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

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

Efficacy and Safety of Single-Dose Pregabalin in Preoperative Pediatric Sedation.

Introduction: This study aimed to investigate the anxiolytic and sedative effects of a single oral dose of 5 mg/kg pregabalin in pediatric patients undergoing elective surgery. It also assessed potential adverse effects and its impact on bispectral index (BIS) responses. Materials and Methods: This prospective randomized clinical trial enrolled 60 pediatric patients undergoing minor elective surgery. Patients were randomly assigned to receive either oral pregabalin (5 mg/kg) or a placebo one hour before induction of anesthesia. Anxiety levels were assessed using the Visual Analog Scale for Anxiety (VAS-A), and sedation levels were evaluated using the Ramsay Sedation Scale (RSS). Results: Pregabalin premedication significantly reduced preoperative anxiety, as indicated by lower VAS-A scores compared to the control group. Sedation levels, measured using the RSS, were significantly higher in the pregabalin group at various time points post-dose. During intubation, skin incision, and recovery, BIS responses were significantly lower in the pregabalin group. Conclusion: The use of single-dose pregabalin preoperatively in children recorded a significant decrease in anxiety and achieved a state of sedation without an increase in adverse effects.

Edward O. Bixler, PhD: from the Apollo project and chimpanzees to sleep epidemiology.

What an honor to write about Dr. Edward O. Bixler's contributions to the sleep field. In 1967, Dr. Bixler published a case report on a chimpanzee with implanted brain electrodes while working at an Air Force base in New Mexico. A few years later, in 1971, he published on the sleep effects of flurazepam in individuals with insomnia together with Dr. Anthony Kales, data that he had collected when the Sleep Research & Treatment Center (SRTC) was housed at the University of California Los Angeles. Dr. Bixler, a meticulous scientist, learned from Dr. Kales, a devoted clinician, to study "the whole patient, and all aspects of sleep," a legacy that continued when the SRTC moved to Penn State in Hershey. Indeed, Dr. Bixler's tenure at Penn State from 1971 until 2019 kept the science of the SRTC focused on that premise and helped translate scientific evidence into clinical care. He not only contributed early to the pharmacology of sleep and the effects of hypnotics, but he was also a pioneer in "sleep epidemiology." His "Prevalence of sleep disorders in the Los Angeles metropolitan area" study of 1979 was the first rigorous epidemiological study on sleep disturbances. Starting in 1990, he established the Penn State Adult Cohort to estimate the prevalence and natural history of sleep-disordered breathing and other sleep disorders in adults. Inspired by life-course epidemiology, he established in 2001 the Penn State Child Cohort to estimate the same phenomena in children. This Living Legend paper captures and highlights Dr. Bixler's enduring legacy to sleep science.

Inhaled volatile anesthetics in the intensive care unit.

The discovery and utilization of volatile anesthetics has significantly transformed surgical practices since their inception in the mid-19th century. Recently, a paradigm shift is observed as volatile anesthetics extend beyond traditional confines of the operating theatres, finding diverse applications in intensive care settings. In the dynamic landscape of intensive care, volatile anesthetics emerge as a promising avenue for addressing complex sedation requirements, managing refractory lung pathologies including acute respiratory distress syndrome and status asthmaticus, conditions of high sedative requirements including burns, high opioid or alcohol use and neurological conditions such as status epilepticus. Volatile anesthetics can be administered through either inhaled route via anesthetic machines/devices or through extracorporeal membrane oxygenation circuitry, providing intensivists with multiple options to tailor therapy. Furthermore, their unique pharmacokinetic profiles render them titratable and empower clinicians to individualize management with heightened accuracy, mitigating risks associated with conventional sedation modalities. Despite the amounting enthusiasm for the use of these therapies, barriers to widespread utilization include expanding equipment availability, staff familiarity and training of safe use. This article delves into the realm of applying inhaled volatile anesthetics in the intensive care unit through discussing their pharmacology, administration considerations in intensive care settings, complication considerations, and listing indications and evidence of the use of volatile anesthetics in the critically ill patient population.

Unveiling the pharmacological potential of Coelogyne suaveolens: An investigation of its diverse pharmacological activities by in vivo and computational studies.

The medicinal potential of Coelogyne suaveolens, a traditional medicinal plant, was investigated through in vivo and molecular docking studies. The ethyl acetate fraction of the plant's acetonic extract was subjected to various bioactivity tests to assess its analgesic, anxiolytic, and sedative effects on Swiss albino mice. Furthermore, we used GCMS to identify the bioactive chemicals in the extract's ethyl acetate fraction. The root and bulb extracts demonstrated significant analgesic activity in acetic acid-induced writhing, hot plate, and tail immersion tests in a dose-dependent manner when compared to the control. Again, the extract exhibited moderate anxiolytic activity in the elevated plus maze test at a dosage of 400 mg/kg body weight, while the root extract showed significant anxiolytic activity in the hole board test at the same dosage. Significant sedative activity was observed in the hole cross, open field, and rotarod tests at a dosage of 400 mg/kg. According to molecular docking studies, the extract has the potential to serve as an analgesic medication by reducing the enzymatic activity of cyclooxygenases 1 and 2. Overall, the findings suggest that C. suaveolens has substantial therapeutic potential for the development of novel treatments for pain, anxiety, and sleep disorders.

Relationship of psychotropic medication use with physical function among postmenopausal women.

To examine cross-sectional and longitudinal relationships of psychotropic medications with physical function after menopause. Analyses involved 4557 Women's Health Initiative Long Life Study (WHI-LLS) participants (mean age at WHI enrollment (1993-1998): 62.8 years). Antidepressant, anxiolytic, and sedative/hypnotic medications were evaluated at WHI enrollment and 3-year follow-up visits. Performance-based physical function [Short Physical Performance Battery (SPPB)] was assessed at the 2012-2013 WHI-LLS visit. Self-reported physical function [RAND-36] was examined at WHI enrollment and the last available follow-up visit-an average of 22 [±2.8] (range: 12-27) years post-enrollment. Multivariable regression models controlled for socio-demographic, lifestyle, and health characteristics. Anxiolytics were not related to physical function. At WHI enrollment, antidepressant use was cross-sectionally related to worse self-reported physical function defined as a continuous (ß = -6.27, 95% confidence interval [CI]: -8.48, -4.07) or as a categorical (< 78 vs. ≥ 78) (odds ratio [OR] = 2.10, 95% CI: 1.48, 2.98) outcome. Antidepressant use at WHI enrollment was also associated with worse performance-based physical function (SPPB) [< 10 vs. ≥ 10] (OR = 1.53, 95% CI: 1.05, 2.21) at the 2012-2013 WHI-LLS visit. Compared to non-users, those using sedative/hypnotics at WHI enrollment but not at the 3-year follow-up visit reported a faster decline in physical function between WHI enrollment and follow-up visits. Among postmenopausal women, antidepressant use was cross-sectionally related to worse self-reported physical function, and with worse performance-based physical function after > 20 years of follow-up. Complex relationships found for hypnotic/sedatives were unexpected and necessitate further investigation.

Medication-Seeking Behaviors and Correlated Characteristics of Zolpidem Users in Taiwan-A Shared Patient Network Analysis.

Increasing insomnia signals a public health problem, alongside rising zolpidem use. This study investigates the factors behind the disproportionate rise in zolpidem prescriptions in Taiwan. It aims to identify the determinants of high-dose zolpidem users in Taiwan's Yilan County and employ an innovative approach to outline their medication-seeking patterns, using Taiwan's healthcare database. The associations between sociodemographic and clinical factors and low-dose and high-dose users were analyzed using multiple logistic regression. Social network analysis was employed to explore medication-seeking behavior among these user groups across different healthcare institutions. Of our 5290 participants, 22.82% are high-dose users. This study found that males face a 1.33-fold higher risk and that having chronic diseases is a major risk factor, contributing to a more than four-times higher risk (adjusted OR = 4.27, 95% CI 1.55-11.70) of being a high-dose user of zolpidem. A social network analysis showed a higher density (0.52) for high-dose users, revealing their frequent visits, for zolpidem, to different healthcare institutions. Psychiatrists have a central role in both low-dose and high-dose user networks, with a greater influence on low-dose users (64.4) than high-dose users (32.2). In sum, patients seeking high doses of zolpidem are driven by personal factors. Future efforts should include regulated dispensing, public health education, and specialized training for healthcare professionals on drug addiction.

Identification of sedative-hypnotic compounds shared by five medicinal Polyporales mushrooms using UPLC-Q-TOF-MS/MS-based untargeted metabolomics.

BACKGROUND: Five Polyporales mushrooms, namely Amauroderma rugosum, Ganoderma lucidum, G. resinaceum, G. sinense and Trametes versicolor, are commonly used in China for managing insomnia. However, their active components for this application are not fully understood, restricting their universal recognition. PURPOSE: In this study, we aimed to identify sedative-hypnotic compounds shared by these five Polyporales mushrooms. STUDY DESIGN AND METHODS: A UPLC-Q-TOF-MS/MS-based untargeted metabolomics, including OPLS-DA (orthogonal projection of potential structure discriminant analysis) and OPLS (orthogonal projections to latent structures) analysis together with mouse assays, were used to identify the main sedative-hypnotic compounds shared by the five Polyporales mushrooms. A pentobarbital sodium-induced sleeping model was used to investigate the sedative-hypnotic effects of the five mushrooms and their sedative-hypnotic compounds. RESULTS: Ninety-two shared compounds in the five mushrooms were identified. Mouse assays showed that these mushrooms exerted sedative-hypnotic effects, with different potencies. Six triterpenes [four ganoderic acids (B, C1, F and H) and two ganoderenic acids (A and D)] were found to be the main sedative-hypnotic compounds shared by the five mushrooms. CONCLUSION: We for the first time found that these six triterpenes contribute to the sedative-hypnotic ability of the five mushrooms. Our novel findings provide pharmacological and chemical justifications for the use of the five medicinal mushrooms in managing insomnia.

Sedative and hypnotic effects of the saponins from a traditional edible plant Liriope spicata Lour. in PCPA-induced insomnia mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Liriope spicata Lour., a species listed in the catalogue of 'Medicinal and Edible Homologous Species', is traditionally used for the treatment of fatigue, restlessness, insomnia and constipation. AIM OF THE STUDY: This study is aimed to evaluate the sedative and hypnotic effect of the saponins from a natural plant L. spicata Lour. in vivo. MATERIALS AND METHODS: The total saponin (LSTS) and purified saponin (LSPS) were extracted from L. spicata, followed by a thorough analysis of their major components using the HPLC-MS. Subsequently, the therapeutic efficacy of LSTS and LSPS was evaluated by the improvement of anxiety and depression behaviors of the PCPA-induced mice. RESULTS: LSTS and LSPS exhibited similar saponin compositions but differ in their composition ratios, with liriopesides-type saponins accounting for a larger proportion in LSTS. Studies demonstrated that both LSTS and LSPS can extend sleep duration and immobility time, while reducing sleep latency in PCPA-induced mice. However, there was no significant difference in weight change among the various mice groups. Elisa results indicated that the LSTS and LSPS could decrease levels of NE, DA, IL-6, and elevate the levels of 5-HT, NO, PGD2 and TNF-α in mice plasma. LSTS enhanced the expression of neurotransmitter receptors, while LSPS exhibited a more pronounced effect in regulating the expression of inflammatory factors. In conclusion, the saponins derived from L. spicata might hold promise as ingredients for developing health foods with sedative and hypnotic effects, potentially related to the modulation of serotonergic and GABAAergic neuron expression, as well as immunomodulatory process.

A modified QuEChERS-based UPLC-MS/MS method for rapid determination of multiple antibiotics and sedative residues in freshwater fish.

Antibiotics and sedatives are used in freshwater fish culture and transportation, and residue in freshwater fish pose potential risks to human health. Therefore, a throughput method was developed to detect antibiotic and sedative residues in fish, simultaneously quantifying 68 antibiotics and 9 sedatives in freshwater fish using a modified QuEChERS extraction method and UPLC-MS/MS. Matrix-matched calibrations demonstrated good correlation coefficients (R2 > 0.995), with a recovery range of 66.2-118.5%. The intra-day and inter-day relative standard deviation (RSD) were below 9.7% and 12.8%, respectively. The limits of detection (LOD) and quantification (LOQ) were 0.08-1.46 µg/kg and 0.25-4.86 µg/kg, respectively. 68.8% of analytes had weak matrix effects, and 13.0% had moderate matrix effects. In addition, diazepam and many types of antibiotics were detected in30 freshwater fish. The validation parameters were in agreement with the acceptable criteria of the Codex guidelines. The method was effective in analyzing antibiotic and sedative residues in freshwater fish.

The interaction of Suk-Saiyasna remedy with GABAA and CB1 receptor-targeting drugs: Enhancing hypnotic and sedative effects in in vivo models.

The Suk-Saiyasna remedy, an herbal treatment, was historically used but ceased due to its cannabis content. After a relaxation of drug control laws in Thailand, its use re-emerged. This study examines the Suk-Saiyasna remedy's impact on rodent behavior and its receptor effects. This study was conducted to assess the sedative-like effects of the remedy on mice. The mice were divided into groups receiving 0.6, 3, 30, and 60 mg/kg extracts, with negative controls for comparison. We also investigated the impact on receptors, utilizing negative controls and pretreatment with receptor blockers, followed by either a negative control or a 60 mg/kg extract. Furthermore, this study investigated the behavioral aspects of mice, including anxiolytic effects, antidepressant-like effects, and motor coordination, utilizing the elevated plus-maze, open-field, and rotarod performance tests. The Suk-Saiyasna remedy (P < 0.05) decreased significantly in the latent period and increased sleeping time in the treated groups. Moreover, the Suk-Saiyasna remedy also showed efficacy in reaction to GABAA receptors and cannabinoid CB1 receptors (P < 0.05). In addition, positive effects were observed regarding the animal behavior in the arena, as the animal activity, behavior, and muscle coordination were reduced (P < 0.05). The Suk-Saiyasna remedy may be involved in a sedative-hypnotic-like effect in rodents under normal conditions through the modulation of GABAergic neurons and induction of the cannabinoid CB1 receptor mechanism.

Randomized controlled trial of remimazolam compared with placebo in Japanese patients undergoing upper gastrointestinal endoscopy: Phase III investigator-initiated clinical trial.

OBJECTIVES: To assess the effectiveness of remimazolam against normal saline (placebo) as a sedative agent for endoscopy in a multicenter, randomized, double-blind, investigator-initiated phase III controlled trial. METHODS: We included 48 Japanese patients undergoing upper gastrointestinal endoscopy. For the procedure, an initial remimazolam dose of 3 mg and additional doses of 1 mg were administered, as determined in the phase II clinical study. The primary study end-point was the successful sedation rate during gastrointestinal endoscopy, determined as a Modified Observer's Assessment of Alertness/Sedation score ≤4 before the start of endoscopy, the completion of gastrointestinal endoscopy, and two or fewer additional doses per 6 min. RESULTS: The successful endoscopy sedation rates were 91.9% and 9.1% in the remimazolam and placebo groups, respectively (P < 0.01). The time from the end of endoscopy to arousal was 0.0 (0.0-0.0) min for both groups. The number of additional doses required to achieve sedation was lower in the remimazolam group than that in the placebo group (P < 0.01). CONCLUSIONS: Remimazolam demonstrated a significantly higher sedation effect during upper gastrointestinal endoscopy in Japanese patients with safe and fast recovery compared with placebo.

Reducing the drug burden of sedative and anticholinergic medications in older adults: a scoping review of explicit decision criteria.

OBJECTIVES: To describe the extent, characteristics, and knowledge gaps regarding explicit decision criteria for deprescribing drugs with anticholinergic or sedative properties (Ach/Sed) in older adults. DESIGN: Scoping review. SETTING AND PARTICIPANTS: Original studies, clinical trial protocols, grey literature, and Summaries of Product Characteristics. METHODS: Searches targeting explicit decision criteria for deprescribing Ach/Sed were performed across MEDLINE, EMBASE, CINAHL, and Web of Science, including trial registries (clinicaltrials.gov, ICTRP, EU-CTR, ANZCTR) for pertinent articles, study protocols. Additionally, to encompass non-traditional or 'grey literature' sources, Google searches and relevant agency websites were explored, alongside the summary of product characteristics for Ach/Sed. RESULTS: The initial literature search identified 8,192 unique data sources. After review, 188 original articles or books, 79 internet sources, and 127 SmPCs were included. Examining these sources for explicit criteria for 154 Ach/Sed, overall, 1,271 explicit criteria guidance for identifying clinical scenarios warranting deprescription of Ach/Sed across 145/154 Ach/Sed were identified. These criteria were identified mainly from qualitative research and Summaries of Product Characteristics. Additionally, 455 criteria-based recommendations suggesting approaches for tapering implementation across 76/154 Ach/Sed were identified, mostly from sources classified as expert opinions. Significant heterogeneity was found across the approaches for tapering Ach/Sed. CONCLUSIONS: This scoping review provides a comprehensive overview of the literature providing guidance for clinical scenarios where Ach/Sed should be deprescribed and highlights the existing knowledge gaps regarding comprehensive guidance on tapering these drugs which warranties future research and development.

Standardization and Pharmacological Evaluation of Ziziphus mauritiana Extract for Sedative and Anticonvulsant Activity in Mice and Rat.

INTRODUCTION: Ziziphus mauritiana, sometimes called Indian jujube or Ber, belongs to the Rhamnaceae group of plants. The aqueous and ethanolic Ziziphus mauritiana formulations were shown to have analgesic, antipyretic, potent analgesic, anti-inflammatory, and anti-emetic properties. AIM & OBJECTIVES: The aim of this study is to investigate the sedative and anticonvulsant activities of Ziziphus mauritiana extract by governing 200 and 400 mg/kg body weight orally. MATERIAL AND METHODS: The leaves are extracted with ethanol and lukewarm water with a soxhlet apparatus for 72 hours. After that acute extract toxicity study was performed and then locomotor activity, pentobarbital induced sleeping time and anticonvulsant activity were performed with the extract. RESULTS: Oral administration of extract at dosages of 200 & 400 mg/kg was employed after an immediate toxicity test. At a dosage of 400 mg/kg, the number of locomotions was reduced significantly lengthened the period of time spent sleeping and there was showed a dosage-dependent reduction in all phases of an epileptic episode. CONCLUSION: In this study, the extract reduced locomotor activity, however, it had a superior profile for an antiepileptic action than phenytoin since it decreased locomotor activity to a lesser level. The considerable increase in pentobarbitone sleep hours with the extracts at a higher dose supported the sedative action of Z. mauritiana.

Cannabidiol Exerts Sedative and Hypnotic Effects in Normal and Insomnia Model Mice Through Activation of 5-HT1A Receptor.

Cannabis sativa has been used for improving sleep for long history. Cannabidiol (CBD) has drown much attention as a non-addictive psychoactive component in Cannabis sativa extract. However, the effects of CBD on sleep architecture and it's acting mechanism remains unclear. In the present study, we evaluated the sedative-hypnotic effect of cannabidiol (CBD), assessed the effects of CBD on sleep using a wireless physiological telemetry system. We further explored the therapeutic effects of CBD using 4-chloro-dl-phenylalanine (PCPA) induced insomnia model and changes in sleep latency, sleep duration and intestinal flora were evaluated. CBD shortened sleep latency and increases sleep duration in both normal and insomnia mice, and those effects were blocked by 5-HT1A receptor antagonist WAY100635. We determined that CBD increases 5-HT1A receptors expression and 5-HT content in the hypothalamus of PCPA-pretreated mice and affects tryptophan metabolism in the intestinal flora. These results showed that activation of 5-HT1A receptors is one of the potential mechanisms underlying the sedative-hypnotic effect of CBD. This study validated the effects of CBD on sleep and evaluated its potential therapeutic effects on insomnia.

Medication Dosage Impact on Mortality in Old-Age Individuals with Schizophrenia: A National Cohort Study.

As the prevalence of old-age individuals with schizophrenia (OAS) increases in a society undergoing demographic aging, the exploration of medication choices becomes increasingly crucial. Due to the current scarcity of literature on OAS, this study seeks to examine how the utilization and cumulative dosages of psychotropic medications influence both overall and cause-specific mortality risks within this population. A national cohort of 6433 individuals diagnosed with OAS was followed up for 5 years. This study involved comparing the mortality rates associated with low, moderate, and high dosages of antipsychotics, antidepressants, mood stabilizers, and sedative/hypnotic drugs against the 'no exposure' category, based on individual dosages. Cox regression was employed for survival analyses to compare overall mortality and specific-cause mortality across various dosage groups. The exposure variable examined was the dosage of a specific psychotropic medication. Covariates were adjusted accordingly. The analysis revealed that patients on low/moderate antipsychotic doses had improved survival compared to non-exposed individuals. Moderate antipsychotic use corresponded to reduced cardiovascular disease mortality risk. Similarly, those exposed to antidepressants had enhanced survival in low and moderate doses. Sedative-hypnotic exposure was linked to decreased mortality risk in low doses. This study observed that low/moderate antipsychotic doses in older adults with schizophrenia were associated with decreased all-cause mortality, emphasizing the significance of precise medication selection and dosing. It underscores the need for vigilant polypharmacy management and tailored medication strategies in addressing the complexities of treating OAS.

The novel non-hallucinogenic compound DM506 (3-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole) induces sedative- and anxiolytic-like activity in mice by a mechanism involving 5-HT2A receptor activation.

The anxiolytic and sedative-like effects of 3-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (DM506), a non-hallucinogenic compound derived from ibogamine, were studied in mice. The behavioral effects were examined using Elevated O-maze and novelty suppressed feeding (NSFT) tests, open field test, and loss of righting reflex (LORR) test. The results showed that 15 mg/kg DM506 induced acute and long-lasting anxiolytic-like activity in naive and stressed/anxious mice, respectively. Repeated administration of 5 mg/kg DM506 did not cause cumulative anxiolytic activity or any side effects. Higher doses of DM506 (40 mg/kg) induced sedative-like activity, which was inhibited by a selective 5-HT2A receptor antagonist, volinanserin. Electroencephalography results showed that 15 mg/kg DM506 fumarate increased the transition from a highly alert state (fast γ wavelength) to a more synchronized deep-sleeping activity (δ wavelength), which is reflected in the sedative/anxiolytic activity in mice but without the head-twitch response observed in hallucinogens. The functional, radioligand binding, and molecular docking results showed that DM506 binds to the agonist sites of human 5-HT2A (Ki = 24 nM) and 5-HT2B (Ki = 16 nM) receptors and activates them with a potency (EC50) of 9 nM and 3 nM, respectively. DM506 was relatively less potent and behaved as a partial agonist (efficacy <80%) for both receptor subtypes compared to the full agonist DOI (2,5-dimethoxy-4-iodoamphetamine). Our study showed for the first time that the non-hallucinogenic compound DM506 induces anxiolytic- and sedative-like activities in naïve and stressed/anxious mice in a dose-, time-, and volinanserin-sensitive manner, likely through mechanisms involving 5-HT2A receptor activation.

Sedative-hypnotics and osteoporotic fractures: A systematic review of observational studies with over six million individuals.

We reviewed and meta-analyzed 20 observational studies to examine the relationship between sedative-hypnotic use and osteoporotic fractures. We searched PubMed, Embase, APA PsycINFO, and Web of Science™ for studies that used cohort, case-control, case-crossover, and self-controlled case series designs. We further assessed the quality of each study and performed meta-analyses of association estimates, e.g., odds ratios (ORs). The analysis included 6,084,083 participants and found a slight association between the use of sedative-hypnotics and osteoporotic fractures, with differing strength of associations between different classes of drugs and greater sedative-hypnotics exposure. The pooled estimates ORs for case-control studies were 1.33 (95% CI 0.98-1.80) with benzodiazepines (BZD) and any fractures, 1.32 (95% CI 1.05-1.66) with BZDs and hip fractures, and case-crossover studies were 1.15 (95% CI 0.95-1.41) with BZDs and any fractures, 1.41 (95% CI 1.08-1.85) with Z-drugs and any fractures. The study suggests that more research is needed to aid medical professionals in balancing this potential risk of osteoporotic fractures associated with sedative-hypnotic use against other reported adverse events and anticipated therapy outcomes.

Remimazolam: A Retrospective Study of Initial Safety and Recovery Data in Diverse Procedural Sedation.

PURPOSE: The new ultra-short-acting benzodiazepine, remimazolam, offers a pharmacokinetic and pharmacodynamic advantage over commonly used procedural sedation medication. This retrospective study explored the real-world utilization of remimazolam during procedural sedation to support the development of a nurse sedation protocol. The primary outcome was to identify associations between recovery time, adverse reactions, and dose-response in expanded patient populations. METHODS: This study reviewed charts of 292 adult patients from 3 hospitals within one institution who received remimazolam during procedural sedation between June 1, 2021 and December 31, 2021. Data were analyzed using logistic and linear regression. FINDINGS: The median time to alert in patients receiving remimazolam alone was 12 minutes (interquartile range 10, 17) and increased when additional sedation medications were utilized. Receiving additional sedative medication significantly increased the odds of hypoxia (OR 2.77, 95% CI 1.30-5.91, P = 0.008) after adjusting for body mass index (BMI), American Society of Anesthesiologists physical status (ASA-PS), and total remimazolam dose. There was a 25% increase in odds of experiencing hypoxia for every 5 kg/m2 increase in BMI (95% CI 1.01-1.54, P = 0.037). IMPLICATIONS: Remimazolam presents as a promising option for nurse procedural sedation, offering minimal impact on hemodynamics and respirations, quick recovery, and no residual sedative effects.