Sedation Research Articles

Intravenous Sedation and Analgesia in a Pediatric Emergency Department: A Retrospective Descriptive Study.

Background Painful procedures in the pediatric emergency department often require the use of sedation and analgesia to ensure adequate pain control, a right of children and adolescents. This study aims to describe the procedural sedation and analgesia with intravenous medications performed in a pediatric emergency department. Methods This is a retrospective descriptive study of intravenous sedoanalgesia used in a pediatric emergency department of a level II district hospital in the Lisbon metropolitan area from October 2018 to December 2023. The type of intervention, drugs used, and adverse events were analyzed. Results A total of 615 patients were included in the study; 65.7% (n=404) were male with a median age of 6 years. The most frequently performed procedures were wound suturing (50.9%, n=313) and fracture reduction (36.3%, n=223). The drugs used for sedation and analgesia were ketamine (99.2%, n=610), midazolam (95.8%, n=589), propofol (1.6%, n=10), and morphine (0.5%, n=3). The majority of patients received midazolam and ketamine in association (93.8%, n=577). A total of 50 adverse events (8.1%) were recorded in 42 patients. The most frequent side effects were transient oxygen desaturation (2%, n=12), vomiting (1.5%, n=9), apnea/bradypnea (1%, n=6), and hallucinations (0.8%, n=5). The occurrence of adverse events was not dose-dependent (p >0.05). Respiratory complications resolved without requiring invasive interventions. Children were sedated by a pediatric intensivist in 68.1% (n=419), by a general pediatrician in 26.7% (n=164), and by a pediatric resident in 2% (n=12). Conclusions The results of this study demonstrate that intravenous sedoanalgesia, particularly the combination of ketamine and midazolam, is a safe method for sedation in pediatric patients, with a low rate of adverse events.

Advantages of remimazolam for sedation in impacted tooth extraction.

This study aims to compare the sedative effects of remimazolam and midazolam during impacted tooth extraction to provide a comfortable sedation treatment for patients with dental anxiety. A prospective randomized controlled trial was conducted, in which 60 patients undergoing intravenous sedation for mandibular impacted third molar extraction were evenly divided into either the remimazolam or midazolam group. Prior to receiving a nerve blocker, the patients were sedated with remimazolam or midazolam. Various parameters were recorded and analyzed, including onset time, awakening time, recovery time, modified dental anxiety scale (MDAS) scores before and after surgery, patient-doctor satisfaction levels, postoperative side effects within 24 hours, heart rate (HR), and mean arterial pressure (MAP) at different time points. Compared with the midazolam group, patients in the remimazolam group demonstrated significantly shorter onset, awakening, and recovery times as well as lower postoperative MDAS scores and higher levels of patient-doctor satisfaction. Fewer postoperative side effects were reported in the remimazolam group, although the differences were not statistically significant. The use of remimazolam demonstrates faster onset and recovery, superior efficacy in reducing dental anxiety, and enhanced satisfaction among patients and doctors, thereby presenting distinct advantages for sedation treatment for patients with dental anxiety.

Abusive use of Zolpidem as a Result of COVID-19 and Perspectives of Continuity of the Problem in the Post-Pandemic Period.

Zolpidem is a non-benzodiazepine hypnotic drug that works as a positive modulator of Gamma-Amino Butyric Acid-A (GABA-A) receptors, with high selectivity for α1 subunits. Given this selective binding, the drug has a strong hypnotic activity. Social isolation during the SARS-CoV-2 pandemic has contributed to increased rates of anxiety, depression, and insomnia. As a result, studies have pointed to a possible increase in the indiscriminate use of drugs with sedative effects, such as Zolpidem, during the pandemic. The aim of this work was to present prospective evidence that warns of the possibility of the abusive use of Zolpidem even after the pandemic. High rates of addiction to this drug have been reported around the world after the emergence of the coronavirus. Data from the National Survey on Drug Use and Health and from Medicaid support the continuing growth in prescription and indiscriminate use of Zolpidem during the pandemic and afterward. Therefore, there is enough evidence to support the indiscriminate use of this drug since the beginning of the pandemic. Rates of indiscriminate use of sedatives may continue to increase in the post-pandemic period, especially if strict control measures are not taken by health authorities.

A Systematic Review on Sedative and Hypnotics

Abstract: Sedative and hypnotic drugs are central nervous system depressants primarily used to induce calmness, reduce anxiety, and promote sleep. These medications include benzodiazepines, barbiturates, and various non-benzodiazepine sleep aids, each varying in their mechanism of action, efficacy, and safety profiles. Benzodiazepines, such as diazepam and alprazolam, enhance the effect of the neurotransmitter gamma-aminobutyric acid (GABA) at the GABA-A receptor, resulting in sedative, anxiolytic, muscle relaxant, and anticonvulsant effects. They are commonly prescribed for anxiety disorders, insomnia, seizures, and muscle spasms. However, their use is associated with risks of tolerance, dependence, and withdrawal symptoms. Barbiturates, such as phenobarbital, were once widely used for their sedative and hypnotic properties but have largely been replaced by benzodiazepines and other safer alternatives due to their higher risk of overdose and dependence. Barbiturates enhance GABAergic transmission but also directly activate GABA receptors, leading to more profound central nervous system depression. Non-benzodiazepine sleep aids, including drugs like zolpidem, eszopiclone, and zaleplon, act on the benzodiazepine receptor site but have a different chemical structure. These drugs are often preferred for short-term treatment of insomnia due to their relatively lower risk of dependence and adverse effects compared to benzodiazepines.

Effects of Local Wound Infiltration Post-Mastectomy Using Bupivacaine Alone, Bupivacaine With Ketamine, and Bupivacaine With Dexmedetomidine: A Randomized Double-Blind Study.

Background and aim While the infiltration of surgical incisions with local anesthetics is not a new practice, it remains a crucial component of contemporary multimodal analgesia protocols. This study aimed to evaluate the efficacy and safety of using adjuvants in combination with local anesthetic wound infiltration for pain management in patients undergoing mastectomy surgery. Methods Eighty-one patients aged 18-60 years, classified as American Society of Anesthesiologists (ASA) grade I or II, were scheduled for unilateral mastectomy and randomly assigned to three groups of 27 each. The groups were designated as Group C (bupivacaine alone), Group D (bupivacaine with dexmedetomidine), and Group K (bupivacaine with ketamine). Group C received 0.25% bupivacaine alone, Group D received 0.25% bupivacaine with 1 mcg/kg dexmedetomidine, and Group K received 0.25% bupivacaine with 1 mg/kg ketamine. The time to achieve a Visual Analogue Scale (VAS) score of 3 following local wound infiltration was recorded for each group. Additionally, total postoperative fentanyl intake during the first 24 hours, as measured by the patient-controlled analgesia (PCA) pump, was compared among the groups. Sedation levels were assessed using the Ramsay Sedation Scale (RSS). Data were analyzed using the Chi-Square test and one-way ANOVA in IBM SPSS Statistics for Windows, Version 28.0 (Released 2021; IBM Corp., Armonk, NY, USA). Results Demographic factors were similar across the three groups. Analysis of the VAS scores revealed that the ketamine group provided better postoperative pain control than the dexmedetomidine group (p < 0.001). Groups D (71.72 ± 71.73) and K (3.53 ± 13.42) had significantly lower 24-hour fentanyl intake (in mcg) compared to Group C (the control group), as measured by PCA. Additionally, Group C had a significantly lower RSS at the sixth hour (p = 0.003) compared to both Groups D and K. Conclusion Ketamine, when used as an adjuvant to bupivacaine for local infiltration, enhances the effectiveness and prolongs postoperative analgesia more effectively than dexmedetomidine in patients undergoing mastectomy.

Effects of music on perioperative anxiety in patients undergoing cesarean section – A randomised prospective controlled study

Premedication with sedative drugs is one of the most preferred methods to reduce anxiety. Due to concerns about maternal and fetal side effects, their use in obstetric anesthesia is not preferred. The primary aim of the authors of this study is to investigate the effect of music on perioperative anxiety in pregnant. The patients were randomized into three groups; Group M was listened to music during the surgery, Group S isolated from ambient noise and Group C was the control group. Anxiety status was measured at the preoperative anesthesia examination, on the morning of surgery, and at the first hour postoperatively. Although we observed the lowest postoperative anxiety in Group M, it wasn’t statistically significant. Music is an easy-to-apply and no-side-effect method. Therefore, we believe that more clinical studies with more patients are needed for clearer results.

FACTORS RELATING TO VENTILATOR-ASSOCIATED EVENT (VAE)

Mechanical ventilation is an oxygen therapy that is effective in saving the lives of critical patients in the intensive care unit (ICU). Prolonged use results in an increased risk of infection, in this case ventilator-associated pneumonia (VAP). In 2013, the United States Centers for Disease Control and Prevention redefined monitoring of the quality of care for patients using ventilators by moving away from the definition of ventilator-associated pneumonia ( VAP) to the definition of a ventilator-associated event (VAE) as a sustained increase in ventilator support after a period of stable or decreased ventilator support. For this reason, it is necessary to search for data regarding factors that influence ventilator-associated events. The literature search method was carried out based on articles published between 2019-2024 in accordance with the inclusion and exclusion criteria that had been determined using 1 database, namely Scopus. This literature search used PRISMA guidelines in carrying out the screening process. From the search results, 60 articles were obtained. After going through the screening process, there were 3 articles that met the criteria and will be analyzed. The results of the study from 3 pieces of literature show that the factors associated with ventilator-associated events are ventilator-associated events, namely the application of SDD (selective digestive decontamination, VILI (ventilator induced lung injury), lung atelectasis, excess fluid, including pulmonary edema, use of medication chlorhexidine mouthwash for oral care, spontaneous breath trials, early mobility, tracheostomy, use of vasopressors, transfusion overload, delirium, type of sedation (continuous or intermittent), type of sedation drug (midazolam, propofol), and analgesia drugs (fentanyl, morphine, remifentanil ), conditions related to infection, gender, age, presence of comorbidities, body mass index, and disease severity index. Reason for intubation. Intubation can be carried out in the ICU or elsewhere.

Impact of cumulative exposure to anticholinergic and sedative drugs on cognition in older adults: a memory clinic cohort study

BackgroundLong-term exposure to anticholinergic and sedative drugs could be a modifiable risk factor for cognitive decline. The objective of this study was to measure the association between previous cumulative anticholinergic and sedative drug exposure (Drug Burden Index) and cognitive decline.MethodsA cohort study (MEMORA cohort) was conducted in a French memory clinic for patients attending a consultation between November 2014 and December 2020, with at least 2 Mini-Mental State Examination (MMSE) measurements (≥ 6 months apart) and available medication data from the local Primary Health Insurance Fund database (n = 1,970). Drug Burden Index was linearly cumulated until each MMSE measurement and was used to categorise patients according to their level of exposure (no exposure, moderate, or high). The longitudinal association between Drug Burden Index and MMSE was assessed using a multivariate linear mixed model, adjusted for age, education level, anxiety disorders, depressive disorders, functional autonomy, and behavioural disorders.ResultsOverall, 1,970 patients were included with a mean follow-up duration of 2.78 years (± 1.54) and 2.99 visits per patients (5,900 MMSE + Drug Burden Index measurements collected). At baseline, 68.0% of patients had moderate cumulative anticholinergic and sedative drug exposure and a mean MMSE of 21.1. MMSE decrease was steeper in patients with moderate and high Drug Burden Index ( -1.74 and -1.70/year, respectively) than in patients with no exposure (-1.26/year) after adjusting for age, education, anxiety and depressive disorders, functional autonomy, and behavioural disorders (p < 0.01).ConclusionsLong-term exposure to anticholinergic and sedative drugs is associated with steeper cognitive decline. Medication review focusing on de-prescribing these drugs could be implemented early to reduce cognitive impairment.

Comparison of safety of general anesthesia and intravenous sedation during third-molar extraction surgery

This study compared the safety of general anesthesia (GA) and intravenous sedation (IVS) in patients who underwent extraction of one or more third molars. Data from 1260 patients (GA group, n = 1043; IVS group, n = 217) were retrospectively analyzed, including demographics, preoperative data, intraoperative hemodynamic parameters (blood pressure, heart rate, and oxygen saturation level), and medications administered intraoperatively and postoperatively. The incidence of intraoperative circulatory variations, surgery and anesthesia durations, postoperative complications, and medication use were assessed and compared. The GA group had longer anesthesia and surgery durations, a higher incidence of hypotension, and a higher frequency of postoperative analgesic use than the IVS group. Dexmedetomidine was the most frequently used sedative agent. The IVS group had a lower incidence of intraoperative hypotension but they had a higher need for vasopressors in the recovery room. Both anesthesia methods maintained satisfactory oxygen saturation levels and sufficient anesthesia throughout the procedure, but they showed different characteristics regarding the duration of surgery and anesthesia duration, hemodynamic stability, and postoperative analgesic needs. IVS may be preferable for patients at risk of cardiovascular complications such as hypotension or tachycardia during surgery.

Less Invasive Surfactant Administration in Preterm Infants in Tertiary Neonatal Intensive Care Units in Germany: A Survey

Introduction: The European guideline for treatment of respiratory distress syndrome recommends less invasive surfactant administration (LISA) as the preferred method of surfactant administration in spontaneously breathing preterm infants. However, there is limited evidence on practical aspects such as sedation and catheter types, leading to considerable variability between centers. Methods: An anonymous online survey (www.soscisurvey.de) was sent to 164 tertiary neonatal intensive care units (NICUs) in Germany including 43 questions on practical aspects of LISA. Results: Of 122 (74%) participating NICUs, 117 (96%) reported experience with LISA with 82% of those reporting LISA as their preferred method of surfactant administration. Indications for surfactant administration differed widely between NICUs. Most (89%) used FiO2-thresholds only or in combination with other criteria, such as Silverman score/signs of dyspnea (41%) or lung ultrasound findings (3%). Prophylactic surfactant was administered by 42%. Differences in use of LISA in extremely immature infants were reported (e.g., 36% did not perform LISA in infants below 24–26 weeks). Preferred drugs for sedation were (Es-)Ketamine, followed by Propofol and Midazolam. Minimum time interval between subsequent LISA procedures was 4 (2–6) h. Catheters specifically designed for LISA were used by most NICUs (69%). Conclusion: This survey shows that LISA is common practice in German NICUs, but with considerable variability in practical aspects. These data may serve as a guidance for NICUs that have not yet implemented LISA and might be helpful design clinical trials with the aim to standardize and/or optimize LISA.

The Efficacy of Inhaled Methoxyflurane Versus Intravenous Sedation for the Reduction of Acute Shoulder Dislocation

Purpose: Anterior shoulder dislocation is one of the most common emergency orthopedic conditions. In general practice, intravenous sedation is the standard treatment to relax patients during shoulder reduction procedures. Sedatives and analgesics are drugs that have side effects after administration, especially when administered intravenously. They can depress neurological function and cause respiratory and cardiovascular system side effects. Self-inhaled methoxyflurane relieves moderate to severe pain. Hospitals may benefit from minimized respiratory and cardiovascular side effects. Methods: This randomized controlled trial included 50 patients who were randomly assigned to two groups: the inhaled methoxyflurane group (Inh Group) and the intravenous sedation group (IV Group). All patients were assessed for efficacy, procedure duration, pain score during reduction, patient satisfaction, and adverse effects. Results: Fifty patients satisfied the inclusion requirement: 25 each in the Inh and IV Groups. Reduction was successfully achieved in 92% and 88% of the patients in the Inh and IV Group, respectively. The mean procedural time was 6.4 min and 15.4 min the Inh and IV Group, respectively. Moreover, the mean recovery time was 22.5 min in the Inh Group and 32.4 min in the IV Group. Conclusions: Inhaled methoxyflurane has better efficacy in reducing acute shoulder dislocation than intravenous sedation alone. Procedural and recovery times were shorter in the Inh Group. Adverse events (hemodynamic instability, desaturation, nausea, vomiting, drowsiness, and dizziness) were more frequent in the IV Group than in the Inh Group.

Catalytic Performance of CuZnAl Hydrotalcite-Derived Materials in the Continuous-Flow Chemoselective Hydrogenation of 2-Methyl-2-pentanal toward Fine Chemicals and Pharmaceutical Intermediates.

Hydrotalcite-derived materials are eco-friendly, cheap, and efficient catalysts of different reactions. However, their application in liquid-phase hydrogenation could be more extensive. Hence, this work concerns the application of three hydrotalcite-derived materials with different CuZnAl molar ratios in the liquid-phase continuous-flow hydrogenation of 2-methyl-2-pentenal (MPEA) at a wide range of temperature (298-378 K) and pressure (1 × 106-6 × 106 Pa). The catalytic investigations were supported by catalysts characterization by ICP-OES, TPR, in situ XRD, XPS, NH3-TPD, CO2-TPD, and TEM measurements on different stages of their biography. It was shown that the catalytic activity of these samples is related to the Cu0/Cu+ ratio. Depending on the reaction conditions, selectivity control is possible. All catalysts were 100% selective to 2-methylpentanal (MPAA)-sedative drug precursor, with low conversion, at temperatures ≤ 338 K at every pressure. However, the selectivity of the second desired product, fragrance intermediate, 2-methyl-2-penten-1-ol (MPEO), increased significantly at higher temperatures and pressures. It reached the unique value of 54% with 60% substrate conversion at 378 K and 6 × 106 Pa for the catalyst with the highest Cu loading. It was revealed that the production of significant amounts of MPEO is related to the reaction conditions, the Cu+ predominance on the surface, the hydrogen spillover effect, and the acid-base properties of these systems.

Effectiveness of buccal administration of dexmedetomidine and ketamine combination in paediatric dental sedation: A randomized controlled clinical trial.

Pain and anxiety can be considerable obstacles while treating paediatric dental patients. Moderate sedation is needed to treat uncooperative patients. This study aimed to compare the effectiveness of buccal administration of dexmedetomidine-ketamine combination versus dexmedetomidine. Fifty-six uncooperative children were randomly assigned into two groups: Group I received buccal dexmedetomidine (2 μg/kg) and ketamine (2 mg/kg) (DEX-KET), whereas Group II received buccal dexmedetomidine (4 μg/kg) (DEX). The effects of drugs were evaluated based on changes in vital signs, onset and duration of sedation, sedation level, analgesia, ease of treatment and procedural adverse effects. There were no significant differences in vital signs or sedation onset between the two groups. DEX-KET group showed shorter recovery time than DEX group (p < .0001). There were no statistically significant differences between both groups regarding sedation level at optimum sedation and during operative procedure (p = .064, p = .069 respectively). The ease of treatment was significantly better in DEX-KET group than in DEX group (p = .048). Procedural side effects and analgesic effects of the sedative drugs were comparable between both groups. The combination of dexmedetomidine and ketamine delivered buccally provided a better method of delivering care to uncooperative children with more rapid recovery than dexmedetomidine.

From Traditional Typing to Intelligent Insights: A Narrative Review of Directions Toward Targeted Therapies in Delirium.

Delirium is a heterogeneous syndrome characterized by an acute change in level of consciousness that is associated with inattention and disorganized thinking. Delirium affects most critically ill patients and is associated with poor patient-oriented outcomes such as increased mortality, longer ICU and hospital length of stay, and worse long-term cognitive outcomes. The concept of delirium and its subtypes has existed since nearly the beginning of recorded medical literature, yet robust therapies have yet to be identified. Analogous to other critical illness syndromes, we suspect the lack of identified therapies stems from patient heterogeneity and prior subtyping efforts that do not capture the underlying etiology of delirium. The time has come to leverage machine learning approaches, such as supervised and unsupervised clustering, to identify clinical and pathophysiological distinct clusters of delirium that will likely respond differently to various interventions. We use sedation in the ICU as an example of how precision therapies can be applied to critically ill patients, highlighting the fact that while for some patients a sedative drug may cause delirium, in another cohort sedation is the specific treatment. Finally, we conclude with a proposition to move away from the term delirium, and rather focus on the treatable traits that may allow precision therapies to be tested.

Clinical effect of acupuncture based on the specific response of jing-well point for intractable insomnia: a randomized controlled trial

To evaluate clinical effect and safety on the basis of detecting the specific response of jing-well point in treatment of intractable insomnia with acupuncture by meridian differentiation. Sixty-four patients with intractable insomnia were randomized into an observation group (32 cases, 1 case dropped out and 1 case was eliminated) and a control group (32 cases, 1 case was eliminated). In the observation group, the meridian imbalance value detected at the jing-well point was taken as the evidence so that the corresponding yuan-source and back-shu points were stimulated with acupuncture. In the control group, the routine acupuncture was operated at Baihui (GV 20), Sishencong (EX-HN 1), and bilateral Shenmen (HT 7), Sanyinjiao (SP 6), Shenmai (BL 62) and Zhaohai (KI 6). Besides, the detection at jing-well point was performed for blindness in the control group. In the two groups, the interventions were delivered once daily, 5 times a weeks and for consecutive 4 weeks. In the two groups, the scores of Pittsburgh sleep quality index (PSQI), insomnia severity index (ISI) and the TCM symptom scale were observed before treatment and after 2 and 4 weeks of treatment; the clinical effect and safety were evaluated after treatment; the changes of meridian imbalance value were observed before and after treatment and the correlation analysis with the total score of PSQI was conducted. After 2 and 4 weeks of treatment, except the scores for hypnotic drug in the two groups and sleep disorder after 2 weeks of treatment in the control group, the scores of the other factors and the total scores of PSQI were all reduced when compared with those before treatment in the two groups (P<0.05). After 4 weeks of treatment, except the scores for hypnotic drug in the two groups and sleep disorder in the control group, the scores of the other factors and the total scores of PSQI were lower than those after 2 weeks of treatment in the two groups (P<0.05). After 2 weeks of treatment, the scores for time to fall asleep, sleep efficiency and daytime dysfunction in the observation group were lower than those of the control group (P<0.05); and after 4 weeks of treatment, except the scores for sleep disorder and hypnotic drug, the scores of the other factors and the total score of PSQI in the observation group were all lower than those of the control group (P<0.05). After 2 and 4 weeks of treatment, ISI scores and the scores of TCM symptom scale decreased when compared with those before treatment (P<0.05), and the scores of these two scales after 4 weeks of treatment were lower than those after 2 weeks of treatment (P<0.05) in the two groups; and the scores in the observation group were lower than thoese in the control group (P<0.05). The total effective rate was 93.3% (28/30) in the observation group, higher than that (90.3% [28/31]) in the control group (P<0.05). Of 64 cases, there was only 1 case of mild hematoma in the control group; and no any other adverse events occurred. Among 64 cases, the meridians, with the imbalance frequency ≥30 times, included the pericardium meridian of hand-jueyin and the heart meridian of hand-shaoyin; those with the imbalance frequency ≥20 times, were the kidney meridian of foot-shaoyin, the triple energizers meridian of hand-shaoyang, the gallbladder meridian of foot-shaoyang, the spleen meridian of foot-taiyin and the stomach meridian of foot-yangming. Except the lung meridian of hand-taiyin in the control group, the imbalance value of each meridian was reduced after treatment (P<0.05, P<0.001, P<0.01), and the meridian imbalance value presented a linear positive correlation with the total score of PSQI in the two groups . Meridian differentiation acupuncture based on detecting the specific response of jing-well point can significantly improve the sleep quality and reduce the related symptoms in the patients with intractable insomnia. This therapy promotes the conversion of the meridians from the imbalance to the balance and is satisfactory in its safe operation.

Study of Two Sedative Protocols for Drug-Induced Sleep Endoscopy: Propofol versus Propofol-Remifentanil Combination, Delivered in Target-Controlled Infusion Mode.

Background and Objectives: Obstructive sleep apnea (OSA) is a prevalent sleep-disordered breathing pathology with significant clinical consequences, including increased cardiovascular risk and cognitive decline. Continuous positive airway pressure (CPAP) is the gold-standard treatment, but alternative strategies are sometimes needed for patients intolerant to CPAP. Drug-induced sleep endoscopy (DISE) is a key diagnostic tool for assessing upper airway obstruction in OSA patients and subsequently tailoring a surgical approach, with sedation protocols playing a crucial role in its efficacy and results accuracy. This study aimed to investigate the effect of adding remifentanil to a propofol target-controlled infusion (TCI) regimen on the sedation parameters and procedural outcomes of DISE. Materials and Methods: The study was conducted at the Central University and Emergency Military Hospital "Dr. Carol Davila" and Ria Clinic in Bucharest between July 2021 and October 2023. Thirty-one patients were enrolled and randomised into two groups: a propofol group (P group, n= 11) and a remifentanil-propofol group (R-P group, n = 20). DISE was performed using standardised protocols, sedative drugs were administered in TCI mode, and data on sedation levels, respiratory and cardiovascular parameters, and procedural incidents were collected. Results: The addition of remifentanil at 1 ng/mL effect-site concentration significantly reduced the effect-site concentration of propofol required for adequate sedation (3.4 ± 0.7 µg/mL in the P group vs. 2.8 ± 0.6 µg/mL in the R-P group, p = 0.035). The time to achieve adequate sedation was also shorter in the R-P group (7.1 ± 2.5 min vs. 9.5 ± 2.7 min, p = 0.017). The incidence of cough, hypoxemia, and cardiovascular events did not significantly differ between the two groups. Conclusions: Adding remifentanil to a propofol TCI regimen for DISE effectively reduces the required propofol effect-site concentration and shortens sedation time without increasing the risk of adverse events. This combination may enhance the safety and efficiency of DISE, offering a promising alternative for patients undergoing this procedure.

Potential for Drug Repositioning of Midazolam as an Inhibitor of Inflammatory Bone Resorption.

Drug repositioning is a method for exploring new effects of existing drugs, the safety and pharmacokinetics of which have been confirmed in humans. Here, we demonstrate the potential drug repositioning of midazolam (MDZ), which is used for intravenous sedation, as an inhibitor of inflammatory bone resorption. We cultured a mouse macrophage-like cell line with or without MDZ and evaluated its effects on the induction of differentiation of these cells into osteoclasts. For in vivo investigations, we administered lipopolysaccharide (LPS) together with MDZ (LPS+MDZ) to the parietal region of mice and evaluated the results based on the percentage of bone resorption and calvaria volume. Furthermore, we examined the effects of MDZ on the production of reactive oxygen species (ROS) in cells and on its signaling pathway. MDZ inhibited osteoclast differentiation and bone resorption activity. In animal studies, the LPS+MDZ group showed a decreasing trend associated with the rate of bone resorption. In addition, the bone matrix volume in the LPS+MDZ group was slightly higher than in the LPS only group. MDZ inhibited osteoclast differentiation by decreasing ROS production and thereby negatively regulating the p38 mitogen-activated protein kinase pathway. Thus, we propose that MDZ could potentially be used for treating inflammatory bone resorption, for example, in periodontal disease.

Evaluating drug withdrawal syndrome risks through food and drug administration adverse event reporting system: a comprehensive disproportionality analysis.

The study aims to identify the drugs associated with drug withdrawal syndrome in the Food and Drug Administration Adverse Event Reporting System (FAERS) and estimate their risks of causing withdrawal syndrome. All the data were collected from FAERS from the first quarter of 2004 to the third quarter of 2023. Disproportionality analyses of odds ratio (ROR) and proportional reported ratio were conducted to identify potential adverse effects signal of drug withdrawal syndrome. A total of 94,370 reports related to withdrawal syndrome from the data. The top 50 drugs with most frequency reported were analyzed, and 29 exhibited a positive signal based on the number of reports. The top three categories of drugs with positive signals included opioids, antidepressant drugs and antianxiety drugs. Other classifications included opioid antagonist, muscle relaxant, antiepileptic drugs, analgesics, hypnotic sedative drugs and antipsychotic drugs. Our analysis of FAERS data yielded a comprehensive list of drugs associated with withdrawal syndrome. This information is vital for healthcare professionals, including doctors and pharmacists, as it aids in better recognition and management of withdrawal symptoms in patients undergoing treatment with these medications.

Psychosocial characteristics of the general population who habitually use hypnotics: Results from a national survey on drug use among the Japanese.

The aim of this study was to examine the characteristics of habitual hypnotic users in Japan. This nationwide, cross-sectional survey used self-administered questionnaires. Data were collected from four national surveys conducted every 2 years between 2015 and 2021. The participants were Japanese individuals who had taken prescription hypnotics in the past year or had never taken them. We divided 13,396 participants into three groups to compare the social background and status of taking medication and controlled drugs, drinking, and smoking among the three groups: people who use hypnotics habitually daily (habitual hypnotic users [HUs]), people who use them only occasionally (occasional hypnotic users [OUs]), and people who do not use them (hypnotic non-users [NUs]). We compared the perception of using hypnotics between the HU and OU groups. HUs were more likely to be older, unemployed, and to habitually use anxiolytics and analgesics than NUs. The main reasons for taking anxiolytics in HUs were alleviating insomnia and reducing anxiety, whereas the main reason for taking analgesics was improving joint pain. Additionally, the HU group had a higher proportion of habitual smokers than the OU group. There was no difference in drinking status or taking of controlled drugs among the three groups. HUs were more likely to use hypnotics and to have concerns about their side-effects than OUs. HUs were more likely to be unemployed, habitually use anxiolytics and analgesics, smoke heavily, and take hypnotic drugs with concerns regarding side-effects. These results may help encourage the appropriate use of hypnotics.

Adult intravenous sedation in general dental practice: indication, effectiveness and patient experiences.

Background Conscious sedation is an option in primary dental care for anxious patients or those undergoing extensive procedures. The objective of this retrospective service evaluation was to study the range of treatments delivered during sedation with intravenous midazolam, together with patient-reported experience measures.Methods Data from 100 consecutive patients treated under sedation at a single private dental practice were evaluated retrospectively. All patients were asked questions about their experience of sedation during a post-operative follow-up phone call.Results Over half of patients were treated under sedation due to anxiety. The mean dose of midazolam was 7.8 mg and the average treatment time was 1 hour 25 minutes. Of note, the average dose for the most extensive procedure - implant immediate full arch loading - was 11.7 mg; however, this equated to an average dose of 4.5 mg per hour. One patient needed supplemental oxygen; flumazenil was never required. Additionally, 91% of patients felt they had enough sedation, and 50% could remember the events of treatment.Conclusion With the British National Formulary recommending a maximum dose of 7.5 mg midazolam, this study demonstrates that this dose can be safely exceeded in dental treatment; therefore, a dose that accounts for the length of the procedure is a more valid approach. Moreover, patients undergoing a variety of dental treatments were satisfied with the amount of intravenous sedation received and age is not an absolute limit for sedating older people.