BACKGROUND: As a new type of intravenous anesthetic, ciprofol has the advantages of fast onset of action, fast recovery and high clearance rate. This study aimed to investigate the effectiveness and safety of ciprofol versus traditional propofol for anesthesia and sedation in and out of the operating room.
METHODS: We searched the literature in PubMed, Web of Science, Cochrane Library, and Embase databases from January 2021 to December 2023. All clinical studies comparing the sedative effects of propofol and ciprofol, both inside and outside the operating room, were included in our trial. The main outcome measures were induction time and incidence of injection-site pain. Data are merged using risk ratio and standardized mean difference with 95% confidence interval. Subgroup analysis, meta-regression, sensitivity analysis, and publication bias were performed. The study protocol was prospectively registered with PROSPERO (CRD42023447747).
RESULTS: A total of 15 randomized, controlled trials involving 2002 patients were included in this study. Compared with propofol, ciprofol has a longer induction time in the operating room but a shorter induction time in non-operating room settings. Ciprofol can effectively reduce the risk of injection-site pain and respiratory depression both inside and outside the operating room. In addition, the risk of drug-related hypotension induced with ciprofol in the operating room is lower, but the awakening time is also longer. Meta-regression analysis showed that neither age nor BMI were potential sources of heterogeneity. Funnel plot, egger and begg tests showed no significant publication bias. Sensitivity analyzes indicate that our results are robust and reliable.
CONCLUSIONS: Ciprofol has absolute advantages in reducing the risk of injection-site pain and respiratory depression, both in and outside operating room. Intraoperative use of ciprofol reduces the risk of drug-related hypotension and may also reduce the risk of intraoperative physical movements. However, ciprofol may have longer induction and awakening time than propofol.

Background and Objectives: Remimazolam, a novel benzodiazepine, is used for procedural sedation and general anesthesia due to its rapid onset and short duration of action. However, remimazolam-induced anaphylaxis (RIA) is a rare but severe complication. This study aimed to analyze RIA characteristics, focusing on cardiovascular collapse, and provide guidelines for safe remimazolam use. Methods: This study conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Research articles retrieved from PubMed on 26 May 2023, using the keywords \'remimazolam AND anaphylaxis\' were evaluated based on the inclusion criteria of being written in English and aligning with the World Allergy Organization criteria for anaphylaxis, while studies not meeting these criteria were excluded. All published articles up to the search date were included without any date restrictions. The review analyzed factors such as age, sex, type of anesthesia, remimazolam dose (bolus/continuous), allergic symptoms and sign, epinephrine use, serum tryptase levels, and skin prick tests. Results: Among eleven cases, the mean age was 55.6 ± 19.6 years, with 81.8% male. Hypotension (81.8%) was the most common symptom, followed by bradycardia (54.5%) and desaturation (36.4%). Two patients experienced cardiac arrest. Serum tryptase levels confirmed anaphylaxis in ten cases. Epinephrine was the primary treatment, with intravenous doses ranging from 0.1 mg to 0.3 mg. Conclusions: Vigilance is crucial when administering remimazolam, adhering to recommended dosages, and promptly treating RIA with epinephrine. Further research is needed to understand the risk factors and refine the management strategies. Guidelines for safe remimazolam use are proposed.

BACKGROUND: Dexmedetomidine and midazolam are commonly used sedatives in children. We conducted a systematic review and meta-analysis to compare the safety and effectiveness of sedation provided by dexmedetomidine combined with midazolam versus other sedatives including chloral hydrate, midazolam and other sedatives in pediatric sedation.
METHODS: The Embase, Web of Science, Cochrane Library, and PubMed databases, and Clinicaltrials.gov register of controlled trials were searched from inception to June 2022. All randomized controlled trials used dexmedetomidine-midazolam in pediatric sedation were enrolled. The articles search, data extraction, and quality assessment of included studies were performed independently by two researchers. The success rate of sedation was considered as the primary outcome. The secondary outcomes included onset time of sedation, recovery time of sedation and occurrence of adverse events.
RESULTS: A total of 522 studies were screened and 6 RCTs were identified; 859 patients were analyzed. The administration of dexmedetomidine combined with midazolam was associated with a higher sedation success rate and a lower incidence of nausea and vomiting in computed tomography, magnetic resonance imaging, Auditory Brainstem Response test or fiberoptic bronchoscopy examinations than the other sedatives did (OR = 2.92; 95% CI: 1.39-6.13, P = 0.005, I2 = 51%; OR = 0.23, 95% CI: 0.07-0.68, P = 0.008, I2 = 0%, respectively). Two groups did not differ significantly in recovery time and the occurrence of adverse reactions (WMD = - 0.27, 95% CI: - 0.93 to - 0.39, P = 0.42; OR 0.70; 95% CI: 0.48-1.02, P = 0.06, I2 = 45%. respectively). However, the results of the subgroup analysis of ASA I-II children showed a quicker onset time in dexmedetomidine-midazolam group than the other sedatives (WMD=-3.08; 95% CI: -4.66 to - 1.49, P = 0.0001, I2 = 30%).
CONCLUSIONS: This meta-analysis showed that compared with the control group, dexmedetomidine combined with midazolam group provided higher sedation success rates and caused a lower incidence of nausea and vomiting in completing examinations, indicating a prospective outpatient clinical application for procedural sedation.

Previous studies have reported inconsistent results about exogenous melatonin\'s sleep-promoting effects. A possible explanation relies on the heterogeneity in administration schedule and dose, which might be accountable for differences in treatment efficacy. In this paper, we undertook a systematic review and meta-analysis of double-blind, randomized controlled trials performed on patients with insomnia and healthy volunteers, evaluating the effect of melatonin administration on sleep-related parameters. The standardized mean difference between treatment and placebo groups in terms of sleep onset latency and total sleep time were used as outcomes. Dose-response and meta-regression models were estimated to explore how time of administration, dose, and other treatment-related parameters might affect exogenous melatonin\'s efficacy. We included 26 randomized controlled trials published between 1987 and 2020, for a total of 1689 observations. Dose-response meta-analysis showed that melatonin gradually reduces sleep onset latency and increases total sleep time, peaking at 4 mg/day. Meta-regression models showed that insomnia status (β = 0.50, p < 0.001) and time between treatment administration and the sleep episode (β = -0.16, p = 0.023) were significant predictors of sleep onset latency, while the time of day (β = -0.086, p < 0.01) was the only significant predictor of total sleep time. Our results suggest that advancing the timing of administration (3 h before the desired bedtime) and increasing the administered dose (4 mg/day), as compared to the exogenous melatonin schedule most used in clinical practice (2 mg 30 min before the desired bedtime), might optimize the efficacy of exogenous melatonin in promoting sleep.

BACKGROUND: Remimazolam is a recently developed, ultrashort-acting benzodiazepine that is used as a general anesthetic. Some cases of remimazolam anaphylaxis have been reported, but its characteristics are not fully understood. We present an interesting case report and review of the literature to better understand remimazolam anaphylaxis.
METHODS: A 75-year-old man scheduled for robot-assisted gastrectomy was administered remimazolam for the induction of general anesthesia. After intubation, low end-expiratory CO2, high airway pressure and concurrent circulatory collapse were observed. Bronchoscopy revealed marked tracheal and bronchial edema, which we diagnosed as anaphylaxis. The patient suffered cardiac arrest after bronchoscopy but recovered immediately with intravenous adrenaline administration and chest compressions. We performed skin prick tests for the drugs used during induction except for remimazolam, considering the high risk of systemic adverse reactions to remimazolam. We diagnosed remimazolam anaphylaxis because the skin prick test results for the other drugs used during anesthesia were negative, and these drugs could have been used without allergic reactions during the subsequent surgery. Furthermore, this patient had experienced severe anaphylactic-like reactions when he underwent cardiac surgery a year earlier, in which midazolam had been used, but it was not thought to be the allergen at that time. Based on these findings, cross-reactivity to remimazolam and midazolam was suspected. However, the patient had previously received another benzodiazepine, brotizolam, to which he was not allergic, suggesting that cross-reactivity of remimazolam may vary among benzodiazepines. In this article, we reviewed the 11 cases of remimazolam anaphylaxis that have been described in the literature.
CONCLUSIONS: Remimazolam is an ultrashort-acting sedative; however, it can cause life-threatening anaphylaxis. In addition, its cross-reactivity with other benzodiazepines is not fully understood. To increase the safety of this drug, further research and more experience in its use are needed.

BACKGROUND: Agitation/delirium is commonly seen in children after anesthesia, and a proper dose of dexmedetomidine can prevent this complication. This study aimed to investigate the effects of different doses of Dexmedetomidine (DEX) on agitation/delirium and other complications in anesthetized children, providing clinical evidence for dose recommendations of DEX.
METHODS: This study was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A systematic search was conducted in the Cochrane Library, PubMed, Web of Science, and EMBASE. Two independent researchers performed literature screening, data extraction, and assessed the methodological quality. Data analysis was conducted using R and STATA 16.0.
RESULTS: In the final analysis, 20 randomized controlled trials (RCTs) involving 2521 children were included. The results showed that in comparison to normal saline, 1 µg/kg, 1.5 µg/kg, and 2 µg/kg intranasal DEX significantly reduced the incidence of post-anesthetic emergence agitation in children with the most effective dose being 2 µg/kg (SUCRA = 0.91). Compared with normal saline, 1 µg/kg, 1.5 µg/kg, and 2 µg/kg intranasal DEX reduced patient\'s need for postoperative analgesia, with the most effective dose being 1.5 µg/kg (SUCRA = 0.78). However, 1 µg/kg DEX performed the best in reducing Pediatric Anaesthesia Emergence Delirium (PAED) Scale score (SUCRA = 0.88).
CONCLUSIONS: Compared with normal saline, intranasal administration of 2 µg/kg DEX and 1.5 µg/kg DEX are the optimal doses to reduce the incidence of agitation and the need for postoperative pain relief in children under general anesthesia. Given effectiveness and safety, intranasal use of 1 µg/kg DEX appears to be the most effective dosage for anesthetized children.

BACKGROUND: Nasal surgeries, addressing anatomical variations for form and function, require careful anesthesia administration, including dexmedetomidine and remifentanil. This meta-analysis evaluates their safety and efficacy variations in nasal surgeries, emphasizing patient comfort and optimal outcomes.
METHODS: Four electronic databases (PubMed, Scopus, Web of Science, and CINAHL Complete) were searched for records in English. Studies that measure the effect of dexmedetomidine versus remifentanil on patients underwent nasal surgery were included. The Cochrane Collaboration\'s tool was used to assess the quality of the included studies. A random-effect model was preferred and statistical analysis was performed by Stata software version 17.
RESULTS: Out of an initial pool of 63 articles, five studies were selected for this analysis. All of these chosen studies were Randomized Controlled Trials (RCTs). The meta-analysis involved a total of 302 participants, with 152 in the remifentanil group and 150 in the dexmedetomidine group. The analysis aimed to compare the effects of Dexmedetomidine and Remifentanil on heart rate (HR) and mean arterial pressure (MAP) during surgery. Both groups exhibited similar MAP and HR, with the exception of a slightly lower HR in the remifentanil group at the 15th minute of surgery (Standardized Mean Difference: -0.24 [-0.83, 0.34]). Furthermore, when evaluating the impact of these medications on post-surgery outcomes, including pain levels, the use of pain relief medications, patient-surgeon satisfaction, agitation scores, and recovery time, no significant differences were observed between the two medications in any of these aspects.
CONCLUSIONS: In summary, the study compared Dexmedetomidine and Remifentanil in nasal surgeries anesthesia. No significant differences were found in heart rate, blood pressure, satisfaction, pain, agitation, or recovery time. The study had limitations, and future research should establish standardized protocols and consider various surgical factors.

BACKGROUND: Considering the persistent nature and higher prevalence of insomnia in cancer patients and survivors compared with the general population, there is a need for effective management strategies. This systematic review and meta-analysis aimed to comprehensively evaluate the available evidence for the efficacy of pharmacological and nonpharmacological interventions for insomnia in adult cancer patients and survivors.
METHODS: Following the PRISMA guidelines, we analyzed data from 61 randomized controlled trials involving 6528 participants. Interventions included pharmacological, physical, and psychological treatments, with a focus on insomnia severity and secondary sleep and non-sleep outcomes. Frequentist and Bayesian analytical strategies were employed for data synthesis and interpretation.
RESULTS: Cognitive-Behavioral Therapy for Insomnia (CBT-I) emerged as the most efficacious intervention for reducing insomnia severity in cancer survivors and further demonstrated significant improvements in fatigue, depressive symptoms, and anxiety. CBT-I showed a large postintervention effect (g = 0.86; 95% confidence interval [CI] = 0.57 to 1.15) and a medium effect at follow-up (g = 0.55; 95% CI = 0.18 to 0.92). Other interventions such as bright white light therapy, sleep medication, melatonin, exercise, mind-body therapies, and mindfulness-based therapies showed benefits, but the evidence for their efficacy was less convincing compared with CBT-I. Brief Behavioral Therapy for Insomnia showed promise as a less burdensome alternative for patients in active cancer treatment.
CONCLUSIONS: CBT-I is supported as a first-line treatment for insomnia in cancer survivors, with significant benefits observed across sleep and non-sleep outcomes. The findings also highlight the potential of less intensive alternatives. The research contributes valuable insights for clinical practice and underscores the need for further exploration into the complexities of sleep disturbances in cancer patients and survivors.

OBJECTIVE: The Drug Burden Index (DBI) calculates a person\'s exposure to anticholinergic and sedative medications. We aimed to review randomized controlled trials (RCTs) of deprescribing interventions that reported the DBI as an outcome, their characteristics, effectiveness in reducing the DBI, and impact on other outcomes.
METHODS: Systematic review with meta-analysis.
METHODS: RCTs of deprescribing interventions where the DBI was measured as a primary or secondary outcome in humans within any setting were included.
METHODS: Electronic databases, citation indexes, and gray literature were searched from April 1, 2007, to September 1, 2023. Quality was assessed using the Cochrane risk-of-bias tool.
RESULTS: Of 1721 records identified, 9 met the inclusion criteria. Six interventions were delivered by pharmacists and 3 were delivered by pharmacists/nurses or pharmacists/geriatricians. All interventions required at least intermediate-level skills and involved multiple components and target groups. Studies were conducted in the community (n = 5), nursing homes (n = 2), and hospitals (n = 2). The mean or median age was ≥75 years and most participants were women in all studies. Most (n = 6) studies were underpowered. The follow-up period ranged from 3 to 12 months. Three studies reported a lower DBI in the intervention group compared with control: 1 pharmacist independent prescriber-delivered in nursing homes (adjusted rate ratio, 0.83; 95% CI, 0.74 to 0.92), 1 pharmacist/nurse practitioner-delivered in hospital (adjusted mean difference (MD), -0.28; 95% CI, -0.51 to -0.04), and 1 geriatrician/pharmacist-delivered in hospital (MD, -0.28; 95% CI, -0.52 to -0.04). Meta-analysis showed no difference in the change in DBI between control and intervention groups in the community including nursing homes (MD, -0.03; 95% CI, -0.08 to 0.01) or hospital setting (MD, -0.19; 95% CI, -0.45 to 0.06). Interventions had inconsistent effects on cognition and no effect on other reported outcomes.
CONCLUSIONS: RCTs of deprescribing interventions had no significant impact on reducing DBI or improving outcomes. Further suitably powered studies are required.

BACKGROUND: Benzodiazepine (BDZP) and/or z-hypnotic dispensing during pregnancy has increased globally, as have rates of autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). This systematic review and meta-analysis aimed to estimate the association between gestational exposure to BDZP and/or z-hypnotics and diagnosis of ASD or ADHD in offspring.
METHODS: We searched MEDLINE, EMBASE, and SCOPUS from inception till December 2023 for relevant English-language articles. Outcomes of interest were risk of ASD and ADHD, two independent primary outcomes, in children exposed anytime during pregnancy to BDZP and/or z-hypnotics versus those unexposed. Secondary outcomes were trimester-wise analyses. Using a random effects model, we pooled the overall and trimester-wise hazard ratios (HRs), with 95% confidence intervals (CIs), separately for risk of ASD and ADHD.
RESULTS: We found six eligible retrospective cohort studies and no case-control studies. There was no increased risk of ASD associated with anytime gestational BDZP and/or z-hypnotic exposure (primary outcome, HR, 1.10; 95% CI, 0.81-1.50; 4 studies; n = 3,783,417; 80,270 exposed, 3,703,147 unexposed) nor after first trimester exposure (HR, 1.15; 95% CI, 0.83-1.58; 3 studies; n = 1,539,335; 70,737 exposed, 1,468,598 unexposed) or later trimester exposures. A very small but significantly increased risk of ADHD was noted with anytime gestational exposure to these drugs (primary outcome, HR, 1.07; 95% CI, 1.03-1.12; 4 studies; n = 2,000,777; 78,912 exposed, 1,921,865 unexposed) and also with (only) second trimester exposure (HR, 1.07; 95% CI, 1.03-1.12; 3 studies; n = 1,539,281; 33,355 exposed, 1,505,926 unexposed). Findings were consistent in sensitivity analyses.
CONCLUSIONS: Gestational exposure to benzodiazepines or z-hypnotics was not associated with an increased risk of ASD and with only a marginally increased risk of ADHD in offspring. Given the likelihood of confounding by indication and by unmeasured variables in the original studies, our findings should reassure women who need these medications for severe anxiety or insomnia during pregnancy.