When Should Pharmacological Interventions for Insomnia Be Recommended?

This commentary on a case describes how social determinants of health also contribute to insomnia and then suggests how to balance risks and benefits of different strategies for managing chronic insomnia. Behaviorally induced insufficient sleep syndrome can exacerbate morning side effects of prescription sleep aids, and there are potentially serious long-term risks (eg, dementia, falls, death) associated with chronic benzodiazepine use. Before trying sleeping pills, chronic insomnia should be treated with cognitive behavioral therapy.

Comparison of hypotension between propofol and remimazolam-propofol combinations sedation for day-surgery hysteroscopy: a prospective, randomized, controlled trial.

BACKGROUND: A combination of remimazolam and propofol could produce more stable sedation. A good medication regimen should consider not only efficacy but also safety, especially hypotension. The aim of the current study was to compare the incidence and amount of hypotension by propofol versus remimazolam-propofol combinations in day-surgery hysteroscopy. METHODS: Patients were randomly assigned to receive either propofol (Group P, n = 125) or remimazolam-propofol combinations (Group RP, n = 125) at a 1:1 ratio. Intravenous injection of sufentanil 0.1ug/kg were administered before sedative medication. In group P, a bolus of 2.5 mg/kg propofol was administered. In group RP, intravenous anesthesia was commenced with 0.125 mg/kg remimazolam and 1 mg/kg propofol. After loss of consciousness, propofol was maintained at 6 mg/kg/h. The primary outcomes were the incidence and amount of hypotension during surgery. Hypotension was defined as a MAP less than 65mmHg for at least 1 min. The amount of hypotension was assessed by time-weighted average intraoperative MAP under a threshold of 65 mmHg. The secondary outcomes were various anesthesia related parameters and some adverse events. RESULTS: In group P, 25 patients (20.0%) experienced hypotension during hysteroscopy compared with 9 patients (7.2%) in group RP, for a difference of 12.8% (RR 2.778, 95%CI [1.352-5.709]). The combination of remimazolam and propofol resulted in significantly lower TWA (Time Weighted Average) threshold 0.14 (0.10-0.56) mmHg in group RP compared to 0.31 (0.15-0.67) mmHg in group P. The total dose of propofol was nearly double in group P compared to group RP. A significantly higher frequency of injection pain and low oxygen saturation was observed in the group P than that of the group RP. Hiccup was observed only in group RP. The incidences of body movement, bradycardia and vomiting were no significant difference between groups. CONCLUSION: The incidence and amount of hypotension by remimazolam-propofol combinations was significantly less than that by propofol sedation in day-surgery hysteroscopy. The optimization of medication regimen would attenuate the harm of hypotension and contribute to patients' rapid recovery in day surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2400079888 (date: 15/01/2024).

The Pharmaceutical Future of Remimazolam as Compared to Propofol and Midazolam: A Literature Review.

INTRODUCTION: Remimazolam is an ultra-short-acting benzodiazepine with a predictable and quick recovery that was FDA approved in 2020. As a relatively new medication, it is not as mainstream as other sedatives such as propofol or midazolam. This research aims to highlight the differences, benefits, and drawbacks of remimazolam in comparison to other short-term sedatives in order to bring greater awareness, and to consolidate the current knowledge of the effects of remimazolam. METHODS: The PubMed database was used to search for current relevant research to review. The search terms used were: "remimazolam", "midazolam", "propofol", and procedural sedation. The search also used qualifiers using only publications in English and published within the last five years. This query yielded 26 articles which were reviewed for content and relevance. RESULTS: Sixteen of the reviewed studies resulted in common themes suggesting remimazolam to be an effective alternative for procedural sedation with fewer adverse effects. Primarily, remimazolam is observed to have decreased procedural hypotension, bradycardia, and injection site pain. With no studies demonstrating an increased frequency of bradycardia, remimazolam is theorized to be superior to propofol in respect to sedation-associated bradycardia. One specific study notes a 14% decrease in frequency of bradycardia compared to propofol. Further benefits of remimazolam over propofol include the availability of an effective and reliable antidote, flumazenil. CONCLUSION: In being that remimazolam has primarily been used and studied in short-term sedation, we can only confidently conclude remimazolam's safety in these settings. There is little research being done in the way of ICU sedation or general anesthesia, but with the relatively similar, or decreased rates of adverse events with remimazolam, we suspect an increase in clinical research of remimazolam in these settings. With continued robust research, remimazolam could become more widely accepted as a safe alternative to current sedatives.

A Comparison of the Use of Propofol versus Midazolam for Pediatric Magnetic Resonance Imaging Sedation: Retrospective Cohort Study.

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

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

The impact of ketamine on emergency rapid sequence intubation: a systematic review and meta-analysis.

BACKGROUND: Rapid sequence intubation (RSI) is a crucial step in the resuscitation process for critically ill patients, and the judicious use of sedative drugs during RSI significantly influences the clinical outcomes of patients. Ketamine is a commonly used anesthetic sedative; however, its impact on the mortality of patients undergoing RSI has yielded inconsistent findings. Therefore, we conducted a systematic review and meta-analysis investigating ketamine's role in RSI to provide insights into selecting appropriate sedatives for critically ill patients. METHODS: In this systematic review and meta-analysis, we conducted a systematic search on MEDLINE (PubMed), Embase, and Cochrane Central Register of Controlled Trials, without restricting to randomized controlled trials (RCTs) or cohort studies. The search was performed from inception until Dec 12, 2023, with no language restrictions. All studies comparing the use of sedatives, including ketamine, and documenting in-hospital mortality were included in this study. RESULTS: A total of 991 studies were identified, out of which 15 studies (5 RCTs and 10 cohort studies) involving 16,807 participants fulfilled the inclusion criteria. No significant impact on in-hospital mortality was observed with the use of ketamine compared to other drugs during RSI (OR 0.90, 95%CI 0.72 to 1.12). Low-quality evidence suggested that ketamine might reduce mortality within the first seven days of hospitalization (OR 0.42, 95%CI 0.19 to 0.93), but it may also have a potential effect on prolonging ICU-free days at day 28 (MD -0.71, 95%CI -1.38 to -0.05). There were no significant differences in the results of the other RSI-related outcomes, such as physiological function and adverse events. CONCLUSIONS: Based on existing studies, ketamine showed no significant difference compared to other sedatives in terms of in-hospital mortality, physiological impact, and side effects following RSI. However, it may reduce mortality within 7 days while probably prolong the length of stay in the ICU. TRIAL REGISTRATION: CRD42023478020.

Midazolam-Induced Seizure-Like Activity in Five Neonates: A case series.

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

Dexmedetomidine versus Ketofol for Moderate Sedation in Endoscopic Retrograde Cholangiopancreatography.

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

Evaluation of Intranasal Fentanyl and Midazolam Among Inpatient Pediatric Patients.

OBJECTIVES: The use of intranasal (IN) analgesics and sedatives has been studied among pediatrics patients in the emergency department and outpatient settings. However, less is known about their usage in inpatient settings. This study aims to evaluate the indications and safety profile for IN fentanyl and midazolam usage in pediatric patients admitted to a large tertiary care children's hospital. METHODS: This study is a retrospective chart review of admitted patients receiving IN fentanyl and/or midazolam over a 6-year period. Indications for medication use, medication dosages, patient characteristics, and any serious adverse drug reactions were recorded. Reported serious adverse outcomes include use of reversal agents as well as any documented respiratory depression, hypotension, or need for escalation of care. RESULTS: Of 156 patients included, 119 (76%) received IN midazolam alone, 20 (13%) patients received IN fentanyl alone, and 17 (11%) patients received both medications. The most common applications for IN medication administration were nasogastric tube placements (n = 62), peripheral intravenous line insertions (n = 30), peripherally-inserted central catheter placements (n = 23), and lumbar punctures (n = 16). No serious adverse events were reported. CONCLUSIONS: This study suggests that IN fentanyl and midazolam were administered to pediatric inpatients undergoing routine procedures without serious adverse drug reactions being reported. Although these findings are encouraging, more prospective studies are needed before wider implementation of IN fentanyl and midazolam administration in pediatric inpatients.

The effect of dexmedetomidine on emergence delirium of postanesthesia events in pediatric department: A systematic review and meta-analysis of randomized controlled trials.

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

Comparative efficacy and safety of ciprofol, propofol, and propofol and etomidate mixture, and ciprofol and etomidate mixture in patients undergoing painless gastroscopy: A randomized, double-blind controlled clinical trial.

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

Delirium event and associated treatment modifications among older adults with Alzheimer's disease: An interrupted time-series analysis of Medicare data.

BACKGROUND: Both Alzheimer's disease (AD) and deliriogenic medications increase the risk of delirium in older adults. This study examined the association between delirium and the subsequent monthly use of anticholinergic, sedative, and opioid medications in the 1 year after delirium in older adults with AD. METHODS: This comparative interrupted time series analysis involved adults (aged 65 years and older) with a diagnosis of AD initiating on cholinesterase inhibitors (ChEIs) based on 2013-2017 Medicare data. Separate patient-level segmented regression models were used for each outcome to evaluate changes in the cumulative anticholinergic burden (CAB), sedative load, and opioid load after the delirium/index event using a 12-month baseline and follow-up period among patients who had a delirium event and those without delirium (control group). Propensity score-based stabilized weights were utilized to balance baseline factors in the delirium and control groups. RESULTS: The study included 80,019 older adults with AD with incident ChEI use; 17.11% had delirium. There was an immediate decline in monthly CAB after the delirium event (mean estimate -0.86, p-value: 0.01) compared to the control group. A similar decline was observed when examining the sedative load (-0.06, p-value: 0.002) after the delirium event. However, there was no decline in opioid load (-0.50, p-value: 0.18). In the long term, CAB (0.13; p-value: <0.0001), sedative load (0.01; p-value: <0.001), and opioid load (0.07; p-value: 0.006) increased over the 1-year post-delirium period in the delirium group compared to those without delirium. CONCLUSION: This study found the burden of deliriogenic medications over the 1-year follow-up showed increasing trends in older adults with AD, even though there was some level shift in CAB and sedative load after the delirium event.

Comparison Between Dexmedetomidine and Midazolam-Fentanyl Combination in Flexible Bronchoscopy: A Prospective, Randomized, Double-blinded Study.

BACKGROUND: Dexmedetomidine has acceptable clinical utility for inducing sedation during flexible bronchoscopy. Reducing its dose may not only ameliorate its cardiovascular side effects, but also maintain its clinical usefulness. METHODS: Patients between 18 and 65 years were randomized to either dexmedetomidine (0.75 µg/kg) or the midazolam-fentanyl group (0.035 mg/kg midazolam and 25 mcg fentanyl). The primary outcome measure was the composite score. Other parameters noted were: oxygen saturation, hemodynamic variables, Modified Ramsay Sedation Score, Numerical Rating Scale (NRS) for pain intensity and distress, Visual Analog Scale score for cough, rescue medication doses, ease of doing bronchoscopy, and patient response 24 hours after bronchoscopy. RESULTS: In each arm, 31 patients were enrolled. The composite score at the nasopharynx was in the ideal category in 26 patients in dexmedetomidine and 21 in the midazolam-fentanyl group (P=0.007). At the tracheal level, the corresponding values were 24 and 16 (P=0.056). There was no significant difference between the 2 groups regarding the secondary outcome measures except hemodynamic parameters. The mean heart rate in the dexmedetomidine and midazolam-fentanyl groups, respectively, was as follows: at 10 minutes after start of FB (90.10±14.575, 104.35±18.48; P=0.001), at the end of FB (98.39±18.70, 105.94±17.45; P=0.016), and at 10 minutes after end of FB (89.84±12.02, 93.90±13.74; P=0.022). No patient developed bradycardia. Two patients (P=0.491) in the dexmedetomidine group developed hypotension. CONCLUSION: Low-dose dexmedetomidine (0.75 µg/kg single dose) appears to lead to a better composite score compared with the midazolam-fentanyl combination.

Comparison of the recovery quality between remimazolam and propofol after general anesthesia: systematic review and a meta-analysis of randomized controlled trials.

Introduction: To evaluate the recovery quality between remimazolam and propofol after general anesthesia surgery. Methods: We included eligible randomized controlled trials (RCTs) in EMBASE, PubMed, Cochrane Central, Scopus, and Web of Science up to June 26, 2024 for comparison the recovery quality of remimazolam and propofol after general anaesthesia. The primary outcomes were the total Quality of Recovery-15 (QoR-15) and five dimensions of QoR-15 on postoperative day 1 (POD1). Secondary outcomes were adverse events, the Quality of Recovery-40 (QoR-40) on POD1, and the intraoperative and postoperative time characteristics. Results: Thirteen RCTs with a total of 1,305 patients were included in this meta-analysis. Our statistical analysis showed that remimazolam group had higher QoR-15 score on POD1, with no significant difference (Mean Difference (MD) = 1.24; 95% confidence interval (CI), [-1.67-4.15]; I2 = 75%; P = 0.41). In the five dimensions of QoR-15, remimazolam group was superior to propofol group in terms of physical independence (MD = 0.79; 95% CI [0.31-1.27]; I2 = 0%; P = 0.001). Remimazolam group was lower than propofol group in incidence of hypotension (Risk Ratio (RR) = 0.48; 95% CI [0.40-0.59]; I2 = 14%; P < 0.00001), bradycardia (RR = 0.18; 95% CI [0.08-0.38]; I2 = 0%; P < 0.0001) and injection pain (RR = 0.03; 95% CI [0.01-0.12]; I2 = 48%; P < 0.00001), respectively. The intraoperative and postoperative time characteristics and the QoR-40 were similar in the two groups. Conclusions: Our analysis showed that the recovery quality of the remimazolam group after general anaesthesia was similar to propofol group, while the incidence of adverse events was low in remimazolam group. As a potential anesthetic, remimazolam can be used in place of propofol for surgical general anesthesia.

Efficacy and safety of insomnia treatment with lemborexant in older adults: analyses from three clinical trials.

BACKGROUND: Insomnia is more common as people age. Several common hypnotics used to treat insomnia often do not adequately alleviate sleep issues in older adults and may be associated with negative residual effects such as an increased risk of falls, cognitive impairment, automobile accidents, and lack of response to auditory stimuli. The objective of these analyses of three clinical studies was to investigate the efficacy and safety of the dual orexin-receptor antagonist lemborexant (LEM) in older adults. METHODS: Study E2006-G000-304 (Study 304; NCT02783729) was a randomized, double-blind, placebo (PBO)-controlled, active-comparator trial where subjects with insomnia disorder received LEM 5 mg (LEM5), LEM 10 mg (LEM10), zolpidem tartrate extended-release 6.25 mg (ZOL), or PBO for 30 days. In crossover Study E2006-E044-106 (Study 106; NCT02583451), healthy subjects (good sleepers) received LEM 2.5 mg, LEM5, LEM10, or PBO for eight nights or zopiclone on days 1 and 8 (and PBO on days 2-7). In crossover Study E2006-A001-108 (Study 108; NCT03008447), healthy subjects received a single dose of LEM5, LEM10, PBO, or ZOL. Sleep assessments included polysomnography-based latency to persistent sleep (LPS), wake after sleep onset (WASO), WASO in the second half of the night (WASO2H), sleep efficiency, postural stability, middle-of-the-night and next-day cognitive performance, middle-of-the-night auditory awakening threshold and return-to-sleep latency, and driving performance. RESULTS: Overall, 453 of 1006 (45%; Study 304), 24 of 48 (50%; Study 106), and 28 of 56 (50%; Study 108) subjects were aged ≥ 65 years. In Study 304, LEM decreased (improved) LPS, WASO, and WASO2H from baseline more than ZOL and PBO; subjects treated with LEM had greater increases in sleep efficiency (improved) than with ZOL or PBO. In both Studies 304 and 108, postural stability was not impaired at waketime in subjects who received LEM compared with PBO. At waketime, LEM did not impair memory compared with PBO. In Study 108, following middle-of-the-night awakening, LEM and ZOL did not affect subjects' ability to awaken to auditory stimuli; LEM did not affect tests of memory and attention. In Study 106, LEM did not impair next-day driving performance in healthy elderly compared with PBO. LEM was well tolerated in subjects aged ≥ 65 years. CONCLUSIONS: LEM provided benefits on sleep variables without next-morning residual effects in subjects aged ≥ 65 years, supporting LEM as a treatment option for older adults with insomnia. TRIAL REGISTRATION NUMBERS AND DATES OF REGISTRATION: Study 304: ClinicalTrials.gov identifier, NCT02783729, date of registration, 26 May 2016. Study 106: ClinicalTrials.gov identifier, NCT02583451, date of registration, 22 October 2015. Study 108: ClinicalTrials.gov identifier, NCT03008447, date of registration, 2 January 2017.

The prevalence of insomnia increases with age; however, some hypnotics used for treating insomnia do not adequately resolve sleep problems in older adults and may be associated with adverse residual effects. Specifically, some hypnotics pose safety concerns in this population of patients who are generally more vulnerable to treatment-related effects, including increasing the risk of falls, risks of cognitive impairment, automobile accidents, and unresponsiveness to auditory stimuli. Safer and more effective insomnia medications are needed to reduce sleep problems with improved side-effect profiles. This analysis of lemborexant clinical studies conducted in adult subjects at least 65 years old found the drug to be effective without impairing memory, attention or balance the following day compared with placebo. These subjects were normal sleepers (for age) or had insomnia disorder. Furthermore, lemborexant was not associated with impaired ability to drive the next morning or awaken to loud middle-of-the-night sounds. Lemborexant was well tolerated in these older adults, similar to findings for adults aged at least 18 years. These findings indicate that lemborexant may be an appropriate treatment option for insomnia in older adults.