side effects. Despite studies showing a negligible impact of remimazolam tosylate on hemodynamics, it has not been reported for partial hepatectomy patients. Its influence on immune function also remains unexplored. This study sought to investigate the differences in immune function and intraoperative hemodynamics between patients who underwent laparoscopic partial hepatectomy with remimazolam tosylate and those who underwent laparoscopic partial hepatectomy with propofol. METHODS: This was a single-center, randomized controlled trial involving 70 patients, who underwent elective laparoscopic partial hepatectomy. The patients were randomly divided into two groups: the remimazolam group (group R) and the propofol group (group P). In this study, the primary outcomes assessed included the patient's immune function and hemodynamic parameters, and the secondary outcomes encompassed the patient's liver function and adverse events. RESULTS: Data from 64 patients (group R, n = 31; group P, n = 33) were analyzed. The differences in the percentages of CD3+, CD4+, CD8+, and NK cells and the CD4+/CD8+ ratio between the two groups were not statistically significant at 1 day or 3 days after surgery. Compared with those in group P, the MAP and HR at T2 and the MAP at T1 in group R were significantly increased(P < 0.05). The differences in HR and MAP at T0, T3, T4, T5, T6, and T7 and HR at T1 between the two groups were not statistically significant. There were no differences in liver function or adverse effects between the two groups, suggesting that remimazolam tosylate is a safe sedative drug(P > 0.05). CONCLUSION: The effects of remimazolam tosylate on the immune function of patients after partial hepatectomy are comparable to those of propofol. Additionally, its minimal effect on hemodynamics significantly decreases the incidence of hypotension during anesthesia induction, thereby enhancing overall perioperative safety. TRIAL REGISTRATION: The trial was registered on May 9, 2022 in the Chinese Clinical Trial Registry, registration number ChiCTR2200059715 (09/05/2022).

Remimazolam to prevent hemodynamic instability during catheter ablation under general anesthesia: a randomized controlled trial.

PURPOSE: Maintaining hemodynamic stability during cardiac ablation under general anesthesia is challenging. Remimazolam, a novel ultrashort-acting benzodiazepine, is characterized by maintaining comparatively stable blood pressure and does not influence the cardiac conduction system, which renders it a reasonable choice for general anesthesia for cardiac ablation. We aimed to evaluate whether remimazolam is associated with a decreased incidence of intraoperative hypotension compared with desflurane. METHODS: In this single-centre, parallel-group, prospective, single-blind, randomized clinical trial, we randomized patients (1:1) into a remimazolam group (remimazolam-based total intravenous anesthesia) or desflurane group (propofol-induced and desflurane-maintained inhalational anesthesia) during cardiac ablation procedures for arrhythmia. The primary outcome was the incidence of intraoperative hypotensive events, defined as mean arterial pressure of < 60 mm Hg at any period. RESULTS: Overall, we enrolled 96 patients between 2 August 2022 and 19 May 2023 (47 and 49 patients in the remimazolam and desflurane groups, respectively). The remimazolam group showed a significantly lower incidence of hypotensive events (14/47, 30%) than the desflurane group (29/49, 59%; relative risk [RR], 0.5; 95% confidence interval [CI], 0.31 to 0.83; P = 0.004). Remimazolam was associated with a lower requirement for bolus or continuous vasopressor infusion than desflurane was (23/47, 49% vs 43/49, 88%; RR, 0.56; 95% CI, 0.41 to 0.76; P < 0.001). No between-group differences existed in the incidence of perioperative complications such as nausea, vomiting, oxygen desaturation, delayed emergence, or pain. CONCLUSIONS: Remimazolam was a viable option for general anesthesia for cardiac ablation. Remimazolam-based total intravenous anesthesia was associated with significantly fewer hypotensive events and vasopressor requirements than desflurane-based inhalational anesthesia was, without significantly more complications. STUDY REGISTRATION: ClinicalTrials.gov (NCT05486377); first submitted 1 August 2022.

RéSUMé: OBJECTIF: Le maintien de la stabilité hémodynamique lors d'une ablation cardiaque sous anesthésie générale est un défi. Le remimazolam, une nouvelle benzodiazépine à action ultra-courte, se caractérise par le maintien d'une tension artérielle relativement stable et son absence d'influence sur le système de conduction cardiaque, ce qui en fait un choix raisonnable pour l'anesthésie générale pour l'ablation cardiaque. Nous avons cherché à déterminer si le remimazolam est associé à une diminution de l'incidence d'hypotension peropératoire comparativement au desflurane. MéTHODE: Dans cette étude clinique randomisée, prospective, en simple aveugle, en groupes parallèles et monocentrique, nous avons randomisé des patient·es (1:1) dans un groupe remimazolam (anesthésie intraveineuse totale à base de remimazolam) et un groupe desflurane (anesthésie volatile induite par propofol et maintenue par desflurane) pendant des interventions d'ablation cardiaque pour arythmie. Le critère d'évaluation principal était l'incidence d'événements hypotensifs peropératoires, définis comme une tension artérielle moyenne de < 60 mm Hg à n'importe quelle période. RéSULTATS: Au total, nous avons recruté 96 patient·es entre le 2 août 2022 et le 19 mai 2023 (47 et 49 personnes dans les groupes remimazolam et desflurane, respectivement). Le groupe remimazolam a montré une incidence significativement plus faible d'événements hypotensifs (14/47, 30 %) que le groupe desflurane (29/49, 59 %; risque relatif [RR], 0,5; intervalle de confiance [IC] à 95 %, 0,31 à 0,83; P = 0,004). Le remimazolam a été associé à des besoins plus faibles de bolus ou de perfusion continue de vasopresseurs que le desflurane (23/47, 49 % vs 43/49, 88 %; RR, 0,56; IC 95 %, 0,41 à 0,76; P < 0,001). Il n'y avait pas de différences entre les groupes dans l'incidence des complications périopératoires telles que les nausées, les vomissements, la désaturation en oxygène, l'émergence retardée ou la douleur. CONCLUSION: Le remimazolam a constitué une option viable pour l'anesthésie générale en vue d'une ablation cardiaque. L'anesthésie intraveineuse totale à base de remimazolam a été associée à un nombre significativement plus faible d'événements d'hypotension et de besoins en vasopresseurs que l'anesthésie par inhalation à base de desflurane, sans complications significativement plus nombreuses. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT05486377); soumis pour la première fois le 1er août 2022.